vitamin-d-2 and Pseudohypoparathyroidism

A rapidly growing understanding of the biochemical and physiological processes that underlie the metabolism of vitamin D has provided new insights into the pathogenesis of oestomalacia. Many of the vitamin D--resistant osteomalacia syndromes can now be explained on the basis of defects in the metabolic conversion of vitamin D to the biologically active dihydroxylated metabolite 1,25(OH)2D and perhaps, in some instances, to impairement of the actions of 1,25(OH)2D on target tissues. The availability of this new information has made possible the synthesis of 1-hydroxylated forms of the vitamin for therapeutic use in states of vitamin D resistance. Although many questions regarding the pathogenesis and most effective approaches in the management of osteomalacia remain unanswered, considerable progress has been made in this direction as a result of continued research on the subject.

Topics: Bone Neoplasms; Chemical Phenomena; Chemistry; Cholecalciferol; Dihydroxycholecalciferols; Ergocalciferols; Giant Cell Tumors; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Hypophosphatemia, Familial; Kidney Failure, Chronic; Metabolism, Inborn Errors; Nephrectomy; Osteomalacia; Phosphates; Pseudohypoparathyroidism; Vitamin D; Vitamin D Deficiency

Intestinal malabsorption of calcium and the development of osteomalacia in conservatively treated renal failure is explained by a quantitative deficiency of 1,25-dihydroxycholecalciferol, which also contributes to the development of hypocalcaemia. Excess of 25-hydroxycholecalciferol can substitute for this deficiency. The presence and healing of azotaemic osteomalacia is unrelated to the prevailing plasma [Ca] x [P] product. The data suggest that "vitamin D" acts directly on bone mineralisation, but the claim that this apparent effect is normally due to 25-hydroxycholecalciferol is considered unproven. Most of the phenomena of azotaemic osteodystrophy are encountered in simple vitamin D deficiency; as in that condition, deficiency of 1,25-dihydroxycholecalciferol may be of primary significance in causing secondary hyperparathyroidism in renal failure.

Topics: Bone Resorption; Calcium; Dihydroxycholecalciferols; Drug Resistance; Ergocalciferols; Humans; Hypoparathyroidism; Kidney Failure, Chronic; Phosphates; Pseudohypoparathyroidism; Uremia; Vitamin D

Topics: Calcium; Calcium, Dietary; Child; Clinical Trials as Topic; Ergocalciferols; Female; Humans; Hypercalcemia; Parathyroid Hormone; Phosphates; Pseudohypoparathyroidism; Thyroidectomy

Pseudohypoparathyroidism type 1B (PHP1B) patients have PTH resistance at the renal proximal tubule and develop hypocalcemia and secondary hyperparathyroidism. Hyperparathyroid bone disease also develops in some patients. PHP1B patients are at theoretical risk of developing tertiary hyperparathyroidism.. Patients were studied in a clinical research center.. Five female PHP1B patients presented with hypercalcemia and elevated PTH.. Patients either underwent parathyroidectomy (n = 4) or received cinacalcet (n = 1).. Serum calcium and PTH were serially measured before and after intervention.. Five PHP1B patients developed concomitantly elevated serum calcium and PTH levels (range, 235-864 ng/liter) requiring termination of calcium and vitamin D therapy (time after diagnosis, 21-42 yr; median, 34 yr), consistent with tertiary hyperparathyroidism. Four patients underwent parathyroidectomy with removal of one (n = 2) or two (n = 2) enlarged parathyroid glands. Calcium and vitamin D therapy was reinstituted postoperatively, and at 93-month median follow-up, PTH levels ranged between 56 and 182 (normal, <87) ng/liter. One patient was treated with cinacalcet, resulting in resolution of hypercalcemia.. PHP1B patients are at risk of developing tertiary hyperparathyroidism and/or hyperparathyroid bone disease and should therefore be treated with sufficient doses of calcium and vitamin D to achieve serum calcium and PTH levels within or as close to the normal range as possible. Surgery is the treatment of choice in this setting. Cinacalcet may be a useful alternative in those who do not undergo surgery.

