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. Ayurvedic College, HYDERABAD

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Hypothyroidism kc002 hyd

  1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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