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)

PTH-like peptide (PLP) is produced by tumors commonly associated with hypercalcemia as well as nonneoplastic tissues and several endocrine glands and tumors. To characterize the distribution of PLP in human endocrine tissues and tumors, we localized PLP in formalin-fixed paraffin-embedded material using the avidin-biotin-peroxidase technique with polyclonal antisera. Among peptide hormone-producing tissues, PLP was identified in nontumorous adenohypophysis and pituitary adenomas; medullary thyroid carcinomas; normal, hyperplastic, and adenomatous parathyroids; adrenal medulla and pheochromocytomas; normal pancreatic islets; and endocrine tumors of pancreas, gut, and lung, including small cell carcinomas. In other endocrine tissues PLP was identified in nontumorous thyroid follicular epithelium, colloid nodules, and follicular neoplasms; normal adrenal cortex, adrenocortical adenomas, and carcinomas; nontumorous testicular Leydig cells; normal ovarian granulosa and thecal cells; an ovarian thecoma and a granulosa cell tumor; placental trophoblast; and decidua. These results demonstrate that PLP is localized in many normal and neoplastic endocrine cells, including those not known to influence extracellular calcium homeostasis. The presence of PLP in a variety of endocrine tissues suggests that it may play a local physiological role in the growth or function of endocrine cells.
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PMID:Parathyroid hormone-like peptide in normal and neoplastic human endocrine tissues. 222 75

The author examined a group of 143 patients with osteomalacia of different origin before treatment and after adequate treatment with vitamin D, using laboratory tests, assessment of body weight and muscular strength (grip of the dominant hand). After treatment there was a significant rise of calcaemia, phosphataemia and calciuria and a drop of alkaline phosphatase activity. The body weight increased within the first month of treatment on average by 1.27 kg, during the second month by another 1.15 kg. The patients gained a total of 2.42 kg. The muscular strength increased during the first month on average by 3.23 kg and during the second month by another 2.16 kg, i.e. a total of 5.39 kg. From these results it may be concluded that vitamin D may have a certain anabolic effect if used in pharmacological does either due to an increased nutrient absorption from the gut because of hypertrophy of the intestinal wall or indirectly via hypercalcaemia which increases the hydrochloric acid secretion in the stomach as well as pepsin secretion, and promotes activation of trypsin and lipase in the duodenum and moreover causes retardation of the intestinal transit. The increased muscular strength in due to a rise of calcaemia, improved muscle contraction and probably also due to the mentioned nutritional factors. There may be also the factor of an improved lifestyle due to the immunomodulating action of vitamin D and disappearance of bone pain.
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PMID:[Anabolic effects of vitamin D in patients with osteomalacia]. 263 59

This investigation addresses a theoretical concept of tumor pathogenesis proposed over 40 years ago, namely that malignancy-associated hypercalcemia can result from endocrine secretion by tumors of a PTH-like factor. These studies demonstrate that a fragment of hHCF alone, without added or tumor-secreted cofactors or hormones, can produce hypercalcemia and other biochemical abnormalities associated with HHM. The hypercalcemia can be generated by hHCF-(1-34)NH2 action on bone, although kidney and gut could contribute to the HHM syndrome when it occurs naturally. No other tumor-secreted peptide displays this biological profile. These studies establish one (PTH-like) mechanism by which human tumors could produce hypercalcemia. Furthermore, the finding that hHCF-(1-34)NH2 is more potent than PTH in some systems is of considerable interest for the future design of hormone analogs. A broad spectrum of biological properties of hHCF-(1-34)NH2, including production of components of the HHM syndrome, can be inhibited by a PTH antagonist. Because [Tyr-34]bPTH-(7-34)NH2 selectively and competitively occupies PTH receptors, our studies demonstrate formally that hHCF-(1-34)NH2 mediates some (and perhaps all) of its actions via receptors conventionally regarded as intended for interaction with PTH, but which actually may be present to allow for expression of bioactivity of both secreted proteins. Although some structural homology is shared by the two hormones and many contribute to interaction with receptors, the disparity in structure, especially within the 1-34 domains responsible for bioactivity in both hormones, is more pronounced. The similarity in biological profiles despite structural differences between hHCF and PTH is emphasized by the inhibitory action of [Tyr-34]bPTH-(7-34)NH2 against the tumor peptide even in the absence of much of the homologous region in the PTH antagonist. This investigation provides impetus for designing more potent antagonists, which must now be regarded more appropriately as inhibitors of both PTH and hHCF. Such antagonists may best be generated from hybrid structures of the two hormones. In any case, these studies establish a promising new approach to therapy of tumor-associated hypercalcemia.
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PMID:A tumor-secreted protein associated with human hypercalcemia of malignancy. Biology and molecular biology. 285 15

