gastrins and Acromegaly

Topics: Acromegaly; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hyperparathyroidism; Ileal Diseases; Pyloric Antrum; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Acromegaly; Adenoma; Adenoma, Islet Cell; Adolescent; Adult; Aged; Calcium; Cushing Syndrome; Diarrhea; Female; Gastric Acid; Gastrins; Glucagon; Humans; Hyperinsulinism; Hyperparathyroidism; Hypoglycemia; Hypokalemia; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Polypeptide; Pancreatitis; Parathyroid Glands; Parathyroid Neoplasms; Pituitary Neoplasms; Syndrome; Thyroid Diseases; Zollinger-Ellison Syndrome

Topics: Acromegaly; Animals; Diabetes Mellitus; Digestive System Physiological Phenomena; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Liver; Nelson Syndrome; Nervous System; Pituitary Gland; Somatostatin; Thyroid Gland

Somatostatin, under physiological conditions, is a regulator of thyroid stimulating hormone, growth hormone, pancreatic islet-cell hormones and gastrin. In pharmacological dosage, gastric acid output, splanchnic blood flow and plasma renin levels, are influenced. A possible therapeutic effect on increased growth hormone secretion, disturbances of carbohydrate metabolism, gastroenteropathies and renal hypertension, is discussed. The clinical application is limited by the short biological half-life of the substance and the unspecific action on several organs.

Topics: Acromegaly; Animals; Diabetes Mellitus; Diabetic Retinopathy; Gastric Juice; Gastrins; Growth Hormone; Humans; Hypertension; Islets of Langerhans; Pancreatitis; Renin; Somatostatin; Thyrotropin; Zollinger-Ellison Syndrome

Topics: Acromegaly; Adenoma, Islet Cell; Animals; Binding Sites; Blood Glucose; Diabetes Mellitus; Diabetic Ketoacidosis; Dose-Response Relationship, Drug; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Secretory Rate; Somatostatin; Thyrotropin

Topics: Acromegaly; Adenoma, Islet Cell; Adrenocorticotropic Hormone; Bronchial Neoplasms; Diabetes Mellitus; Gastrins; Glucagon; Growth Hormone; Humans; Hypoglycemia; Neoplasms; Pancreatic Neoplasms; Somatostatin; Thyrotropin; Zollinger-Ellison Syndrome

Somatostatine is the hypothalamic factor which inhibits the secretion of growth hormone. The administration of a synthetic form decreased growth hormone levels by 50 to 75% in 5 acromegalic patients. The action is rapid but the effect is not prolonged. Prolactin was reduced in only case with galactorrhea. Thyreostimulin, as well as gastrin, are unaffected. Plasma insulin levels, and to a lesser extent those of glucagon, are decreased by somatostatine which causes no variation in either cortisol or blood glucose. Somatostatine, by correcting the pathological secretion of hormone, opens the way to medical treatment of acromegaly.

Topics: Acromegaly; Adult; Aged; Blood Glucose; Clinical Trials as Topic; Depression, Chemical; Female; Galactorrhea; Gastrins; Glucagon; Growth Hormone; Hormones; Humans; Hydrocortisone; Insulin; Islets of Langerhans; Male; Middle Aged; Pituitary Gland, Anterior; Pregnancy; Prolactin; Somatostatin; Thyrotropin; Time Factors

Topics: Acromegaly; Adult; Anemia, Pernicious; Blood Glucose; Fasting; Female; Food; Gastric Juice; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Infusions, Parenteral; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides; Radioimmunoassay; Time Factors; Zollinger-Ellison Syndrome

