THYROID DISORDERS

blood flow thrill bruit Thyroid hormone - - metabolism Iodine metabolism iodine inorganic iodide thyroid hormone 3 1. Iodide transport2. Oxidation iodine organic iodination3. iodothyronineIodide transportIodide active transport Na-K ATPase system iodide thyroid stimulating hormone (TSH) autoregulation thyroid Oxidation iodine organic iodination iodine iodide oxidation iodination tyrosine thyroglobulin monoiodothyrosine (MIT) diiodothyrosine (DIT) peroxidase activity peroxidase TSH autoregulation thyroid iodothyronine coupling MIT+DIT triiodothyronine (T3) DIT+DIT thyroxine (T4) T3 T4 thyroid receptor nucleus affinity T3 T4 10 T3 metabolic potency T4 3 thyroid hormone thyroid hormone thyroid hormone 99% bound form thyroid hormone binding protein

thyroid hormoneThyroid hormone hypothalamic-pituitary feedback control thyroid hormone thyrotropin releasing hormone (TRH) hypothalamus TSH thyroid hormone TSH diurnal rhythm , estrogen, alpha adrenergic agonist dopamine antagonist thyroid hormone, glucocorticoid, dopamine, somatosatatin T3, T4 negative feedback mechanism TSH negative feedback thyroid autoregulation iodine autoregulation Wolff-Chaikoff effect

Hyperthyroidism

Hyperthyroidism thyroid 1. Toxic diffuse goiter (Graves disease) auto immune disease thyroid stimulating immnunoglobulin Graves disease 2. Toxic adenoma 3. Toxic multinodular goiter (Plummers disease) 4. Thyroditis 5. Iodine-induced hyperthyroidism6. Excessive pituitary TSH, trophoblastic disease7. Excessive ingestion of thyroid hormone hyperthyroidism (2% vs 0.2%)Thyrotoxicosis thyroid thyroid hormone metabolism hyperthyroidism hormone hormone Euthyroid sick syndrome T4 T3 peripheral tissue thyroid function test total T3 T4 , FT4 (free T4), TSH starvation, psychosis disorders, neoplastic disorder, acquire immunodeficiency syndrome, renal, hepatic disorder euthyroid hyperthyroidism, Nervousness and irritability Palpitation and tachycardia Heat intolerance or increasing sweating Tremor Weight loss or gain Alteration in appetite Frequent bowel movements or diarrhea Dependent lower-extremity edema Sudden paralysis Exertional intolerance and dyspnea Menstrual disturbance (decreased flow) Impaired fertility Mental disturbances Sleep disturbances (including insomnia) Changes in vision, photophobia, eye irritation, diplopia, or exophthalmos Fatigue and muscle weakness Thyroid enlargement (depending on cause) Pretibial myxedema (in patients with Graves disease): hyperthyroidism

NameNormal ValueHypothyroidismHyperthyroidism

Thyroid Stimulating Hormone (TSH)

0.5-4.7 mU/L

High

Low

Total T4 Immunoassay

5 11 g/dL or 64 142 nmol/L

LowHigh

Free T4 Index

16-50 mmol/L

LowHigh

Total T3 Immunoassay

70-132 ng/dL or 1.1-2.0 nmol/L

Normal or LowHigh

Free T3 Index

0.28-0.75 nmol/dl18-49 ng/dL

Normal or LowHigh

hyperthyroidism Atrial FibrillationCongestive Heart FailureHypoparathyroidismHypothyroidismOsteoporosis hyperthyroidism , thyroid, , , 3 1. : , , thyroid , 2. : , thyroid , 3. radioactive iodine: , , , , thyroid hyperthyroidism 1. hyperthyroidism, thyroid hormone 2. thyroid storm3. goiter4. systemic embolism5. osteoporosis6. 7.

EfficacyFailureAdverse event

(30%) 2 ?30-40%-Graves diseaseRelapse 60%Hypothyroidism 5-10%,

(5%) ( 1 )5,000-20,00070-80%-Graves disease-Toxic multinodular goiter-Toxic adenomaRelapse 20-30%Hypothyroidism 20-30% (laryngeal nerve palsy)1: 500 Hypoparathyroidism 1:500

(60%) 1 1,800-3,00070-80%-Graves disease-Toxic multinodular goiter-Toxic adenomaHypothyroidism 3-6%Teratogenicity

Propylthiouracil (PTU) Methimazole (MMI) thioamide*Adverse drug event

PTU150 mg/day devided to three times a day thyroid hormone peripheral conversion T4 T3Most common: rash, itching, hives, abnormal hair loss, and skin pigmentationLess common: swelling, nausea, vomiting, heartburn, loss of taste, joint or muscle aches, numbness and headacheRare: Hepatitis, hepatic necrosis, dose independent agranulocytosis - placenta

