Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It may sometimes be difficult to distinguish Cushing's disease from ectopic ACTH syndrome. A case is described here of a patient with a Cushing's syndrome and diagnostic difficulties. Initial features were consistent with a Cushing's disease (in particular metopirone test was positive). Because of relapse of hypercortisolism after mitotane therapy, total adrenalectomy was performed. Thereafter features occurred that evoked Nelson's syndrome, including high plasma ACTH levels and a pituitary mass syndrome. Pituitary reserve testings by vasopressin or corticotropin-releasing factor were positive, although inconstantly, in that plasma ACTH increased. A lung tumor was discovered about 20 yr after the first clinical signs of hypercortisolism. Its removal led to the discovery of a bronchial carcinoid tumor and was followed by normalization of plasma ACTH levels. An analysis of proopiomelanocortin-related peptides was performed postoperatively on the blood drawn before and after the tumor resection and on the tumor; the results of this study would have been contributive to the diagnosis of occult ectopic ACTH tumor. In conclusion this case demonstrates the limitations of the conventional procedures in the diagnosis of the ectopic ACTH syndrome. At contrast the newer biochemical procedures may be very useful in determining the type of hypercortisolism.
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PMID:A case of pseudo-Nelson's syndrome: cure of ACTH hypersecretion by removal of a bronchial carcinoid tumor responsible for Cushing's syndrome. 217 23

Sixty pmoles of a material with molecular size, immunological, and RP-HPLC characteristics identical to that of h beta MSH(5-22) were purified from a bronchial carcinoid tumor responsible for the ectopic ACTH syndrome. The first 16 cycles of microsequencing revealed the following sequence: Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-X-Phe-Arg-Trp-Gly-X-Pro- Pro-, identical to the first 16 amino acids of h beta MSH(5-22). Since this material was recognized by an antibody which requires the free COOH-terminal Asp22 residue, it can be assumed that it is indeed h beta MSH(5-22). We also show that neither the 5 N acetic acid nor the 1 N HCl extraction procedure artefactually generated h beta MSH-like material in normal or tumoral human pituitaries and in nonpituitary tumors. We conclude that h beta MSH(5-22) is a normal maturation product of proopiomelanocortin in the human nonpituitary tissues which express its gene, including the hypothalamus and ACTH-secreting tumors.
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PMID:Microsequencing evidence for the maturation of human proopiomelanocortin into an 18 amino acid beta-melanocyte stimulating hormone [h beta MSH(5-22)] in nonpituitary tissue. 274 27

A male patient with corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH)-producing syndrome is described. Soon after being referred to us the patient developed pneumonia, anaemia, oedema and respiratory distress, and died on the 24th day after admission. Autopsy and histology revealed that he had a rare type of multiple endocrine neoplasia (type 1 + paraganglioma) with a mediastinal paraganglioma, parathyroidal hyperplasia, pancreatic islet cell adenoma, duodenal multiple carcinoid tumours and adrenocortical nodular hyperplasia. It was not possible to examine the pituitary. The paraganglioma contained a large amount of immunoreactive (IR)-CRF (606 ng/g wet weight), IR-ACTH (59.4 ng/g wet weight), IR-human proopiomelanocortin n-terminal (1-76) peptide (hNT, 156.8 ng/g wet weight) and IR-beta-lipotropin (beta-LPH, 146.9 ng/g wet weight). The major IR-ACTH, beta-LPH and IR-hNT were eluted at ACTH-(1-39), beta-LPH and hNT marker positions, respectively. Big ACTH was not detected. IR-CRF eluted at the human CRF marker position on Sephadex G-75 chromatography and high performance liquid chromatography (HPLC). The IR-CRF fraction from the HPLC showed CRF bioactivity which paralleled that of synthetic human CRF in monolayer cultured rat anterior pituitary cells. Our results suggest that not only ACTH but CRF produced by the paraganglioma was responsible for the patient's Cushing's syndrome.
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PMID:Multiple endocrine neoplasia with Cushing's syndrome due to paraganglioma producing corticotropin-releasing factor and adrenocorticotropin. 287 33

