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.
BACKGROUND: This research was performed to determine the prevalence of iodine deficiency disorder (IDD) and the effects of iodized salt supplementation on thyroid status amongst Orang Asli in Hulu Selangor, Malaysia.
METHODS: Study respondents were from three target groups, i.e. pre-school children (PSC), primary school-going children (SGC) and adult women. Each household was supplied with iodized salt fortified with iodate fortificant for a period of 12 months and the iodine levels in the salt ranged from 20 to 30 μg/L. Samples collected before and after 6 and 12 months of introduction to iodized salt were urine from all groups, as well as serum samples from adult women.
RESULTS: A total of 200 respondents were recruited; 58 (29.0%) PSC, 65 (32.5%) SGC and 77 (38.5%) adult women. The median urine-iodine concentration (mUIC) in all groups were of moderately low before the iodized salt intervention, but increased significantly in all study groups after 6 and 12 months of intervention. However, at the end of the study, there was an increase in severe iodine deficiency (mUIC <20 μg/L) from 7.5% to 12% and about 9% of PSC and SGC respondents had mUIC level of more than 300 μg/L while the adult women showed a significant increase in free triiodothyronine (fT3) levels.
CONCLUSION: The study demonstrated that iodized salt supplementation was able to show an improvement in iodine level amongst Orang Asli. However, an increase in severe iodine deficiency and iodine excess indicated that the iodized salt programme needs to be carefully monitored.
We evaluated the usefulness of sensitive thyrotrophin hormone (TSH) measurements in determining the thyroid status in the follow-up of Graves' patients undergoing medical treatment with thionamides. Out of a total of 186 serum samples tested, TSH levels were suppressed in 123 (66.1%), normal in 32 (17.2%) and elevated in 31 (16.7%) cases. Total T4, or T3 or both were elevated only in 97 (74.8%) cases of TSH-suppressed patients, indicating that TSH is less discriminatory as a first-line test for patients under treatment due to the hypothalamic-pituitary lag period. No comparisons with free T4 or free T3 were done in this study. Both total T4 (120 +/- 28 nmol/l) and TBII (23 +/- 21%) levels were significantly greater (p < 0.02) in the euthyroid group with suppressed TSH. This may suggest that persistence of a thyrotoxic state may still be present.