Approach to patients with thyrotoxicosis R4. 손 정 일 / Prof. 전 숙

Thyroid Hormone O OH I I I I O NH 2 Thyroxine (T 4 ) O OH I I I O NH 2 3,5,3’-Triiodothyronine (T 3 )

Synthesis of Thyroid Hormone 1. 요오드의 trapping 2.MIT, DIT 합성 ( 요오 드의 유기화 ) 3.Coupling (T3, T4, rT3) 4. 여포강 내에서의 thyroglobulin 결합 5.Thyroglobulin 의 protease 분해

Action of Thyroid Hormone Required for homeostasis of all cells Influence cell differentiation, growth, and metabolism Considered the major metabolic hormones because they target virtually every tissue Growth and Development Neural development of CNS Cardiovascular Hemodynamics Reproductive System Skeletal system

Thyrotoxicosis vs. Hyperthyroidism Thyrotoxicosis : STATUS Defined as the clinical, physiologic and biochemical findings that result when the tissues are exposed to and respond to excess thyroid hormone. Rather than being a specific disease, thyrotoxicosis can originate in a variety of ways. Hyperthyroidism : DISEASE Denotes only those conditions in which sustained hyperfunction of the thyroid gland leads to thyrotoxicosis. Thyroid storm Extreme manifestation of thyrotoxicosis

Causes of thyrotoxicosis Harrison, Internal Medicine, 18 th edition

Symptoms and Signs Organ systemSymptomsSigns Neuropsychiatric/ Neuromuscular Emotional lability Anxiety Confusion Coma Muscle wasting Hyperreflexia Fine tremor Periodic paralysis GastrointestinalHyperdefecation Diarrhea ReproductiveOligomenorrhea Decreased libido Gynecomastia Spider angiomas Thyroid glandNeck fullness Tenderness Diffuse enlargement Bruit CardiorespiratoryPalpitations Dyspnea Chest pain Atrial fibrillation Sinus tachycardia Hyperdynamic precordium Congestive heart failure DermatologicHair lossPretibial myxedema Warm, moist skin Palmar erythema OpthalmologicDiplopia Eye irritation Exopthalmos Opthalmoplegia

Differential Diagnosis of Thyrotoxicosis

Other considerations Thyroid peroxidase Ab (TPO Ab) Hashimoto thyroiditis Graves’ disease Thyroglobulin Ab (Tg Ab) Hashimoto thyroiditis (Subacute thyroiditis) Thyroid stimulating hormone receptor Ab (TSH-R Ab) Graves’ disease TSH receptor inhibitinig immunoglobulin(TBII), Thyroid stimulating immunoglobulin(TSI) Graves’ disease ESR/CRPSubacute thyroiditis

Graves’ disease Accounts for 60–80% of thyrotoxicosis Caused by auto-antibodies to the TSH receptor Typical features Diffusly enlarged thyroid Opthalmopathy Dermopathy

Elevated TBII or TSI : most reliable Diffusely elevated radioiodine uptake

Toxic multinodular goiter & Toxic adenoma Toxic MNG The presence of functional autonomy in multinodular goiter It is more common in iodine-deficient regions but also occurs in r egions of iodine sufficiency, reflecting multiple genetic, autoimm une, and environmental influences on the pathogenesis Toxic adenoma A solitary, autonomously functioning thyroid nodule Activating mutations in either the TSH-R or the G S subunit genes are identified in >90% of patients with solitary hyperfunctioning n odules. Mild thyrotoxicosis + presence of the thyroid nodule, and by the absence of clinical features suggestive of Graves' disease or oth er causes of thyrotoxicosis Definitive Diagnosis : Thyroid scan

Subacute thyroiditis (DeQuervain’s, Granulomatous, Viral) Most common cause of painful thyroiditis Often follows a URI FNA may reveal multinuleated giant cells or granulomatous change. Course Pain and thyrotoxicosis (3-6 weeks) Asymptomatic euthyroidism Hypothyroid period (weeks to months) Recovery (complete in 95% after 4-6 months)

Diagnosis Elevated ESR Anemia (normochromic, normocytic) Low TSH, Elevated T4 > T3, Low anti-TPO/TgAb Low RAI uptake (same as silent thyroiditis)

Radioactive Iodine Uptake(RAIU) Diagnostic imaging procedure to evaluate the thyroid gland Radioactive tracer that is selectively absorbed by the thyroi d is administered either orally or intravenously => measure the concentration of the radioactive tracer in th e thyroid gland Normal : About 10~25% at 24 hour

Treatment Graves’ disease : N Engl J Med 2005;352:

N Engl J Med 2008; 358:

Treatment Toxic multinodular goiter Antithyroid drugs + beta blockers -> can normalize thyroid function and address clinical features of thyrotoxicosis, but spontaneous remission does not occur Radioiodine => multiple autonomous regions emerge as soon as others are treated Surgery => definitive treatment Toxic adenoma Radioiodine ablation is usually the treatment of choice Because normal thyroid function is suppressed, radioiodine is co ncentrated in the hyperfunctioning nodule with minimal uptake a nd damage to normal thyroid tissue Enucleation of the adenoma or lobectomy

Treatment Subacute thyroiditis Relatively large doses of aspirin (e.g., 600 mg every 4–6 h) or N SAIDs are sufficient to control symptoms Glucocorticoids(starting dose : 40–60 mg prednisone) Beta blockers for symptoms of hyperthyroidism PTU not indicated since excess hormone results from leak instead of hyperfunction