Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lithium carbonate is known to alter calcium metabolism by lowering urinary calcium excretion and increasing serum calcium concentrations. Several investigators have reported increases in serum immunoreactive PTH (iPTH) values after a few weeks or months of lithium treatment, and several cases of primary hyperparathyroidism developing during lithium treatment have been reported. To determine whether the increases in serum iPTH might be the result of increased renal retention of inactive PTH fragments rather than stimulation of parathyroid function, we measured plasma intact PTH by immunoradiometric assay and estimated parathyroid size by ultrasonography in men who had received short term (less than 6 months) or long term (greater than 3 yr) lithium treatment and in normal subjects. Serum ionized calcium was higher by 0.03-0.04 mmol/L in subjects treated short term (mean, 1.7 months) with lithium than in normal subjects, but plasma intact PTH and serum midregion iPTH values were not different. The absence of a reciprocal decrease in PTH values is compatible with a lithium-induced shift in the set-point for the inhibition of PTH secretion by calcium toward a higher calcium value. Both plasma intact PTH and serum midregion PTH values were higher in subjects during longer term (mean, 103 months) lithium treatment, and estimated parathyroid volume was 3-fold higher. Serum phosphate was lower, and serum chloride and plasma 1,25-dihydroxy-vitamin D values were higher in those treated with lithium long term, probably from the biological action of the increased PTH. We conclude that long term lithium treatment increases circulating biologically active PTH and causes parathyroid enlargement. Whether this chronic stimulus to parathyroid growth might lead to adenoma formation in certain susceptible individuals and whether a PTH-induced increase in skeletal remodelling occurs that might hasten the appearance of osteopenia remain to be determined.
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PMID:Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume. 291 61

Availability of immunoassays for specific regions of the parathyroid hormone (PTH) molecule allows discrimination with a high level of surety between primary hyperparathyroidism and tumoral hypercalcemic states associated with circulating PTH-like substances. Assay for intact, N-terminal PTH currently has the highest discriminant function. Prostaglandin-dependent and osteoclast-activating factor-mediated hypercalcemic states associated with neoplasia have suppressed serum PTH levels. PTH-like substances are detected by immunoassays, but in the intact, N-terminal system they are seen as normal-range or low values. The frequency with which any tumor produces only authentic PTH is very low. The serum chloride:phosphate ratio has limited clinical utility in distinguishing tumoral hypercalcemia from hyperparathyroid hypercalcemia, and measurements of nephrogenous cyclic AMP do not distinguish between the effects of circulating authentic PTH and PTH-like substances elaborated by tumors. Additional measures that, in the future, may help to distinguish between parathyroid and tumoral hypercalcemias include quantitative bone biopsy histomorphometry and in vitro bioassays for PTH activity in the separate plasma fractions, obtained by gel filtration, in which PTH and PTH-like substances are found.
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PMID:Diagnosis of hyperparathyroidism. 298 31

Chronic administration of 1,25(OH)2D or PTH increases the set point at which plasma bicarbonate concentration is regulated by the kidney and thereby maintains metabolic alkalosis in a variety of species. The renal mechanism(s) responsible for the chronic acid excretory response to 1,25(OH)2D and PTH administration have not been defined, but indirect evidence suggests effects on distal nephron segments. With either hormone in dogs, but not in rats, metabolic alkalosis is generated in part by extrarenal mechanisms. Contrary to the variable finding of hyperchloremic acidosis in human primary hyperparathyroidism, a steady state of mild metabolic alkalosis of renal origin is achieved in normal human subjects infused chronically with PTH. The multiple potential mechanisms responsible for this discrepancy will require careful consideration in future investigations. The acute and chronic effects of plasma calcium concentration on both renal and extrarenal acid-base homeostasis are incompletely understood and require extensive further investigation. Studies in rats have suggested that phosphate depletion results in important counterbalancing renal acidosis and extrarenal alkalosis-producing effects. Chronic hypophosphaturia in the absence of appreciable hypophosphatemia can also result in impaired renal acidification by virtue of phosphate's property as a luminal buffer.
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PMID:Effects and interrelationships of PTH, Ca2+, vitamin D, and Pi in acid-base homeostasis. 298 44

