Hypothyroidism kc002 hyd
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A clinical study of the effect of kanchanara guggulu and sigru patra kwadha on hypothyroidism, V. Vijaya lakshmi prasuna, 2007, Dr. N.T.R UNIVERSITY OF HEALTH SCIENCES, VIJAYAWADA, Dr.BRKR Govt. ...

A clinical study of the effect of kanchanara guggulu and sigru patra kwadha on hypothyroidism, V. Vijaya lakshmi prasuna, 2007, Dr. N.T.R UNIVERSITY OF HEALTH SCIENCES, VIJAYAWADA, Dr.BRKR Govt. Ayurvedic College, HYDERABAD



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Hypothyroidism kc002 hyd Document Transcript

  • 1. A CLINICAL STUDY OF THE EFFECT OF KANCHANARA GUGGULU AND SIGRU PATRA KWADHA ON HYPOTHYROIDISM Dissertation submitted in partial fulfilment for the degree of DOCTOR OF MEDICINE (AYURVEDA) In KAYACHIKITSA By Dr.V. Vijaya lakshmi prasuna B.A.M.S. GUIDE Dr. PRAKASH CHANDER M.D. (Ay.) Professor & HOD, Post Graduate Dept.of Kayachikitsa Dr. B.R.K.R. Govt.Ayurvedic College, Hyderabad. Dr. N.T.R UNIVERSITY OF HEALTH SCIENCES VIJAYAWADA Dr.BRKR Govt. Ayurvedic College, HYDERABAD 2007
  • 2. Dr. N.T.R. UNIVERSITY OF HEALTH SCIENCES VIJAYAWADA POST GRADUATE DEPARTMENT OF KAYACHIKITSA Dr. B.R.K.R. GOVT. AYURVEDIC MEDICAL COLLEGE / HOSPITAL HYDERABAD CERTIFICATE This is to certify that the present dissertation embodies the outcome of originalobservations made by Dr. V. Vijaya Lakshmi Prasuna on ‘A Clinical Study onthe effect of Kanchanara Guggulu and Shigru patra kwatha onHypothyroidism’’ for the degree of ‘Doctor of Medicine’ (Ayurveda). Thiswork has been completed under my direct supervision after a series of a scientific discussion. The scholar has put in commendable effort for designing and executing the methodsand plans for the study. Hence I recommend this dissertation to be submitted for adjudication. GUIDEDate: Dr. PRAKASH CHANDERPlace: Hyderabad. MD (Ayu) Professor& HOD, Post graduate Department of Kayachikitsa Dr. BRKR Govt. Ayurvedic Medical College, Hyderabad.
  • 3. Dr. N.T.R. UNIVERSITY OF HEALTH SCIENCES VIJAYAWADA POST GRADUATE DEPARTMENT OF KAYACHIKITSA Dr. B.R.K.R. GOVT. AYURVEDIC MEDICAL COLLEGE / HOSPITAL HYDERABAD CERTIFICATE This is to certify that Dr. V. Vijaya Lakshmi Prasuna of M.D. (Ayu)Kayachikitsa has worked for the thesis on the topic ‘A Clinical Study of the effect ofKanchanara Guggulu and Shigru patra kwatha on Hypothyroidism’’ as perrequirements of the order laid by the N.T.R. University of Health Sciences, for the purpose. Thehypothesis submitted by her in the first year MD (Ayu) is one and the same to that of thedissertation submitted. I am fully satisfied with her work and hereby forward the dissertation for the evaluationof the adjudicators.Date: Dr.PRAKASH CHANDERPlace: Hyderabad MD (Ayu) Professor& HOD, Post graduate Dept. of Kayachikitsa Dr BRKR Govt. Ayurvedic Medical College, Hyderabad.
  • 4. CONTENTS CHAPTER Page no’sPART-I 1. Introduction. 2. Historical aspect of Hypothyroidism. 3. Shareera: i) Anatomy. ii) Physiology. iii) Role of iodine. iv) Physiological actions of thyroid hormone.PART-II 1. Etiology 2. Pathogenesis 3. Clinical features 4. Pathology of hypothyroidism 5. Investigations 6. Complications 7. Goiter 8. Ayurvedic Aspect i. Galaganda ii. Ayurvedic Aspect of Hypothyroidism 9. Sadhyadsadhya’sPART-III 1. Chikitsa yojana 2. PathyapathyaPART-IV 1. Criteria for selection. 2. Kanchanara guggulu. 3. SigruPART-V 1. Materials and methods. 2. Observations and Results. 3. Discussion. 4. Conclusion. 5. Summary.REFERENCESAPPENDICES 1. Bibliography 2. Case sheet 3. BMI Chart.
  • 5. ACKNOWLEDGEMENTS I offer my humble and sincere prostrations to the lotus feet of mySadguru Sri Sri Sri Ganapathi Sacchidananda Swamiji for his ever lastingsupport and guidance, which have had a profound influence on my life. I would like to express my gratitude and respect to my guideDr. Prakash chander, professor, HOD, PG Dept of Kaya Chikitsa, Hyderabad,for giving me the opportunity to work in a very interesting area and for his supportand guidance during my thesis work. My most sincere thanks to Dr. M Srinivasulu for his advice,confidence and the vision, that started this project and for his constantencouragement through out my thesis work. I am especially grateful to Dr. V.Vijay Babu, Reader, P.G Dept ofKaya Chikitsa, for sharing with me his wealth of knowledge, his valuablesuggestions made me complete my thesis work. I would have been lost withouthim. It is difficult to overstate my gratitude to Dr. PVV SatyanarayanaM.D (Gen) Associate professor, Rangaraya Medical College, Kakinada. With hisenthusiasm, his inspiration and his great efforts to explain things clear and simply,helped to make my thesis work without any trouble. I would like to express my sincere thanks to Dr. B. Venkataiah,HOD Shalakya Dept, Dr. Ravindranath, Dr. J. Srinivasulu,Dr. RCM SharmaM.D(Homeo), for their valuable suggestions and useful discussions during mystudies. I express my sincere thanks to my lecturers Dr. M L Naidu, Dr. M.Bhaswantha Rao, Dr. Ramalingeswara Rao, Dr. Vijayalakshmi for their usefulsuggestions.
  • 6. It’s a pleasure to express my gratitude towards my seniors Dr.Badrinarayana, Dr. Amaranath, my classmates Dr. Lavanya, Dr.K Sirisha,Dr.Priya, Dr. Sivanarayana, Dr. Perumal, Dr. Gayatri, Dr. Govindamma for all theemotional support, companionship, entertainment and caring they provided. My heartfelt thanks to Mr. Dattu Rao, Mr. Udaypal Yadav,Mr.Maheswara Singh of Pathology Dept. Ayurvedic Hospital, and Mr. Sunder Rajof thyrocare center for their collaboration during the investigations. It is immense pleasure to convey my thanks to my brother Mr. Kalicharan, M.Tech (CS), for his affectionate guidance in the computer work. I am forever indebted to my parents for their understanding,endless patience and encouragement. Special thanks to my mother. I have nowords to express my gratitude for her encouragement, inspiration and compassionand love for me. Finally I like to thank all my patients for their kind cooperation. Dr. PRASUNA
  • 7. LIST OF FIGURESS.No. Name of the diagram Page No. 1. 1.1 Anatomy of the thyroid gland. 2. 1.2 Detailed anatomy of the thyroid gland. 3. 1.3 Histology of the thyroid gland. 4. 1.4 Thyroid hormone synthesis. 5. 1.5 Thyroid hormone synthesis in detail. 6. 1.6 Thyroid hormone synthesis and structure. 7. 1.7 Metabolism of thyroid hormones 8. 4.1 Kanchanara guggulu and Shigru kwatha churnam. 9. 4.2 Guggulu 10. 4.3 Kanchanara 11. 4.4 Shigru
  • 8. LIST OF TABLES Pg.S.No. Name of the Table No. 1. 1.1. The kinetics of thyroid hormones. 2. 1.2. The physiological actions of thyroid hormones on different systems 2.1. The normal and abnormal functions of agni related to 3. Hypothyroidism. 4. 5.1 Incidence of hypothyroidism a/c to Age. 5. 5.2 Incidence of hypothyroidism a/c to Sex. 6. 5.3 Incidence of hypothyroidism a/c to Occupation. 7. 5.4 Incidence of hypothyroidism a/c to SES. 8. 5.5 Incidence of hypothyroidism a/c to Diet 9. 5.6 Incidence of hypothyroidism a/c to Family history. 10. 5.7. Incidence of hypothyroidism a/c to Previous drug/ medical history 11. 5.8 Incidence of hypothyroidism a/c to Prakriti. 12. 5.9 Incidence of hypothyroidism a/c to Sara. 13. 5.10 Incidence of hypothyroidism a/c to BMI. 14. 5.11 TSH levels before and after treatment in fresh cases 15. 5.12 TSH levels before and after treatment in chronic cases. 16. 5.13. The symptomatic relief percentage 17. 5.14. The result of over all treatment.
  • 9. Introduction INTRODUCTION Thyroid gland is one of the most important and sensitive endocrinegland. As it easily responds to stress and stimuli the global incidence ofhypothyroidism is increasing day by day. Hypothyroidism occurs when the thyroid gland fails to produceenough thyroid hormone. Recent studies show that nearly 10% of the population issuffering from hypothyroidism. As all the drugs used in this condition are well known for their sideeffects a need arises to search a safer drug with similar efficacy. Due to inadequate success in combating the disease with modernmedications, there is an increasing demand to treat the diseases with Ayurvedicsystem of medicine. Like many other diseases of the modern days it is not mentioned(exact correlation yet to be made) in Ayurvedic texts. The recent research work done by Dr. Tripathi and others. Animalstudies have revealed that guggul supports healthy thyroid function, mostly byincreasing the conversion of less active Thyroxin (T4) to more activeTriiodotyronine (T3) through increasing thyroid proteolytic activity and the uptakeof iodine into thyroxin, and without increasing the production of ThyroidStimulating Hormone. As Hypothyroidism results from the under active thyroid gland, thethyroid stimulatory drug is beneficial here. The present trial drug kanchanara guggulu (Sa. Sam), is found inusage for many years for Gandhamala, Apache, Arbuda, Grandhi, Kushta, etc, hasHypothyroidism 1
  • 10. Introductionbeen selected to evaluate the efficacy of this drug in hypothyroidism. Its manyingredients kanchanara, varuna, triphala, trikatu, trijataka may also useful inhypothyroidism. Sigru is a well-known plant in India. It is rich in iodine, which is anessential component of thyroid hormones, T3 and T4. It has deepana, pacahna,kapha vata hara properties. It is recommended in galaganda, kandu, sotha, apachi,vrana, medoroga, vidradhi, gulma etc.is selected as anupana along with KNG. Itappears to provide it with the nutrition and substitutes the Iodine, thyroid glandrequire. Hence the drug is selected for the study. The main aim of the study is 1. To normalize the levels of TSH in the fresh cases. 2. To maintain the TSH levels in the patients who are already using the allopathic drug thyronorm and gradually replacing the allopathic drug with the trail drug. For fresh cases the trial drug started immediately after the diagnosisconfirmed. For the patients who are already using thyronorm they were advisedto withdraw the 25 mcg of the drug before starting the trail drug. The patients wereobserved carefully for 1 month, if they are comfortable with the drug and dosageand TSH levels are maintained well they are advised to withdraw another 25mcg.This way the drug will be totally replaced with the trail drug. The trail was conducted on 32 patients from the Govt AyurvedicHospital, Erragadda; the progress of the patient is observed and recorded. Analysiswas made to assess the results in relation to various factors.Hypothyroidism 2
  • 11. Historical aspects ENDOCRINOLOGY: HISTORICAL LANDMARKS The history of thyroid disease is an example f the close inter-relationship of basic and clinical sciences. Although we can see a slowadvancement in knowledge about the clinical features of thyroid disease since thedawn of the 20th century, the methods of investigation and treatment advancedrapidly. Some endocrine facts, such as the sequel of castration, are deeplyrooted in the past. Frederick Ruysch, a Dutch anatomist, was the first tospeculate, in 1690, that an organ such as the thyroid pours into the bloodsubstances of physiological importance1. The French scientist Theophile deBordeu had a similar theory 1.The Ruysch and Bordeu speculations were easilycriticized by the lack of any experimental proof. But the real father ofendocrinology who set its principles as a formal discipline was Frenchphysiologist Claude Bernard. In 1855, Bernard introduced the term “internalsecretions” By the end of the 19th century a number of diseases such as Gravesdisease and acromegaly were described along with their probable relation to aglandular dysfunction2. English physiologists, William Bayliss and ErnestStarling isolated a substance, giving it the name “secretin”. When secretin wasinjected into the bloodstream of an experimental animal, it resulted in markedincreased secretion from the pancreas. This result reinforced Bernard’s concept ofinternal secretion2 In 1905 Starling coined the term “hormone” for this internalsecretion (including his secretin). The word hormone was derived from a Greekphrase meaning “to set in motion”. Thus, secretin was the first hormone to beisolated.Hypothyroidism 3
  • 12. Historical aspects The history of endocrinology is not complete without a mention ofthe master of the endocrine glands, the pituitary. The pituitary gland was namedby the Belgian anatomist Andreas Vesalius who believed that it secreted mucusthrough the nose (derived from the Latin word pituita which means mucus)1.Later, the German physician Conrad Victor Schneider cast doubt on the mucussecreting function of the pituitary when he first described the cribriform plate ofthe ethmoid1. But this view persisted until Pierre Marie detected two cases ofacromegaly with associated pituitary enlargement in 1886 and 18882. Since then alarge body of knowledge has accumulated about the pituitary which led LangdonBrown in 1935 to describe it as the “leader of the endocrine orchestra”. ANATOMY OF THE THYROID The anatomy of the thyroid gland can be traced back as far as thefirst century AD when Galen, the famous Greek doctor, briefly described it. In1543 Vesalius gave a full description of the organ; he believed that it consisted oftwo separate parts1. Later, the anatomist Bartolomeo Eustachius recognized theisthmus and considered the thyroid as a single organ1. But the controversy aboutwhether the thyroid was a single or double organ was finally resolved byGiovanni Bathista Morgagni who demonstrated that the gland had two lobesconnected by the isthmus. Thomas Wharton of London named the thyroid in1656, from the Greek word thyreos meaning “oblong shield”2. The histology ofthe thyroid was studied from the start of the microscopy era. PHYSIOLOGY OF THE THYROID Throughout history, the function of the thyroid has beencontroversial. Galen suggested that it functioned to lubricate the larynx and thisview was accepted for a long time. Wharton in 1656 suggested that the purposeof the thyroid was to beautify the neck by giving it a rounded contour throughHypothyroidism 4
  • 13. Historical aspectsfilling the vacant spaces around the larynx2. In 1829 Astley Cooper proposed thatthe thyroid was a lymphatic gland when he noticed lymph passing from it to thethoracic duct1. Even up to 1880 the thyroid was proposed as a receptacle of wormsor even a vascular shunt to cushion the brain against a sudden increase in bloodflow. Thomas King first suggested the concept of an internal secretary functionfor the thyroid. King’s idea was that the thyroid formed and secreted a vitalmaterial into the circulation at a time of emergency. In 1856 Moritz Schiff of Berne carried out thyroidectomies on dogsand guinea pigs with fatal results2. French physiologist Eugene Gley described theparathyroid glands in 1891. In 1882–83, Ludwig Rehn and Jacques-LouisReverdin noticed the appearance of symptoms of hypothyroidism afterthyroidectomy operations on patients with Graves disease. In 1884 Schiff carriedout experiments on dogs and succeeded in preventing the effects of thyroidectomyby grafting the thyroid onto another part of the animal body. Unfortunately, thebody soon absorbed the gland. Thereafter, the function of the thyroid gland wasthought to neutralize or remove poisons from the body and hence that thyroiddeficiency leads to toxaemia. The definite function of the thyroid as a controller of metabolismwas studied and confirmed by George Murray, Hector Mackenzie and EdwardFox. These studies were based on following up the successful effects of givingthyroid extracts by different routes to patients with myxoedema. From around1895 thyroid researchers began to study the chemistry of the gland secretions. Thisfield was pioneered by Eugen Baumann, who was the first to recognize the roleof iodine in the work of the thyroid gland when he discovered a high concentrationHypothyroidism 5
  • 14. Historical aspectsin the gland. In1896, he isolated a compound containing iodine (iodothyrin) andsuggested a relation to iodine metabolism. In the same year, English pediatricianRobert Hutchison found that iodine was concentrated in the colloidal materialwithin the glandular follicles. In 1899 Oswald extracted an iodized protein which he termed“thyeroglobin”. The presence of organic iodine in the plasma was indicated byGley and Bourcet in 1900 whereas in 1905 di-iodotyrosine was prepared byWheeler and Jamieson2. Tri-iodothyronine, in plasma and thyroid, wasrecognized in 1952 by Gross and Pitt-Rivers. The big success came in 1914when Edward Kendall isolated an iodine-containing crystalline product fromalkaline hydrolyses of thyroid tissues and named it “thyroxine”. He described it asa “stirring activator of metabolism and probably the hormone of the thyroid”. Bythen, the active principle of the thyroid gland had been identified and thensynthesized in 1927 by Charles Harrington and George Barger.HYPOTHALAMUS, PITUITARY AND THYROID: The association betweenthe pituitary gland and endocrine disease was first recognized by Pierre Marie in1890, Thyroid-stimulating hormone (TSH), was identified, by Collip andAnderson in 1935. In 1938 it was first suggested that the engineering concept of“feedback control” could be applied to biological systems. Soon after, this wasapplied by Hoskins in endocrinology, who coined the term “thyrostat”. The phrase“pituitary–thyroid axis” was first used in the 1940s to describe the relationship ofthe two glands. In 1955 Saffran, Schally and Benfey postulated that first-orderhormones interacted in the hypothalamus to regulate the secretion of the pituitaryhormones and they coined the term “releasing factors” for these hormones.Hypothyroidism 6
  • 15. Historical aspectsSIMPLE GOITRE AND CRETINISM: Descriptions of goitre have been foundin sushruta samhita by the name Galaganda, as two encapsulated swellings in theanterior region of the neck. The Chinese used burnt sponge and seaweed in thetreatment of goitre1. Hippocrates was aware of goitre. In the Middle Ages goitrewas mentioned in the book Lives of saints and around this time, the word “goitre”was coined1. The presence of goitre was considered a sign of beauty in somesocieties. Also, the high prevalence of goitre in adults made it difficult to associateit with disease. Only from the work of Caleb Parry and Giuseppe Flajani at thebeginning of the 19th century was goitre recognized as a source of pathologicaleffects. Chatin in 1853 in France was the first to describe the correlation betweenthe iodine content of water, soil and air and the prevalence of goitre. Thisinformation was neglected until confirmed in 1923 by Von Fellenverg inSwitzerland and Orr in England1. But the question was raised whether iodinedeficiency was the only cause for goitre. Robert McCarrison hypothesized thepresence of “goitrogens” that inhibit thyroid function in the drinking water as acause of goitre. In 1928 Chesney and his co-workers were the first to observe thatcabbage may contain goitrogens and cause goitre in rabbits (originally they wereworking on syphilis research and were using cabbage-fed rabbits). During the nextdecade a large number of vegetables were found to be goitrogenic e.g.cauliflowers, turnip and Brussels sprouts. Burnt sponge and seaweed have beenused in the treatment of goitre since the 12th century. After extensive work with these materials, the chemist BernardCourtois in France extracted a substance in 18121. This was examined byHumphry Davy, then at Paris who named it iodine. The first genuine therapeutictrial to use iodine was made by Jean-Francois Coindet of Geneva in 1820. TheHypothyroidism 7
