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)

Posterior reversible encephalopathy syndrome (PRES) is a leukoencephalopathy clinically characterized by headache, altered mental status, visual loss and seizures. Neuroimaging demonstrates symmetrical posterior cortical and subcortical lesions. The exact pathophysiology is unknown but there is a strong association with immunosuppressants and hypertension. We report two cases of PRES in normotensive patients with severe hypercalcemia as the only identifiable cause. Possible pathophysiological mechanisms are discussed.
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PMID:Posterior reversible encephalopathy syndrome due to severe hypercalcemia. 1242 98

We report a case of genital sarcoidosis that presented characteristic features on MRI. A 25-year-old man sarcoidosis patient with ocular and lung lesions presented a painful mass in the left scrotum together with systemic symptoms of fever, appetite loss, headache, and stomach-ache during the tapering of steroids. The patient was hypercalcemic, and this was thought to be the cause of his systemic symptoms. MRI showed multiple nodules of bilateral testes and enlargement of bilateral epididymis; the patient was diagnosed with testicular and epididymal lesions of sarcoidosis. An increased steroid dosage improved his hypercalcemia and genital lesions.
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PMID:Sarcoidosis with bilateral epididymal and testicular lesions. 1258 27

Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis. The production of monoclonal immunoglobulins with or without light chains is a major feature of the disease. Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma. The usual presenting features of MM include bone pain, weakness, fatigue, fever and infection. Neurologic symptoms are less common but one must not forget that MM may present with a neurologic disease. Careful neurologic history and examination are mandatory in patients with MM. Neurologic symptoms may be a direct manifestation of MM or may be due to the immune effect of monoclonal proteins directed against different neural structures. Finally, metabolic consequences (uremia, hypercalcemia, hyperviscosity) of MM may produce a broad spectrum of different neurologic symptoms including headache, blurring of vision, drowsiness, precoma, coma, vertigo, ataxia, hemiparesis and epileptiform seizures. The most common location of bone changes in MM is the thoracic spine, where it causes osteolytic changes with consequent compressive fractures. The most disastrous sequel is paraplegia. Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur. Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space. However, patients with solitary extradural myeloma have been reported. Skull myeloma is frequently asymptomatic. It may grow externally or, rarely, there is intracranial expansion. Involvement of the cranial nerves is not rare, with II, V, VI, VII and VIII cranial nerves being most often affected. Isolated intracerebral plasmacytomas are extremely rare. Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass. Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty. Therapeutic approach is dictated by the presenting symptoms. In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate. Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy. Surgical decompression is used in patients with vertebral collapse and vertebral instability. Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies. A viscous cement is injected into the cavity by a balloon-like inflatable bone tampon. It has been successfully employed to improve the quality of life, to reduce pain, and to increase overall functioning in patients with vertebral compression fractures by restoring most of the original height of the vertebral body. Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism. It seems that bisphosphonates, by inhibiting bone resorption, alter the microenvironment in which the MM cells grow.
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PMID:[Neurologic sequelae of bone changes in multiple myeloma and its therapy]. 1263 Mar 41

Tazarotene is an acetylenic retinoid which is metabolised to tazarotenic acid and which binds selectively to the retinoid receptors RARbeta and RARgamma. The safety, toxicity and pharmacokinetics of oral tazarotene were determined over 12 weeks of treatment in 34 patients with advanced cancer. Commonly seen toxicities were mucocutaneous symptoms, musculoskeletal pain and headache. Dose-limiting toxicities were hypercalcaemia, hypertriglyceridaemia and musculoskeletal pain. The maximum tolerated dose of tazarotene in this schedule is 25.2 mg day(-1). Plasma concentrations of tazarotenic acid were found to peak rapidly within 1-3 h of dosing and thereafter declined quickly. The C(max) and AUC values on day 0, and weeks 2 and 4 were similar indicating no drug accumulation. The dose-normalised C(max) and AUC values at different dose levels and different study days appeared to be similar indicating linear pharmacokinetics. No objective responses were seen, although stable disease was seen in six out of eight evaluable patients receiving the three highest dose levels of tazarotene (16.8, 25.2 or 33.4 mg day(-1)). We conclude that oral tazarotene is well tolerated when administered daily for 12 weeks, has a favourable toxicity profile compared with other retinoids and merits further investigation as an anticancer therapy.
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PMID:A phase 1 study of tazarotene in adults with advanced cancer. 1294 9

The ideal treatment of osteoporosis should preferably prevent fractures through normalization of bone mass and bone micro-architecture. Biosynthetic human parathyroid hormone 1-34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2-3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 microg/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged.
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PMID:Teriparatide (biosynthetic human parathyroid hormone 1-34): a new paradigm in the treatment of osteoporosis. 1522 97