In 6 of 8 adults with severe hypocalcemia and osteomalacia due to vitamin D depletion, basal excretion of nephrogenous cAMP (NcAMP) was increased, but the mean renal phosphate threshold (TmP/GFR) was normal, indicating that the steady state phosphaturic response to cAMP generated by endogenous PTH was impaired, as in pseudohypoparathyroidism type II. In all 6 patients, correction of hypocalcemia by administration of vitamin D and calcium restored the normal relationship between NcAMP and TmP/GFR. By contrast, in 13 patients with normocalcemic osteomalacia due to vitamin D depletion, TmP/GFR was reduced, with a significant negative regression on NcAMP, and rose to normal after treatment. Bone histomorphometry after double tetracycline labeling did not differ significantly between the 2 groups. In 72 patients with primary hyperparathyroidism, the slope of the negative regression of TmP/GFR on NcAMP was the same as in normocalcemic secondary hyperparathyroidism, but the adjusted mean for TmP/GFR was significantly lower. We conclude that the effect of endogenous PTH on phosphate reabsorption varies with the level of plasma calcium, and that dissociation between this effect and the generation of cAMP is nonspecific and can be a consequence of hypocalcemia. Exclusion of vitamin D depletion should be an additional diagnostic criterion for pseudohypoparathyroidism type II.
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PMID:Dissociation between the effects of endogenous parathyroid hormone on adenosine 3',5'-monophosphate generation and phosphate reabsorption in hypocalcemia due to vitamin D depletion: an acquired disorder resembling pseudohypoparathyroidism type II. 298 17

Eighty-five (23%) of 375 patients undergoing surgery for primary hyperparathyroidism were found to have enlargement (greater than 50 mg) of two or three parathyroid glands. Of 76 patients followed from 12 to 140 months after surgery, eight (10.5%) developed hypercalcemia at 1, 4, 45, 64, 74, 79, 84, and 133 months. In a comparison of pertinent preoperative biochemical and pathologic data between 55 patients with two- or three-gland hyperparathyroidism and 55 age- and sex-matched patients with single-gland hyperparathyroidism, only the preoperative serum phosphate differed significantly, being lower in the patients with single-gland disease (2.4 +/- 0.1 vs. 2.6 +/- 0.1; p less than 0.04). In the eight patients with two- or three-gland hyperparathyroidism who developed postoperative hypercalcemia, the preoperative concentrations of serum calcium were lower (10.8 +/- 0.2 vs. 11.5 +/- 0.2; p less than 0.019), the preoperative concentrations of serum phosphate were higher (3.1 +/- 0.2 vs. 2.5 +/- 0.1; p less than 0.020), and the weights of the excised parathyroid tissues were less (356 +/- 72 mg vs. 1354 +/- 215 mg; p less than 0.02) than those of patients with two- or three-gland disease who did not develop postoperative hypercalcemia, indicating a milder form of hyperparathyroidism. In the 68 patients without recurrent hypercalcemia, there was no tendency for the serum calcium concentration to increase with time. Patients with primary hyperparathyroidism associated with two or three enlarged parathyroid glands have an appreciable incidence of persistent or recurrent hypercalcemia, which may increase even further with longer observation.
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PMID:Hyperparathyroidism associated with the enlargement of two or three parathyroid glands. 299 50

We found that a few patients with urolithiasis had normal parathyroid hormone levels but high cyclic AMP excretion. The purpose of this paper was to study the endocrinological mechanism. Male rats were given intraperitoneally dibutyryl cyclic AMP (DBcAMP), a derivative of cyclic AMP, per 100 gm of body weight for 50 days. Feed and water were supplied ad libitum. Crystal formation or calcification in mainly the dystal tubules and collecting system were found in 3 out of 10 rats, and renal calcium stones in 2 rats. The cyclic AMP of the renal parenchyma, especially the renal medulla, was elevated by more than 100 times after DBcAMP administration. Serum calcium levels, urinary calcium and phosphate excretion, and the adrenaline levels of the renal parenchyma were significantly increased. Serum parathyroid hormone was slightly enhanced, but vitamin D and the noradrenaline levels of the renal parenchyma were not changed. Based on these findings, it is suspected that stone formation in rats injected DBcAMP occurs through the action of DBcAMP on the renal tubules to increase urinary calcium excretion and to make renal stones as a form of primary hyperparathyroidism.
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PMID:[Studies on the endocrinological metabolism of the parathyroid. I. The production of renal calcinosis by cyclic AMP injection in rat]. 300 37

A patient with primary hyperparathyroidism whose bone scan showed signs of extensive pulmonary and gastric calcifications is described. The patient also had renal insufficiency. A review of the literature and of data of 13 patients with primary hyperparathyroidism who were seen in the Department of Internal Medicine at the University Hospital of Maastricht, led to the conclusion that only in patients with renal insufficiency could ectopic calcifications be expected to occur. Phosphate retention, rather than the hyperphosphaturia that occurs in that particular situation, is cited as the cause.
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PMID:A patient with primary hyperparathyroidism and an abnormal bone scan. 302 69