  • 16. Historical aspectsuse of iodine to prevent goitre was established in 1909–13 when Marine andLenhart, in the USA, demonstrated the role of iodine deficiency in causing goitrein black trout and other animals. The surgical treatment of goitre was probablyfirst attempted by Albucasis, a prominent Arab surgeon in the Middle Ages. Thefirst surgeon who achieved successful results with thyroidectomy was TheodorBillroth at Vienna in 1849. But the techniques of this operation were highlyimproved by Theodor Kocher at Berne1. He was awarded the Noble prize in 1909for pathology and surgery of thyroid disease, the first surgeon to win the prize. HYPOTHYROIDISM Up to 1850 doctors were familiar with the syndrome of cretinism butonly in that year was the occurrence of features similar to cretinism in adults (i.e.myxodema) first reported by Thomas Blizzard Curling. William Gull aprominent pathologist gave a complete description of myxoedema in 1873,describing five cases of cretinism in adult women. But it was William Ord who in1878 coined the term “myxoedema” when he found extensive deposits of mucin inthe skin of feet of his patients at autopsy. In 1882, Reverdin noted the occurrenceof symptoms of myxoedema after thyroidectomy. Around the same time, VictorHorsley produced artificial myxoedema in dogs after thyroidectomy2. FelixSemon put an end to this controversy by stating that myxoedema and cachexiastruamiprivia were one disease and, together with cretinism, were due to onecause: loss of thyroid function2. Semon’s statement was investigated andconfirmed by a committee appointed by the Clinical Society of London (included,among others, Victor Horsley and Moritz Schiff). The road was now paved topropose a suitable treatment for hypothyroidism. George Murray in 1891 andHowitz in 1892 tried to treat myxoedema with injection of thyroid extracts withsuccessful results. One of Murray’s patients lived for a further 28 years after hewas treated with hypodermic injections of glycerine extract of sheep thyroid tissueHypothyroidism 8
  • 17. Historical aspectsfor 6 months. At the same time, Hector Mackenzie was successful in givingpatients fresh thyroid extract by mouth. But most patients had to wait untilthyroxine was isolated and then synthesized 35 years later. Riedel in 1896described a chronic non-malignant involvement of the thyroid gland (chronicthyroiditis). In 1912, Hashimoto first described the disease that now bears hisname. The first evidence of a possible role for autoimmunity in thyroid diseasewas the tendency of Hashimoto disease to pass sooner or later into hypothyroidismor even an early phase of thyrotoxicosis. In 1936 a third variety of thyroiditis(subacute and non-suppurative) was described by De Quervain and now bears hisname.Hypothyroidism 9
  • 18. Shareera SHAREERA The term endocrine (Greek, Endon- within, Crinen- to set apart)was coined by Starling to contrast the actions of hormones secreted internally butthe real Father of endocrinology was French physiologist Claude Bernardintroduced the term ‘’internal secretions’’. Hormones are named from the Greekword hormo, meaning ‘’to urge or excite’’ because they were first discovered toplay a role in hunger, sex, fight or flight response and many other basic drives.Hormones serve within the body as invaluable messengers, governors ofdevelopment, and regulators of metabolism. 2 The classical endocrine glands Pituitary, Thyroid, Parathyroid,Pancreatic islets, Adrenals, and Gonads communicate broadly with other organsthrough the nervous system, hormones, cytokinines, and growth factors andimmune system of the body. 3 The thyroid gland is one of the largest endocrine glands in thebody. It is situated in the lower part of the neck, anterior to the trachea. It is highlyvascular and soft in consistency. It controls metabolism by producing hormonescalled thyroxine (T4) and triiodothyronine (T3). Levels of these hormonesinfluence heart rate, body temperature, alertness, mood and many other functions.The thyroid is controlled by the pituitary gland; located deep within the brain. Noorgan packs so much critical function into so little space as the pituitary. Hence itis described as the ‘’leader of endocrine orchestra’’. The Hypothalamus controlsalmost all secretions of the pituitary.ANATOMY OF THE THYROID GLAND The anatomy of the thyroid gland was first described by thefamous Greek doctor Galen in the first century. He suggested that it functioned toHypothyroidism 10
  • 19. Shareeralubricate the larynx. Wharton in 1656 suggested that the purpose of the gland towas to beautify the neck by giving it a rounded contour through filling the vacantspaces around the larynx.3DEVELOPMENT:6 The thyroid development commences at 24th day as amidline thickening and then as an outpouching of the endodermal floor of thepharyngeal cavity. This primordium of the thyroid eventually forms a sac likediverticulum between the first and second pharyngeal pouches. By the sixth toseventh week it is clearly bilobed and as the embryo the tongue grows forward,the thyroid descends in the neck but remains attached to its point of origin by anarrow canal, the thyroglossal duct. During the fifth and sixth weeks ofdevelopment, the distal ends of the third and fourth paired pharyngeal pouchesdifferentiate into the primordia of the four para thyroid glands. The neural crestderivatives from the ultimobronchial body gives rise to thyroid medulllary c cellsthat produce calcitonin, a calcium lowering hormone.The thymus is derived fromthe cells that arise from the ventral portion of the third pharyngeal pouch andmigrate caudally with the thyroid and parathyroids. If the parathyroids or theultimobronchial bodies do not become attached to or incorporated into the thyroid,they form ectopic glands. Normally the thyroglossal duct ruptures and the cells atrophy or areabsorbed by the second month, leaving only a small dimple (foramen caecum) atthe junction of the middle and posterior third of the tongue; persistent thyroglossalduct tissue may give rise to cysts. Cells in the lower portion of the ductdifferentiate into thyroid thyroid tissue, forming the pyramidal lobe of the gland asan upward, finger like extension. By the seventh week of development, whenconnection of the human thyroid to the pharynx is lost, the cells of the thyroid aregrouped into clusters. At about 11weeks, a central lumen appears in each cluster,completely surrounded by a single layer of cells. Although the thyroid isfunctionally capable of trapping iodide and releasing hormone at this stage, it doesHypothyroidism 11
  • 20. Shareeranot actually respond to pituitary secretion of thyrotrophin until this occurs ataround 22nd week.ANATOMICAL POSITION 3,4,5 The thyroid gland is located in the neck, anterior to the trachea,between the Cricoid cartilage and the Suprasternal notch. It lies deep to theSternothyroid and Sternohyoid muscles from the level of fifth cervical to the firstthoracic vertebrae. An isthmus unites the lobes over the trachea usually anterior tothe 2nd and 3rd tracheal rings. It is ensheathed by the pretracheal layer of the deepcervical fascia. So it is a well-known clinical sign that thyroid moves upward onswallowing. The thyroid gland consists of two lateral lobes, each lobe is about 5cm. long; its greatest width is about 3 cm, and its thickness about 2 cm, joined by anarrow isthmus. A conical pyramidal lobe often ascends from the isthmus or theadjacent part of either lobe (more often the left) toward the hyoid bone, to which itmay be attached by a fibrous or fibromuscular band, the levator of the thyroidgland. Its weight is somewhat variable, but is usually about 30 grams, andhas a bow tie shape. It is usually smaller in regions of the world where supplies ofdietary iodine are abundant. It is nearly always asymmetric, and is usually largerin the women than men, and it enlarges during puberty, in pregnancy, duringlactation and in the latter part of the menstrual cycle; seasonal changes have alsobeen reported between summer and winter, during which period a decrease inthyroid mass frequently occurs. Four parathyroid glands are located in the posterior region of thethyroid. The recurrent laryngeal nerves traverse the lateral borders of the thyroidgland and must be identified during thyroid surgery to avoid vocal cord paralysisHypothyroidism 12
  • 21. ShareeraHISTOLOGY OF THE THYROID7 Microscopically the thyroid gland consists of follicles or vesicleslined by cuboidal epithelium. Under the appropriate stimulation of the TSH thelow cuboidal epithelium may be converted into tall columnar epithelium.Epithelial cells are of 2 types: Principal Cells (i.e. follicular) and ParafollicularCells (ie, C, clear, light cells). Principal cells are responsible for formation of thecolloid (iodothyroglobulin), whereas parafollicular cells produce the hormonecalcitonin, a protein central to calcium homeostasis. Parafollicular cells lieadjacent to the follicles within the basal lamina. The interior of the follicle is filledwith colloid, a protenaceous material containing principally Thyroglobulin, whichis the main storage form of thyroid hormone. In addition a lesser number ofmitochondrial rich high cuboidal cells are also present between the follicular cellsare the parafollicular cells, containing particular Fluorogenicamines and highconcentration of alpha Glycerophosphate dehydrogenase and synthesize ahormone Thyrocalitonin which reduces the calcium level of blood.VESSELS OF THE THYROID GLAND 4ARTERIES: The thyroid has a very rich bloodsupply and its estimated bloodflow of 4-6ml/g/min exceeds even that of the kidney. The arteries supplying thethyroid gland are the Superior Thyroid Artery which is the first branch of theexternal carotid and Inferior Thyroid artery which is the branch of subclavianartery. The Thyroid Ima is a single vessel, which originates, when present, fromthe aortic arch or the innominate artery and enters the thyroid gland at the inferiorborder of the isthmus.VEINS: Three pairs of thyroid veins the superior thyroid veins drain the superiorpoles of the thyroid gland, the middle thyroid veins drain the middle of the lobes,and the inferior thyroid veins drain the inferior poles. The superior and middleHypothyroidism 13
  • 22. Shareerathyroid veins drain into the IJV’s and the inferior thyroid veins drains into theBrachiocephalic Veins posterior to the manubrium of the sternum.LYMPHATIC DRAINAGE: It has a large lymphatic drainage through whichpart of the stored Thyroglobulin may enter the circulation. Lymphatic vessels ofthe thyroid gland run in the interlobar connective tissue, often around the arteries,and communicate with a capsular network of lymphatic vessels. From here thevessels pass into prelaryngeal, pretracheal and para tracheal lymph nodes.Laterally, lymphatic vessels located along the superior thyroid veins pass to theinferior deep cervical lymph nodes. Some lymphatic vessels may drain into thebrachiocephalic lymph nodes or into the thoracic duct.NERVESUPPLY: Principal innervation of the thyroid gland derives from theautonomic nervous system. Parasympathetic fibers come from the vagus nerves,and sympathetic fibers are distributed from the superior, middle, and inferiorganglia of the sympathetic trunk. These small nerves enter the gland along withthe blood vessels. Autonomic nervous regulation of the glandular secretion is notclearly understood, but most of the effect is postulated to be on blood vessels,hence the perfusion rates of the glands.Hypothyroidism 14
  • 23. Shareera THYROID HORMONE SYNTHSESIS, METABOLISM & ACTION The syntheses of thyroid hormones are controlled at 3 differentlevels. 1. at the level of hypothalamus, by modifying TRH secretion; 2. At thepituitary level, by inhibition or stimulation of TSH secretion, and 3. At the levelof thyroidHYPO THALAMO-PITUTORY AXIS 8 Thyroid hormone synthesis is controlled by both hypothalamic andpituitary TSH secretion in a classic negative feed back loop. Low levels of T3 andT4stimulates the release of TSH and TRH. TSH stimulates the thyroid tosynthesize T3and T4. When T3and T4 levels rise sufficiently, the release of TSHand TRH is suppressed. TRH is a tripeptide pyroglutamil-histidyl-prolineamide, synthesizedby neurons in the supra optic and supra ventricular nuclei of the hypothalamus. Itis stored in the median eminence of the hypothalamus and then transported viapituitary portal venous system down the pituitary stalk to the anterior pituitarygland, where it controls synthesis and release of TSH and Prolactin. TRH stimulated TSH secretion occurs in a pulsatile fashionthroughout the 24hrs. Normal subjects will have mean TSH pulse amplitude ofabout 0.6uU/mL and an average frequency of one pulse every 1.8hrs. In additionnormal subjects show a circadian rhythm, with a peak serum TSH at night,usually between midnight 4AM. In hypothyroid patients the amplitude and thenocturnal surges are much larger than normal. TRH secretion is stimulated bydecreased serum t4 or t3, alpha adrenergic agonists, and by arginine vasopressin.Conversely, TRH secretion is inhibited by increased serum t4 or t3 and alphaadrenergic blockade.Hypothyroidism 15
  • 24. ShareeraTHYROID HORMONE SYNTHESIS 8,9 Thyroid hormones are derived from Thyroglobulin, a precursor of allthyroid hormones. It is a large glycoprotein molecule containing 5496 aminoacids, 140 tyrosil residues and about 10% carbohydrate in the form of mannose.The iodotyrosine residues are iodinated and coupled to form the active thyroidhormones. TG is synthesized on the rough ER of the follicular cells and theglycosylation occurs in the Golgi apparatus.1. Iodide transport: As iodine is a trace element, an effective mechanism ispresent for the selectively trapping iodide in the thyroid follicular cells. Iodine istaken up as an inorganic iodide; this active transport system referred to as theiodide trap. Iodide uptake by thyroid cells is dependent on membrane ATPase.The protein responsible for iodide transport, the so-called Sodium/Iodidesymporter or NIS, is located at the basolateral plasma membrane of thyrocytes.Two potential iodide transporters have been proposed: PENDRIN and the recentlycharacterized protein named AIT for Apical Iodide Transporter.2. Oxidation of iodide: Once within the follicular cell, the iodide is oxidized intoan active intermediate. Thyroperoxidase(TPO) oxidizes iodide in the presence ofH2O2.3. Organification (Iodination): The attachment of iodine to tyrosyl residues inTg produce MIT and DIT Mon iodo tyrosine and Di iodo tyrosine residues in theTG molecule.This process occurs at the apical plasma membrane-follicle lumenboundary and involves H2O2, iodide, TPO, and glycosylated Tg. All rendezvous atthe apical membrane to achieve Tg iodination.The molecule has about 132 tyrosylresidues among its two identical chains; at most, only about 1/3 of the tyrosyls areiodinated.Hypothyroidism 16
  • 25. Shareera4. Coupling: The final step in hormone synthesis is the coupling of twoconsenting iodotyrosyl residues to form iodothyronine.Two DIT form T4; one DITand one MIT form T3. Coupling takes place while both acceptor and donoriodotyrosyl are in peptide linkage within the Tg molecule.The reaction is catalyzedby TPO, required H2O2 and is stringently dependent on Tg structure.5. Storage: The thyroid hormones are stored as a part of the TG molecule in thelumen of the follicle. This TG is referred to as colloid.Secretion: When thyroid hormone is needed, Tg is internalized at the apical poleof thyrocytes, conveyed to endosomes and lysosomes and digested by proteases,particularly the endopeptidases cathepsins B, L, D and exopeptidases. After Tgdigestion, T4 and T3 are released into the circulation. Nonhormonal iodine, about70% of Tg iodine, is retrieved intrathyroidally by an iodotyrosine deiodinase andmade available for recycling within the gland.THYROID HORMONE TRANSPORT 8 The thyroid hormones, thyroxine and Triiodothyronine (T3)circulate in blood by reversibly binding to carrier proteins. The functions ofserum binding proteins are to 1) increase the pool of circulating hormones, 2)delay hormone clearance and, 3) modulate hormone delivery to selected tissuesites. Although only 0.3% or less of T3 and T4 circulates unbound, it is this freehormone fraction that is metabolically active at the tissue and cellular level. Thereare 3 major thyroid hormone transport proteins, 1. Thyroxine binding globulin(TBG) has high affinity for thyroid hormones and carries about 80% of the boundhormones. 2. Transthyretin (TTR, formerly known as TBPA) carries about 10%of T4 but little T3. 3. Albumin (HSA, human serum albumin) has relatively lowaffinity and binds up to 10% of T4 and 30% of T3.Hypothyroidism 17
  • 26. ShareeraKINETICS OF THYROID HORMONES: T4 T3 rT3Serum levels Total, ug/dL(nmol) 8 (103) 0.12 (1.84) 0.04 (0.51)Free, ng/dL(nmol) 1.5 (19) 0.28 (4.3) 0.24 (3.69)Body pool ug(nmol) 800(1023) 46 (70.7) 40 (61.5)Production rate ug/day 90 32 -Relative metabolic potency 0.3 1 0Half-life in plasma(t1/2) (days) 7 1 0.2Metabolic clearance 1 22 90rate(MCR)L/d METABOLISM OF THYROID HORMONES 8 1. Predominant pathway for Thyroid hormone metabolism isprogressive deiodination. Most plasma pool of T3 is produced from peripheralmetabolism of T4 by the deiodinase enzymes. Deiodination of the outer ring of T4produces T3, on the other hand deiodination of the inner ring of T4 producesreverse T3 (rT3), which is metabolically inert. Triodothyronines can beHypothyroidism 18
  • 32. Shareeraprogressively deiodinised to T2, T1, and T0, none of these show any biologicactivity. 2. Conjugation with sulfate or glucuronate and secretion in the bile.3. Alanine side chains of the T4 and T3 under goes oxidative deamination andtransamination to form tetraiodo thyroacetic acid (TETRAC) and tri iodothyroacetic acid (TRIAC). This transmitter formation appears to be the mode ofrenal metabolism of thyroid homones. 4. Decorboxylation gives rise to aminederivatives T3 amine and T4 amine.Hypothyroidism 19
  • 33. Shareera ROLE OF IODINE 10 Iodine is the essential raw material for the synthesis of thyroidhormones. Iodine is an indispensable component of the thyroid hormones,comprising 65% of T4s weight, and 58% of T3s. The thyroid hormones are theonly iodine-containing compounds with established physiologic significance. Toolittle of iodine causes mental retardation, goiter, hypothyroidism, and otherfeatures of the so-called iodine deficiency disorders. Too much iodine increasesthe incidence of iodine-induced hyperthyroidism especially multinodular goiters,autoimmune thyroid disease and perhaps thyroid cancer. Iodine deficiency is now recognized as a global problem with largepopulations at risk who are living in an environment where the soil has beendeprived of iodine. The mountainous regions of Europe, the Northern IndianSubcontinent, Ganges Valley in India, the extensive mountain ranges of China, theAndean region in South America and the lesser ranges of Africa are all iodinedeficient. Some countries have areas with very high iodine intake, from dietarycustom (e.g., seaweeds in Japan) or rich soil and water (e.g., a few places inChina). The burden of iodine deficiency disorders (IDD) in India is of majorproportions. Approximately 150 million people are at risk of IDD, of whom 54million have goiter, 2.2 million are cretins, and 6.6 million have milder neurologicdeficits. Small surveys conducted over the past two decades have identified IDDin 24 of the 25 states. The National Goiter Control Program was launched in 1962with iodization of salt as its primary strategy for control of IDD. The effects of iodine deficiency on growth and development can beconsidered at the various stages of life as follows,1. Iodine deficiency in the fetus--Pathogenesis of mental retardation: Iodinedeficiency in the fetus is the result of iodine deficiency in the mother. Aninsufficient supply of thyroid hormones to the developing brain may result inmental retardation. Thyroid hormone action is exerted through the binding of T3Hypothyroidism 20
