11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome.

2.50
Hdl Handle:
http://hdl.handle.net/10541/98101
Title:
11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome.
Authors:
Stewart, P M; Walker, B R; Holder, G; O'Halloran, Domhnall J; Shackleton, C H
Abstract:
A characteristic feature of the ectopic ACTH syndrome is a state of mineralocorticoid excess, although the etiology remains obscure. Some forms of endocrine hypertension, such as licorice ingestion, have been explained by cortisol acting as a mineralocorticoid in the setting of inhibition or deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme is responsible for the conversion of cortisol (F) to hormonally inactive cortisone, and its activity in vivo can be inferred from the ratio of the urinary excretion of tetrahydrocortisol (THF) and its isomer (5 alpha THF) to tetrahydrocortisone. Twenty-two patients with Cushing's syndrome (11 pituitary dependent, 9 ectopic, and 2 adrenal adenomas) and 13 controls were studied. Compared to controls. Cushing's patients had a significant increase (P < 0.001) in the excretion of all principal metabolites of F, secondary to a 5- to 6-fold increase in the cortisol secretion rate [median, 34.0 (range, 13.3-327) mg/day in Cushing's vs. 6.1 (range, 2.5-10.3) mg/day in controls]. The THF plus 5 alpha THF/tetrahydrocortisone ratio was significantly increased in Cushing's syndrome regardless of etiology [mean, 1.81 (range, 1.09-9.99) in Cushing's vs. 0.81 (range, 0.51-1.47) in controls; P < 0.001), indicative of defective 11 beta HSD activity. Furthermore, compared to patients with pituitary-dependent Cushing's, this ratio was significantly higher in patients with the ectopic ACTH syndrome (4.12 vs. 1.49; P < 0.01) and was inversely correlated with serum potassium levels (r = -0.57; P = 0.01; n = 22). One explanation for the mineralocorticoid excess state of the ectopic ACTH syndrome appears to be that cortisol gains inappropriate access to the mineralocorticoid receptor through failure of its normal metabolism by 11 beta HSD. The reason for the defective 11 beta HSD activity is unclear, but it may be secondary to substrate saturation, inhibition by other adrenal steroids, or product inhibition.
Affiliation:
Department of Medicine, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Citation:
11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome. 1995, 80 (12):3617-20 J. Clin. Endocrinol. Metab.
Journal:
The Journal of Clinical Endocrinology and Metabolism
Issue Date:
Dec-1995
URI:
http://hdl.handle.net/10541/98101
DOI:
10.1210/jc.80.12.3617
PubMed ID:
8530609
Type:
Article
Language:
en
ISSN:
0021-972X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorStewart, P Men
dc.contributor.authorWalker, B Ren
dc.contributor.authorHolder, Gen
dc.contributor.authorO'Halloran, Domhnall Jen
dc.contributor.authorShackleton, C Hen
dc.date.accessioned2010-05-06T16:27:36Z-
dc.date.available2010-05-06T16:27:36Z-
dc.date.issued1995-12-
dc.identifier.citation11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome. 1995, 80 (12):3617-20 J. Clin. Endocrinol. Metab.en
dc.identifier.issn0021-972X-
dc.identifier.pmid8530609-
dc.identifier.doi10.1210/jc.80.12.3617-
dc.identifier.urihttp://hdl.handle.net/10541/98101-
dc.description.abstractA characteristic feature of the ectopic ACTH syndrome is a state of mineralocorticoid excess, although the etiology remains obscure. Some forms of endocrine hypertension, such as licorice ingestion, have been explained by cortisol acting as a mineralocorticoid in the setting of inhibition or deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme is responsible for the conversion of cortisol (F) to hormonally inactive cortisone, and its activity in vivo can be inferred from the ratio of the urinary excretion of tetrahydrocortisol (THF) and its isomer (5 alpha THF) to tetrahydrocortisone. Twenty-two patients with Cushing's syndrome (11 pituitary dependent, 9 ectopic, and 2 adrenal adenomas) and 13 controls were studied. Compared to controls. Cushing's patients had a significant increase (P < 0.001) in the excretion of all principal metabolites of F, secondary to a 5- to 6-fold increase in the cortisol secretion rate [median, 34.0 (range, 13.3-327) mg/day in Cushing's vs. 6.1 (range, 2.5-10.3) mg/day in controls]. The THF plus 5 alpha THF/tetrahydrocortisone ratio was significantly increased in Cushing's syndrome regardless of etiology [mean, 1.81 (range, 1.09-9.99) in Cushing's vs. 0.81 (range, 0.51-1.47) in controls; P < 0.001), indicative of defective 11 beta HSD activity. Furthermore, compared to patients with pituitary-dependent Cushing's, this ratio was significantly higher in patients with the ectopic ACTH syndrome (4.12 vs. 1.49; P < 0.01) and was inversely correlated with serum potassium levels (r = -0.57; P = 0.01; n = 22). One explanation for the mineralocorticoid excess state of the ectopic ACTH syndrome appears to be that cortisol gains inappropriate access to the mineralocorticoid receptor through failure of its normal metabolism by 11 beta HSD. The reason for the defective 11 beta HSD activity is unclear, but it may be secondary to substrate saturation, inhibition by other adrenal steroids, or product inhibition.en
dc.language.isoenen
dc.subject.mesh11-beta-Hydroxysteroid Dehydrogenases-
dc.subject.meshACTH Syndrome, Ectopic-
dc.subject.meshCushing Syndrome-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshHydrocortisone-
dc.subject.meshHydroxysteroid Dehydrogenases-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMineralocorticoids-
dc.subject.meshTetrahydrocortisol-
dc.subject.meshTetrahydrocortisone-
dc.title11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medicine, Queen Elizabeth Hospital, Birmingham, United Kingdom.en
dc.identifier.journalThe Journal of Clinical Endocrinology and Metabolismen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.