Gibson S, Ray DW, Crosby SR, Dornan TL, Jennings AM, Bevan JS, Davis JRE, White A
J Clin Endocrinol Metab. 1996;81:497-502.
The regulation and secretion of the ACTH precursors POMC and pro-ACTH were assessed
directly using a 2-site immunoradiometric assay in six patients with pituitary macroadenomas
(> or = 1.2 cm in diameter) and 27 patients with Cushing's disease due to a microadenoma.
ACTH precursor levels were elevated in patients with macroadenomas (150-3690 pmol/L;
normal range, < 5-40 pmol/L) and significantly higher than those in microadenoma patients
(median, 29 pmol/L; range, 9-104 pmol/L; P < 0.001). Patients with macroadenomas also
had increased ACTH precursor/ACTH ratios (15-181:1) compared with microadenoma patients
(median, 5:1, range, 0.7-18.5:1; P < 0.001). ACTH precursors were unresponsive to
high dose dexamethasone in patients with macroadenomas, whereas ACTH and cortisol
responses varied. After CRH administration, ACTH precursors were unchanged, whereas
cortisol increased significantly, suggesting the release of biologically active ACTH.
This study clearly demonstrates reduced processing of POMC to ACTH in large pituitary
tumors, a characteristic usually associated with tumors causing the ectopic ACTH syndrome,
and provides evidence for differential regulation of ACTH precursors and ACTH by glucocorticoid
and CRH. Variation in the clinical symptoms of patients with corticotroph macroadenomas
may be attributable to differences in biological potency between the ACTH precursors