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Graves’
hyperthyroidism and
anti-thyroid drugs
By 蔡文欽
Case
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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(+);
tremor(+)
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Treatment
PTU(50mg/tab) 2# BID
 Propranolol 2# TID
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Graves' disease
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Patient with biochemically confirmed
thyrotoxicosis, diffuse goiter on palpation,
ophthalmopathy, positive TPO antibodies,
and often a personal or family history of
autoimmune disorders.
Introduction
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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
T4T3 within the thyroid and in peripheral
tissues
 Immunosuppressive effects
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 TRAb,
intracellular adhesion molecule, IL-2
and IL-6 receptors.
clinical pharmacology
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Rapid GI absorbtion.
No dosed adjustment in children, elderly, liver
disease or renal failure.
PTU
 T1/2:
90mins
 80-90% bound to albumin
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Methimazole
 T1/2:
6hrs
 Free form
clinical use of drugs
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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.
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Randomized trial comparing antithyroid drugs,
radioiodine, and surgery
patient satisfaction was more than 90 percent
for all three,
Lowest medical costs in ATD.
choice of drugs
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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.
practical considerations
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methimazole vs PTU1:10;
underestimate
 10mg85%;
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40mg92% after six weeks
Follow-up every 4-6 weeks2-3 months
after 3-6 months; then 4-6 months
Remission
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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.
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.
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Minor side effect
Dose-related in methimazole.
 Cross-reactivity50%.
 Arthragiaantithyroid arthritis syndrome.
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Major side effect
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Agranulocytosis(90 days; 0.35% vs 0.37%)
 Autoimmune
process; ANCA. 1000-1500.
 Fever and sore throat; stop drugs and G-CSF.
 Pseudomonas aeruginosa.
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Hepatotoxicity(0.1-0.2%)
 Hepatocellular
injury in PTU and cholestatsis in
methimazole
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Vasculitis (PTU>methimazole)
 Lupus;
self-limited
 Steroid or cyclophosphamide; H/D.
Use of antithyroid drugs during
pregnancy and lactation
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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