Thyroid physiology & Hypothyroidism

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An overview of the physiology of the thyroid and a discussion on management of hypothyroidism.

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Thyroid physiology & Hypothyroidism

  1. 1. A C ASE PRO FIL E O F TH YRO ID D ISEASE - Dr.Mohammed Siraj - Dr.Parvez Khan - Dr.Mohammed Sadiq Azam - Dr.Praneetha Gayathri 1
  2. 2. TH YRO ID GL AN DH O RM O N O GEN ESIS 2
  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 3
  4. 4. 4www.drsarma.in
  5. 5. In the Thyroid GlandThere the following 5 steps in the hormonogenesis Trapping of inorganic Iodine from dietary Iodides Activation of Iodine to high valance I2 Incorporation of I2 into Tyrosine of Thyroid Globulin Coupling of formed MIT and DIT to form T4 & T3 Proteolysis of Thyroglobulin to release T4 & T3 5
  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 6 Only Free T4 and Free T3 are metabolically active
  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 7 - 20% of hormone secreted is T3
  8. 8. Throid hormones in peripheral tissues• Plasma transport by thyroxine binding globulin TBG -75 -80%bound• Transthyretin 10-15%• Albumin 5-10% 8
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  10. 10. Thyroid Function Tests  TSH  Free T4  Free T3  Anti-Thyroid Antibodies  Nuclear Scintigraphy  FNAC of nodule 10
  11. 11. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH NORMAL LOW LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 11
  12. 12. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH NORMAL EUTHYROID LOW LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 12
  13. 13. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH NORMAL PRIMARY LOW HYPOTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 13
  14. 14. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH PRIMARY HYPERTHYROID NORMAL LOW LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 14
  15. 15. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH NORMAL SECONDARY LOW HYPOTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 15
  16. 16. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH SECONDARY HYPERTHYROID NORMAL LOW LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 16
  17. 17. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH NORMAL SUB-CLINICAL HYPERTHYROID LOW LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 17
  18. 18. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH NORMAL SUB-CLINICAL HYPOTHYROID LOW LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 18
  19. 19. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH NORMAL LOW NON THYROID ILLNESS or NTI LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 19
  20. 20. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH NTI or Pt. on ELTROXIN NORMAL LOW LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 20
  21. 21. BASIC THYROID EVALUATIONFREE THYROXINE or FT4 HIGH PRIMARY NTI or Pt. SECONDARY HYPERTHYROID on ELTROXIN HYPERTHYROID NORMAL SUB-CLINICAL SUB-CLINICAL HYPERTHYROID EUTHYROID HYPOTHYROID SECONDARY NON THYROID PRIMARY LOW HYPOTHYROID ILLNESS - NTI HYPOTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH 21
  22. 22. THYROID HORMONES TEST REFERENCE RANGE TSH Normal Range 0.3 - 4.0 mU/L Free T4 Normal Range 0.7-2.1 ng/dLTSH upper limit will soon be revised to 2.5 mU/L 22
  23. 23. Thyroid Antibodies • Anti Microsomal (TM ) Antibodies • Anti Thyroglobulin (TG) Antibodies • Anti Thyroxine Per Oxidase (TPO) Ab. • Anti Thyroxine antibodies • Thyroid Stimulating (TSA) Antibodies High titres TPO Ab in Hashimotos & Reidle’s thyroiditis Anti thyroxine Ab in peripheral resistance to Thyroxine TSA (TSI) in Graves’ Hyperthyroidism 23
  24. 24. hypothyroidism 24
  25. 25. Hypothyroidism• Epidemiology • Most common endocrine disease • Females > Males – 8 : 1• Presentation • Often unsuspected and grossly under diagnosed • 90 % of the cases are Primary Hypothyroidism • Menstrual irregularities, miscarriages, growth retard. • Vague pains, anaemia, lethargy, gain in weight 25
  26. 26. Disease Burden 5% of the general population are Sub-clinically Hypothyroid 15 % of all women > 65 yrs. are hypothyroid Detecting sub-clinical hypothyroidism in pregnancy is highly essential – order for TSH and FT4 routinely in all pregnant women at the beginning of each trimester All persons aged above 60 years – Order for TSH26
