Gillian Rumsby

Menstrual disturbance and hypersecretion of progesterone in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

OBJECTIVE While menstrual disturbance is often quoted as a feature of congenital adrenal hyperplasia (CAH), little is known about the mechanism of this symptom. We set out to determine the relationship between menstrual pattern and biochemical characteristics of women with CAH due to 21‐hydroxylase deficiency.

Reassessing fecundity in women with classical congenital adrenal hyperplasia (CAH): normal pregnancy rate but reduced fertility rate

Objective  Fertility in women with classical congenital adrenal hyperplasia (CAH) has been reported low; however, the true pregnancy rate for women trying to conceive with this condition is unknown. Our aim was to calculate pregnancy rate for women with CAH calculated as a proportion of those who had attempted conception. Fertility expressed as live birth rate is also calculated.

Genotype‐phenotype analysis in late onset 21‐hydroxylase deficiency in comparison to the classical forms

To establish the type and frequency of mutations causing late onset 21‐hydroxylase deficiency and associated clinical and biochemical phenotypes and to compare these findings to those from heterozygotes and homozygotes for classical 21‐hydroxylase deficiency.

Carrier status for steroid 21‐hydroxylase deficiency is only one factor in the variable phenotype of acne

Previous endocrine studies of women with acne have produced diverse results. This study was designed to seek evidence, from endocrine and genetic studies, for impaired steroid biosynthesis in patients with acne.

Strategies for the prenatal diagnosis of primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is a potentially lethal autosomal recessive disorder of glyoxylate metabolism caused by a deficiency of the liver‐specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Over the past 13 years, various strategies have been adopted for its prenatal diagnosis, including (1) glyoxylate metabolite analysis of amniotic fluid in the second trimester; (2) AGT enzyme assay, immunoassay, and immuno‐electron microscopy of fetal liver biopsies also in the second trimester; and (3) linkage and mutation analysis of DNA isolated from chorionic villus samples in the first trimester. These methods have evolved in parallel with our increased understanding of the molecular aetiology and pathogenesis of the disease. Although the usefulness of metabolite analysis remains unproven, all the other methods have been successfully applied to the prenatal diagnosis of PH1. In this review, examples of the use of the available methodologies are provided, and their pros and cons are discussed with reference to specific cases.

Prenatal diagnosis of congenital adrenal hyperplasia by direct detection of mutations in the steroid 21‐hydroxylase gene

OBJECTIVE Our aim was to develop a rapid and accurate method for the prenatal diagnosis of congenital adrenal hyperplasia using the polymerase chain reaction to detect mutations in the steroid 21‐hydroxylase gene. These procedures will help to minimize exposure to dexametha‐sone treatment of either affected males or unaffected females.

Deoxycorticosterone, 11 β-hydroxylase and the adrenal cortex

We report a child in whom DOC excess secondary to congenital adrenal hyperplasia (CAH, 11β‐hydroxylase deficiency) caused malignant hypertension. Clinical and metabolic control could be achieved only by replacement of both glucocorticoid and mineralocorticoid, thus confirming in clinical practice the hypothesis that DOC is produced from both the zonae fasciculata and glomeru‐losa of the adrenal cortex under the independent control of the ACTH and renin‐angiotensin systems respectively.