Hypogonadotrophic hypogonadism associated with prelingual deafness due to a connexin 26 gene mutation.

In Mediterranean countries, almost half the incidence of non-syndromic congenital hearing loss is caused by mutations in the gap junction (GJ) connexin 26 gene (GJB2/DFNB1 locus). In this form of deafness the cochlear defect is usually isolated. We describe here the first case of hypogonadotrophic hypogonadism in association with this particular cochlear defect.

Genetic, biochemical, and clinical studies of patients with A328V or R213C mutations in 11betaHSD2 causing apparent mineralocorticoid excess.

Apparent mineralocorticoid excess is a recessively inherited hypertensive syndrome caused by mutations in the 11beta-hydroxysteroid dehydrogenase type 2 gene, which encodes the enzyme normally responsible for converting cortisol to inactive cortisone. Failure to convert cortisol to cortisone in mineralocorticoid-sensitive tissues permits cortisol to bind to and activate mineralocorticoid receptors, causing hypervolemic hypertension. Typically, these patients have increased ratios of cortisol to cortisone and of 5alpha- to 5beta-cortisol metabolites in serum and urine.

The cortisol-cortisone shuttle in children born with intrauterine growth retardation.

We evaluated the involvement of a possible dysfunction of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the fetal growth retardation and poor growth rates of children born with intrauterine growth retardation (IUGR). Children with IUGR have a nephron deficit and are also at risk of developing cardiovascular diseases, high blood pressure, glucose intolerance, and dyslipidemia later in life. The major site of 11beta-HSD2 production is the kidney and its deficit causes hypertension.

A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction.

The adipocyte-specific hormone leptin, the product of the obese (ob) gene, regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure. Leptin acts through the leptin receptor, a single-transmembrane-domain receptor of the cytokine-receptor family. In rodents, homozygous mutations in genes encoding leptin or the leptin receptor cause early-onset morbid obesity, hyperphagia and reduced energy expenditure.

Radioimmunoassay of cortisone in serum, urine, and saliva to assess the status of the cortisol-cortisone shuttle.

We have developed a new assay for cortisone (E) in serum, saliva, and urine involving Celite chromatography followed by RIA with 125I-labeled E and scintillation proximity assay. The chromatography step separates cortisol (F) from E, and in combination with their RIAs, permits assessment of the status of the F-E shuttle. We report the results of basal, postcorticotropin (ACTH), and postdexamethasone E and F concentrations and their circadian fluctuations in the serum, saliva, and urine of healthy volunteers.