Hyperglycemic chorea-ballism or acute exacerbation of Huntington's chorea? Huntington's disease unmasked by diabetic ketoacidosis in type 1 diabetes mellitus.

CONTENT: Hyperglycemic chorea-ballism is predominantly observed in older type 2 diabetic patients, and it is rare in type 1 diabetes and diabetic ketoacidosis (DKA). Huntington's disease (HD) is one of several genetic syndromes associated with diabetes, although the reported prevalence of the association varies. There are few opportunities for most physicians to diagnose early-stage HD. OBJECTIVE: We describe bilateral hyperglycemic chorea-ballism in a 40-yr-old female type 1 diabetes patient with DKA and HD. SETTING: The study was conducted in a tertiary care referral hospital. RESULTS: On admission, the patient exhibited severe involuntary movement of bilateral extremities with DKA, and hyperglycemic chorea-ballism was diagnosed. She recovered from chorea-ballism with admission of fluids and insulin, but mild choreatic movement persisted in the upper extremities. Brain magnetic resonance imaging and DNA analysis revealed HD. Although it has been considered that depletion of striatal γ-aminobutyric acid (GABA) content is rare in DKA, it is largely decreased in HD. Therefore, it is probable that hyperglycemic chorea-ballism or exacerbation of Huntington's chorea resulted from transient depletion of GABA. CONCLUSION: The present case provides important insights on the role of GABA in hyperglycemic chorea-ballism and on the clinical issues associated with HD diagnosis.

Association of Lys173Arg polymorphism with CYP11B2 expression in normal adrenal glands and aldosterone-producing adenomas.

CONTEXT: CYP11B2, the gene encoding aldosterone synthase, has several frequent polymorphisms. In particular, the Lys173Arg (K173R) polymorphism is in complete genetic linkage disequilibrium with the -344T/C polymorphism in the promoter of CYP11B2 that involves a binding site for the steroidogenic factor-1 transcription factor. These polymorphisms have been associated with cardiovascular parameters, including hypertension, but not directly with gene expression. OBJECTIVE: The objective of this study was to correlate CYP11B2 genotype with gene expression in adrenal tissue. DESIGN: We measured mRNA levels of CYP11B2 [presented as a ratio against glyceraldehyde-3-phosphate dehydrogenase (B2/G)] and CYP11B1 in relation to the K173R polymorphism. SUBJECTS: We studied 28 subjects with aldosterone-producing adenomas (APA) and 18 subjects with normal adrenals. MAIN OUTCOME MEASURE: The main outcome measure was CYP11B2 expression levels. RESULTS: Preoperative treatment with spironolactone or beta-blocker in five APA patients was associated with higher B2/G. The B2/G and B2/B1 ratios were much higher even in the remaining 23 APA patients than in subjects with normal adrenals. The B2/G and B2/B1 ratios in normal adrenals and APA were higher in the KK genotype than in the RR genotype. In patients with APA, urinary aldosterone excretion was higher in those with the KK genotype than in those with the KR genotype. Measurement of cDNA band intensities from normal and APA samples of the KR genotype revealed that the R173 allele was transcribed at levels 46.6 +/- 12.2% (mean +/- sd; n = 7) and 49.1 +/- 20.8% (n = 6), respectively, those of the K173 allele. CONCLUSIONS: A CYP11B2 haplotype including -344T and K173 is associated with higher gene expression than the -344C/R173 haplotype, supporting reported associations of -344T with higher aldosterone production and blood pressure.

Glycyrrhizic acid suppresses type 2 11 beta-hydroxysteroid dehydrogenase expression in vivo.

Licorice-derivatives such as glycyrrhizic acid (GA) competitively inhibit 11 beta-hydroxysteroid dehydrogenase(11 beta-HSD) type 2 (11-HSD2) enzymatic activity, and chronic clinical use often results in pseudoaldosteronism. Since the effect of GA on 11-HSD2 expression remains unknown, we undertook in vivo and in vitro studies. Male Wistar rats were given 30, 60 or 120 mg/kg of GA twice a day for 2 weeks. Plasma corticosterone was decreased in those given the 120 mg dose, while urinary corticosterone excretion was increased in those given the 30 and 60 mg doses but decreased in those given 120 mg GA. NAD(+)-dependent dehydrogenase activity in kidney microsomal fraction was decreased in animals receiving doses of 60 and 120 mg GA. The 11-HSD2 protein and mRNA levels were decreased in those given 120 mg GA. In contrast, in vitro studies using mouse kidney M1 cells revealed that 24h treatment with glycyrrhetinic acid did not affect the 11-HSD2 mRNA expression levels. Thus, in addition to its role as a competitive inhibitor of 11-HSD2, the chronic high dose of GA suppresses mRNA and protein expression of 11-HSD2 possibly via indirect mechanisms. These effects may explain the prolonged symptoms after cessation of GA administration in some pseudoaldosteronism patients.