To study the effects of the somatostatin analog octreotide on gastric mucosal function and histology during short-term (3 months) preoperative treatment in patients with acromegaly.. Open design clinical study.. 10 patients were studied before treatment with octreotide (pre-tx), on day 1 of 300 microg octreotide/day (d300), after 1 week on 300 (w300), 600 (w600) or 1500 (wl500) microg octreotide/day, and after an additional 2.5 months on 1500 microg octreotide/day (M3). An 8h gastrin profile was obtained and ambulatory intragastric 23h pH-metry carried out at the indicated time points. Gastroscopy was performed at pre-tx and M3 and multiple mucosal biopsy specimens taken.. The mean serum gastrin concentration at first declined during octreotide therapy to a nadir at w1500, then recovered despite ongoing therapy (probably in response to reduced gastric acidity) and was similar to pre-tx values at M3 (mean+/-S.E.: 87+/-26, 50+/-11 and 98+/-46ng/l for pre-tx, w1500 and M3 respectively; P<0.05, pre-tx vs w1500). Gastric acidity had also declined at d300(P<0.05, d300 vs pre-tx), then recovered (despite the increase in the octreotide dose), but declined again at M3 (mean pH (95% confidence interval): 2.4 (1.7-3.2), 3.3 (2.4-4.3), 2.6 (1.8-:3.5, n=8) and 2.9 (1.6-4.2, n=7) at pre-tx, d300, w1500 and M3 respectively). The gastrin concentration at M3, although similar to pre-tx values, remained inadequately low for the reduced gastric acidity. The reduction in gastric acidity was marked during the daytime (0900-2200 h; P<0.01, d300 vs pre-tx and P=0.028, M3 vs pre-tx). However, while the stimulated postprandial gastric acid secretion was reduced at d300 (P<0.01, d300 vs pre-tx) and at M3 (n=7; P=0.027, M3 vs pre-tx), fasting and preprandial acidity was not affected. During the night, gastric acidity was reduced from 2200 to 0300 h, but the reduction was less marked than during the daytime. Paradoxically, the physiological intermittent late nocturnal reduction in acidity ('pH peaks' (0300-0800 h)) was abolished rather than enhanced. No patient acquired new Helicobacter pylori infection. The mean gastritis scores for antrum and body (n=8, Sidney classification) increased marginally from 1.7 to 1.9 (chronicity) and from 0.7 to 0.9 (atrophy), while the activity score was slightly reduced from 1.2 to 1.0.. Three months of preoperative octreotide treatment profoundly and persistently altered gastric mucosal function (gastrin suppression, reduced acidity), but caused only minor variations in the pre-existing gastritis scores.

Topics: Acromegaly; Adult; Aged; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Octreotide; Preoperative Care

We studied a possible persistence of low GH concentrations after drug withdrawal in eight acromegalic patients who had been receiving octreotide treatment continuously for 42 months. Since octreotide induces chronic active gastritis, intragastric pH and serum gastrin were also determined before and during drug withdrawal. Results were compared to the respective pretreatment (pre-Tx) values. GH and insulin-like growth factor-I (IGF-I) increased after 4 weeks of octreotide withdrawal to pre-Tx values (GH, 12-h profile, 4.5 +/- 0.6, 2.6 +/- 0.7, and 5.6 +/- 1.1 micrograms/L; IGF-I, three samples, 3.4 +/- 0.4, 0.8 +/- 0.1, and 2.5 +/- 1.0 IU x 10(3)/L; means +/- SE, pre-Tx, on and off octreotide). A reduced insulin and augmented glucose response to oral glucose during therapy normalized after octreotide withdrawal (insulin, 527 +/- 84, 289 +/- 62, and 733 +/- 110 pmol/L; glucose, 6.2 +/- 0.3, 8.5 +/- 0.4, and 6.8 +/- 0.2 mmol/L; pre-Tx, on and off octreotide, means +/- SE). During octreotide treatment, the median 24-h intragastric pH value was 2.8 (pre-Tx pH not determined), and the median serum gastrin concentration (areas under the curve of 12-h profiles) was 1275 +/- 153 ng/L.12 h (n = 7). During octreotide withdrawal, pH decreased to 1.4, while serum gastrin increased to a median of 2937 +/- 472 ng/L.12 h. We conclude that GH and IGF-I suppression by long term octreotide therapy does not persist after drug withdrawal, indicating a need for life-long treatment. Octreotide-induced insulin suppression and glucose elevation are reversible. A high gastric pH during treatment may facilitate the development of octreotide-related gastritis. The gastrin increase during octreotide withdrawal probably reflects a response to chronic active gastritis after release from octreotide-induced gastrin inhibition.

