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 sodium phosphate co-transporters Npt2a and Npt2c play important roles in the regulation of phosphate homeostasis. Slc34a1, the gene encoding Npt2a, resides downstream of the gene encoding coagulation factor XII (f12) and was inadvertently modified while generating f12(-/-) mice. In this report, the renal consequences of this modification are described. The combined single allelic mutant Slc34a1m contains two point mutations in exon 13: A499V is located in intracellular loop 5, and V528M is located in transmembrane domain 11. In addition to the expected coagulopathy of the f12(-/-) phenotype, mice homozygous for the double allelic modification (f12(-/-)/slc34a1(m/m)) displayed hypophosphatemia, hypercalcemia, elevated levels of alkaline phosphatase, urolithiasis, and hydronephrosis. Strategic cross-breedings demonstrated that the kidney-related pathology was associated only with autosomal recessive transmission of the slc34a1(m) gene and was not influenced by the simultaneous inactivation of f12. Npt2a[V528M] could be properly expressed in opossum kidney cells, but Npt2a[A499V] could not. These results suggest that a single amino acid substitution in Npt2a can lead to improper translocation of the protein to the cell membrane, disturbance of phosphate homeostasis, and renal calcification. Whether point mutations in the SLC34A1 gene can lead to hypophosphatemia and nephrolithiasis in humans remains unknown.
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PMID:A missense mutation in the sodium phosphate co-transporter Slc34a1 impairs phosphate homeostasis. 1865 Apr 75

Renal involvement in sarcoidosis displays a wide range of manifestations, and kidney dysfunction may involve all three mechanisms of renal failure. We report a new case of systemic sarcoidosis presenting as a severe renal failure due to hypercalcemia, sarcoidosis-related bilateral nephrolithiasis and granulomatous interstitial nephritis. A prostate adenocarcinoma was also diagnosed, but has to be regarded as an unrelated disease.
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PMID:Sarcoidosis and the kidney: not only the granulomatous interstitial nephritis. 1920 14

Primary hyperparathyroidism (PHPT) is characterized by the autonomous production of parathyroid hormone (PTH), in which there is hypercalcemia or normal-high serum calcium levels, in the presence of elevated or inappropriately normal serum PTH concentrations. Exceptionally, in symptomatic patients, a diagnosis can be established on the basis of clinical data. PHPT must always be evaluated in patients with clinical histories of nephrolithiasis, nephrocalcinosis, osseous pain, subperiosteal resorption, and pathologic fractures, as well as in those with osteoporosis-osteopenia on dual-energy X-ray absorptiometry (DEXA), a personal history of neck irradiation, or a family history of multiple endocrine neoplasia syndrome (types 1 or 2). Diagnosis of PHPT is biochemical. Asymptomatic hypercalcemia (total serum calcium corrected by albumin), without guiding signs or symptoms, is the most frequent manifestation of the disease. For the differential diagnosis, PTH(1-84) must be measured, as well as phosphate, chloride, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and calcium-to-creatinine clearance. Suppressed or inappropriately low PTH1-84 guides the diagnose toward tumoral hypercalcemia and less frequently to granulomatous disease (sarcoidosis, tuberculosis, etc.), inadequate intake of 1alpha-hydroxyvitamin D or calcitriol, vitamin D or A intoxication, lithium intake, endocrinopathies (hyperthyroidism, Addison's disease, etc.) or treatment with thiazides, among other possibilities. Diagnosis of PHPT is confirmed by demonstrating persistent hypercalcemia (or normal-high serum calcium levels) in the presence of inappropriately normal or elevated serum PTH(1-84) concentrations, unless the urinary calcium-to-creatinine clearance ratio is lower than 0.01. In these cases, in the absence of thiazide intake or severe vitamin D deficiency, diagnosis should focus on benign familial hypercalcemic hypocalciuria. Parathyroid gland imaging is useful for localization of PHPT, but not for diagnosis of this entity.
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PMID:[Diagnostic evaluation and differential diagnosis of primary hyperparathyroidism]. 1962 56

