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)

Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation. Basal GH, GHRH, IGF-I and PRL levels, as well as plasma GH response to glucose load and TRH administration were abnormal before the operation, and became normal thereafter. The somatostatin analogue SMS 201-995 was found to be a potent inhibitor of the ectopic GHRH and the GH secretion (greater than 500 to 42 ng/l and 15.4 micrograms/l to 0.8 microgram/l, respectively). The effect on GHRH proved to be due to direct effect of somatostatin on the tumour cells, as demonstrated in tissue culture studies. A mixed meal was found immediately to suppress GHRH levels without such an effect on GH secretion. We conclude that the neuroendocrine tests usually practised in acromegaly cannot differentiate between ectopic GHRH secretion and pituitary adenoma. High plasma GHRH levels may serve as a diagnostic test for excessive GHRH production, which is almost always ectopic. These high levels are suppressible by somatostatin and a mixed meal.
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PMID:Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli. 168 1

Acromegaly was diagnosed in a 37-year-old woman with classical physical and biochemical findings; an enlarged sella on computed tomography suggested the presence of a pituitary macroadenoma. Radiologic evidence of a lung mass prompted radioimmunoassay of plasma growth hormone-releasing factor (7,500 pg/ml; normal less than 100 pg/ml). After resection of a bronchial carcinoid, which stained positive for growth hormone-releasing factor, circulating growth hormone-releasing factor levels normalized. Subsequently, her clinical, biochemical, and radiologic evidence for acromegaly resolved. This case represents the first reported use of the human pancreatic growth hormone-releasing factor 1-40 radioimmunoassay to preoperatively diagnose this rare etiology of acromegaly.
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PMID:Preoperative diagnosis of acromegaly by growth hormone-releasing factor radioimmunoassay. 192 54

Two patients with acromegaly secondary to ectopic GHRH secretion by metastatic carcinoid tumors were studied before and during therapy with the somatostatin analog octreotide (SMS 201-995). GH and GHRH secretory patterns were assessed during intermittent sc administration, continuous sc infusion (CSI), and continuous iv infusion of octreotide. Octreotide reduced serum GH and plasma GHRH levels in the two patients, although there was differential sensitivity of GH and GHRH. Intermittent sc therapy transiently lowered serum GH in both patients. A higher iv dose was required to reduce plasma GHRH by 50% than to reduce serum GH by 50% (2.0 vs. 0.05 micrograms/kg.h, respectively; patient 1). A similar pattern was found during CSI octreotide administration in the same patient. Chronic therapy with intermittent sc and CSI octreotide was assessed by serial 24-h profiles of GH and GHRH secretion in patient 2. Mean hourly serum GH levels decreased from a pretreatment level of 31.5 +/- 3.5 (+/- SE) to 9.5 +/- 1.5 micrograms/L during CSI therapy (1000 micrograms/day or 0.40 micrograms/kg.h). In contrast, plasma GHRH levels were less effectively suppressed. The mean serum GH levels and the variation in hourly GH values were reduced to a greater extent with CSI than with intermittent sc therapy. Serum insulin-like growth factor I also declined from 5.9 x 10(3) to 2.5 x 10(3) U/L during chronic CSI therapy (patient 2). CSI therapy with octreotide can be more effective than intermittent sc therapy in controlling GH excess in the rare syndrome of ectopic GHRH secretion, although serum GH may not decline to normal.
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PMID:Octreotide suppresses both growth hormone (GH) and GH-releasing hormone (GHRH) in acromegaly due to ectopic GHRH secretion. 249 33

We examined formalin-fixed, paraffin-embedded human tumors (42) from autopsies and surgical specimens for the presence of human pancreatic GRF-40 using the unlabeled antibody peroxidase-antiperoxidase method to assess the prevalence of tumors containing GRF, to define their primary sites and cellular derivations, and to correlate clinical and pathological features. Two paragangliomas, 1 pancreatic endocrine tumor, 1 bronchial carcinoid and 1 ganglioneuroma were immunoreactive for GRF. Of the GRF-containing tumors, only one bronchial carcinoid and one paraganglioma were associated with acromegaly.
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PMID:[Immunohistochemical detection of growth hormone-releasing factor (GRF) in neuroendocrine tumors]. 284 43