Topics: Acromegaly; Adult; Aged; Blood Glucose; Female; Gastric Acidity Determination; Gastrins; Glucose Tolerance Test; Growth Hormone; Humans; Hydrogen-Ion Concentration; Insulin; Insulin-Like Growth Factor I; Male; Middle Aged; Octreotide

Acromegaly is rarely caused by the ectopic secretion of growth hormone releasing factor (GRF) from peripheral neuroendocrine tumours. We evaluated the ability of a recently developed somatostatin analogue (SMS 201-995, Sandoz) to reduce hormone levels and pituitary size in a young woman with acromegaly and Zollinger-Ellison syndrome secondary to a metastatic pancreatic islet cell tumour secreting GRF and gastrin. Gastrin, GRF, and growth hormone (GH) levels declined dramatically following the initiation of therapy with the analogue by continuous iv infusion. Although intermittent sc therapy was not effective in suppressing hormone levels, continuous sc infusion of SMS 201-995 has provided good control of both GRF and GH levels for nine months. Moreover, treatment with SMS 201-995 was associated with a substantial reduction in pituitary enlargement and an improvement in her gastric symptoms. Continuous sc infusion of SMS 201-995 may be useful in treating enlarged pituitaries resistant to other modes of therapy.

Topics: Acromegaly; Adenoma, Islet Cell; Adult; Female; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Octreotide; Pancreatic Neoplasms; Somatostatin; Zollinger-Ellison Syndrome

A young woman presented with acromegaly and amenorrhea-galactorrhea with hypersomatotropinemia and hyperprolactinemia. In addition, she had hypergastrinemia with abnormal secretory dynamics and evidence of a large pituitary tumor with suprasellar extension and erosion of the floor of the sella turcica. Evaluation of secretory diarrhea revealed a large abdominal tumor, which on removal was found to be a carcinoid of the jejunum. Postoperatively, the acromegaly, amenorrhea-galactorrhea, and hypergastrinemia resolved, and the pituitary returned to normal size, with regrowth of the sella floor. The carcinoid tumor was shown by immunoperoxidase staining to contain GH-releasing hormone.

Topics: Acromegaly; Adult; Amenorrhea; Carcinoid Tumor; Diarrhea; Female; Galactorrhea; Gastrins; Humans; Jejunal Neoplasms; Lactation Disorders; Paraneoplastic Endocrine Syndromes; Pituitary Gland; Pregnancy; Tomography, X-Ray Computed

A young woman with acromegaly and Zollinger-Ellison syndrome associated with a GH-releasing factor (GRF)- and gastrin-secreting metastatic islet cell carcinoma was studied by means of specific antisera which recognize various regions of the GRF molecule. Using specific immunohistochemical techniques, the tumor cells were shown to contain GRF, gastrin, and gastrin-releasing peptide, but not GH. During a 4-h period, plasma GRF levels averaged 5.6 +/- 1.4 ng/ml (+/- SD), while GH levels averaged 148 +/- 71 ng/ml. GH secretion was pulsatile and increased after TRH administration. GRF RIAs may be useful in establishing the diagnosis of acromegaly secondary to the ectopic secretion of GRF.

Topics: Acromegaly; Adenoma, Islet Cell; Adult; Female; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

Topics: Acromegaly; Adult; Female; Gastrins; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged

Topics: Acromegaly; Adenocarcinoma; Adolescent; Adult; Chromaffin System; Enterochromaffin Cells; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Stomach Neoplasms; Stomach Ulcer

Topics: Acromegaly; Adenoma; Adult; Female; Gastrins; Growth Hormone; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin

Topics: Acromegaly; Gastrins; Humans; Infusions, Parenteral; Somatostatin

Somatostatin, a peptide isolated from ovine hypothalami, prevents growth hormone secretion in vivo and in vitro. Moreover, somatostatin interferes with the secretion of various other hormones: TSH insulin, glucagon, gastrin, VIP and GIP. Under certain conditions a blunting effect on the secretion of prolactin and ACTH can be demonstrated.

