beta-endorphin and Hyperplasia

Corticotroph adenoma is a benign tumor composed of adenohypophyseal cells; carcinoma with metastasis and ectopic adenoma have also been reported. In our pathological series, the frequency of this type of adenoma is 13% (250/1863 tumors removed between 1970 and 2001). Usually, corticotroph adenomas synthesize peptides derived from POMC maturation: ACTH, ss-endorphine, and ssLPH. In the great majority of cases, ACTH induces hypercorticism with clinical and biological signs of Cushing's disease. However, some tumors the pathologist identifies as corticotroph adenomas are not associated with clinical signs of hypercorticism (20% of the corticotroph adenomas in our series). Corticotroph adenoma is a basophilic or chromophobe tumor composed of cells which remain regulated by cortisol. This may explain the small size of this type of adenoma in 80% of the cases. In contrast, "silent" adenomas or macroadenonas which synthesize high-weight POMC are aggressive invasive tumors. Neurosurgery is indicated for the treatment of corticotroph adenoma. Recurrence is explained by incomplete removeal of the tumor. Peroperative studies may be necessary to find microadenomas. In some cases, the whole pituitary must be removed and cut in serial sections to find a tumor measuring<2 mm. In our opinion, the existence of corticotroph hyperplasia inducing Cushing's disease remains to be proven (we have never observed one). The pituitary origin of the tumor is based on its monoclonality. The general mechanism of tumorigenesis is known, but the specific factors involved and markers of aggressiveness remain to be discovered.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; beta-Endorphin; beta-Lipotropin; Biomarkers, Tumor; Cell Cycle Proteins; Corticotropin-Releasing Hormone; Cushing Syndrome; Cytokines; Growth Substances; Humans; Hyperplasia; Hypothalamo-Hypophyseal System; Mice; Mice, Knockout; Mice, Transgenic; Neoplasm Proteins; Pituitary Gland, Anterior; Pituitary Neoplasms; Pituitary-Adrenal System; Pro-Opiomelanocortin; Receptors, Glucocorticoid; Retrospective Studies

Among 436 patients with hypertension unrelated to any renal lesion, renovascular damage, pheochromocytoma, Cushing's syndrome or hyperthyroidism, 15 patients had low plasma renin activity (PRA) and elevated plasma aldosterone concentrations in the upright position and resultant high aldosterone/PRA ratios: 8 with aldosterone-producing adenoma (APA; group 1) and 7 with idiopathic hyperaldosteronism (IHA; group 2). Thirty-nine patients had suppressed PRA in the presence of normal plasma aldosterone levels and moderately elevated aldosterone/PRA ratios (group 3). Thirty of them had elevated plasma 11-deoxycorticosterone (DOC) and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) concentrations (group 3a) and 9 of them had normal levels of those mineralocorticoids (group 3b). The rest of them (382 patients) had low aldosterone/PRA ratios (group 4). Adrenal scintigraphy with dexamethasone pretreatment revealed [13I]-cholesterol accumulation not only in patients with APA (unilateral) or IHA (bilateral), but also in patients of group 3a (bilateral). In patients in groups 3a and 3b adrenal size (especially thickness), as measured by computed tomography (CT scan), was enlarged, as in patients with IHA (group 2), and was significantly greater than in patients of group 4 (p less than 0.001). Spironolactone reduced blood pressure in all tested patients of group 3a, and the removal of adrenal tumor or hyperplastic tissue normalized blood pressure in patients of groups 1, 2 and 3a. Excised adrenal glands exhibited cortical hyperplasia with or without nodular hyperplasia in patients of group 3a. Good agreement was found between the actual size of the excised tissue and the measurement obtained by CT scan. Since beta-endorphin and beta-lipotropin were depressed in patients of group 3a, it is suggested that an unknown pituitary substance stimulates the adrenal cortex to release too large amounts of DOC and 18-OH-DOC and inappropriate secretion of aldosterone.

Topics: 18-Hydroxydesoxycorticosterone; Adrenal Glands; Adrenocortical Hyperfunction; Adult; Aged; Aldosterone; beta-Endorphin; beta-Lipotropin; Blood Pressure; Desoxycorticosterone; Female; Humans; Hyperplasia; Hypertension; Male; Middle Aged; Renin; Tomography, X-Ray Computed; Zona Glomerulosa

Endocrine cells of the duodenal bulb producing adrenalin, noradrenalin, serotonin, histamine and beta-endorphine were assayed in 12 patients with preulcer and 39 patients with duodenal ulcer. It is shown that preulcer was mainly characterized by hyperplasia of endocrine cells in the duodenal bulb mucosa, secreting adrenalin and noradrenalin in the presence of the deficiency of beta-endorphine-producing cells. The recurrent duodenal ulcer was associated with a dramatic fall in the number of catecholamine-containing endocrine cells in the duodenal bulb.