  27. 27. • Primary hypothyroidism with Goitre Aquired Hashimotos thyroiditis Iodine deficiency Drugs blocking synthesis or release of T4 Goitrogens Cytokines Thyroid infiltration Causes of Congenital Iodide transport or utilization defect Hypothyroidism Iodotyrosine dehalogenase deficiency TPO deficiencyn nd dysfunction 27 Defects in thyroglobulin synthesis
  28. 28. • ATROPHIC HYPOTHYROIDISM Acquired HASHIMOTOS DISEASE Postablative due to 131 Iodine surgery Congenital Thyroid agenesis or dysplasia TSH receptor defects Thyroidal Gs protein abnormalities Idiopathic TSH unresponsiveness TRANSIENT HYPOTHYROIDISM 28 following subacute painless or postpartum thyroiditis
  29. 29. • CONSUMPTIVE HYPOTHYROIDISM• hemangiomas ,hemangioendoheliomas• CENTRAL HYPOTHYROIDISM• Acquired• pituatary origin• hypothalamic disorders• dopamine & or severe stress• Congenital• TSH deficiency/structural abnormality• TSH receptor defect• RESISTANCE TO THYROID HARMONE 29• generalised or pituatary dominant
  30. 30. Multi system effects - Hypothyroidism General Neuromuscular •Lethargy, Somnalence •Aches and pains •Weight gain, Goitre •Muscle stiffness •Cold Intolerence •Carpel tunnel syndrome Cardiovascular •Deafness, Hoarseness •Bradycardia, Angina •Cerebellar ataxia •CHF, Pericardial Effusion •Delayed DTR, Myotonia •HyperlipIdemia, Xanthelsma •Depression, Psychosis Haematological Gastro-intestinal Iron def. Anaemia, •Constipation, Ileus, Ascites Normo cytic /chromic Anaemia Dermatological Reproductive system •Dry flaky skin and hair •Infertility, Menorrhagia •Myxoedema, Malar flushes 30 •Impotence, Inc. Prolactin •Vitiligo, Carotenimia, Alopecia
  31. 31. Clinical Signs of Hypothyroidism Coarse Hair; Dry cool and pale skin Goitre (not in all cases), Hoarseness of voice Non-pitting oedema (myxoedema) Puffiness of eyes and face Delayed relaxation of DTR Slow hoarse speech and slow movements Thinning of lateral 1/3 of eye brows Bradycardia, pericardial effusion 31
  32. 32. Thyroid Failure - Organ SystemsCardiovascular• Decreased ventricular contractility• Increased diastolic blood pressure• Decreased heart rateCentral Nervous• Decreased concentration• General lack of interest• DepressionGastro-instestinal• Decreased GI motility• Constipation 32
  33. 33. Thyroid Failure - Organ SystemsMusculoskeletal Muscle stiffness, cramps, pain, weakness, myalgia Slow muscle-stretch reflexes, muscle enlargement, atrophyRenal Fluid retention and oedema Decreased glomerular filtration 33
  34. 34. Thyroid Failure - Organ SystemsReproductive• Arrest of pubertal development• Reduced growth velocity• Menorrhagia, Amenorrhea• Anovulation, InfertilityHepatic• Increased LDL / TC• Elevated LDL + triglycerides 34
  35. 35. Thyroid Failure - Organ SystemsSkin and Hair Thickening and dryness of skin Dry, coarse hair, Alopecia Loss of scalp hair and / or lateral eyebrow hair 35
  36. 36. HORMONAL EFFECTS ON THYROID FUNCTION• Glucocorticoid Excess-decreased TSH,TBG,TTR• Decreased serum T3/T4 and increase Rt3 production• Decreased T4 and increased T3 in graves disease• Deficiency-Increased TSH• Estrogen-Increased TBG sialylation and half life in serum• Increased TSH in post menopausal women• Increased T4 requirement in hypothyroid patients• Androgen-Decreased TBG• Decreased T4 requirment in hypothyroid patient 36• Growthhormone-Decreased D3 activity
  37. 37. 37www.drsarma.in
  38. 38. Cassava Plant Topiaco - Sago (Javva Arisi) 38
  39. 39. Tapioca Root - Sago Tapioca (tubers) Dried Tapioca - Sago 39
  40. 40. My xedema 40
  41. 41. My xedema 41
  42. 42. Co-morbidity• Hypercholosterolemia• Depression• Infertility – Menstrual Irregularities• Diabetes mellitus 42
  43. 43. Hypothyroidism andHypercholesterolemia • 14% of patients with elevated cholesterol have hypothyroidism • Approximately 90% of patients with overt hypothyroidism have increased cholesterol and / or triglycerides 43
  44. 44. Lipids in Patient with Hypothyroidism Hypercholesterolemia (>200 mg/dL) Hypertriglyceridemia (>150 mg/dL) Hypercholesterolemia and mild Hyper TG N= 268 Normal Lipids 44
  45. 45. Effect of Thyroxine therapyon Hypercholesterolemia inPatients with mild Thyroid failure “The decrease in total cholesterol achieved with [Thyroxine replacement] substitution therapy in patients with subclinical hypothyroidism [mild thyroid failure] may be considered as an important decrease in cardiovascular risk favouring treatment.” 45