  • 34. Shareerato nuclear receptors which regulate the expression of specific genes in differentbrain regions following a precise developing schedule during fetal and earlypostnatal life. Brain growth is characterized by two periods of maximal growthvelocity. The first one occurs during the first and second trimesters between thethird and the fifth months of gestation. This phase corresponds to neuronalmultiplication, migration and organization. The second phase takes place from thethird trimester onwards up to the second and third years postnatally. Itcorresponds to glial cell multiplication, migration and myelisation. The first phaseoccurs before fetal thyroid has reached its functional capacity. It is now largelyagreed that during this phase, the supply of thyroid hormones to the growing fetusis almost exclusively of maternal origin while during the second phase, thesupply of thyroid hormones to the fetus is essentially of fetal origin. In humans, T4 can be found in the first trimester coelomic fluid from6 weeks of gestational age, long time before the onset of secretion of T4 by thefetal thyroid, which occurs at the 24th week of gestation. Nuclear T3 receptors andthe amount of T3 bound to these receptors increase about six to tenfold between10 and 16 weeks, also before the secretion of hormones by the fetal thyroid.2. Iodine deficiency in the neonate: The brain of the human infant at birth hasonly reached about one third of its full size and continues to grow rapidly until theend of the second year. The thyroid hormone, dependent on an adequate supply ofiodine, is essential for normal brain. The apparent thyroidal iodine turnover ratewas much higher in young infants than in adults and decreased progressively withage. In order to provide the normal rate of T4 secretion, the turnover rate forintrathyroidal iodine must be 25-30 times higher in young infants than inadolescents and adults Iodine deficiency also causes an increased uptake of theradioiodide, resulting from exposure to nuclear radiation.Hypothyroidism 21
  • 35. Shareera3. Iodine deficiency in the child: Abnormalities in the psychoneuromotor andintellectual development of children and adults were observed.4. Iodine deficiency in the adult: Reduced mental function due tohypothyroidism effects on their capacity for initiative and decision-making werenoted. In addition to this impact to brain and neuro intellectual development,iodine deficiency at any period in life, including during adulthood, can induce thedevelopment of goiter with mechanical complications and/or thyroid insufficiency. AVAILABILITY OF IODINE SOME COMMON SOURCES OF IODINE IN ADULTS Dietary iodine Daily intake (µg)1. Dairy products 522. Grains 783. Meat 314. Mixed dishes 265. Vegetables 206. Desserts 207. Eggs 108. Iodized salt 380Other iodine sources (µg)1. Vitamin/mineral prep (per tablet) 1502. Amiodarone (per tablet) 75,0003. Povidone iodine (per mL) 10,0004. Ipodate (per capsule) 308,000 The recommended daily intake of Iodine is 150ug/day for adults, 90-120ug/d for children, and 200ug/d in pregnant women. Breast milk contains largeamounts of iodide, mainly during the first 24 hours after ingestion.Hypothyroidism 22
  • 36. Shareera PHYSIOLOGICAL ACTIONS OF THYROID HORMONES 6,7,8,9 The major function of thyroxine is to control the rate of metabolism.Cells in the body take their "cue" from thyroxine. The amount of stimulation thecells receive from thyroxine will determine how "quickly" they perform theirfunctions. Essentially all the cells in the body are target cells of thyroidhormones. The major function of the thyroid hormones is to stimulate thesynthesis of protein once they have entered the cell nucleus. Another importantfunction is to stimulate the activity of the cells mitochondria. These intracellularorganelles are the sites at which there is a controlled exchange of energy. Someenergy is conserved for the bodys functioning’s, while the remainder is dissipatedas heat. The proportion of energy devoted to each of these processes is controlledby the thyroid hormones. Cells respond to thyroid hormone with an increase in metabolicactivity. Metabolic activity, or metabolism, is a term used to describe theprocesses in the body that produce energy and the chemical substances necessaryfor cells to grow, divide to form new cells, and perform other vital functions. If we think of each cell in the body as a motor car, then thyroidhormone acts as if tapping on the accelerator pedal. Its message is "go."1. Metabolism: Thyroid hormones stimulate diverse metabolic activities most tissues,leading to an increase in Basal Metabolic Rate. Each mg raises BMR to about1000C. One consequence of this activity is to increase body heat production,which seems to result, at least in part, from increased oxygen consumption andrates of ATP hydrolysis. By way of analogy, the action of thyroid hormones isHypothyroidism 23
  • 37. Shareeraakin to blowing on a smoldering fire. A few examples of specific metabolic effectsof thyroid hormones includea) Lipid metabolism: Increased thyroid hormone levels stimulate fat mobilization,leading to increased concentrations of fatty acids in plasma. Plasma concentrationsof cholesterol and triglycerides are inversely correlated with thyroid hormonelevels.b) Carbohydrate metabolism: Thyroid Hormone’s increase the rate of GI tractabsorption of glucose and enhancement of insulin-dependent entry of glucose intocells and increased gluconeogenesis and glycogenolysis to generate free glucosec) Protein metabolism: Thyroid Hormone’s increase cellular uptake of aminoacids and incorporation of these amino acids into proteins.2. Cardiovascular system: Thyroid hormones increases heart rate, cardiaccontractility and cardiac output and also have effects on myocardium. They alsopromote vasodilatation, which leads to enhanced blood flow to many organs.3. Central nervous system: They regulate neuronal proliferation anddifferentiation, myelogenesis, neuronal outgrowth and synapse formation. Toolittle thyroid hormone and the individual tend to feel mentally sluggish, while toomuch induces anxiety and nervousness.4. Actions on skeletal muscles: Thyroid Hormone’s have direct action on muscle.They increase both the content of the plasma lemma electrogenic Na-K pump andincrease the resting membrane potential. They also increase the rate and amount ofcalcium uptake in the sarcoplasmic reticulum, there by increasing calciumavailability on stimulation. They influence the isotope availability of myosin andincrease myosin ATP ase activity. Thyroid Hormone’s stimulate increased boneturnover, increasing bone resorption and to a lesser degree bone formation.Hypothyroidism 24
  • 38. Shareera5. Kidneys: Thyroid Hormone’s 1. increases Nitrogen excretion, 2. increases urinevolume by raising the general metabolism and thus increasing nitrogenous endproducts which acts as diuretics.6. Gastrointestinal system: Thyroid hormones stimulate gut motility.Table 1.1showing the physiological actions of thyroid hormones on differentsystems: S.no System or Event Actions of T3/T4 Affected 1 Basal Increases basal metabolic rate. Metabolism Increases body temp (calorigenesis). Increases appetite. 2 Carbohydrate, Promotes glucose catabolism for energy. lipid & protein Stimulates protein synthesis. Metabolism Increases lipolysis. Enhances cholesterol excretion in bile. 3 Heart Promotes normal cardiac function. 4 Nervous System Promotes normal neuronal development in fetus and infant. Promotes normal neuronal function in adult. Enhances effects of sympathetic nervous system. 5 Musculoskeletal Promotes normal body growth and maturation of skeleton. Promotes normal function and development of muscles. 6 Reproductive Promotes normal female reproductive ability and lactation.Hypothyroidism 25
  • 39. Nidana NIDANA 6,7,10,11 Hypothyroidism results from inadequate production of thyroidhormone. Any structural or functional defects of thyroid gland that significantlyimpairs its output of hormones will lead to the hypo metabolic state ofhypothyroidism.Hypothyroidism may be classified as1. Primary (thyroid failure), Hypothyroidism caused by the inability of the thyroid gland to makeT3 and T4 is called primary hypothyroidism.2. Secondary (due to pituitary TSH deficit), and 3. Tertiary (due to hypothalamicdeficiency of TRH) Since the thyroid gland is regulated by the pituitary gland andhypothalamus, disorders of these organs can cause the thyroid gland to producetoo little thyroid hormone as well. This condition is called secondaryhypothyroidism.4. Peripheral resistance to the action of thyroid hormones.1. PRIMARY: Primary hypothyroidism is a condition of decreased hormoneproduction by the thyroid gland. It accounts for 95 per cent of hypothyroidismcases, and only 5 per cent or less are suprathyroid in origin. The most commoncause of primary hypothyroidism isi). iodine deficiency ii). AITD’s. iii). Drugs; iv). Iatrogenic; v). CongenitalTransient hypothyroid includes silent and part partum thyroiditis.Hypothyroidism 26
  • 40. Nidana1. IODINE DEFICIENCY: iodine very essential for the production of TSH.When dietary iodine intake is inadequate for thyroid hormone synthesis, the serumT4 level initially falls and a number of processes ensue to restore adequate thyroidhormone production. The pituitary gland senses low levels of circulating T4 andreleases more TSH.2. DRUGS: Certain drugs can block hormone synthesis produce Hypothyroidism.The most important drugs causing hypothyroidism are: lithium carbonate, para-amino salicyclic acid, amiodarone, sulfonamides and phenylbutazona.3. AITD’s: The body recognizes the thyroid antigens as foreign, and a chronicimmune reaction ensues, resulting in lymphocytic infiltration of the gland andprogressive destruction of functional thyroid tissue. Up to 95% of affectedindividuals have circulating antibodies to thyroid tissue. Antimicrosomal orantithyroid peroxidase (anti-TPO) antibodies are found more commonly thanantithyroglobulin antibodies (95% vs 60%). These antibodies may not be presentearly in the disease process and usually disappear over time. In situations where the immune system no longer treats tissues ofthe host as normal conditions of the body but reacts against them as it worksagainst a foreign tissue the ensuing disease is known as autoimmune disorders.Thyroid autoimmune diseases are a group of autoimmune disorders, which arecharacterized by circulating antibodies and lymphocytes infiltration of their tissuesof particular organs.4. IATROGENIC: The most common cause of hypothyroidism is destruction ofthe thyroid gland by disease or as a consequence of vigorous ablative therapies tocontrol thyrotoxicosis.Hypothyroidism 27
  • 41. Nidana5. SURGERY AND RADIATION: It is an important cause of hypothyroidism inpatients who undergo Total or subtotal thyroidectomy for Graves disease ormultinodular goiter. External irradiation (for head and neck neoplasms, breastcancer, or Hodgkin disease) and Postradioactive iodine (I-131) therapy forhyperthyroidism may result in hypothyroidism.Infiltrative diseases of the thyroid: Progressive systemic sclerosis (scleroderma)can cause hypothyroidism from immune and non-immune mechanisms. The non-immune mechanism is due to severe fibrosis involving the thyroid gland. Theseconditions may also cause central (secondary) hypothyroidism from pituitaryinfiltration. Hypothyroidism due to sarcoidosis is rare.2. SECONDARY HYPOTHYROIDISM: In adults, it is almost always due topituitary disease. These patients often have other associated pituitary dysfunction.It may also be seen due to autoimmunity against thyrotrophs (cells that produceTSH).3. TERTIARY HYPOTHYROIDISM: is due to hypothalamic diseases likesarcoidosis, tumours etc.4. THYROID HORMONE RESISTANCE SYNDROMEIn this condition, there is a decrease in sensitivity of peripheral tissue receptors tothyroid hormones.Hypothyroidism 28
  • 42. Samprapti SAMPRAPTI 12 Hypothyroidism is a clinical syndrome resulting from a deficiency ofthyroid hormones which in turn results in a generalized slowing down ofmetabolic process. The clinical manifestations of the hormone lack depend on the agewhen it first appears. It is seen in 3 groups of patients, in the new born termed ascretinism or congenital hypothyroidism, in the childhood or adolescence known asjuvenile hypothyroidism, in the adult usually termed as myxedema. CONGENITAL HYPOTHYROIDISM 12, 15 In the newborn it is known as congenital hypothyroidism,previously called as cretinism. The French term meaning ‘’ Christ like’’ and wasapplied to those unfortunates because they were considered to be incapable ofsinning.10The most common causes are agenesis and dysgenesis.Ectopic thyroid gland: Hypothyroidism may result from failure of thyroid gland todescend during embryonic development from its origin at the base of the tonguedo its usual size in the lower anterior neck which results in ectopic thyroid glandthat functions poorly. Placental transfer to the embryo TSH- RAb( block) from a motherwith hashinoto’s thyroiditis may result in agenesis of thyroid gland and“athyreotic cretinism”. Rare causes include administration of iodides, antithyroid drugs or radioactiveiodine for thyrotoxocosis.Hypothyroidism 29
  • 43. Samprapti The symptoms of congenital hypothyroidism include jaundice poorfeeding, hoarse cry, umbilical hernia, constipation, somnolence, delay in reachingnormal mile stones of development, short stature coarse features with protrudingtongue, broad flat nose, widely set eyes, impaired mental development and markedretardation of none maturation. Absence of proximal tibial and distal femoralepiphysis strongly suggests congenital hypothyroidism. Since the disorder causes severe mental retardation, unless promptlytreated, since it is not always possible to make a clinical diagnosis at birth,universal screening of; all neonates is now common in many countries like US andUK. This is normally based on TSH assay of heel prick or cord blood. 11,12Pendred’s syndrome16: Pendred’s syndrome is caused by a genetic defect thatlimits the incorporation of iodine into thyroid hormone, which wrecks the structureof the hormone it is characterized by overt or sub clinical hypothyroidism, goiterand mild to moderate sensorineural hearing impairment. JUVENILE HYPOTHYROIDISM 13 Atrophy of the gland or defective function of thyroid gland,thyroiditis, and secondary pituitary deficiency are the common causes. It ischaracterized by dwarfism with delayed skeletal maturation, apathy physical andmental torpor, constipation slow teething, and large tongue pot belly withumbilical hernia deep voice, myxedema and delayed sexual development. ADULT HYPOTHYROIDISM 7,18,12 It is also called as myxedema. 95%of the cases are due to primaryhypothyroidism, thyroid gland malfunction either by structural or functionalimpairment. The main causes are,Hypothyroidism 30
  • 44. SampraptiIODINE DEFICIENCY14 : The main causes of primary hypothyroidism which may be attributeto dietary factors or to inefficient iodine conservation due to intra thyroid andperipheral tissue deiodinase enzyme deficiency is the main cause forhypothyroidism. Impaired transport of iodine, deficient peroxidase with impairedoxidation of iodinate into iodine and failure to incorporate, impaired coupling ofiodinated tyrosines to T3 and T4 these all cause impaired production of thyroidhormones presumably results in increased TSH production and consequently inhypothyroidism.AUTOIMMUNE THYROID DISORDERS 17, 12 Immunologic defense against foreign substances involvesmacrophages that ingest and digest the foreign material and present peptidefragments on the cell surface in association with a class II protein coded by theHLA-DR region of the MHC gene complex. This complex is recognized by aT cell receptor on a CD 4 helper T cell, which stimulates the release of cytokinessuch as interleukin-2(IL-2).these cytokines amplify the response by inducingT cell activation and division, induction of killer cell activity in CD8 suppressorcells, and stimulation of antibody formation against the foreign antigen by Blymphocytes. Eventually the activation process is muted by the activation of CD8suppressor cells. There are three major thyroidal auto antigens: thyroglobulin (Tg),thyroxyperoxidase (TPO) and the TSH receptor (TSH-R) auto antibodies to theseantigens are useful markers for the presence of auto immune thyroid diseases.HASHIMOTO’S THYROIDITIS 12,22 Characterized by the destruction of thyroid cells by various cellsand antibody mediated immune processes. It is a histologic diagnosis firstdescribed by Hakaru Hashimoto, a Japanese surgeon.Hypothyroidism 31
  • 45. Samprapti Genetic factors most likely play some role in autoimmunethyroiditis. For example, many patients with Hashimotos thyroiditis express agene called the Fas gene, which interacts with thyroid cells and trigger a processcalled apoptosis, in which the cells begin to self-destruct. The Fas gene is linked togenes that regulate tumor necrosis factors, which are products of the immunesystem that trigger a damaging inflammatory response in cells. In Hashimotos thyroditis TSH-R blocking immunoglobulins bind tothe receptor and block TSH function causing hypothyroidism. There is markedlymphocytic infiltration of the thyroid with germinal centre formation, atrophy ofthe thyroid follicles accompanied by oxyphyl metaplasia, absence of colloid andmild to moderate fibrosis. In the early stages of hashimoto’s thyroditis, the thyroidmay produce too much thyroid harmone but as the thyroid is slowly destroyed thepatients thyroid harmone levels drop, at the latter stages it may become atrophicthyroiditis.3. IATROGENIC CAUSES12: The most common cause of hypothyroidism is destruction of thethyroid gland by disease or as a consequence of vigorous ablative therapies tocontrol thyrotoxicosis. Thyroid destruction secondary to radioactive iodine orsurgery, as treatment for hyperthyroidism can also cause hypothyroidism. Patientswho have been treated for a hyperthyroid condition (such as Graves disease) andreceived radioactive iodine may be left with little or no functioning thyroid tissueafter treatment. Similarly, removal of the thyroid gland during surgery will befollowed by hypothyroidism.4. DRUGS18:Certain drugs can block hormone synthesis and produce hypothyroidism.1. Antithyroid drugs (eg, propylthiouracil, methimazole, carbimazole).Hypothyroidism 32
  • 46. Samprapti2. Lithium inhibits thyroidal iodide transport and release of T4 and T3 and maycause hypothyroidism.3. Amiodarone has large iodine content, and can cause hypothyroidism byinhibiting peripheral T4-to-T3 conversion.4. Interferon alpha may induce thyroid autoimmunity in 10-20% of patients. Itleads to production of anti-Tg, anti-TPO, and TSH receptor-blocking antibodies.5. Phenytoin, carbamazepine, and rifampin increase the hepatic clearance oflevothyroxine by induction of cytochrome P-450 enzymes. This can lead to anincreased levothyroxine requirement in patients on replacement therapy. Hypothyroidism may be transient and require no or only short-termtherapy, as in patients with painless thyroiditis or postpartum thyroiditis.5. THYROID HORMONE RESISTANCE SYNDROME 19,14 Thyroid hormone resistance has only been described in relativelyrecent times. In this, there is a decrease in sensitivity of peripheral tissue receptorsto thyroid hormones. The clinical syndrome of hypothyroidism ensues, despiteexcess thyroid hormones in the circulation. In contrast to this, a far rarer conditionhas been described when the pituitary gland does not sense the circulating thyroidhormones, inhibiting the feedback mechanism so that the pituitary gland continuesto secrete an excess amount of TSH, which, in turn, stimulates the thyroid gland,producing an excess amount of T3 and T4. This is called selective pituitaryresistance and can produce hyperthyroidism. The defect lies in a mutation of thethyroid receptor gene. About 300 families with these disorders have beenidentified but the population prevalence is difficult to tell.2. CENTRAL (SECONDARY/TERTIARY) HYPOTHYROIDISM 12,17 Pituitary or Hypothalamic disease can also lead to condition ofhypothyroidism. If for some reason the pituitary gland or the hypothalamus isunable to signal the thyroid and instruct it to produce thyroid hormones, aHypothyroidism 33
