HIGH PLASMA PROOPIOMELANOCORTIN IN AGGRESSIVE ADRENOCORTICOTROPIN-SECRETING TUMORS

A specific proopiomelanocortin (POMC) immunoradiometric assay was deve loped using antibodies directed against ACTH and beta-endorphin (beta end). Partially purified standard POMC was prepared from the human sma ll cell lung carcinoma cell line DMS-79 culture medium. Ten units (U) POMC had the same displacement ability as one pg beta end in a C-termi nal beta end radioimmunoassay and thus were close if not equal to 10 p g POMC. This POMC assay was used to investigate patients with ACTH-dep endent Gushing's syndrome. Plasma POMC was undetectable (<60 U/mL) in 17 normal controls and in 4 patients with Addison's disease (concomita nt ACTH plasma levels between 362 and 1058 pg/mL). Forty-two patients with Gushing's disease were studied, either before (n=25) or after (n= 17) bilateral adrenalectomy: 7 patients with highly invasive macroaden omas had high POMC plasma levels, between 240 and 4200 U/ml (concomita nt ACTH plasma levels between 77 and 5730 pg/mL); 35 patients, includi ng one with an invasive macroadenoma, had undetectable POMC plasma lev els (concomitant ACTH plasma levels between 31 and 2820 pg/mL). Among 20 patients with histologically proven ectopic ACTH syndrome, 16 had h igh POMC plasma levels, between 80 and 8000 U/mL (concomitant ACTH pla sma levels between 45 and 9265 pg/mL); all those tumors were malignant , and the highest POMC/ACTH plasma levels ratios (taken as an index of altered POMC processing) were observed in the 3 patients with small c ell carcinomas of the lung; in one of these patients, ACTH and POMC pl asma levels both decreased during the course of chemotherapy, in paral lel with the reduction of the tumoral mass, Four patients with ectopic ACTH syndrome had undetectable POMC, plasma levels (concomitant ACTH plasma levels between 78 and 335 pg/mL): they were all typical bronchi al carcinoids. These data show that high POMC plasma level is neither specific for nor constant in ectopic ACTH syndrome. Rather it should b e considered as a marker of tumor aggressivity, in pituitary- and non- pituitary tumors. Its diagnostic help appears limited for the most fre quent cause of occult ectopic ACTH syndrome, the typical bronchial car cinoids.