Simultaneous assay of immunoreactive beta-lipotropin, gamma-lipotropin, and beta-endorphin in plasma of normal human subjects, patients with ACTH/lipotropin hypersecretory syndromes, and patients undergoing chronic hemodialysis.
(17/26)
We have studied the relative concentrations of the human immunoreactive (IR) peptides gamma-lipotropin (hgammaLPH, [1-58]hbetaLPH), beta-lipotropin (hbetaLPH), and beta-endorphin (hbetaEND, [61-91]hbetaLPH) using gel exclusion chromatography together with a specific radio-immunoassay (RIA) for hgammaLPH and a RIA that (because hbetaEND is the COOH-terminus of the hbetaLPH molecule) measures both hbetaEND and hbetaLPH on an equimolar basis. In normal subjects, basal plasma IR-hgammaLPH was often undetectable (<12.5 fmol/ml), but ranged up to 21 fmol/ml, and IR-hbetaEND/hbetaLPH was 10.8+/-0.7 fmol/ml; previous studies by others suggest that most of the IR-hbetaEND/hbetaLPH was probably hbetaLPH. Both IR-hgammaLPH and IR-hbetaEND/hbetaLPH were significantly elevated (P < 0.001) in patients undergoing chronic hemodialysis (101.5+/-12.7 and 23.8+/-2.0 fmol/ml, respectively). Their IR-hgammaLPH coeluted with standard hgammaLPH as a single peak, and IR-hbetaEND/hbetaLPH coeluted with hbetaLPH; no distinct peak of IR-hbetaEND was observed. In patients with ACTH/LPH hypersecretion due to Addison's disease, Nelson's syndrome, or ectopic ACTH syndrome, IR-hgammaLPH and IR-hbetaEND/hbetaLPH were both elevated, and IR-hbetaEND/hbetaLPH eluted as two peaks, one coeluting with hbetaLPH and the other with hbetaEND. The molar concentrations of all three peptides were significantly correlated with one another. The lower concentrations of endogenous IR-hbetaEND observed may be due in part to its apparent shorter plasma half-life, as estimated in an Addison's patient given a cortisol infusion. The biologic significance of these three peptides in circulating blood is still unknown. The increased levels of hbetaLPH and hgammaLPH in plasma of patients with chronic renal failure suggest that the kidney may be an important organ for their metabolism. (+info)
Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro.
(18/26)
In an attempt to delineate the mechanism and the site of action of cyproheptadine and dopaminergic agonists as well as hormones including thyrotropin-releasing hormone (TRH) and hydrocortisone, the effects of these substances on ACTH secretion from corticotroph adenoma cells in culture were examined. Dispersed cells of pituitary adenomas obtained at surgery from four patients with Nelson's syndrome and one subject with Cushing's disease formed a monolayer and actively secreted ACTH into the medium. When TRH (0.1 microM) was added to the medium, a significant increase in ACTH secretion was demonstrated by adenoma cells from two patients who responded to TRH preoperatively. Moreover, a dose-response relationship between TRH concentrations and ACTH secretion was observed. Incubation of cells with cyproheptadine (1 or 0.1 microM) resulted in a significant decrease in ACTH release, and inhibited stimulation produced by TRH in one experiment. This effect of cyproheptadine was blocked when equimolar concentrations of serotonin was coincubated, whereas serotonin by itself did not affect ACTH secretion. Dopamine (0.1 microM) lowered ACTH accumulation in the medium, which was blocked by the addition of haloperidol. When hydrocortisone was added to the culture, dose-dependent suppression of ACTH secretion was demonstrated. TRH at an equimolar concentration reversed this effect, but, failed to overcome the inhibition induced by a higher concentration of hydrocortisone in cells from one adenoma studied. Cultured normal corticotrophs obtained from a patient with metastatic breast cancer, on the other hand, did not show any response to these substances, except for hydrocortisone. We suggest that TRH, cyproheptadine, dopamine affect ACTH secretion in patients with ACTH-producing pituitary adenomas by their direct action on the adenoma. (+info)
Multiple cellular forms of corticotrophs in surgically removed pituitary adenomas and periadenomatous tissue in Cushing's disease.
(19/26)
Transsphenoidally removed samples of pituitary adenomas from 14 patients with Cushing's disease and 5 patients with Nelson's syndrome always contained groups of uniform small ACTH-cells. Antibodies against the pro-opiocortin precursor fragments beta-endorphin, ACTH, and 16k-peptide recognized material in typical adenoma cells. A subpopulation of these cells, varying in number from sample to sample, specifically exhibited alpha-melanotropin immunoreactivity. Most periadenomatous samples showed signs of severe degeneration. Typical Crooke cells only occurred in samples from patients with Cushing's syndrome, but, with this exception, no clear differences between pituitaries of patients with Cushing's and Nelson's syndromes could be discerned. Two other forms of ACTH-immunoreactive cells were observed: rare, single, highly immunoreactive cells, with characteristics of both normal and Crooke cells, and numerous syncytial groups of cells in an advanced state of disintegration, presumably the remnants of hyperplastic follicles. The four different corticotrophs are characterized according to their fine structure and immunoreactivity in this study. (+info)
Conservative removal of small pituitary tumours: is it justified by the pathological findings?
