ACTH-producing Pituitary Tumors Research Articles

Gamma irradiation effects on human ACTH-producing pituitary tumors in organ culture

Morphology (studied by light and electron microscopy) and hormone secretion were followed in organ cultures of adrenocorticotropic hormone (ACTH)-secreting hormones after in vitro irradiation with a single dose of 70 Gy. The increase is ACTH secretion immediately after exposure was interpreted as an irradiation-induced direct effect on cell membrane permeability. The low secretional capacity for 120 h after irradiation is probably caused by an impairment of cell metabolism. Cell morphology slightly deteriorated 24-48 h after exposure. Later, cell morphology was restored and specimens investigated 5 days after irradiation showed normal morphology. It is concluded, that the fluctuations in serum ACTH in patients with Cushing's disease treated by stereotactic radiosurgery are caused by changes in the tumor cells proper rather than being due to hypothalamic influence.

Activation of virilizing adrenal rest tissues by excessive ACTH production: An unusual presentation of Nelson's syndrome

Nelson's syndrome occurs in 10 to 35 percent of patients treated for Cushing's disease by bilateral adrenalectomy and features an ACTH-producing pituitary tumor and hyperpigmentation. Cortisol-producing testicular tumors activated by markedly elevated ACTH levels have been described in male patients with Nelson's syndrome. We now describe a female patient with Nelson's syndrome who presented with virllization. Abdominal exploration revealed adrenal rest tumors in the paraovarian tissues and adrenal beds. Iodocholesterol scanning gave negative results. This case illustrates the need for follow-up study of patients with bilateral adrenalectomy for Cushing's disease and describes some of the unusual features these patients may present.

Characterization of gamma-melanotropin-like immunoreactivity and its secretion in an adrenocorticotropin-producing mouse pituitary tumor cell line.

gamma MSH, a putative hormone in the N-terminal region of the ACTH/beta-endorphin (beta-EP) precursor protein, was studied by RIA with an antiserum against gamma 3MSH in ACTH-producing mouse pituitary tumor cells, AtT-20/D16v. Serial dilution of the culture medium or the cell extract gave parallel lines to the standard curve in the RIA for gamma MSH. Rat median eminence extracts enhanced the release of gamma MSH-like immunoreactivity (gamma MSH-LI) concomitant with ACTH-like immunoreactivity (ACTH-LI) and beta-EP-like immunoreactivity (beta-EP-LI). Dexamethasone suppressed the release of gamma MSH-LI as well as ACTH-LI and beta-EP-LI. Gel exclusion chromatography of the culture medium and the cell extract has revealed that gamma MSH-LI consists of two peaks; one eluted near the elution position of beta-lipotropin and the other near the elution position of beta-EP. There was no peak corresponding to the elution position of synthetic gamma 3MSH. However, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) has demonstrated that gamma MSH-LI migrated at five positions with molecular weights of 31K, 21-23K, 16-17K, 13-14K, and 3.8K, respectively. The 31K gamma MSH coincided with the migration position of 31K ACTH of 31K beta-EP, and 21-23K gamma MSH coincided with the position of 21-23K ACTH on SDS-PAGE. The 16-17K gamma MSH coincided with the mouse 16K fragment (reported by Eipper and Mains) of ACTH-beta-lipotropin precursor protein in the migration in SDS-PAGE and in immunoreactivity to anti-gamma MSH antiserum. [3H]Glucosamine was incorporated into 16K, 13K, and 3.8K gamma MSH. These results suggest that AtT-20/D16v cells produce gamma MSH-LIs with molecular weights of 31K, 21-23K, 16-17K, 13-14K, and 3.8K, and they are secreted concomitantly with ACTH-LI and beta-EP-LI.

INHIBITION BY SOMATOSTATIN OF ACTH SECRETION IN NELSON'S SYNDROME

Somatostatin (GHIF), when administered as a 1-hr infusion (500 mug/hr) to 5 patients with Nelson's Syndrome;resulted in a sustained, progressive fall in plasma ACTH in each patient to 40% to 71% of basal values with a return toward initail levels after cessation of the infusion. The meanreduction in plasma ADTH was 48% (p less than 0.005). These finding suggest that GHIF receptors not fuctional or present in normal pituitary tissue are present in ACTH-producing pituitary tumors.

Depigmentation in Cushing's Syndrome

THE endocrinological control of pigmentation has been a subject of considerable interest and much investigation. Lerner et al¹and Lerner,²in comprehensive reviews, discussed the etiological factors associated with melanin pigmentation. They observed that primary adrenal insufficiency is usually associated with hyperpigmentation, but that adrenal insufficiency secondary to hypopituitism is not. They further suggested that this hyperpigmentation is dependent upon an increase in the circulating levels of the melanocyte stimulating hormone (MSH) and could be controlled by maintenance doses of hydrocortisone. In addition, increased levels of MSH have been detected in the urine of patients suffering from Addison's disease.³ Hyperpigmentation has also been reported following adrenalectomy for Cushing's syndrome where an excessive production of adrenocorticotrophic hormone (ACTH) has persisted following operation.⁴In some of these cases an ACTH-producing pituitary tumor has become manifest and the implication has been that the increase of pigment in these patients

ACTH-producing pituitary tumors following adrenalectomy for Cushing's syndrome.

Excerpt Since describing a single patient who, following bilateral adrenalectomy for Cushing's syndrome associated with adrenal hyperplasia, subsequently developed an ACTH-producing tumor of the pi...