Brown tumor is a focal lesion of the bone caused by primary or, less commonly, secondary or tertiary hyperparathyroidism (HPT). While the mandible is the most frequently involved bone in the head and neck region, atypical involvement of the cranium in the area of the sphenoid sinus is exceedingly rare. In the literature, a unique case of brown tumor of the sphenoid sinus was reported in a patient with primary HPT. We present a case of sphenoid sinus and occipital bone brown tumor associated with primary HPT. A 47-yr-old woman presented a 2-yr history of headaches, dizziness, diffuse body and articular pain, fatigue, and a 6-month history of intermittent nausea and vomiting, polydipsia, and polyuria. Magnetic resonance imaging (MRI) demonstrated an expansive mass lesion in the sphenoid sinus with erosion of the sellar floor and medial wall of the right orbit, and expansion in the medulla of bone. Examination of biopsy specimens obtained from sphenoid sinus mass confirmed the diagnosis of brown tumor. The biochemical laboratory studies showed elevation of parathyroid hormone and confirmed the diagnosis of primary HPT. Excision of a parathyroid adenoma affected the metabolic status into normalizing. At the follow-up of 12 months postoperatively, the size of sphenoid sinus brown tumor decreased and the mass of occipital bone disappeared. In conclusion, this is a first report of primary HPT masquerading as a destructive fibrous sphenoid sinus brown tumor associated with a mass lesion of occipital bone and hypercalcemia in the literature.
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PMID:Sphenoid sinus brown tumor, a mass lesion of occipital bone and hypercalcemia: an unusual presentation of primary hyperparathyroidism. 1523 58

Familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) are consequent to inactivating mutations of the calcium-sensing receptor (CaR) gene. FHH is usually associated with heterozygous inactivating mutations of the CaR gene, whereas NSHPT is usually due to homozygous inactivation of the CaR gene. FHH is generally asymptomatic and is characterized by mild to moderate lifelong hypercalcemia, relative hypocalciuria, and normal intact PTH, whereas individuals with NSHPT frequently show life-threatening hypercalcemia. In this study, we report a novel inactivating mutation of the CaR gene, identified in a 9-yr-old Brazilian girl who was found to be severely hypercalcemic during investigation of a 6-month history of headaches and vomits. Direct sequencing of the CaR gene from this patient showed a novel homozygous mutation (L13P) in exon 2. Functional characterization by intracellular calcium measurement by fluorometry showed that the mutant receptor had a dose-response curve shifted to the right relative to that of wild type. The proband's consanguineous parents, who had mild asymptomatic hypercalcemia, showed the same mutation in the heterozygous form. The mutation described in this study is the inactivating missense mutation present at the most N-terminal end among the known CaR missense mutations. This study reinforces the fact that patients with homozygous inactivation of the CaR gene may present with severe hypercalcemia in different phases of life.
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PMID:Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating mutation of the calcium-sensing receptor. 1557 40

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

(1) Oral alendronic acid is the reference drug for women with osteoporosis and a previous vertebral fracture. In a placebo-controlled trial in women who were also taking calcium and vitamin D, treatment with alendronic acid for three years reduced the incidence of symptomatic vertebral fractures (2.3% versus 5%) and wrist fractures (2.2% versus 4.1%) and, albeit with a lower level of evidence, the incidence of hip fractures (1.1% versus 2.2%). (2) Teriparatide, a biotech drug, reproduces the 34 N-terminal amino acids of parathormone. It is marketed in Europe for subcutaneous treatment of "proven" postmenopausal osteoporosis. (3) The cornerstone of the clinical evaluation dossier is a randomised placebo-controlled double-blind trial in 1637 women also taking calcium and vitamin D. The two doses of teriparatide (20 micrograms/day and 40 micrograms/day), given for a median of 19 months, reduced the risk of new radiologically documented vertebral fractures (about 4% versus 14% in the placebo group) and spinal pain (about 16% versus 23% in the placebo group), but not the risk of hip fracture. (4) In a double-blind trial in 146 postmenopausal women also taking calcium and vitamin D, 40 micrograms/day teriparatide given subcutaneously for 14 months increased spinal mineral bone density significantly more than 10 mg/day alendronic acid given orally. The trial was not designed to show a difference in clinical outcome (fractures). (5) The main adverse effects of teriparatide reported to date are nausea, headache, cramp, hypercalcemia and hyperuricemia. (6) A rat study showed an increased risk of osteosarcoma. This tumour is rare in humans, and the number of patients so far enrolled in clinical trials is insufficient to document a possible increase in risk associated with teriparatide. (7) The need for daily subcutaneous injections and for refrigeration of the prefilled syringes are two notable disadvantages of teriparatide therapy. (8) In practice, alendronic acid is better assessed and remains the reference treatment, combined with calcium and vitamin D, for secondary prevention of osteoporotic fracture in postmenopausal women.
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PMID:Teriparatide: new preparation. Osteoporosis: less well evaluated than alendronic acid. 1574 48

Pheochromocytoma is a rare tumor of chromaffin cells that secrete catecholamines and several cytokines. The clinical manifestations are protean and may include hypertension, weight loss, sweating, palpitation, headache, anxiety, tremor, nausea, vomiting, and hypercalcemia. The tumor can mimic many unrelated diseases, leading to significant delay and difficulty in diagnosis. We report a case of a 37-yr-old male admitted with jaundice, dark urine, fever, and signs of a systemic inflammatory response. Abdominal computed tomography revealed a heterogeneously enhancing tumor between the pancreatic tail and left kidney. There was no evidence of obstruction to bile flow, neoplastic involvement of the liver or bile ducts, or infectious etiology. The tumor was removed and found to be a pheochromocytoma. Immunohistochemical analysis revealed the presence of interleukin-1beta in the tumor cells. After surgery, the jaundice resolved without further treatment, leading us to the conclusion that it was a paraneoplastic phenomenon possibly related to interleukin-1beta production. We suggest that occult pheochromocytoma should be added to the differential diagnosis of unexplained intrahepatic cholestasis.
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PMID:Intrahepatic cholestasis as a paraneoplastic syndrome associated with pheochromocytoma. 1588 66


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