High plasma proopiomelanocortin in aggressive adrenocorticotropin-secreting tumors.

Abstract

A specific propiomelanocortin (POMC) immunoradiometric assay was developed using antibodies directed against ACTH and beta-endorphin (beta end). Partially purified standard POMC was prepared from the human small 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-terminal beta end radioimmunoassay and thus were close if not equal to 10 pg POMC. This POMC assay was used to investigate patients with ACTH-dependent Cushing's syndrome. Plasma POMC was undetectable (< 60 U/mL) in 17 normal controls and in 4 patients with Addison's disease (concomitant ACTH plasma levels between 362 and 1058 pg/mL). Forty-two patients with Cushing's disease were studied, either before (n = 25) or after (n = 17) bilateral adrenalectomy: 7 patients with highly invasive macroadenomas had high POMC plasma levels, between 240 and 4200 U/ml (concomitant ACTH plasma levels between 77 and 5730 pg/mL); 35 patients, including one with an invasive macroadenoma, had undetectable POMC plasma levels (concomitant ACTH plasma levels between 31 and 2820 pg/mL). Among 20 patients with histologically proven ectopic ACTH syndrome, 16 had high POMC plasma levels, between 80 and 8000 U/mL (concomitant ACTH plasma 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 cell carcinomas of the lung; in one of these patients, ACTH and POMC plasma levels both decreased during the course of chemotherapy, in parallel 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 bronchial carcinoids. These data show that high POMC plasma level is neither specific for nor constant in ectopic ACTH syndrome. Rather it should be considered as a marker of tumor aggressivity, in pituitary- and non-pituitary tumors. Its diagnostic help appears limited for the most frequent cause of occult ectopic ACTH syndrome, the typical bronchial carcinoids.

PlasmaACTHPrecursors in Cats with Pituitary‐Dependent Hyperadrenocorticism

“…These results suggest that corticotropic tumors in cats are associated with high plasma concentrations of ACTH precursors. In humans, it is assumed that the impairment of POMC processing in less differentiated pituitary tumors derived from corticotroph cells leads to an increase in the secretion of ACTH precursors into the plasma . In dogs, high plasma ACTH precursor concentrations is correlated with the size of the pituitary tumor .…”

“…This precursor is first processed to pro‐ACTH which is then cleaved to ACTH by the prohormone convertase 1 (PC1) . Plasma ACTH precursor (POMC and pro‐ACTH) concentrations are high in large or aggressive pituitary corticotrophic tumors in both humans and dogs, but no equivalent information is available for cats. The aim of this study was to describe plasma ACTH precursor (POMC and pro‐ACTH) concentrations in cats with PDH and to estimate the utility of such determinations for the diagnosis of this condition, by comparing the results obtained with those for 3 other groups of cats: cats with DM but not HAC, cats with DM and confirmed acromegaly but not HAC, and healthy cats.…”

Aggressive Pituitary Tumors

“…However, a critical analysis of the well-documented published series of atypical adenomas (table 2) has revealed that approximately half of these tumors are nonfunctioning, whereas atypical GH-secreting adenomas appear more frequent than atypical ACTH or PRL tumors. Symptoms related to hormonal hypersecretion usually do not differ from those encountered in patients with benign adenomas, and there are no hormonal level cutoffs that differentiate aggressive from benign or malignant macroadenomas, although higher pro-opiomelanocortin levels may be associated with a more aggressive course in patients with Cushing's disease [75]. Very high levels of PRL, ACTH, and/or GH despite apparent surgical clearance of the tumor should raise suspicion for the presence of more aggressive or potentially malignant pituitary tumors.…”

Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor

“…This patient's initially normal 24 h urinary free cortisol and lack of clinical signs of Cushing's syndrome despite an elevated plasma ACTH level may have been due to the rapidity of his tumor growth that did not permit signs to become manifest. Alternatively, initial tumoral secretion could have been that of biologically inactive ACTH and precursor of ACTH (POMC) which has been demonstrated in some invasive atypical macroadenomas [18]. The nature of ACTH produced by this patient's tumor may have changed or eventually, as the tumor volume increased, enough biologically active ACTH was produced to lead to Cushing's syndrome.…”