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)

Controlled studies in 1990-1992 with Danish, Sardinian, and Hongkong-Chinese patients consistently revealed a prevalence of goiter of about 50% in lithium treated patients. This is far beyond the frequency generally assumed for Germany, the whole country still known to be an endemic goiter area. Hypothyroidism as a side effect of lithium occurs in a clearly different group of patients and is much less frequent, the overall incidence being not substantially different from the incidence in the general population. But the risk of becoming hypothyroid as well as hyperparathyroid during lithium prophylaxis is markedly higher in women over 45 years of age, who in the general population are also prone to both endocrine dysfunctions. Lithium is considered to have a provoking role. Lithium is known to be accumulated in the bone and an impact on bone metabolism was shown in animal studies. The data reviewed prohibit the use of lithium during lactation and enforce strict indication in children. In adults the effect of lithium on bone should be considered only in osteomalacia and severe osteoporosis. This review is illustrated by the case of a 60-year-old woman, who after 4 years of successful treatment with lithiumcarbonate because of schizoaffective psychosis, developed a syndrome of hypercalcemia. Exstirpation of a parathyroid adenoma rendered her normocalcemic. Moreover, a pre-existing diffuse goiter had grown to a large nodular goiter within the course of her 5-year treatment. As she finally became paraparetic, she was admitted to our rehabilitation center for the diseases of the spinal cord. Her paraparesis may have been caused not only by the lithium-induced primary HPT, but in part by lithium itself. There are a few reports on lithium causing peripheral neuropathy at toxic levels. A transient deterioration of a pre-existing neuropathy, as in our case study, may have happened at lithium serum levels not far beyond the upper limit of 0.8 mmol/l.
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PMID:[Lithium and its effects on the endocrine system, bones and peripheral nerves--a current review]. 775 53

Humoral hypercalcemia of malignancy (HHM) is a common paraneoplastic syndrome mediated by tumor-derived parathyroid hormone-related peptide (PTHRP), which bears structural and functional similarities to PTH. Thus the clinical features of HHM are very similar to those of primary hyperparathyroidism (1 degree HPT), a prototype of humoral hypercalcemia caused by PTH. On the other hand, HHM syndrome differs from 1 degree HPT in several aspects, including serum 1,25(OH)2D levels, acid-base balance, and bone remodeling process, the reason of which remains largely unknown. We approached these questions using a unique animal model of HHM, nude rats implanted with PTHRP-overproducing human carcinomas. In this review we will summarize the results and discuss the implications in understanding the disease mechanism.
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PMID:Humoral hypercalcemia of malignancy: some enigmas on the clinical features. 776 74

PTH clearly plays a role in maintaining the hypercalcemia of familial benign hypercalcemia (FBH or familial hypocalciuric hypocalcemia). To better define the abnormalities of parathyroid function in FBH and primary hyperparathyroidism (1 degree HPT), we used a two-site immunochemiluminometric assay for intact PTH to examine PTH suppressibility in normal individuals and patients having FBH or 1 degree HPT. Twelve normal, 11 FBH, and 7 1 degree HPT subjects were given calcium (Ca) iv with frequent sampling for ionized Ca and intact PTH. In normal and FBH subjects, plasma PTH levels decreased essentially identically in response to iv Ca. In the 1 degree HPT group, PTH was not normally suppressible. However, there was a spectrum of responsiveness in 1 degree HPT patients, with a significant correlation between tumor mass and degree of PTH nonsuppressibility (r = 0.87, P = 0.01). Analysis of the relationship between plasma PTH and ionized Ca values in the three groups demonstrated a shift to the right in the FBH curve, with no difference of slope, consistent with the notion of a simple "set-point" error in FBH. In contrast, the curve in 1 degree HPT was not only shifted to the right but also differed from normal in slope (normal, -8.92; 1 degree HPT, -3.92, P = 0.04). Thus, we propose that the parathyroid functional abnormality in FBH represents a simple set-point error, whereas the defect in 1 degree HPT consists of a set-point error combined with varying degrees of Ca nonsuppressible PTH secretion that may be related to tumor mass.
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PMID:Calcium infusion suggests a "set-point" abnormality of parathyroid gland function in familial benign hypercalcemia and more complex disturbances in primary hyperparathyroidism. 844 32

