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NALOXONE STIMULATION OF ACTH SECRETION DURING PETROSAL SINUS SAMPLING IN CUSHING'S SYNDROME
Author(s) -
Torpy David J.,
Jackson Richard V.,
Grice Jeffrey E.,
Hockings Gregory I.,
Strakosch Christopher R.,
Topliss Duncan J.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01688.x
Subject(s) - medicine , endocrinology , inferior petrosal sinus , dexamethasone , adrenocorticotropic hormone , endogenous opioid , (+) naloxone , basal (medicine) , hormone , opioid , surgery , receptor , cavernous sinus , insulin
SUMMARY 1. Petrosal sinus sampling has been used to establish the source of adrenocorticotropin (ACTH) in ACTH‐dependent Cushing's syndrome. Naloxone, an opioid antagonist, stimulates ACTH secretion, probably via release of endogenous hypothalamic corticotropin releasing hormone (CRH). 2. Three patients with hypercortisolism were studied. Two showed suppressed (>50%) urinary‐free cortisol excretion with high‐dose dexamethasone treatment (2 mg every 6h for 2 days), one did not suppress. The patients were subjected to bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) with simultaneous peripheral venous (forearm) samples. Basal (unstimulated) samples were taken and naloxone (125 pg/kg bodyweight) was given intravenously with subsequent simultaneous sampling. Plasma ACTH was measured by radio‐immunoassay (RIA). 3. All cases exhibited a marked rise in immunoreactive (IR)‐ACTH levels (pmol/L) after naloxone injection, basal to peak: case 1, left 11.5–22.1, right 9.8 with no rise, peripheral 9.1–9.5; case 2, left 456–863, right 125–501, peripheral 59–82; case 3, left 12.7–13.0, right 277–431, peripheral 12.1–11.7. All results indicate pituitary Cushing's syndrome, with a central to peripheral ratio >2.3:1. Pituitary Cushing's syndrome was confirmed on the results of trans‐sphenoidal pituitary surgery in cases 1 and 3. 4. It is suggested that naloxone injection during petrosal sinus sampling in Cushing's syndrome may assist in the diagnosis of ACTH source, by enhancing ACTH release from a pituitary micro‐adenoma.