Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relatives of 25 index patients with primary parathyroid hyperplasia were tested for hypercalcemia. At least 13 of these patients had one or more first degree relatives with hypercalcemia. Two familial syndromes each with autosomal dominant transmission were recognized. Two index patients were part of large kindreds categorized as having familial hypocalciuric hypercalcemia (FHH). Manifestations of multiple endocrine neoplasia type I were present in the kindreds of at least four other index patients (FMEN I). In seven other kindreds there were too few affected members to allow definitive classification. Differences between manifestations of FHH and FMEN I were described. Among offspring of affected persons in kindreds with FHH, as distinct from FMEN I, the prevalence of hypercalcemia approached the theoretic maximum of 50 per cent during the first two decades. In FHH, nephrolithiasis and peptic disease were unusual; moderate hypercalcemia occurred without hypercalciuria; and subtotal parathyroidectomy did not abolish hypercalcemia. Concentrations of peptide hormones other than parathyroid hormone (PTH) were normal in those with FHH; in FMEN I high concentrations of glucagon in plasma were found in five of six patients tested, and high concentrations of gastrin were found in three of 12 patients. Hypergastrinemia generally accompanied obvious peptic disease. Distinction of the two conditions is important since patients with FHH may not benefit from subtotal parathyroidectomy, but they generally have a better clinical prognosis than do patients with FMEN I.
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PMID:Family studies in patients with primary parathyroid hyperplasia. 87 Nov 27

A case of giant metastatic liver VIPoma manifesting WDHA syndrome is described. The patient was a 33-year-old Japanese male who was admitted because of persisting watery diarrhea and weight loss. Laboratory examinations revealed marked hypokalemia, mild hypercalcemia and highly elevated plasma vasoactive intestinal peptide (VIP) and glucagon levels. Intensive imaging examinations disclosed two large tumors in the liver but not in other organs, including the pancreas. Laparoscopy disclosed a slightly elevated purplish-colored large tumor on the surface of the apparently normal liver. At operation, however, a small hard nodule was observed in the tail of the pancreas. Histologically, it was revealed to be a VIPoma resembling a carcinoid or an islet cell tumor, and was identical to the liver tumors. Thus, this neoplasm was considered to be a VIPoma of pancreatic origin, with metastatic lesions in the liver.
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PMID:Giant metastatic VIPoma in the liver. 165 53

In the submitted review the author pays attention to mechanisms of control of insulin secretion and the mutual interaction of other messengers (cAMP, calcium and inisitol triphosphate) with special attention to the calcium signal which plays a most important role in the stimulation of the excitable B cell. The trigger of the two-stage insulin secretion is cyclic accumulation of calcium in the cytosol of the B cell and the mutual harmony between calcium of the intra- and extracellular compartment. In the early stage of insulin secretion in particular the intracellular compartment is the source of calcium; from there the ion is released due to the action of inositol triphosphate (IP3) activated by phospholipase C. Calcium of the extracellular compartment is mobilized also in the early secretory stage by opening of the depolarization-dependent calcium channels, it plays, however, a more important part during the second stage. Activation of the other messengers, incl. the calcium signal, depends on the type of secretagogue stimulus. During systemic changes of calcium homeostasis in vivo the calcium signal of the B cell is activated or inhibited in different ways. In the course of hypercalcaemia, in particular if acute, the direct influence of calcium ions on insulin secretion is modulated by further factors, e.g. somatostatin, calcitonin, cholecystokinin, glucagon, adrenocortical hormones, opioids and other substances released into the blood stream. In chronic hypercalcaemia which is the result of primary hyperparathyroidism or vitamin D intoxication the action of calcium on the metabolic and hormonal response is enhanced by the ionophoretic action of parathormone or active vitamin D metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The calcium signal in the regulation of insulin secretion]. 269 62

Evidence is increasing that many anesthetics and cardiovascular agents alter cellular Ca kinetics and flux. In prior work we demonstrated that the tachycardic effects of glucagon were significantly blunted by Ca channel blockade, but not by beta adrenergic receptor blockade. Thus, the chronotropic effects of glucagon may be dependent upon extracellular Ca levels. Based upon these observations, we tested the hypothesis that changes in circulating ionized Ca concentrations may alter glucagon's ability to increase heart rate in rats. In conscious normocalcemic rats, glucagon's tachycardic actions were dose related with peak effects obtained at 1 to 2 min and persisting approximately 10 min after 1.0 mg/kg of glucagon. The effects of altered Ca levels on glucagon tachycardia were evaluated in three groups of rats: 1) rats rendered hypercalcemic by the infusion of Ca chloride (10, 50 or 100 mg/ml/hr); 2) rats rendered hypocalcemic by infusion of the Ca chelator EDTA (15 or 30 mg/ml/hr); and 3) normocalcemic rats infused with saline. Normocalcemic rats had a mean ionized Ca level of 4.73 mg/dl. In rats, increasing Ca chloride doses resulted in increasing mean serum ionized Ca levels (5.24, 8.35 and 15.2 mg/dl, respectively), whereas increasing doses of EDTA produced progressive decreases in mean ionized Ca (3.62 and 2.13 mg/dl, respectively). Severe hypo (2.13 mg/dl)- or hypercalcemia (15.2 mg/dl) significantly blunted glucagon's chronotropic action (51 and 44%, respectively). From these data, we conclude that glucagon has its maximal tachycardic action at physiologic Ca levels (being blunted by both hyper- and hypocalcemia), indicating that this effect of glucagon is Ca dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucagon's chronotropic action is calcium dependent. 288 9

