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)

Parathyroid hormone-related protein (PTHrP) plays a central role in humoral hypercalcemia of malignancy (HHM), which is one of the most frequent paraneoplastic syndromes. PTHrP produced by the tumor acts through a common PTH/PTHrP receptor to promote bone resorption, inhibit calcium excretion from the kidney, and induce hypercalcemia. Patients with HHM often develop cachexia associated with typical symptoms such as anorexia, malaise, nausea, constipation, polyuria, polydipsia, and confusion. The etiology of the cachexia is not fully understood but is thought to be caused by hypercalcemia and various cytokines such as interleukin-6, tumor necrosis factor-alpha, leukemia inhibitory factor, and others. In this study, we investigated the role of PTHrP in hypercalcemia and cachexia in HHM by using humanized anti-PTHrP antibody. A mouse monoclonal antibody that binds to PTHrP amino acid sequence 1-34 and inhibits PTHrP function has been humanized to create a specific and potent agent for the treatment of patients with HHM. The mouse monoclonal antibody has been shown to have antihypercalcemic activity against nude mice bearing human tumors. Because a mouse antibody is highly immunogenic in human patients, the complementarity-determining regions from the mouse antibody were grafted into a human antibody. The resulting humanized antibody specifically recognizes PTHrP(1-34) and neutralizes PTHrP functions in vitro and in vivo. The humanized anti-PTHrP antibody was administered intravenously to HHM model animals bearing tumors such as LC-6 human lung carcinoma. These animals showed symptoms similar to those of patients with HHM (eg, hypercalcemia and cachexia). The humanized anti-PTHrP antibody-treated animals responded with normalization of blood ionized calcium level through an improvement of bone metabolism and calcium excretion. Moreover, the treated animals also showed an improvement in body weight, ultromotivity, metabolic alkalosis, food consumption, water intake, serum phosphorus, and renal function. Consequently, the humanized antibody-treated animals experienced complete resolution of hypercalcemia and cachexia. These results suggest that the humanized antibody would be an effective and beneficial agent for patients with HHM, and that PTHrP is a major pathogenetic factor of hypercalcemia and cachexia in patients with HHM.
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PMID:Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody. 1461 38

Primary hyperparathyroidism is the most frequent cause of hypercalcemia in ambulatory patients. The condition is most common in postmenopausal women, although it can occur in persons of all ages, including pregnant women. If symptoms are present, they are attributable to hypercalcemia and may include weakness, easy fatigability, anorexia, or anxiety. However, most persons have no symptoms, and primary hyperparathyroidism usually is diagnosed after an elevated serum calcium level is found incidentally on multiphasic chemistry panel testing. Persistent hypercalcemia and an elevated serum parathyroid hormone level are the diagnostic criteria for primary hyperparathyroidism. Other causes of hypercalcemia are rare, and usually are associated with low (or sometimes normal) parathyroid hormone levels. Malignancy is the most frequent cause of hypercalcemia in hospitalized patients. Parathyroidectomy is the definitive treatment for primary hyperparathyroidism. When performed by experienced endocrine surgeons, the procedure has success rates of 90 to 95 percent and a low rate of complications. Asymptomatic patients who decline surgery and meet criteria for medical management must commit to conscientious long-term monitoring. Any unexplained elevation of the serum calcium level should be evaluated promptly to prevent complications from hypercalcemia.
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PMID:Hyperparathyroidism. 1566 24

A 48-year-old woman was referred to our hospital because of secondary hypothyroidism. Upon admission a left adrenal tumor was also detected using computed tomography. Laboratory data and adrenal scintigraphy were compatible with Cushing syndrome due to the left adrenocortical adenoma, although she showed no response to the TRH stimulation test. Hypercortisolism resulting in secondary hypothyroidism was diagnosed. After a left adrenalectomy, hydrocortisone administration was begun and the dose was reduced gradually. After discharge on the 23rd postoperative day, she began to suffer from anorexia. ACTH level remained low, and serum cortisol, free thyroxine and TSH levels were within the normal range. Since her condition became worse, she was re-admitted on the 107th postoperative day at which time serum calcium level was high (15.6 mg/dl). Both ACTH response to the CRH stimulation test and TSH response to the TRH stimulation test were restored to almost normal levels, but there was no response of cortisol to CRH stimulation test. We diagnosed that the hypercalcemia was due to adrenal insufficiency. Although the serum calcium level decreased to normal after hydrocortisone was increased (35 mg/day), secondary hypothyroidism recurred. It was suggested that sufficient glucocorticoids suppressed TSH secretion mainly at the pituitary level, which resulted in secondary (corticogenic) hypothyroidism. However, both postoperative glucocorticoid deficiency and adequate amounts of thyroxine due to the elimination of inhibition of TSH secretion by glucocorticoids might cause hypercalcemia possibly through increased bone reabsorption of calcium.
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PMID:A case of cushing syndrome with both secondary hypothyroidism and hypercalcemia due to postoperative adrenal insufficiency. 1500 16

Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (>12 <13.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (>13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca >13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.
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PMID:Hyperparathyroidism. 1524 24

A 36-yr-old woman began to suffer from headache, anorexia and general fatigue at 35 weeks' gestation. About 2 or 3 months after the delivery, fever, tachycardia and generalized musculoskeletal disorder appeared. Thereafter, they worsened rapidly, accompanied by a disturbance of consciousness and hypercalcemia. Thyrotoxicosis, due to a post-partum thyroiditis, and glucocorticoid deficiency, due to a pituitary failure, probably associated with lymphocytic hypophysitis, were also observed. All the symptoms and hypercalcemia disappeared after the glucocorticoid replacement therapy and the normalization of thyroid hormone levels. Serum and urinary bone resorption markers, such as urine pyridinoline (U-Pyr), urine deoxypyridinoline (U-DPD), urine amino-terminal telopeptide of type I collagen (U-NTx) and serum carboxy-terminal telopeptide of type I collagen (ICTP), were extremely high at the hypercalcemic state. In this case, they were 10 to 20 times higher than the normal upper limits, and then markedly decreased in a normocalcemic state, thereby showing an extreme acceleration of bone resorption in a state of both thyrotoxicosis and glucocorticoid deficiency.
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PMID:Elevated bone resorption markers in a patient with hypercalcemia associated with post-partum thyrotoxicosis and hypoadrenocorticism due to pituitary failure. 1563 35

There is a high prevalence of protein-energy malnutrition (PEM) in chronic dialysis patients. Causes of PEM include the catabolic effects of hemodialysis treatments, acidemia associated with end-stage renal disease, common comorbid conditions, and uremia-induced anorexia. Morbidity and mortality increase with PEM. Before considering parenteral nutrition (PN) as a nutrition intervention in a maintenance dialysis patient, all other efforts to promote optimal nutrition need to be exhausted. The first step is careful evaluation of protein-energy status, followed by intensive nutrition counseling. If necessary, this is followed by oral nutrition supplementation, appetite stimulation, enteral tube feedings, and finally PN. Short-term parenteral nutrition (PN) became a crucial component of the management of a 38-year-old hemodialysis (HD) patient who endured serious complications after kidney transplant rejection. A profound and prolonged malnourished state followed her treatment for necrotizing pancreatitis. She had developed persistent hypercalcemia believed secondary to tertiary hyperparathyroidism (HPT) and immobilization. Later, she developed hungry bone syndrome (HBS) after parathyroidectomy (PTX). She also developed refeeding syndrome after initiation of PN. The patient's persistent, poorly understood hypercalcemia did not resolve even after PTX and removal of all other sources of vitamin D and calcium from her feedings, medications, and dialysis bath. The close communication of the inpatient and outpatient dialysis multidisciplinary teams became a key component to the successful outcome in this complex patient.
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PMID:The use of parenteral nutrition in a severely malnourished hemodialysis patient with hypercalcemia. 1620 98

A review of records from the AnTox database of the American Society for the Prevention of Cruelty to Animals Animal Poison Control Center identified 43 dogs that developed increased blood urea nitrogen concentration, serum creatinine concentration, or both as well as clinical signs after ingesting grapes, raisins, or both. Clinical findings, laboratory findings, histopathological findings, treatments performed, and outcome were evaluated. All dogs vomited, and lethargy, anorexia, and diarrhea were other common clinical signs. Decreased urine output, ataxia, or weakness were associated with a negative outcome. High calcium x phosphorus product (Ca x P), hyperphosphatemia, and hypercalcemia were present in 95%, 90%, and 62% of the dogs in which these variables were evaluated. Extremely high initial total calcium concentration, peak total calcium concentration, initial Ca x P, and peak Ca x P were negative prognostic indicators. Proximal renal tubular necrosis was the most consistent finding in dogs for which histopathology was evaluated. Fifty-three percent of the 43 dogs survived, with 15 of these 23 having a complete resolution of clinical signs and azotemia. Although the mechanism of renal injury from grapes and raisins remains unclear, the findings of this study contribute to an understanding of the clinical course of acute renal failure that can occur after ingestion of grapes or raisins in dogs.
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PMID:Acute renal failure in dogs after the ingestion of grapes or raisins: a retrospective evaluation of 43 dogs (1992-2002). 1623 10

