Dharma Lindarto Div. Endokrin-Metabolisme dan Diabetes. Dep Ilmu Penyakit Dalam FK USU / RSUP HAM Medan

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1 HYPERTHYROIDISM Dharma Lindarto Div. Endokrin-Metabolisme dan Diabetes. Dep Ilmu Penyakit Dalam FK USU / RSUP HAM Medan

2 Anatomy of the Thyroid Gland

3 Tiroid Disease Multi N Aspect fungtion morphology eutiroid, hypertiroid, hypotiroid normal, atrophic, nodule, diffus

4 Hypothalamus- Pituitary- Thyroid Axis

5 Typical Thyroid Hormone Levels in Thyroid Disease TSH T 4 T 3 Hypothyroidism High Low Low Hyperthyroidism Low High High Subclinical Hypothyroidsm Subclinical Hyperthyroidsm High normal normal Low normal normal

6 Thyrotoxicosis and Hyperthyroidism Definitions Thyrotoxicosis The clinical syndrome of hypermetabolism that results when the serum concentrations of free T 4, T 3, or both are increased Hyperthyroidism Sustained increases in thyroid hormone biosynthesis and secretion by the thyroid gland The 2 terms are not synonymous Braverman LE, et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed

7 Thyroid Storm Rare complication of hyperthyroidism where manifestations of thyrotoxicosis become life threatening. Also may be termed Thyrotoxic Crisis. Apathetic Thyrotoxicosis Rare form usually occurring in the elderly. Often presents as single organ failure (CHF). Patient may develop thyroid storm without the typical manifestations.

8 Prevalence of Thyrotoxicosis In a cross-sectional study of urban and rural adults, the prevalence of thyrotoxicosis ranged from 1.9% to 2.7% in women 0.16% to 0.23% in men Tunbridge WMG, et al. Clin Endocrinol. 1977;7:

9 Hyperthyroidism Etiology Graves disease Multinodular goiter Autonomous nodule Exogenous thyroid hormone Transient subacute thyroiditis, postpartum thyroiditis Drugs amiodarone

10 Causes of Thyrotoxicosis Divided by Degree of Radioiodine Uptake High I 123 Uptake Graves disease I Toxic nodular goiter 123 TSH-mediated thyrotoxicosis Pituitary tumor Pituitary resistance to thyroid hormone HCG-mediated thyrotoxicosis Hydatidiform mole Choriocarcinoma Other HCG-secreting tumors Thyroid carcinoma (very rare) Low I 123 Uptake Subacute thyroiditis Hashitoxicosis Drug-induced Iodide Thyroid hormone Struma ovarii Factitious I 123

11 Common Signs and Symptoms of Thyrotoxicosis Symptoms Nervousness Fatigue Weakness Increased perspiration Heat intolerance Tremor Hyperactivity Palpitations Appetite/weight changes Menstrual disturbances Signs Hyperactivity Tachycardia Systolic hypertension Warm, moist, or smooth skin Stare and eyelid retraction Tremor Hyperreflexia Muscle weakness Braverman LE, et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed

12 SYSTEMIC EFFECTS RESPIRATORY Dyspnea, panting, hyperventalation respiratory muscle weakness increased tissue carbon dioxide levels +/- congestive heart failure

13 SYSTEMIC EFFECTS CARDIOVASCULAR Thyrotoxic cardiomyopathy Hypermetabolic state Systemic hypertension Direct T3 and T4 action on heart muscle LV hypertrophy, IVS hypertrophy, RA and aortic dilation, enhanced contractility

14 1. Graves Disease (Toxic Diffuse Goiter) The most common cause of hyperthyroidism Accounts for 60% to 90% of cases Incidence in the United States estimated at 0.02% to 0.4% of the population Affects more females than males, especially in the reproductive age range Graves disease is an autoimmune disorder possibly related to a defect in immune tolerance

