gastrins and Pituitary-Neoplasms

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

The familial aggregation of peptic ulcer disease has been well established, as has its association with such clear-cut genetic factors as blood group O and nonsecretor status. However, the genetics of this disorder, or group of disorders, is still in question. Polygenic inheritance is the prevailing hypothesis that has been proposed for peptic ulcer. This hypothesis was based primarily on the exclusion of a simple mode of inheritance for all ulcer disease. Genetic heterogeneity is an alternative hypothesis that can explain both the familial aggregation of peptic ulcer disease and the lack of a simple Mendelian pattern of inheritance. The evidence for genetic heterogeneity in peptic ulcer disease is reviewed, and studies are proposed to test this hypothesis.

Topics: ABO Blood-Group System; Antigens; Chromosome Aberrations; Chromosome Disorders; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Pepsinogens; Peptic Ulcer; Phenotype; Pituitary Neoplasms; Stomach Ulcer; Werner Syndrome

Topics: Adenoma, Islet Cell; Blood Glucose; Calcium; Endocrine System Diseases; Gastrins; Humans; Insulin; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Pheochromocytoma; Pituitary Neoplasms; Radioimmunoassay; Syndrome; Thyroid Neoplasms; Zollinger-Ellison Syndrome

A group of 13 consecutive regularly menstruating women who gained at least 5 kg the previous year (Group I) was compared to a control group of similar age, parity, and social class (Group II). The two groups were similar in estimated and observed food intakes; pre- and postprandial gastrin levels; hourly 24-h profiles of cortisol and insulin; urinary cortisol and 17-hydroxycorticosteroids. Group I had higher serum prolactin concentrations at all times than Group II (mean values 14.60 micrograms/l vs. 8.84 micrograms/l; p = .0121). Galactorrhea was observed in 5 women from Group I and in none of the women from Group II (p < .05). Group I also differed from Group II in a higher incidence of meaningful life-events the year preceding the study, higher prevalence of sexual dysfunction (9/13 vs. 4/13; p < .01) and higher indexes (p < .05) of several parameters in the MMPI and SCL 90. Median serum cortisol and prolactin concentrations were negatively correlated, both in Group I (R = -.669; p = .012) and in the whole sample (R = -.453; p = .0298). It is suggested that the rapid weight gain is part of a neuroendocrine response to environmental stimuli also characterized by hyperprolactinemia. The significant negative correlation between serum prolactin and cortisol indicates that this response differs from, and is possibly an alternative to, the sympathoadrenal "stress" response.

Topics: Adult; Energy Intake; Feeding Behavior; Female; Gastrins; Hormones; Humans; Hydrocortisone; Insulin; Life Change Events; Obesity; Personality Assessment; Pituitary Neoplasms; Prolactin; Prolactinoma; Pseudopregnancy; Psychophysiologic Disorders; Reference Values; Stress, Psychological; Weight Gain

Gastrin (G17) has a CCKB receptor-mediated growth-promoting effect on the AR42J rat acinar cell line that is linked to induction of both mitogen-activated protein kinase (MAPK) and c-fos gene expression. We investigated the mechanisms that regulate the growth factor action of G17 on the rat pituitary adenoma cell line GH3. Both AR42J and GH3 cells displayed equal levels of CCKB receptor expression and similar binding kinetics of 125I-labeled G17. G17 stimulation of cell proliferation was identical in both cell lines. G17 stimulation of GH3 cell proliferation was completely blocked by the CCKB receptor antagonist D2 but not by the MEK inhibitor PD-98059 or the protein kinase C inhibitor GF-109203X, which completely inhibited G17 induction of AR42J cell proliferation. G17 induced a c-fos SRE-luciferase reporter gene plasmid more than fourfold in the AR42J cells, whereas it had no effect in the GH3 cells. In contrast to what we observed in the AR42J cells, G17 failed to stimulate MAPK activation and Shc tyrosyl phosphorylation and association with the adapter protein Grb2. Epidermal growth factor induced the MAPK pathway in the GH3 cells, demonstrating the integrity of this signaling system. G17 induced Ca2+ mobilization in both the GH3 and AR42J cells. The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited AR42J cell proliferation by 20%, whereas it completely blocked G17 induction of GH3 cell growth. The Ca2+ ionophore ionomycin stimulated GH3 cell proliferation to a level similar to that observed in response to G17, but it had no effect on AR42J cell proliferation. Thus there are cell type specific differences in the requirement of the MAPK pathway for the growth factor action of G17. Whereas in the AR42J cells G17 stimulates cell growth through activation of MAPK and c-fos gene expression, in the GH3 cells, G17 fails to activate MAPK, and it induces cell proliferation through Ca2+-dependent signaling pathways. Furthermore, induction of Ca2+ mobilization in the AR42J cells appears not to be sufficient to sustain cell proliferation.