  • 47. Sampraptidecreased level of circulating T4 and T3 may result, even if the thyroid gland itselfis normal. If this defect is caused by pituitary disease, the condition is called"secondary hypothyroidism." If the defect is due to hypothalamic disease, it iscalled "tertiary hypothyroidism."1. Loss of functional tissue: 1. Tumors (Pituitary adenoma, Craniopharyngioma,Meningioma, Dysgerminoma, Glioma, Metastases), 2. Trauma(surgery,irradiation, head injury), 3. Vascular (Ischemic necrosis, Hemorrhage, Stalkinterrruption, Aneurysm of internal carotid artery), 4. Infections (Abcess,Tuberculosis, Syphilis, Toxoplasmosis), 5. Infiltrative (Sarcoidosis, Histiocytosis,Hemochromatosis),6.Chronic lymphocytic hypophysitis, 7. Congenital (Pituitaryhypoplasia, Septooptic dysplasia, Basal encephalocele).2. Functional defects in TSH biosynthesis and release: 1. Mutations in genesencoding for TRH receptor, TSHß, or Pit-1, 2. Drugs: Dopamine;Glucocorticoids; L-thyroxine withdrawal.Hypothyroidism 34
  • 48. Clinical features CLINICAL FEATURES OF HYPOTHYROIDISM12, 17,18 Hypothyroid disease is one of the most underdiagnosed and mis-diagnosed diseases as its clinical features for hypothyroidism are notorious.Hypothyroidism doesn’t have any characteristic symptoms. There are nosymptoms that people with hypothyroidism always have and many symptoms ofhypothyroidism can occur in people with other diseases. The manifestations ofhypothyroidism are as below.1. METABOLIC CHANGES IN HYPOTHYROIDISM: 1. Weight gain: usually only 5-10lbs, rarely a cause of morbid obesity, decreased oxygen consumption- per unit body surface area. 2. Cold intolerance: decreased rate of heat production. 3. Hyperlipidemia(cholesterol, tryglycerides, phospholipids) – a decrease in cholesterol synthesis with a greater decrease in its removal results in hypercholesterolemia which predisposes to atherogenesis. 4. Hyperhomocystenemia: predisposes to increased atherogenesis. 5. Hypoglycemia: Rare, suspected in secondary hypothyroidism. 6. Effusions: Increased interstitial fluid and increased CSF protein. Increased albumin synthesis and increased capillary permeability to albumin. 7. Growth retardation: 8. Decreased in metabolism of drugs, hormones, enzymes.2. CUTANEOUS MANIFESTATIONS OF HYPOTHYROIDISM: 1. Dry, rough, and thick skin covered with fine superficial scales especially prominent over elbow, knees and heels.Hypothyroidism 35
  • 49. Clinical features 2. Pale waxy, cool skin, sometimes with a yellow tint. 3. Periorbital edema: mucopolysachharide deposition with increased osmatic effect and fluid accumulation. 4. Coarse, brittle, dull hair can’t hold wave. 5. Alopecia: involving scalp, lateral third of eyebrows or generalized (sec hypothyroidism) 6. Brittle nails with transverse striations 7. Lack of sweating- atrophy of sweat glands. Histological features include thinning of epidermis withhyperkeratosis of stratum corneum which is infiltrated withmucopolysachhaarides, hyaluronic acid and chondrantin sulfate. It is found mainlyin the papillary dermis around the blood vessels and the cutaneous appendages.3. NEUROMUSCULAR SYSTEM OF HYPOTHYROIDISM: 1. Sensory complaints such as tingling in a stock glove distribution or painful dysesthesias. 2. Carpal tunnel syndrome: 3. Generalized peripheral neuropathy with upper extremities disproportionately involved. 4. Myasthenia gravis 5. Muscle stiffness, aching, myalgias, cramps, weakness and fatigue. 6. Slow muscle stretch reflex with delay in both contraction and relaxation phases.Hypothyroidism 36
  • 50. Clinical features 7. Myoedema 8. Hoffman syndrome: Muscle enlargement with normal or reduced strength. 9. Elevation of Creatine phospokinase(CPK), the dominant iso enzyme being MM type indicative of skeletal muscle course.4. NEUROPSYCHIATRIC: 1. Disturbances in concentration, memory, and intellect. 2. Lack of ambition 3. Slow thought, and slow speech. 4. Depression, agitation, psychosis (myxedema madness). 5. Drowsiness, lethargy, increased need for sleep. 6. Hallucinations (late) 7. Myxedema coma (late)5. CARDIAC SYSTEM IN HYPOTHYROIDISM: 1. Pericardial effusion-usually asymptomatic. 2. Exertional dyspnoea, fatigue, decreased exercise tolerance. 3. Pulse<81 or frank bradycardia. 4. Normal blood pressure, hypertension and sometimes hypotension. 5. Hyper cholstrelemia and hyper triglyceridemia. 6. Hyperhomocystenemia.Hypothyroidism 37
  • 51. Clinical features 7. Coronary artery disease- symptoms modified by decreased cardiac oxygen consumption and decreased work load; therefore low frequency of angina or infarction. 8. Ventricular septal hypertrophy 9. Cardiac dilatation 10. Congestive heart failure-uncommon in absence of underlying heart disease and in severe hypothyroidism.6. RESPIRATORY SYSTEM IN HYPOTHYROIDISM: 1. Pleural effusion 2. Reduced max. Breathing capacity and diffusing capacity 3. Upper airway obstruction from thyroid enlargement or elongated tongue. 4. Obstructive sleep apnea due to obstruction of upper air way and in some cases altered respiratory drive. 5. Alveolar hypoventilation and co2 retention due to depression of both respiratory muscles and the hypoxic and hypercapnic ventilatory drive. 6. Prolonged theophylline half life predisposing to toxicity.7. HEMATOLOGICAL SYSTEM IN HYPOTHYROIDISM: 1. Anemia: • Normochromic normocytic. • Hypochromic microcytic due to iron deficiencyHypothyroidism 38
  • 52. Clinical features • Macrocytic due to vit B12 deficiency, folate deficiency or Thyroid hormone deficiency, 2. Bleeding: abnormal platelet function Deficiencies of factors,- VII, VIII, IX, XI.8. CATECHOLAMINES IN HYPOTHYROIDISM: 1. Ptosis. 2. Hypothermia: failure of cold or sepsis to increase thermo genesis due to a lack off response to catecholamine. 3. Normal secretion and plasma epinephrine levels. 4. Elevated secretion of plasma norepinephrine levels: 5. Decreased plasma cAMP response to epinephrine. 6. Decreased B-adrenergic receptors. 7. Bradycardia.9. GASTRO INTESTINAL SYSTEM IN HYPOTHYROIDISM: 1. Weight gain: modest but marked increase in weight almost a feature. 2. Anorexia 3. Decreased intestinal motility- Gastroparesis, constipation, gaseous distension, paralytic ileus, megacolon, 4. Ascitis: unusual to be clinically detectable although increased fluid is common.Hypothyroidism 39
  • 53. Clinical features 5. Autoimmune gastritis with achlorhydria and failure to absorb vitB12, and failure to absorb vitB12. 6. Elevated transaminase levels due to delayed clearance.10. RENAL SYSTEM AND ELECTROLYTES: 1. Fluid retention-a large extra vascular accumulation of albumin due to enhanced vascular permeability and altered endothelial cell bodies and a lack of compensatory increase in the flow of lymph. 2. Excessive urinary sodium loss 3. Decreased plasma volume 4. Increase in ADH. 5. Hyponatremia. 6. Increased renal vaso constriction. 7. Decrease in glomerular filtration and renal plasma flow. 8. Increase in plasma rennin angiotension II but decrease in plasma aldosterone.11. REPRODUCTIVE SYSTEM IN HYPOTHYROIDISM: 1. Menorrhagia or meno-metrorrhagia-anovulatry cycles, endometrial proliferations, breakthrough bleeding. 2. Amenorrhoea in primary or secondary hypothyroidism; however there is an increased incidence of hashimoto’s thyroiditis with turner’s syndrome. 3. Galactorrhoea seen in primary or secondary hypothyroidism.Hypothyroidism 40
  • 54. Clinical features 4. Decreased fertility and increased abortions, still births and prematurity. 5. Delayed puberty in both sexes. 6. Van Wyk-Grumbach syndrome-precoceous puberty, galctorrhea, sella enlargement in juvenile hypothyroidism 7. Diminished libido, impotance and conflicting data regularly testicular functions.Hypothyroidism 41
  • 55. Pathology PATHOLOGY OF HYPOTHYROIDISM 6,18,20,21 The characteristic pathologic finding in hypothyroidism is a peculiarmucinous nonpitting edema (myxedema), which is most obvious in the dermis butcan be present in many organs. The myxedema is due to accumulation ofhyaluronic acid and other glycosaminoglycans in interstitial tissue; thesehydrophilic molecules attract much water. The deposits of glycosaminoglycanshave been related to loss of the inhibitory effects of thyroid hormone on thesynthesis of hyaluronate, fibronectin and collagen by fibroblasts. The skin is distinctly abnormal. There is hyperkeratotic pluggingof sweat glands and hair follicles. The dermis is edematous, and the collagenfibers are separated, swollen, and frayed. Skeletal muscle cells are swollen andappear grossly to be pale and edematous. Alternatively, the normal striations arelost, and degenerative foci are seen in the cells. The heart may be dilated andhypertrophied. Interstitial edema and an increase in fibrous tissue are present. Theindividual muscle cells may show the same changes seen in skeletal muscle. Theserous cavities may all contain abnormal amounts of fluid with normal or highprotein content. The liver may appear normal or may show evidence of edema. Themitochondria tend to be spherical and their limiting membranes smooth, whereasthose of the liver in thyrotoxicosis vary in shape and have wrinkled outermembrane. The skeleton may be unusually dense on radiographic examination. Inchildren, bone maturation is usually retarded, and typical epiphyseal dysgenesis ofhypothyroidism is present. The brain may show atrophy of cells, gliosis, and foci ofdegeneration. There is neuronal hypoplasia, retarded myelination, and decreasedvascularity.Hypothyroidism 42
  • 56. Pathology The blood vessels often show prominent atherosclerosis. In theintestinal tract there is an accumulation of mast cells and interstitial mucoidmaterial, especially near the basement membrane. The smooth muscle cells may show lesions similar to those seen inskeletal muscle. The mucosa of the stomach, small bowel, and large bowel may beatrophic. The rest of the gastrointestinal tract, especially the colon, may be muchdilated (myxedema megacolon). The uterus typically has a proliferative oratrophic endometrium in premenopausal women. The kidney is grossly normal. Microscopic studies showedthickening of the glomerular and tubular basement membranes, proliferation of theendothelial and mesangial cells, intracellular inclusions, and extracellulardeposition of amorphous material with characteristics of acidmucopolysaccharides. Pituitary fossa enlargement and pituitary tumors are observed incongeneatl hypothyroidism. In pituitary hypothyroidism the pituitary may bereplaced by fibrous and cystic structures, granulomas, or neoplasia. The adrenalsmay be normal or their cortex may be atrophied, and is thought to be ofautoimmune etiology. The testes may show Leydig cells with involutionary nucleus andcytoplasm, hyalinization, or involution of the tubular cells, and proliferation ofintertubular connective tissue in hypothyroidism with onset before puberty.Hypothyroidism 43
  • 57. Sick euthyroid syndrome SICK EUTHYROID SYNDROME ( SES)12 Several systemic illnesses can upset thyroid hormone secretion,transport and/or metabolism. Thus, biochemical assessment of the thyroid statecan vary widely without there being an intrinsic problem with the gland. Thissituation has been called sick euthyroid syndrome (SES). A very high percentage (40-70 per cent) of patients with a non-thyroid illness may have one or more abnormalities of the thyroid function tests.The severity of illness is usually more important than its nature. This can bedivided into three main types - low T3 state, low T3 - T4 state and a high T4 state,all with normal TSH. The common conditions encountered in day-to-day clinicalpractice are caloric deprivation (usually secondary to systemic illness), liverdisease, poorly controlled diabetes mellitus, nephrotic syndrome, chronic renalfailure, systemic infection and psychiatric disorders. The vast majority is euthyroidand requires no specific thyroid related therapy. Many pharmacological agents affect the results of the thyroidfunction tests, either by acting on the thyroid gland or by altering the peripheraldistribution and metabolism of the hormone. Common drugs that alter the thyroidhormone indices are glucocorticoids, dopamine, androgens, salicylates, frusemide,heparin, amiodarone (discussed later) and propranolol. Some of these effects canbe exploited in clinical practice, for example, the use of propranolol andcorticosteroids in thyrotoxic crisis.Hypothyroidism 44
  • 58. Investigations INVESTIGATIONS 22,18 The function of the thyroid gland may be evaluated in manydifferent ways. (l) Tests of thyroid hormones in blood, (2) evaluation of thehypothalamic pituitary thyroid axis, (3) assessment of iodine metabolism, (4)estimation of gland size, (5) thyroid biopsy, (6) observation of the effects ofthyroid hormones on peripheral tissues and (7) measurement of thyroid autoantibodies.1. TESTS OF THYROID HORMONES IN BLOOD: Thyroid hormones are transported in serum bound to carrierproteins. The 0.04% of T4 and 0.4% of T3 that is free is the biologically activeform. Measurement of thyroid hormone levels is done as follows:1. Serum Total Thyroxin (T4, normal value 4-12 microg/dL). This test measuresboth free and bound T4. In healthy patients (without abnormalities in thyroidbinding proteins), total T4 reflects thyroid hormone activity.2. Serum Total Triiodothyronine (T3, normal values 80-200 ng/dL). This testmeasures both free and bound T3.TBG: Thyroid Binding Globulin (TBG) is the major thyroid hormone bindingproteins. The level of TBG in the blood is not routinely measuredFree Thyroid Hormone: As the free thyroid hormone is the biologically active, itis important that a measurement of free thyroid levels be done.2. EVALUATION OF THE HYPOTHALAMICPITUITARY THYROIDAXISThe TRH stimulation test is rarely needed now because of improved TSH assays.TSH: Serum TSH is the best SCREENING test for the diagnosis ofhypothyroidism or hyperthyroidism in healthy ambulatory individuals. It is theinitial test done to assess thyroid function and the only test needed if it is normal.Hypothyroidism 45
  • 59. InvestigationsHowever, if hypothalamic/pituitary disease is suspected or significant alterationsin binding proteins are expected, then a measure of free T4 (index or direct assay)is needed together with TSH.In most healthy patients, TSH values are 0.5-1.5mU/L, but reference ranges vary up to 5 mU/L. A modern or delayed rise may be seen in patients with hypothalamicdisease and hypothyroidism. Measurement of TSH has become the most sensitive,most convenient and most specific test for the diagnosis of both hyperthyroidismand hypothyroidism. TSH levels also rise for a week and then fall in conditions ofnon-thyroidal illness, including surgery, trauma or infection.3. IODINE METABOLISM & BIOSYNTHETIC ACTIVITY Radioactive iodine allows assessment of the turnover of iodine bythe thyroid in vivo. Iodine 123 is the ideal isotope for this purpose.4. ESTIMATION OF GLAND SIZE:THYROID IMAGING1. Radionuclide imaging: Radionuclide scan provide information about the size and shape ofthyroid gland and the geographic distribution of functional activity in the gland.Functioning thyroid nodules are called ‘’hot’’ nodules and nonfunctioning onesare called ‘’cold’’ nodules.2. Fluorescent scanning: The iodine content can be determined and an image of thyroid glandcan be obtained by fluorescent scanning without administration.THYROID ULTRA SONOGRAPHY: It is particularly useful for measuring the size of the gland orindividual nodules. It is useful for differentiating solid from cystic lesions.Hypothyroidism 46
  • 60. InvestigationsTHYROID MAGNETIC RESONANCE IMAGING: MRI provides an excellent image of the thyroid gland, includingposterior or substernal extension of a goiter or malignancy.5. THYROID BIOPSY:Fine Needle Aspiration Biopsy: Fine-needle aspiration (FNA) biopsy is theprocedure of choice to evaluate suspicious nodules and has proved the best methodfor the differentiation of benign from malignant thyroid diseases.6. OBSERVATION OF THE EFFECTS OF THYROID HORMONES ONPERIPHERAL TISSUES:BMR: it is raised in hyperthyroidism and decreased in hypothyroidism.Tendon reflexes: particularly ankle jerk and knee jerk are tested. The relaxation isquite slow in hypothyroidism.Serum cholesterol is usually lowered in hyperthyroidism and elevated inhypothyroidism.7. THYROID AUTO ANTIBODIES:The diagnosis of autoimmune hypothyroidism is usually confirmed by thepresence of particular antibodies in the blood.1. Thyroglobulin antibody ( Tg Ab)2. Thyroperoxidase antibody (TPO Ab)3. TSH receptor antibody either stimulating or inhibiting (TSH-R Ab(stim) andTSH-R Ab(block)).It is measured by Heamagglutination, ELISA or RIA. These tests will clarify thecause of illness.Hypothyroidism 47
  • 61. Complications COMPLICATIONS 13,17,20Untreated hypothyroidism can lead to a number of health problems:Goiter: Constant stimulation of the thyroid to release more hormones may causethe gland to become larger — a condition known as goiter. Hashimotos thyroiditisis one of the most common causes of a goiter. Although generally notuncomfortable, a large goiter can affect the appearance and may interfere withswallowing or breathing.Heart problems: Hypothyroidism may also be associated with an increased riskof heart disease, primarily because high levels of low-density lipoprotein (LDL)cholesterol — the "bad" cholesterol — can occur in people with an underactivethyroid. Even subclinical hypothyroidism, a more benign condition than truehypothyroidism, can cause an increase in total cholesterol levels and impair thepumping ability of the heart. Hypothyroidism can also lead to an enlarged heartand heart failure.Mental health issues: Depression may occur early in hypothyroidism and maybecome more severe over time. Hypothyroidism can also cause slowed mentalfunctioning.Myxedema. This rare, life-threatening condition is the result of long-term,undiagnosed hypothyroidism. Its symptoms include intense cold intolerance anddrowsiness followed by profound lethargy and unconsciousness. A myxedemacoma may be triggered by sedatives, infection or other stress on the body.Birth defects: Babies born to women with untreated thyroid disease may have ahigher risk of birth defects than do babies born to healthy mothers. These childrenare more prone to serious intellectual and developmental problems.Infants with untreated hypothyroidism present at birth are also at risk of seriousproblems with both physical and mental development.Hypothyroidism 48