A 59-yr-old woman with a disseminated carcinoid tumor was evaluated for acromegaly. She had previously undergone a hypophysectomy for acromegaly and an enlarged pituitary, with a reduction in her serum GH levels from 100 to 4 micrograms/L. Recurrence of acromegalic symptoms 2 yr later was accompanied by elevated serum GH (16 micrograms/L) and insulin-like growth factor I (IGF-I; 528 micrograms/L) and plasma GHRH levels (12 micrograms/L; normal, less than 30 ng/L). Computed tomographic scan did not reveal pituitary enlargement. Metastatic carcinoid tissue in bone removed at biopsy contained GHRH (100 pg/mg tissue). High performance liquid chromatography of plasma GHRH revealed predominantly GHRH-(3-40)-OH, a biologically inactive GHRH metabolite, along with mature GHRH forms, while carcinoid tissue contained both GHRH-(1-40)-OH and GHRH-(1-44)-NH2. Treatment with pergolide initially resulted in reduction in serum GH and IGF-I levels and amelioration of symptoms of acromegaly. However, after 14 months of pergolide therapy, serum GH levels increased despite administration of up to 1000 micrograms pergolide/day. Plasma GHRH levels remained elevated throughout the treatment period. Subsequent treatment with SMS 201-995, a long-acting somatostatin analog, for over 1 yr resulted in sustained reductions of ectopic GHRH secretion, GH hypersecretion, and IGF-I levels. Plasma GHRH levels correlated with simultaneously measured serum GH levels in response to acute SMS 201-995 administration. SMS 201-995 was an effective medical treatment for acromegaly caused by ectopic GHRH production in this patient.
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PMID:Medical management of acromegaly due to ectopic production of growth hormone-releasing hormone by a carcinoid tumor. 289 89

A selection of 90 mainly endocrine but nonpituitary tumors have been tested for their content of specific somatostatin receptors using receptor autoradiography. Somatostatin receptors were detected in the following tumors: in all 5 meningiomas tested; in 3 of 39 malignant breast tumors; and in 3 growth hormone releasing factor-producing tumors, i.e., one mediastinal carcinoid, one intestinal carcinoma, and its liver metastasis. Receptor density varied greatly among individual tumors. Some of the positive tumors were biochemically characterized using in vitro binding assay and were shown to have saturable and high affinity receptors with pharmacological specificity for somatostatin. The following tumors did not contain somatostatin receptors: prostate carcinomas (n = 17); prostate hyperplasia (n = 2); ovarian carcinomas (n = 6); endometrial carcinomas (n = 4); primary liver cell carcinomas (n = 3); pheochromocytomas (n = 3); aldosteronomas (n = 2); medullary thyroid carcinomas (n = 2); one adrenocorticotropic hormone-secreting pulmonary carcinoid; one astrocytoma; one neurofibroma; one lung tumor; and one bladder tumor. Somatostatin receptors can be found in benign or malignant tumors, originating in part from tissue not primarily known as a somatostatin target. The biological function of such receptors is, therefore, partly unknown. If they can mediate antiproliferative properties, as has been suggested to be the case for somatostatin receptors in selected endocrine tumors in rats and humans, the present data could be of potential therapeutic interest.
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PMID:Somatostatin receptors in human endocrine tumors. 302 22