Bone and vitamin D metabolism are examined in patients with primary hyperparathyroidism (1 degree HPT), humoral hypercalcemia of malignancy (HHM), and local osteolytic hypercalcemia (LOH) with normal renal function. Among the bone resorption markers, T scores of total deoxypyridinoline (Dpyd) were highest in HHM and were significantly higher than those in 1 degree HPT. Among the formation markers, T scores of osteocalcin (OC) were highest in 1 degree HPT but were negative in HHM. The elevation in total Dpyd was associated with an increase in OC in 1 degree HPT, and the ratios of total Dpyd/OC were similar to those in controls. In contrast, many patients with HHM and LOH exhibited elevated total Dpyd and suppressed OC with increased total Dpyd/OC ratios, but the ratios varied widely. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was elevated in 1 degrees HPT but was suppressed in HHM and LOH at any serum Ca levels. These results demonstrate that increased bone resorption is associated with enhanced bone formation in 1 degrees HPT but are uncoupled in many of the HHM and LOH patients, and that total Dpyd/OC ratio can be a useful index to estimate the coupling state of bone. It is suggested that the reduction in serum 1,25(OH)2D cannot be explained by an elevation in serum Ca in HHM and LOH, and that the differences in bone and vitamin D metabolism in HHM and LOH from those in 1 degree HPT may be caused by a common mechanism such as the secretion of some cytokines from tumors.
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PMID:Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia. 863 76

To determine the relative importance of parathyroid gland enlargement and alterations in calcium sensing (set-point changes) in the pathogenesis of uremic secondary hyperparathyroidism (2 degrees HPT), we investigated the relationship between estimates of parathyroid gland size and calcium-mediated parathyroid hormone (PTH) suppression in 19 normocalcemic 2 degrees HPT patients on chronic maintenance hemodialysis. We compared our results to calcium-mediated PTH suppression in 12 normal volunteers, 12 patients with familial benign hypocalciuric hypercalcemia (FBHH), a disorder of abnormal calcium sensing, and 9 subjects with primary hyperparathyroidism (1 degree HPT), which is characterized by both calcium set-point abnormalities and parathyroid gland enlargement. We found that the 2 degrees HPT group displayed a distinctive pattern of calcium-mediated PTH suppression characterized by a failure to normally suppress PTH at supraphysiologic ionized calcium concentrations, similar to 1 degree HPT, but without the rightward shift of the calcium-PTH suppression curve that characterizes calcium sensing abnormalities in FBHH and 1 degree HPT. In the patients with 2 degrees HPT, hypercalcemic suppression resulted in an ending PTH (as a percent of baseline) that was significantly higher (39.8 +/- 4.47%), and a slope of the calcium-PTH suppression curve that was significantly less negative (-4.8 +/- 0.53), compared to respective values of 19.4 +/- 1.81% (P = 0.0009) and -9.0 +/- 1.02 (P = 0.001) in normals and 19.1 +/- 2.49% (P = 0.001) and -9.6 +/- 1.11 (P = 0.0006) in FBHH. Values of ending PTH and slope in 2 degrees HPT patients, however, were similar to those found in 1 degree HPT (49.8 +/- 6.35%, P = 0.21 and -4.5 +/- 0.74, P = 0.72). The ionized calcium concentration required to attain half maximal PTH suppression (EC50) in 2 degrees HPT (1.20 +/- 0.02 mmol/liter) was not significantly different from normals (1.25 +/- 0.01 mmol/liter, P = 0.12) but was significantly less than in 1 degree HPT (1.52 +/- 0.02 mmol/liter, P < 0.0001) and in FBHH (1.44 +/- 0.02 mmol/liter, P < 0.0001). More importantly, we found a significant linear correlation between the natural logarithm of gland size and ending PTH suppression (r = 0.71, P < 0.001) and slope of the calcium-PTH curve (r = 0.67, P = 0.002) in 2 degrees HPT. Thus, calcium non-suppressible PTH secretion in 2 degrees HPT does not represent a simple set-point error, but rather correlates with the degree of parathyroid gland enlargement.
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PMID:Non-suppressible parathyroid hormone secretion is related to gland size in uremic secondary hyperparathyroidism. 891 34

Secondary hyperparathyroidism (2'HPT) improves after renal transplantation (RTx) along with recovered function of the renal allograft. However, normal renal function does not last long due to rejection, drug-induced nephrotoxic nepthropathy, or recurrence of post-transplant glomerulonephritis. Therefore, improved calcium and phosphate metabolism, and parathyroid function after RTx fluctuate in accordance with the function of the renal allograft. In cases with severe 2'HPT, parathyroidectomy should be performed before RTx because hypercalcemia due to secondary or tertiary hyperparathyroidism aggravates the renal allograft function. In the follow-up of mild 2'HPT after RTx, hypercalcemia and vascular calcification should be monitored carefully by serum parathyroid hormone, calcium and phosphate concentrations, alkaline phosphatase activity, and bone X-ray film. If serum calcium level exceeds 12 mg/dl, parathyroidectomy (PTx) should be performed to prevent the acceleration of vascular calcification. Total PTx with forearm allograft is a preferred surgical procedure for 2'HPT even after RTx.
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PMID:Renal transplantation and secondary hyperparathyroidism. 908 65

