ELEVATED LEVELS OF ADRENOCORTICOTROPIN (ACTH) PRECURSORS IN POST-ADRENALECTOMY CUSHINGS-DISEASE AND THEIR REGULATION BY GLUCOCORTICOIDS

The ACTH precursor pro-opiomelanocortin (POMC) undergoes specific endo proteolytic cleavages in the anterior pituitary gland to give ACTH-(1- 39). ACTH precursors circulate in normal subjects and are high both in the ectopic ACTH syndrome and in patients with aggressive pituitary a denomas. This study examines plasma levels of ACTH precursors and ACTH in 24 patients with post-adrenalectomy Gushing's disease, in 10 of wh om computed tomography showed evidence of tumor progression. ACTH prec ursors were higher in post-adrenalectomy Gushing's disease (median 97. 5 pmol/L, range 26-647 pmol/L) than in untreated Gushing's disease (me dian 29 pmol/L, range 9-104 pmol/L) and normal controls (5-40 pmol/L) (P < 0.001) and were significantly higher in patients with larger tumo rs (median 175 pmol/L, range 52-647 pmol/L) than in the remainder (med ian 41 pmol/L, range 26-510 pmol/L) (P = 0.02). Surprisingly, pro-opio melanocortin (POMC) processing to ACTH was enhanced in post-adrenalect omy patients (ratio 1 +/- 0.5) compared with Gushing's disease (5.6 +/ - 0.8) and normal subjects (5.3 +/- 0.9). After hydrocortisone ACTH pr ecursors rose in 36% of post-adrenalectomy patients (increase 15-78%) and remained within 10% of basal levels in 46%. Six patients had a ris e in precursors and a fall in ACTH suggesting differential regulation of these peptides. In conclusion, whereas ACTH precursors are high in post-adrenalectomy Gushing's disease and higher levels correlate with tumor progression, processing of precursors to ACTH is enhanced.