Topics: Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport; Adenoma; Animals; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinases; Cell Division; Cell Line; Enzyme Activation; Epidermal Growth Factor; Gastrins; Gene Expression; Growth Substances; Pancreas; Phosphorylation; Pituitary Neoplasms; Protein Kinase C; Proteins; Proto-Oncogene Proteins c-fos; Rats; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Shc Signaling Adaptor Proteins; Src Homology 2 Domain-Containing, Transforming Protein 1

Interferon-alpha (IFN alpha) may exert direct inhibitory effects on cell proliferation and on the production of different peptide hormones. We investigated the effect of IFN alpha on hormone production by 15 GH-secreting pituitary adenomas, 4 clinically nonfunctioning or gonadotroph pituitary adenomas, and 4 prolactinomas in vitro. In the GH-secreting pituitary adenoma cultures, a short term (72-h) incubation with IFN alpha (50-100 U/mL) significantly inhibited GH secretion in 3 of 7 cases and PRL secretion in 6 of 7 cultures. During prolonged incubation (14 days) with IFN alpha, GH and/or PRL secretion was significantly inhibited in 7 of 8 cultures (GH, 17-78% inhibition; PRL, 39-88% inhibition). In the clinically nonfunctioning or gonadotroph cultures, incubation with IFN alpha resulted in inhibition of the secretion of gonadotropins and/or alpha-subunit in all cases (27-62%), whereas in the prolactinoma cultures PRL secretion was inhibited by IFN alpha in all cases (37-76%). The effect of IFN alpha was additive to the inhibitory effects of the dopamine agonist bromocriptine (10 nmol/L) or the somatostatin analog octreotide (10 nmol/L). The inhibition of hormone secretion by IFN alpha was accompanied by inhibition of the intracellular hormone concentrations. The effect of IFN alpha was dose dependent, with an IC50 for inhibition of hormone secretion of 2.3 +/- 0.3 U/mL (n = 5), which is relatively low compared with the concentrations that are reached in patients treated with IFN alpha for various malignancies. In conclusion, the potent antihormonal effect of IFN alpha on cultured pituitary adenomas suggests that this drug might be of benefit in the treatment of selected patients with secreting pituitary adenomas. As treatment with IFN alpha is associated with considerable adverse reactions, studies with this drug should only be considered in inoperable, invasive aggressive, and dopamine agonist- and/or somatostatin analog-resistant functioning pituitary macroadenomas.

Topics: Adenoma; Bromocriptine; Dopamine Agonists; Gastrinoma; Gastrins; Human Growth Hormone; Humans; Insulin; Insulin Secretion; Insulinoma; Interferon alpha-2; Interferon-alpha; Octreotide; Pancreatic Neoplasms; Pituitary Neoplasms; Prolactin; Prolactinoma; Recombinant Proteins; Somatostatin; Tumor Cells, Cultured

A 48-year-old male with type A atrophic gastritis developed multiple gastric carcinoids and a pituitary adenoma. Laboratory tests revealed high levels of serum gastrin and growth hormone (GH). He underwent subtotal gastrectomy, resulting in a return of the previously elevated gastrin level to normal. Serum GH concentration remained high. Three months after the surgery, the pituitary tumor, composed greatly of GH-immunoreactive cells, was partially removed. Since hypergastrinemia plays a pivotal role in gastric carcinoid formation and induces GH-releasing factor (GHRH) release resulting in GH-producing pituitary tumor formation, GH-producing pituitary adenoma might be a clinical manifestation in type A gastritis.

