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Hypothyroidism                                 Dr.Vitrag Shah                                 Second Year Resident        ...
Introduction According to a projection from various studies on thyroid    disease, it has been estimated that about 42 mi...
Thyroid Regulation       HYPOTHALAMUS - TRH        ANT. PITUITARY - TSH                             TSH -R          THYROI...
In the Thyroid GlandThere the following 5 steps in the hormonogenesis1.      Trapping of inorganic Iodine from dietary Iod...
Thyroid hormone biosynthesis         Thyroid hormone synthesis includes the following steps: (1) iodide (I -) trapping by ...
The Thyronines Mono Iodo Tyrosine – MIT Di Iodo Tyrosine – DIT Tri Iodo Thyronine – T3 – half life 6 hours Tetra Iodo Thyr...
The ThyroxinesTri Iodo Thyronine – T3     - 10% is from thyroid gland     - 90% derived from conversion of T4 to T3Tetra I...
Classification of Hypothyroidism Primary hypothyroidism(90%) is characterized by a high    serum thyrotropin (TSH) concen...
vitrag24 - www.medicalgeek.com
GOITROGENSDRUGS Anti-thyroid Cough medicines Sulfonamides Lithium Phenylbutazone PAS Oral hypoglycemic agentsvitrag24 - ww...
GOITROGENS FOOD   Soybeans   Millet   Cassava   Cabbagevitrag24 - www.medicalgeek.com
vitrag24 - www.medicalgeek.com
vitrag24 - www.medicalgeek.com
Congenital Hypothyroidism The majority of infants appear normal at birth, and   <10% are diagnosed based on clinical feat...
vitrag24 - www.medicalgeek.com
Congenital Hypothyroidismvitrag24 - www.medicalgeek.com
vitrag24 - www.medicalgeek.com
vitrag24 - www.medicalgeek.com
vitrag24 - www.medicalgeek.com
Diagnosis & Treatment Because of the severe neurologic consequences of untreated  congenital hypothyroidism, neonatal scr...
Autoimmune Hypothyroidism Autoimmune hypothyroidism may be associated with a  goiter (Hashimotos, or goitrous thyroiditis...
Epidemiology The mean age at diagnosis is 60 years, and the   prevalence of overt hypothyroidism increases with   age. I...
Pathogenesis In Hashimotos thyroiditis, there is a marked   lymphocytic infiltration of the thyroid with germinal   cente...
vitrag24 - www.medicalgeek.com
Associated conditions Other Autoimmune disorders: (MC)   Type 1 diabetes mellitus   Addisons disease   Pernicious anem...
Other causes of hypothyroidism Iatrogenic hypothyroidism is a common cause of  hypothyroidism. In the first 3–4 months a...
 Iodine deficiency is responsible for endemic goiter and  cretinism but is an uncommon cause of adult  hypothyroidism unl...
Clinical Manifestations The onset is usually insidious, and the patient may become aware    of symptoms only when euthyro...
vitrag24 - www.medicalgeek.com
Differentian between Primary &secondary hypothyroidismFeatures                 Primary                   SecondarySkin    ...
CLINICAL MANIFESTATIONS Many of the manifestations of hypothyroidism reflect one  of two changes induced by lack of thyro...
vitrag24 - www.medicalgeek.com
Skin The skin is cool and pale in patients with hypothyroidism    because of decreased blood flow.   The epidermis has a...
Myxoedema with Carotineamiavitrag24 - www.medicalgeek.com
Eyes Periorbital edema Thinning of outer third of eyebrows (Madarosis) Graves ophthalmopathy may persist when   hypothy...
Hematologic Decrease in red blood cell mass Normochromic, normocytic hypoproliferative anemia Pernicious anemia occurs ...
Cardiovascular system Decrease in cardiac output that is mediated by reductions in    heart rate and contractility   Thy...
Respiratory system Fatigue, shortness of breath on exertion, rhinitis,  and decreased exercise capacity Hypoventilation ...
Gastrointestinal disorders Decreased gut motility results in constipation Decreased taste sensation. Gastric atrophy du...
Reproductive abnormalities Decreased fertility Early abortion Hypermenorrhea-menorrhagia (More common). Or  oligo- or a...
Neurological dysfunction Affects both CNS & PNS Slow growth and delayed facial maturation, delayed    appearance of perm...
Hashimotos encephalopathy Hashimotos encephalopathy has been defined as a  steroid-responsive syndrome associated with TP...
vitrag24 - www.medicalgeek.com
Musculoskeletal symptoms Joint pains, aches, and stiffness Increased prevalence of hyperuricemia and gout Elevated AST,...
Metabolic abnormalities Hyponatremia may result from a reduction in free  water clearance. Hypothyroidism must be exclude...
Drug clearance The clearance of many drugs, including   antiepileptic, anticoagulant, hypnotic and opioid   drugs, is dec...
Myxedema coma Myxedema coma is defined as severe hypothyroidism leading to    decreased mental status, hypothermia, and o...
Lab Evaluation                        Thyroid Function Tests Total T4 (thyroxine), Total T3 (triiodothyronine) Free T4 ,...
Thyroid Antibodies         Anti Microsomal (TM ) Antibodies         Anti Thyroglobulin (TG) Antibodies         Anti Thy...
Tests of thyroid functionTest                                     Reference Ranges*TSH                                    ...
Thyroxine (T4) and Triiodothyronine (T3) Thyroxine (T4) is the principal hormone secreted by the  thyroid gland, but the ...