Plasma cell leukemia (PCL) is a rare disease and is the least common variant of multiple myeloma accounting for 2-3% of all plasma cell dyscrasias. We report a patient who presented with history of high grade fever, weakness, palpitations, loss of appetite, bone pains and mental confusion for twenty days. Initial evaluation revealed plasmacytosis with blood plasma cell count of 5184/cumm. His hemoglobin (Hb) was 11.3 gm/dl, platelets were 75000/cumm and total leucocyte count (TLC) was 21600/cumm (24% plasma cells). Bone marrow examination revealed >60% plasmablasts. Serum LDH was high at 3117 U/L and serum calcium was also elevated at 13.9 mg/dl. A diagnosis of PCL was made and the patient was started on treatment for hypercalcaemia with Melphalan/Prednisolone regime along with supportive care. Patient deteriorated very rapidly despite treatment and died on the eighth day. A detailed report of this case and a review of PCL is presented here.
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PMID:Plasma cell leukemia: case report of a rare and aggressive variant of multiple myeloma. 1630 56

Primary hyperparathyroidism (PHPT) is characterized by excessive PTH secretion in respect to calcium homeostasis needs, due to parathyroid adenoma (80% of cases), hyperplasia (15-20%), or carcinoma (1-2%). In familial forms of PHPT, several mutations have an established role: menin gene for MEN type 1, RET for MEN type 2a, calcium-sensing receptor gene for familial hypocalciuric hypercalcemia, parafibromin gene for PHPT-jaw tumour and carcinoma. Etiology of sporadic adenomas (80% of PHPT cases) is less defined, being most commonly found a mutation of menin gene or activation of PRAD1 oncogene. In recent years, the classical features of the disease became less common. Typically, bone involvement is now represented by a reduced bone mass at skeletal sites more rich in cortical tissue. Prominently trabecular skeletal sites are relatively spared, because of the anabolic effects of a slight PTH excess on trabecular tissue. PHPT patients may have increased fracture risk, though it is not clear why bone damage is more severe in a subgroup of patients. Clinical features of hypercalcemia may be fatigue, anorexia, thirst, and polyuria. Vague neurological and psychiatric symptoms, such as weakness, anxiety, depression, paresthesias, and muscular cramps may ameliorate after parathyroidectomy. Recent reports indicate increased cardiovascular mortality in PHPT patients. Diagnosis is based on the detection of hypercalcemia, together with inappropriately high serum PTH levels. Preoperative localization of the diseased glands is mandatory in persistent or recurrent PHPT, as like as when minimally invasive surgery is planned. High resolution ultrasonography and SPECT double-phase 99m Tc-sestamibi scintigraphy are the most commonly employed techniques. Intraoperatory PTH assay may confirm successful surgery when serum concentrations decrease more than 50%. Surgical therapy is indicated in patients with renal or skeletal complications, such as in those with previous parathyrotoxic crisis. Many surgeons in recent years adopted minimally invasive parathyroidectomy. Medical treatment is an option for patients unwilling or unfitted for surgery because of severe concomitant diseases. Employed therapy includes estrogens, SERMs, bisphosphonates and calcimimetics.
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PMID:[Primary hyperparathyroidism]. 1638 70

Hypercalcemia associated with malignancies is reported in up to 20 to 30% of patients with cancer during the course of the disease, and points to a poor prognosis. Symptoms related to the central nervous system, as progressive mental impairment, stupor and coma, predominate. Alterations in kidney function (water-concentrating defect leading to polyuria) and gastrointestinal tract (anorexia, nausea, vomiting) corroborate to dehydration and a further increase in serum calcium. Cancer-induced hypercalcemia may be classified as: 1) local osteolytic hypercalcemia (LOH), due to marked increase in osteoclastic bone resorption in areas surrounding the malignant cells within the marrow space; 2) humoral hypercalcemia of malignancy, caused by the secretion of parathyroid hormone-related protein (PTHrP) by the malignant tumor; 3) ectopic hyperparathyroidism; 4) 1,25(OH)2 D-secreting tumors. Adequate control of hypercalcemia is necessary to give the patient time to respond to anti-cancer therapy. Volume expansion with saline will correct dehydration, improve glomerular filtration and increase urinary calcium excretion, which may be further stimulated by loop diuretics. Intravenous bisphosphonates are the most effective agents to control hypercalcemia, as they block osteoclastic osteolysis and also have antitumoral effects, decreasing bone metastases. New approaches to control the skeletal manifestations of malignancies are anti-PTHrP and anti-RANKL antibodies, osteoprotegerin, and also proteasome inhibitors in the case of multiple myeloma.
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PMID:[Hypercalcemia of malignancy: clinical features, diagnosis and treatment]. 1644 66


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