A case of prostatic carcinoma with the cellular patterns of an adenocarcinoma and carcinoid tumor is reported. The tumor contained ultrastructural dense core neuroendocrine granules, and immunoperoxidase staining revealed prostatic acid phosphatase, prostatic-specific antigen, chromogranin, neuron-specific enolase, serotonin, adrenocorticotrophic hormone (ACTH), somatostatin, parathormone, calcitonin, bombesin, and glucagon but no insulin. The patient had exhibited hypercalcemia that may have been related to hormone production by the tumor. The literature on the endocrine aspect of the prostate and its tumor is reviewed.
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PMID:Prostatic carcinoma with endocrine features. A report of a neoplasm containing multiple immunoreactive hormonal substances. 289 Dec 93

To further gain insights into the mechanisms underlying impaired urine concentration in hypercalcemia, effects of increasing Ca2+ concentrations in the incubation medium on cAMP production in response to 10(-8) M arginine vasopression (AVP) were examined in thick ascending limbs of Henle (MTAL) and collecting tubules (MCT) dissected from outer medulla of mouse kidney. Increasing Ca2+ in the incubation medium from 1.0 mM to either 2.0 mM or 5.0 mM inhibited AVP-dependent cAMP production in MTAL but not in MCT. This inhibition of AVP-dependent cAMP production by 2.0 mM Ca2+ in MTAL was not reversed by verapamil or diltiazem. Also, Ca2+ ionophore A23187 did not inhibit AVP-dependent cAMP production in MTAL in the presence of 1.0 mM Ca2+. Increasing medium Ca2+ from 1.0 to 5.0 mM inhibited cAMP production in MTAL in response to both glucagon and forskolin by the magnitude comparable to that seen in response to AVP. These results show that high Ca2+ inhibits AVP-dependent cAMP production only in MTAL and not in MCT. In addition, the lack of effects of Ca2+ channel blockers and Ca2+ ionophore suggests that high ambient Ca2+ per se may inhibit AVP-dependent cAMP production in MTAL. The fact that high Ca2+ also suppressed cAMP production in response to glucagon or forskolin suggests that Ca2+ may inhibit AVP-dependent adenylate cyclase at postreceptor site(s), one of which is the catalytic unit of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High Ca2+ inhibits AVP-dependent cAMP production in thick ascending limbs of Henle. 301 Jul 37

The present study was undertaken to investigate the cAMP system in isolated vasopressin (AVP)-sensitive segments of the hypercalcemic rat. Hypercalcemia was produced by supplementation of diet with dihydrotachysterol, achieving a mean serum calcium of 12.6 mg%. Maximal urinary concentration was only 1982 +/- 119 mOsm/kg H2O in pair, watered hypercalcemic rats when compared to 2478 +/- 93 mOsm/kg H2O in controls (N = 7) (P less than 0.01). Vasopressin stimulated adenylate cyclase activity at concentrations of vasopressin between 10(-9) and 10(-7) M was indistinguishable in the outer medullary collecting duct (OMCD) and inner medullary collecting duct (IMCD) of tubules dissected from hypercalcemic rats or normocalcemic rats. Likewise, in situ cAMP accumulation in response to 10(-7) M AVP was not significantly different in either OMCD or IMCD of hypercalcemic or normocalcemic rats at either isotonic or hypertonic media conditions. In contrast, while 10(-7) M AVP significantly (P less than 0.05) increased cAMP accumulation in the medullary ascending limb (MAL) of normocalcemic rats it failed to do so in the MAL of hypercalcemic rats. This failure to accumulate cAMP appears to be due to impairment in AVP-stimulated adenylate cyclase rather than to enhanced phosphodiesterase activity. A similar decrement in glucagon stimulated adenylate cyclase occurred with 10(-6) M glucagon. The results demonstrate that in chronic hypercalcemia the cAMP system in the OMCT and IMCD of the rat is intact, but the MAL demonstrates abnormal AVP responsiveness due to impaired adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cAMP system in vasopressin-sensitive nephron segments of the vitamin D-treated rat. 303 55