What tests should I order ?      As per the Guidelines of the AACE and ATA, ITS      1. TSH alone if Hypothyroidism is sus...
Which Lab to choose ?1.   Depends on the method of estimation of hormones2.   Equilibrium Dialysis is the gold Standard fo...
Indications to test for hypothyroidism   Clinical symptoms and signs   Fatigue                       Laboratory test abnor...
Indications to test for hypothyroidism                         Risk factors for hypothyroidismAutoimmune thyroiditis      ...
How to interpret results ?The Nine Square GameTo evaluate our Thyroid patientAs per the AACE and ITS Guidelines  vitrag24 ...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                               LOW        NORMAL       HIGH              ...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                                         EUTHYROID                       ...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                                                     PRIMARY             ...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                               PRIMARY                             HYPERT...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                              SECONDARY                             HYPOT...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                                                    SECONDARY            ...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                              SUB-CLINICAL                             HY...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                                                   SUB-CLINICAL          ...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                                         NON THYROID                     ...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                                           NTI or Pt.                    ...
BASIC THYROID EVALUATION    FREE THYROXINE or FT4                               PRIMARY      NTI or Pt. SECONDARY         ...
vitrag24 - www.medicalgeek.com
Common Patterns of Thyroid FunctionTests in Critically Ill PatientsNon-Thyroidal Ilness       Free T4          Free T3    ...
T.F.T. in Progressive Hypothyroidism                                    TSH      Mild                     Moderate       S...
vitrag24 - www.medicalgeek.com
vitrag24 - www.medicalgeek.com
vitrag24 - www.medicalgeek.com
Algorithm for Hypothyroidism                                           Measure TSH                 Elevated TSH           ...
Treatment Goal : Normalize TSH level regardless of cause of   hypothyroidism Treatment of choice is thyroxine Brand con...
Determinants of ThyroxineRequirements Age Severity and duration of hypothyroidism Weight Malabsorption Pregnancy Pre...
Treatment : Outline Goal : normalize TSH level, , ideally in the lower half of    the reference range.   Single daily do...
vitrag24 - www.medicalgeek.com
Treatment : Clinical Hypothyroidism If there is no residual thyroid function, the daily replacement dose    of levothyrox...
Follow-up After 6 to 8 Weeks ofThyroxine TherapyIf Repeat TSH is                 Then> 4.0 mU/L                       Incr...
 There is no place for liothyronine alone as long-term  replacement, because the short half-life necessitates three  or f...
Over - and Under-Replacement Risks Over-replacement Risks Reduced bone density/osteoporosis Tachycardia, arrhythmia : A...
Recovery after L-Thyroxinevitrag24 - www.medicalgeek.com
Recovery after L-Thyroxinevitrag24 - www.medicalgeek.com
Treatment : Subclinical Hypothyroidism By definition, subclinical hypothyroidism refers to    biochemical evidence of thy...
Special Treatment Considerations Women with a history or high risk of hypothyroidism should  ensure that they are euthyro...
Treatment : Myxedema coma Levothyroxine can initially be administered as a single IV    bolus of 500 µg, which serves as ...
Supportive Treatment : Myxedema coma External warming is indicated only if the temperature is <30°C,    as it can result ...
Diet in Iodine deficiency         Iodized salt         Selenium supplementation         Avoid Cassava         Avoid ca...
References Williams Textbook of Endocrinology – 12th Edition Harrison’s Principles of internal medicine – 18th Edition ...
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  1. 1. Hypothyroidism Dr.Vitrag Shah Second Year Resident MD, Medicine GMC,Suratvitrag24 - www.medicalgeek.com
  2. 2. Introduction According to a projection from various studies on thyroid disease, it has been estimated that about 42 million people in India suffer from thyroid diseases. Congenital hypothyroidism is common in India, the disease occurring in 1 out of 2640 neonates. The prevalence of hypothyroidism was 3.9% Second only to DM as most common endocrine disorder. Incidence increases with age. More common in females. 2-3% of older women. The term myxedema, formerly used as a synonym for hypothyroidism, refers to the appearance of the skin and subcutaneous tissues in the patient who is in a severely hypothyroid state. vitrag24 - www.medicalgeek.com
  3. 3. Thyroid Regulation HYPOTHALAMUS - TRH ANT. PITUITARY - TSH TSH -R THYROID T4 and T3 PLASMA T4 + FT4 PLASMA T3 + FT3 TISSUES FT4 to FT3, rT3 vitrag24 - www.medicalgeek.com
  4. 4. In the Thyroid GlandThere the following 5 steps in the hormonogenesis1. Trapping of inorganic Iodine from dietary Iodides2. Activation of Iodine to high valance I23. Incorporation of I2 into Tyrosine of Thyroid Globulin4. Coupling of formed MIT and DIT to form T4 & T35. Proteolysis of Thyroglobulin to release T4 & T3 vitrag24 - www.medicalgeek.com
  5. 5. Thyroid hormone biosynthesis Thyroid hormone synthesis includes the following steps: (1) iodide (I -) trapping by the thyroid follicular cells; (2) diffusion of iodide to the apex of the cells; (3) transport of iodide into the colloid; (4) oxidation of inorganic iodide to iodine and incorporation of iodine into tyrosine residues within thyroglobulin molecules in the colloid; (5) combination of two diiodotyrosine (DIT) molecules to form tetraiodothyronine (thyroxine, T4) or of monoiodotyrosine (MIT) with DIT to form triiodothyronine (T3); (6) uptake of thyroglobulin from the colloid into the follicular cell by endocytosis, fusion of the thyroglobulin with a lysosome, and proteolysis and release of T4, T3, DIT, and MIT; (7) release of T4 and T3 into the circulation; and (8) deiodination of DIT and MIT tovitrag24 yield tyrosine. T3 is also formed from monodeiodination of T4 in the thyroid and in peripheral - www.medicalgeek.com tissues. Modified from Scientific American Medicine, Scientific American, New York, 1995.
