Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reduced bone formation has been documented in both children and adults following burn injury of > or = 40% total body surface area. In children, reduced bone formation and hypercalciuria may be the underlying causes of acute and sustained reduction in bone mineral density. The possible consequences of this reduction are an increase in extrapolated annual fracture incidence and reduced peak bone mass. Excessive endogenous glucocorticoid production, immobilization, bone marrow suppression, and magnesium depletion are all postulated as underlying causes. The most promising potential management agent is recombinant human growth hormone, which can stimulate bone formation via production of insulin-like growth factor I(IGF-I) and its associated binding protein, IGFBP-3, which correlates with bone mineral density in adults. Long-term treatment may be necessary to see a positive effect on bone formation and bone density. Correcting any detected magnesium depletion, and exercise as tolerated, are two other management strategies that might improve bone formation in this population.
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PMID:The management of acute bone loss in severe catabolism due to burn injury. 943 50

We have shown that Walker 256/S mammary carcinoma caused osteoporosis-like changes in young female rats, accompanied by low serum estradiol and hypercalciuria without changes in the serum levels of calcium, phosphorus, and parathyroid hormone-related peptide. In this study, we investigated the cause of bone loss after Walker 256/S inoculation into female 6-week-old Wistar Imamichi rats, focusing on the sex hormone balance in the host animal. Walker 256/S-bearing rats showed characteristic osteoporosis, with a significant increase in spleen weight and a significant decrease in uterine weight by 14 days after s.c. tumor inoculation. In the in vitro bone marrow culture, mineralized nodule formation ability decreased according to the time after tumor inoculation, and tartrate-resistant acid phosphatase-positive multinucleated cell formation increased at 7 days after tumor inoculation, but it began to decrease at 14 days after tumor inoculation. This indicates that after inoculation with Walker 256/S tumor, the progenitors of osteoblasts and ostroclasts lost their balance in the bone turnover, resulting in bone resorption. On the other hand, Walker 256/S carcinoma expressed luteinizing hormone-releasing hormone (LH-RH) mRNA, and in Walker 256/S-bearing rats, the serum LH-RH level increased significantly from 3 days after tumor inoculation, whereas in the healthy control rats, this level was very low. Consequently, the serum levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone were significantly lower in the tumor-bearing rats than in the healthy control rats. Because the LH-RH gene is located in the long prolactin release-inhibiting factor (PIF) gene and mRNA amplified by reverse transcription-PCR in this study contained whole LH-RH and a part of PIF, the Walker 256/S tumor is thought to express PIF. Indeed, the serum prolactin level decreased in tumor-bearing rats. The serum level of growth hormone, one of the other pituitary hormones, was not changed. Moreover, the level of an osteolytic cytokine, tumor necrosis factor alpha, increased in the serum of Walker 256/S-bearing rats, although this may be a result of the immune response of the host animal to tumor growth as well as an enlarged spleen. In conclusion, the Walker 256/S tumor lowers estrogen secretion through ectopical oversecretion of LH-RH, and then osteolytic cytokines, such as tumor necrosis factor alpha, increase in tumor-bearing rats, escape the control of estrogen, and activate osteoclasts, resulting in bone loss in a short period.
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PMID:Walker 256/S carcinosarcoma causes osteoporosis-like changes through ectopical secretion of luteinizing hormone-releasing hormone. 1009 51