In order to assess the mechanisms of proopiomelanocortin (POMC) gene expression in human ACTH-producing tumors, we performed the simultaneous evaluation of POMC products and messenger RNA (mRNA) in tissue fragments obtained from two corticotropic adenomas, five nonpituitary tumors, and two normal human pituitaries. The POMC products were examined using a combination of gel exclusion chromatography and four different radioimmunoassays directed against gamma 3 melanocyte stimulating hormone (gamma 3MSH), ACTH, gamma-lipotropin (gamma LPH), and beta-endorphin. The POMCmRNA was detected and analyzed by dot and northern blot hybridization using a single-stranded genomic DNA probe corresponding to the coding region of the human POMC gene. Tissue concentrations of POMC products and mRNA showed parallel distributions. Immunoreactive gamma 3MSH and gamma LPH patterns revealed only 16-kD fragment- and gamma LPH-like peptides in normal and tumoral pituitaries; additional gamma 3MSH- and/or beta MSH-like peptides were found in all five nonpituitary tumors. A single POMCmRNA of approximately 1,200 bases (b) was detected in normal and tumoral pituitaries; a single identical POMCmRNA was also found in four nonpituitary tumors. A thymic carcinoid tumor, in addition to the 1,200-b POMCmRNA, contained equal amounts of a second larger POMCmRNA of approximately 1,450 b. It is concluded that POMC gene expression appears qualitatively unaltered in corticotropic adenomas. In nonpituitary tumors, in contrast, abnormal POMC processing is frequent; in addition, an extra POMCmRNA was detected in a thymic tumor with a greater length than the normal mRNA; the mechanisms and pathophysiological implications of these modifications remain to be elucidated.
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PMID:Altered proopiomelanocortin gene expression in adrenocorticotropin-producing nonpituitary tumors. Comparative studies with corticotropic adenomas and normal pituitaries. 299 96

To differentiate between ectopic ACTH syndrome and Cushing's disease, gene expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH levels in all patients with Cushing's disease and in five patients with ectopic ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders, CRH was not detected in tumors that contained no CRH mRNA or that contained only long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in three patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRH mRNA and PMA-induced POMC gene expression. In addition, there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited usefulness in differentiating between Cushing's disease and ectopic ACTH syndrome.
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PMID:Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin-producing tumors in vitro. 825 33

A 26 year-old man with suspected Cushing's disease underwent transsphenoidal exploration of the pituitary without any evidence of microadenoma or hyperplasia. Progressive hypercortisolism necessitated bilateral adrenalectomy. Postoperatively, skin pigmentation gradually developed with a marked elevation of plasma ACTH levels, and CT scanning uncovered a thymic mass. Following removal of the thymic mass, skin pigmentation disappeared and plasma ACTH levels fell to normal. The excised mass was found to be a benign thymic hyperplasia without epithelial or carcinoid tumor cells. However, gel chromatography showed that the thymic tissue extract contained high ACTH content comparable to that of ectopic ACTH-producing tumors with a major component corresponding to ACTH(1-39). Northern blot analysis and in situ hybridization revealed the expression of proopiomelanocortin transcripts in lymphocytes of thymic hyperplasia. This report suggests that lymphocytes in thymic hyperplasia are the most likely site of deregulated ACTH expression causing ectopic ACTH syndrome.
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PMID:Thymic hyperplasia as a source of ectopic ACTH production. 1107 32

There are roughly two types of ectopic ACTH syndrome (EAS). one associated with overt malignancies and one with occult neoplasms. The prototype of the first condition is Cushing's syndrome sustained by small-cell lung cancer (SCLC), while bronchial carcinoid tumors are the most common occult sources of ACTH. Patients with EAS and SCLC may have an atypical presentation with muscle wasting and weight loss that are more frequently observed than the classic cushingoid features. These patients have a poor prognosis because SCLC associated with the EAS is more resistant to chemotherapy and the severe hypercortisolism is responsible for a high rate of life-threatening complications during treatment. Conversely, the clinical and biochemical features of the EAS associated with carcinoid may overlap those seen in pituitary-dependent Cushing's syndrome. An extensive radiological and hormonal work-up is necessary to detect the extrapituitary source of ACTH. However, the differentiation between the pituitary, or eutopic, from the non-pituitary, or ectopic, source of ACTH secretion may be extremely difficult in some cases despite the wide diagnostic armamentarium available. Molecular biology studies have demonstrated that the carcinoid cells achieve a process of corticotroph differentiation being able to express the proopiomelanocortin (POMC) gene and to process POMC correctly to release large amounts of intact ACTH. Conversely, SCLC processes POMC in an aberrant way releasing high concentrations of ACTH precursors and less intact ACTH in the circulation.
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PMID:Ectopic ACTH syndrome: molecular bases and clinical heterogeneity. 1176 58