  6. 6. The Thyronines Mono Iodo Tyrosine – MIT Di Iodo Tyrosine – DIT Tri Iodo Thyronine – T3 – half life 6 hours Tetra Iodo Thyronine – T4 half life 7 days Reverse T3 - metabolically inactive T4 is 99.9% protein bound to TBG, TPA, TA T3 is 99.5% protein bound to TBG, TPA, TA Bound hormones are inactive – should not be measured Only Free T4 and Free T3 are metabolically active vitrag24 - www.medicalgeek.com
  7. 7. The ThyroxinesTri Iodo Thyronine – T3 - 10% is from thyroid gland - 90% derived from conversion of T4 to T3Tetra Iodo Thyronine – T4 - Is exclusively from thyroid glandFrom the thyroid gland - 80% of hormone secreted is T4 - 20% of hormone secreted is T3vitrag24 - www.medicalgeek.com
  8. 8. Classification of Hypothyroidism Primary hypothyroidism(90%) is characterized by a high serum thyrotropin (TSH) concentration and a low serum free thyroxine (T4) concentration. Subclinical hypothyroidism is defined biochemically as a normal free T4 concentration in the presence of an elevated TSH concentration. Other terms for this condition are mild hypothyroidism, early thyroid failure, preclinical hypothyroidism, and decreased thyroid reserve. Secondary (central) hypothyroidism is characterized by a low serum T4 concentration and a serum TSH concentration that is not appropriately elevated. Transient or temporary hypothyroidism can be observed as a phase of subacute thyroiditis. Consumptive hypothyroidism, identified in an increasing number of clinical settings, is the result of accelerated inactivation of thyroid hormone by the type 3 iodothyronine deiodinase (D3). vitrag24 - www.medicalgeek.com
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  10. 10. GOITROGENSDRUGS Anti-thyroid Cough medicines Sulfonamides Lithium Phenylbutazone PAS Oral hypoglycemic agentsvitrag24 - www.medicalgeek.com
  11. 11. GOITROGENS FOOD Soybeans Millet Cassava Cabbagevitrag24 - www.medicalgeek.com
  12. 12. vitrag24 - www.medicalgeek.com
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  14. 14. Congenital Hypothyroidism The majority of infants appear normal at birth, and <10% are diagnosed based on clinical features, which include prolonged jaundice, feeding problems, hypotonia, enlarged tongue, delayed bone maturation, and umbilical hernia. Importantly, permanent neurologic damage results if treatment is delayed. Typical features of adult hypothyroidism may also be present. Other congenital malformations, especially cardiac, are four times more common in congenital hypothyroidism. vitrag24 - www.medicalgeek.com
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  16. 16. Congenital Hypothyroidismvitrag24 - www.medicalgeek.com
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  20. 20. Diagnosis & Treatment Because of the severe neurologic consequences of untreated congenital hypothyroidism, neonatal screening programs have been established based on measurement of TSH or T4 levels in heel-prick blood specimens. When the diagnosis is confirmed, T4 is instituted at a dose of 10–15 µg/kg per day, and the dose is adjusted by close monitoring of TSH levels. T4 requirements are relatively great during the first year of life, and a high circulating T4 level is usually needed to normalize TSH. Early treatment with T4 results in normal IQ levels, but subtle neurodevelopmental abnormalities may occur in those with the most severe hypothyroidism at diagnosis or when treatment is delayed or suboptimal. vitrag24 - www.medicalgeek.com
  21. 21. Autoimmune Hypothyroidism Autoimmune hypothyroidism may be associated with a goiter (Hashimotos, or goitrous thyroiditis) or, at the later stages of the disease, minimal residual thyroid tissue (atrophic thyroiditis). Because the autoimmune process gradually reduces thyroid function, there is a phase of compensation when normal thyroid hormone levels are maintained by a rise in TSH. Though some patients may have minor symptoms, this state is called subclinical hypothyroidism. Later, unbound T4 levels fall and TSH levels rise further; symptoms become more readily apparent at this stage (usually TSH >10 mIU/L), which is referred to as clinical hypothyroidism or overt hypothyroidism. vitrag24 - www.medicalgeek.com
  22. 22. Epidemiology The mean age at diagnosis is 60 years, and the prevalence of overt hypothyroidism increases with age. Iodine deficiency is most common cause of hypothyroidism worldwide while Autoimmune hypothyroidism is most common cause in iodine sufficient regions.vitrag24 - www.medicalgeek.com
  23. 23. Pathogenesis In Hashimotos thyroiditis, there is a marked lymphocytic infiltration of the thyroid with germinal center formation, atrophy of the thyroid follicles accompanied by oxyphil metaplasia, absence of colloid, and mild to moderate fibrosis. In atrophic thyroiditis, the fibrosis is much more extensive, lymphocyte infiltration is less pronounced, and thyroid follicles are almost completely absent. Atrophic thyroiditis likely represents the end stage of Hashimotos thyroiditis rather than a distinct disorder. Genetic Associations: HLA-DR (3,4,5) & CTLA-4 (Cytotoxic T Lymphocyte associated antigen 4) polymorphism Modifying Environmental Factor : Chronic exposure to high iodine diet No role of infection except Congenital Rubella Syndrome vitrag24 - www.medicalgeek.com
