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

52 patients with Cushing syndrome were studied. According to the appearance of X-ray film of bones, they were divided into three groups: (I) Without osteoporosis, 12 cases (23.1%), (II) Mild osteoporosis, 17 cases (32.7%), (III) Severe osteoporosis with fractured ribs and/or wedge-shaped vertebrae, 23 cases (44.2%). It was found that the mean level of serum calcium in the patients was significantly lower than that in 94 normal subjects (mean +/- S 2.3 +/- 0.2 versus 2.4 +/- 0.1 mmol/L P less than 0.001). The mean concentrations of blood alkaline phosphatase and parathyroid hormone in the patients were much higher than those in normal subjects (65.0 +/- 27.6 versus 42.6 +/- 15.6 IU/L P less than 0.001, 44.6 +/- 22.4 versus 20.6 +/- 8.0 pg/ml P less than 0.001 respectively). The mean level of serum 25 (OH)-D in the patients was significantly lower than that in controls (10.9 +/- 5.6 versus 16.2 +/- 4.6 ng/ml P less than 0.001). Urinary calcium excretion increased in the patients as compared with that in controls (P less than 0.01). The urinary calcium excretion correlated well with the blood total cortisol and urinary free cortisol. It is suggested that hypercalciuria might cause decrease of serum calcium. Thus the parathyroid glands were stimulated and the parathyroid hormone (PTH) secretion was increased. Excess of PTH stimulates bone resorption. All of these factors are involved in the pathogenesis of osteopenia in Cushing's syndrome.
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PMID:[Metabolism of calcium and phosphorus in Cushing syndrome with osteoporosis]. 262 28

To clarify the mechanism for the impaired mineral metabolism in Cushing's syndrome, the clinical features, biochemical parameters before and after oral calcium load, and vitamin D metabolism were compared between two groups of patients of endogenous Cushing's syndrome (17 cases) with and without osteopenia. The patients with osteopenia [OP (+): 7 cases, all female] were older (42.7 +/- 8.3 y. o.) and had a longer duration (117 +/- 75 M) of the syndrome than those without osteopenia [OP (-): 33.8 +/- 8.9 y. o., 36 +/- 25 M]. OP (-) showed a blunted hypercalciuria after oral calcium load (63.7 +/- 20.4 to 90.9 +/- 36.1 mg/g X Cr), while OP (+) had higher levels of urinary excretion of calcium (fasting: 120.4 +/- 37.5, and after oral calcium load: 235.6 +/- 72.6 mg/g X Cr), of cyclic AMP (7.6 +/- 1.1 nmol/dl X GF), and of plasma 1.25(OH)2D (76.6 +/- 34.0 pg/ml) than OP (-) (u-cAMP: 3.2 +/- 2.0 nmol/dl X GF, 1,25(OH)2D: 27.9 +/- 16.3 pg/ml). These results indicate that 1) elderly female patients with Cushing's syndrome of long duration are susceptible to OP, 2) during the early phases of the syndrome, reduced intestinal calcium absorption with sustained calciuria (probably through the inhibition of calcium reabsorptive effect of PTH by glucocorticoid) induces negative calcium balance, leading to 3) a development of secondary hyperparathyroidism which stimulates 1,25(OH)2D synthesis. Thus, the mechanism involving bone resorption stimulated by excess PTH along with the direct inhibition of bone formation by glucocorticoid seems to play an important role in a progressive development of OP in Cushing's syndrome.
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PMID:Impaired mineral metabolism in Cushing's syndrome: parathyroid function, vitamin D metabolites and osteopenia. 375 23

The authors presented the results of a study of the indices of phosphorocalcium homeostasis, metabolism of osseous tissue and calcium regulating hormones in 44 patients with Icenko-Cushing's syndrome with regard to severity of disease and expression of osteoporosis. It was shown that disturbances of phosphorocalcium homeostasis and an increase in the level of the parathyroid hormone were characteristic for the active stage of Icenko-Cushing's disease and were most noticeable in a severe course of disease accompanied by sharply marked osteoporosis. Hypocalcemia, hypophosphatemia, hypercalciuria, a decrease in phosphate maximum resorption and an increase in AP activity in the blood serum were revealed in this form of disease. Patients with the average gravity of disease and weakly pronounced osteoporosis were characterized by hypercalcemia and an increase in calcium intestinal absorption. Patients with the active stage of hypercorticism were characterized by hypermagnesemia. Secondary hyperparathyrosis was found in 25% of patients with the active stage of Icenko-Cushing's disease.
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PMID:[Phosphorus-calcium metabolism and calcium-regulating hormones in endogenous hypercorticism]. 380 24

The pathogenesis of nephrolithiasis in Cushing's syndrome is still not completely clarified. The current study aimed at investigating prevalence of nephrolithiasis and role of different lithogenic factors in Cushing's disease (CD). Forty-six CD patients (24 with active and 22 with cured disease) and 46 sex- and age-matched controls entered the study. Body mass index, blood pressure, fasting glucose and insulin, serum and urinary creatinine, urea, uric acid, electrolytes, and cystine, urinary volume, pH, oxalate, and citrate levels, and renal ultrasonography (US) were performed in all patients and controls. Nephrolithiasis was found in 50% of active patients, 27.3% of cured patients, and 6.5% of controls (P < 0.001). Compared with controls, patients with active disease had a significantly increased prevalence of obesity, arterial hypertension, diabetes mellitus, hypercalciuria, hypocitraturia, and hyperuricosuria, significantly higher levels of serum and urinary cystine, urinary creatinine, urea, uric acid, potassium, calcium, phosphorus, and oxalate, significantly lower levels of urinary citrate levels. Compared with controls, patients cured from CD had a significantly increased prevalence of obesity, systemic arterial hypertension, and diabetes mellitus, whereas urinary citrate was significantly decreased. At multivariate analysis, a significantly increased risk to develop kidney stones was independently associated with urinary excretion of uric acid (odds ratio = 1.6, confidence interval = 1.0-2.5) and systemic arterial blood pressure (odds ratio = 2.6, confidence interval = 1.1-6.6). In conclusion, patients with active CD have an increased prevalence of nephrolithiasis compared with general population, which decreases but not disappears in patients successfully cured from the disease. This complication is likely caused by the synergic effect of different hypercortisolism-dependent metabolic and hemodynamic abnormalities, among which systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role.
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PMID:Nephrolithiasis in Cushing's disease: prevalence, etiopathogenesis, and modification after disease cure. 1272 57