The proopiomelanocortin (POMC) gene is occasionally expressed in nonpituitary tumors leading to Cushing's syndrome. Bronchial carcinoid tumors, one of the most frequent source for ectopic ACTH secretion, often display numerous features of the corticotroph phenotype. To identify new markers of corticotroph differentiation in these tumors, we compared the pattern of gene expression in ACTH-secreting (ACTH+) and nonsecreting (ACTH-) bronchial carcinoids by differential display/RT-PCR. Using groups of ACTH+ and ACTH- tumors, we initially selected approximately 300 differentially expressed genes. Fifteen were considered differentially expressed after further characterization by RT-PCR on a larger series of 8 ACTH+ and 12 ACTH- bronchial carcinoids; 11 were restricted to--or overexpressed in--ACTH+ and four in ACTH- tumors. In ACTH+, beside the expected POMC gene, we identified cFos, and KIAA1775, a large expressed sequence tag encoding a putative protocadherin-related protein. On the other hand, the tetraspanin TM4SF5 gene was specifically expressed in ACTH-. Dot blot analysis confirmed the specific expression of KIAA1775 in ACTH+ bronchial carcinoids. However, the expression of most of the differential genes, including KIAA1775, was detected by RT-PCR in pituitary or lung tumors, whether secreting ACTH or not, excepted for TM4SF5, which was only detected in some nonendocrine lung tumors. Our results show that corticotroph differentiation of bronchial carcinoid tumors is accompanied by induction and repression of specific genes. The nature of some of these genes, identified here, underlines the importance of cell-cell or cell-extracellular matrix interactions in the establishment of neoplastic corticotroph phenotype. These genes should help to better characterize ACTH+ bronchial carcinoids as well as other bronchial carcinoid subtypes.
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PMID:Identification of genes associated with the corticotroph phenotype in bronchial carcinoid tumors. 1241 66

A 56-yr-old woman was referred with a diagnosis of Cushing's disease. Hypertension and severe hypokalemia were present and high urinary free cortisol/cortisone ratio was detected, raising a suspicion of an ectopic ACTH syndrome. Inferior petrosal sinus sampling, thoracic computed tomography, and octreotide scans were negative. Remission and relapse periods lasting 3-4 months were observed during the 3.5 yr of follow-up. Finally a thoracic computed tomography scan showed a basal paracardic nodule in the left lung. After surgery, a well-differentiated neuroendocrine tumor (typical bronchial carcinoid) was diagnosed, staining positively for ACTH. RT-PCR revealed expression of proopiomelanocortin, CRH receptor, and V3 vasopressin receptor. Somatostatin receptor type 1, 2, 3, and 5 mRNA was detected only in tumoral tissue. Interestingly, we observed the simultaneous presence of ghrelin and both GH secretagogue (GHS) receptors (1a and 1b) mRNA in tumoral tissue but not in the normal lung. This finding correlates with the in vivo ACTH hyperresponsiveness to hexarelin (a GHS). This is the first report of a cyclical ectopic ACTH-secreting tumor with an in vivo ACTH response to hexarelin coupled with the tumoral expression of ghrelin and GHS receptors. This finding might imply an autocrine/paracrine modulatory effect of ghrelin in bronchial ACTH-secreting tumors.
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PMID:Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors. 1467 Nov 77

Discrepancy of plasma ACTH levels measured by different immunoradiometric assays (IRMA) in a case with malignant gastric carcinoid causing ectopic ACTH syndrome was examined by gel chromatography and immunohistochemical analysis. A 49-year-old male was found to have a large gastric tumor, with muscle wasting, hypertension, diabetes and hypokalemia caused by hypercortisolemia. His plasma ACTH levels, although initially elevated, were found to be almost in normal ranges. The discrepancy of plasma ACTH levels was proven to be due to different IRMA kits used; the initial assay was performed by a kit that could recognize high-molecular weight (HMW) form as well as ACTH(1-39), but the later assay by another kit that could recognize only ACTH(1-39). Pathological examination of the gastric tumor was consistent with the diagnosis of malignant carcinoid. Immunohistochemical study revealed that immunoreactivity of proopiomelanocortin (POMC) was positive within the tumor cells, whereas those of ACTH and prohormone convertase 1/3 were negative. Molecular sieving analysis of patient's plasma by gel chromatography coupled with ACTH radioimmunoassay which could recognize HMW form and ACTH(1-39) and two different IRMAs revealed that the predominant form of ACTH was HMW form with a minor peak of ACTH(1-39). This is a rare case of ectopic ACTH syndrome caused by malignant gastric carcinoid with preferential production of HMW form of ACTH, possibly due to unprocessed POMC.
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PMID:Malignant gastric carcinoid causing ectopic ACTH syndrome: discrepancy of plasma ACTH levels measured by different immunoradiometric assays. 1641 Jun 67


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