15 Graves Disease Autoimmune disorder Production of TSH receptor autoantibodies Stimulate thyroid hormone overproduction Characterized by the presence of B- and T- lymphocytes in thyroid tissue TSH receptor activation Thyroglobulin and thyroid peroxidase antibodies Sodium/iodide cotransporter (NIS) activity enhanced (increased RAI) Autoantigens Abbott Laboratories Diagnostics Division Web site. Available at: et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed

16 Graves' Disease Goiter Hyperthyroidism Exophthalmos Localized myxedema Thyroid acropachy Thyroid stimulating immunoglobulins

17 Clinical Characteristics of Goiter in Graves Disease Diffuse increase in thyroid gland size Soft to slightly firm Non-nodular Bruit and/or thrill Mobile Non-tender Without prominent adenopathy

18 Graves Disease - Localized Myxedema Margins sharply demarcated Nodularity Thickened skin Margins sharply demarcated

19 Graves Ophthalmopathy Class one: spasm of upper lids with thyrotoxicosis Class two: periorbital edema and chemosis Class three: proptosis Class four: extraocular muscle involvement Class five: corneal involvement Class six: loss of vision due to optic nerve involvement

20 DIAGNOSTICS Endocrine Testing Total T4: 5-10% will be normal Total T3: 30% will be normal Free T4: false negative with NTI and shipping ft4 better T3 supression TRH stimulation and TSH response

21 DIAGNOSTICS RADIONUCLIDE IMAGING Pertechnetate imaging extent of involvement detect metastasis to other gland no palpable enlargement (within thorax) Carcinoma metastasis

22 2. Toxic Multinodular Goiter More common in places with lower iodine intake Accounts for less than 5% of thyrotoxicosis cases in iodine-sufficient areas Evolution from sporadic diffuse goiter to toxic multinodular goiter is gradual Thyrotropin receptor mutations and TSH mutations have been found in some patients with toxic multinodular goiters Th/ Surgery or 131 I is recommended treatment Braverman LE, et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed

23 Toxic Multinodular Goiter MNG is an enlarged thyroid gland containing multiple nodules The thyroid gland becomes more nodular with increasing age In MNG, nodules typically vary in size Most MNGs are asymptomatic MNG may be toxic or nontoxic Toxic MNG occurs when multiple sites of autonomous nodule hyperfunction develop, resulting in thyrotoxicosis Toxic MNG is more common in the elderly

24 3. Toxic Adenoma Autonomously functioning thyroid nodule hypersecreting T3 and T4 resulting in thyrotoxicosis (Plummer s disease) Almost never malignant Manage with antithyroid drugs followed by either I-131 or surgery

25 Laboratory Testing in Thyroid Disease TSH: Pituitary hormone which stimulates thyroid May rise transiently in recovery from other illness Free T4: direct measure of thyroxine activity May be transiently suppressed in severe acute illness Free T3: suspect hyperthyroid but normal FT4 Thyroid peroxidase/thyroperoxidase antibody: Anti-TPO High levels in Hashimoto s (95%) & Graves TSH receptor stimulating Ab measures activity in Graves-use in pregnancy

26 Scans/Ultrasound Radioiodine uptake (RAIU) Thyroid Scan Ultrasound Fine needle Aspiration

27 Treatment of Hyperthyroidism 1. Antithyroid drugs 2. Surgical resection 3. Radioactive iodine therapy Braverman LE, et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed

28 1. Antithyroid Drug Therapy Acute hyperthyroid symptoms Goal of therapy: Inhibit peripheral conversion of T4 to T3 Inhibit synthesis and release of T4 and T3 from thyroid gland Propylthiouracil (PTU) Methimazole [generic] or Tapazole

29 Antithyroid Drug Therapy A. PTU: Inhibits peripheral conversion of T4 to T3 Inhibits thyroid hormone synthesis and release from thyroid gland B. Methimazole [generic]: Inhibits thyroid hormone synthesis and release from thyroid gland