The negative effect on bone due to the glucocorticoid excess is mediated by the direct action of cortisol in reducing bone apposition and increasing bone resorption, and by indirect mechanisms such as the calcium malabsorption, hypercalciuria and hypogonadism. The condition of overt hypercortisolism, also called Cushing's syndrome, leads to osteoporosis and fractures in up to the 70% of cases, even in the presence of normal gonadal status and in males. The recovery from Cushing's syndrome leads to a normalization of bone mineral density only after several years, even if some data show that the risk of fractures normalizes after one year from the cure. Alendronate has been demonstrated to be useful to accelerate the restoration of normal bone mass after the cure of Cushing's syndrome Several studies, even not all, have been demonstrated that also the condition of asymptomatic or "subclinical" hypercortisolism (often associated to adrenal adenoma) is associated to a reduction of bone mineral density and increased prevalence of fracture even in the presence of eugonadal status and in males. Unfortunately, data regarding the effect of the normalization of cortisol secretion on bone mass and risk of fractures are lacking. On the other hand, it is known that osteoporotic fractures may be the clinical presentation of an otherwise asymptomatic hypercortisolism. In a recent study we have demonstrated that in a population of outpatients with established osteoporosis and without known or clinically evident secondary causes, the prevalence of subclinical hypercortisolism is about 10%. This finding suggests that the presence of subclinical hypercortisolism has to be taken in to account when evaluating patients with unexplainable established osteoporosis.
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PMID:[Role of cortisol hypersecretion in the pathogenesis of osteoporosis]. 1871 63

Glucocorticoids (GCs) affect renal development and function in fetal and mature kidneys both indirectly, by influencing the cardiovascular system, and directly, by their effects on glomerular and tubular function. Excess GCs due to endogenous GC overproduction in Cushing's syndrome or exogenous GC administration plays a pivotal role in hypertension and causes increased cardiac output, total peripheral resistance and renal blood flow. Glucocorticoids increase renal vascular resistance (RVR) in some species and experimental settings and decrease RVR in others. Short term administration of adrenocorticotrophic hormone or GCs causes an increased glomerular filtration rate (GFR) in humans, rats, sheep and dogs. Interestingly, chronic exposure may cause a decreased GFR in combination with a higher cardiovascular risk in human patients with Cushing's syndrome. Glomerular dysfunction leads to proteinuria and albuminuria in canine and human Cushing's patients, and some cases also show histological evidence of glomerulosclerosis. Tubular dysfunction is reflected by an impaired urinary concentrating ability and disturbed electrolyte handling, which can potentially result in increased sodium reabsorption, hypercalciuria and urolithiasis. Conversely, chronic kidney disease can also alter GC metabolism. More research needs to be performed to further evaluate the renal consequences of Cushing's syndrome because of its implications for therapeutic aspects as well as the general well-being of the patient. Because there is a high incidence of Cushing's syndrome in canines, which is similar to the syndrome in humans, dogs are an interesting animal model to investigate the link between hypercortisolism and renal function.
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PMID:Cushing's syndrome, glucocorticoids and the kidney. 2065 18

Cushing's syndrome, which is characterized by excessive circulating glucocorticoid concentrations, may be due to ACTH-dependent or -independent causes that include anterior pituitary and adrenal cortical tumors, respectively. ACTH secretion is stimulated by CRH, and we report a mouse model for Cushing's syndrome due to an N-ethyl-N-nitrosourea (ENU) induced Crh mutation at -120 bp of the promoter region, which significantly increased luciferase reporter activity and was thus a gain-of-function mutation. Crh(-120/+) mice, when compared with wild-type littermates, had obesity, muscle wasting, thin skin, hair loss, and elevated plasma and urinary concentrations of corticosterone. In addition, Crh(-120/+) mice had hyperglycemia, hyperfructosaminemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, and hyperleptinemia but normal adiponectin. Crh(-120/+) mice also had low bone mineral density, hypercalcemia, hypercalciuria, and decreased concentrations of plasma PTH and osteocalcin. Bone histomorphometry revealed Crh(-120/+) mice to have significant reductions in mineralizing surface area, mineral apposition, bone formation rates, osteoblast number, and the percentage of corticoendosteal bone covered by osteoblasts, which was accompanied by an increase in adipocytes in the bone marrow. Thus, a mouse model for Cushing's syndrome has been established, and this will help in further elucidating the pathophysiological effects of glucocorticoid excess and in evaluating treatments for corticosteroid-induced osteoporosis.
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PMID:An N-ethyl-N-nitrosourea induced corticotropin-releasing hormone promoter mutation provides a mouse model for endogenous glucocorticoid excess. 2430 25