ABSTRACT
Over 30 years ago Werder et al. described a case of a 3-year-old girl with short stature,
polydipsia and polyuria without obvious external abnormalities (including genitalia), and
who had features of mineralocorticoid hypertension with hypokalemia and metabolic
alkalosis (1). She had suppressed plasma renin and aldosterone; gas-chromatographic
analysis of her urinary steroid profile excluded hypertensive forms of congenital adrenal
hyperplasia, but showed an unexpected steroid profile (1). The author did not appreciate
the underlying defect affecting that girl, a syndrome later recognized and biochemically
characterized by Ulick and New (2,3). At that time radiological investigation of the
adrenal was limited, and to contrast the adrenal with surrounding tissue translumbar
retroperitoneal carbon dioxide insufflation was used (4); this procedure revealed no
enlargement of the patient’s adrenal. Subsequently the patient withdrew from further
medical evaluation and management, her whereabouts unknown, until 25 years later she
presented with intracranial haemorrhage and end-stage renal disease (ESRD). We have
analyzed her relevant DNA sequences and found (unpublished) that she was a compound
heterozygote, with two mutations in the gene encoding the enzyme 11b-hydroxysteroid
dehydrogenase type 2 (11bHSD2), an enzyme that plays a crucial role in miner-
alocorticoid regulated renal sodium transport. In this overview we briefly discuss the
subsequent cloning, physiology, pathophysiology, and clinical relevance of the 11b-
hydroxysteroid dehydrogenase (11bHSD) enzymes.
