Ectopic adrenal rests in congenital adrenal hyperplasia as a cause of androgen excess after adrenalectomy detected by pelvic venous sampling.

BACKGROUND: Patients with classic congenital adrenal hyperplasia (CAH) due to CYP21 deficiency are treated with supraphysiological doses of glucocorticoids to suppress elevated androgen production. This implies also side effects of high-dose glucocorticoids, possibly leading to iatrogenic Cushing's syndrome. Bilateral adrenalectomy has been suggested as the ultimate therapy in severe cases, when insufficient androgen suppression was obtained despite high glucocorticoid doses. Usually, ACTH levels rise after bilateral adrenalectomy, and this could imply an increased risk for the development of ectopic adrenal rests. In female CAH patients ovarian adrenal rests are not commonly detected by conventional radiological techniques. METHODS: We report the case of an adult female CAH patient who underwent bilateral adrenalectomy in early puberty because of poorly controlled CAH. RESULTS AND CONCLUSIONS: Several years after surgery, she developed secondary amenorrhea and hair loss as a result of androgen overproduction in ovarian adrenal rests that appeared to be detectable only by pelvic venous sampling. After unilateral oophorectomy androgen levels normalized.

Spread of the epidemic European fusidic acid-resistant impetigo clone (EEFIC) in general practice patients in the south of The Netherlands.

OBJECTIVES: We evaluated the susceptibility to fusidic acid, mupirocin and retapamulin of Staphylococcus aureus isolated from nasal and wound swabs. METHODS: The susceptibility to the three agents of S. aureus isolated from general patients in the south of The Netherlands with a skin or soft tissue infection was determined between January 2007 and December 2008. Fusidic acid-resistant isolates were tested for the presence of fusidic acid-resistant genes and compared with the epidemic European fusidic acid-resistant impetigo clone (EEFIC). RESULTS: Fusidic acid resistance was found in 23% of the nasal and 35% of the wound isolates, the majority (~90%) being fusB positive. Most of the isolates belonged to spa type t171 and were isolated from younger patients. One isolate was retapamulin resistant (MIC 8 mg/L) and two were mupirocin resistant. CONCLUSIONS: The EEFIC clone was relatively highly prevalent among the isolated S. aureus. The usefulness of fusidic acid as first-line agent for the treatment of impetigo is questionable. As mupirocin is used in The Netherlands for eradication of methicillin-resistant S. aureus, it is not an alternative; retapamulin might be useful, but further in vivo studies are warranted.

Decreased methylene tetrahydrofolate reductase activity due to the 677C-->T mutation in families with spina bifida offspring.

Periconceptional folate intake reduces both the occurrence and recurrence risk of neural tube defects. Plasma homocysteine levels can be elevated in mothers of a child with a neural tube defect, suggesting a dysfunctional folate metabolism. Very recently we showed that a common 677C-->T mutation in the 5,10-methylene tetrahydrofolate reductase gene, causing thermolability of the enzyme, is a risk factor for spina bifida offspring. Restriction enzyme analysis of the genomic 5,10-methylene tetrahydrofolate reductase polymerase chain reaction fragment revealed a significantly higher prevalence of a +/+ genotype among spina bifida patients and their mothers. The risk for spina bifida offspring is the strongest if both the mother and her child have the mutation in the homozygous state. Enzymatic analysis showed that homozygosity for the 677C-->T mutation causes a decreased 5,10-methylene tetrahydrofolate reductase activity, resulting in elevated plasma homocysteine and red blood cell folate levels and lowered plasma folate and cysteine values. This extended study demonstrates that a nucleotide substitution in the coding region of 5,10-methylene tetrahydrofolate reductase, resulting in reduced activity and an impaired homocysteine and folate metabolism, is a genetic risk factor for spina bifida.

Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida.

Periconceptional folate supplementation reduces the risk of neural-tube defects. We studied the frequency of the 677C-->T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in 55 patients with spina bifida and parents of such patients (70 mothers, 60 fathers). 5% of 207 controls were homozygous for the 677C-->T mutation compared with 16% of mothers, 10% of fathers, and 13% of patients. The mutation was associated with decreased MTHFR activity, low plasma folate, and high plasma homocysteine and red-cell folate concentrations. The 677C-->T mutation should be regarded as a genetic risk factor for spina bifida.