  • 62. Goiter GOITRE 23,21,16 The term goiter is derived form the French word ‘goitre’ (latin-gutter) –means throat. We use the term goiter to denote enlargement of the thyroidglandirrespective of its cause.Goiter is classified as follows-1. Simple goiter-i) diffuse hyperplastic goiter, ii)nodular goiter, iii)colloid goiter. .2. Toxic goiter- i) diffuse toxic goiter, ii) toxic nodular goiter, iii) toxic nodule.3. Neoplastic goiter- i) benign tumours, ii) malignant tumours.4. Thyroiditis - i) hashimoto’s thyroiditis, ii)subaacute thyroiditis, iii) reidelsthyroiditis.Some of them are explained below.Simple goiter: results from TSH stimulation, which in turn results frominadequate thyroid hormone synthesis. Iodine deficiency was the most commoncause for endemic goiter in low iodide intake areas. Iodine deficiency causesimpaired hormone synthesis and, increase in TSH secretion which induces diffusethyroid hyperplasia followed by development of new focal or nodular hyperplasia.Goiter may be seen in some families; inborn errors in metabolism cause lowthyroxine levels which leads to raise in TSH production and causing hyperplasiaof the follicular cells. Goitrogens like lithium carbonate and some vegetable food stuffssuch as goitrin, found in certain roots and seeds; and cyanogenic glycosides, foundin cassava and cabbage, that release thiocyanates which may cause goiterparticularly in the presence of iodide deficiency. Phenols, phthalates, pyridines,Hypothyroidism49
  • 63. Goiterand polyaromatic hydrocarbons found in industrial waste water are alsogoitrogens. If the thyroid is markedly enlarged it can cause tracheal oresophageal compression. Substernal goiter may obstruct the thoracic inlet.Pemberton’s sign refers to symptoms of faintness with evidence of facialcongestion and external jugular vein obstruction when the arms are raised abovethe head.Nontoxic multi nodular goiter (MNG): Iodine deficiency, Genetic, Autoimmune and Environmental causesinfluence the pathogenesis of the disease. Histology reveals hyper cellular regionsto cystic areas filled with colloid. Most nodules within the colloid are polyclonalin origin, suggesting a hyper plastic response to locally produced growth factorsand cytokines. MNG’s are usually extraordinarily large and develop fibrotic areasthat cause compression. Sudden pain in MNG, hoarseness reflecting laryngealnerve involvement suggests malignancy.Toxic MNG: It is similar to that of notoxic MNG but major difference being thepresence of functional autonomy in toxic MNG. The clinical presentation includessubclinical hyperthyroidism or mild thyrotoxicosis.Benign thyroid nodules: These include focal areas of chronic thyroiditis, a dominant portionof a MNG, a cyst involving thyroid tissue, para thyroid tissue, or thyroglossal ductremnants, and agenesis of one lobe of thyroid, with hypertrophy of other lobe.Hypothyroidism50
  • 64. GoiterBenign neoplasms include follicular adenomas such as colloid or macrofollicularadenomas, fetal adenomas and embryonal adenomas.Hyper functioning solitary nodule: It is referred to as toxic adenoma due to functional effects ofmutations that stimulate the TSH R signaling pathway.THYROID CANCER Radiation exposure increases the risk of malignant thyroid nodules,which predisposes to chromosomal breaks, presumably leading to geneticrearrangement and loss of tumor suppressor genes. Papillary carcinoma ofthyroid gland usually presents as a nodule that is firm, solitary, cold on isotopescan, solid on thyroid ultra sound, and clearly different from the rest of the gland.It is diagnosed by the presence of laminated calcified spheres called ‘’psammomabodies’. They grow very slow and remain cofined to the thyroid gland and locallymph nodes for many years. Follicular carcinoma is somewhat more aggressivethan papillary carcinoma. These tumours often retain the ability concentrateradioactive iodine; synthesize thyroglobulin and T3, T4. Medulalary carcinomais a disease of Ccells, with a prominent feature, calcification.Thyroiditis:i), Hashimoto’s thyroidits is an immunological disorder in which lymphocytesbecome sensitized to thyroidal antigens and auto antibodies are formed that reactwith antigens. Destruction of the thyroid gland results in a fall in serum T3 and T4and a raise in TSH with thyroid gland enlargement.ii) Subacute thyroiditis (also called de Quervains thyroiditis) is thought to becaused by a viral infection and often is associated with viral sore throat. Theviruses implicated are influenza, echo, adeno and Coxsackie virus. Some ofthese patients eventually develop autoimmune thyroid disease. A characteristicclinical feature is pain in the region of the thyroid gland with or without fever. TheHypothyroidism51
  • 65. Goitergland is firm and tender to palpation.Histologically, the cells differ from Hashimotos thyroiditis by their patchydistribution. Affected follicles are infiltrated by mononuclear cells with partial orcomplete loss of colloid. The follicular changes may progress to granuloma withmultinuclear giant cells. When the disease process subsides, an essentially normalhistological appearance is restored.iii) Postpartum thyroiditis Postpartum thyroiditis is recognised as anautoimmune thyroid disease (AITD) presenting three to six months after givingbirth, with a transient phase of destruction followed by a period of primaryhypothyroidism and eventual return to a euthyroid state within a year.A painlessgoitre on clinical examination and a positive result for thyroid microsomalantibody in immunological screening are usually found.iv) Silent or painless thyroiditis is that form of AITD where there is no pain overthe thyroid area. The underlying mechanism is autoimmune dysregulation withextensive lymphocyte infiltration, presence of plasma cells and circulatingautoantibodies. The course is mostly benign and self-limited.v) Reidels thyroiditis (chronic sclerosing thyroiditis) is very rare. A very hard,painless goitre is usual and this can be associated with fibrosis elsewhere(retroperitoneal or mediastinal fibrosis).vi) Infective: Acute pyogenic (suppurative) thyroiditis is fortunately rare. Thecommonest infective organism is Staphylococcus aureus. Usually the infection isfrom a septic focus outside the thyroid gland. Surgical drainage is indicated whenpus is present. It is characterised by excruciating tenderness over the thyroid areaassociated with systemic symptoms. Other rare infective causes of thyroid diseaseare tuberculosis, coccidiodomycosis and pneumocystis. Tuberculous orPneumocystis carinii infection could indicate an acquired immunodeficiency stateas the underlying diseaseHypothyroidism52
  • 66. Galaganda GALAGANDA There is no direct mention of thyroid gland in ayurveda. But adisease by the name galaganda is mentioned in samhitas. The earliest descriptionof neck swelling is found in atharva veda by the name apachi. Charaka firstdescribed abt the disease galaganda. He mentioned this in sutra sthana 20th chapter(maharogadhayaya) under the 20 varieties of sleshma vikaras. Susutha has described that out of seven layers of the skin, the sixthlayer known as ‘’Rohini’’ is responsible for the development of galaganda. “Shasti rohini nama vreehi pramanaa grandhyapachyamarbuda sleepda galagandadhisthna”’ (Su. Sa. 4/4)It is presumed that 1. The location indicated beneath the skin. 2. The sixth layer of the skin is the seat of various disorders includingGalaganda. A definite anatomical description of thyroid gland could be seenSusrutha samhita where he has described ‘’Nibadddah swayadhuryasya mushkavallambhate gale mahan yadiva hraswo galagandam tamadiset’’ (Su. Sam. N.11) Two encapsulated small or big swellings in the anterior angle of theneck which hang like scrotum, is called as ‘’Galaganda’’. This view with similardescriptions was also supported by another ancient Indian author i.e bhoja andmadhukosa.Hypothyroidism 53
  • 67. Galaganda On the other hand, Charaka and Harita have mentioned that there is asolitary swelling in the neck. “Galasya parswe ganda ekah” (Cha. Chi.11) Coming to the etiological factors may be broadly divided intointrinsic and extrinsic factor. The intrinsic factors are 1. Dosha- Vata and Kapha 2. Dushya- Meda The extrinsic factors include climatic conditions, water supply,dietary conditions and other surroundings etc. As regards geographical distribution of the disease and its role in theaetiology Bhela samhitakara has described that sleepda and galaganda are morecommon in prachya (eastern part) of the country. “Sleepada galagandam cha prachysteshu drishyate” Kashyapa samhitakara added that any part of the country which iscold, damp, with densely grown long trees, water stagnation and heavy rains maybe prone for the development of Galaganda.( Ka. Khi. 25) Susrutha stated that rivers flowing towards east may give rise tothe occurrence of goiter. Although this concept was given many centuries ago, butstill it is an accepted fact that sub-Himalayan range is known as goitrous belt. Apart from this Bhela Samhitakara has also emphasized on dietaryfactor, where he described that persons consuming predominantly fish on theirregular diet every day are liable to develop galgaganda.Hypothyroidism 54
  • 68. Galaganda “Matsya anna bhojino nityam prachyaah syu kapha bittinah sleepdam galagandam cha prachya sastheshu drishyate.” ( Bhe. Sam) Harita samhitakara described the role of contaminated water, lownutritional and bacterial infections in the precipitation of Galaganda “Dustambu panaka…………krimijadosha ganasha gandat”(Ha. Sam)Samprapti: Samprapti of goiter mentioned by different authors resembles almostsimilar. As per charaka vitiated kapha gets accumulated in the exterior of the neckand also due to involvement of mamsa dhatu and causes gradual onset of swellingknown as Galaganda. Where as sushruta is of opinion that galaganda is produced, whenvitiated vata & kapha dosa induces metabolic disbalance of meda and majja dhatuin the neck region.Types: Vataja, Kaphaja and Medaj are the three verities of Galaganda.Treatment The treatment of Galaganda includes sodhana and samanatherapies like Vamana, Nasya, Rakta Mokshana,Chedana, Bahya lepas, andTeekshna ushna aushadhi’s.Asadhya lakshana’s: A case of galaganda attended with difficult respiration, a softeningof the whole body, weakness, a non relish for, loss of voice as well as the onewhich is more than of a year’s standing should be abandoned by the physicians tobe incurable.Hypothyroidism 55
  • 69. Galaganda Galaganda can be correlated with goiter and some tumourpathology, where thyroid functions may or may not be affected. But hypothyroidism is not a mere localized disease. It has manysymptoms related to many systems of the body. So it is better not to restricthypothyroidism to the disease mentioned as Galaganda.Hypothyroidism 56
  • 70. Hypothyroidism in ayurveda HYPOTHYROIDISM IN AYURVEDA Lot of attempts has made to put an ayurvedic frame to thedisease hypothyroidism. There are quite a few concepts which may probablyresemble few symptoms of the disease.Some of them are1. Agnimandya, including Jatharagni, Bhutagni and Dhatwagni.2. Kaphaja sodha, “peedite no nnamati” with myxedema.3. Astaunindita purusha, atihraswa with cretinism.Agnimandhya: The major function of thyroid gland is to control the rate ofmetabolism. The principle function of it is to act as a catalyst –of the nature of a‘’spark’’ for the maintenance of oxidative metabolism in most tissues. Cells in thebody take their "cue" from thyroxine. The amount of stimulation the cells receivefrom thyroxine will determine how "quickly" they perform their functions. Agni is derived from the word “angati vyapnoti iti agnihi” meanswhich is capable of penetrating into minute spaces. So some believe that thyroxinehas a close resemblance with agni. All the ayurvedic physicians are very much aware about theimportance of Agni.Vagbhata enumerated agni25 as • Jatharagni • Bhutagni • DhatwagniHypothyroidism 57
  • 71. Hypothyroidism in ayurveda If these Agni’s fail to perform their optimum function, their subnormality leads to agnimandhya at different levels. The following points willsupport the concept of agnimandhya i.e Jatharagni, Bhutagni, Dhatwagni mandhyain hypothyroidism. Table showing the normal and abnormal functions of the agni related to hypothyroidism. Agni Normal function Features of Mandagni /hypothyroidism Jatharagni Digestion and assimilation Diminished power of digestion, of food constituents. assimilation, constipation, poor appetite, Rasagni Supply of absorbed nutritive Easy fatigability, dry skin, material to all body tissues irritability, lack of sweating for growth and repair. As artava is the upadhatu, menstrual irregularities come under this. Raktagni Responsible for tissue Anemia, Skin infections like vitiligo, nutrition, adequate alopecia, haemopoeisis, which in turn Edema, brittle dull hair, brittle nails, gives luster to the body. cold intolerance etc. Mamsagni Maintenance of adequate Physical strength lowered. Muscle muscle mass, physical cramps, stiffness etc noted strength.& greasyness to the skin. Medogni With adequate fat and Hyperlipidemia, obesity, goiter, sweating gives unctuous skin &physical strength Asthyagni Creation of healthy bones, Loss of body hair, pains in the bones joints, body hair, nails etc. and joints and easy fatigability physical and mental activeness Majjagni Adequate unctuousness of Lowered physical strength, vertigo body, maintaining fertility Sukragni Maintaining fertility and Decreased libido, infertility etc libido of the individualHypothyroidism 58
  • 72. Hypothyroidism in ayurveda In Susruta Samhita Sareera Stahna 3rd chapter he described about thehump-backed, crooked armed, lame dwarf child occurring due to the desires of thedouhrada not being gratified30. This can be correlated with congenitalhypothyroidism. Similar description is found Astanindita Purusha description, inwhich Atihraswa purusha may be correlated with cretin child.Kaphaja sodha27: some consider kaphaja sodha as myxedema. The onlysymptoms correlates here was “peedite nonnamati”, non pitting edema.Hypothyroidism 59
  • 73. Sadhyasadhya SADHYASADHYA As a general rule, the disease without any Upadravas, or ArishtaLakkshanas which is nearly manifested and in which more than one dosha isinvolved is sukhasadhya. The term Asadhya denotes the bad prognosis of aparticular disease. Asadhya is two types. Those are Yapya and Pratyakhyeya.Yapya means that the treatment should continue jeevana paryantam andpratyakhyeya indicates achikitsavastha of vyadhi27. The following are the AsadhyaLakshanas. Hypothyroidism is classified into primary and centralhypothyroidism. Central hypothyroidism results when there is any defect in thehypothalamus or pituitary level. This form is very rare and may not be amicable toayurvedic treatment. The extra thyroidal causes like thyroid hormone resistance isalso not curable. The causes of primary hypothyroidism may be classified into thefollowing types11. 1. Genetical and Hereditary. 2. Congenital. 3. Autoimmune thyroid deceases 4. Iodine deficiency. 5. Side effects of surgery and allopathic medicines. l. Genetical and hereditary defects that cause hypothyrodism come underAdibala Pravritta Vyadhi and no treatment is suggested in the text. 2. Congenital defects comes under Janma Bala Pravritta Vyadhi and it maybe due to two causesHypothyroidism 60
  • 74. Sadhyasadhya i) Rasakritah this is due to under nourishment during intra uterine like. ii) Dauhridapacharakritah: Unfulment of desires during pregnency causescertain defects to the foutes. These deceases are preventable if followed pathyapathya duringpregnenancy as prescribed in ayurvedic texts. 3. Autoimmune thyroid diseases: autoimmune thyroid disease ischaracterized by gradual lymphatic infiltration and progressive destruction of thefunctional thyroid tissue. So it may be Yapya, means that the treatment should becontinued Jeevanaparvantam. 4. Iodine deficiency: is easily treatable by supplementing iodine, it comesunder Sukha Sadhya. 5. Side effects of surgery and allopathic medicines: If hypothyroidismresults due to surgery, radiation and allopathic drugs, there will be some loss offunctional thyroid tissue. So it may be Kasta Sadhya. 6. If hypothyrodism results due to functional defects in thyroid hormonebiosysnthesis and release it is sadhya. 7. The patient who has complications like heart diseases like bradycardiaand cardiomagaly, myxedema coma, are Pratyakhyeya indicates Achikitsavasthaof Vyadhi.Hypothyroidism 61
  • 75. Chikitsa yojana CHIKITSA YOJANA24 ‘’Vikaranamakusalo na jihriyat kadachana Nahi sarva vikaranam namoto asti dhrivasthitih’’ --Cha. Chi. 18/44 Ayurveda doesn’t emphasize on the exact nomenclature of thedisesase rather than it insists on diagnosis of the constitutional status of the diseaseas mentioned in charaka. On the basis of Ayurvedic principles the following are the maincauses for hypothyroidism. 1. Genetical and hereditary defects comes under adibala pravritta vyadhis, so no treatment suggested. 2. Congenital defects come under janmabala pravritta vyadhis. Thyroid gland Agenesis, Dysgenesis, Ectopic thyroid gland comes under this category. 3. Iodine deficiency is the main common cause for hypothyroidism. So ‘’Sarvadha sarva bhavanam samanyam vriddhikaranam25’’ applies here. 4. Auto immunity is another common cause so Immuno modulatory drugs are recommended here. 5. Side effects of surgery and radiation: kasta sadhya. 6. For transient hypothyroidism no specific treatment is required.Hypothyroidism 62
  • 76. Chikitsa yojana 7. If there is functional loss of thyroid tissue or functional defects thyroid stimulatory drugs are beneficial. 8. Selection of drugs acting at various levels: 1. At hypothalamo pituitary level: anti stress drugs, medhya rasayana drugs, nasya karma may be beneficial. 2. At thyroid gland level: thyroid stimulatory drugs are recommended here. 3. At metabolism level: deepana, pacahana, ushna, teekshna, sukshma, ,lekhana drugs which pep-up body metabolism is recommended. 4. Immuno modulatory drugs for autoimmune related hypothyroidism. “Samprapti vighatana” is one of the main principles of treatment.Whatever may be the etiology of the disease, it results in under active condition ofthe thyroid gland and ultimately slowing down of the body’s metabolism. So thetreatment should aim to stimulate the thyroid gland. Thyroid stimulatory drugslike guggul should be selected to treat the disease. As the symptoms of hypothyroidsm are notorious, the symptomatictreatment is followed according to the suitabily of the individual cases, i.e.,sthoulya, sodha etc. Selenium is required for a number of enzymes known asselenoproteins. The chemical reaction, which converts thyroid hormone T4 intoT3, is catalyzed by specific selenoproteins. Selenium deficiency can impairthyroid function. In recent studies Selenium supplementation reduced thyroidantibodies (TPOAb) by 40% in three months in a blinded controlled prospectiveHypothyroidism 63
  • 77. Chikitsa yojanastudy in female patients with autoimmune thyroiditis. Selenium is also a cofactorfor type I hepatic 5-deiodinase, the enzyme that converts T4 to the more activeT3, and degrades rT3. The drug Pippali, increases the absorption of Selenium it isvery helpful in this condition; this may be cause for the effectiveness ofvardhamana pipppli in hypothyroid conditions. Shilajit is believed to be useful in hormonal imbalance conditions,nasya with anutaila, pushpadhanwaras, arogya vardhinivati,punarnravamandura, chandraprabhavati, navakaguggulu,kumbha jatuvati,loha rasayana are found in usage, but requires scientific studies to know itsefficacy, dosage, complications, duration etc. Zinc is required for the action of Thyroid Stimulating Hormone. Thezinc/copper balance also has a big influence on the progesterone/estrogen balancein women, which has a significant influence on thyroid function.so the drugswhich contain zinc may be useful. Iron is essential for the conversion of phenylalanine, an essentialamino acid, to tyrosine. So the iron containing medications may be useful. Heavy metals such as cadmium, lead & mercury can inhibit thyroidfunction. So care must be taken when prescribing lead and mercury preperations tothe hypothyroid patients. Further research is required to proove the efficacy of these drugs.Hypothyroidism 64
