Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated a new IRMA developed commercially for the measurement of corticotropin (ACTH) in human plasma. The assay involves purified polyclonal goat capture antibodies specific for ACTH 26-39 and an 125I-labeled monoclonal signal antibody specific for ACTH 1-17. CVs for intraassay and total precision at ACTH concentrations between 9 and 801 ng/L ranged from 2.5% to 4.7% and from 3.3% to 9.3%, respectively, with an assay detection limit of 1.7 ng/L. The reference interval determined for adults with the new method (16-52 ng/L) differed significantly (P < 0.05) from that for an established ACTH IRMA (9-54 ng/L). Method comparison with clinical samples (n = 179) revealed a correlation coefficient of 0.970 and a best-fit equation of y (new IRMA) = (1.011 +/- 0.019)x + (4.17 +/- 3.31) with Sylx = 40.2. Both methods showed equivalent clinical sensitivity in evaluating Cushing disease, adrenal tumors, ectopic ACTH-producing tumors, hypopituitarism, steroid suppression, surgical adrenalectomy, Nelson syndrome, Addison disease, and corticotropin-releasing hormone stimulation. We conclude that the new IRMA is technically simple to perform and provides a specific and sensitive method for evaluating of adrenocortical function.
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PMID:Clinical and analytical evaluation of an immunoradiometric assay for corticotropin. 760 Jun 82

Previous series of pediatric pituitary adenomas have been small and have not been analyzed by age group. We analyzed the frequency, manifestation, course, and biology of these tumors before, during, and after puberty in 136 children younger than 20 years old at surgery, identified by review of 2230 patients treated from 1969 to 1993. Tumors were classified by clinical phenotype. Adrenocorticotropic hormone-releasing adenomas were most common before puberty, and prolactinomas were most common during and after. The frequencies of adrenocorticotropic hormone-releasing adenomas, prolactinomas, and endocrine-inactive adenomas differed from those in adults. Growth arrest was common with all types except growth hormone (GH)-releasing adenomas; menstrual irregularities were common with all but adenomas causing Nelson syndrome. Among girls with prolactinomas, the preoperative duration of primary amenorrhea was longer than that of other symptoms. Tumor size differed by adenoma type. Serum hormone levels shortly after surgery correlated with the recurrence of prolactinomas and GH-releasing adenomas. The prolactinoma size correlated with the maximum preoperative serum prolactin level; boys had larger tumors and higher preoperative and postoperative prolactin levels. We conclude that pediatric pituitary adenomas vary in size, age at symptom onset, and frequency before, during, and after puberty. Most adenomas can cause menstrual irregularities, and primary amenorrhea should prompt investigation of the sella. Growth arrest is common with all adenomas except GH-releasing adenomas. Serum prolactin and GH levels measured at 1 to 5 days after surgery indicate the risk of recurrence of prolactinomas and GH-releasing adenomas, respectively.
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PMID:Pediatric pituitary adenomas. 773 5

Familial glucocorticoid resistance (FGR) is a rare hereditary disorder characterized by hypercortisolism and the absence of stigmata of Cushing's syndrome. The inability of glucocorticoids to exert their effects on target tissues is compensated for by increases in circulating corticotropin (ACTH) and cortisol, the former causing excess secretion of both adrenal androgens and adrenal steroid-biosynthesis intermediates with salt-retaining activity. There is considerable variability in the clinical presentations of FGR ranging from asymptomatic, to isolated chronic fatigue and to hypertension with or without hypokalemic alkalosis or to hyperandrogenism, or both. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men it may lead to infertility and in children to precocious puberty. The reported molecular defects in FGR, such as point mutations and a microdeletion of the glucocorticoid receptor (GR) gene, cause partial resistance by, respectively, compromising the function of the GR or decreasing its intracellular concentration in glucocorticoid target tissues. Complete glucocorticoid resistance is believed to be incompatible with life in humans. Hence, the glucocorticoid resistance cases reported have been partial and of variable degree. The extreme variability in the clinical manifestations of the disorder can, additionally, be explained by differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps by different biochemical defects of the glucocorticoid receptor, causing selective resistance of certain glucocorticoid responses in specific tissues. Isolated tissue-resistance from a somatic mutation of the GR in a corticotropinoma from a patient with Nelson's syndrome was also found, suggesting that this may be a mechanism of tumorigenesis. There is additional evidence that defects of GR function can appear surreptitiously in a variety of clinical conditions, suggesting that glucocorticoid resistance in humans may be involved in the pathogenesis and/or clinical picture of a plethora of disease states, of which FGR is the archetype.
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PMID:Glucocorticosteroid resistance in humans. Elucidation of the molecular mechanisms and implications for pathophysiology. 782 90