Topics: Adenoma; Carcinoid Tumor; Follow-Up Studies; Gastrectomy; Gastrins; Gastritis, Atrophic; Gastroscopy; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasms, Multiple Primary; Pituitary Neoplasms; Stomach Neoplasms; Tomography, X-Ray Computed

We have investigated the prevalence of MEN 1 in patients with recognized pituitary adenomas. Since hyperparathyroidism is present in nearly 95-100% of patients with MEN 1 and frequently is the first condition to be identified, the study was limited to the identification of patients with hyperparathyroidism while the screening for gastroenteropancreatic (GEP) lesions was carried out in patients with both pituitary and parathyroid lesions.. Serum total and ionized calcium, phosphate and intact PTH 1-84 (EASIA) were measured in 166 patients (68 with non-functioning pituitary adenoma, 42 with prolactinoma, 35 with GH-secreting adenoma, 17-with ACTH-screening adenoma, 1 with TSH-secreting adenoma, 1 with FSH-secreting adenoma and 2 with an only alpha-subunit secreting adenoma) referred to our clinic from 1990 to 1996. Plasma gastrin, somatostatin, pancreatic polypeptide and vasoactive intestinal peptide were measured by RIA in patients with hyperparathyroidism.. Eight of 166 patients (4.8%) were found to have primary hyperparathyroidism and among these 2 also had a gastrinoma while there was no evidence of other GEP tumours. Considering the tumour type, 6 had prolactinoma (14.3%), 1 GH-secreting adenoma (2.8%) and 1 non-functioning adenoma (1.5%). In most patients the diagnosis of pituitary tumour was made several years before that of hyperparathyroidism (from 1 to 15 years) although 6 patients had previously suffered from urolithiasis and one had undergone gastric resections for recurrent peptic ulcers. One patient was identified as a MEN 1 gene carrier and 2 had relatives with signs and symptoms referable to parathyroid or GEP lesions.. The study shows a prevalence of 4.8% of primary hyperparathyroidism in unselected patients with known pituitary tumours similar to that reported in a previous study. By contrast, the prevalence of MEN 1 in patients with prolactinoma was definitely high (14.3%). In most patients the diagnosis of pituitary tumours was made several years before that of hyperparathyroidism. Although the patients were believed to harbour a sporadic pituitary tumour, most of them had had signs and/or symptoms referable to one or both of the other organs involved in MEN 1, often concomitantly with those of pituitary tumours. These data indicate that the diagnosis of MEN 1 syndrome is missed in a substantial proportion of patients with prolactinomas and therefore the screening of these patients for the syndrome is strongly recommended.

Topics: Adenoma; Adolescent; Adult; Aged; Biomarkers; Calcium; Female; Gastrinoma; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreatic Polypeptide; Parathyroid Hormone; Phosphates; Pituitary Neoplasms; Prevalence; Prolactinoma; Somatostatin; Vasoactive Intestinal Peptide

A case of MEN type I in a 64-year-old man is reported. He had undergone partial duodenectomy because of gastric ulcer and multiple duodenal polyps (gastrin secreting carcinoid). Blood examination revealed hypercalcemia, hyperPTHemia, and hyperprolactinemia. Neck US and CT showed enlargement of 4 parathyroid glands. Brain MRI revealed the microadenoma in left pituitary gland. Total parathyroidectomy with auto-transplantation in the left forearm were performed. Histological examination showed the hyperplasia of the parathyroid. Three and a half year after parathyroidectomy, there was no evidence of recurrence of gastrin secreting tumor and hyperparathyroidism, and enlargement of pituitary microadenoma. This is the first MEN type I case in Japan which have detected 3 endocrine tumors clinically with gastrin secreting duodenal carcinoid.

