dihydrotachysterol and Hypercalcemia

Hypercalcemia is not a rare event and can lead to severe consequences. Its main etiologies are primary hyperparathyroidism and neoplasic conditions. The iatrogenic etiology by vitamin D intoxication is more rarely found.. A 76-year-old finish woman comes to the emergency room for chest pain. Her medical history is impossible to specify due to the language barrier and initial confusion. She has severe hypercalcaemia (4.14mmol/L), renal insufficiency, cardiac arrhythmia later complicated by an ischemic cardiac episode. Clinic and biologic examinations initially guided the research towards a hematological and neoplasic pathology. The iatrogenic etiology will be permitted by the contribution of details on its medical history and treatment learnt secondly. She was treated for post-surgical hypoparathyroidism by dihydrotachysterol, a vitamin D derivative. The cessation of substitution, treatment with hydration and biphosphonates allowed the rapid correction of hypercalcemia.. Dihydrotachysterol intoxication is a rare etiology of hypercalcemia. Because of the longer half-life of this molecule, the risk of hypercalcemia seems to be greater than with other vitamin D derivatives. This molecule, withdrawn from the French market in 1982, is not detected by the dosage of 25 and 1.25 OH vitamin D.. We report an original case of intoxication by dihydrotachysterol. The risk of hypercalcemia encountered with this molecule must be known. The close medical follow-up recommended in case of hypoparathyroidism seems to be particularly necessary in case of supplementation by this molecule.

Topics: Aged; Calcium; Dihydrotachysterol; Diphosphonates; Female; Fluid Therapy; Humans; Hypercalcemia; Hypoparathyroidism; Iatrogenic Disease; Vitamin D

The half synthetic Vitamin D analogue dihydrotachysterol (DHT) is widely used for hypocalcaemic hypoparathyroidism following surgical removal of parathyroids. Such treatment generally initiated by surgeons right after surgery has to be continued in clinical practice. Unfortunately, the required careful monitoring of calcium metabolism is often lacking and as demonstrated may lead to life-threatening conditions.. Here we report on five patients referred to our nephrology unit because of unknown impairment of renal function during therapy with DHT. All patients had clinical signs of hypercalcaemia. Since most symptoms are nonspecific they were not perceived by primary care physicians. In fact DHT treatment was continued for 4 - 50 years. In all cases calcium levels were determined after inadequate long intervals ranging from 3.08 to 4.97 mmol/l. Creatinine levels ranged from 277 to 365 micromol/l. All patients suffered from symptoms of severe hypercalcaemia, three of them needing intensive care unit treatment.. All patients were treated effectively with a regimen consisting of intravenous saline, a loop diuretic, and application of bisphosphonates. As confirmed by renal biopsy persisting alleviation of renal function was due to calcifications. After discontinuation of DHT therapy patients were safely switched to shorter acting vitamin D derivates maintaining a normal calcium level.. In comparison to short acting vitamin-D derivates hypercalcaemic episodes with DHT appear to last longer and may therefore occur with higher incidence. A future option could be the use of synthetic parathyroid hormone (s-PTH) recently shown to be safe and effective. Nevertheless a customized therapy and careful monitoring is indispensable in any case to prevent irreversible organ damage.

Topics: Aged; Dihydrotachysterol; Drug Monitoring; Female; Humans; Hypercalcemia; Hypoparathyroidism; Male; Renal Insufficiency; Vitamin D

Topics: Adenoma; Child; Dihydrotachysterol; Female; Humans; Hypercalcemia; Hyperparathyroidism; Hypoparathyroidism; Infant, Newborn; Infant, Newborn, Diseases; Parathyroid Diseases; Parathyroid Neoplasms; Pregnancy; Pseudohypoparathyroidism; Vitamin D

1. Hypo- and hypercalcemia can be explained as derangements of the calcium homeostasis. Hypocalcemic tetany usually alarming the patient tremendously is, at least in adults, rarely life-threatening. Hypercalcemia leads in 30% of the cases to clinical symptoms which may inadvertedly pass into a state of hypercalcemic crisis. This latter requires an often difficult emergency treatment. 2. Hypocalcemic tetany may be reversed by administering calcium i.v. or, in severe cases, by a calcium infusion. Only rarely are magnesium supplements necessary to let the tetany disappear. Vitamin D or dihydrotachysterol (DHT) do not correct hypocalcemia immediately, since their effects may be delayed up to 15-25 days. In order to normalize the serum calcium permanently, vitamin D or DHT treatment should be instituted as rarely as possible. 3. Initially, hypercalcemic crisis is best treated by forced intravenous fluid administration with normal saline (and furosemide) in combination with high doses of prednisone. Fluid-, sodium- and potassium balances ought to be checked during this type of treatment. A first evaluation of the effectiveness of these measures is recommended after 24 hours: treatment is continued in patients who respond favorably, while subjects who do not show a significant decrease of the serum calcium may either be given a phosphate infusion or mithramycine as a bolus. Calcitonin appears to be useful only to start treatment before institution of a phosphate infusion.