  • 78. Pathyapathya PATHYAPATHYA24AHARA: The diet should be high in fibre and low in calorie. It should alsocontain adequate proteins, fat, minerals and vitamins. But high protein diet willworsen constipation if that is one of the symptoms. The fat allowance should notexceed more than 30 gm per day. Salt intake should be kept at a minimum andlimited to 1-2 tsp per day. Avoid salted confectioneries, chips and pickles. Eating goitrogenic foods such as rapeseed, cabbage, Brussels sprouts,broccoli, cauliflower, sweet potatoes, maize, lima beans, soya and pearl milletshould be limited. These foods contain natural goitrogens, which are chemicalsthat cause the enlargement of the thyroid gland by interfering with thyroidhormone synthesis. Cooking is known to make the goitrogens elements lesseffective but it would be wise not eat these foods raw. Fats, sugars, sodium chloride, red meat and egg intake should also berestricted. Avoid caffeine drinks like coffee, cola. Caffeine and other stimulantsinterfere with T3 and adrenal hormone metabolism while in the body. Smoking depresses TH levels and produces a chronic underlyinghypothyroidism. Research shows that nicotine increases the synthesis of T3 fromT4 in the brain, while alcohol and opiates block the breakdown of T3 in the brain. Paradoxically, some substances labelled depressants such as alcoholor opiates can increase T3 levels by impairing the breakdown of T3 in the brain,thus lifting mood. This may be one reason why these substances are so addictive. Foods that contain iodine such as kelp, beetroot, radish, parsley,potatoes, fish, oatmeal and bananas should be kept in the diet.Hypothyroidism 65
  • 79. Pathyapathya Certain foods, supplements and medications can impair absorption ofsynthetic thyroid hormone. These include: 1. Iron supplements or vitaminsupplements containing iron; 2.Calcium supplements; 3.Soybean flour; 4.Aluminum hydroxide, a popular antacid; 5. Sucralfate, an ulcer medication;6.Some cholesterol-lowering drugs, such as cholestyramine and colestipolVIHARA: Another important factor in the treatment of hypothyroidism isexercise. Exercise increases tissue sensitivity to the thyroid hormone andstimulates thyroid gland secretion. An exercise regime of between 15-20 minutesper day will be beneficial with hypothyroidism. This exercise needs to bestrenuous enough to raise the heartbeat, an exercise such as walking, swimming,running and cycling. But in patients who have hypothyroidism have generalizedhypotonia and may be at risk for ligamental injury, particularly from excessiveforce across joints. Thus, patients should exercise caution with certain activities,such as contact sports or heavy physical labor. Patients with uncontrolledhypothyroidism may have difficulty maintaining concentration in low-stimulusactivities and may have slowed reaction times. Patients should use caution if anactivity has a risk of injury (e.g.operating presses or heavy equipment, driving). Physical and emotional stress inhibits the thyroid gland secretion dueto reduction of thyrotrophin output. So reduction of the stress is very essential forproper functioning of the gland.YOGA: Sarvangasana is the most suitable and effective asana for the thyroidgland. An enormous pressure is placed on the gland by this powerful posture. Asthyroid gland has one of the largest blood supplies of the any organ, the pressureHypothyroidism 66
  • 80. Pathyapathyahas dramatic change on its function, improving circulation and squeezing outstagnant secretions. After sarvangasana practice of matsyasana and halasna isbeneficial. Other effective asanas include surya namaskara, pavanamuktasana withemphasis on head and neck exercises, yoga mudra, sputa vajrasana and allbackward bending asanas.PRANAYAMA: The most effective pranayama is ujjayi. It acts on the throat and itsrelaxing and stimulating effects are most probably due to stimulation of ancientreflex pathways within the throat area, which are controlled by brain stem andhypothalamus. Nadi sodhana pranayama is useful in re-balancing metabolism.Hypothyroidism 67
  • 81. Criteria for the drug selection CRITERIA FOR THE SELECTION OF THE DRUG KNG AND SHIGRU PATRA KWADHA The present trial drug Kanchanara Guggulu24 (Sa. Sam.), isfound in usage for many years for Gandhamala, Apachi, Arbuda, Grandhi, Kushta,etc, has been selected to evaluate the efficacy of this drug in hypothyroidism. The main ingredient Guggulu has thyroid stimulating propertyalong with tridosha hara, rasayana, antiinflammatory, hypo-cholesterogenic, hypo-lipodemic, reduces total serum cholesterol and serum lipid-phosphorus, appetizer,antisuppurative, aphrodisiac; these are all very beneficial in hypothyroidconditions. This research work was done by Dr. Tripathi and others. Animalstudies have revealed that Guggulu supports healthy thyroid function, mostly byincreasing the conversion of less active Thyroxin (T4) to more activeTriiodotyronine (T3) through increasing thyroid proteolytic activity and the uptakeof iodine into thyroxin, and without increasing the production of ThyroidStimulating Hormone.33KANCHNARA26,28: The synonym of Kanchanara as “gandari” itself indicates itsproperty as anti goiter drug. The action of kanchanara in cases of goiter is mostprobably by its prabhava not merely by rasa, guna, veerya or vipaka. It hasPrabhava (specific action) – Gandmalanashak. It is a specific herb for swollenlymph nodes, cervical adenitis, scrophularia or swollen glands in general. Iteffectively flushes the lymphatic system of toxins, sluggishness and accumulatedwastes. Also may be beneficial where the sinuses are congested because of thesluggish lymphatic system. It is a powerful decongestant.Hypothyroidism 68
  • 82. Criteria for the drug selection The other ingredients triphala, trikatu, trijataka are also may beuseful in hypothyroid condition as these are deepana and pachana drugs they maybe helpful to pep up body’s sluggish metabolism and also may enhance the actionof the drug Guggulu.SHIGRU PATRA28: Iodine is an essential component of thyroid hormones, T3 and T4.Iodine is essential for the formation of thyroid hormones. Iodine deficiency is oneof the main causes of hypothyroidism. So according to sarvadha sarvabhavanamsamanyam vriddikaranam iodine deficiency is supplemented by administering thedrug which contains iodine. Shigru leaves rich in iodine, appears to provide itwith the nutrition and substrates the thyroid gland requires. It contains essentialaminoacids, vitamins, having deepana properties, vatakapha hara, sodhahara,chakshushya properties and is indicated in gandamala, medo roga, apache,vidradhi etc.Hypothyroidism 69
  • 85. GUGGULU
  • 86. SHIGRU
  • 87. Kanchanara guggulu DRUG REVIEWKANCHANARA GUGGULU 24 Kanchanara guggulu a well-known drug in Ayurveda is found inusage from many years for apache, arbuda, gandhamala etc. “Kanchanara twacho grahyam palanam dasakam budhaih Triphala shatphala kaarya trikatusyatphalatrayam Palaikam varunam kuryadela twakpatrakam tadha Ekaikam karsha matram syat sarvanyekatra churnayet Yavadchurnamidam sarvam tavanmatrastu gugguluh Sankutya sarvamekatra pindam kritwa cha dharayet Gutika ssanikah karyah pratargrahyayadochitah Gandamaala jayantyugram mapachimarbudanicha Grandhin vranamscha gulmanscha kustanicha bhagandaram” (Sa. Sam) 10 palas of bark of Kanchanara, 6palas of Triphala, 3palas ofTrikatu, 1 pala of bark of Varuna, karsha each of Ela, Twak, Patra, Gugguluequal to the quantity of above are rolled into pills of sana. It is indicated in Gandamala, Apachi, Arbuda, Granthi, Vrana, Gulma,Kusta, Bhagandara etc.Dosage: 2-3 tab b.dHypothyroidism 70
  • 88. Kanchanara guggulu INGREDIENTS OF KANCHANARA GUGGULU1. GUGGULU 26,27,28:Synonyms: Kousika, Devadhupa, Palamkasha, Pura Botanical name: Commiphera mukul Family: Burseraceae Vernacular names: Hindi: Guggula Telugu: Guggilam Kannada: KanthaganaGana: Sanjna sthapana (Charaka), Eladi ( Susrutha & Vagbhata)Gunas: Rasa: Tikta, katu Guna: Laghu, Ruksha, Visada, Sukshma, Sara(old), Snigdha and Picchala (new) Virya: Usna Vipaka: KatuKarma: Tridosha hara, Deepana, Brimhana, Vrsya(nava), Lekhana (purana), Rasayana.Indications: Medo roga, Prameha, Kusta, Ashmari, Amavata, Sopha, Grandhi, Apachi, Gandamala, Arshas, kusta etc.Useful part: NiryasaResearch work28,33,35:The primary chemical constituents of Guggula include phytosterols, gugulipids, andguggulsterones. • Animal studies have revealed that guggul supports healthy thyroid function, mostly by increasing the conversion of less active Thyroxin (T4) to more active Triiodotyronine (T3) through increasing thyroid proteolytic activity andHypothyroidism 71
  • 89. Kanchanara guggulu the uptake of iodine into thyroxin, and without increasing the production of Thyroid Stimulating Hormone33. • Z guggulsterone also increased the thyroid activity as evidenced by increased the thyroid activity and increased iodine uptake and increase in proteolytic and peroxidase activity. • Guggul helps reduce high cholesterol, because it lowers harmful low-density lipoproteins while elevating the beneficial high-density lipoproteins. It appears to work through several mechanisms, including inhibition of HMG-CoA reductase (the enzyme which controls the body’s synthesis of cholesterol), increasing the release of excess lipids through the feaces, an action similar to the drug Cholesrymine, and its support of thyroid hormone production. • It prevented the deposition of fat in the adipose tissue, probably due to increased lipolysis. • In order to find out the effect of Guggulu on endogenous hyperlipimia, its effect on neomercazole and estrogen induced hypercholesterolemia and hyperlipidemia was also studied. This reveals an important fact that it successfully neuturalized the action of neomercazole on thyroid. This gave a lead that hypocholesterolemic and hypolipidemic action of this drug is medicated through the thyroid gland. • It helps prevent blood platelet aggregation and breaks up already formed blood clots and keeps potentially deadly blood clots in check by increasing fibrinolysis. Thus, it helps prevent heart disease and stroke. • Its effect on aortic atherosclerosis and coronary thrombosis was also extended and it was observed that Guggulu retarded the process of atherosclerosis to a great extent and prevented the process of thrombosis. • Guggul lipid stimulates the activity of white blood cells in the body, contributing to the build-up of the immune system. • Guggul lipid also helps eliminate and expel dead tissues, wastes, and toxins from the body.Hypothyroidism 72
  • 90. Kanchanara guggulu • Guggul lipid has been known to relieve coughing and lung congestion, soothe mucous membranes and alleviate other respiratory problems. • Guggul lipid may also be used to treat arthritis and reduce inflammation of the joints. • A small controlled trial compared oral guggulipid against tetracycline for the treatment of acne, and reported equivalent results. • There were also significant reductions in skin fold body fat measurements at the triceps, calf, and shoulder; biceps skinfold fat was also considerably reduced in the mildly overweight • Several animal studies have supported an anti-inflammatory effect for Guggul – a traditional use for this herb. • Guggul has also traditionally been used for support in a variety of skin disorders. One small trial found Guggul to be as good as tetracycline for people suffering with scarring, cystic acne, an effect most strongly noted in those with very oily skin. Cautions: • Guggul is traditionally believed to stimulate the menstrual cycle and the tone of the uterus; it is therefore best avoided in cases of pelvic inflammatory disease or menorrhagia. • Guggul should not be used in cases of hyperthyroidism. • May potentiate or alter the effects of thyroid medications. • Mild GI problems have been noted in a few people. • A small subset of Guggul users may develop a rash, which disappears when they stop taking the supplement. • Guggul reduces the bioavailability of blood pressure drugs diltiazem (Cardizem®) and propranolol (Inderal®), as well as the cancer drug cyclophosphamide. Guggul must not be taken with acetaminophen (eg. Tylenol)Hypothyroidism 73
  • 91. Kanchanara guggulu KANCHANARA 27,2830Synonyms: Gandari, Sonapushpaka, Kancanaka, Kovidara, Swalpakesari, Yugmapatraka, Camarika. Botanical name: Bauhinia variegata Family: Caesalpinaceae Vernacular names: Telugu: Devakanchanamu Hindi: KachnarGanas: Vamanopaga (charaka) Kashaya varga ( susrutha )Gunas: Rasa: Kasaya Veerya: Seta Guna: Ruksha, Laghu Vipaka: KatuKarma: Kapha-pittahara, Grahi, DeepanaIndications: Gandamala, Rakta pradara, Rakta pitta, Mutra kricchra, Vrana, Arsa, Masurika.The synonym of kanchanara as gandari itself indicates its property as antigoiterdrug.It is a specific drug for swollen lymph glands or swollen glands in general.Traditionally it is used to treat thyroid diseases and glandular enlargements. VARUNA 27,28,30Synonyms: Varana, Kumaraka, Tikta saka, Setu, Saka druma, Tamalaka, Swetapushpa Botanical name: Crataeva religiosa Family: Capparidaceae Vernacular names: Hindi: varuna Telugu: ulimiri chettuHypothyroidism 74
  • 92. Kanchanara gugguluGanas : Tikta skanda (charaka), varunadi, vata samsamana, kaphasamsamana(susrutha), varunadi ( vagbhata).Gunas:Rasa: tikta, kashaya Veeerya: ushnaGuna: laghu, ruksa Vipaka: katuKarma: Kapha vata hara, Deepana, KrimighnaIndications: Asmari, Mutrakricchra, Vidradhi, Gulma, Gandamala.It contains lupeol, a chemical that deactivates enzymes that needed to manufactureinflammation inducing leukotraines and also reduces the levels of variouslaboratory markers of kidney damage.Scientific research has confirmed that varuna deactivates the enzyme glycolateoxidase. This reduces the bodys production of oxalates, which combine withcalcium to form kidney stones. TRIPHALA30 “Pathya vibhita dhtrinam phalsyat tripala samai” Bha. Pra. Purva-5/45/46Haritaki, vibhitaki, amalaki these are three drugs in equal quantity is called astriphala or phalatrika or vara.Karma: kaphapitta hara, deepaneeya, chakshushya, vishama jwara, prameha,kustaharam. It is an excellent laxative which takes away fats from the body andreduces weight. It is said to promote normal appetite, good digestion. It has strongpurifying and antioxidant qualities. TRIKATU30 “Vishwopkulya maricham trayam trikatu kadyate” Bha. Pra. Purva-5/70Trikatu contains three ingredients i.e vishwa (shunti), upakulya (pippali),MareechaGunas: katu – rasa, ushna- veerya, madhuara – vipaka.Karmas: Deepana, Gulma, Medoroga, Prameha, Sleepada, Peenasa, Swasa, Kasahara.Hypothyroidism 75
  • 93. Kanchanara guggulu TRIJATAKA30 “Twagela patrakai stulyai strisugandi trijatakam” Bha. Pra.Purva.5/87 Twak, Ela, Patri in equal parts is called as trijataka.Gunas: rooksha, teekshna, ushna,Karma: Mukha durgandha nasaka, Laghu, Pitta-agni krit, varnyam, kapha vatavishapaham.Hypothyroidism 76
  • 94. Shigru SHIGRU 27,28Synonyms:Shobanjana: “Susthu bhanakti mukham sobhanjanah”Shigru: “Shinoti taikshnyat sigruh”Tikshna gandha: “Tteekshnam gandho asyah teekshna gandhah”Mochaka: “Munchati rogaan iti mochakah”Aksheeva: “Ksheebyantyanena vrishytwad aksheeva”Bahupatra: “Bahu patraat” Botanical name: Moringa oleifera Family: Moringaceae. Vernacular names- Hindi: Sahijana English: Drumstick tree Telugu: MunagaGanas: Krimighna, swedopaga, sirovirechanopaga, katuka skanda (charaka),varunadi and sirevirechana gana’s (susrutha) varunadi gana (vagbhata).Guna’sRasa: Katu, tikta Guna: Laghu, rooksha, teekshnaVeerya: Ushna Vipaka: KatuKarma: Kapha vata hara, sukrala, grahi, dipana, hridya, krimighna, chakshushyaIndications: Kapha vata hara, pliha roga, galaganda, sirahsoola, kandu, sotha,apachi, vrana, medoroga, vidradhi, gulma etc.Useful parts: Root, bark, stem, leaves, flowers, seeds.Root: Root bark contains 2 alkaloids moringine and moringinine. First one wascompetitively inert, but moringine acts n sympathetic nerve endings as well ascardiac and smooth muscles all over the body. It produces raise of blood pressurestimulation of heart and contraction of blood vessels. It relaxes bronchioles,inhibits tone and movement of the intestines and contracts the uterus in guinea pigHypothyroidism 77
  • 95. Shigruand rabbits. Root bark contains an antibiotic pterigospermin, which is active atph5 and less active at ph 8. It is stable in the presence of blood and gastric juicebut breaks down in the presence of pancreatic juice. It is active againstSolmonella, E.coli, Shigella, Micro coccus, and Mycobacterium etc and alsoactive against Fungi. 50%Ethanolic extract of root bark showed anti viral activity.It contains an alkaloid named Spirochin, its pharmacological and chemical trailsshowed action directly on myocardium. It also contains traces of essential oil,phytosterol, waxes and resins.Stem: Stem bark contains sterols and terpens, which show anti fungal activityagainst candida albicans, etc. Gum exudates contains Arabinose,Galactose,Glucaronic acid, Rhamnose, Mannose and Xylose in molar ratio of14.5, 11.3, 3.2, 1, 1 ratio.Leaves:Leaves contain per 100 g 8.Protein: 6.7 g 1. H2O-7.5 g 9.Fat: 1.7 g 2. Total carbohydrate-14.3 g 10.Fiber: 0.9 g 3. Ca-440 mg 11.P- 70mg 4. Fe-7 mg 12. Cu- 110mg 5. Iodine- 5.1 mg 13.Vit A-11,300 IU 6. Vit B-120 mg 14.Nicotinic acid-0.8 mg 7. Ascorbic acid- 220 mg 15. Tocopherol- 7.4 mgLeaf amino acids: 1. Arginine -6.0 g 7.N-16 g 2. Histidine- 2.1g 8. Lysine- 4.3 g 3. Phenylalanine-6.4 g 9. Tryptophane- 1.9 g 4. Methionine-2.0 g 10.Lucine-9.3 g 5. Threonine- 4.9 g 11.Isoleucine-6.3 g 6. Valine-7.1 gHypothyroidism 78
  • 96. ShigruResearch works: • It contains 4-[(4-O-acetyl-alpha-L-rhamnosyloxy) benzyl] iso thiocyanate and the thiocarbamate glycosides niaziminin A and B isolated from ethanolic extract of Moringa oleifera, showed hypotensive activity • The fresh leaf juice and aqueous extracts from the seeds inhibited the growth of Pseudomonas aeruginosa and Staphylococcus aureus when tested by a disk diffusion method. • Estrogenic substances, including the anti-tumor compound, b-sitosterol, and a pectinesterase are also reported • In a study conducted it was found that administration of the crude leaf extract of Moringa oleifera along with high-fat diet decreased the high-fat diet- induced increases in serum cholesterol level to a statistically significant extent • Niazimicin an alkaloid isolated from seeds of Moringa oleifera when subjected to in vivo test was found to have potent antitumor promoting activity in the two-stage carcinogenesis in mouse skin using 7,12-dimethylbenz (a)anthracene (DMBA) as initiator and TPA as tumor promoter. • Three thiocarbamate (TC) - and isothiocyanate (ITC)-related compounds, isolated from the leaves of Moringa oleifera, are observed to be inhibitors of tumor promoter teleocidin B-4-induced Epstein-Barr virus (EBV) activation in Raji cells in a study conducted. • The methanol fraction of Moringa oleifera leaf extract was found to possess significant protective actions in acetylsalicylic acid; serotonin and indomethacin induced gastric lesions in experimental rats. • In another study, a significant enhancement of the healing process in acetic acid-induced chronic gastric lesions was observed with the extract-treated animals. • It contains 4times Calcium than Milk, 4times Vit A than Carrots, 3times vit C than oranges, 2times Vit K than banana and 2times protein than milk.Hypothyroidism 79