We have shown previously that chronic hyperchloremic metabolic acidosis (CMA) induces severe negative nitrogen balance and renal phosphate depletion and decreases serum insulin-like growth factor-1 (IGF-1) in association with growth hormone (GH) insensitivity in humans. The present study investigated whether acidosis-induced renal nitrogen wasting and renal phosphate depletion are mediated by GH insensitivity/low IGF-1 and thereby responsive to GH treatment. The effects of GH on acidosis-induced changes in divalent cation metabolism and acidosis-induced hypothyroidism were also investigated. CMA (delta[HCO3], -10.5 mmol/L) was induced in six healthy male subjects ingesting 4.2 mmol NH4Cl/kg body weight [BW]/d for 7 days. Recombinant human GH (0.1 U/kg BW/12 h subcutaneously) was administered for 7 days while acid feeding was continued. GH increased serum IGF-1 from 22.1 +/- 1.4 to 87 +/- 8.4 nmol/L (control level, 36.4 +/- 2.2). GH decreased urinary nitrogen excretion, resulting in a cumulative nitrogen retention of 2,404 mmol, thereby correcting the acidosis-induced cumulative increase in nitrogen excretion (2,506 mmol) despite continued acid feeding. GH attenuated the acidosis-induced hyperphosphaturia (cumulative phosphate retention, 91 mmol) and corrected the hypophosphatemia. GH did not affect acidosis-induced ionized hypercalcemia, but further exacerbated acidosis-induced hypercalciuria (cumulative loss, 27.3 mmol). GH significantly further increased serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and further decreased intact PTH (from 10 +/- 1 to 6 +/- 1 pg/mL). Acidosis also induced hypomagnesemia and hypermagnesuria (cumulative loss, 9.4 mmol, ie, renal magnesium wasting), a novel finding, which was significantly attenuated by GH (cumulative retention, 5.0 mmol). In conclusion, GH corrected acidosis-induced renal nitrogen wasting, which may be caused, at least in part, by decreased IGF-1 levels. GH further increased serum 1,25(OH)2D and the systemic calcium load, which account for the suppression of parathyroid hormone (PTH) despite renal PO4 retention and correction of hypophosphatemia. GH attenuated acidosis-induced renal magnesium wasting.
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PMID:Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans. 1038 Nov 52

Two Japanese patients, belonging to unrelated families, with idiopathic low-molecular-weight proteinuria (LMWP; Japanese Dent's disease) showed novel mutations of the gene encoding renal-specific chloride channel 5 (CLC-5). Proteinuria was first noticed at the ages of 2 and 3 years in patients 1 and 2, respectively. During follow-up, marked increases in urinary ss(2)-microglobulin levels, hypercalciuria, and high levels of urinary excretion of growth hormone were observed in both patients. Nephrocalcinosis was detected in patient 2. Renal biopsy specimens from both patients showed minimal alterations in glomeruli and tubulointerstitium, except for mild mesangial proliferation in patient 2. DNA sequence analysis of the entire 2,238-bp coding region and exon-intron boundaries of the CLCN5 gene showed the presence of two novel mutations in exon 10, consisting of one missense mutation (I524K) in patient 1 and one nonsense mutation (R637X) in patient 2. DNA analysis and measurement of urinary ss(2)-microglobulin levels in family members indicated an X-linked mode of inheritance in patient 1 and sporadic occurrence in patient 2. These results have expanded our understanding of the association between idiopathic LMWP (Japanese Dent's disease) and mutations of the CLCN5 gene.
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PMID:Identification of two novel mutations in the CLCN5 gene in Japanese patients with familial idiopathic low molecular weight proteinuria (Japanese Dent's disease). 1113 79

Metabolic acidosis is an important acid-base disturbance in humans. It is characterised by a primary decrease in body bicarbonate stores and is known to induce multiple endocrine and metabolic alterations. Metabolic acidosis induces nitrogen wasting and, in humans, depresses protein metabolism. The acidosis-induced alterations in various endocrine systems include decreases in IGF-1 levels due to peripheral growth hormone insensitivity, a mild form of primary hypothyroidism and hyperglucocorticoidism. Metabolic acidosis induces a negative calcium balance (resorption from bone) with hypercalciuria and a propensity to develop kidney stones. Metabolic acidosis also results in hypophosphataemia due to renal phosphate wasting. Negative calcium balance and phosphate depletion combine to induce a metabolic bone disease that exhibits features of both osteoporosis and osteomalacia. In humans at least, 1,25-(OH)2 vitamin D levels increase, probably through phosphate depletion-induced stimulation of 1-alpha hydroxylase. The production rate of 1,25-(OH)2 vitamin D is thus stimulated, and parathyroid hormone decreases secondarily. There is experimental evidence to support the notion that even mild degrees of acidosis, such as that occurring by ingestion of a high animal protein diet, induces some of these metabolic and endocrine effects. The possible role of diet-induced acid loads in nephrolithiasis, age-related loss of lean body mass and osteoporosis is discussed.
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PMID:Metabolic and endocrine effects of metabolic acidosis in humans. 1141 68