Topics: Calcium; Dihydrotachysterol; Emergencies; Furosemide; Homeostasis; Humans; Hypercalcemia; Hypocalcemia; Prednisone; Sodium Chloride; Tetany; Vitamin D; Water-Electrolyte Balance

Topics: Animals; Anticonvulsants; Biotransformation; Contraceptives, Oral; Diet; Dihydrotachysterol; Diuretics; Drug Resistance; Emotions; Estrogens; Female; Homeostasis; Humans; Hydroxycholecalciferols; Hypercalcemia; Hypocalcemia; Hypoparathyroidism; Magnesium Deficiency; Parathyroid Hormone; Phosphates; Stress, Psychological; Tranquilizing Agents; Vitamin D

Topics: Adult; Age Factors; Calcinosis; Child, Preschool; Dihydrotachysterol; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperplasia; Kidney Failure, Chronic; Kidney Transplantation; Parathyroid Glands; Parathyroid Hormone; Postoperative Complications; Preoperative Care; Pruritus; Transplantation, Homologous; Vitamin D

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper (p = 0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

Topics: Calcitriol; Child; Child, Preschool; Dihydrotachysterol; Double-Blind Method; Female; Glomerular Filtration Rate; Growth Disorders; Humans; Hypercalcemia; Infant; Kidney Failure, Chronic; Male; Prospective Studies; Treatment Outcome

Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI.

Topics: Animals; Aquaporin 2; Autophagy; Chromatography, Liquid; Diabetes Insipidus, Nephrogenic; Dihydrotachysterol; Disease Models, Animal; Down-Regulation; Fluorescent Antibody Technique; Half-Life; Humans; Hypercalcemia; Intercellular Junctions; Kidney Tubules, Collecting; Lysosomal Membrane Proteins; Male; Microscopy, Immunoelectron; Microtubule-Associated Proteins; Parathyroid Hormone; Phosphorylation; Proteolysis; Proteomics; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Topics: Bone Density Conservation Agents; Calcium Carbonate; Dihydrotachysterol; Diphosphonates; Female; Gastroenteritis; Humans; Hypercalcemia; Hypocalcemia; Hypoparathyroidism; Middle Aged; Pamidronate; Renal Insufficiency; Thyroiditis

The effect of tumor necrosis factor-alpha (TNF) on cyclooxygenase-2 (COX-2) expression in the renal outer medulla (OM) was determined in a model of dihydrotachysterol (DHT)-induced hypercalcemia. Increases in serum calcium and water intake were observed during ingestion of a DHT-containing diet in both wild type (WT) and TNF deficient mice (TNF(-/-)). Polyuria and a decrease in body weight were observed in response to DHT treatment in WT and TNF(-/-) mice. A transient elevation in urinary TNF was observed in WT mice treated with DHT. Moreover, increased urinary levels of prostaglandin E(2) (PGE(2)) and a corresponding increase in COX-2 expression in the OM were observed in WT mice fed DHT. Increased COX-2 expression was not observed in TNF(-/-) mice fed DHT, and the characteristics of PGE(2) synthesis were distinct from those in WT mice. This study demonstrates that COX-2 expression in the OM, secondary to hypercalemia, is TNF-dependent.

Topics: Animals; Cyclooxygenase 2; Dihydrotachysterol; Hypercalcemia; Kidney Medulla; Male; Mice; Polyuria; Tumor Necrosis Factor-alpha

Topics: Anti-Inflammatory Agents; Calcium; Carcinoma, Papillary; Diagnosis, Differential; Dihydrotachysterol; Drug Overdose; Female; Glucocorticoids; Hospitalization; Humans; Hypercalcemia; Hypoparathyroidism; Middle Aged; Postoperative Complications; Prednisone; Prognosis; Thyroid Neoplasms; Thyroidectomy; Thyroxine; Time Factors

This report describes a forty-seven-year-old female patient with a complex medical history. She was suffering from an unspecified interstitial lung disease, papillary thyroid carcinoma which had been treated, hypoparathyroidism after thyroidectomy for which she was receiving dihydrotachysterol and calcium, and atrial fibrillation and congestive heart failure as a result of mitral stenosis. Shortly after mitral valve replacement she developed a severe hypercalcemia (serum calcium 5.95 mmol/l) during a febrile illness. At that time anti-tuberculous agents were also being administered for presumed tuberculosis. The possible mechanisms for this severe elevation of the calcium level are discussed. Immobilization, while Paget's bone disease was present, and perhaps enhanced activation of dihydrotachysterol by rifampicin, could have led to increased calcium-release into the circulation. Continuous supplecation of calcium and vitamin D, provoked dehydration and the mechanism of the milk-alkali syndrome also contributed to this extremely high calcium level. It is concluded that hypoparathyroid patients being treated with vitamin D and calcium should be carefully monitored in the case of an intercurrent illness or a change in medication.

