METYRAPONE PRETREATED INFERIOR PETROSAL SINUS SAMPLING IN THE DIFFERENTIAL-DIAGNOSIS OF ACTH-DEPENDENT CUSHINGS-SYNDROME

BACKGROUND Inferior petrosal sinus sampling (IPSS) is a useful investi gative technique in the differential diagnosis of ACTH-dependent Gushi ng's syndrome. Diagnostic accuracy is improved by the administration o f corticotrophin releasing-factor (GRF) during the procedure to stimul ate ACTH secretion. We hypothesized that, given the unavailability of GRF in Australia, stimulation of ACTH secretion from tumorous corticot rophs with metyrapone treatment before IPSS may be useful. AIMS To des cribe our clinical experience with a novel diagnostic test, and to com pare results between IPSS with and without metyrapone pre-treatment. S ETTING Metropolitan, Australian university teaching hospital. PATIENTS 18 patients were studied on 21 occasions: three with Gushing's diseas e without metyrapone treatment prior to IPSS (M-), 11 with Gushing's d isease with metyrapone pretreatment (M+), three with ectopic ACTH synd rome, and one with pseudo-Cushing's syndrome. TREATMENT Patients recei ved oral metyrapone, median dose 750 mg 6 hourly, for 24 h before IPSS . RESULTS No major side effects were noted. Metyrapone increased serum 11-deoxycortisol concentration to a median of 400 nmol/l (range 36-13 10) on the morning of the test. Radiological confirmation of correct c atheter 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+ pitu itary adenomas (range 8-54.1), and 1.6 for M+ ectopic ACTH syndrome ca ses (range 1.2-3.4). Repeat studies in unoperated patients with ectopi c ACTH syndrome showed ratios <1.6. IPSS showed median peak ACTH conce ntrations 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 ca ses (range 47-220). IPSS correctly identified the pituitary source of ACTH production in all cases of Gushing's disease (except one technica l failure where MRI revealed a lesion). MRI scanning correctly identif ied a lesion in 3/14 operated Gushing's disease cases. IPSS correctly lateralized 1/3 M- and 7/8 M+ Gushing's disease cases where the proced ure was technically successful and surgical descriptions adequate. Pit uitary exploration revealed a visible lesion in 75% of cases correspon ding to the side predicted by IPSS; 'blind' hemi-hypophysectomy was pe rformed on the side predicted from IPSS in the remainder. All cases of Gushing's disease were cured or improved following surgery, with a me dian follow-up of 2.8 years (range 0.7-5.9). CONCLUSIONS Metyrapone pr e-treated inferior petrosal sinus sampling is safe, and appears to ind uce high ACTH output from pituitary corticotroph adenomas. The techniq ue has allowed accurate localization and treatment of pituitary cortic otroph microadenomas.