The regulation of plasma calcium involves many factors acting at the gut, bone and kidney levels. The mechanism leading to hypercalcemia in malignant neoplasm may well differ according to the type of tumor, the presence or otherwise of bone metastasis, the stage of the disease as well as additional factors such as the state of hydration. Increased bone resorption would certainly play an important role. However, increased tubular reabsorption of calcium could be the main hypercalcemic mechanism in some types of malignant tumor. Therapeutically, the approach has so far been to reduce the input of calcium from gut and bone and/or improve its renal clearance. Until now, the most efficient action appears to be the blockage of bone resorption. Among several bone resorption inhibitors, the diphosphonate compounds have been shown in several reports to be quite efficient in normalising calcemia.
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PMID:[Tumoral hypercalcemia: physiopathology and treatment]. 315 14

Pharmacological treatment of hypertension can cause clinically significant alterations in endocrine function through effects on glucose homeostasis, thyroid and parathyroid hormones, adrenal steroid metabolism and reproductive/pituitary physiology. Long term use of thiazide diuretics causes deterioration in glucose tolerance, probably secondary to potassium depletion. Hypoglycaemic complications of beta-blockers (mainly the non-selective compounds) can be dramatic, especially in type I diabetics. Clonidine, diazoxide and calcium antagonists have all been associated with deterioration in glucose tolerance and their long term use should be avoided in type II diabetics if possible. Propranolol lowers T3 levels by decreasing the conversion of T4 to T3. Prazosin causes elevations in T4 and thyroid-stimulating hormone, while sodium nitroprusside use may result in hypothyroidism. Numerous agents are associated with sexual dysfunction, including methyldopa, reserpine, clonidine and spironolactone. Thiazide diuretics may cause hypercalcaemia, particularly in patients with hyperparathyroidism, by decreasing urinary calcium as well as directly influencing bone and gut calcium handling. Conversely, propranolol may decrease circulating parathyroid hormone levels and correct the hypercalcaemia seen in hyperparathyroidism. Awareness of drug-induced changes in endocrine function will facilitate the rational management of the hypertensive patient.
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PMID:Effects of antihypertensive drugs on endocrine function. 614 2

A study of 28 consecutively admitted patients with active acromegaly revealed the following results with regards to calcium and phosphate metabolism. When compared with controls, there was an increase in serum calcium levels corrected for total protein, urinary calcium was increased, but the tubular re-absorption of calcium was normal. There was a negative correlation between the urinary cAMP and calcium excretion indicating that hyperabsorption of calcium from the gut is the cause of the increased urinary calcium excretion. Serum phosphate values were increased in acromegalics and correlated well with TmP/GFR which was also increased. Immunoreactive parathyroid hormone (PTH) was increased in 5 patients, three of whom had hypercalcaemia. In the remaining patients the PTH values were scattered within the normal range. The urinary cAMP/creatinine ratio was increased in acromegalics, but most of this difference was abolished when urinary cAMP was expressed relative to 100 ml of glomerulus filtrate. It is concluded that parathyroid hyperactivity is a feature of acromegaly.
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PMID:Calcium and phosphate metabolism in acromegaly. 625 98

Twenty-seven hypercalcaemic subjects were identified in three generations of a family. There were no clinical complications of chronic hypercalcaemia, but five had had parathyroid surgery which was unsuccessful in four. Twenty of the twenty-seven subjects were compared with twenty-four normocalcaemic controls from the same family and the findings were also compared with those from forty patients with surgically proven primary hyperparathyroidism. The relation between the serum and urinary calcium levels was studied by means of an oral calcium loading test. The ratio of calcium clearance to creatinine clearance was normal in this family (but elevated in the patients with primary hyperparathyroidism) and the concentration of parathyroid hormone was normal, as was the total urinary excretion of cyclic AMP. Thus, there was no evidence of either suppressed or increased parathyroid activity in this familial condition. Basal urinary calcium excretion was normal under steady-state conditions indicating that the hypercalcaemia could not be attributed to either increased bone resorption or increased calcium absorption from the gut. In accordance with this, the serum levels of 1,25-dihydroxycholecalciferol were normal. The hypercalcaemia in this condition can be accounted for in full by an increase in renal tubular reabsorption of calcium, and thus differs from that of primary hyperparathyroidism in which there is increased production of calcium from gut and/or bone as well as an increase in renal tubular reabsorption of calcium. Although the serum phosphate and renal tubular reabsorption of phosphate were both low in patients with familial benign hypercalcaemia, they were not as low as in patients with the same degree of hypercalcaemia due to primary hyperparathyroidism. The changes in phosphate transport in familial benign hypercalcaemia could be explained as a secondary effect of the increased filtered load of calcium in the kidney. The tendency towards hypermagnesaemia in our patients, which contrasts with a tendency towards hypomagnesaemia in primary hyperparathyroidism, could also be explained as a secondary effect of the abnormality of renal tubular reabsorption of calcium. Increased renal tubular calcium reabsorption and persistent normal functioning of the parathyroid glands in the face of hypercalcaemia remain the sole definite abnormalities of the syndrome.
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PMID:Familial benign hypercalcaemia. Study of a large family. 631 Jun 72