Topics: Calcium; Dihydrotachysterol; Female; Heart Valve Prosthesis Implantation; Humans; Hypercalcemia; Hypoparathyroidism; Middle Aged; Osteitis Deformans; Polypharmacy; Postoperative Complications; Proteus Infections; Renal Dialysis; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome; Urinary Tract Infections

During vitamin-D therapy drug accumulation and intoxication should be considered. In the present study we report on five patients with renal insufficiency during therapy with dihydrotachysterol or calcitriol. Four patients received dihydrotachysterol for 29 (7-44) years and one patient received calcitriol for 4 years to treat hypoparathyroidism after thyroid surgery. As confirmed by renal biopsy impairment of renal function was due to calcifications as a consequence of prolonged hypercalcemia. The effective duration of dihydrotachysterol is ten days as compared with five days for calcitriol. Severe hypercalcemic episodes with dihydrotachysterol are longer-lasting than those with the shorter acting vitamin-D derivatives. Further, they occur with higher incidence as was shown by our own observations and previously published data by other workers. Hence, impairment of renal function during therapy with dihydrotachysterol should be considered as being due to hypercalcemia and hypercalciuria.

Topics: Aged; Calcitriol; Calcium; Creatinine; Dihydrotachysterol; Drug Overdose; Female; Humans; Hypercalcemia; Kidney; Male; Middle Aged; Renal Insufficiency; Ultrasonography

Hypercalcemia is frequently associated with a urinary concentrating defect and overt polyuria. The molecular mechanisms underlying this defect are poorly understood. Dysregulation of aquaporin-2 (AQP2), the predominant vasopressin-regulated water channel, is known to be associated with a range of congenital and acquired water balance disorders including nephrogenic diabetes insipidus and states of water retention. This study examines the effect of hypercalcemia on the expression of AQP2 in rat kidney. Rats were treated orally for 7 d with dihydrotachysterol, which produced significant hypercalcemia with a 15 +/- 2% increase in plasma calcium concentration. Immunoblotting and densitometry of membrane fractions revealed a significant decrease in AQP2 expression in kidney inner medulla of hypercalcemic rats to 45.7 +/- 6.8% (n = 11) of control levels (100 +/- 12%, n = 9). A similar reduction in AQP2 expression was seen in cortex (36.9 +/- 4.2% of control levels, n = 6). Urine production increased in parallel, from 11.3 +/- 1.4 to a maximum of 25.3 +/- 1.9 ml/d (P < 0.01), whereas urine osmolality decreased from 2007 +/- 186 mosmol/kg x H2O to 925 +/- 103 mosmol/kg x H2O (P < 0.01). Immunocytochemistry confirmed a decrease in total AQP2 labeling of collecting duct principal cells from kidneys of hypercalcemic rats, and reduced apical labeling. Immunoelectron microscopy demonstrated a significant reduction in AQP2 labeling of the apical plasma membrane, consistent with the development of polyuria. In summary, the results strongly suggest that AQP2 downregulation and reduced apical plasma membrane delivery of AQP2 play important roles in the development of polyuria in association with hypercalcemia.

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Body Water; Cell Polarity; Dihydrotachysterol; Diuresis; Hypercalcemia; Immunoenzyme Techniques; Kidney Cortex; Kidney Medulla; Kidney Tubules, Collecting; Male; Microscopy, Immunoelectron; Osmolar Concentration; Polyuria; Rats; Rats, Wistar; RNA, Messenger; Subcellular Fractions; Urine

In chronic hypercalcemia, inhibition of thick ascending limb sodium chloride reabsorption is mediated by elevated intrarenal PGE2. The mechanisms and source of elevated PGE2 in hypercalcemia are not known. We determined the effect of hypercalcemia on intrarenal expression of cytosolic phospholipase A2 (cPLA2), prostaglandin H synthase-1 (PGHS-1), and prostaglandin H synthase-2 (PGHS-2), enzymes important in prostaglandin production. In rats fed dihydrotachysterol to induce hypercalcemia, Western blot analysis revealed significant upregulation of both cPLA2 and PGHS-2 in the kidney cortex and the inner and outer medulla. Immunofluorescence localized intrarenal cPLA2 and PGHS-2 to interstitial cells of the inner and outer medulla, and to macula densa and cortical thick ascending limbs in both control and hypercalcemic rats. Hypercalcemia had no effect on intrarenal expression of PGHS-1. To determine if AT1 angiotensin II receptor activation was involved in the stimulation of cPLA2 and PGHS-2 in hypercalcemia, we treated rats with the AT1 receptor antagonist, losartan. Losartan abolished the polydipsia associated with hypercalcemia, prevented the increase in cPLA2 protein in all regions of the kidney, and diminished PGHS-2 expression in the inner medulla. In addition, losartan completely prevented the increase in urinary PGE2 excretion in hypercalcemic rats. Intrarenal levels of angiotensin II were unchanged in hypercalcemia. These data indicate that hypercalcemia stimulates intrarenal cPLA2 and PGHS-2 protein expression. Our results further support a role for angiotensin II, acting on AT1 receptors, in mediating this stimulation.