According to modern knowledge, acromegaly can develop in at least three ways. A pituitary adenoma with growth hormone overproduction is the most frequent. Much rarer is ectopic growth hormone secretion by extra-hypophyseal tumors. A further possibility is the production of growth hormone releasing factor (GRF) by hypothalamic or ectopic tumors. This involves the secretion of a substance which selectively stimulates the GH producing cells of the pituitary. Special features of the clinical and morphological picture of this condition are described, based on the authors own observations. Two patients developed acromegaly: one had a retroperitoneal paraganglioma and the other a bronchial carcinoid. Ectopic GRF secretion could be confirmed radioimmunologically and immunohistologically in both cases. As a result of the on-going, tumor related GRF stimulation the patients developed nodular or diffuse GH-cell hyperplasia in the adenohypophysis. Since ectopic GH secretion does not cause hyperplasia of the adenohypophyseal cells, morphologic examination of the hypophysis can contribute to the differential diagnosis in such cases.
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PMID:[New aspects of the pathogenesis of acromegaly-somatoliberinomas]. 308 70

Ectopic production of growth hormone-releasing factor (GRF) is a rare cause of acromegaly. In addition to its production by gangliocytomas, both hypothalamic and intrasellar, in rare cases various neuroendocrine neoplasms produce the substance, with resultant growth hormone cell hyperplasia of the pituitary and acromegaly. We report an endocrinologically well-documented case of a GRF-producing bronchial carcinoid tumor in which the associated acromegaly was cured by lobectomy.
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PMID:A rare cause of acromegaly: ectopic production of growth hormone-releasing factor by a bronchial carcinoid tumor. 310 52

A 29 year old woman with an enlarged pituitary fossa and classical acromegaly, possibly present for ten years, had biochemical and partial somatic resolution of the disorder after removal of a bronchial carcinoid tumour. In addition, galactorrhea stopped, menstruation returned after two years, and amenorrhea and elevated prolactin levels fell towards normal. Immunocytochemistry showed numerous growth hormone releasing factor (GRF) staining cells in the tumour. The tumour cells, when cultured, produced a supernatant selectivity stimulating human pituitary somatotrophic cell cultures to produce growth hormone (GH). The bronchial carcinoid did not secrete detectable GH, but extracts of it, and preoperative serum contained GRF immunoreactivity which coeluted with synthetic human pancreatic GRF.
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PMID:Resolution of acromegaly after removal of a bronchial carcinoid shown to secrete growth hormone releasing factor. 311 10

Neuroendocrine tumours of upper gastrointestinal tract fall into two main categories. First carcinoid tumours of the stomach and duodenum and secondly endocrine pancreatic tumours. The endocrine tumours of the gastric mucosa include two main types, so called ECL-oma of the corpus and fundic region and gastrin producing carcinoids or hyperplasia of the antrum and duodenum. The endocrine tumours of pancreas include entopically secreting insulinomas, glucagonomas, somatostatinomas, PP-omas, and ectopically secreting tumours, such as gastrinomas and tumours producing ACTH, GHRH, and calcitonin. The diagnosis of a neuroendocrine tumour of the upper gastrointestinal tract is based on the recognition of certain clinical syndromes and the determination of certain humoral products. A broad battery of radioimmunological assays for determination of different peptides is mandatory for the diagnosis and follow up of these patients. The diagnosis is also based on histological and immunocytochemical investigation of tissue specimens obtained at operation or by biopsy. Ultrasound investigation is the best non-invasive technique to detect metastases from neuroendocrine gut and pancreatic tumours, but angiography might unveil metastases down to a size of less than 5 mm. Surgery is still the primary treatment procedure but other treatments are needed because many patients have metastases already at the time of diagnosis. Chemotherapy with streptozocin combined with 5-fluorouracil or adriamycin and human leucocyte interferon has demonstrated objective response rate of about 70%. The new somatostatin analogue SMS 201-995 is an important adjunct in controlling clinical symptoms in patients with neuroendocrine gut and pancreatic tumours. A combination of different treatment procedures is needed for long-term management of these patients.
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PMID:Neuroendocrine tumours of the upper gastrointestinal tract and pancreas. 329 22


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