  • 97. ShigruPod: Per 100 g, the pod is reported to contain 1. H2O- 86.9 g 8.Protein- 2.5 g 2. Fat-0.1 g 9.Total carbohydrate- 8.5 g 3. Fiber -4.8 g 10.Ash-2.0 g 4. Ca-30 mg 11.P-110 mg 5. Fe-5.3 mg 12.Niacin- 0.2 mg 6. Vit.A-184 IU 13.Ascorbic acid-120 mg 7. Cu-310 mg 14.Iodine-1.8 mgPod amino acids: Arginine: 3.6 g N:16 g Histidine: 1.1 g Lysine: 1.5 g Tryptophane:0.8 g Phenylalanine:4.3 g Methionine:1.4 g Threonine: 3.9 g Leucine: 6.5 g Isoleucine:4.4 g Valine :5.4 gSeeds:Seed oil composed essentially of Oleine, Margarine and Stearine. It is usefulexternally for relieving pains. Biological activity studies have confirmed the antiinflammatory, antispasmodic and diuretic action of the seeds.Seed kernel (70–74% of seed) contains 4.08 H2O, 38.4 g crude protein, 34.7%fatty oil, 16.4 g N free extract, 3.5 g fiber, and 3.2 g ash.Flowers:Flowers contain Quercetin and Kaempferol. It acts as a tonic and increases theflow of Bile.Hypothyroidism 80
  • 98. Material and methods MATERIALS AND METHODSMATERIALS:1. PATIENTS: To evaluate the efficacy of the drug Kanchanara Guggulu andShigru Patra Kwatha in the management of Hypothyroidism, 32 patients ofhypothyroidism were selected from the O.P Dept of Dr. B.R.K.R.Govt AyurvedicHospital, Hyderabad. 32 patients were included and examined thoroughly examinedand the Diagnosis of hypothyroidism is based on a persons medical history, aphysical examination, and blood tests. Of the blood tests for hypothyroidism, theTSH is the most sensitive test. The role of TSH is to stimulate the thyroid gland toproduce thyroid hormone when the level of hormone in the body drops. If the TSHlevel is above 6, then a diagnosis of hypothyroidism was made. The symptoms of hypothyroidism vary widely, from nosymptoms to marked symptoms. The symptoms of hypothyroidism are notoriousfor their nonspecific nature and for the way in which they mimic many symptomsof other diseases. As Hypothyroidism doesn’t have any characteristic symptoms,the following most common symptoms were carefully screened.Inclusion criteria: 1. Weight gain/unable to loss weight 2. Vertigo 3. Easy fatigability 4. Lethargy 5. Cold intolerance 6. Hair lossHypothyroidism 81
  • 99. Material and methods 7. Slowness of memory, intellect and thought 8. Anorexia 9. Constipation 10. Gaseous distention 11. Hoarseness/slowness of voice 12. Menstrual irregularities 13. Oligomenorrhoea /Amenorrhea 14. Parasthesias 15. Muscle cramps and weakness 16. Muscle stiffness and aching 17. Dry skin 18. Coarse, brittle, dull hair 19. Puffiness of the face, hands, feet 20. Slow reflexes 21. GoiterExclusion criteria:1. Patients with Cardiomegaly and Bradycardia.2. Patients who are above 65 yrs and using the allopathic drug thyronorm.3. Patients who are suffering from hypothyroidism for more than 10 years.2. DRUGS: 1. KANCHANARA GUGGULU ( Sa. Sam ) The drug Kanchanara guggulu a compound Ayurvedic preparation consists of Guggulu, Kanchanara, Varuna, Triphala, Trikatu and Trijataka (preparation of the drug mentioned in drug aspect). It is one of the safest and the very useful drug in ayurveda, is found in usage for many years for gandhamala, apachi, Arbuda, Granthi, Vrana, Gulma, Kusta, Bhagandara etc. In the present study KNG is evaluated for thyroid stimulating activity.Hypothyroidism 82
  • 100. Material and methods2. SHIGRU PATRA KWATHA: Shigru is a well-known plant in India. It has deepana, pachana,kapha vata hara properties. It is recommended in galaganda, kandu, sotha, apachi,vrana, medoroga, vidradhi, gulma etc. As it is rich in iodine, which is the maincause for hypothyroidism, is selected as anupana along with KNG. Shigru leaves are dried and the powder was given to the patientsand advised them to make decoction.Kwatha preparation: To the coarse powder of one part of drug, add 8 parts ofwater, boil and reduce them to 1/4th and filter it.THE METHODOLOGY:The aim of the study of the study: 1. Normalize the levels of TSH in the fresh cases. 2. To maintain the TSH levels in the patients who are already using the allopathic drug thyronorm and gradually replacing the allopathic drug with the trail drugType of trial: Open trailMode of administration: OralMethod of administration: 1. For fresh cases started immediately after the diagnosis confirmed. 2. For the patients who are already using thyronorm advised withdraw the 25 mcg of the drug before starting the rail drug. 3. The patients were observed carefully for I month, if they are comfortable with the drug and dosage and TSH levels are maintained well they are advised to withdraw another 25mcg. This way the drug is totally replaced with the trail drug.Hypothyroidism 83
  • 101. Material and methodsDose of the drug: i) Kanchanara guggulu 250mg b.d. ii) Shigru patra kwatha 250ml b.dPeriod of study: 3 monthsPatients were advised not to take Kapha and Medo vardhaka Ahara and Vihara’slike diwaswapna, madhura guru dravya sevana etc.CLINICAL ASSESSMENT: The progress of the patient is observed and recorded after every15 days. This procedure is followed for duration of 90 days. After the completionof the duration the results are assessed basing on observations. The results areassessed in terms of complete relief, marked, moderate and mild relief and norelief. 1. Complete relief: TSH levels normalized and 100% symptoms relieved. 2. Marked relief: TSH levels normalized and symptomatic relief up to 75%. 3. Moderate relief: TSH levels normalized and symptomatic relief up to 50- 75%. 4. Mild relief: TSH levels normalized and symptomatic relief up to 25-50%. 5. No relief: no change in the TSH levels and no symptomatic relief.Hypothyroidism 84
  • 102. Observation and results OBSERVATIONS AND RESULTS 32 patients were selected from OP and IP departments of Dr. BRKRGovt.Ayurvedic hospital, Erragadda; for the study on the effect of Kanchanara Gugguluand Shigru patra kwatha on hypothyroidism. The patients included in the study were examined thoroughly and thediagnosis of Hypothyroidism is based on the patient’s symptoms and blood test,i.e. thyroid profile. If the TSH levels are above 6, they were selected for the study. The patients were classified into various groups according to their age, sex,socioeconomic status, occupation, prakriti, sara, previous medical history, familyhistory, BMI etc and tabulated as shown below.Classification of groups:1. ACCORDING TO AGE: 32 patients were classified according to the ages as shown in table 4.1.Maximum number of cases was seen in 20-30 yr age group. Table 5.1 showing the incidence of hypothyroidism a/c to ages: Age group No. of patients Percentage 10-20 3 9.37% 20-30 14 43.75% 30-40 12 37.5% 40-50 6.25% 2 50-60 1 3.125%Hypothyroidism 85
  • 103. Observation and results2. ACCORDING TO SEX: Out of 32 cases 30 cases were females, and only 2 male cases were seen. Table 5.2, showing the incidence of hypothyroidism a/c to sex. Sex No .of patients Percentage Male 2 6.25% Female 30 93.75%3. ACCORDING TO OCCUPATION: As hypothyroidism is seen more in those who adopt sedentary lifestyle, the occupation of the patient and nature of work is observed carefully.Among the 32 cases the occupations were as summarized in the table. Table 5.3 showing the incidence of hypothyroidism a/c to occupation. Occupation No. of patients percentage Housewife 18 56.25% Student 7 21.87% Hard worker 1 3.12% Sedentary work 6 18.75%4. SOCIO ECONOMIC STATUS: The patients were observed as per the socio economic statusbased on their monthly income. If the income is between 10,000- 20, 000 theywere taken as ordinary middle class. Above 20,000 as upper middle class, from5,000-10,000 they were considered as lower middle class. If their income is belowHypothyroidism 86
  • 104. Observation and results1000 rupees per month they were considered as poor. In the present study theincidence of hypothyroidism is seen more in upper middle class people. Table 5.4 showing the incidence of hypothyroidism a/c to SES. Socio economic status No. of patients Percentage Upper middle class 16 50% Middle class 10 31.25% Lower middle class 5 15.65% Poor 1 3.125%5. ACCORDING TO DIET: According to their diet 30 patients were non-vegetarians and 2 patientswere vegetarians out of 32 patients. Table 5.5 showing the incidence of hypothyroidism a/c to diet. Diet No.of patients Percentage Vegetarian 2 6.25% Non vegetarian 30 93.75%6. ACCORDING TO FAMILY HISTORY: Thyroid disorders are hereditary disease and runs in families. So familyhistory of autoimmune disorders, thyroid disorders are very important inhypothyroidism.Hypothyroidism 87
  • 105. Observation and results Table 5.6 showing the incidence of hypothyroidism a/c to family history. Family history No. of patients percentage Parents DM 6 18.75% Mother hypothyroid 3 9.37% Siblings hypothyroid 5 15.62% Daughter hypothyroid 2 6.25% Not associated 14 43.75%7. PREVIOUS DRUG/MEDICAL HISTORY: Previous Drug/Medical History is the main cause of the disease. So thepatients were observed carefully for their previous medical history.Table 5.7 showing the incidence of hypothyroidism, a/c to previous drug/ medical history. Previous medical No. of patients Percentage history Depression/insomnia 3 9.37% Hysterectomy 6 18.75% Steroids 1 3.125% RA 1 3.125% Not associated 21 65.62%Hypothyroidism 88
  • 106. Observation and results8. ACCORDING TO PRAKRITI: The patients were assessed according to their prakriti. Kaphapredominance is seen more in the selected 32 patients. Table 5.8showing the incidence of hypothyroidism, a/c to Prakriti. Prakriti No. of Patients Percentage Vata predominant 1 3.125% Pitta predominant 2 6.25% Kapha predominant 9 28.12% Vatapitta 3 9.37% Vatakapha 4 12.75% Kaphapitta 13 40.629. ACCORDING TO SARA Twak,Mamsa and Medo Sara predominance is seen more in the selected32cases. Table 5.9 showing the incidence of Hypothyroidism, a/c to Sara Sara No. of patients Percentage Twak 11 34.37% Mamsa 15 46.87% Medo 6 18.75%Hypothyroidism 89
  • 107. Observation and results10. ACCORDING TO BMI: Maximum incidence was found in those patients whose BMI is more than 20. Table 5.10 showing the incidence of Hypothyroidism, a/c to BMI. BMI No. of patients percentage Below 20 1 3.12% 20-25 12 37.5% Above 25 19 59.37%Hypothyroidism 90
  • 108. Observation and results RESULTS 32 patients were recruited in the study and the assessment was donefor every 15days. Of the 32 patients 16 patients were fresh cases and 16 patients arealready using the modern medicine eltroxin. The results of the patients who completed the treatment of 90dayswere analyzed. In the 16 fresh cases the TSH levels came to normal range after thecompletion of the treatment. The 16 who are already using allopathic medicinewere gradually replaced with the trial drug and the TSH levels were in normalrange as summarized in table 4.11 and 4.12.Table 5.11 showing the levels of TSH before and after treatment: Before treatment After treatment S.no O.P.NO. TSH (mU/L) TSH (mU/L) 1 16884 9.66 3.93 2 22490 >100 3.29 3 5869 99.21 0.32 4 7289 11.13 0.01 5 11960 25.99 6.67 6 12460 116.6 1.09 7 6430 6.68 2.08 8 5892 10.73 3.56 9 6478 12.97 3.22 10 12926 22.38 0.90 11 11872 10.38 0.04 12 13482 48.72 1.47 13 5340 10.67 1.21 14 1792 11.32 3.54 15 8762 10.12 2.29 16 7280 100 5.89Hypothyroidism 91
  • 109. Observation and results For the patients who are already using thyronorm advisedwithdraw the 25 mcg of the drug before starting the trail drug. The patients wereobserved carefully for I month, if they are comfortable with the drug and dosageand TSH levels are maintained well they are advised to withdraw another 25mcgand the drug was totally replaced withTrial drug. Table 5.12 showing the levels of TSH before and after the treatment in chronic cases. Before After treatment S.no O.P.No. Duration Dosage of treatment thyronorm TSH (mU/L) TSH (mU/L) 1. 2970 5yrs 50mcg 5.66 4.56 2. 5290 8yrs 75mcg 0.90 1.25 3. 3472 8mon 25mcg 1.47 1.81 4. 8960 2yrs 50mcg 2.27 3.46 5. 5269 5mon 25mcg 3.22 3.67 6. 6840 2yrs 100mcg 2.07 1.90 7. 10964 4mon 25mcg 4.12 3.54 8. 4263 6yrs 25mcg 4.12 3.57 9. 3940 7mon 50mcg 3.8 5.07 10. 10164 1yr 75mcg 2.68 1.21 11. 4170 21/2yr 50mcg 3.44 5.12 12. 3680 1yr 25mcg 1.11 1.80 13. 2865 1mon 25mcg 6.84 4.79 14. 6430 2yrs 75mcg 5.54 3.68 15. 10890 3yrs 25mcg 1.77 2.34 16. 5128 8yrs 50mcg 4.74 3.21 Many of the symptoms of hypothyroidism are non-specific. Themost common symptoms observed in the 32 selected patients, before and aftertreatment were summarized as shown in below table.Hypothyroidism 92
  • 110. Observation and results The most commonly seen symptoms are weight gain or unable toloss weight, menstrual irregularities, vague body pains, constipation, puffiness ofthe face, hands and feet. The rare symptoms are recurrent attacks of infections,respiratory symptoms etc. Table 5.13 showing the symptomatic relief percentage: S.no The most common symptoms observed in BT AT Relief % 32 pt’s 1. Weight gain/unable to loss weight 21 14 33.33% 2 Vertigo 14 2 85.7% 3 Easy fatigability 20 4 80% 4 Lethargy 26 8 69.2% 5 Cold intolerance 13 6 53.84% 6 Hair loss 18 7 61.1% 7 Slowness of memory, intellect and thought 23 7 69.5% 8 Anorexia 12 4 66% 9 Constipation 23 1 95.6% 10 Gaseous distention 16 1 93.75% 11 Hoarseness/slowness of voice 15 5 66.66% 12 Menstrual irregularities 16 2 87.5% 13 Oligomenorrhoea /Amenorrhea 12 5 58.3% 14 Parasthesias 19 7 63.15% 15 Mucle cramps and weakness 16 10 37.5% 16 Muscle stiffness and aching 15 7 53.33% 17 Dry skin 23 10 56.52% 18 Coarse, brittle, dull hair 11 4 63.63% 19 Puffiness of the face, hands, feet 22 3 86.36% 20 Slow reflexes 9 6 33.33% 21 Goiter 11 6 45.45%The over all relief percentage: The TSH levels became normal in the fresh 16 cases, showed ap value of 0.0174, statistically significant. In 2 patients after withdrawl of the drugno recurrence is noted even after 6months. In the chronic cases that are alreadyusing the allopathic drug Thyronorm, the drug was gradually replaced with thetrail drug. The TSH levels were maintained during the replacement time.Hypothyroidism 93
  • 111. Observation and results Out of the 32 recruited cases 6 cases shown marked relief. These 6cases were fresh cases. Moderate relief was observed in chronic cases and in thosethyronorm withdrawal cases. 4 cases with long duration showed mild relief.Complete relief and no relief were not observed in the present study. Table 5.14 showing the result of overall treatment: Relief No. of patients Percentage Complete relief 0 0% Marked relief 6 18.75% Moderate relief 22 68.75% Mild relief 4 12.50% No relief 0 0%Hypothyroidism 94
  • 112. GRAPH 5.1 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO AGE. Graph5.1 show ing the incidence of hypothyroidism a/c to age 50 40 30 20 10 0 age bet 10-20 20-30 30-40 40-50 50-60 age bet 10-20 20-30 30-40 40-50 50-60GRAPH 5.2 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO SEX. Graph 2 showing the incidence of hypothyroidism a/c to sex 100 90 80 70 60 50 93.75 40 30 20 10 6.25 0 male femaleGRAPH 5.3: SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TOOCCUPATION Graph5.3 show ing the incidence of hypothyroidism a/c to occupation 60 , 40 , 56.25 20 , , 21.87 , 18.75 0 , , , 3.12 , house w ife student sedentary w ork hard w ork
  • 113. GRAPH 5.4 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO SES. 60 poor 40 low er middle class 20 middle class upper middle class 0 upper middle class middle class low er middle class poorGRAPH 5.5 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO DIET 100 80 60 93.75 40 20 0 veg mixeddietGRAPH5.6 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO F/H Family history 50 40 30 20 10 0 parents DM m other hypothyroid siblings hypothyroid daughter hypothyroid not associated
  • 114. GRAPH 5.7 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO P/H 20 15 10 not associated 5 RA steroids hysterectomy 0 depression/insomniaGRAPH 5.8 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TOPRAKRITI 45 40 35 30 25 20 40.62 15 28.12 10 5 9.37 12.75 6.25 03.12 vata predominent pitta predominent kapha predominent vatapitta vatakapha pittakapha
  • 115. GRAPH 5.9 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO SARA 50 45 40 35 30 25 46.87 20 34.37 15 10 18.75 5 0 twak mamsa medoGRAPH 5.10 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO BMI 59.37 60 50 40 37.5 30 20 10 3.12 0 below 20 20-25 above 25
  • 116. GRAPH 5.11 SHOWING THE LEVELS OF TSH BEFORE AND AFTERTREATMENT: 140 120 100 80 60 40 20 0 BT AT 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16GRAPH 5.12 SHOWING THE SYMPTOAMTIC RELIEF PERCENTAGE 30 25 20 15 10 5 0 BT AT wt.gain vertigo Easy fatigability lethargy cold intolerence hair loss slowness iof memory , anorexia constiaption gaseous distension voice changes mens.irregularites oligo/amenorrhoea parasthesia muscle cramps muscle stiffness dry skin dull hair edema slow reflexes goiter
  • 117. GRAPH 5.13 SHOWING THE OVER ALL RELIEF PERCENTAGE: Over all relief percentage 70 60 50 40 30 20 10 0 Complete relief Marked relief Moderate relief Mild relief Norelief
  • 118. Discussion DISCUSSION Hypothyroidism results when the thyroid gland produces less thannormal amounts of thyroid hormones. The result is the slowing down of manybodily functions. Since body has the ability to compensate for a failing thyroid glandby increasing the stimulation to it, much like pressing down on the acceleratorwhen climbing a hill to keep the car going at the same speed. However as thyroidhormone production decreases the body’s metabolism slows. Hypothyroidism doesn’t have any characteristic symptoms. Thereare no symptoms that people with hypothyroidism always have and manysymptoms of hypothyroidism can occur in people with other diseases.Hypothyroidism is sometimes referred to as a "silent" disease because earlysymptoms may be so mild that no one realizes anything is wrong. Kanchanara Guggulu (Sa. Sam), a well-known Ayurvedic drug isselected for this trail to evaluate its efficacy on hypothyroidism. The trail wasconducted on 32 patients from the Govt Ayurvedic Hosp, Erragadda; Analysis wasmade to assess the results in relation to various factors. It is a well-known fact that the disease Hypothyroidism is morecommon in women than men, probably because hormonal imbalance acts as atrigger for thyroid problems. Women’s bodies have a delicate balance of hormonessuch as estrogen and progesterone, which can be upset when the body is understress and not receiving enough support. And also estrogens increases theconcentration of TBG and of total T3 and T4 levels. In the present clinical studyalso out of 32 patients 30 were female and 2 of them were male.Hypothyroidism 95
  • 119. Discussion Hypothyroidism can develop at any point in the life span. It is morecommon in adults. In this clinical trail age incidence is high in the 2nd and 3rddecades, 80% of the cases were found in this age group. It may be because themedical Practioners and the patients are now more aware of this disease than in thelast few decades. Actually the women, especially those older than 50, are more likelyto have hypothyroidism. But the symptoms of hypothyroidism are often subtle, orpeople believe their symptoms are due to stress, depression, or "getting older," ormay frequently mistake for other conditions; it is not unusual for someone withhypothyroidism to go undiagnosed, sometimes for many years. And also becausethe symptoms of hypothyroidism and menopause are so similar, hypothyroidismmay easily be missed. In the recent year’s peculiar changes in the cultural and social areasforcing the human beings to arenas of tremendous stress. It is becoming moreprevalent in the modern society and upper socio economic classes. As thyroidgland is one of the sensitive glands in the body it stimulates to stress easily theincidence is high in this group. Whereas iodine deficiency hypothyroidism isassociated with lower/poor socio economic classes due to poor nutrition. The disease is seen more in 1. Kapha prakriti predominents,2.Mamsa, Medo sara predominants; 3. Non- vegetarians; 4. Those who consumesaturated fatty diet 5. People who takes rest for more than 10-15 hrs/day;6. Whose BMI is above 20. These all come under one umbrella ‘’the sedentary life style’’. Heredity plays a role in both under active and overactive thyroid;Recent studies show that 20% of the diabetic daughters area at the risk ofHypothyroidism 96