Topics: Angiotensin II; Animals; Blotting, Western; Calcium; Cyclooxygenase 1; Cyclooxygenase 2; Dihydrotachysterol; Dinoprostone; Fluorescent Antibody Technique; Hypercalcemia; Isoenzymes; Kidney; Kidney Cortex; Kidney Medulla; Losartan; Male; Membrane Proteins; Phospholipases A; Phospholipases A2; Prostaglandin-Endoperoxide Synthases; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin

The aim of the present study was to elucidate the correlation between the Renin secretion and increased Plasma Calcium concentration and the role of Calmodulin in this process. Plasma Renin activity was determined radioimmunologically in 31 white rats, that were grouped as follows: group I - 7 controls loaded for 6 days perorally with 0.5 ml/200 g b.w. glycerin and injected i.m. for 6 days with 0.1 ml/200 g b.w. with 0.9% NaCl; group II - 8 rats, treated for 6 days with Tachistin 0.0025 mg/200 g b.w., dissolved in glycerin 0.5 ml/200 g b.w.; group III - 5 rats, treated with Tachistin 0.005 mg/200 g b.w. in the same manner; group IV - 5 rats injected i.m. with Chlorazin 0.5 mg/200 g b.w. for 6 days; group V - 6 rats, loaded with double dose Tachistin and with Chlorazin 0.5 mg/200 g b.w. for 6 days. Blood samples were taken intracardially on the seventh day from the beginning of the experiment and were analyzed with kits of Sorin-Biomedica-Italy. Our results suggest that the hypercalcemia induced by Tachistin caused a dose-dependent increase of PRA and Ca-Calmodulin complex is the dominant second messenger of Renin secretion.

Topics: Animals; Antipsychotic Agents; Calcium; Chlorpromazine; Dihydrotachysterol; Dose-Response Relationship, Drug; Hypercalcemia; Male; Rats; Rats, Wistar; Renin; Stimulation, Chemical

The hypothesis that endogenous PGE2 mediates defective thick ascending limb (TAL) Cl reabsorption (percent delivered load: FRCl%) in rats with vitamin D-induced chronic hypercalcemia (HC) was tested by measuring FRCl% in loop segments microperfused in vivo in HC and control rats treated acutely with indomethacin (Indo) or its vehicle, and obtaining the corresponding outer medullary [PGE2]. Microperfusion conditions were developed in which FRCl% was exclusively furosemide sensitive. To determine the cellular mechanism, tubules were perfused acutely with forskolin (FSK), cAMP, or the protein kinase C inhibitor staurosporine (SSP). Outer medullary [PGE2] in HC rats was 9 to 10 times greater than control and could be normalized by Indo. FRCl% was 20% lower in HC rats infused with vehicle, and Indo, FSK, and cAMP returned FRCl% to normal despite sustained HC. Indo or FSK had no effect on FRCl% in control rats and Indo did not prevent inhibition of FRCl% by luminal PGE2 (1 microM). Luminal SSP (10(-7), 10(-8) M) in HC did not return FRCl% to control values. We conclude that impaired TAL FRCl% in HC occurs at a pre-cAMP site and is due to endogenous PGE2 and not to HC.

Topics: Alkaloids; Animals; Biological Transport, Active; Chlorides; Chronic Disease; Colforsin; Cyclic AMP; Dihydrotachysterol; Dinoprostone; Furosemide; Hypercalcemia; In Vitro Techniques; Indomethacin; Kidney Medulla; Kidney Tubules, Collecting; Male; Perfusion; Rats; Rats, Sprague-Dawley; Staurosporine

Topics: Anthropometry; Calcitriol; Child; Data Interpretation, Statistical; Dihydrotachysterol; Growth Disorders; Humans; Hypercalcemia; Incidence; Kidney Failure, Chronic; Research Design; Sampling Studies; Statistics as Topic

The reported coincidence of primary hyperparathyroidism and cholelithiasis led us to investigate the effects of acute and chronic hypercalcemia on bile secretion in cats. Acute hypercalcemia (6-7 mmol/liter) was induced by an intravenous calcium infusion. Chronic hypercalcemia (3-4 mmol/liter) was induced and maintained for 8-10 weeks by treatment with subcutaneous vitamin D3, oral dihydrotachysterol, and feeding a calcium-rich diet. Bile secretion was then studied in acute experiments. We found that calcium concentrations in serum and hepatic bile were similar during all experimental normo- or hypercalcemic conditions (y = 1.12x - 0.85; r = 0.76). Biliary volume outputs were significantly decreased during both acute (P less than 0.002) and chronic (P less than 0.05) hypercalcemia compared with normocalcemic controls. Acute hypercalcemia also decreased total bile acid outputs (P less than 0.05), but had no effect on biliary bile acid concentrations. The inhibitory effect of acute hypercalcemia on biliary fluid and bile acid secretion was dose dependent and not antagonized by atropine. These findings suggest that calcium is secreted in hepatic bile at similar concentrations as present in the serum and that elevations of serum calcium concentration inhibit biliary volume and bile acid secretion in cats. Similar effects of hypercalcemia on bile composition in humans might promote calcium salt precipitation in bile.

