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

Ewen Downie Metabolic Unit Melbourne, Australia
Ewen Downie Metabolic Unit and Monash University Department of Immunology and Pathology, Alfred Hospital Melbourne, Australia
The Medical Research Centre, Prince Henry's Hospital Melbourne, Australia

Address all correspondence and requests for reprints to: Dr. J. W. Funder, Medical Research Centre, Prince Henry's Hospital, St. Kilda Road, Melbourne, Victoria, Australia 3004.

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 cultured in suspension, propagated, and passaged sequentially for over 20 passages. Using this cell line, we demonstrated that the biosynthesis of POMC, its pattern of processing, and the release of POMC/ir-/9EP/ir-ACTH in vitro were consistent with the in vivo evidence of autonomous secretion and abnormal processing of POMC by this pituitary tumor.

^* This work was presented in part at the Annual Scientific Meeting of the Endocrine Society of Australia, Sydney, August 1982.

Received April 27, 1983.

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