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Graves’ hyperthyroidism and anti-thyroid drugs

Graves’ hyperthyroidism and anti-thyroid drugs. By 蔡文欽. Case. The patient is a 77 years female with history of hypertension with regular treatment for many years.

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Graves’ hyperthyroidism and anti-thyroid drugs

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  1. Graves’ hyperthyroidism and anti-thyroid drugs By 蔡文欽

  2. Case • The patient is a 77 years female with history of hypertension with regular treatment for many years. • She suffered from poor appetite, body weight loss, diarrhea, sweating, insomnia, palpitation, weakness, anxiety and hand tremor difficult swallow function for two months. • She went to our OPD and was admitted for further evaluation and management .

  3. PE • Conscious:clear • Skin: warm and moist • HEENT: no protrudent eye; fine air • Neck: no palpable mass • Heart: tachycardia; RHB. • Limbs: proximal weakness; edema(+); tremor(+)

  4. Treatment • PTU(50mg/tab) 2# BID • Propranolol 2# TID

  5. Graves' disease • Patient with biochemically confirmed thyrotoxicosis, diffuse goiter on palpation, ophthalmopathy, positive TPO antibodies, and often a personal or family history of autoimmune disorders.

  6. Introduction • Thionamides, a sulfhydryl group and a thiourea moiety within a heterocyclic structure • Propylthiouracil (PTU, 6-propyl-2-thiouracil). • Methimazole (1-methyl-2-mercaptoimidazole); in US, Asia and Europe. • Carbimazle (analogue of methimazole); in UK. • Inhibit TPO-mediated iodination

  7. Introduction • Propylthiouracil block the conversion of T4T3 within the thyroid and in peripheral tissues • Immunosuppressive effects • TRAb, intracellular adhesion molecule, IL-2 and IL-6 receptors.

  8. clinical pharmacology • Rapid GI absorbtion. • No dosed adjustment in children, elderly, liver disease or renal failure. • PTU • T1/2: 90mins • 80-90% bound to albumin • Methimazole • T1/2: 6hrs • Free form

  9. clinical use of drugs • Primary treatment for hyperthyroidism or as preparative therapy before radiotherapy or surgery. • Weighed against the risks and benefits of the more definitive therapy, such as radioiodine and surgery. • Ophthalmopathy, pregnancy and most children and adolescents. • Randomized trial comparing antithyroid drugs, radioiodine, and surgery patient satisfaction was more than 90 percent for all three, Lowest medical costs in ATD.

  10. choice of drugs • oncedaily in methimazole; better adherence and rapid improvement in T3 and T4 than PTU. • PTU (300 mg daily)  $408 /year • Methimazole (15 mg daily, $360; or 30 mg daily, $720). • Side-effect profiles of the two drugs methimazole. • PTU is preferred during pregnancy.

  11. practical considerations • methimazole vs PTU1:10; underestimate • 10mg85%; 40mg92% after six weeks • Follow-up every 4-6 weeks2-3 months after 3-6 months; then 4-6 months

  12. Remission • Less remission if more severe degrees of hyperthyroidism, large goiters, high TRAb or a high T3/T4 after course of drug treatment. • High relapse if depression, paranoia and problem of daily life. • Poor clinical or biochemical predictor in 300 patients study. • TRAb(+) after treatmentrelapse; normal relapse(30-50%). • Duration and dose vs relapse. • 12 to 18 months is recommended.

  13. Discontinuation of drug treatment • Stopped or tapered after 12 to 18 ms except children and adolescents. • Relapse after 3-6 ms; 50-60%. • Pregnancypostpartum relapse or thyroiditis. • ↑Failure rate of radioiodine in PTU.

  14. Minor side effect • Dose-related in methimazole. • Cross-reactivity50%. • Arthragiaantithyroid arthritis syndrome.

  15. Major side effect • Agranulocytosis(90 days; 0.35% vs 0.37%) • Autoimmune process; ANCA. 1000-1500. • Fever and sore throat; stop drugs and G-CSF. • Pseudomonas aeruginosa. • Hepatotoxicity(0.1-0.2%) • Hepatocellular injury in PTU and cholestatsis in methimazole • Vasculitis (PTU>methimazole) • Lupus; self-limited • Steroid or cyclophosphamide; H/D.

  16. Use of antithyroid drugs during pregnancy and lactation • Congenital anomalies, esp aplasia cutis while methimazole (1/2000 births). • Methimazole embryopathy; 2/241 vs. 1/2500 to 1/10,000 (esophageal atresia and choanal atresia). No increase in other studies. • Class D (risk of fetal hypothyroidism). • No risk in breast milk

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