Topics: Acute Disease; Animals; Bile; Bile Acids and Salts; Calcium; Calcium, Dietary; Cats; Cholecalciferol; Chronic Disease; Dihydrotachysterol; Female; Hypercalcemia; Male

The mechanism of the concentrating defect of hypercalcemia is explored by examining the effect of concomitant phosphate restriction. Rats were pair fed a normal phosphorus diet, without (group 1) or with dihydrotachysterol (group 2), or a low-phosphorus diet (group 3). Hypercalcemia was comparable in groups 2 (12.1 +/- 0.6 mg/dl) and 3 (11.8 +/- 0.4 mg/dl), but serum phosphate was lower in group 3 than group 2 (3.8 +/- 0.7 vs. 7.1 +/- 1.1 mg/dl, P less than 0.005). Group 2 rats had impaired maximum urinary concentration after 24 h of fluid deprivation (2,441 +/- 450 mosmol/kg H2O, P less than 0.001) compared with group 1 (3,263 +/- 466 mosmol/kg H2O) or group 3 (3,332 +/- 515 mosmol/kg H2O) animals. Polydipsia and polyuria were found in group 2 rats only. Tubular calcium reabsorption was higher in group 2 (83.1 +/- 33.5 mg/24 h, P less than 0.001) than group 1 (47.0 +/- 26.1 mg/24 h) or group 3 (52.8 +/- 19.3 mg/24 h) animals, and medullary calcium concentration was higher in group 2 (7.57 +/- 3.08 nmol/mg dry wt, P less than 0.05) as compared to group 1 (5.04 +/- 1.37 nmol/mg dry wt) or group 3 (5.32 +/- 0.98 nmol/mg dry wt) rats. Total medullary solute concentration was significantly higher in group 3 than group 2 animals. Thus phosphate restriction prevents the defect of urinary concentrating ability of chronic hypercalcemia, probably by decreasing tubular uptake and tissue accumulation of calcium.

Topics: Animals; Calcium; Dihydrotachysterol; Hypercalcemia; Kidney; Kidney Concentrating Ability; Kidney Diseases; Phosphates; Rats; Rats, Inbred Strains

In hypercalcaemic crisis sonographic identification of an enlarged parathyroid permits the indication for parathyroidectomy. This is particularly important as determination of the parathormone concentration to find out the cause of hypercalcaemia takes too long and thus delays diagnosis and therapy. In two patients with symptoms of crisis successful parathyroidectomy was performed solely on the basis of a raised serum calcium concentration and a sonographically proven enlarged parathyroid.

Topics: Acute Kidney Injury; Adenoma; Adult; Calcium; Creatinine; Dihydrotachysterol; Female; Humans; Hypercalcemia; Male; Middle Aged; Pancreatitis; Parathyroid Hormone; Parathyroid Neoplasms; Renal Dialysis; Ultrasonography

After 13 days therapy with 30 mg dihydrotachysterol (dihydrotachysterin, AT 10 (DHT3 daily in a 33-year-old female patient a severe intoxication developed. In addition to this the patient was twice administered calcium gluconate and vitamin D. Typical clinical symptoms of the developing hypercalcaemia syndrome consisted in adynamia, vomiting and obstipation. The occurring clinical symptom and findings are discussed on the basis of recent knowledge concerning efficacy and metabolism of DHT3 as well as vitamin D3.

Topics: Adult; Calcium; Dihydrotachysterol; Female; Humans; Hypercalcemia; Hypocalcemia

We treated 24 patients who had chronic renal insufficiency and renal osteodystrophy with either calcitriol (1,25-dihydroxyvitamin D3) or dihydrotachysterol. Renal function was evaluated before and during treatment to determine if these vitamin D analogues caused an accelerated rate of renal function deterioration. An accelerated rate of increase in the serum creatinine level was found in three of 12 patients in each treatment group after therapy was started, but the mean rate of increase during treatment did not differ significantly from the rate during the pretreatment control period in either group. The occurrence of hypercalcemia or an excessive serum calcium x phosphorus-product did not correlate with the rate of change in renal function during treatment with either drug. We concluded that children receiving calcitriol are not at greater risk for an accelerated rate of renal function deterioration than are children treated with dihydrotachysterol. Furthermore, neither vitamin D analogue could be directly implicated as a cause of an accelerated rate of renal function deterioration when episodes of hypercalcemia were transient and occurred infrequently.

Topics: Adolescent; Adult; Calcitriol; Calcium; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Creatinine; Dihydrotachysterol; Humans; Hypercalcemia; Infant; Kidney; Kidney Failure, Chronic; Phosphorus; Retrospective Studies; Risk

The metabolism of vitamin D is essential in the control of bone and mineral metabolism. Hyperthyroidism as well as hypothyroidism effect the metabolism of bone tissue and vitamin D. We present a dihydrotachysterol-calcium treated patient with post-operative hypothyroidism, who developed hypercalcaemia, when the thyroxine dosage was increased.

