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DEGHAS LECTURE THYROID DYSFUNCTION. Thyroid Hormone Control.

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Presentation on theme: "DEGHAS LECTURE THYROID DYSFUNCTION. Thyroid Hormone Control."— Presentation transcript:

1 DEGHAS LECTURE THYROID DYSFUNCTION

2

3 Thyroid Hormone Control

4 TSH THS regulation- TRH , T3,T4  TSH  synthesis of T3,T4 TSH  thyroid gland growth

5 FUNKCE ŠTÍTNÉ ŽLÁZY

6 T3 RECEPTOR

7 THYROID HORMONES Most of the T4 nda T3 in plasma bound to TBG Only free hormones are active ! The fT3 has 8 x higher activity than the fT4 20% of the T3 comes directly from the thyroid 80 % of the T3 se formed in tissues (esp. liver and kidney) from T4 by 5’-deiodase Identic amount of rT3 formed by 5-deiodase

8 THYROID HORMONE FUNCTION Body growth (  gene expression GH) Maturation of CNS Adrenergic effect–  β-1 receptor response to catecholamines  basal metabolic rate (  cytochromes of the respiratory chain, cytochromoxidase and Na + -K + -ATPase)  mobilize energy stores and  catabolism (lipolysis, glycogenolysis, gluconeogenesis)

9 GOITER

10 TYPES OF GOITER ACCORDING TO FUNCTION: Euthyroid Hypothyroid Hyperthyroid ACCORDING TO STRUCTURE: Diffuse (colloid) Nodular

11 HYPOTHYROIDISM-SYMPTOMS Fatigue, somnolence, muscle weakness, letargy, depression Bradypsychia, memory and concentration problems Bradycardia, decreased DBP Cold intolerance Constipation Body weight gain Diminished deep tendon reflexes Eybrow loss, dry skin, decreased sweating Pericardial and pleural effusions Forearm edema Hoarseness

12 LABORATORY FINDINGS: PRIMARY HYPOTHYROIDISM:  TSH,  fT3,fT4 SECONDARY HYPOTHYROIDISM:  TSH,  fT3,fT4 TERTIARY HYPOTHYROIDISM:  TRH,  TSH,  fT3,fT4 HYPOTHYROIDISM:  cholesterol is typical

13 72-year old woman with hypothyroidism

14 Cretenism

15 HYPOTHYROIDISM-CAUSES PRIMARY HYPOTHYROIDISM (origin in the thyroid):  Chronic lymphocytic thyroiditis – CLT (Hashimoto)  Thyroidectomy  Radiation therapy or nuclear catastrophy  Lack or excess of iodine  Drugs (methimazol, sunitinib, carbamazepin, amiodaron,)  Infiltrative dieseases (e.g. Riedel’s goiter)

16 HYPOTHYROIDISM SECONDARY HYPOTHYROIDISM – origin in the pituitary Craniopharyngioma, chromophobe adenoma, teratoma TERTIARY HYPOTHYROIDISM – origin in the hypothalamus Extremely rare

17 CLT (HASHIMOTO) The most common cause of hypothyroidism ! Women y! 9 x higher incidence in women than in men Positive PA/FA for autoim.dis., HLA-DR3, -DR4, -DR5, often vitiligo or alopecia Hepatitis C history Often as part of the “polyglandular syndrom” Autoimmun. inflam.-cellular and humoral resonse (cytotoxic T cells, auto-antibodies: anti TPO, anti TGB, anti TSH-R)

18 CLT - DIAGNOSIS SYMPTOMS – initially unapparent (sometimes hyperthyroid ) Most of the cases dg. as advanced disease, when hypothyroidism is clinically present LAB TESTS:  TSH,  fT3,fT4 Anti TPO (95%), anti TGB (70%), anti TSH-R US: non-homogenic, hypoechogenic, often diminished thyroid FNAC: lymphocytic thyreoiditis, later fibrosis

19 DIFF. DG. OTHER CAUSES OF HYPOTHYROIDISM Low T3/T4 syndrome  fT3,fT4,  rT3, clinically irrelevant no thyroxin supplementation needed

20 CLT - THERAPY L-thyroxin replacement 25, 50, 75, 100, 150 μ g tablets Avarage replacement dose 1.6 μ g/kg/ PO daily Goal: TSH 0.5 – 2.0 mIU/l