Ten hypercalcaemic patients with solid tumours were studied to evaluate the renal response on PTH infusion as assessed by nephrogenous cAMP excretion and maximum tubular re-absorption of phosphate. In addition, 20 normocalcaemic patients, 11 with an adenocarcinoma and 9 with a squamous cell carcinoma, were studied. All cancer patients had moderately extensive disease. Results were compared with those of 9 patients with primary hyperparathyroidism and with 10 elderly controls. All groups studied had comparable renal function, magnesium and 25-hydroxy-vitamin D levels. Comparable results were obtained in patients with an adenocarcinoma and in controls. cAMP response (delta nephrogenous cAMP) was significantly lower in the hypercalcaemic patients with a solid tumour compared with the controls (8.13 +/- 4.68 nmol/100 ml glomerular filtrate vs 29.52 +/- 25.62 nmol/100 ml glomerular filtrate; P less than 0.005). In the group of patients with primary hyperparathyroidism delta nephrogenous cAMP was 13.41 +/- 7.54 nmol/100 ml glomerular filtrate (P less than 0.06 vs controls). The group of patients with a squamous cell cancer showed an intermediate value of 14.83 +/- 10.74 nmol/100 ml glomerular filtrate (P less than 0.025 vs the normocalcaemic adenocarcinoma patients, but NS vs controls). In two hypercalcaemic patients with a solid tumour in whom PTH infusion was repeated after normalization of serum calcium no influence on renal responsiveness was observed. Responses of maximum tubular re-absorption of phosphate were lowest in the group of hypercalcaemic patients with a solid tumour and in the patients with primary hyperparathyroidism compared with controls (0.11 +/- 0.10 vs 0.22 +/- 0.09 mmol/l and 0.09 +/- vs 0.22 +/- 0.09 mmol/l; P less than 0.025 and P less than 0.005, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:End-organ resistance to PTH infusion in hypercalcaemic and normocalcaemic patients with solid tumours. 302 41

The hypothesis that chronic metabolic acidosis encountered in some patients with primary hyperparathyroidism is due to inhibition of proximal HCO3 reabsorption has recently been challenged. Indeed, this action of parathyroid hormone (PTH) has only been observed in acute studies, whereas in animal models of chronic hyperparathyroidism a metabolic alkalosis has been induced, probably owing to the release of alkaline salts from bone tissue, and to the stimulation of tubular acid secretion by hypercalcaemia. Studies were, therefore, performed to determine the effect of PTH on the renal handling of HCO3 in an animal model in which changes in plasma calcium and phosphate, and nephrocalcinosis, all known to affect tubular acidification, did not occur. Thyroparathyroidectomized (TPTX) rats were infused with synthetic bovine hormone fragment bPTH 1-34 via Alzet minipumps at the rate of 0.7 U h-1 to simulate normal endogenous production of PTH (group I) and at the three-fold higher rate of 2.1 U h-1 (group II). In order to prevent changes in serum calcium and phosphate, and nephrocalcinosis, animals of group II were fed a Ca- and P-free diet prior to TPTX (compared with a regular diet for group I) and both groups were treated with dichloromethylene-diphosphonate (Cl2MDP, 10 mg kg-1 day-1) and a Ca-free diet during PTH infusion. During the course of PTH infusion both groups of animals had stable and normal levels of plasma calcium and phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid hormone directly inhibits tubular reabsorption of bicarbonate in normocalcaemic rats with chronic hyperparathyroidism. 312 45

Hypercalcemia is associated with a few primary malignant neoplasms and with a variety of tumors that have spread by metastases. Hyperparathyroidism is a diagnosis that is usually not considered in these patients. At our institution, 18 patients with malignant tumors presented over a 6-year period with hypercalcemia caused by hyperparathyroidism. There were five men and 13 women with a mean age of 48 years (range 24-87 years). Primary tumors in these patients included colon carcinoma (four cases), breast carcinoma (four cases), lymphoma (four cases), thyroid carcinoma (four cases), Paget's disease (one case), and lung carcinoma (one case). Metastases of the primary tumor occurred in seven patients, and in 11 patients the tumor was not metastatic or recurrent. Serum levels of calcium, phosphate, and chloride averaged 11.8 mg/dl, and 100 mEq/liter, respectively. C-terminal parathyroid hormone (PTH) levels ranged from 300 to 1,900 pg/ml with an average of 1,150 pg/ml (normal 50-340 pg/ml). At operation, a single parathyroid adenoma was discovered in 15 patients, and four-gland hyperplasia was noted in three patients. In all cases, serum levels of calcium returned to normal after operation. We conclude that patients with malignant tumors and concomitant hypercalcemia should be evaluated for the possibility of hyperparathyroidism. In cases of primary hyperparathyroidism, elevated C-terminal PTH level should be diagnostic. If hyperparathyroidism is determined to be the cause of hypercalcemia, neck exploration and parathyroidectomy are indicated.
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PMID:Malignancy and concomitant primary hyperparathyroidism. 333 14


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