MMI7.5-15 mg/day once daily dose thyroid hormoneMost common: rash, itching, hives, abnormal hair loss, and skin pigmentationLess common: swelling, nausea, vomiting, heartburn, loss of taste, joint or muscle aches, numbness and headache Rare:Hepatitis, hepatic necrosis, dose dependent agranulocytosis (>15 mg/day)- placenta

* 2 euthyroidism thyroid hormone , 2 , 6 3 agranulocytosis PTU MMI agranulocytosis 6 agranulocytosis , , , agranulocytosis rechallenge maculopapular rash antihistamine thioamides cross sensitivity Beta blockers propranolol, atenolol, metoprolol hormone peripheral tissue , , beta blockers selective non selective beta blockers beta blockers intrinsic sympathomimetic activity heart rate beta blocker beta blockers 1-2 euthyroidism

radioactive iodine (131I) congenital malformation 6 , 1-2 euthyroid hypothyroidism 131I 7 131I , 8 , 131I 5 5

Hyperthyroidism - PTU first choice hyperthyroidism postpartum recurrence hyperthyroidism

Thyroid crisis, thyroid stormThyroid crisis, thyroid storm hyperthyroidism 20-30%1. 39-40 2. Arrhythmia supraventricular tachycardia sinus tachycardia atrial fibrillation pulse rate 140 3. , , 4. , 5. agitation, psychosis, coma6. dehydration Thyroid crisis, thyroid storm 1. thyroid 2. radioactive iodine3. 4. PTU, MMI5. 6. 7. iodine iodine amiodarone8. thyroid hormone 1. hyperthyroidism hormone PTU 1200-1500 mg/day 6 thyroid hormone thyroid saturated solution of potassium iodide; SSKI Lugols solution) 1 iodine 50 mg iodide 200-500 mg 12 PTU 1 peripheral conversion T4 T3 dexamethasone 8-12 mg/day thyroid hormone plasmapheresis 2. 5%dextrose paracetamol aspirin free form hormone binding site , beta blocker 3. thyroid crisis, thyroid storm

Hypothyroidism

Hypothyroidism thyroid hormone hypothyroidism (1.4% vs 0.1%) autoimmune disease (Diabetes Mellitus, rheumatoid), thyroid disorder primary hypothyroidism chronic autoimmune thyroiditis (Hashimotos disease) primary hypothyroidism thyroid, , uptake iodide, tumor, lithium interferon secondary hypothyroidism pituitary, hypothalamus/ Fatigue Weight gain from fluid retention Dry skin and cold intolerance Yellow skin Coarseness or loss of hair Hoarseness Goiter Reflex delay, relaxation phase Ataxia Constipation Memory and mental impairment Decreased concentration Depression Irregular or heavy menses and infertility Myalgias Hyperlipidemia Bradycardia and hypothermia Myxedema fluid infiltration of tissues

TSH : , , psychosis, /: , creatine phosphokinase (CPK ) , : CHD hypothyroidism thyroid hormone Na l-thyroxin (levothyroxine 0.1 mg 0.05 mg) thyroid hormone 1. hypothyroidism 2. pituitary-thyroid axis TSH thyroid, thyroid cancer : 1. hormone 0.075-0.15 mg/day pituitary-thyroid axis 0.15-0.20 mg/day2. 3. 4. TSH5. thyroid 6. 12.5 microgram 6 narrow therapeutic range drug interaction levothyroxine cholestyramine, ferrous sulfate, sucralfate, calcium, antacid levothyroxine anticonvulsants metabolism levothyroxine rifampin TSH T4 secondary hypothyroidism TSH TSH hypothyroidism 1. thyroid hormone 2. hypothyroidism3. goiter4. serum cholesterol5. 6. myxedema7. Adverse effect 1. Hyperthyroidism, thyrotoxicosis2. Osteoporosis3. Drug allergy4. Adrenal crisis adrenal insufficiencyHypothyroidism hypothyroidism postpartum hemorrhage, hypertension, preeclampsia, anemia, spontaneous abortion fetal death , mild hypothyroidism levothyroxine TSH hypothyroidism TSH 6

Myxedema comaMyxedema coma hypothyroidism , , 30%1. hypothyroidism2. hypothyroidism 3. myxedema coma - psychosis - hypoventilation- Hypothermia- Hyponatremia myxedema coma1. 2. , transquilizer, nacrotic analgesic3. thyroid hormone amiodarone, lithium carbonate4. 5. CHF, 1. thyroid hormone : levothyroxine 1 mg PO 2. steroid: hydrocortisone 300 mg/day adrenal insufficiency3. 4. precipitating causes