Hypercalcemia occurs in sarcoidosis because of 1,25-dihydroxyvitamin D production by pulmonary alveolar macrophages. Long-standing hypercalcemia and hypercalciuria may cause such complications as nephrocalcinosis, nephrolithiasis, and soft tissue calcification, which can be at least partially reversible with treatment. Here we present a 43-year-old African-American man with diffuse soft tissue calcifications and acute kidney injury owing to sarcoidosis-induced hypercalcemia, probably exacerbated by sun exposure and phosphorus intake in the form of dietary cola drinks. Soft tissue calcifications resolved and kidney function improved significantly with hydration and glucocorticoid therapy. We discuss the pathophysiology of the hypercalcemia of sarcoidosis and current treatment options.
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PMID:Hypercalcemia and soft tissue calcification owing to sarcoidosis: the sunlight-cola connection. 2020 Sep 68

The kidney is one of the classical target organs of PTH action. Symptomatic primary hyperparathyroidism (PHPT) is nowadays less frequent but mostly occurs with renal symptoms, in particular kidney stones. Nephrocalcinosis and polyuria, the latter closely related to the severity of hypercalcemia, are uncommon. Parathyroidectomy leads to a marked and long-lasting improvement of nephrolithiasis, whereas it has a limited effect on nephrocalcinosis. Kidney failure is one of the long-term complications of PHPT and is associated with a more severe clinical expression of the disease and a higher risk of morbidity and mortality. Current guidelines on the management of asymptomatic PHPT, the most common presentation of PHPT today, recommend surgical treatment if renal function is decreased. However, in this particular clinical setting it is unclear whether PHPT is really associated with a more rapid decline of renal function or whether successful parathyroidectomy could protect renal function.
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PMID:[Renal function in primary hyperparathyroidism]. 2092 3

Growth hormone excess has been associated with hypercalciuria and nephrolithiasis. Hypercalcemia in acromegaly is rare and usually due to coexistent primary hyperparathyroidism. To report two cases of 1,25-dihydroxyvitamin D (1,25 (OH)(2) D)-dependent hypercalcemia in cromegaly. A 50 year-old female with 2 years history of hypercalcemia presented with features of acromegaly. Serum calcium (Ca) was 10.9 mg/dl (8.6-10.2), parathyroid hormone (PTH) 20 pg/ml (10-65), PTH-related peptide undetectable, and 1,25 (OH)(2) D 119 pg/ml (15-75). Insulin-like growth factor 1 (IGF1) was 911 ng/ml (49-292) and growth hormone (GH) 14.5 ng/ml (0.03-10). MRI showed a 1.7 cm pituitary tumor. Transsphenoidal adenectomy (TSA) resulted in normalization of IGF1, GH, Ca, and 1,25 (OH)(2) D (50 pg/ml) and complete tumor resection. A 52-year-old female was diagnosed with visual field deficits on routine exam. MRI showed a 3 cm invasive pituitary macroadenoma. IGF1 was 416 ng/ml (87-238) and GH 75.8 (0-6.0) ng/ml. Incidentally, she was found with high Ca of 10.8 mg/dl (8.9-10.3) associated with PTH 19 pg/ml and 1,25 (OH)(2) D66 pg/ml. Postoperatively, IGF1 and GH remained abnormal (440 and 12.8 ng/ml, respectively), while MRI showed parasellar tumor residue. Ca remained high (10.1-11.1 mg/dl), along with elevated 1,25 (OH)(2) D level (81.3 pg/ml). In both cases, other causes of hypercalcemia were ruled out. We present 2 cases of 1,25 (OH)(2) D-dependent hypercalcemia associated with growth hormone excess. Complete resection of tumor produced biochemical remission of acromegaly and normalization of calcium and 1,25 (OH)(2) D levels, while incomplete resection was associated with persistent 1,25 (OH)(2) D-dependent hypercalcemia. Acromegaly should be considered a cause of 1,25 (OH)(2) D-dependent hypercalcemia.
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PMID:Acromegaly as a cause of 1,25-dihydroxyvitamin D-dependent hypercalcemia: case reports and review of the literature. 2118 40