POMC processing is frequently altered in ACTH-secreting nonpituitary tumors in which intermediate lobe-like peptides such as corticotropin-like intermediate lobe peptide (CLIP) are occasionally generated. In rodent pituitaries, the exclusive presence of prohormone convertase PC2 in the melanotrophs of the intermediate lobe is responsible for the specific conversion of ACTH to alpha MSH and CLIP, by contrast with corticotrophs of the anterior lobe, which do not contain PC2 and, therefore, only produce ACTH. The goal of our study was to look for PC2 expression in ACTH-secreting nonpituitary tumors in man. Using Northern blot analysis, PC2 transcripts were detected in five nonpituitary tumors that contained large proportions of CLIP (from 40-95% of the total C-terminal immunoreactive ACTH). A predominant PC2 messenger ribonucleic acid migrated with an apparent mol wt of 5 kilobases, and a minor signal at 3 kilobases was also detected. No PC2 messenger ribonucleic acid could be detected in the small cell carcinoma of the lung-derived DMS-79 human cell line, which produces unprocessed POMC, or in three pituitary tumors responsible for Cushing's disease or Nelson's syndrome, which produced intact ACTH, but no CLIP. These data strongly suggest that, as in rodents, PC2 is responsible for the production of smaller POMC end products, such as CLIP, frequently observed in ACTH-secreting nonpituitary tumors in man.
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PMID:Expression of the prohormone convertase PC2 correlates with the presence of corticotropin-like intermediate lobe peptide in human adrenocorticotropin-secreting tumors. 796 50

The authors have reviewed the results of transsphenoidal surgery for pituitary adenomas done on 66 children (younger than 16 yr of age) between 1966 and 1992. Ninety-four percent (62 of 66) showed clinical evidence of pituitary hormonal hypersecretion. The most common type was the adrenocorticotropic hormone-secreting adenoma (n = 36), followed by the prolactinoma (n = 18) and the growth hormone-secreting types (n = 8). There were four cases of nonfunctioning adenomas. Adrenocorticotropic hormone-secreting tumors in children had presentations and surgical results similar to those seen in adults. Twenty-three of 33 patients with Cushing's disease had simple adenomectomy or subtotal hypophysectomy without symptomatic recurrence. Four of 10 initial treatment failures had subsequent successful surgical intervention, resulting in an overall cure rate of 78%. Postoperative hypocortisolism was suggestive of surgical success but was not absolute. Of three patients with Nelson syndrome, none were successfully treated with surgery alone and two developed invasive disease. Prolactin-secreting and growth hormone-secreting tumors in children occurred more commonly with suprasellar expansion than did their adult counterparts. Transsphenoidal surgery was capable of controlling disease in only 12% (1 of 8) of growth hormone-secreting tumors, and 67% (12 of 18) of prolactin-secreting tumors required postoperative medical therapy or radiotherapy for persistently elevated prolactin levels. Special difficulty was noted in boys with prolactinomas and in girls with primary amenorrhea. As in adults, preoperative prolactin levels correlated with ultimate surgical success rates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transsphenoidal surgery for pituitary adenomas in children. 817 79

Pituitary adenomas are uncommon in childhood. Between 1975 and 1988, 36 patients underwent transsphenoidal resection at the Mayo Clinic before their 17th birthday. Fifteen (41.7%) had prolactin (PRL)-secreting tumors, 16 (44.4%) had adrenocorticotropic hormone (ACTH)-secreting tumors (including two patients with Nelson-Salassa syndrome), and three (8.3%) had tumors secreting growth hormone (GH); two patients (5.6%) had clinically nonfunctioning tumors. Of the 36 patients, 21 (58.3%) were girls, and girls predominated in every group except that with ACTH-secreting tumors, where they accounted for only 37.5% of the patients. The average age at the time of surgery was 14.7 +/- 2.2 years, the youngest patient being 7.3 years old. The ACTH-secreting tumors were associated with an earlier onset of symptoms than the other tumor types: six (37.5%) of 16 patients became symptomatic before 10 years of age, compared with two (10.0%) of the 20 other patients. Presenting symptoms primarily reflected endocrine dysfunction, with neurological presentation (visual field deficits) occurring in only two patients. There were no deaths in this patient group. Significant operative morbidity included steroid-induced psychosis in one patient and diabetes insipidus in three, which resolved in two. Plurihormonal tumors, broadly defined as tumors producing more than one hormone, were common, comprising five (36%) of 14 PRL-secreting tumors, all three GH-secreting tumors, and one of two clinically nonfunctioning tumors, or 25.7% overall. Macroadenomas accounted for 89% of plurihormonal tumors. Long-term follow-up review (median > 5 years) revealed good control of PRL-secreting tumors (although five of 15 patients had received postoperative radiotherapy), contrasted with a 25% late recurrence rate for ACTH-secreting tumors, which had an 80% initial remission rate. The majority of patients had good endocrine function, including reproductive function. It is concluded that: 1) although pediatric pituitary adenomas occur primarily in adolescence, Cushing's disease is found at any age; 2) transsphenoidal surgery is feasible and safe in this age group; 3) plurihormonal tumors occur more frequently in the pediatric age group than in adults; and 4) long-term control rates in PRL- and ACTH-secreting tumors are probably similar to those seen in adults.
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PMID:Pituitary adenomas in childhood and adolescence. Results of transsphenoidal surgery. 828 58