Topics: Calcium; Dihydrotachysterol; Female; Humans; Hypercalcemia; Hypocalcemia; Hypothyroidism; Middle Aged; Postoperative Complications; Thyroxine

The discovery and chemical synthesis of several biologically active derivatives of vitamin D have increased the number of compounds available for the treatment of disorders of bone and mineral metabolism. Calcitriol is the most active natural metabolite of vitamin D, but analogues like dihydrotachysterol and calcifediol also are safe and effective therapeutic agents. These vitamin D congeners have been useful in the treatment of renal osteodystrophy, hypoparathyroidism, and other disorders refractory to vitamin D therapy. Certain analogues may offer distinct advantages over vitamin D, depending on the nature of the defect. All vitamin D derivatives should be used cautiously, with frequent monitoring of serum calcium levels to prevent toxic reactions.

Topics: Bone Diseases, Metabolic; Calcifediol; Calcitriol; Dihydrotachysterol; Humans; Hydroxycholecalciferols; Hypercalcemia; Kidney; Liver; Models, Biological; Vitamin D

Hypercalcaemia is a recognised complication of hypothyroidism. We describe three patients who developed hypercalcaemia after thyroidectomy when thyroid supplements were discontinued. They were treated with thyroxine, dihydrotachysterol, and calcium after operation, and in all three cases serum calcium concentrations remained constant during combined treatment. Thyroxine treatment was discontinued several weeks before a radioiodine scan was performed; dihydrotachysterol and calcium were continued throughout. Serum calcium concentrations rose to hypercalcaemic levels in all cases. Elimination of dihydrotachysterol from plasma may be delayed in hypothyroidism, resulting in hypervitaminosis D. It is advisable to reduce the dose of dihydrotachysterol and to check serum calcium concentrations regularly in patients whose thyroid treatment is interrupted.

Topics: Adult; Calcium; Calcium Gluconate; Dihydrotachysterol; Drug Therapy, Combination; Female; Humans; Hypercalcemia; Hypothyroidism; Middle Aged; Thyroidectomy; Thyroxine

A case of hypercalcaemia in a pregnant patient on substitution therapy for hypoparathyroidism is reported. The clinical picture included transient cerebral disturbances, acute pancreatitis and persistent partial blindness. Calcium metabolism in pregnancy is discussed, and a possible mechanism for the sequence of events is postulated. The relevant literature is reviewed.

Topics: Adult; Dihydrotachysterol; Female; Humans; Hypercalcemia; Male; Pregnancy; Pregnancy Complications

Topics: Adult; Dihydrotachysterol; Ethinyl Estradiol; Female; Humans; Hypercalcemia; Hypoparathyroidism; Menopause; Substance Withdrawal Syndrome

Topics: Animals; Calcinosis; Calcium; Dihydrotachysterol; Etidronic Acid; Heart; Hypercalcemia; Isoproterenol; Myocardium; Nifedipine; Rats

Topics: Acute Disease; Adult; Brain Diseases; Bromides; Calcium; Calcium Gluconate; Dihydrotachysterol; Disaccharides; Female; Gluconates; Humans; Hypercalcemia

Topics: Bone Diseases; Calcium; Dihydrotachysterol; Female; Genes, Dominant; Humans; Hypercalcemia; Hyperparathyroidism; Infant, Newborn; Infant, Newborn, Diseases; Parathyroid Glands; Pedigree

The rate of reversal of hypercalcaemia or hypercalciuria induced by calciferol, dihydrotachysterol, 1-alpha-hydroxycholecalciferol (1-alpha-OHD3), or 1-alpha, 25-dihydroxycholecalciferol (1-alpha, 25-(OH)2D3) was measured in three normal subjects, two patients with osteoporosis, and 14 patients with disorders resistant to vitamin D. The half time for reversal after stopping 1-alpha, 25 (OH)2D3 was less than that after stopping 1-alpha-OHD3, calciferol, or dihydrotachysterol. The differences observed were independent of the dose given or length of treatment. When 1-alpha-OHD3 or 1-alpha-25-(OH)2D3 was stopped patients with vitamin D resistant states (hypoparathyroidism, renal tubular hypophosphataemia, or chronic renal failure) showed less rapid reversal of hypercalcaemia and hypercalciuria than did normal subjects. These studies show one potential advantage of 1-alpha-25-(OH)2D3 over vitamin D, and possibly over 1-alpha-OHD3, in the management of vitamin D resistant states.

Topics: Calcium; Dihydrotachysterol; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Hypercalcemia; Time Factors; Vitamin D

Topics: Calcium; Child; Diet; Dihydrotachysterol; Ergocalciferols; Humans; Hypercalcemia; Hypocalcemia; Hypoparathyroidism; Magnesium; Male; Phosphorus; Vitamin D

In three women intoxication with vitamin D or dihydrotachysterol occurred. Two patients died from complications despite successful lowering of the serum calcium, the third died after a pulmonary embolus during hypercalcaemia 5 months after cessation of vitamin D. Correct observation of the narrow therapeutic range of vitamin D preparations appears most important in the treatment of hypoparathyroidism and other indications. Particular attention should be given to the prophylaxis of over dosage. Apart from regular serum calcium estimations instruction of the patient and relatives as to the dangers and symptoms of intoxication is recommended. The issuing of a therapy identity card would meet these requirements.