Topics: Adenoma; Carcinoid Tumor; Duodenal Neoplasms; Gastrins; Humans; Hyperparathyroidism; Hyperplasia; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Parathyroid Glands; Pituitary Neoplasms; Prolactin

Several reports have shown an increase in serum gastrin levels in patients with Cushing's syndrome (CS). However, the actual origin of this hypergastrinaemia is not known. Two hypotheses have been proposed: concomitant ACTH and gastrin secretion by corticotrophic pituitary adenomas or hypergastrinaemia induced by hypercortisolism.. We performed simultaneous, bilateral inferior petrosal sinus (IPS) sampling in nine patients with Cushing's disease (CD), proven by histological studies. In all of them, blood samples were taken from both IPS and a peripheral vein to measure plasma ACTH and serum gastrin. In addition, we measured peripheral serum gastrin levels after an overnight fast in 10 patients with CS (seven with pituitary tumours and three with adrenal tumours) before and after surgical treatment.. Petrosal-peripheral and interpetrosal gradients of ACTH were higher than 2.0 and 1.4, respectively, confirming the pituitary origin of ACTH. Mean serum gastrin levels were 149.1 +/- 53.6 ng/l in peripheral vein, 183.4 +/- 71.7 ng/l in dominant IPS and 181.4 +/- 68.9 ng/l in non-dominant IPS. No significant differences in gastrin concentrations in these locations were found. Mean preoperative gastrin level in patients with CD was 194.6 +/- 47.9 ng/l, whereas in patients with adrenal tumours it was 247.3 +/- 125.9 ng/l. After surgical treatment, the gastrin levels decreased to 62.1 +/- 13.2 ng/l (P < 0.05) and 90.3 +/- 50.3 ng/l (NS), respectively.. These results suggest that hypergastrinaemia is a common finding in patients with Cushing's syndrome. The lack of significant petrosal-peripheral gradient in individuals with Cushing's disease and the reduction in gastrin level following adrenal tumour resection argues against the hypothesis of a predominantly pituitary source of gastrin, suggesting a glucocorticoid related mechanism as an explanation for the hypergastrinaemia.

Topics: Adenoma; Adolescent; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Female; Gastrins; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary Gland; Pituitary Neoplasms; Postoperative Period

Cholecystokinin (CCK) is detected in pituitary tumors but its role remains unknown. On the hypothesis that CCK may facilitate the cell growth in pituitary tumors, we have examined the effect of CCK on cell growth using a rat pituitary tumor cell line, GH3, cultured in a serum-free, chemically defined medium. Addition of sulfated CCK-(26-33) (CCK-8) in two different concentrations (0.5 approximately 1 nM) caused a significant increase in the number of GH3 cells. The antagonist (1 microM) for CCK-B receptor, but not CCK-A receptor, significantly inhibited the number of GH3 cells. Northern blot analysis revealed a significant expression of CCK-B receptor mRNA in GH3 cells, but not in normal rat pituitary glands. In addition, immunoreactive CCK/gastrin was detected by RIA in the GH3 cell extracts as well as the serum-free culture medium. In GH3 cell extracts, both CCK-8 and gastrin like peptides were identified by gel chromatography. These findings provided the first evidence for an autocrine/paracrine role of CCK and gastrin on stimulation of GH3 cell growth through the CCK-B receptor.