  • 120. Discussiondeveloping thyroid disorders. In the present trail 50% of the patients had a familyhistory of autoimmune disorders like DM, hypothyroidism, psoriasis etc., People with many autoimmune diseases have a higher risk forhypothyroidism. One patient suffered from Rheumatoid Arthritis and DiabetesMellitus. Another patient was ASMA +ve (Anti Smooth Muscle Antibodies) withchronic autoimmune hepatitis and Hasimoto’s Thyroiditis and Vitiligo. Anotherwas a case associated with Hyper Parathyroidism and Osteoporosis, Casupplement was added along with the trail drug. Another case a 25 yr female c/o unable to attain menarche withhypothyroidism diagnosed as turners syndrome with streak ovaries, she wascounseled properly as turners syndrome is highly impossible to treat and wasgiven treatment for hypothyroidism only. Numerous medications can affect the thyroid. Some drugs given fornonthyroid conditions have the side effect of inhibiting production of thyroidhormone within the thyroid gland. If these drugs are taken in large dosages or for along time, hypothyroidism may result. Nitroprusside, lithium, or iodides in theform of cough syrups, steroid and beta-blocker proponolol etc, and can inducehypothyroidism. Among the 32 patients 2 patients had a history of using steroids and3 patients had a history of using medications for depression and insomnia, 2patients had a history of using immunosuppressants. 6 patients had a history ofhysterectomy. It may be because hypothyroidism, in the early stages presents withMenorrhagia, which may be easily misdiagnosed. Another was a case of Juvenile Hypothyroidism, a 13 yr old boywith a BMI of more than 38 (wt 78kilos) with typical dull expressionless face,myxedamatous, thick, rough, cold doughy skin, hypercholestremia and delayedHypothyroidism 97
  • 121. DiscussionDTR’s, deep slow voice and other symptoms. Unfortunately the case was a dropout. The TSH levels became normal in the fresh 16 cases, in 2 patientsafter with drawl of the drug no recurrence is noted even after 6months. In thechronic cases that are already using the allopathic drug Thyronorm the drug wasgradually replaced with the trail drug. The TSH levels were maintained during thereplacement time. 4 patients were advised to continue the medication along withthe allopathic drug, as they are at the perimenopausal stages, and the chronicity ofthe disease is high. Coming to the results, 33% of relief was observed in those whocomplained of weight gain or unable to loss weight. Good results were observedin the fresh cases and who exercised regularly. But in the chronic cases that werehabituated to sedentary life style no significant results were observed. In thepatients who got relief there was 4/5 kilo of weight loss was observed in the threemonths duration. Exercise is especially important for weight loss amonghypothyroidism sufferers. Menstrual irregularities are the main symptom in hypothyroidpatients, which brings them to the hospital. In among the 32 patients 50% of thepatients complained of menstrual irregularities, most of them also complained ofoligomenorrhoea. 87.5% relief was observed in these cases. In 2 patients whocomplained of infertility one had altered FSH levels and Anovulatory cycles,another patient complained of repeated abortions. In both of these patientsinfertility was not relieved in 3 months durations of the course. Another main symptom constipation, poor appetite, gaseousdistention was 95% relieved after the treatment, as the all the ingredients in thetrail drug acts as Deepana and Pachana.Hypothyroidism 98
  • 122. Discussion Vertigo, mood disturbances, easy fatigability, tiredness, lethargy,slowness of memory, intellect and thought were the early symptoms and markedrelief was observed in these symptoms. Parasthesia’s, muscle cramps, weakness, muscles stiffness andaching were the main complaints of the chronic cases. 50-60% of relief wasobserved in these cases, as Guggulu acts as anti-inflammatory and analgesic. 15 patients complained of occasional voice changes like hoarseness;slowness of voice etc. 66% relief was noted. Hair loss was seen in 18 patients and60% of relief was observed in these cases. Dry, rough skin is seen in 70% casesand half of the patients got relief. 35% of cases showed dry, brittle, lusterless hair.Brittle nails, recurrent attacks of infections were observed in many patients. 85%of the cases showed significant improvement in puffiness of the face, feet andpalms. One patient’s only complaint was chronic rhinitis. Cardiac and respiratory symptoms are rarely observed in 32 patients.One patient aged 65yrs with Bradycardia, Cardiomegaly was seen. But it wasunder exclusion criteria. Goiter was seen in 11 cases, the trail drug showed effective in acuteand grade I Goiter. No significant results were observed in chronic cases. In onecase of euthyroid and MNG (multi nodular goiter) since 6yrs, the recent nodulenoted 3months back was reduced and other nodules become soft in consistency inthe duration of 3 months. Thinning of the lateral thirds of the eyebrows (Queen Anne’s sign)was noticed in one patient.Hypothyroidism 99
  • 123. DiscussionComplications: During the replacement of the allopathic drug puffiness of the face,mood disturbances, feeling of heaviness, muscle cramps were noted in 4 patients.But it was adjusted by increasing the dosage of the trial drug. Gastritis was another complaint seen in 2 patients, but it wasnegligible and was controlled after minimizing the dosage of KanchanaraGuggulu.Hypothyroidism 100
  • 124. Conclusion CONCLUSION 1. As the symptoms of hypothyroidism vary widely, and its clinical features mimics that to many other diseases, so it is often remains undiagnosed or misdiagnosed. 2. Clinical features for hypothyroidism are notorious, so it remains in the individuals without even diagnosed. 3. The incidence of hypothyroidism is seen in those with a family history of autoimmune disorders, history of autoimmune disorders, previous medication of antidepressants, steroids etc, those who adopt sedentary life style. 4. The incidence is high in females compared to males, may be probably due to hormonal imbalance triggers the disease. 5. Of the blood tests for hypothyroidism, the TSH is the most sensitive and best test for hypothyroidism. The normal range of TSH is 0.30-5.5uIU/ml. If the TSH level is above 6, then a diagnosis of hypothyroidism was made. But most people feel best when their TSH level is between 0.5 and 2.5. 6. But FT4 is the accurate diagnosis for the disease. 7. The trail drug Kanchanara Guggulu and Shigru Patra Kwatha is found to be beneficial in recently diagnosed cases. 8. Mild to moderate relief was noted in patients who are already using the drug thyronorm and it can be completely replaceable with the trail drug depending upon the rogi bala and rogibala. TSH levels and the clinical features should be carefully monitored.Hypothyroidism 101
  • 125. Conclusion 9. The patients who are in perimenopausal or menopausal stages, who has a chronicity of more than 10yrs, who has a history of autoimmune disorders it would be advisable to continue the medication along with the thyronorm. 10. Further research is recommended in i) The patients who are allergic to Guggulu. ii) The patients suffering from complicated symptoms like bradycardia, cardiomegaly, sleep apnea etc. iii) In pregnant and elderly 11. Further drug research need to be done i) Thyroid stimulatory drugs ii) Iodine rich drugs iii) Selenium containing drugs or helps in absorbing Se like Pippali etc. iv) Immuno modulator drugs useful in AITD’s. 12. It will be very beneficial if we can exactly correlate the disease hypothyroidism in Ayurveda.Hypothyroidism 102
  • 126. Summary SUMMARYIn Part I: • Importance of the disease hypothyroidism in present days and criteria for selection of the disease was described in the chapter Introduction. • History of hypothyroidism from the beginning of endocrinology to modern days was described in the chapter Historical aspect of Hypothyroidism. • Anatomy, physiology of the thyroid gland and the role of iodine was described in the shareera.In Part II:Disease review was explained under sub heads • Nidana of hypothyroidism the etiological factors of hypothyroidism primary, secondary and tertiary hypothyroidism and their causes were explained. • In Samprapti, pathogenesis of the disease iodine deficiency hypothyroidism, Autoimmune Thyroid Diseases were explained. • In Rupa of the disease, the clinical features of the hypothyroidism according to the systemic manifestation of the disease were explained. • Lakshanika Samprapti the effects of decreased thyroid hormone and how they cause different symptoms and pathological changes in different systems was explained. • Galaganda as explained in the Ayurvedic classics was described.Hypothyroidism 103
  • 127. Summary • Investigations for hypothyroidism: Estimation of T3, T4, TSH, FT4, FT3, ultrasound, FNAC, etc were explained. • Complications of hypothyroidism: goiter, heart problem, myxedema coma were the main complications for hypothyroidism. • Goiter and its types were explained in this chapter. • Ayurvedic Concept of Hypothyroidism including Galaganda, Agnimandya etc. were explained. • Sadhyasadhyata of Hypothyroidism explained as per the causes of Hypothyroidism.In part III • Chikitsa yojana: The chikitsa of hypothyroidism, the thyroid stimulators, immuno modulators, iodine rich drugs, deepana, pachana drugs were discussed here. • Pathyapathya the ahara and vihara’ s which are suitable and non suitable for the patient were described.In part IV • Drug review: The drug Kanchanar Guggulu and Shigru Patra Kwatha were selected for clinical study, were described here.In part V • Material and methods: materials required for the study were the patients, drug. Both subjective and objective parameters were taken into consideration. The dosage of the drug was 250mg b.d and 200ml of Shigru patra kwatha. The duration of the treatment was 3months.Hypothyroidism 104
  • 128. Summary • Observations: The conditions of the patient were observed carefully and the data was analysed carefully. • Results: Based on the observations made the results are assessed. The results are assessed as complete relief, marked relief, moderate relief, mild relief, and no relief from the clinical features of the disease. • Discussion and conclusion: disease, drug aspects observations and results are discussed elaborately on various angles. From this the conclusions are drawn.In Appendices • Bibliography, Case sheet, and BMI chart were included.Hypothyroidism 105
  • 129. References REFERENCES 1. A SHORT HISTORY OF MEDICINE, Singer C, Underwood EA. a. 2nd Ed, oxford, oxford university press, 1962. 2. A HISTORY OF ENDOCRINOLOGY, Hudhes AF, journal of the history of medicine and allied sciences, 1977 3. PRINCIPLES OF ANATOMY AND PHYSIOLOGY; Gerard J Tortora, Harper & ROW publications, 1984. 4. Grays text book of anatomy-Henry gray 5. Clinically oriented anatomy 6. Human physiology by C.C. CHUTTERJEE, medical allied agency, Calcutta, 1988. 7. Endocrine Pathophysiology Hershman, J.M; lea and fibriger, 1998. 8. Applied Physiology –By best And Taylor. 9. Clinical guide to nutrition and dietary supplements in disease management, Jennifer R. Jamison. Churchill Livingston, 2003 10. Robbins Text book of pathology –Robbin 11. Current Medical Diagnosis and Treatment. 12. Principles of internal medicine-Harrisons-12th ed 1991 13. Essential endocrinlogy By Charles Brooks,Nicholas marshall; Blackwell series, 3rd ed. 14. A clinical hand book of endocrinology and metabolic disesases by Neil I Robin, partheton publications, 1995. 15. Clinical Endocrinolgy And Diabetis, Edited by michel C. Shepard and Gayne A franklyn, Pub: Churchill Livingston 1988. 16. Essential Endocrinology by Oxford University Press, 1966. 17. Human Endocrinology by Paul R. GUARD, Taylor and Francis, 1988 18. Oxford Hand Book Of Endocrinology And Diabetis by Turner, Helen, Wass, John., Oxford U.P, 2001Hypothyroidism
  • 130. References 19. Essential Endocrinology by John F. Leycock, Peter H Wise, OXFORD UNIVERSITY PRESS.1999 20. Endocrinology by Andrew lewy, Stafford lightman, Oxford university press, 1997. 21. Endocrinology by Martin Hartog , Blackwell Scientific, 1987. 22. Diagnostic tests in endocrinology and diabetis; Ed-By P-Boulax and LH Brooks. 23. Text book of surgery by Das, Dr.S.Das, calcutta2001. 24. Sarangadhara Samhita 25. Astanga Hridayam V.Ramaswamy and sons. Madras, 1954 26. Bhava Prakasa; mukkamala venkata sastry, Panduranga printing works,VJA.1959 27. Charaka samhita ; agnivesa, V.Ramaswamy and sons. Madras. 28. Nighnatu Adarsh- Bapalal G Vaidya, Choukhambha Bharathi academy.Varanasi. 29. Indian medicinal plants, Kirtikar and Basu; Jayyed press, Delhi, 1975. 30. Susrutha Samhita by Ambika Datta Sastry, Choukhambha samsthan. Varanasi. 31. Kashyapa Samhita 32. www.ayurvedaforu.com 33. Clinical researches by Dr.Tripati & others 34. Dravyaguna vignana by J.L.N.Sastry.Hypothyroidism
  • 131. BIBILOGRAPHY1. A short History of Medicine, Singer C, Underwood EA, 2nd edition; Oxford, Oxford university press.1962.2. A History of Endocrinology, Hudhes AF, journal of the history of medicine and allied sciences.3. Applied physiology by Best and Taylor.4. A Clinical Hand book of Endocrinology and Metabolic Diseases By Neil I Robin, Partheton Publications, 1995.5. Astanga sangraham, V Rangacharyulu. Telugu academy Hyd. 19796. Astanga Hridaya V Ramaswamy and Sons, Madras, 1954.7. Bhava Prakasa, Mukkamala venkata sastry, Panduranga Printing Works , VJA, 1959.8. Bhava prakasha nighantu, Dr Krishna Chandra Chunekar, Choukhambha Sanskrit sansthan, varanasi, 5th ed 1959.9. Bhaishajya kalpana, dr k nisteswar, AP Ayurved Literature Improvement Trust.10. Bhaishajya Ratnavali, Ambika Datta Sastry, 1969,11. Bhela samhita, SVS Sastry, CRR sarma, CCRIM&H, New delhi, 1977.12. Charaka samhita, Agnivesha, V Ramaswamy and sons, Madras.13. Clinically Oriented Anatomy14. Clinical Guide to Nutrition and Dietary Supplements in Disease Management, Jennifer R Jemison, Churchill Livingston 2003.15. Concept of Ama in Ayurveda, Dr M Srinivasulu, Chaukhambha Sanskrit series, Varanasi, 2005.16. Concept of Agni in Ayurveda, Bhagvan Das, Chaukhambha Sanskrit series,17. Compendium of Indian Medicinal plants By Ram P Rastogi, BN Mehrotra, Central Drug Research Institute, Lucknow.18. Current Medical Diagnosis and Treatment,
  • 132. 19. Clinical Endocrinology and Diabetis, Edited By Micheal C Shepeard and Gayne A Franklyn Publications, Churchill Livingstone, 1988.20. Diagnostic tests in Endocrinology and Diabetis, Ed by P Boulax and LH Books.21. Digestion and metabolism in ayurveda.C Dwarakanath, Vaidyanath Ayurved Bhavan, 1947.22. Dravyaguna Vignanam By K Nisteswar, AP Literature Improvement Trust.23. Dravyaguna Vignan by JLN Sastry, Chaukhambha Sanskrit series.24. Endocrine Patho Physiology, Hershman, JM Lea and Fibriger, 1998.25. Essential endocrinology Charles Brooks, Nicholas Marshal, Blackwell series, 3rd Ed.26. Essential endocrinology by Oxford University Press, 1966.27. Essential endocrinology by John f Leycock , Peter H Wise, Oxford University Press. 1999.28. Essentials of Medical Pharmacology, KD Tripathi, Jaypee Publications, 4th ed, 1999.29. Essential Pediatrics, OP Ghai, Interprint Publications.30. Endocrinology by Andrew lewy, Stafford lightman, Oxford University Press , 1997.31. Endocrinology by Martin Hartog, Blackwell Scientific, 1987.32. Gray’s textbook of anatomy Henry Gray.33. Human physiology by CC Chuttarjee. Medical allied Agency, Calcutta, 1988.34. Human Endocrinolgy by Paul R Guard, Taylor and Francis, 1988.35. Harita samhita by harita, Sri Venkateswara Press, 1849.36. Indian medicinal plants, Kirtikar and Basu, Jayyed Press, Delhi, 1975.37. ICMR, Medicinal Plants of India, 1976.38. Indian Material Medica, Nadkarni.
  • 133. 39. Kashyapa Samhita, Pt Hemaraj Sharma, Choukambha Sanskrit Series, Varanasi.40. Madhava Nidana, Sri Yadundanopadhyaya, Choukambha Sanskrit Series, Varanasi.41. Nighntu Adarsh, Bapalal G Vaidya, Choukambha Sanskrit Series, Varanasi.42. Oxford handbook of endocrinology and Diabetes by Turner Helen Wass, John, Oxford University Press, 2001.43. Principles of Anatomy and Physiology Gerard J Tortora, Harper and Row Publications, 1984.44. Principles of Internal Medicine, Harrisons 12th ed 1991.45. Robbins text book of pathology, Robbin46. Sarangadhara Samhita, Sarangadhara, Vavilla Ramaswamy and sons, 1952.47. Shabda Sthoma Mahanidhi, Sri Daranath, Takravachaspathi Bhttacharya, Vidanyantara press, Calcutta 1976.48. Susruth Samhita, Ambika Datta Sastry, Choukambha Sanskrit series, Varanasi.1954.49. Textbook of Surgery by Das, Dr. S das, Calcutta 2001.50. Priciples of practice and medicine by Davidson, 17th ed.51. Yoga Ratnakram by Yeturu Srinivasacharyulu, Nellore, 1939.
  • 134. PATIENT CONSENT FORM I____________________________________________________exercising my free power of choice, hereby give you my complete consent to beincluded as a subject in the Clinical trial on "A CLINICAL STUDY ON THEEFFECT OF KANCHANARA GUGGULU AND SHIGRU PATRAKWATHA ON HYPOTHYROIDISM". I have been informed to mysatisfaction by the attending Doctor, the purpose of the Clinical Trial and thenature of drug treatment, follow-up and probable complications. I am also readyto undergo necessary Laboratory Investigations to monitor and safeguard mybody functions. I am also aware of my right to opt out of the trial at any time during thecourse of the trial without having to give the reasons for doing so. Signature of the Doctor Signature of the Patient / Guardian (Dr.VVL Prasuna) vi
  • 135. Post graduate department of Kayachikitsa Dr. BRKR Govt. Ayurvedic College HYDERABAD Special case sheet for hypothyroidismSerial no:Date: Occupation:Name: Marital status:Age: Socio economic status:Sex: Address: 1. Chief complaints and duration: 2. Associated symptoms: 3. History of Present illness: 4. History of Previous illness: 5. Personal history: 6. Family history: 7. Present/ Previous drug history:
  • 136. 8. Astha sthana pariksha: 1. Nadi: 5. Sabda: 2. Mutram: 6. Sparsha: 3. Malam: 7. Drik: 4. Jihwa: 8. Akriti:9. Dasavida pariksha: 1. Prakriti: 6. Vayah: 2. Vikriti: 7. Satwam: 3. Sara: 8. Satmyam: 4. Samhanana: 9. Ahara sakti: 5. Pramana: 10. Vyayama sakti:10. Vikriti pariksha: 1. Nidana: 2. Purvarupa: 3. Rupa: 4. Upasaya: 5. Samprapti:11. General examination:1. BMI:2. CVS:3. Nervous system: Reflexes: Rt: Lt: UL: 1. Biceps: 2. Triceps: 3. Supinator: LL: 1. Knee jerk: 2. Ankle jerk:4. Skin& hair:5. Thyroid:
  • 137. 12. Clinical study (subjective parameters): Symptoms Before Tt During Tt During Tt After Tt Dt: Dt: Dt: Dt: Genl: 1.Vertigo 2.Wt. gain Neuro muscular: 3.easy fatigability 4. lethargy 5.Myalgia 6. GI disturbances: poor appetite: Constipation: 7. Dermatological: 8. Menstrual irregularities 9. Speech disturbances: 10. Others if any
  • 138. 14. Objective parameters: Investigations: Before Tt After Tt Dt: Dt: Thyroid profile: 1. T3 2. T4 3. TSH15. Observation:14. Result: 1. Cured: 2. Partially cured: 3. No responseSignature Signature SignatureP.G.Scholar co-supervisor supervisor