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  25. 25. Associated conditions Other Autoimmune disorders: (MC) Type 1 diabetes mellitus Addisons disease Pernicious anemia Vitiligo Alopecia areata Celiac disease Dermatitis Herpatiformis Chronic Active Hepatitis RA, SLE, Sjogren syndrome Thyroid associated ophthalmopathy( in 5% of pt) Turner syndrome, Down’s syndrome Type 1 or 2 polyglandular autoimmune syndromevitrag24 - www.medicalgeek.com
  26. 26. Other causes of hypothyroidism Iatrogenic hypothyroidism is a common cause of hypothyroidism. In the first 3–4 months after radioiodine treatment, transient hypothyroidism may occur due to reversible radiation damage. Low-dose thyroxine treatment can be withdrawn if recovery occurs. Because TSH levels are suppressed by hyperthyroidism, unbound T4 levels are a better measure of thyroid function than TSH in the months following radioiodine treatment. Mild hypothyroidism after subtotal thyroidectomy may also resolve after several months, as the gland remnant is stimulated by increased TSH levels. vitrag24 - www.medicalgeek.com
  27. 27.  Iodine deficiency is responsible for endemic goiter and cretinism but is an uncommon cause of adult hypothyroidism unless the iodine intake is very low or there are complicating factors, such as the consumption of thiocyanates in cassava or selenium deficiency. Paradoxically, chronic iodine excess (Rx with amiodarone, lithium) can also induce goiter and hypothyroidism, individuals with autoimmune thyroiditis are especially susceptible. Secondary hypothyroidism is usually diagnosed in the context of other anterior pituitary hormone deficiencies; isolated TSH deficiency is very rare. TSH levels may be low, normal, or even slightly increased in secondary hypothyroidism; the latter is due to secretion of immunoactive but bioinactive forms of TSH. The diagnosis is confirmed by detecting a low unbound T4 level. vitrag24 - www.medicalgeek.com
  28. 28. Clinical Manifestations The onset is usually insidious, and the patient may become aware of symptoms only when euthyroidism is restored. Patients with Hashimotos thyroiditis may present because of goiter rather than symptoms of hypothyroidism. The goiter may not be large, but it is usually irregular and firm in consistency. Hypothyroidism is less prominent clinically and better tolerated when there is a gradual loss of thyroid function (as in most cases of primary hypothyroidism) than when it develops acutely after thyroidectomy or abrupt withdrawal of exogenous thyroid hormone. The symptoms of central hypothyroidism are usually milder & less obvious than in primary hypothyroidism because of concurrent symptoms of coexisting hormone deficiencies. i.e. hot flashes due to hypogonadism may mask the cold intolerance of hypothyroidism. When hypothyroidism follows treatment of Graves hyperthyroidism, some manifestations of Graves disease, such as ophthalmopathy and vitiligo, may persist throughout the patients life. vitrag24 - www.medicalgeek.com
  29. 29. vitrag24 - www.medicalgeek.com
  30. 30. Differentian between Primary &secondary hypothyroidismFeatures Primary SecondarySkin Thick, without wrinkles Thin with fine wrinklesHair Coarse FineMenstrual disturbances Menorrhagia AmenorrheaSecondary sexual Normal PoorcharacteristicsHeart size May be enlarged NormalGoiter May be present AbsentSoft tissue edema Marked AbsentBP Normal/High LowCholesterol Increased NormalTSH High LowPlasma Cortisol Normal LowTRH stimulation test Exaggerated response No responseThyroid- Autoantibodies May be present vitrag24 www.medicalgeek.com Absent
  31. 31. CLINICAL MANIFESTATIONS Many of the manifestations of hypothyroidism reflect one of two changes induced by lack of thyroid hormone: A generalized slowing of metabolic processes. This can lead to abnormalities such as fatigue, slow movement and slow speech, cold intolerance, constipation, weight gain (but not morbid obesity), delayed relaxation of deep tendon reflexes, and bradycardia. Accumulation of matrix glycosaminoglycans in the interstitial spaces of many tissues. This can lead to coarse hair and skin, puffy facies, enlargement of the tongue, and hoarseness. These changes are often more easily recognized in young patients, and they may be attributed to aging in older patients. vitrag24 - www.medicalgeek.com
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  33. 33. Skin The skin is cool and pale in patients with hypothyroidism because of decreased blood flow. The epidermis has an atrophied cellular layer and hyperkeratosis that results in the characteristic dry roughness of the skin. Sweating is decreased because of decreases in calorigenesis and acinar gland secretion. A yellowish tinge may be present if the patient has carotenemia, while hyperpigmentation may be seen when primary hypothyroidism is associated with primary adrenal failure Hair may be coarse, hair loss is common, and the nails become brittle. Nonpitting edema (myxedema) occurs in severe hypothyroidism and may be generalized. It results from infiltration of the skin with glycosaminoglycans with associated water retention. Vitiligo and alopecia areata may be present in patients with hypothyroidism after treatment of Graves‘ hyperthyroidism. vitrag24 - www.medicalgeek.com
  34. 34. Myxoedema with Carotineamiavitrag24 - www.medicalgeek.com
  35. 35. Eyes Periorbital edema Thinning of outer third of eyebrows (Madarosis) Graves ophthalmopathy may persist when hypothyroidism develops after treatment of Graves hyperthyroidismvitrag24 - www.medicalgeek.com