The effect of estrogens on human growth hormone (HGH) and serum sulfation factor was studied in 4 acromegalic and 3 growth hormone-deficient men. Estrogen treatment (.5-1 mg/day) of acromegalic patients for 7-18 days reduced elevated sulfation factor levels, hypercalciuria, and hydroxyprolinuria levels without markedly affecting HGH levels. Increases in blood urea nitrogen and urinary nitrogen reflected the antianabolic effect of estrogen. Subnormal sulfation factor concentrations in HGH-deficient patients were increased to normal or high levels during 4-6 days of HGH administration and returned to pretreatment levels within 2 days of the last treatment. Combined estrogen and HGH treatment inhibited the elevation of serum sulfation factor, urinary calcium, and hydroxyproline excretion, but did not affect the anabolic response to HGH. Urinary calcium and hydroxyproline levels varied in a fashion similar to serum sulfation factor. The response to HGH in estrogen-treated hypopituitary patients seems to indicate that the stimulation of serum sulfation factor is not required for the anabolic action of HGH.
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PMID:Suppression of growth hormone-dependent human serum sulfation factor by estrogen. 1233 22

Bartter syndrome is a rare autosomal recessive, salt-losing disorder characterized by hypokalemic hypochloremic metabolic alkalosis. A 10-year-old boy had severe growth retardation (height standard deviation score -8.15). He had a thin, triangular face, prominent ears and forehead, and big eyes. Megacystis, bilateral hydroureteronephrosis, and residual urine were detected in ultrasonography, but there was no vesicoureteral reflux. Lumbosacral magnetic resonance (MR) showed posterior disc bulging at L4-5. Serum sodium and chloride levels were normal, but mild hypokalemia was overlooked initially. During follow-up, hypokalemic hypochloremic metabolic alkalosis developed, with high urinary chloride and potassium excretion (52 and 43 mEq/L, respectively). The patient, with renal salt loss, was thought to have classic Bartter syndrome due to absence of nephrocalcinosis, presence of persistent hypercalciuria and sensorineural deafness, and presence of relatively mild clinical and laboratory findings, except polyuria initially. The child was treated with indomethacin, spironolactone, and oral potassium in addition to growth hormone (GH). During treatment, he had considerable increase in weight and height compared with the period of GH therapy only. We present this case because, although growth retardation is a major feature of Bartter syndrome, associated GH deficiency is rarely reported in the literature. Diagnosis of Bartter syndrome was made later, as our patient was followed for megacystis and megaureter secondary to the neurogenic bladder and GH deficiency initially; and proteinuria associated with focal segmental glomerulosclerosis responded to treatment for Bartter syndrome.
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PMID:A patient with Bartter syndrome accompanying severe growth hormone deficiency and focal segmental glomerulosclerosis. 2012 83

Dent disease is an X-linked recessive disorder affecting the proximal tubule and is characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis/nephrolithiasis with a variable number of features of Fanconi syndrome. It is most often associated with mutations in CLCN5, which encodes the endosomal electrogenic chloride/proton exchanger ClC-5. Renal acidification abnormalities are only rarely seen in Dent disease, whereas the hypokalemic metabolic alkalosis associated with hyperreninemic hyperaldosteronism (Bartter-like syndrome) has been reported in only one patient so far. We report on a 5-year-old boy with Dent disease caused by mutation in CLCN5 gene, c.1073G>A, who presented with hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism persisting over the entire follow-up. No mutations were found in NKCC2, ROMK, NCCT, or ClC-Kb genes. In addition, the patient exhibited growth failure associated with partial growth hormone (GH) deficiency. Coexistence of Bartter-like syndrome features with LMWP should prompt a clinician to search for Dent disease. The Bartter syndrome phenotype seen in Dent disease patients may represent a distinct form of Bartter syndrome, the exact mechanism of which has yet to be fully elucidated. Growth delay that persists in spite of appropriate therapy should raise suspicion of other causes, such as GH deficiency.
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PMID:A novel CLCN5 mutation in a boy with Bartter-like syndrome and partial growth hormone deficiency. 2068 Mar 51

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

Acromegaly a common pituitary disorder has significant adverse effects on well-being and survival. The slight increase in the prevalence of hypertension in acromegaly is well known and is proposed to be the direct effects of growth hormone. The hypertension for calculating the prevalence in most series was defined as diastolic more than 100 mmHg, but hypertensive emergency is rarely ever described in the literature. Growth hormone excess has been associated with renal manifestations such as hypercalciuria and nephrolithiasis, but never with renal failure. We present a case referred to a tertiary care nephrology center with malignant hypertension. This is the first case of a patient of acromegaly presenting with hypertensive emergency progressing to malignant nephrosclerosis and renal failure.
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PMID:Hypertensive emergency: A unique manifestation of a pituitary disorder. 2396


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