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PubMed · 233679

"Normal suppression" to dexamethasone in Cushing's disease: an expression of decreased metabolic clearance for dexamethasone.

J F Caro·A W Meikle·J H Check·S N Cohen
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Abstract

The adrenal cortical function of a patient with pituitary-dependent Cushing's syndrome exhibited normal responsiveness to conventional doses of dexamethasone (Dex) over several years of evaluation. "Periodic hormonogenesis" did not seem to explain the phenomenon. Plasma concentrations of Dex were measured to ascertain whether an abnormality in Dex metabolism might explain the apparent discrepancy in Dex responsiveness. Plasma levels of Dex after oral administration of the steroid were higher than normal, suggesting that decreased clearance of Dex accounts for the phenomenon of "normal suppression" in this patient with Cushing's syndrome.

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Adrenocorticotropic HormoneCushing SyndromeDexamethasoneFemaleHumansHydrocortisoneKineticsMetabolic Clearance RateMiddle AgedSteroidsCase ReportsJournal Article

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J F Caro, A W Meikle, J H Check, S N Cohen. 1978. "Normal suppression" to dexamethasone in Cushing's disease: an expression of decreased metabolic clearance for dexamethasone.. https://doi.org/10.1210/jcem-47-3-667

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PubMed1979

[Factor(s) controlling the secretion of adrenocorticotropin (ACTH) in peripheral plasma (author's transl)].

The factor(s) controlling the secretion of ACTH in peripheral plasma are not well known. The effects of non-extracted and extracted plasma on ACTH secretion were investigated using rat anterior pituitary cell cultures. Medium ACTH was assayed by radioimmunoassay, and the corticotropin releasing activity (CRA) was expressed as ACTH released. One hundred ul of non-extracted plasma showed significant CRA, whereas greater volumes of plasma showed reduced activity. Non-extracted plasma (250 approximately 500 microliter) rather reduced the secretion of ACTH evoked by hypothalamic extract (HE). When plasma was extracted with 0.2 N-acetic acid-acetone and divided into an acid phase and an acetone-ether phase by adding ether, the CRA was recovered in the acid phase while no significant activity was observed in the acetone-ether phase. The acid phase extract of plasma showed a positive dose-response relationship between the amount of plasma extract (50 approximately 800 microliter plasma equivalent) and ACTH release in pituitary cell cultures. The organic phase of plasma extract inhibited HE-induced release of ACTH, and this ACTH-release inhibiting activity was presumed to be corticosterone. When the acid phase extract of 20 ml plasma was applied to a Sephadex G-25 (fine) and eluted with 0.2 N acetic acid, two peaks of CRA were observed. One eluted in the region of void volume and another eluted in the retarded region where no activity was found in chromatography of HE. HE increased both ACTH and cyclic AMP release, but the plasma extract reduced cyclic AMP release. These results suggest that plasma contains both CRA and ACTH release inhibiting activity which can be extracted separately, and that plasma CRA is different from the hypothalamic corticotropin releasing factor.

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