Topics: Animals; Blotting, Northern; Cell Division; Cholecystokinin; Chromatography, Gel; Dose-Response Relationship, Drug; Gastrins; Pituitary Neoplasms; Radioimmunoassay; Rats; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Time Factors; Tumor Cells, Cultured

Biologically active peptide hormones are synthesized from larger precursor proteins by a variety of posttranslational processing reactions. Endoproteolytic cleavage at the Lys74-Lys75 dibasic processing site of progastrin is the major determinant for the relative distribution of gastrin heptadecapeptide and tetratriacontapeptide in tissues. Thus, we explored the ability of two prohormone convertases, PC1/PC3 and PC2, to cleave this important site within progastrin. We expressed wild-type human gastrin cDNA and mutant cDNAs in which the Lys74Lys75 site was changed to Lys74Arg75, Arg74Arg75, and Arg74Lys75 residues in AtT-20 cells. Because AtT-20 cells express Pc1/PC3 but not PC2, we also coexpressed a cDNA encoding PC2 in both wild-type and mutant gastrin-producing AtT-20 cells. Wild-type Lys74Lys75 and mutant Arg74Arg75 progastrin processing sites were efficiently cleaved in AtT-20 cells only after coexpression of PC2. Mutant Lys74Arg75 progastrin was readily processed in cells in the presence or absence of PC2 coexpression, but, in contrast, mutant Arg74Lys75 progastrin was inefficiently cleaved regardless of PC2 coexpression. Northern analysis revealed the presence of PC2 but not PC1/ PC3 in canine antral gastrin-producing G cells. These data suggest that PC2 but not PC1/PC3 is responsible for the cleavage of the Lys74Lys75 site in wild-type progastrin.

Topics: Amino Acid Sequence; Animals; Arginine; Cell Line; Cell Line, Transformed; Dogs; Furin; Gastrins; Humans; Lysine; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Pituitary Neoplasms; Protein Precursors; Protein Processing, Post-Translational; Recombinant Proteins; Substrate Specificity; Subtilisins; Transfection; Tumor Cells, Cultured

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocortical Hyperfunction; Aged; Carcinoma; Carcinoma, Papillary; Female; Gastrins; Humans; Hypercalcemia; Hypothyroidism; Multiple Endocrine Neoplasia; Pituitary Neoplasms; Thyroid Neoplasms

Detection of subjects from a multiple endocrine neoplasia type 1 family must rest on clinical, biochemical and radiological data, since study of the genome is unable to detect these subjects. In the new family described here, 6 out of the 14 subjects explored were affected. One had a confirmed pancreatic endocrine tumour and in 3 others a pancreatic endocrine tumour was highly probable, since insulin and glucagon levels, as well as ultrasonic exploration of the pancreas were pathological. Measurements of gastrointestinal hormones gave normal results in all cases. We conclude that to detect this endocrine neoplasia in subjects at risk it seems necessary to measure plasma insulin levels and perform an abdominal ultrasonography.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Child; Female; Gastrins; Glucagon; Humans; Insulin; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Pituitary Neoplasms; Risk Factors; Substance P; Ultrasonography; Vasoactive Intestinal Peptide

The presence of gastrin in pituitary tissue as well as gastrin hypersecretion by some pituitary adenomas have been documented using different methodological approaches. In the present study, serum gastrin levels were measured in 93 patients with nonfunctioning pituitary adenoma, i.e. a condition lacking a reliable marker of the disease. Elevated gastrin levels (85-2, 180 ng/l; normal range: 15-80 ng/l) were found in 14/93 patients (15%), the highest values being observed in one patient with MEN I syndrome. In all but MEN I hypergastrinemic patient, a severe gastric hypochlorhydria (Basal Acid Output: 0.04 +/- 0.1 mmol H+/h) unresponsive to pentagastrin (Maximum Acid Output: 0.1 +/- 0.2 mmol H+/h) was seen. Secretin injection caused gastrin to increase in the patient with MEN I and in another hypergastrinemic patient. Antiparietal cells autoantibodies were positive in 3/11 patients. No changes in gastrin concentrations were found after administration of several agents usually employed in the evaluation of pituitary function, except a significant gastrin reduction after octreotide injection. In two hypergastrinemic patients who underwent pituitary adenomectomy, the high gastrin levels did not change after surgery. Finally, gastrin was undetectable in the culture media of 15 pituitary adenomas surgically removed from both normo- and hypergastrinemic patients and immunocytological studies of tumor cells did not show any gastrin staining. In conclusion, although in patients with pituitary adenomas serum gastrin evaluation is indicated in order to document the presence of a MEN I syndrome, the present data show that high gastrin levels cannot be taken as a specific marker of nonfunctioning pituitary adenomas unless the peripheral origin of hypergastrinemia is excluded.

