Disease relevance of dihydrotachysterol

• 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 [1].
• Persistent hypophosphataemia and osteomalacia in dialysis patients not on oral phosphate-binders: Response to dihydrotachysterol therapy [2].
• Many clinicians continue to prefer dihydrotachysterol (DHT) as the initial vitamin D agent of choice in hypoparathyroidism and renal osteodystrophy because of its long history of efficacy and safety [3].
• Dihydrotachysterol seems to be effective in the treatment of renal patients with osteitis fibrosa; its low cost makes therapy with this compound a reasonable alternative, although it should not be used in the treatment of patients with liver disease [4].
• In rats, the Ca2+ antagonist verapamil not only prevented arterial calcinosis due to overdoses of vitamin D and dihydrotachysterol but also counteracted age-dependent Ca2+ accumulation [5].

High impact information on dihydrotachysterol

• Bone deficit in ovariectomized rats. Functional contribution of the marrow stromal cell population and the effect of oral dihydrotachysterol treatment [6].
• Rats were treated orally for 7 d with dihydrotachysterol, which produced significant hypercalcemia with a 15 +/- 2% increase in plasma calcium concentration [7].
• Fifteen subjects with XLH receiving standard treatment [1,25(OH)2 D3 or dihydrotachysterol plus phosphate] were evaluated, supplemented with placebo, and reevaluated one yr later [8].
• In one patient from whom the dihydrotachysterol therapy was withdrawn, both immunoreactive and bioactive PTH concentrations increased [9].
• Upon the institution of cortisol therapy, while still under the effects of a vitamin D analog dihydrotachysterol (DHT), the patient exhibited severe hypocalcemia and tetany [10].

Chemical compound and disease context of dihydrotachysterol

• Intracellular Ca2+ overload proved to the common denominator in the pathogenesis of severe myocardial fibre injury and death produced under the following circumstances: Overdoses of beta-adrenergic catecholamines, dihydrotachysterol or vitamin D3, alimentary K+ or Mg2+ deficiency, hereditary cardiomyopathy of Syrian hamsters [11].
• Fourteen patients with pseudohypoparathyroidism, 17 with idiopathic hypoparathyroidism, and 12 with postoperative hypoparathyroidism were treated with vitamin D2, dihydrotachysterol, 1 alpha-hydroxyvitamin D3)1 alpha-OHD3), and 1,25-dihydroxyvitamin D3 for 6-18 months [12].
• There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency [13].
• As a multicenter, controlled clinical trial designed to study the relative efficacy of 1,25-dihydroxyvitamin D3 and dihydrotachysterol in the treatment of renal osteodystrophy, no prior vitamin D exposure and a creatinine clearance of 25 to 75 ml/min/1.73 m2 were criteria for entrance into the clinical trial [14].
• Treatment of renal osteodystrophy in children with dihydrotachysterol and 24,25-dihydroxyvitamin D3 [15].

Biological context of dihydrotachysterol

• 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) [13].
• In rats, dihydrotachysterol (DHT) induces AQP2 water channel downregulation despite unaltered AQP2 mRNA expression and thus we investigated the mechanism of AQP2 degradation [16].
• Differences in the bioavailability of dihydrotachysterol preparations [17].
• With dihydrotachysterol as sole treatment for more than 2.5 years he had normal exercise tolerance and no features of cardiac failure [18].
• We have demonstrated via marrow stromal cell cultures and the osteoinductive response to demineralized bone grafts (DBM) that the cortical bone deficit in the ovariectomized (OVX) rat (6 weeks postop) is primarily due to impaired osteoprogenitor cell proliferation, and that dihydrotachysterol (DHT) treatment can be protective [19].

Anatomical context of dihydrotachysterol

• It is advisable to reduce the dose of dihydrotachysterol and to check serum calcium concentrations regularly in patients whose thyroid treatment is interrupted [20].
• During hypercalcaemia (induced by dihydrotachysterol), a calcium overloading of the cell membrane and intracellular buffer organelles without calcification was observed [21].
• Defective calcium absorption in the proximal small intestine in chronic renal failure: effect of dihydrotachysterol [22].
• 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 [23].

Associations of dihydrotachysterol with other chemical compounds

• A retrospective study of the comparative effects of vitamin D, dihydrotachysterol and 1alpha-hydroxyvitamin D3 was undertaken in twenty-eight patients with hypoparathyroidism [24].
• A comparative study of cholecalciferol, dihydrotachysterol and alfacalcidol in the treatment of elderly patients with hypocalcaemia [25].
• The effect of administration of 25 micrograms 24,25-dihydroxyvitamin D3 (24,25(OH)2D) combined with dihydrotachysterol (DHT2) on clinical, radiological, biochemical and bone histological parameters was assessed in ten children on chronic hemodialysis [15].
• A subgroup of children with demonstrated primary hypoparathyroidism received dihydrotachysterol (AT-10) and/or Ca supplementation [26].

Gene context of dihydrotachysterol

• Acute increases of plasma calcium were without significant effect on the MCR of hCT, but chronic hypercalcemia, induced by dihydrotachysterol treatment, reduced the MCR of hCT by 30% (P less than 0.05) and glomerular filtration rate (GFR) by 40% (P less than 0.02) [27].
• Neuropsychic disturbances and epilepsy resolved completely in both patients after treatment with calcium and dihydrotachysterol [28].

Analytical, diagnostic and therapeutic context of dihydrotachysterol

• In this study we showed that dihydrotachysterol was metabolized in vivo into a significant polar metabolite observed on straight-phase high performance liquid chromatography (HPLC) which subsequently split into two peaks on reverse-phase HPLC [29].
• She was not responsive to large doses of parenterally administered dihydrotachysterol and calcium, but she was responsive to the oral administration of 25-hydroxyvitamin D3 (25-OHD3) [30].
• In this double-blind study dihydrotachysterol (DHT) was given orally to eight psychotic patients; in each case marked increases in psychosis and agitation accompanied increases in serum calcium and phosphorus within two weeks after active drug was substituted for placebo [31].
• The ferret improved after treatment with dihydrotachysterol (a vitamin D analog) and calcium carbonate [32].
• Hypercalcaemia due to dihydrotachysterol treatment in patients with hypothyroidism after thyroidectomy [20].

References