title: Dexamethasone-suppressible hyperaldosteronism: studies on overproduction of 18-hydroxycortisol in three affected family members.
abstract: We report a newly diagnosed family in which a father and his two sons were found to be hypertensive and to have the rare familial condition dexamethasone-suppressible hyperaldosteronism (DSH). All three patients became normotensive on dexamethasone treatment alone and have been successfully maintained on low doses of the drug for 6 months since diagnosis. Each of the patients had extremely high plasma and urinary concentrations of the recently discovered steroid 18-hydroxycortisol, which were more than ten times higher than the upper normal limit. Plasma levels were readily suppressed by dexamethasone treatment. The hypothesis that 18-hydroxycortisol might derive from 18-hydroxylation of recirculating cortisol was tested by measuring plasma 18-hydroxycortisol levels during low-dose and high-dose hydrocortisone infusions, in a normal subject and in one of the patients with DSH. During the high-dose infusions (with plasma cortisol levels of 3000-5000 nmol/l) there was net production of 18-hydroxycortisol within 8 h, but this was not observed during the low-dose infusions (plasma cortisol levels 300-400 nmol/l). The origin of 18-hydroxycortisol remains uncertain: these findings do not support the recirculation theory, but lend weight to the alternative hypothesis that 18-hydroxycortisol is produced in transitional adrenocortical tissue. This steroid is of considerable value in the differential diagnosis of primary hyperaldosteronism and may also be important as a marker of transitional adrenal cell function.
authors.affiliation: Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Davis
authors.forename: D
authors.initials: D
authors.lastname: Burt
authors.forename: J E
authors.initials: JE
authors.lastname: Corrie
authors.forename: C R
authors.initials: CR
authors.lastname: Edwards
authors.forename: M C
authors.initials: MC
authors.lastname: Sheppard
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism; D000328:Adult; D003907:Dexamethasone / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D006929:Hyperaldosteronism / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008297:Male
chemical_list: D003907:Dexamethasone; C033689:18-hydroxycortisol; D006854:Hydrocortisone