Topics: Aged; Biopsy; Bone and Bones; Calcium; Dihydrotachysterol; Dose-Response Relationship, Drug; Female; Humans; Hypercalcemia; Hypoparathyroidism; Middle Aged; Osteoporosis; Pulmonary Embolism; Vitamin D

Immobilization of normal people causes reabsorption of calcium from bone, a small rise in serum ionized calcium, and, rarely, frank hypercalcaemia. The hazard is increased when patients with renal osteodystrophy are immobilized because of pathological fractures.

Topics: Adult; Calcium Carbonate; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Humans; Hypercalcemia; Immobilization; Male; Middle Aged; Renal Dialysis

Topics: Acute Disease; Adenoma; Blood Volume; Central Venous Pressure; Dihydrotachysterol; Female; Furosemide; Humans; Hypercalcemia; Hyperparathyroidism; Middle Aged; Parathyroid Neoplasms; Phosphates; Plasma Substitutes; Renal Dialysis

Focal areas of calcification are frequent in rat myocardium 30 and 60 days after administration of dihydrotachysterol. These areas are PAS-positive, stain deeply with alcian blue and show high affinity for colloidal iron. Calcification is almost completely confined to intracellular structures. Small clusters of needle-shaped crystals are first found in apparently undamaged mitochondria in undamaged myocardial cells. When all the mitochondria are calcified, the cell degenerates, and inorganic crystals are laid down in relationship with its myofilaments. In other myocardial cells, clusters of amorphous or finely granular inorganic substance are found in both mitochondria and myofibrils. Both structures show signs of advanced degeneration. Inorganic substance has only occasionally been found within the structures of the sarcoplasmic reticulum. These structures do not seem to be involved in myocardial calcification under the present experimental conditions. Calcification of myocardial cells gives rise to a cellular reaction. Many macrophagic cells surround the calcified areas, which are rapidly reabsorbed. The present results show that myocardial mitochondria are actively engaged in controlling the intracellular concentration and movement of calcium ions. Their role in the myocardial contraction-relaxation cycle and the possible mechanism of myocardial calcification are discussed.

Topics: Animals; Calcinosis; Cardiomyopathies; Dihydrotachysterol; Disease Models, Animal; Edetic Acid; Female; Hypercalcemia; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Rats

Topics: Dihydrotachysterol; Humans; Hypercalcemia; Hypoparathyroidism; Long-Term Care; Time Factors

Topics: Adenosine Triphosphate; Animals; Calcinosis; Cell Membrane Permeability; Collagen; Dihydrotachysterol; Glycosaminoglycans; Hypercalcemia; Rats; Skin Diseases

Topics: Animals; Cell Nucleus; Cytoplasm; Dihydrotachysterol; Endoplasmic Reticulum; Female; Gestational Age; Hypercalcemia; Hypocalcemia; Maternal-Fetal Exchange; Microscopy, Electron; Mitochondria; Organoids; Parathyroid Glands; Pregnancy; Rats

Topics: Animals; Breast; Breast Diseases; Breast Neoplasms; Calcinosis; Dihydrotachysterol; Endoplasmic Reticulum; Estrogens; Female; Humans; Hypercalcemia; Hyperparathyroidism; Microscopy, Electron; Middle Aged; Mitochondria; Neoplasm Metastasis; Premedication; Progesterone; Rats

Topics: Animals; Calcification, Physiologic; Calcinosis; Calcium; Dihydrotachysterol; Hair; Hypercalcemia; Keratins; Male; Phosphorus; Rats; Skin; Time Factors; X-Ray Diffraction

Topics: Animals; Calcium; Creatinine; Dihydrotachysterol; Female; Furosemide; Hypercalcemia; Magnesium; Male; Phosphorus; Potassium; Rats; Sodium; Water-Electrolyte Balance

Topics: Animals; Calcium; Dihydrotachysterol; Dogs; Hydrogen-Ion Concentration; Hypercalcemia; Pancreas; Pancreatic Juice; Phosphorus; Proteins; Vitamin D

Topics: Animals; Calciphylaxis; Cholecalciferol; Dihydrotachysterol; Ergocalciferols; Female; Heart; Hypercalcemia; Kidney; Male; Nephrocalcinosis; Pregnancy; Pregnancy, Animal; Rats; Reserpine

Topics: Adult; Bone Diseases; Calcium; Dihydrotachysterol; Female; Humans; Hypercalcemia; Hyperparathyroidism; Hypokalemia; Lactates; Male; Middle Aged; Polyuria; Prednisolone; Sodium; Sulfates; Urinary Calculi

Topics: Analysis of Variance; Animals; Body Weight; Bone Resorption; Calcium; Diet; Dihydrotachysterol; Ergocalciferols; Hypercalcemia; Intestinal Absorption; Kidney; Magnesium; Phosphorus; Rats; Rats, Inbred Strains; Stomach; Tibia; Time Factors