Topics: Acromegaly; Animals; Digestive System; Exocrine Glands; Gastrins; Glucagon; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Insulin; Insulin Secretion; Pituitary Hormones, Anterior; Platelet Adhesiveness; Somatostatin; Thyrotropin

Topics: Acromegaly; Adrenocorticotropic Hormone; Animals; Gastrins; Glucagon; Gonadotropins; Humans; Infusions, Parenteral; Insulin; Pituitary Hormone-Releasing Hormones; Prolactin; Rats; Somatostatin; Thyrotropin

The development of radioimmunoassay by the late Solomon A. Berson and Rosalyn S. Yalow during the late 1950s represents a milestone in the history of the application of radionuclide methodology to biology and to medical investigation and practice. The method offers a technique to assay materials otherwise unmeasureable or detectable only with difficulty. Radioimmunoassay is based upon the competition between labeled and unlabeled antigen for specific antibody sites, forming antigen-antibody complexes. This reaction is described by the expression see journal for formula. At equilibirum, the radioactive complex (bound) is separated from the radioactive antigen (free). The B/F ratio is dependent upon the amount of nonradioactive antigen. Antigen concentration in unknown samples is determined by comparing the B/F ratio to the B/F ratios obtained by incubating varying amounts of known nonradioactive antigen with the same amount of antibody as in the unknown sample under similar assay conditions. Sensitivity of the order of 10-12 moles/liter may be achieved through the preparation and use of a labeled antigen of high specific activity and the production and selection of antisera with appropriately high affinity constants. Specificity is dependent upon the ability of the antiserum to recognize subtle structural features of the antigen molecule. The ability to conveniently assay large numbers of samples with good precision has led to the application of this technique to quantitate substances (such as steroids) already measurable but by more cumbersome methods. Since the initial description of competitive binding radioassay techniques, there have been numerous contributions to its further development, refinement, and application. This article reviews the conception and development of this invaluable contribution to our understanding of health and disease.

Topics: Acromegaly; Adrenocorticotropic Hormone; Amino Acid Sequence; Binding, Competitive; Calcitonin; Cell Membrane; Cross Reactions; Cytosol; Dose-Response Relationship, Drug; Female; Gastrins; Gonadotropins; Growth Hormone; Humans; Immune Sera; Insulin; Iodine Radioisotopes; Isotope Labeling; Male; Oxytocin; Parathyroid Hormone; Pregnancy; Proinsulin; Prolactin; Radioimmunoassay; Receptors, Cell Surface; Thyrotropin; Vasopressins

Oral glucose tolerance tests (OGTT) were performed for two subsequent days in 4 patients with active acromegaly, 2 patients with prolactin-producing pituitary adenomas and one insulinoma patient. Thirty minutes before the second OGTT 250 mug of somatostatin were injected intravenously as a bolus followed by a somatostatin infusion (500 mug) over 21/2 hours. The OGTTs were pathologic due to the hGH- and hPRL-induced insulin antagonism; they could not be normalized or improved by somatostatin. Only the peak of the blood sugar curve was shifted from one to two and a half hours after glucose administration; insulin and hGH levels were regularly suppressed after somatostatin whereas hPRL remained unchanged in most instances. Gastrin levels increased in all patients during the OGTT, the increase was suppressed in 4 patients. These findings show that the pathologic glucose tolerance due to insulin antagonism could not be improved by somatostatin in contrast to the deteriorated glucose tolerance in insulinopenic states.

Topics: Acromegaly; Adenoma, Islet Cell; Administration, Oral; Blood Glucose; Female; Gastrins; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Male; Pituitary Neoplasms; Prolactin; Somatostatin; Time Factors

Topics: Acromegaly; Anemia, Pernicious; Duodenal Neoplasms; Gastric Mucosa; Gastrins; Humans; Hyperparathyroidism; Pancreatic Neoplasms; Peptic Ulcer; Pyloric Antrum; Time Factors; Zollinger-Ellison Syndrome

Topics: Acromegaly; Dietary Proteins; Gastrectomy; Gastrins; Gastrointestinal Diseases; Humans; Kidney Diseases; Liver Cirrhosis; Peptic Ulcer; Radioimmunoassay; Stomach Neoplasms

Topics: Acromegaly; Adenoma; Adult; Anemia, Pernicious; Animals; Biopsy; Gastric Mucosa; Gastrins; Guinea Pigs; Histocytochemistry; Humans; Hyperparathyroidism; Microscopy, Electron; Rats; Zollinger-Ellison Syndrome