Topics: Adenoma; Adult; Aged; Analysis of Variance; Biomarkers, Tumor; Bromocriptine; Corticotropin-Releasing Hormone; Female; Gastrins; Gonadotropin-Releasing Hormone; Growth Hormone-Releasing Hormone; Humans; Male; Middle Aged; Octreotide; Pentagastrin; Pituitary Gland; Pituitary Neoplasms; Secretin; Thyrotropin-Releasing Hormone

A 74-year-old acromegalic found to have an intrasellar gangliocytocytoma and GH-secreting pituitary adenoma is described. The gangliocytoma contained immunoreactive gastrin and, to a lesser extent, GHRH, and the adenoma immunostained for GH. Gastrin has not been previously reported in hypothalamic gangliocytomas. Since this peptide has been demonstrated in normal hypothalamus and pituitary, and provokes GH release when administered intraventricularly, it may have caused GHRH release from the gangliocytoma by a local paracrine action and led to adenoma formation and acromegaly.

Topics: Adenoma; Aged; Ganglioneuroma; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Hypothalamic Neoplasms; Male; Neoplasms, Multiple Primary; Pituitary Neoplasms

Six patients were studied with pituitary adenomas and elevated concentrations of gastrin similar to those found in cases of benign antral gastrinoma syndrome. Chromatography of the serum using Sephadex-G50 revealed different molecular forms of gastrin according to the type of adenomas. In those cases of acromegaly and gonadotrophinoma, gastrin-34 and unsulphated gastrins constitute the predominant forms. In contrast, in cases of Cushing's disease, gastrin-17, sulphated as well as non-sulphated were the predominant types; the chromatographic pattern was similar to that observed in two patients with antral gastrinoma syndrome who acted as controls. These findings demonstrate that pituitary adenomas might secrete gastrin. Taking into account that gastrin-34 and unsulphated gastrins were the predominant forms in cases of acromegaly, gonadotrophinoma and non-functioning adenoma, it is assumed that those molecular forms are mainly produced in the anterior lobe of the hypophysis. Conversely, gastrin-17 was the principal molecular form in cases of Cushing's disease confirming the close relationship of the synthesis of gastrin and corticotrophin peptides. The cases with Cushing's disease exhibited a serum gastrin pattern similar to that observed in the two cases with antral syndrome in which the predominant immunoreactive form of gastrin in gastrin-17 exhibiting a degree of sulphation corresponding to that of antral gastrin. It is concluded that the circulating excess of gastrin originated in the pituitary tumour tissue and the molecular form varied with the type of pituitary adenoma.

Topics: Adenoma; Adult; Chromatography, Gel; Female; Gastrins; Humans; Male; Middle Aged; Pituitary Hormones; Pituitary Hormones, Anterior; Pituitary Neoplasms; Protein Precursors

Twelve of 87 pituitary adenomas from patients with acromegaly, Cushing's syndrome. Nelson's syndrome, hyperprolactinaemia and without symptoms of hormone hypersecretion contained gastrin in concentrations from 0.5 to 166 pmol/g. Only ACTH-producing tumours contained gastrin, which occurred in forms smaller than those present in the normal adenohypophysis. The results indicate that corticotropic tumours may synthesize gastrin in moderate amounts.