We report the use of a genetic test for therapeutic decision making in a case of primary hyperparathyroidism associated with Cushing's disease (CD). A 20-year-old woman was evaluated for gradual weight gain, asthenia, muscle pain, and hypertension. Biochemical and radiologic tests confirmed CD and she underwent transsphenoidal surgery. Immunohistochemistry of the microadenoma was positive for adrenocorticotropic hormone (ACTH). On follow-up, hypercalcemia with high parathyroid hormone (PTH) levels was detected, associated with nephrolithiasis and low bone mineral density in the spine and hip. Parathyroid scintigraphy showed tracer uptake in the inferior region of the left thyroid lobe, and cervical ultrasound showed a heterogeneous nodule in the same area, suggestive of a parathyroid adenoma (PA). Genetic testing detected mutation in the MEN 1 gene and total parathyroidectomy with the implantation of a fragment of one gland in the forearm was performed. Pathology showed a PA and 3 normal parathyroid glands, without hyperplasia, despite the diagnosis of MEN 1. This case illustrates the role of genetic testing in defining the therapeutic approach for sporadic MEN 1.
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PMID:Application of genetic testing to define the surgical approach in a sporadic case of multiple endocrine neoplasia type 1. 2134 Jan 56

Although parathyroidectomy remains the only curative approach to most primary hyperparathyroidism cases, medical treatment with cinacalcet HCl has been proven to be a reasonable alternative for several patient subgroups. Cinacalcet almost always controls hypercalcemia and hypophosphatemia sufficiently. PTH levels are lowered, and cognitive parameters improve. While an increase in bone mineral density DEXA scan scores was not demonstrated in cinacalcet trials, the same applies to more than half of patients after parathyroidectomy. Medical therapy should be first choice in patients with hyperplasia in all glands rather than an isolated adenoma (10-15%), patients with persisting HPT following unsuccessful surgery or inoperable cases due to comorbidities, and patients detected in lab screens for hypercalcemia before developing symptoms who should be treated early but are usually reluctant to undergo surgery. Nephrolithiasis was not found to occur more frequently in cinacalcet trial groups, but urine calcium excretion as one major risk factor of this complication of primary HPT may increase on cinacalcet. Patients carrying the rs1042636 polymorphism of the calcium-sensing receptor gene respond more sensitively to cinacalcet and have a higher risk of calcium stone formation. Cinacalcet is usually administered twice daily but three or four doses per day should be discussed to mimic the beneficial pulsatile PTH-pattern.
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PMID:Cinacalcet treatment of primary hyperparathyroidism. 2146 94

Sotos syndrome is characterized by overgrowth, a typical facial appearance, and learning difficulties. It is caused by heterozygous mutations, including deletions, of NSD1 located at chromosome 5q35. Here we report two unrelated cases of Sotos syndrome associated with nephrocalcinosis. One patient also had idiopathic infantile hypercalcemia. Genetic investigations revealed heterozygous deletions at 5q35 in both patients, encompassing NSD1 and SLC34A1 (NaPi2a). Mutations in SLC34A1 have previously been associated with hypercalciuria/nephrolithiasis. Our cases suggest a contiguous gene deletion syndrome including NSD1 and SLC34A1 and provide a potential genetic basis for idiopathic infantile hypercalcemia.
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PMID:Sotos syndrome, infantile hypercalcemia, and nephrocalcinosis: a contiguous gene syndrome. 2159 70

Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolic pathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, and renal handling, but hypercalcemia occurs when at least 2 of these 3 metabolic pathways are altered. Calcium metabolism mainly depends on the activity of parathyroid hormone (PTH). Its secretion is strictly controlled by the ionized serum calcium levels through a negative feed-back, which is achieved by the activation of calcium-sensing receptors (CaSRs) mainly expressed on the surface of the parathyroid cells. The PTH receptor in bone and kidney is now referred as PTHR1. The balance of PTH, calcitonin, and vitamin D has long been considered the main regulator of calcium metabolism, but the function of other actors, such as fibroblast growth factor-23 (FGF-23), Klotho, and TPRV5 should be considered. Primary hyperparathyroidism and malignancy are the most common causes of hypercalcemia, accounting for more than 90% of cases. Uncontrolled hypercalcemia may cause renal impairment, both temporary (alteration of renal tubular function) and progressive (relapsing nephrolithiasis), leading to a progressive loss of renal function, as well as severe bone diseases, and heart damages. Advances in the understanding of all actors of calcium homeostasis will be crucial, having several practical consequences in the treatment and prevention of hypercalcemia. This would allow to move from a support therapy, sometimes ineffective, to a specific and addressed therapy, especially in patients with chronic hypercalcemic conditions unsuitable for surgery.
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PMID:Calcium metabolism & hypercalcemia in adults. 2175 30


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