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BENIGN DISEASES OF THE THYROID. Rivka Dresner Pollak M.D Endocrinology. Thyroid gland- anatomy. Thyroid gland- anatomy. sternocleidomastoid. strap muscles. trachea. thyroid. jugular v. esophagus. carotid a. vertebra. Recommended and Typical Values for Dietary Iodine Intake.

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BENIGN DISEASES OF THE THYROID


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    1. BENIGN DISEASES OF THE THYROID Rivka Dresner Pollak M.D Endocrinology.

    2. Thyroid gland- anatomy

    3. Thyroid gland- anatomy sternocleidomastoid strap muscles trachea thyroid jugular v. esophagus carotid a. vertebra

    4. Recommended and Typical Values for Dietary Iodine Intake Recommended Daily Intake μg I/day Adults 150 During pregnancy 200 Children 90-120 Typical Iodine intakes North America 75-300 Europe (Germany, Belgium) 50-70 Switzerland 130-160 Chile <50-150

    5. Free T4, T3 P Protein Bound Thyroid hormone Serum thyroid hormone binding Feedback control Thyroid secretion Tissue action Hormone metabolism Fecal excretion

    6. THYROXINE BINDING GLOBULIN Estrogen  Androgen = Glucocorticoids = Acute illness N Chronic illness  Liver dis.  THYROID HORMONES TRANSPORT AND METABOLISM TRANSPORT TBG = thyroxine binding globulin TTR = transthyretin % binding- mostly to TBG T4 - 99.5 T3- 95 METABOLISM DEIODINASE TYPE 1 & 2

    7. T4 T4 T4 T4 T4 T4 TBG T4 T4 TBG Serum protein binding of thyroid hormones “Pill effect” Total T4 Bound Free  synthesis By liver

    8. Hypothalamus Regulation of Thyroid hormone secretion (-) TRH (+) Pituitary (+) TSH (-) T4, T3 Thyroid

    9. Assessment of bioactive thyroid hormones Check free hormone levels: Free T4 Free T3 Check thyroid hormone “biosensor’: TSH

    10. Thyroid function tests FT4 pmol/L FT3 nmol/L TSH 21 3.0 1.2 10 4 0.15 Hypo Hyper Hypo Hyper 1o Hypo 1o Hyper

    11. Laboratory tests in thyroid disease Anti-thyroid antibodies: Anti-thyroid peroxidase (TPO) Thyroid stimulating antibodies: TSI-Thyroid stimulating imunoglobulins TSH receptor Antibody Thyroglobulin

    12. 2. Thyroid scanning Radioactive isotopes of I (131I, 123I) Pertechnetate Generates Data on: - Anatomy - Physiology

    13. Normal thyroid scan

    14. “Hot nodule”

    15. “Cold” nodule

    16. Multinodular goiter (MNG) Pertechnetate scan CHEST X-RAY

    17. Radio Active Iodine Uptake (RAIU) 50 Hyperthroidism 40 Normal 30 Hyperthyroidism with Rapid turnover 20 10 Hypothroidism 0 2 0 6 12 18 24 Time (hours)

    18. Function Structure Thyroiditis Goiter Hyperthyroidism Hypothyroidism Etiology Nodular Diffuse RX Function nl  Benign Malignant Thyroid abnormalities

    19. Hyperthyroidism-Etiology • Diffuse toxic goiter (Graves’ disease)- most common in young people • Toxic adenoma (Plummers’ diesease) • Toxic mulitinodular goiter (MNG) • Subacute thyroiditis-Hyperthyroid phase • Hyperthyroid phase of Hashimotos’ thyroiditis • (“Hashitoxicosis) • Factitious hyperthyroidism • Rare causes: -TSHoma • -Hydatidiform mole/choriocarcinoma • - Multiplex pregnancy • - Struma ovarii

    20. Graves’ disease • Diffuse toxic goiter • Opthalmopathy • Dermopathy • Acropathy (clubbing) Etiology: Autoimmune Anti-TSH receptor antibodies (stimulating, blocking, neutral) Anti-thyroid antibodies  expression of HLA-DR3  association with: -diabetes mellitus-type 1 myasthenia gravis -Addison’s disease lupus - pernicious anemia

    21. Graves’ disease • Epidemiology : incidence 0.3-1.5/1000 • Female: Male 5:1 • Most Common cause of hyperthyroidism

    22. T4, T3 (+) (-) TSH (+) Thyroid Stimulating Immunoglobulins (TSI) Thyroid and pituitary function in Graves’ disease

    23. Graves’ disease- Clinical features Signs: Symptoms: Fatigue palpitations Weight loss Heat intolerance Frequent bowel movements Sweating hyperkinesia Tachycardia Muscle wasting  pulse pressure Eye signs Diffuse goiter Lymphadenopathy Splenomegaly Hyperreflexia In the elderly: cardiovascular symptoms, myopathy

    24. Graves’ Disease- Goiter

    25. Graves disease- Opthalmopathy Extrathyroidal TSHR is present in retro-orbital adipocytes, muscle cells and fibroblasts

    26. Grave’s Opthalmopathy Class 0 — No symptoms or signs Class I — Only signs, no symptoms (eg, lid retraction, stare, lid lag) Class II — Soft tissue involvement Class III — Proptosis Class IV — Extraocular muscle involvement Class V — Corneal involvement Class VI — Sight loss (optic nerve involvement)