  36. 36. Hematologic Decrease in red blood cell mass Normochromic, normocytic hypoproliferative anemia Pernicious anemia occurs in 10 percent of patients with hypothyroidism caused by chronic autoimmune thyroiditis : macrocytic anemia with marrow megaloblastosis Women in the childbearing years may develop iron deficiency anemia, secondary to menorrhagia. In patients with IDA and hypothyroidism, combined therapy with levothyroxine and oral iron supplements results in correction of the anemia, which may be refractory to treatment with iron alonevitrag24 - www.medicalgeek.com
  37. 37. Cardiovascular system Decrease in cardiac output that is mediated by reductions in heart rate and contractility Thyroid hormoneregulation of genes coding for specific myocardial enzymes involved in myocardial contractility and relaxation is responsible for the decrease in contractility. Reduced cardiac output probably contributes to decreased exercise capacity and shortness of breath during exercise. Pericardial effusion Hypercholesterolemia, which is caused by a decrease in the rate of cholesterol metabolism Hyperhomocystemia Diastolic Hypertension, because of an increase in peripheral vascular resistance. In normotensive patients, blood pressure increases are small (<150/100). ECG : Low voltage, sinus bradycardia, non-specific ST-T changesvitrag24 - www.medicalgeek.com
  38. 38. Respiratory system Fatigue, shortness of breath on exertion, rhinitis, and decreased exercise capacity Hypoventilation occurs because of respiratory muscle weakness and reduced pulmonary responses to hypoxia and hypercapnia Sleep apnea occurs in some patients with hypothyroidism, mostly as a result of macroglossia.vitrag24 - www.medicalgeek.com
  39. 39. Gastrointestinal disorders Decreased gut motility results in constipation Decreased taste sensation. Gastric atrophy due to the presence of antiparietal cell antibodies Celiac disease is four times more common in hypothyroid patients Modest weight gain (despite poor appetite)due to decreased metabolic rate and accumulation of fluid Ascites is a rare findingvitrag24 - www.medicalgeek.com
  40. 40. Reproductive abnormalities Decreased fertility Early abortion Hypermenorrhea-menorrhagia (More common). Or oligo- or amenorrhea (later stage) Low serum sex hormone-binding globulin concentration Hyperprolactinemia may occur, and is occasionally sufficiently severe to cause amenorrhea or galactorrhea Decreased libido, erectile dysfunctionvitrag24 - www.medicalgeek.com
  41. 41. Neurological dysfunction Affects both CNS & PNS Slow growth and delayed facial maturation, delayed appearance of permanent teeth Myopathy, with muscle swelling, is more common in children than in adults. In most cases, puberty is delayed, but precocious puberty sometimes occurs Intellectual impairment if the onset is before 3 years and the hormone deficiency is severe. Carpal tunnel and other entrapment syndromes Slow relaxation of tendon reflexes and pseudomyotonia Memory and concentration are impaired, Bradylalia Rare neurologic problems include reversible cerebellarvitrag24 - www.medicalgeek.com psychosis, and myxedema coma. ataxia, dementia,
  42. 42. Hashimotos encephalopathy Hashimotos encephalopathy has been defined as a steroid-responsive syndrome associated with TPO antibodies, myoclonus, and slow-wave activity on electroencephalography. Hashimotos encephalopathy is believed to be an immune-mediated disorder rather than representing the direct effect of an altered thyroid state on the central nervous system.vitrag24 - www.medicalgeek.com
  43. 43. vitrag24 - www.medicalgeek.com
  44. 44. Musculoskeletal symptoms Joint pains, aches, and stiffness Increased prevalence of hyperuricemia and gout Elevated AST, CK, LDHvitrag24 - www.medicalgeek.com
  45. 45. Metabolic abnormalities Hyponatremia may result from a reduction in free water clearance. Hypothyroidism must be excluded in any hyponatremic patient before making the diagnosis of the syndrome of inappropriate antidiuretic hormone secretion. Reversible increases in serum creatinine Hypercholesterolemia and hypertriglyceridemia Hyperhomocysteinemiavitrag24 - www.medicalgeek.com
  46. 46. Drug clearance The clearance of many drugs, including antiepileptic, anticoagulant, hypnotic and opioid drugs, is decreased in hypothyroidismvitrag24 - www.medicalgeek.com
  47. 47. Myxedema coma Myxedema coma is defined as severe hypothyroidism leading to decreased mental status, hypothermia, and other symptoms related to slowing of function in multiple organs. It is a medical emergency with a high mortality rate. There may be a history of treated hypothyroidism with poor compliance, or the patient may be previously undiagnosed. Myxedema coma almost always occurs in the elderly and is usually precipitated by factors that impair respiration, such as drugs (especially sedatives, anesthetics, antidepressants), pneumonia, congestive heart failure, myocardial infarction, gastrointestinal bleeding, or cerebrovascular accidents, sepsis. Hypoventilation leading to hypoxia and hypercapnia, plays a major role in pathogenesis; Exposure to cold, Hypoglycemia and dilutional hyponatremia also contribute to the development of myxedema coma. The diagnosis should be considered in any patient with coma or depressed mental status who also has hypothermia, hyponatremia, and/or hypercapnia. Additional clues to the possible presence of myxedema coma in a poorly responsive patient are the presence of a thyroidectomy scar or a history of I-131 therapy or hypothyroidism. vitrag24 - www.medicalgeek.com