Topics: Acute Kidney Injury; Calcium; Dihydrotachysterol; Follow-Up Studies; Humans; Hypercalcemia; Hypoparathyroidism; Kidney Diseases; Kidney Function Tests; Urea; Vitamin D

Topics: Animals; Aorta; Body Weight; Calcinosis; Calcium; Dihydrotachysterol; Estrogens, Conjugated (USP); Female; Femur; Hypercalcemia; Kidney; Organ Size; Osteoporosis; Progeria; Rats; Tail

Topics: Animals; Calcinosis; Calcitonin; Calcium; Chlorides; Chromium; Dihydrotachysterol; Hypercalcemia; Injections, Intravenous; Injections, Subcutaneous; Lung; Nephrocalcinosis; Rats; Stomach

Topics: Animal Feed; Animals; Calcitonin; Calcium, Dietary; Cell Membrane; Cytoplasmic Granules; Diet; Dihydrotachysterol; Female; Glycerophosphates; Hypercalcemia; Hypocalcemia; Parathyroid Glands; Parathyroid Hormone; Phosphates; Rats

Topics: Acute Kidney Injury; Adult; Coma; Diagnosis, Differential; Dihydrotachysterol; Female; Humans; Hypercalcemia; Meningioma; Neurologic Manifestations

Topics: Animals; Anti-Bacterial Agents; Calcinosis; Diabetes Mellitus; Dihydrotachysterol; Hypercalcemia; Joint Diseases; Male; Rats

Topics: Animals; Breast; Breast Diseases; Calcinosis; Calciphylaxis; Calcium; Dihydrotachysterol; Ethionine; Female; Histocytochemistry; Hypercalcemia; Kidney; Lactation; Liver; Lung; Mammary Glands, Animal; Mice; Milk; Milk, Human; Myocardium; Pregnancy; Stomach

Topics: Animals; Calcium; Dihydrotachysterol; Dogs; Female; Fibrinolytic Agents; Glomerular Filtration Rate; Humans; Hydrogen-Ion Concentration; Hypercalcemia; Hypoparathyroidism; Kidney; Middle Aged; Parathyroid Hormone; Phosphates; Water-Electrolyte Balance

Topics: Animals; Blood Proteins; Dihydrotachysterol; Hypercalcemia; Progeria; Rats

Topics: Adult; Aged; Calcium; Dihydrotachysterol; Female; Humans; Hypercalcemia; Hypoparathyroidism; Magnesium; Middle Aged; Phosphates; Thyroid Function Tests

Topics: Animals; Calcinosis; Calcium; Dihydrotachysterol; Diphosphates; Female; Hypercalcemia; Parathyroid Hormone; Rats; Skin

Topics: Adolescent; Adrenal Insufficiency; Adult; Child; Child, Preschool; Dihydrotachysterol; Ergocalciferols; Female; Humans; Hypercalcemia; Hypoparathyroidism; Male; Rickets; Vitamin D

Topics: Adult; Aged; Anabolic Agents; Animals; Dihydrotachysterol; Dogs; Estrogens; Female; Humans; Hypercalcemia; Male; Mice; Nephrocalcinosis; Rabbits; Species Specificity; Vitamin D

Topics: Calcium; Child; Child, Preschool; Dihydrotachysterol; Female; Humans; Hypercalcemia; Hypocalcemia; Hypophosphatemia, Familial; Infant; Male; Rickets; Switzerland; Vitamin D

Topics: Aging; Animals; Animals, Newborn; Aortic Diseases; Arteriosclerosis; Blood; Body Weight; Calcinosis; Coronary Disease; Dihydrotachysterol; Female; Hypercalcemia; In Vitro Techniques; Kidney Diseases; Lactation; Pregnancy; Pregnancy, Animal; Rats

Topics: Dihydrotachysterol; Drug Therapy; Humans; Hypercalcemia; Nephrocalcinosis; Tetany; Toxicology

Topics: Calcinosis; Dermatology; Dihydrotachysterol; Hypercalcemia; Nephrocalcinosis; Pathology; Rats; Research; Skin Diseases; Toxicology

Topics: Dihydrotachysterol; Hypercalcemia; Pharmacology; Toxicology

Topics: Dihydrotachysterol; Humans; Hypercalcemia; Hypoparathyroidism; Prednisolone; Prednisone

Topics: Cataract; Dihydrotachysterol; Ergocalciferols; Humans; Hypercalcemia; Lens, Crystalline; Tetany

Topics: Calcification, Physiologic; Calcinosis; Dihydrotachysterol; Humans; Hypercalcemia; Hypophysectomy; Nephrocalcinosis; Osteitis; Osteitis Fibrosa Cystica; Parathyroid Hormone

Topics: Animals; Calcium; Dihydrotachysterol; Dogs; Hematologic Tests; Hypercalcemia

Topics: Calcium; Dihydrotachysterol; Humans; Hypercalcemia; Kidney; Kidney Diseases; Renal Insufficiency

Topics: Calcium; Calcium, Dietary; Cholestanes; Dihydrotachysterol; Humans; Hypercalcemia; Vitamin D; Vitamins