    27. Graves’ disease dermopathy

    28. Graves disease- diagnosis • Clinical hyperthyroidism • Biochemistry: FT4, TT3 , TSH • cholesterol  • Serology: anti-TSH receptor antibodies • anti-thyroid antibodies

    29. 1. Antithyroid drugs: Thionamides- Propylthiouracil (PTU) Methimazole (MMI) b-blockers 3. Definitive therapy: 131I- side effects: hypothyroidism Surgery- subtotal thyroidectomy side effects: anesthesia morbidity hypoparathyroidism recurrent laryngeal nerve damage hypothyroidism Treat for 12 months ~30% remission 70% Recurrence Or non-remission Follow-up Graves’ disease- therapy

    30. Anti-thyroid thionamide drugs PTU (propylthiouracil) MMI (methimazole) Dosage:TID Once daily Effect: T4, T3  synthesis T4, T3  synthesis inhibits T4→T3(high dose) (slow) Agranulocytosis*: Non-dose dependent Dose dependent (> 40 mg/day)   > 40 yrs Pregnancy:  placental transfer  placental transfer aplasia cutis *occurrence 0.3-0.6%

    31. Treatment of Graves' Orbitopathy • Treatment of patients with Graves' orbitopathy has three components: • Reversal of hyperthyroidism, if present • Symptomatic treatment • Treatment with a glucocorticoid, orbital irradiation, orbital decompression surgery to reduce inflammation in the periorbital tissues • Anti thyroid drugs and thyroidectomy are safe; Radioactive iodine may worsen the situation.

    32. FT 3 FT 4 The effect of high- dose PTU Pulse rate: 140 50 10 9 45 8 120 7 40 6 Normal range 100 35 5 4 30 3 80 2 25 Upper limit of normal 1 20 0 0 1 2 3 4 5 6 Days 1200 PTU dose mg/day: 600

    33. Subacute thyroiditis Etiology: (Post) viral inflammation of thyroid Symptoms & signs: Hyperthyroidism Painful swelling of thyroid Pain irradiation to ear Fever Sometimes “silent” Laboratory: ESR  acute phase reactants (CRP)

    34. Subacute thyroiditis- therapy A self limited disease Therapy depends on symptoms/signs Non-steroid anti-inflammatory agents (NSAIDS) b-blockers Corticosteroids Outcome - in 6 months 90% euthytroid

    35. Primary - TSH↑ 1. Hashimoto’s thyroiditis 2. Post 131I therapy for Grave’s disease 3. Post thyroidectomy 4. Excessive I intake (amiodarone-procor) Secondary TSH↓ or normal: Hypopituitarism due to adenoma, destructive lesion, ablation TSH↓ Tertiary: Hypothalamic dysfunction (rare) Hypothyroidism- classification

    36. Hypothyroidism- clinical features Signs: Symptoms: Fatigue Weakness Weight gain Cold intolerance Constipation Cramps Paresthesias (carpal tunnel) Coarse features Bradycardia Myxedema Anemia Laboratory: serum thyroid hormones,  cholesterol anemia (iron def., megaloblastic)

    37. Hypothyroidism

    38. Hypothyroidism- myxedema

    39. Hypothyroidism- differential diagnosis Serum FT4 and TSH FT4, TSH normal/low Secondary hypothyroidism FT4, TSH borderline high TSH TRH test Excessive response Primary hypothyroidism

    40. Hypothyroidism- therapy • Levothyroxine 0.05-0.3 mg/day • Combined L-T4 and L-T3 may be beneficial with • respect to well-being • In elderly patients (at high risk for CVD), • “go low, go slow”

    41. Hypothyroidism- treatment After Before

    42. Thyroid Storm and Myxedema Coma – rare endocrine emergencies

    43. THYROID STORM Acute life threatening exacerbation of thyrotoxicosis Clinical setting History of Graves’ disease and discontinuation of medications/ previously undiagnosed hyperthyroidism. Acute onset of hyperpyrexia (over 40 ˚C) Sweating Marked tachycardia, often with atrial fibrillation Nausea, vomiting, diarrhea Agitation, tremulousness, delirium Occasionally “apathetic” – without restlessness and agitation, but with weakness, confusion, and cardio-vascular dysfunction.

    44. THYROID STORM DIAGNOSIS: Largely based on the clinical findings and clinical suspicion. Elevated serum FT4, FT3. Low TSH MANAGEMENT 1. Supportive care Fluids, Oxygen, Cooling blanket,cetaminophen 2. Specific measures Propranolol, 40-80 mg every 6 hours. Antithyroid drugs – PTU. Glucocorticoids - Dexamethasone, 2 mg every 6 hours (due to reduction in glucocorticoids half life)

    45. Myxedema Coma Extreme hypothyroidism: • Coma • Hypothermia • Hypoventilation • Hypoglycemia • Hyponatremia • Bradycardia Laboratory: FT4 , FT3, TSH Co2 retention

    46. Myxedema Coma- therapy Ventilation Precipitating factors Treat: T4 or T3 I.V. Corticosteroids-50-100mg hydrocortisone every 8 hours