21 THYROIDECTOMY INDICATIONS for thyroidectomy: Graves’ disease Toxic adenoma, toxic multinodular goiter Thyroid carcinoma

22 I 131 THERAPY Graves’ disease Thyroid carcinoma

23 EXTERNAL RADIATION ( > 25 Gy) Hodgkin’s lymphoma– neck lymphadenopythy Malginant tumors of the head and neck Nuclear catastrophy

24 DRUGS Lithium Amiodarone Phenytoin Carbamazepine Ethonamide (anti-TBC) Overdose with thyreostatic drugs: Methimazole Propylthiouracil TPO inhibitors: sunitinib, sorafenib, imatinib

25 INFILTRATIVE DISEASE (less common) Riedel’s fibrotic goiter Hemochromatosis Sclerodermia Leukemias Amyloidosis

26 Riedel’s goiter Synonym: Riedel’s thyroiditis Extremely rare Etiology: unknown Slowly growing goiter-extremely solid consistency Painless Fibrotic inflammation w. lymphocytic infiltration Dif.dg.: tumor ! Possible destruction of the parathyroid glands Retrosternal expansion: stridor, dysphagia

27 DIAGNOSIS OF HYPOTHYROIDISM TSH, fT3, fT4 Ultrasound Fine Needle Aspiration Cytology (FNAC) Antibody titre measurement (anti TPO, anti TGB, anti R-TSH) Scintigraphy (I 131 accumulation)

28 THYROID ULTRASOUND

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30 SEVERE HYPOTHYRODISM-MYXEDEMA EMERGENCY (result of prolonged and severe hypothyroidism) Triggered by: infection, trauma, surgery, cold Weakness, impaired conciousness to COMA Hypothermia Hypotension Hypoventilation Hypoglycemia Hyponatremia Edema, swollen tongue

31 THERAPY OF MYXEDEMA INTENSIVE CARE UNIT Support of vital functions, ventilation support Glucocorticoids Glucose infusion Sodium supplementation L-thyroxin μ g IV initially Slow rewarming in hypothermia

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33 HYPERTHYROIDISM NEUROPSYCHIATRIC SYMPTOMS Restlessness Irritability Insomnia Anxiety Emotional lability Personality changes Psychosis Hyperactive deep tendon reflexes

34 HYPERTHYROIDISM CARDIOVASCULAR SYMPTOMS  cardiac output (tachycardia,  periph. resistance)  SBP,  DBP Atrial fibrillation (in %) Congestive heart failure Cardiomyopathy Mitral valve prolapse, mitral regurgitation

35 HYPERTHYROIDISM GASTROINTESTINAL SYMPTOMS Increased peristaltics Malabsorption Hyperphagia in young patients Loss of appetite in older patients Vomiting Dysphagia due to enlarged goiter Liver enzyme elevation, esp. ALP, rarely steatosis

36 HYPERTHYROIDISM METABOLIC SYMPTOMS Weight loss  total cholesterol,  HDL cholesterol Hyperglycemia (insulin action antagonism)  cortisol

37 HYPERTHYROIDISM MUSCLE SYMPTOMS Adynamia Muscle weakness (esp. thigh muscles)

38 HYPERTHYROIDISM BONE SYMPTOMS  Bone resorption Porosity of the cortical bone, thinner trabecular bone  ALP,  osteocalcin (higher bone turnover) Hypercalcemia leading to PTH suppression  conversion of D 2 to D 3  Ca 2+ resorption from the gut  Ca 2+ renal elimination OSTEOPOROSIS in chronic hyperthyroidism

39 HYPERTHYROIDISM GENITOURINARY SYMPTOMS Polyuria, polydypsia  SHBG MEN:  total but  free testosteron: gynecomastia, loss of libido, erectile dysfunction, impaired spermatogenesis WOMEN:  total, but  free estradiol: oligo-, amenorrhea, infertility

40 HYPERTHYROIDISM LUNG SYMPTOMS Dyspnea  O 2 consumption,  CO 2 production Respiratory muscle weakness Trachea stenosis by enlarged goiter

41 HYPERTHYROIDISM – SKIN SYMPTOMS Sweating Warm, moist, fine skin Fine hair Fine nails, onycholysis Hyperpigmentation Vitiligo Alopecia areata

