Carbimazole, in 3 divided daily doses, is commonly prescribed for the treatment of thyrotoxicosis. However, based on its long intra-thyroid half-life, the drug may be effective when used as a single or twice daily dose. This study was undertaken to determine the effect of once, twice or thrice daily doses of carbimazole on thyroid function in patients with thyrotoxicosis. Seventy previously untreated thyrotoxic patients were randomly allocated to receive carbimazole 30 mg once (group 1), 15 mg twice (group 2) and 10 mg thrice (group 3) daily. All patients were also prescribed propranolol 20 mg thrice daily for the first 4 weeks. Blood was taken for total T3, T4, TSH, blood counts and liver enzymes determinations at the beginning and at 6 weeks of treatment. Only 48 (68.6%) patients were included in the analysis, as the rest defaulted follow-up (20.0%) or blood samples were not available at review (11.4%). Of the 48 patients, 17 were in group 1, 16 in group 2 and 15 in group 3. Following 6 weeks of treatment, there was no significant difference in the mean serum levels of total T3 and T4 between the 3 groups. However, there was a significant decrease in the mean serum levels of total T3 and T4 as compared to the start of the treatment. Four patients (23.5%) in group 1, 4 patients (25%) in group 2 and 3 patients (20%) in group 3 were still thyrotoxic at 6 weeks of treatment, whilst 10 patients (58.8%) in group 1, 6 patients (37.5%) in group 2 and 3 (20%) in group 3 were biochemically hypothyroid.(ABSTRACT TRUNCATED AT 250 WORDS)
Thyrotoxicosis gives rise to a high output cardiac failure. Rarely, it can cause a dilated cardiomyopathy with severe impairment of myocardial function which improves significantly following treatment.
Drug-induced agranulocytosis is a potentially fatal complication despite advances in supportive care. A patient with carbimazole-induced agranulocytosis associated with marked depletion of granulocytic precursors in the marrow was treated with granulocyte-macrophage colony stimulating factor (GM-CSF) at a dose of 5 micrograms/kg subcutaneously daily for one week. The absolute neutrophil count rose above 1 x 10(9)/L after one week of GM-CSF therapy. The GM-CSF probably expedited the recovery of the neutrophil count. Further studies are warranted to delineate the role of GM-CSF in the treatment of drug-induced agranulocytosis.
We report a 33-year-old Malay lady who presented with fever, tonsillitis and pharyngitis a month after initiation of antithyroid therapy (carbimazole 15 mg tds) for thyrotoxicosis by her general practitioner. She was still clinically and biochemically thyrotoxic but not in thyroid storm. At that time, she was also confirmed to be four weeks pregnant. Her full blood count revealed neutropaenia with an absolute neutrophil count of 0.036 × 109/L. Bone marrow aspirate and trephine were compatible with carbimazole-related agranulocytosis. Carbimazole was discontinued and she was given broad spectrum antibiotics and Granulocyte Colony Stimulating Factor (GCSF), to which she responded. Verapamil was used for symptomatic heart rate control instead of beta-blockers as she had a history of bronchial asthma. The patient subsequently opted for termination of pregnancy after which she was given radioactive iodine I131 (10 mCi) for definitive therapy of her thyrotoxicosis. In conclusion, carbimazole-related agranulocytosis is an important entity to recognise and treat early to prevent morbidity and mortality. Termination of pregnancy was carried out as the treatment given during the episode of agranulocytosis may have negative effects on foetal viability and growth.
Antithyroid drugs have been used for more than 50 years for the management of hyperthyroidism. Most patients tolerate treatment well, but some may develop rare life threatening side effects such as agranulocytosis and aplastic anaemia. Clinical experience with the latter condition is extremely limited. We report on a case of carbimazole-induced aplastic anaemia caused by hypocellular bone marrow and associated plasmacytosis in a thyrotoxic patient chronically treated with carbimazole. This resolved after substitution with propylthiouracil. The clinical course was complicated by neutropaenic septicaemia and atrial fibrillation.
Study site: University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Twenty eight patients with hyperthyroidism complicating their pregnancies were seen at the Obstetrics and Gynaecology Department, University Hospital, Kuala Lumpur, Malaysia in a six-year period. All patients were treated with antithyroid drugs, carbimazole being the mainstay of treatment. The incidence of the disease was 0.9 per 1000 births and was similar with other series. No cases of fetal goitre were noted. The mean birth weight was 2952 g; there was no significant difference in the birth weight of term live births in patients treated with carbimazole alone or carbimazole combined with propranolol.
The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.