We report a case of 77-year-old woman who presented with lumbago and hypercalcemia. Multiple myeloma (MM) was first diagnosed by serum protein electrophoresis and bone marrow aspiration, but intact parathyroid hormone (intactPTH) was also found to be high in the presence of persistent hypercalcemia with anorexia and nausea. After lowering serum calcium with bisphosphonate administration, parathyroidectomy was performed. Upon histologic examination, the tumor was determined to be parathyroidal chief-cell hyperplasia and the patient was treated with melphalan and prednisolone. The relationship between MM and primary hyperparathyroidism (I degree HPT) remains unknown. Although the co-existence of MM and I degree HPT was reported in 12 reports from various parts of the world, there was only 1 report in Japan. The present case is an example of successful treatment for a complicated disorder, and suggests that patients suffering from bone pain or hypercalcemia need to be examined both endocrinologically and hematologically.
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PMID:A case of primary hyperparathyroidism accompanying multiple myeloma. 915 21

Parathyroidectomy should be considered in every patient with hypercalcaemia and primary hyperparathyroidism even if the symptoms are vague. Cervical exploration is a safe operation with very satisfactory results. Our experience in 214 patients over 25 years shows permanent postoperative normocalcaemia in 95% of cases with a complication rate of 2.8%. All patients with primary HPT, regardless of age or the severity of symptoms should be candidates for cervical exploration.
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PMID:Cervical exploration for primary hyperparathyroidism--A 25 year experience. 934 31

The calcium-dependent secretion of parathyroid hormone (PTH) is mediated through an extracellular G protein-coupled calcium receptor (CaR). Inactivating point mutations of this receptor have been found in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. These diseases feature a decreased calcium sensitivity of the parathyroid glands, resulting in a rightward shift of the Ca2(+)-PTH relationship. Severe non-suppressible renal hyperparathyroidism (rHPT) is often characterized by similar setpoint shifts to the right. Thus, point mutations of the CaR gene could contribute to non-suppressible rHPT. We examined genomic DNA of hyperplastic or mainly nodular tissues of 39 parathyroids from 25 rHPT-patients with resistance to calcitriol therapy. Amplification of the six exons of the CaR gene was followed by single-strand conformation polymorphism (SSCP) analysis. DNA sequencing was performed where band shifts were observed. No point mutations in the coding sequence of the CaR gene were detected using the PCR-SSCP strategy. Point mutations in the coding regions of the CaR gene probably play no role in the evolution of renal HPT and are not responsible for the calcitriol resistance of PTH secretion.
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PMID:Point mutations of the human parathyroid calcium receptor gene are not responsible for non-suppressible renal hyperparathyroidism. 950 99

Calcium-sensing by the parathyroids is abnormal in familial benign hypocalciuric hypercalcemia and in primary hyperparathyroidism (primary HPT), but the role of a calcium-sensing defect in uremic secondary hyperparathyroidism (secondary HPT) remains controversial. To study the regulation of PTH release by calcium, set point estimates were obtained using the four parameter model during in vivo dynamic tests of parathyroid gland function in 31 patients with secondary HPT, 8 patients with advanced secondary HPT studied shortly before undergoing parathyroidectomy (Pre-PTX), 3 patients with primary HPT, and 20 subjects with normal renal function (NL); the response to 2-h i.v. calcium infusions was also evaluated. Neither blood ionized calcium (iCa+2) levels nor the set point for calcium-regulated PTH release differed between secondary HPT and NL; iCa+2 levels and set point values were moderately elevated in Pre-PTX and markedly elevated in primary HPT. Compared with values obtained in NL, the lowest serum PTH levels achieved during calcium infusions, expressed as a percentage of pre-infusion values, were incrementally greater in secondary HPT, Pre-PTX, and primary HPT, whereas the slope of the relationship between iCa+2 and PTH, expressed as the natural logarithm (ln) of percent preinfusion values, decreased incrementally in secondary HPT, Pre-PTX, and primary HPT. The inhibitory effect of calcium on PTH release is blunted both in secondary HPT and primary HPT because of increases in parathyroid gland mass, but a calcium-sensing defect is a late, rather than early, consequence of renal secondary HPT.
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PMID:Calcium-sensing by parathyroid glands in secondary hyperparathyroidism. 970 44


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