Many neurological diseases like myopathy, periodic paralysis, ophthalmoplegia, and myasthenia gravis are known associations of thyrotoxicosis. However the association of neuropathy with thyrotoxicosis is not frequently recognized. First described by Charcot in 1889, thyrotoxic neuropathy or 'Basedow's Paraplegia' is a rarely reported entity. We describe here a case of a young woman with subacute distal neuropathy as the presenting manifestation of thyrotoxicosis. The neuropathy improved on antithyroid treatment. A careful literature search leads us to believe that peripheral neuropathy in thyrotoxicosis is under recognised. Thyroid function tests can be helpful in the diagnosis of this treatable neuropathy and should be included in the routine work up.
Cardiac arrhythmias are common in patients with thyrotoxicosis. Conduction abnormalities have been seen in a few thyrotoxic patients, but these, in particular high grade atrioventricular (AV) block, often occur in the presence of other conditions. Three thyrotoxic patients with conduction abnormalities are described: two were associated with severe hypokalaemia and the third had congestive cardiac failure. Conditions predisposing to conduction abnormality should be identified when this occurs in a thyrotoxic patient as their correction may help resolve or explain the conduction abnormality.
Thirty-eight normal volunteers and 10 patients with untreated thyrotoxicosis were each given 0.5 ml of Lugol's solution daily for 10 days. On days 0, 5, 10, 15 and 20, serum levels of T4, free T4, T3 and TSH (by sensitive immunoradiometric assay) were measured. In normal subjects, the serum concentrations of free T4 declined significantly at day 10 while TSH levels were significantly increased at days 5, 10 and 15. Serum levels of T4 and T3 did not change significantly. All the observed changes took place within the limits of normal ranges for the hormones mentioned. In contrast, in the thyrotoxic subjects, both T4 and T3 were significantly decreased at days 5 and 10, while serum TSH remained below detection limit (0.14 mU/l) throughout the study. Short exposure to excessive iodide in normal subjects affects T4 and T3 release and this effect could be partially overcome by compensatory increase in TSH. In thyrotoxicosis, lack of compensatory increase in TSH results in rapid decreases in T4 and T3 levels. The integrity of the hypothalamo-pituitary-thyroidal axis may be effectively assessed by measuring TSH response to iodide suppression, using a highly sensitive immunoradiometric assay.
Thyrotoxic periodic paralysis (TPP) is a medical emergency characterised by sudden onset of muscle weakness with hypokalemia that resolves with the treatment of hyperthyroidism. We report three cases of thyrotoxic periodic paralysis seen at the Accident and Emergency Care Department, University of Malaya Medical Centre in a period of four months. We also review the clinical presentation, pathophysiology, biochemical features and management of TPP. All three patients were young Asian males, presenting with muscle weakness of sudden onset. The first patient presented with lower limb weakness and had symptoms of thyrotoxicosis and goitre. He had a previous similar episode which resolved spontaneously. The second patient presented with quadriplegia, respiratory acidosis and had no signs and symptoms of thyrotoxicosis. The electrocardiogram of this patient showed normal sinus rhythm with U wave in V3 and a flat T wave, which are characteristic of hypokalaemia. The third patient, who was a known case of thyrotoxicosis, was admitted thrice for hypokalemic paralysis during the study period. All cases had low serum potassium, suppressed TSH and elevated T4 confirming thyrotoxic periodic paralysis. Potassium therapy was useful during the crisis; however prophylactic potassium has not been shown to prevent attacks as seen in one of our cases.
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.