Topics: Adenoma; Chromatography, Gel; Gastrins; Humans; Molecular Conformation; Pituitary Gland, Anterior; Pituitary Neoplasms; Radioimmunoassay

Results of preparathyroidectomy and postparathyroidectomy studies in a patient with multiple endocrine neoplasia type I and gastrinoma suggest that hyperparathyroidism unmasks occult gastrinoma and related secretory abnormalities. Three of four diagnostic findings were later obscured by parathyroidectomy and normalization of serum calcium concentration. Basal acid output, basal acid output/maximal acid output ratio, and serum gastrin concentration were decreased from values consistent with gastrinoma to normal. The secretin stimulation test, though still positive, was attenuated. These observations suggest that in multiple endocrine neoplasia type I, normal values for serum gastrin concentration, gastric secretion, and secretin stimulation may not exclude gastrinoma. The investigations clarify the interpretation of a voluminous but confusing literature on the interrelationship between hyperparathyroidism and altered gastric function in the presence or absence of Zollinger-Ellison syndrome.

Topics: Adenoma; Adult; Calcium; Drug Interactions; Female; Gastric Acid; Gastrins; Humans; Hyperparathyroidism; Multiple Endocrine Neoplasia; Parathyroid Hormone; Pituitary Neoplasms; Secretin; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Neuroendocrine tumours of the lung and gut are known to possess bombesin-like immunoreactivity. The recent observation that gastrin releasing peptide (GRP), a 27 amino acid peptide isolated from the porcine intestine, may be the mammalian analogue of bombesin led us to look for this peptide in a variety of human neoplasms. Formalin-fixed tissues from 85 tumours were examined by the immunoperoxidase technique, using specific antisera to the GRP molecule (1-27) and the GRP fragment (1-16). Intense cytoplasmic GRP immunoreactivity was seen in thyroid medullary carcinomas (3/3), carcinoids of lung, pancreas, and intestine (22/36), and paragangliomas (2/3). Less frequent staining was present in pulmonary small cell (oat cell) carcinomas (1/8) and pituitary adenomas (1/6). Complete absence of immunoreactivity was observed in three phaeochromocytomas, five Merkel cell tumours, six neuroblastomas and 15 non-neuroendocrine tumours. Normal neuroendocrine cells of the thyroid (C-cells) and bronchial mucosa (Kulchitsky cells) exhibited GRP immunoreactivity; nerve fibres from all sites failed to demonstrate staining for GRP. In each positive case, the pattern of staining for GRP (1-27) and GRP (1-16) was identical, although the GRP (1-16) immunostaining was weaker. These findings indicate that bombesin immunoreactivity in human neuroendocrine cells and tumours is attributable to GRP-like molecules and that GRP is a useful marker of neuroendocrine differentiation in many tumours.

Topics: Adenoma; Adrenal Gland Neoplasms; Amino Acid Sequence; Bombesin; Carcinoid Tumor; Carcinoma, Small Cell; Gastrin-Releasing Peptide; Gastrins; Humans; Intestinal Neoplasms; Lung Neoplasms; Neoplasms; Neurosecretory Systems; Pancreatic Neoplasms; Peptides; Pheochromocytoma; Pituitary Neoplasms; Thyroid Neoplasms

Immunohistochemical and histological investigations were undertaken on 24 surgically-removed pituitary adenomas. By histology (haemalu-eosin staining), 7 chromophobe, 12 acidophil and 5 basophil pituitary adenomas were revealed. For immunohistochemical purposes the peroxidase-antiperoxidase technique was applied. Primary antisera against 10 hormones were used. By immunohistochemistry, 7 prolactin-containing, 2 TSH-containing, 2 GH-containing and 1 beta-endorphin-containing pituitary adenomas were identified. Furthermore, 1 mixed thyrotropic-prolactin human pituitary adenoma was detected. A possible connection between histological and immunocytochemical findings is discussed.

