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Hyperthyroidism TRH –Thyrotropin-releasing hormone Produced by Hypothalamus Release is pulsatile Downregulated by T3 Travels through portal venous system to adenohypophysis Stimulates TSH formation TSH – Thyroid-stimulating hormone Produced by Adenohypophysis Upregulated by TRH Downregulated by T4, T3 Travels through portal venous system to cavernous sinus, body. Stimulates: Iodine uptake Growth of thyroid gland Thyroid Hormone Majority of circulating hormone is T4 98.5% T4 1.5% T3 Total Hormone load is influenced by serum binding proteins Albumin 15% Thyroid Binding Globulin 70% Transthyretin 10% Hyperthyroidism Primary hyperthyroidism Secondary hyperthyroidism (TSH) Tertiary hyperthyroidism (TRH) Hyperthyroidism Normal Thyroid Inactive Thyroid Hyperactive Thyroid Hyperthyroidism 1. Graves’ disease Toxic multinodular goiter Toxic adenoma Graves’ disease Most common cause of thyrotoxicosis Autoimmune condition with anti-TSH antibodies Onset of disease may be related to severe stress which alters the immune response Graves’ disease Etiology: Is most often seen in women 20-40 years of age Toxic nodular goiter Toxic adenomas Subacute thyroiditis Graves’ disease - History Weight loss Increased appetite Heat intolerance, increase sweating Nervousness Weakness Increased bowel frequency Menstrual abnormalities Graves’ disease – Clinical features Warm, moist skin Goiter Sinus tachycardia or atrial fibrillation Thyroid bruit Tremor Hyperactive reflexes Graves’ disease - Exophthalmos Proptosis and lid retraction results from: 1) lymphocytic infiltration 2) edema of the extraocular muscles Graves’ disease - Evaluation Suppressed TSH Elevated Total T4 TRH Increased free T3, T4 Thyroglobulin Antibodies: Anti-TSH Graves’ disease - Treatment 1. Beta blockers for symptoms 2. Thionamide medications May re-establish euthyroidism in 6-8 weeks 40% - 60% incidence of disease remission 3. Radioiodine ablation 10% incidence of hypothyroidism at 1 year 55% - 75% incidence of hypothyroidism at 10 years Graves’ disease - Treatment Surgery Used for compressive symptoms Hypothyroidism occurs in up to 70% of subtotal thyroidectomy patients Pre-surgical stabilization with thionamide medications Hyperthyroidism - Treatment Antithyroid drugs: Methimazole Carbimazole Propylthiouracil Complications Thyroid storm – extreme hyperthyroidism Symptoms include: high fever, dehydration, tachycardia high-output cardiac failure coma Complications Treatment of a thyroid storm: B-blocker (propranolol) Propylthiouracil (PTU) Iodine Cooling measures Toxic Adenoma Treatment Radioiodine Surgery Preferred for children and adolescents Preferred for very large nodules when high I131 doses needed