A patient with familial hypocalciuric hypercalcaemia (FHH) is reported. Seven years after total parathyroidectomy he remained hypocalcaemic, with biochemical evidence of hypoparathyroidism (enhanced renal tubular reabsorption of phosphate, low nephrogenic cyclic AMP excretion, and reduced serum concentration of 1,25-dihydroxycholecalciferol in the presence of normal renal function and normal serum 25-hydroxyvitamin D levels). Iv infusions of calcium were given before and 6 years after total parathyroidectomy. The renal tubular reabsorption of calcium was compared in these two situations. No difference was found. Before and after parathyroidectomy there was enhanced renal tubular reabsorption of calcium. It is concluded that the enhanced renal tubular reabsorption of calcium in FHH is independent of parathyroid hormone. Total parathyroidectomy corrects the hypercalcaemia in FHH by a reduction in the input of calcium into the extra-cellular fluid from gut and or bone perhaps as a result of reduced renal synthesis of 1,25-dihydroxycholecalciferol.
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PMID:Familial hypocalciuric hypercalcaemia: evidence for continued enhanced renal tubular reabsorption of calcium following total parathyroidectomy. 647 56

Long-term studies of gastrointestinal radio-calcium absorption were undertaken in adult greyhounds before and during two treatment regimes with human parathyroid hormone fragment 1-34 (hPTH 1-34). The results were correlated with plasma vitamin D metabolite levels and kinetic indices related to the balance of fluxes of calcium between plasma and the rapidly exchangeable calcium pools of bone. Compared with adult man, results obtained before treatment started showed lower indices of gastrointestinal calcium absorption and considerably higher concentrations of 24-hydroxycalcidiol in the dogs. Daily injections of hPTH 1-34 at 1.7 microgram day-1 kg-1 significantly increased indices of radiocalcium absorption and plasma calcitriol concentrations, while only causing transient calcaemic responses. The individual magnitudes of the calcaemic response correlated positively with indices of radiocalcium retention in the exchangeable pools of bone which in turn correlated positively with 'late-phase' absorption of radiocalcium from the gut. Subcutaneous infusions of hPTH 1-34 at 0.5 microgram day-1 kg-1 to the same dogs were just insufficient to cause hypercalcaemia, but increased plasma calcitriol concentrations. Indices of radiocalcium absorption were not increased. Continuous parathyroid hormone (PTH) infusion is now known to substantially down-regulate renal PTH receptor density, whereas recovery after a brief exposure to PTH occurs within 24 h. It is possible that the differences in response of the gut to the two regimes may in part be related to their differing effects on some PTH receptors.
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PMID:Intestinal absorption of calcium in greyhounds: the response to intermittent and continuous administration of human synthetic parathyroid hormone fragment 1-34 (hPTH 1-34). 654 27

A case of primary hyperparathyroidism with clinical signs of rickets in a 15-year-old boy of South Morocco is presented. X-ray findings include a diffusely osteoporotic skeleton with areas of subperiostal resorption, cysts and metaphyseal rachitic changes. Hypercalcaemia, hypophosphataemia, increased alkaline phosphatase are found together with low calcidiol and high calcitriol plasma levels. The surgical removal of a chief-cell adenoma of a parathyroid gland leads to very rapid bone healing as well as normalization of blood chemistry. Reviewing the literature shows that 10 similar cases have been described. However, no correlation can be established between the occurrence of rachitic lesions and the Ca X P product. When limited calcium is available from the gut, elevated calcitriol then contributes to mobilize more mineral from bone, in conjunction with parathormone. In addition, the interaction of these 2 hormones on the renal tubule maintains a phosphate leak, creating proper conditions for the development of rachitic lesions.
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PMID:Primary hyperparathyroidism and rickets. A case report and review of the literature. 654 55


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