Topics: Adenoma; Cholecystokinin; Gastrins; Glucagon; Hormones, Ectopic; Humans; Immunoenzyme Techniques; Insulin; Insulin Secretion; Paraneoplastic Endocrine Syndromes; Pituitary Gland; Pituitary Hormones; Pituitary Neoplasms

The role of radioimmunoassay (RIA) in the diagnosis and management of endocrine tumors, such as pituitary tumors, insulinomas, and gastrinomas, has long been well established. A variety of nonendocrine tumors are capable of elaborating one or more humoral substances that resemble immunologically well-known, well-characterized biologically active hormones or their prohormone precursors or metabolic products. The possible value of mass screening for carcinoma of the lung by the detection of precursor adrenocorticotropic hormone (ACTH) in plasma was tested. However, the usefulness was limited by the potential for false-positive, i.e., elevation of marker concentration in the plasma of heavy smokers even in the absence of invasive carcinoma. Although on occasion a dramatic decrease of plasma ACTH after surgical resection or on some chemotherapeutic schedules has been observed, this does not occur with sufficient regularity to serve definitely as an objective measure of efficacy of therapy. The limitations of nonhormonal tumor markers, such as carcinoembryonic antigen (CEA), are also considered.

Topics: Adrenocorticotropic Hormone; Animals; Diagnosis, Differential; Endocrine System Diseases; Gastrins; Humans; Insulin; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Pituitary Neoplasms; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adult; Gastrins; Humans; Hyperparathyroidism, Secondary; Male; Multiple Endocrine Neoplasia; Parathyroid Hormone; Parathyroid Neoplasms; Pituitary Neoplasms; Prolactin; Zollinger-Ellison Syndrome

The radioimmunoassay technique, first developed for the determination of hormones, has been applied to many substances of biologic interest by clinical and research laboratories around the world. It has had an enormous effect in medicine and biology as a diagnostic tool, a guide to therapy, and a probe for the fine structure of biologic systems. For instance, the assays of insulin, gastrin, secretin, prolactin, and certain tissue-specific enzymes have been invaluable in patient care. Further refinements of current methods, as well as the emergence of new immunoassay techniques, are expected to enhance precision, specificity, reliability, and convenience of the radioimmunoassay in both clinical and research laboratories.

Topics: Acid Phosphatase; Amylases; Animals; Cimetidine; Creatine Kinase; Dogs; Female; Gastrins; Hexosaminidases; Hormones, Ectopic; Humans; Hyperthyroidism; Insulin; L-Lactate Dehydrogenase; Middle Aged; Pancreatic Elastase; Pepsinogens; Peptic Ulcer; Peptides; Pituitary Neoplasms; Prolactin; Radioimmunoassay; Secretin; Species Specificity; Swine; Thyrotropin; Thyrotropin-Releasing Hormone

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

The authors present a brief report on a familial case of Wermer's syndrome, and review the principal characteristics of this "multiple endocrine neoplasm" which usually affects the parathyroids, pancreas, and anterior pituitary.

Topics: Adult; Female; Gastrins; Glucagon; Humans; Insulin; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Pituitary Neoplasms; Syndrome; Vasoactive Intestinal Peptide

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: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adult; Aged; Biopsy; Carcinoid Tumor; Female; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Male; Microscopy, Electron; Middle Aged; Pedigree; Pituitary Neoplasms; Prospective Studies; Pyloric Antrum; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenoma; Adolescent; Adrenal Gland Neoplasms; Adult; Calcium; Diabetes Complications; Female; Gastrins; Humans; Hyperparathyroidism, Secondary; Male; Parathyroid Diseases; Parathyroid Neoplasms; Pituitary Neoplasms

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adult; Aged; Biological Assay; Female; Gastrectomy; Gastric Acidity Determination; Gastrins; Humans; Hyperinsulinism; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Peptic Ulcer; Pituitary Neoplasms; Radiography; Thyroid Neoplasms; Zollinger-Ellison Syndrome