graves’ hyperthyroidism and anti-thyroid drugs by 蔡文欽

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.

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 .

PE

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

mor(+)

Treatment

PTU(50mg/tab) 2# BID Propranolol 2# TID

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.

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

Introduction

Propylthiouracil block the conversion of T4T3 within the thyroid and in peripheral tissues

Immunosuppressive effectsTRAb, intracellular adhesion molecule, IL-2 an

d IL-6 receptors.

clinical pharmacology

Rapid GI absorbtion. No dosed adjustment in children, elderly, liver di

sease or renal failure. PTU

T1/2: 90mins 80-90% bound to albumin

Methimazole T1/2: 6hrs Free form

clinical use of drugs Primary treatment for hyperthyroidism or as prep

arative therapy before radiotherapy or surgery. Weighed against the risks and benefits of the mo

re definitive therapy, such as radioiodine and surgery. Ophthalmopathy, pregnancy and most children and a

dolescents. Randomized trial comparing antithyroid drugs, ra

dioiodine, and surgery patient satisfaction was more than 90 percent

for all three, Lowest medical costs in ATD.

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 methimaz

ole. PTU is preferred during pregnancy.

practical considerations

methimazole vs PTU1:10; underestimate10mg85%; 40mg92% after six weeks

Follow-up every 4-6 weeks2-3 months after 3-6 months; then 4-6 months

Remission Less remission if more severe degrees of hypert

hyroidism, 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 treatmentrelapse; normal relapse(30-50%).

Duration and dose vs relapse. 12 to 18 months is recommended.

Discontinuation of drug treatment Stopped or tapered after 12 to 18 ms exc

ept children and adolescents. Relapse after 3-6 ms; 50-60%. Pregnancypostpartum relapse or thyroid

itis. ↑Failure rate of radioiodine in PTU.

Minor side effect

Dose-related in methimazole. Cross-reactivity50%. Arthragiaantithyroid arthritis syndrome.

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 methi

mazole Vasculitis (PTU>methimazole)

Lupus; self-limited Steroid or cyclophosphamide; H/D.

Use of antithyroid drugs during pregnancy and lactation Congenital anomalies, esp aplasia cutis while m

ethimazole (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