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Metyrapone pre-treated inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome

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BACKGROUNDInferior petrosal sinus sampling (IPSS) is a useful investigative technique in the differential diagnosis of ACTH-dependent Cushing’s syndrome. Diagnostic accuracy is improved by the administration of corticotrophin releasing-factor (CRF) during the procedure to stimulate ACTH secretion. We hypothesized that, given the unavailability of CRF in Australia, stimulation of ACTH secretion from tumorous corticotrophs with metyrapone treatment before IPSS may be useful.

AIMSTo describe our clinical experience with a novel diagnostic test, and to compare results between IPSS with and without metyrapone pre-treatment.

SETTINGMetropolitan, Australian university teaching hospital.

PATIENTS18 patients were studied on 21 occasions: three with Cushing’s disease without metyrapone treatment prior to IPSS (M−), 11 with Cushing’s disease with metyrapone pretreatment (M+), three with ectopic ACTH syndrome, and one with pseudo-Cushing’s syndrome.

TREATMENTPatients received oral metyrapone, median dose 750 mg 6 hourly, for 24 h before IPSS.

RESULTSNo major side effects were noted. Metyrapone increased serum 11-deoxycortisol concentration to a median of 400 nmol/l (range 36–1310) on the morning of the test. Radiological confirmation of correct catheter placement was shown in 36/42 inferior petrosal sinuses (86%). Median peak central : peripheral ACTH ratios were 9.8 for M− pituitary adenomas (range 5.7–13.6), 12.9 for the technically successful M+ pituitary adenomas (range 8–54.1), and 1.6 for M+ ectopic ACTH syndrome cases (range 1.2–3.4). Repeat studies in unoperated patients with ectopic ACTH syndrome showed ratios <1.6. IPSS showed median peak ACTH concentrations of 190 ng/l for M− pituitary adenomas (range 83–205), 595 ng/l for the technically successful M+ pituitary adenomas (range 80–7630; P = 0.035 compared to M−), and 62 ng/l for M+ ectopic ACTH syndrome cases (range 47–220). IPSS correctly identified the pituitary source of ACTH production in all cases of Cushing’s disease (except one technical failure where MRI revealed a lesion). MRI scanning correctly identified a lesion in 3/14 operated Cushing’s disease cases. IPSS correctly lateralized 1/3 M− and 7/8 M+ Cushing’s disease cases where the procedure was technically successful and surgical descriptions adequate. Pituitary exploration revealed a visible lesion in 75% of cases corresponding to the side predicted by IPSS; ‘blind’ hemi-hypophysectomy was performed on the side predicted from IPSS in the remainder. All cases of Cushing’s disease were cured or improved following surgery, with a median follow-up of 2.8 years (range 0.7–5.9).

CONCLUSIONSMetyrapone pre-treated inferior petrosal sinus sampling is safe, and appears to induce high ACTH output from pituitary corticotroph adenomas. The technique has allowed accurate localization and treatment of pituitary corticotroph microadenomas.
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Document Type: Research Article

Affiliations: 1: Metabolic Research Unit, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Departments of 2: Diabetes and Endocrinology, 3: Diagnostic Imaging, 4: Chemical Pathology, 5: Neurosurgery, and 6: Anaesthetics, Princess Alexandra Hospital, Brisbane, Australia

Publication date: May 1, 1997

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