No abstract

Muscle weakness in patients with thyrotoxicosis during hypokalemic episodes (thyrotoxic periodic paralysis [TPP]) occurs sporadically and mostly in males. It is treated by infusion or oral supplementation with potassium and with resolution of the thyrotoxicosis state. The clinical features of TPP resemble familial hypokalemic periodic paralysis (hypoKPP), which has been linked to two mutations in the gene encoding the skeletal muscle calcium channel alpha-1 subunit (CACN1AS; Arg528His and Arg1239His) and to the sodium channel alpha-subunit (SCN4A; Arg672His). We screened for the mutations (CACN1AS by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]; SCN4A by single-strand conformation polymorphism analysis) described in hypoKPP in 20 unrelated patients with documented episodes of TPP (mean age, 40.0 +/- 12.3 years 19 males). Forty-eight patients with hyperthyroidism resulting from Graves' disease (48.5 +/- 12.3 years; 13 males), 1 patient with idiopathic hypoKPP (a 32-year-old male) and 32 healthy subjects (41.0 +/- 19.1 years; 16 males) were included. We found none of the TPP patients carry CACN1AS and SCN4A mutations. The hyperthyroid patients and control subjects were also negative for the mutations. The patient with idiopathic hypoKPP was genotyped to have the Arg528His mutation. These results suggest that despite close similarities between TPP and hypoKPP, a likely genetic basis for TPP does not involve the same gene mutations associated with hypoKPP.

The HLA-A, -B antigens in 159 Chinese patients with Graves' disease were compared with those of 330 controls. The HLA-DR antigens of the patients were also studied in 100 normals. Analysis of the increased prevalence of Bw46, according to the sex and age of onset of disease of the patients, showed that the strong association of Bw46 resided with male patients (n = 58), Pc = 0.0000052, RR = 4.2. Although the frequency of Bw46 was also increased in female patients (n = 101), it was statistically not significant. For the DR9 antigens, the strong association with male patients was also observed, viz. Pc = 0.019, RR = 3.2. Males also had higher risks of Graves' disease if they had homozygous Bw46 at presentation. Further analysis by age of onset of disease revealed the segregation of significant association with Bw46 for the males at 1-19 yr, Pc = 0.0011, RR = 17.5 HLA associations (Bw46 and DR9) with Graves' disease in Chinese are observed primarily in males, especially those whose known ages of onset of the disease are between 1-19 yr (Bw46).

HLA locus A and B typing was performed on 86 Chinese thyrotoxicosis (Graves' Disease) patients and 238 normal Chinese subjects. The frequency of HLA-Bw46 (Sin 2) was found to be significantly higher among the patients than controls (x2 = 26.15, corrected P less than .003, relative risk = 3.74). The risk associated with Bw46 was reflected in the Bw46 heterozygotes. The relative risks of the joint occurrence of Bw46/B40 and Bw46/B13 were 8.74 and 5.88 respectively.

A CAT-scan performed six days after the first symptoms disclosed areas of decreased attenuation with a remarkable specific localisation to the putamens. It is tempting to suggest that the transient difficulties in articulation and swallowing, as well as the pyramidal tract symptoms, were due to the influence of oedema on corticobulbar and corticospinal fibres adjacent to the putamen.The CAT-scan finding (figure) is of special interest in relation to the neuropathological findings in fatal cases of methanol intoxication.1-4 Orthner3 found symmetrical areas of necrosis in the putamens in 41 of 42 deaths from methanol. Thus the present case suggests that methanol intoxication should be seriously considered when a CATscan shows bilateral low-attenuating areas in the putamens.