Plasma insulin dynamics were evaluated in 10 patients with primary hyperparathyroidism before and after parathyroidectomy and correction of hypercalcemia. Before surgery fasting plasma insulin concentrations and insulin responses to administered glucose, tolbutamide, and glucagon were significantly greater than postoperative values. Hyperinsulinemia was not associated with altered glucose curves during glucose or glucagon tolerance tests, but a relatively greater insulin response to tolbutamide resulted in an increased hypoglycemic effect following its administration. The glucose-lowering action of intravenous insulin was slightly impaired before treatment. Intramuscular injections of parathormone to six normal men for 8 days induced mild hypercalcemia and hypophosphatemia and reproduced augmented plasma insulin responses to oral glucose and intravenous tolbutamide. 4-hr intravenous infusions of calcium to another group of six normal men raised serum calcium concentrations above 11 mg/100 ml. This did not alter glucose or insulin curves during oral glucose tolerance but markedly accentuated insulin responses to tolbutamide and potentiated its hypoglycemic effect. When highly purified parathormone was incubated with isolated pancreatic islets of male rats, glucose-stimulated insulin secretion was unaffected. These findings suggest that chronic hypercalcemia of hyperparathyroidism sustains a form of endogenous insulin resistance that necessitates augmented insulin secretion to maintain plasma glucose homeostasis. This state is insufficient to oppose tolbutamide-induced hypoglycemia because of an additional direct, selective enhancement of hypercalcemia on pancreatic beta cell responsiveness to the sulfonylurea. The possible direct role of parathormone in these events has not been established.
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PMID:Plasma insulin disturbances in primary hyperparathyroidism. 512 11

Clinical and laboratory data, histologic, electron microscopic and immunocytochemical findings of the tumors of eight patients suffering from Cushing's syndrome and of one patient with hypercalcemia are described. The unlabeled antibody enzyme method was used for the detection of insulin, glucagon, somatostatin, pancreatic polypeptide, corticotropin, beta-lipotropin, calcitonin, parathyroid hormone, and gastrin. Ectopic Cushing's syndrome was caused by pancreatic endocrine tumors, medullary thyroid carcinoma, a bronchial, a gastric and a thymic carcinoid, and a carcinoid of the mediastinum. Hypercalcemia in one patient was related to a pancreatic endocrine tumor. After surgery the clinical symptoms disappeared in two patients, but persisted or relapsed in five patients. ACTH-immunoreactivity could be demonstrated in six of eight tumors; calcitonin-immunoreactivity was found in the tumor of the patient suffering from hypercalcemia. ACTH-immunoreactivity could be localized to secretory granules by immunoelectron microscopy, and the presence of ACTH and beta-LPH in the same tumor cells could be shown in one pancreatic tumor. A combination of production of orthotopic and ectopic hormones was found in one, and secretion of two ectopic hormones was detected in another pancreatic endocrine tumor.
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PMID:Ectopic hormone production by endocrine tumors: localization of hormones at the cellular level by immunocytochemistry. 627 90

Two 8-yr-old children, a boy and girl, are described with Cushing's syndrome secondary to ectopic ACTH-secreting pancreatic islet cell carcinomas. The girl, seen 28 yr ago, had strong presumptive evidence of ectopic ACTH production and hypercalcemia. The boy, studied recently, had strikingly elevated concentrations of plasma ACTH (1,500 pg/ml) and beta-lipotropin (beta LPH; 2,500 pg/ml) and showed no suppression of urinary 17-hydroxycorticoids or cortisol with low and high dose dexamethasone. He had increased plasma calcitonin (257 pg/ml), glucagon (442 pg/ml), lactate dehydrogenase (497 IU/liter), and alpha-fetoprotein (5,144 pg/ml). He also had hypokalemic alkalosis with elevated plasma deoxycorticosterone (70 ng/ml) and PRA (6.9 ng/ml.h) but normal plasma aldosterone (8.2 ng/dl) and 18-hydroxycorticosterone (7.6 ng/dl). Preoperative localization of the tumor was accomplished by computed tomographic scan of the abdomen with concurrent barium enema. Cell-free translation of the tumor mRNA produced authentic proopiomelanocortin of 35,000 mol wt, indicating that the ACTH and beta LPH were produced by the tumor from a common precursor. After removal of a large amount of metastatic tissue from the boy, clinical progression of the remaining tumor was monitored by measuring plasma ACTH and beta LPH. Episodic secretion of ACTH and beta LPH was demonstrated by taking frequent plasma samples while suppressing pituitary ACTH with oral dexamethasone. Chemotherapy and radiation proved ineffective in controlling the growth of his tumor.
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PMID:Endocrine, histological, and biochemical studies of adrenocorticotropin-producing islet cell carcinoma of the pancreas in childhood with characterization of proopiomelanocortin. 630 81


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