  46. 46. Suspect Hypothyroidism 1. Amenorrhea 2. Oligomenorrhea 3. Menorrhogia 4. Galactorrhea 5. Premature ovarian failure 6. Infertility 7. Decreased libido 8. Precocious / delayed puberty 9. Chronic urticaria 46
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  48. 48. 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 48 No tests Sick Euthyroid Others Drugs effect
  49. 49. Hormonereplacement 49
  50. 50. Treatment • Goal : Normalize TSH level regardless of cause of hypothyroidism • Treatment : Once daily dosing with Levothyroxine sodium (1.6µg/kg/day-1.8ug/kg/day) • Monitor TSH levels at 6 to 8 weeks, after initiation of therapy or dosage change 50
  51. 51. Treatment• Treatment of choice is levothyroxin• Not recommended for use :  Desiccated thyroid extract  Combination of thyroid hormones  T3 replacement except in Myxedema coma 51
  52. 52. Dosage Adjustments• Age (in elderly start with half dose)• Severity and duration of hypothyroidism (↑ dose)• Weight (0.5µg/kg/day ↑ upto 3.0µg/kg/day)• Malabsorption (requires ↑ dose)• Concomitant drug therapy (only on empty stomach)• Pregnancy ( 25% -50%↑ in dose), safe in lactating mother• Presence of cardiac disease (start alt. day Rx) 52
  53. 53. Start Low and Go Slow• Goal : normalize TSH level – 25, 50 and 100 mcg tablets avail.• Starting dose for healthy patients < 50 years at 1.0 µg/kg/day• Starting dose for healthy patients > 50 years should be < 50 µg/day. Dose ↑ by 25 µg, if needed, at 6 to 8 weeks intervals.• 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 intervals 53
  54. 54. How the patient improves Feels better in 2 – 3 weeks Reduction in weight is the first improvement Facial puffiness then starts coming down Skin changes, hair changes take long time to regress TSH starts showing decrements from the high values TSH returns to normal eventually 54
  55. 55. Drug Interactions• Malabsorption Syndromes  Drugs that affect metabolism• Reduced Absorption  Rifampin  Cholestyramine resin  Carbamazepine  Sucralfate  Phenytoin  Ferrous sulfate  Phenobarbitol  Soybean formula  Aluminum hydroxide  Amiodarone  Colestipol hydrochloride 55
  56. 56. Inappropriate DosageOver-replacement risks• Reduced bone density / osteoporosis• Tachycardia, arrhythmia. atrial fibrillation• In elderly or patients with heart disease, angina, arrhythmia, or myocardial infarction2Under-replacement risks• Continued hypothyroid state• Long-term end-organ effects of hypothyroidism• Increased risk of hyperlipidemia 56
  57. 57. 20.2.98Massive Pericardial Effusion in Hypo 57
  58. 58. 26.7.98 58Clearing of Pericardial Effusion with Rx.
  59. 59. 14.9.99Reappearance of Pericardial Effusion 59 after treatment is discontinued
  60. 60. • CENTRAL HYPOTHROIDISM• AFTER SURGERYFT4 evaluation 60
  61. 61. Diet in Iodine deficiency • Iodized salt • Selenium supplementation • Avoid Cassava • Avoid cabbage (goitrogens) • Avoid formula milk • Fish, meat, milk & eggs 61
  62. 62. Specialsituations 62
  63. 63. My xedema Coma • Precipitating factors :  Infection, trauma, stroke, cardiovascular, hemorrhage drug overdose, diuretics • Signs and Symptoms :  Mental confusion, hypothermia, bradycardia, older age,  ↓ Na, ↓ glucose, ↑ CO2, ↓ WBC, ↓ Hct, ↑ CPK  ↓ EKG voltage, myxedema, b-carotnenemia • Treatment Initial IV THYROXINE 500-800 mcg/day ,followed by daily dose of I.V thyroxine 100 mcg thereafter ,alt I.V leothyronine 25mcg b.d 63
  64. 64. Sick Euthyroid Syndrome  Total T3 reduced  FT3 reduced  Total T4 reduced  FT4 Normal  TSH Normal  Clinically Euthyroid 64
  65. 65. • T3 -0.04nmo/l 0.93-2.33nmol/lit• T4-59.70nmol/l 60-120 nmol/lit• TSH-2.52IU/ml >7.0-hypothyroid <0.2 hyperthyroid Case-1 65
  66. 66. • T3 -1.42nmol/l• T4-106.96nmol/l• TSH-<0.05IU/mlCase 2 66
  67. 67. The Commandments Highly suspect hypothyroidism  All obese patients TSH a must Growth and pubertal delay  For all pregnant -test TSH, FT4 Unexplained depression  Postmenopausal 15% Hypothy TSH is the test in Hypothy.  Start low and go slow TSH, FT4 to confirm Dx.  Use Levothyroxine only Nine square magic  Always on empty stomach Test cord blood for TSH  Thyroxine - avoid empirical use 67
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