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Elevated plasma 19‐hydroxyandrostenedione levels in Cushing's disease: stimulation with ACTH and inhibition with metyrapone
Author(s) -
Mune T.,
Morita H.,
Yasuda K.,
Murayama M.,
Yamakitat N.,
Miura K.
Publication year - 1993
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1993.tb01005.x
Subject(s) - medicine , endocrinology , metyrapone , adrenal adenoma , cushing's disease , cushing syndrome , adenoma , aldosterone , androstenedione , basal (medicine) , dexamethasone , androgen , hormone , disease , insulin
Summary OBJECTIVE The regulation of 19‐hydroxyandrostenedione secretion has been suggested to be under the control of both the ACTH‐adrenal axis and renin‐angiotensin system. We undertook the present study to evaluate the effect of the chronic excess of ACTH, or the short‐term excess of ACTH due to metyrapone, on 19‐hydroxyandrostenedione secretion in patients with Cushing's disease DESIGN AND PATIENTS We measured plasma 19‐hydroxyandrostenedione levels simultaneously with plasma Δ 4 ‐androstenedione, corticosterone, 11‐deoxycorticosterone, aldosterone and Cortisol levels after HPLC separation in 13 patients with Cushing's disease under basal conditions and during a dexamethasone suppression test or metyrapone test. Seven patients with Cushing's syndrome due to adrenal adenoma were used for comparison. RESULTS The basal levels of 19‐hydroxyandrostenedione in Cushing's disease were elevated (mean ± SD; 323 ± 193 pmol/l, n = 13), while those in Cushing's syndrome due to adrenal adenoma were low (92 ± 24 pmol/l, n = 7), compared to those in normal subjects (117 ± 33 pmol/l, n = 54). The basal levels of Δ 4 ‐androstenedione were mildly elevated In Cushing's disease (9.0 ± 6.5 vs 3.6 ± 2.6 nmol/l of normal subjects) but not in Cushing's syndrome due to adrenal adenoma (3.1 ± 3.0 nmol/l). In the overnight 8 mg dexamethasone suppression test in Cushing's disease ( n = 12), plasma levels of 19‐hydroxyandrostenedione and Δ 4 ‐androstenedlone decreased from 277 ± 172 to 156 ± 99 pmol/l and from 9.2 ± 6.8 to 4.7 ± 3.4 nmol/l, respectively, whereas the overnight 1 mg dexamethasone suppression test did not induce significant changes. Metyrapone administration in Cushing's disease ( n = 9) increased plasma Δ 4 ‐androstenedione level from 9.5 ± 6.7 to 47.2 ± 28.1 nmol/l, but decreased plasma 19‐hydroxyandrostenedione level from 301 ± 196 to 196 ± 105 pmol/l. CONCLUSIONS These data indicate that plasma levels of 19‐hydroxyandrostenedione in patients with Cushing's disease are elevated due to chronic ACTH excess, and that metyrapone can inhibit 19‐hydroxylation in humans.