(20/26)
Operation by the trans-sphenoidal route allows removal of small pituitary adenomata with conservation of normal gland. Histological examination of tissue obtained at operation and necropsy in 73 cases showed that surgical methods at present in use are likely to leave tumour behind in the pituitary gland and in the dura mater of the pituitary fossa. The clinical significance of these findings will only become evident after following patients for an extended period, but there appears to be a strong indication for routine postoperative radiotherapy. (+info)
The nature of the immunoreactive lipotropins in human plasma and tissue extracts.
(21/26)
This study was designed to establish definitively the nature of immunoreactive lipotropin (IR-LPH) in human plasma and tissue extracts. Using gel filtration, gel filtration under denaturing conditions, cationic exchange chromatography, immunoprecipitation, and radioimmunoassay, we have studied normal and tumorous human pituitaries, ectopic ACTH- and LPH-secreting tumors, plasma from normal subjects before and after dexamethasone administration, and plasma from patients with primary adrenal insufficiency and pituitary and nonpituitary ACTH- and LPH-secreting tumors. Except in the plasma and tumors of occasional patients with ectopic ACTH syndrome, the smallest IR-LPH appears to be lambda-lipotropin (lambdaLPH), which is often the predominant and occasionally the only IR-LPH present. The other major peptide appears to be betaLPH, a 91-amino acid molecule that contains lambdaLPH as its 1-58 sequence. Larger immunoreactive materials were observed in some specimens, but the "big" LPH in one plasma was shown to be lambdaLPH bound to IgG.The weak melanocyte-stimulating activity of LPH suggests that ACTH may be the principal pigmentary hormone in man. The fact that lambdaLPH, rather than betaLPH, is the predominant form in plasma suggests that the enkephalin-endorphin opiate peptides, which are contained in the "missing" 59-91 sequence from the betaLPH precursor of lambdaLPH, may be secreted in parallel with ACTH under both physiological and pathological conditions in man. (+info)
Hyperadrenalism in childhood and adolescence.
(22/26)
Hyperadrenalism in childhood and adolescence has unique features that influence diagnosis and management. We reviewed our experience with 18 patients, ranging in age from 18 months to 18 years. Nine had bilateral adrenal hyperplasia, eight had adrenal neoplasms, and one had micronodular hyperplasia. Patients with congenital adrenal hyperplasia and hyperaldosteronism were excluded. Six patients with Cushing's disease diagnosed in earlier years were treated by total adrenalectomy and recently two patients underwent transsphenoidal removal of pituitary tumors. Bilateral adrenalectomy was carried out in one patient with micronodular hyperplasia and in a second because of elevated adrenocorticotrophic hormone (ACTH) levels from an undefined source. Eight patients had adrenal neoplasms, including five adenomas and three carcinomas. We found no reliable criteria to differentiate before surgery between adrenal adenomas and adrenal carcinomas. The most recognizable characteristic of malignancy was tumor size, specifically weight greater than 75 gms. Of the three patients with adrenal carcinoma, one expired 20 months after adrenalectomy and 8 months after receiving palliative partial hepatectomy for liver metastasis. Two patients are well with normal growth and development at 11 and 20 years following adrenalectomy. With the exception of one patient who died 6 years after surgery from a glioblastoma multiforme, all patients with adrenal adenomas are well. Eight patients underwent bilateral adrenalectomy for hypercortisolism. Five of the six who have reached their adult stature are significantly stunted. Four of six patients with Cushing's disease, treated by total adrenalectomy, have developed Nelson's syndrome at 2, 6, 10, and 12 years after surgery. Of the two patients undergoing transsphenoidal surgery, one had recurrent disease at 2 years and was treated by pituitary irradiation with recovery. The patients undergoing adrenalectomy for micronodular hyperplasia and ectopic ACTH are well at 2 and 4 years, respectively. Cushing's disease in children and adolescents is best treated by transsphenoidal removal of the pituitary adenoma. Adrenalectomy, once the most accepted approach, plays a secondary role and is indicated primarily in micronodular adrenal hyperplasia, in patients with ectopic ACTH production of an undefined source, and in recurrent Cushing's disease following prior pituitary irradiation. The high incidence of Nelson's syndrome in children treated by adrenalectomy mandates that patients at risk be monitored lifelong for the progression of a pituitary tumor.(ABSTRACT TRUNCATED AT 400 WORDS) (+info)
Treatment of acromegaly, Cushing disease and Nelson syndrome.
(23/26)
Since 1957 we have treated more than 429 patients who had pituitary neoplasms, most of which were hormone-secreting tumors. Long-term follow-up in the large group of patients treated for acromegaly shows a median survival of better than 16 years, with improvement over time. The short-term follow-up results in patients with Cushing* disease, Nelson syndrome and chromophobe adenoma are very encouraging. To compare these excellent results with those following surgical procedures, a large study of patients followed for a long period after the operations is needed. (+info)
Adrenal autotransplantation after total adrenalectomy: delayed determined function.
(24/26)
Adrenal autotransplantation after bilateral total adrenalectomy has been utilized to eliminate the need for replacement therapy and to prevent the late occurrence of Nelson's syndrome in some patients with Cushing's disease. It is possible to follow these cases up closely today, owing to the highly developed hormonal evaluation and imaging techniques. In this study, two patients who underwent bilateral total adrenalectomy and cortex autotransplantation are presented. The autografts were found functional and the patients had not required any steroid replacement therapy. (+info)