  48. 48. Lab Evaluation Thyroid Function Tests Total T4 (thyroxine), Total T3 (triiodothyronine) Free T4 , Free T3 TSH T3 -Uptake Free T4 Index, Free T3 Index Anti-Thyroid Antibodies Nuclear Scintigraphy FNAC of nodulevitrag24 - www.medicalgeek.com
  49. 49. Thyroid Antibodies  Anti Microsomal (TM ) Antibodies  Anti Thyroglobulin (TG) Antibodies  Anti Thyroperoxidase (TPO) Ab  Anti Thyroxine antibodies  Thyroid Stimulating (TSA) Antibodies High titres TPO Ab in Hashimoto’s & Reidle’s thyroiditis Anti thyroxine Ab in peripheral resistance to Thyroxine TSA (TSI) in Graves’ Hyperthyroidism vitrag24 - www.medicalgeek.com
  50. 50. Tests of thyroid functionTest Reference Ranges*TSH 0.3- 4.0 mU/ LFree T4 0.7- 2.1 ng/ dLT4 4- 11 μg/ dLT3 75- 175 ng/ dlLaboratory tests of thyroid function can be abnormal in 70% ofhospitalized patients and in up to 90% of critically ill patients.In most cases, the abnormality represents an adaptive response to non-thyroidal (systemic) illness and is not a sign of pathologic thyroiddisease.Adopted from:Stockigt JR . In : Werner and Ingbar’s The Thyroid , 7th ed . 1996: 399*Reference ranges may vary according to laboratory Testsvitrag24 - www.medicalgeek.com
  51. 51. Thyroxine (T4) and Triiodothyronine (T3) Thyroxine (T4) is the principal hormone secreted by the thyroid gland, but the active form is triiodothyronine (T3), which is formed by deiodination of thyroxine in extrathyroidal tissues. Both T3 and T4 are extensively (.99%) bound to plasma proteins, especially thyroxine-binding globulin. Approximately 0.2% of the total T3 is in the unbound or physiologically active form. Because of the minor representation of unbound T3 and T4 in plasma, and the potential for plasma protein concentrations to vary in ICU patients, only measurements of free T3 and T4 should be performed in ICU patients.vitrag24 - www.medicalgeek.com
  52. 52. What tests should I order ? As per the Guidelines of the AACE and ATA, ITS 1. TSH alone if Hypothyroidism is suspected 2. TSH and Free T4 only if Hyperthyroidism is suspected or for routine evaluation 3. Free T3 if T3 toxicosis is suspected 4. For follow-up of treatment only TSH 5. Don’t order for Total T4 or Total T3 6. Never order RIU in pregnancy or lactation vitrag24 - www.medicalgeek.com
  53. 53. Which Lab to choose ?1. Depends on the method of estimation of hormones2. Equilibrium Dialysis is the gold Standard for TSH3. Radio-immuno assay - 3rd or 4th gen. RIA is the best4. Reliability of ELISA is not adequate5. Chemiluminescence immuno assay - CIA is the gold standard for FT4 but expensive and less widely available Choose- www.medicalgeek.com vitrag24 a lab which offers 3rd or 4th generation RIA method
  54. 54. Indications to test for hypothyroidism Clinical symptoms and signs Fatigue Laboratory test abnormalities Cold intolerance Constipation Hypercholesterolaemia Impaired memory Slowed mental processing Hyponatraemia Depression Hyperprolactinaemia Nerve entrapment syndromes Ataxia Hyperhomocysteinaemia Muscle weakness Anemia Muscle cramps Menstrual disturbance Creatine phosphokinase Infertility elevation Bradycardia Radiological abnormalities Diastolic hypertension Hoarseness Pericardial and pleural effusions Goitre Periorbital oedema Pituitary gland enlargement Weight gainvitrag24 - www.medicalgeek.com Galactorrhoea
  55. 55. Indications to test for hypothyroidism Risk factors for hypothyroidismAutoimmune thyroiditis Previous thyroid injuryEstablished serological or tissue Thyroidectomy or other neck surgerydiagnosis Radioactive iodine therapyDiffuse goitre External radiotherapyPrevious Graves disease, de Quervains Exposure to polybrominated andthyroiditis, or painless (postpartum) polychlorinated biphenyls, and resorcinolthyroiditis Postpartum statusFamily history of autoimmune thyroid Drugs impairing thyroid functiondisease Lithium carbonateDowns syndrome AmiodaronePersonal or family history of associated Aminoglutethimideautoimmune disorders (eg, vitiligo,pernicious anaemia, adrenal Interferon αinsufficiency, diabetes mellitus type 1, Thalidomideovarian failure, coeliac disease,Sjögrens syndrome) Betaroxine StavudinePrimary pulmonary hypertension Hypothalamic disorders vitrag24 - www.medicalgeek.comMultiple Sclerosis Pituitary disorders
  56. 56. How to interpret results ?The Nine Square GameTo evaluate our Thyroid patientAs per the AACE and ITS Guidelines vitrag24 - www.medicalgeek.com
  57. 57. BASIC THYROID EVALUATION FREE THYROXINE or FT4 LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  58. 58. BASIC THYROID EVALUATION FREE THYROXINE or FT4 EUTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  59. 59. BASIC THYROID EVALUATION FREE THYROXINE or FT4 PRIMARY HYPOTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  60. 60. BASIC THYROID EVALUATION FREE THYROXINE or FT4 PRIMARY HYPERTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  61. 61. BASIC THYROID EVALUATION FREE THYROXINE or FT4 SECONDARY HYPOTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  62. 62. BASIC THYROID EVALUATION FREE THYROXINE or FT4 SECONDARY HYPERTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  63. 63. BASIC THYROID EVALUATION FREE THYROXINE or FT4 SUB-CLINICAL HYPERTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  64. 64. BASIC THYROID EVALUATION FREE THYROXINE or FT4 SUB-CLINICAL HYPOTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  65. 65. BASIC THYROID EVALUATION FREE THYROXINE or FT4 NON THYROID ILLNESS or NTI LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  66. 66. BASIC THYROID EVALUATION FREE THYROXINE or FT4 NTI or Pt. on ELTROXIN LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  67. 67. BASIC THYROID EVALUATION FREE THYROXINE or FT4 PRIMARY NTI or Pt. SECONDARY HYPERTHYROID on ELTROXIN HYPERTHYROID SUB-CLINICAL SUB-CLINICAL HYPERTHYROID EUTHYROID HYPOTHYROID SECONDARY NON THYROID PRIMARY HYPOTHYROID ILLNESS - NTI HYPOTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSHvitrag24 - www.medicalgeek.com