30 C. Beta-blocker therapy: Ameliorates tachycardia, sweating, tremor, nervousness Propanolol: starting dose mg PO q6h Caution in patients with CHF or bronchospasm

31 2. Subtotal Thyroidectomy Surgical complications: Vocal cord paralysis (1%) Hypothyroidism (up to 43% after 10 years) Hypoparathyroidism Recurrence of hyperthyroidism (10-15%)

32 3. Radioactive Iodine 131 [I] Ablation Treatment of choice in patients > 21 years old with Graves Disease Treatment of choice in patients < 21 years old without remission after antithyroid drug therapy Treatment of choice in patients with toxic multinodular goiter or toxic thyroid adenoma

33 Radioactive Iodine Ablation (cont ) Single dose of 131 [I] orally 80% euthyroid after single dose > 50% of patients will develop hypothyroidism Assay TSH every 3 months after therapy

34 Radioactive Iodine Ablation (Cont ) Levothyroxine therapy when patient becomes hypothyroid Life-long Levothyroxine therapy RIA contraindicated in pregnancy, lactation, iodine allergy Screen pre-menopausal women for pregnancy prior to treatment

35 Thyroid Storm A life-threatening crisis. Estimated mortality : 20-30%. the result of thyroid surgery. Caused more often by antecedent Grave s disease.

36 Precipitants of Thyroid Storm Surgery. Radioiodine therapy. Iodinated contrast dyes. Thyroid hormone ingestion. Diabetic Ketoacidosis. Cerebrovascular accident. Pulmonary embolism and CHF.

37 Pathophysiology of Thyroid Storm 1) An acute decrease in thyroxinebinding globulin => high levels of free hormone. 2) Thyroid hormone increases the density of beta-adrenergic receptors & alters responsiveness to catecholamines at a postreceptor level.

38 Laboratory Diagnosis of Thyroid Storm A combination of low TSH and elevated free T4 => makes the diagnosis. If TSH is lower than normal and free T4 is normal => free T3 testing is recommended. ED measurement of thyroglobulin or thyroid antibodies : No indication.

39 Treatment of Thyroid Storm Block hormone synthesis with either : a) Propylthiouracil mg loading PO or NG, mg q4h for total daily dose of mg ; or b) methimazole 20 mg PO ( mg range ) q 4h.

40 Treatment of Thyroid Storm ( continued ) Inhibit hormone release : Iodides Potassium iodide ( SSKI ) 5 drops PO Q6-8H, or Lugol s solution 7-8 drops ( 1 ml PO Q6H ) or Ipodate 1-3 g daily ( as 1 g Q8H for 24 hours, then 500 mg Q12H ). If severe iodide allergy, lithium carbonate 300 mg Q6H.

41 Treatment of Thyroid Storm ( continued ) Glucocorticoids : Hydrocortisone ( 300 mg IV, then 100 mg IV q8h ) ; dexamethasone ( 2 mg Q6H ). Adrenergic blockade : Propranolol ( mg IV over 15 minutes slow IV, then mg PO Q4H ) ; Esmolol ( mcg/kg loading, infusion of mcg/kg/min ).

42 Adjunctive Therapy for Thyroid Storm Treat fever aggressively with acetaminophen. IV fluid containing 10% dextrose are recommended. Administer vitamin supplements, including thiamine. Treat CHF with conventional methods.

43 Adjunctive Therapy for Thyroid Storm ( continued ) Identify the precipitating event, including infection. Consider plasmapheresis, Consider plasmapheresis, hemodialysis or peritoneal dialysis for removal of metabolically active hormone.

44 Thyrotoxic Periodic Paralysis Most common cause of hypokalemic periodic paralysis Flaccid paralysis Lower extremities affected most often Ocular and bulbar muscles uninvolved, respiratory muscles rarely involved Most often starts during sleep Precipitated following exercise, high salt intake or high carbohydrate diet Hypokalemia during the paralysis

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