A pool of human pituitaries obtained from allegedly healthy subjects (traffic victims) and plasma samples from patients with Nelson's syndrome were analyzed by high performance liquid chromatography, and the corticosteroidogenic bioactivity and ACTH immunoreactivity were measured. Three bioactive forms of ACTH were detected in plasma samples and pituitary extract. The major form (peak III) coeluted with human ACTH-(1-39), showed a bioactive to immunoreactive ratio (B/I ratio) of about 1, and represented about 80% of the total bioactivity in both the plasma samples and the pituitary extract. Peak I, with a B/I ratio greater than 1, represented about 5%, and peak II, with a highly variable B/I ratio, represented about 7% of the bioactivity in both the plasma and pituitary extracts. A fraction with a very low B/I ratio was found to coelute with corticotropin-like intermediate lobe peptide. These data suggest that in Nelson's syndrome, ACTH secretion by the pituitary gland does not differ from that in normal subjects, at least qualitatively.
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PMID:Multiple forms of bioactive and immunoreactive adrenocorticotropin in human pituitary and blood of patients with Nelson's syndrome. 839 86

Pro-opiomelanocortin (POMC) mRNA was demonstrated in pituitary adenomas from 16 patients with Cushing's disease and 10 with Nelson's syndrome. The intensity of signal was significantly greater in Nelson's syndrome than in Cushing's disease and there was a trend towards a greater proportion of positive cells. This probably reflects inhibition of POMC gene expression by the high circulating levels of cortisol in Cushing's disease. In the para-adenomatous gland, the intensity of signal was variable in cells showing Crooke's hyaline change, ranging from negative to strongly positive, in keeping with the functional heterogeneity of corticotrophs. In one case, junctional corticotrophs were present and these were more intensely stained than anterior lobe corticotrophs in the same gland. This supports the concept that these cells are subject to different regulatory influences from corticotrophs in the anterior lobe. Whether this is related to differences in embryological origins or to local factors is at present unclear.
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PMID:Demonstration of pro-opiomelanocortin mRNA in pituitary adenomas and para-adenomatous gland in Cushing's disease and Nelson's syndrome. 849 26

We have administered octreotide, 100 micrograms tid, to a 27-year-old man with Nelson's syndrome. After seven days of therapy, adrenocorticotropin levels fell to 54% of initial values, and some shrinkage of the tumour was observed. This study indicates that octreotide therapy may have a role in the treatment of Nelson's syndrome.
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PMID:The effects of octreotide in a patient with Nelson's syndrome. 874 87

The effects of somatostatin and its analogs have been studied in different subclasses of patients with Cushing's syndrome (due to Cushing's disease, ectopic corticotropin [ACTH]- and/or corticotropin-releasing hormone [CRH]-secreting tumors, or ACTH-independent Cushing's syndrome) and in patients with Nelson's syndrome. In most patients with untreated Cushing's disease, octreotide does not suppress ACTH release, a finding that is supported by in vitro studies. However, octreotide or somatostatin inhibits pathological ACTH secretion in Nelson's syndrome. Short-term octreotide treatment has caused a significant initial response (decreased serum cortisol, ACTH, and cortisoluria) in 24 of 38 (64%) patients with ectopic ACTH/CRH Cushing's syndrome, and long-term treatment caused a persistent response in 10 of 14 (71%) cases. Pentetreotide scintigraphy may help to identify those patients with ectopic ACTH/CRH tumors who will have an initial response to octreotide, and is useful for locating ectopic ACTH/CRH-secreting tumors and their metastases. To date, octreotide has been shown to temporarily suppress gastric inhibitory peptide (GIP)-induced cortisol secretion in GIP-dependent (ACTH-independent) Cushing's syndrome, but has not shown any therapeutic benefit in other forms of ACTH-independent Cushing's syndrome.
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PMID:Is there a role for somatostatin and its analogs in Cushing's syndrome? 876 91


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