42 HYPERTHYROIDISM HEMATOLOGY SYMPTOMS  erytrocyte volume (MEV) Normocytic normochromic anemia (due to increased plasma volume)  ferritin autoimmune hematologic diseases (pernicious anemia, idiopatic trombocytopenic purpura=ITP) Risk of thrombosis (  fibrinogen,  v. Willebrand f.,  thrombocyte aggregation)

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44 HYPERTHYROIDISM-ETIOLOGY GRAVES' DISEASE (60-80 % of hyperthyroidism) Toxic multinodular goiter (15-20%) Thyroid adenoma (single thyroid nodule 3-5%) Subacute de Quervain thyroiditis Drugs: thyroxin excess (hyperthyreosis factitia), amiodarone, iodine (contrast agents) Second. hyperthyroidism (pituitary adenoma)-rare

45 GRAVES’ DISEASE Autoimmune disease Genetic background-HLA-DQA1*0501 Viral infection as trigger ? Production of TSH-receptor antibodies = = TSI (thyroid stimulating antibodies) In GD sometimes initially hypothyroid period

46 GRAVES' DISEASE DIAGNOSIS CLINICAL SYMPTOMS OF HYPERTHYROIDISM GRAVES' ORBITOPATHY LAB TESTS:  TSH,  fT3,fT4 TSI (> 95%) Anti TPO (70%)

47 HYPERTHYROIDISM – GRAVES' ORBITOPATHY 25 % patients with Graves’ disease Correlation of orbitopathy with the severity of hypothyroidism Deposition of collagen and glycosaminoglycans in the muscles, enlargement of the retroorbital space Exophtalmos Upper eyelid retraction Von Greafe’s sign (lid lag on infraduction) Koch’s sign (bulbus lag on supraduction) Lagophtalmos

48 GRAVES’ ORBITOPATHY

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50 GRAVES' DISEASE THERAPY Beta blockers Thyrostatic drugs-blocking MJT and DJT synthesis (methimazole, thiamazole, propylthiouracil) Radiactive iodine 131 I (dos MBq)- thyreostatics before and after the procedure recom. EUTHYROIDISM RESTORED AFTER SEV.MONTHS Subtotal thyroidectomy (after sev.months) if large goiter, thyreotoxic crisis)

51 DIFF.DG. OTHER CAUSES OF HYPERTHYROIDISM Vegetative instability Psychosis High fever Cocaine, Amphetamine Tachycardia of different origin

52 THYROTOXIC CRISIS Etiology: spontaneously in Graves disease autonomic adenomas (nodes) iodine agents thyroxin overdose inefficient thyrostatic therapy

53 THYROTOXIC CRISIS STAGES Stage I: Tachycardia > 150, AF, Fever > 41°, sweating, psychomotoric agitation, diarrhea, vomiting, adynamia Stage II: + somnolence, psychotic symptoms Stage III: coma w/wo adrenal failure, shock

54 THYROTOXIC CRISIS THERAPY EMERGENCY-INTENSIVE CARE UNIT Thiamazol 80 mg IV every 8 hours Beta-blockers Corticosteroids Fluid: 3-4 Liters IV/D Calorie intake: 3000 kcal/D Lowering body temperature (ice) Sedation Thromboembolic prophylaxis

55 THYREOTOXIC CRISIS THERAPY IN SEVERE CASES (e.g. iodine induced): PLASMAPHERESIS SUBTOTAL THYROIDECTOMY

56 SUBACUTE de QUERVAIN'S THYROIDITIS Rare cause of hyperthyroidism Incidence 5 x higher in women than men Etiology: probably viral infection, often after respiratory infection Clinical signs: hyperthyroidic-euthyr-hypothyroidic, painful thyroid, Lab tests:  ESR,  CRP, normal leukocytes Therapy: mostly spontaneous healing, NSA, rednisolon are optional

57 MULTINODULAR GOITER AUTONOMOUS ADEMOMA DIAGNOSIS: 131 I accumulation on thyroid scan, US CLINICAL SYMPTOMS of hyperthyroidism THERAPY: thyreostatics, radioactive iodine

58 MULTINODULAR GOITER

59 ULTRASOUND OF A THYROID NODULE

60 THYROID SCAN – normal accumulation

61 THYROID ADENOMA


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