Topics: APUD Cells; beta-Endorphin; Cell Count; Duodenal Ulcer; Duodenitis; Duodenum; Epinephrine; Humans; Hyperplasia; Norepinephrine; Serotonin

The immunohistochemical characterization of 92 surgically resected abnormal pituitaries showed 24 cases with ACTH immunoreactivity. These included two cases of nodular hyperplasias, 20 functional adenomas, and two silent corticotropic adenomas. Both patients with nodular hyperplasia and 19 patients with functional adenomas had Cushing's disease, while one patient with a functional adenoma had Nelson's syndrome. The two silent corticotropic adenomas were not associated with Cushing's disease, although both patients had slightly elevated serum prolactin levels. The tumors, which were stained for beta-endorphin (12 cases) and alpha and beta-MSH (five cases) were all positive for these peptides. These results show that immunohistochemical staining is indispensable in the diagnosis of nodular hyperplasia and silent corticotropic adenomas and that it is extremely helpful in confirming the diagnosis of ACTH-producing adenomas.

Topics: Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; Endorphins; Female; Humans; Hyperplasia; Male; Melanocyte-Stimulating Hormones; Pituitary Gland; Pituitary Neoplasms; Staining and Labeling

Immunoreactive plasma levels of the proopiolipomelanocortin-derived peptides, ACTH, beta-endorphin-lipotropin, and gamma 3MSH, were measured in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism. Plasma peptide concentrations in patient groups were not different from those in normal controls. Removal of aldosterone-producing adenomas in three patients and of an aldosterone-producing adrenocortical carcinoma in one patient did not affect plasma peptide concentrations. Furthermore, infusion of the opiate antagonist naloxone (0.2 mg/min) in one patient with bilateral adrenal hyperplasia had no effect on either plasma aldosterone or cortisol. These results suggest that the proopiolipomelanocortin-derived peptides are not overproduced in states of hyperaldosteronism.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenocorticotropic Hormone; beta-Endorphin; Carcinoma; Dexamethasone; Endorphins; Humans; Hyperaldosteronism; Hyperplasia; Melanocyte-Stimulating Hormones; Pituitary Hormones, Anterior; Pro-Opiomelanocortin; Protein Precursors

The pituitary glands of 18 patients with untreated Addison's disease were studied by histologic and immunocytochemical methods. Adrenal destruction was caused by tuberculosis (13 cases) or autoimmune adrenalitis (five cases), and the duration of the adrenal insufficiency ranged from one to 16 years. Both diffuse and nodular hyperplasia of corticotropic cells were evident in each case, and the extent of hyperplasia correlated with the duration of disease. In five cases, nodular proliferations with morphologic features between those of hyperplasia and those of adenoma, termed tumorlets, were identified, as were two microadenomas, only one of which was available for study. In all instances, the proliferating corticotrophs stained positively with PAS and were immunoreactive for adrenocorticotropic hormone and beta-endorphin. We conclude that diffuse and nodular corticotroph hyperplasia are common in untreated Addison's disease, although frank adenoma formation seems to be rare. The latter may be related to the short duration of disease or may imply the absence of additional, unknown factors that are required for adenoma growth.

Topics: Addison Disease; Adenoma; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cytoplasmic Granules; Endorphins; Female; Humans; Hyperplasia; Male; Middle Aged; Periodic Acid-Schiff Reaction; Pituitary Gland, Anterior; Pituitary Neoplasms

Pituitary adenomas were found in 21 (84%) of 25 dogs with spontaneous pituitary-dependent hyperadrenocorticism. Six dogs had pars intermedia adenomas, whereas 15 had tumours of the pars distalis. Diffuse corticotroph cell hyperplasia was found in 1 of the 4 pituitaries without adenoma; in 2 dogs with pituitary adenoma, coexisting hyperplasia of the surrounding corticotrophs was also present. Immunocytochemical staining of the pituitaries revealed positive staining for ACTH, beta-lipotrophin, and beta-endorphin in the majority of both pars distalis and pars intermedia adenomas. The most frequent and intense staining was found with anti-beta-endorphin. In most part intermedia tumours, many cells stained strongly for alpha-MSH; double immunostaining of one pars intermedia adenoma for ACTH and alpha-MSH showed that some tumour cells stained only for ACTH or alpha-MSH whereas others contained both peptides. Only occasional cells stained for alpha-MSH in pars distalis adenomas.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Dogs; Endorphins; Female; Fluorescent Antibody Technique; Hyperplasia; Male; Melanocyte-Stimulating Hormones; Pituitary Gland; Pituitary Neoplasms