  68. 68. vitrag24 - www.medicalgeek.com
  69. 69. Common Patterns of Thyroid FunctionTests in Critically Ill PatientsNon-Thyroidal Ilness Free T4 Free T3 TSHEarly systemic illness Normal ↓ NormalEarly critical illness ↓ ↓ NormalChronic critical illness ↓ ↓ Normal/↓(>2 days)Sick Euthyroid SyndromeEuthyroid sick syndrome, sick euthyroid syndrome, non-thyroidalillness syndrome or low T3 low T4 syndrome is a state of adaptationor dysregulation of thyrotropic feedback control where the levels of T3and/or T4 are at unusual levels, but the thyroid gland does not appearto be dysfunctional. This condition is often seen in starvation, criticalillness orwww.medicalgeek.com vitrag24 - patients in intensive care unit.
  70. 70. T.F.T. in Progressive Hypothyroidism TSH Mild Moderate Severe Normal Range Free T3 Free T4 vitrag24 - www.medicalgeek.com
  71. 71. vitrag24 - www.medicalgeek.com
  72. 72. vitrag24 - www.medicalgeek.com
  73. 73. vitrag24 - www.medicalgeek.com
  74. 74. Algorithm for Hypothyroidism Measure TSH Elevated TSH Normal TSH Measure FT4 Considering Pituitary Normal Low No YesSub-clinical hypo Primary hypothyroid No tests Measure FT4TPO + TPO - TPO + TPO - Low NormalT4 repl Annual FU Hashimoto Evaluate Pituitary Sick Euthyroid No tests vitrag24 - www.medicalgeek.com Others Drugs effect
  75. 75. Treatment Goal : Normalize TSH level regardless of cause of hypothyroidism Treatment of choice is thyroxine Brand consistency recommended Not recommended for routine use :  Desiccated thyroid hormone  Combination of thyroid hormones  T3 TSH should be measured at 6 to 8 weeks after any change in L-thyroxine brand or dosevitrag24 - www.medicalgeek.com
  76. 76. Determinants of ThyroxineRequirements Age Severity and duration of hypothyroidism Weight Malabsorption Pregnancy Presence of cardiac disease Concomitant drug therapyvitrag24 - www.medicalgeek.com
  77. 77. Treatment : Outline Goal : normalize TSH level, , ideally in the lower half of the reference range. Single daily dose of levothyroxine as half life is 7 days. Always take on empty stomach Starting dose for healthy patients <50 years should be at 1.6 μg/kg/day Starting dose for healthy patients >50 years should be <50 μg/day. Dose should be increased by 12.5-25 μg/day, if needed, at 6 to 8 weeks intervals. (Start low and go slow) Starting dose for patients with heart disease should be 12.5 to 25 μg/day and increase by 12.5 to 25 μg/day, if needed, at 6 to 8 weeks intervalsvitrag24 - www.medicalgeek.com
  78. 78. vitrag24 - www.medicalgeek.com
  79. 79. Treatment : Clinical Hypothyroidism If there is no residual thyroid function, the daily replacement dose of levothyroxine is usually 1.6 µg/kg body weight (typically 100– 150 µg). In many patients, however, lower doses suffice until residual thyroid tissue is destroyed. In patients who develop hypothyroidism after the treatment of Graves disease, there is often underlying autonomous function, necessitating lower replacement doses (typically 75–125 µg/d). TSH responses are gradual and should be measured about two months after instituting treatment or after any subsequent change in levothyroxine dosage. The clinical effects of levothyroxine replacement are slow to appear. Patients may not experience full relief from symptoms until 3–6 months after normal TSH levels are restored. Adjustment of levothyroxine dosage is made in 12.5- or 25 µg increments if the TSH is high; decrements of the same magnitude should be made if the TSH is suppressed. Once full replacement is achieved and TSH levels are stable, follow-up measurement of TSH is recommended at annual intervals and may be extended to every 2–3 years if a normal TSH is -maintained over several years. vitrag24 www.medicalgeek.com
  80. 80. Follow-up After 6 to 8 Weeks ofThyroxine TherapyIf Repeat TSH is Then> 4.0 mU/L Increase daily thyroxine dose by 12.5- 25 μg/d & repeat TSH in 6 to 8 week0.3 to 4.0 mU/L Continue dose; repeat TSH in 6 months and then annually or if symptomatic If TSH remain normal for several years, then monitor every 2-3 years<0.4 mU/L Decrease daily thyroxine dose by 12.5 to 25 μg/d and repeat in 6 to 8 weeksvitrag24 - www.medicalgeek.com
  81. 81.  There is no place for liothyronine alone as long-term replacement, because the short half-life necessitates three or four daily doses and is associated with fluctuating T3 levels. It is important to ensure ongoing adherence, however, as patients do not feel any symptomatic difference after missing a few doses of levothyroxine, and this sometimes leads to self-discontinuation. In patients of normal body weight who are taking 200 µg of levothyroxine per day, an elevated TSH level is often a sign of poor adherence to treatment. Such patients often have normal or high unbound T4 levels, despite an elevated TSH, because they remember to take medication for a few days before testing; this is sufficient to normalize T4, but not TSH levels. Because T4 has a long half-life (7 days), patients who miss a dose can be advised to take two doses of the skipped tablets at once. vitrag24 - www.medicalgeek.com
