A Pituitary Tumor Producing High Molecular Weight Adrenocorticotropin-Related Peptides: Clinical and Cell Culture Studies*

The tissue-specific processing of proopiomelanocortin (POMC), the precursorof ACTH, β-endorphin, and their related peptides, is currently of considerable interest. We report a patient with a large aggressive pituitary tumor, Cushing's syndrome, and hyperpigmentation managed by transsphenoidal hypophysectomy, bilateral adrenalectomy, and sellar irradiation.Preoperatively, plasma levels of immunoreactive ACTH (ir-ACTH; 280 ng/liter) and β-endorphin (ir-βEP; 520 ng/liter) were moderately elevated. Chromatography of the plasma showed two peaks of ACTH immunoreactivity, with the major peak eluting in the void volume, and two major peaks of ir-βEP, corresponding to the elution positions of β-lipotropin and 0-endorphin standards. Plasma ir-ACTH and ir-βEP were not suppressed by high doses of glucocorticoid or bromocriptine, a degree of autonomy more commonly found with POMC production from ectopic sources than that from pituitary tumors. Tissue removed at operation was enzymatically dispersed, and the cells were...