  82. 82. Over - and Under-Replacement Risks Over-replacement Risks Reduced bone density/osteoporosis Tachycardia, arrhythmia : Atrial fibrillation In elderly or patients with heart disease, angina, arrhythmia, or myocardial infarction Under-replacement Risks Continued hypothyroid state Long-term end-organ effects of hypothyroidism Increased risk of hyperlipidemiavitrag24 - www.medicalgeek.com
  83. 83. Recovery after L-Thyroxinevitrag24 - www.medicalgeek.com
  84. 84. Recovery after L-Thyroxinevitrag24 - www.medicalgeek.com
  85. 85. Treatment : Subclinical Hypothyroidism By definition, subclinical hypothyroidism refers to biochemical evidence of thyroid hormone deficiency in patients who have few or no apparent clinical features of hypothyroidism. Routine treatment not recommended when TSH levels are below 10 mU/L. Any elevation of TSH must be sustained over a 3-month period before treatment is given. Treatment is administered by starting with a low dose of levothyroxine (25–50 µg/d) with the goal of normalizing TSH. If thyroxine is not given, thyroid function should be evaluated annually. There is a risk that patients will progress to overt hypothyroidism, particularly when the TSH level is elevated and TPO antibodies are present.vitrag24 - www.medicalgeek.com
  86. 86. Special Treatment Considerations Women with a history or high risk of hypothyroidism should ensure that they are euthyroid prior to conception and during early pregnancy as maternal hypothyroidism may adversely affect fetal neural development and cause preterm delivery. Thyroid function should be evaluated immediately after pregnancy is confirmed and at the beginning of the second and third trimesters. The dose of levothyroxine may need to be increased by 50% during pregnancy and returned to previous levels after delivery. Elderly patients may require 20% less thyroxine than younger patients. In the elderly, especially patients with known coronary artery disease, the starting dose of levothyroxine is 12.5–25 µg/d with similar increments every 2–3 months until TSH is normalized. In some patients, it may be impossible to achieve full replacement despite optimal antianginal treatment. Emergency surgery is generally safe in patients with untreated hypothyroidism, although routine surgery in a hypothyroid patient should be deferred until euthyroidism is achieved. vitrag24 - www.medicalgeek.com
  87. 87. Treatment : Myxedema coma Levothyroxine can initially be administered as a single IV bolus of 500 µg, which serves as a loading dose. Although further levothyroxine is not strictly necessary for several days, it is usually continued at a dose of 50–100 µg/d. If suitable IV preparation is not available, the same initial dose of levothyroxine can be given by nasogastric tube (though absorption may be impaired in myxedema). An alternative is to give liothyronine (T3) intravenously or via nasogastric tube, in doses ranging from 10 to 25 µg every 8– 12 h. This treatment has been advocated because T4 to T3 conversion is impaired in myxedema coma. However, excess liothyronine has the potential to provoke arrhythmias. Another option is to combine levothyroxine (200 µg) and liothyronine (25 µg) as a single, initial IV bolus followed by daily treatment with levothyroxine (50–100 µg/d) and liothyronine (10 µg every 8 h). Recovery within 24 hours is usual. vitrag24 - www.medicalgeek.com
  88. 88. Supportive Treatment : Myxedema coma External warming is indicated only if the temperature is <30°C, as it can result in cardiovascular collapse. Space blankets should be used to prevent further heat loss. Parenteral hydrocortisone (50 mg every 6 h) should be administered, because there is impaired adrenal reserve in profound hypothyroidism. Any precipitating factors should be treated, including the early use of broad-spectrum antibiotics, pending the exclusion of infection. Ventilatory support with regular blood gas analysis is usually needed during the first 48 hours. Hypertonic saline or IV glucose may be needed if there is severe hyponatremia or hypoglycemia; hypotonic IV fluids should be avoided because they may exacerbate water retention secondary to reduced renal perfusion and inappropriate vasopressin secretion. The metabolism of most medications is impaired, and sedatives should be avoided if possible or used in reduced doses. Medication blood levels should be monitored, when available, to guidewww.medicalgeek.com vitrag24 - dosage.
  89. 89. Diet in Iodine deficiency  Iodized salt  Selenium supplementation  Avoid Cassava  Avoid cabbage (goitrogens)  Avoid formula milk  Fish, meat, milk & eggs vitrag24 - www.medicalgeek.com
  90. 90. References Williams Textbook of Endocrinology – 12th Edition Harrison’s Principles of internal medicine – 18th Edition AFP journal UpToDate 19.3 eMedicine Publications from the American Thyroid Association, American Association of Clinical Endocrinologists, and the Endocrine Society The ICU Book, 3rd Edition - Paul L. Marino vitrag24 - www.medicalgeek.com
  91. 91. vitrag24 - www.medicalgeek.com
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