Topics: Adolescent; Age of Onset; Calcitriol; Calcium; Child, Preschool; Disease Progression; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Hypocalcemia; Male; Middle Aged; Muscular Diseases; Osteitis Fibrosa Cystica; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Pseudohypoparathyroidism; Seizures; Syntaxin 16; Young Adult

Topics: Calcifediol; Calcitriol; Calcium; Dihydrotachysterol; Ergocalciferols; Genetic Counseling; Humans; Pseudohypoparathyroidism; Vitamin D

A patient treated with massive doses of vitamin D for pseudohypoparathyroidism who had a convulsive episode due to hypocalcemia is reported. Evaluation of the patient's vitamin D status led us to conclude that the patient was non-compliant with vitamin D treatment.

Topics: Adolescent; Ergocalciferols; Humans; Hypocalcemia; Male; Patient Compliance; Pseudohypoparathyroidism; Seizures

In 23 patients with hypoparathyroidism or pseudohypoparathyroidism treated with vitamin D, and in whom the dosage was adjusted downward or upward in response to hypercalcemia or hypocalcemia respectively, assays of serum 25-hydroxyvitamin D (25-OHD) were carried out in addition to the usual serum calcium assays. In 120 assays there was a significant correlation between serum 25-OHD levels and serum calcium levels (corrected for serum albumin). There was, however, no clear distinction between the 25-OHD levels of patients who were hypocalcemic, normocalcemic or hypercalcemic. The highest serum 25-OHD level found in a hypocalcemic patient was 1193 nmol/L and the lowest serum 25-OHD level found in a hypercalcemic patient was 605 nmol/L. It was not possible to predict subsequent episodes of hypocalcemia or hypercalcemia from the serum 25-OHD levels. The 25-OHD assay was found to be useful only in checking compliance. We conclude that the assay of serum 25-OHD is of no more value than serum calcium alone in the management of compliant patients.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Calcium; Ergocalciferols; Female; Humans; Hypoparathyroidism; Male; Middle Aged; Pseudohypoparathyroidism

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. The optimal maintenance dose or minimum daily dose of 1,25-dihydroxyvitamin D3 to maintain serum calcium at approximately 8.5 mg/100 ml and control all the clinical symptoms was 1.3 +/- 0.16 micrograms/day (mean +/- SE) in pseudohypoparathyroidism, 1.5 +/- 0.18 micrograms/day in idiopathic hypoparathyroidism, and 1.9 +/- 0.50 micrograms/day in postoperative hypoparathyroidism. There was no significant difference in the optimal maintenance dose among the 3 groups. The optimal maintenance dose of 1 alpha-OHD3, however, was 2.0 +/- 0.12 micrograms/day in pseudohypoparathyroidism, significantly lower than that in idiopathic hypoparathyroidism (3.5 +/-0.29 micrograms/day; P less than 0.001) and in postoperative hypoparathyroidism (4.89 +/- 0.54 micrograms/day; P less than 0.001). Significantly lower doses were required in the treatment of idiopathic hypoparathyroidism than in postoperative hypoparathyroidism (P less than 0.05). No significant difference was found in the optimal maintenance dose of dihydrotachysterol and vitamin D2 among the 3 groups. The average pretreatment serum calcium levels and clinical manifestations were indistinguishable among the 3 groups of patients. This suggests that such a difference in the optimal maintenance dose of 1 alpha-OHD3 is ascribed not to the difference in the severity of hypoparathyroidism, but most probably to differences in the pathophysiological processes in pseudohypoparathyroidism and idiopathic or postoperative hypoparathyroidism. The excess parathyroid hormone levels in blood of patients with pseudohypoparathyroidism (and not in other types of hypoparathyroidism) may explain such a difference.

Topics: Adolescent; Adult; Aged; Body Weight; Calcifediol; Calcitriol; Calcium; Dihydrotachysterol; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Postoperative Complications; Pseudohypoparathyroidism; Vitamin D

The basal values of plasma vitamin D metabolites were evaluated in patients with primary hyperparathyroidism (1 degree HPT, n = 31), hypoparathyroidism (HP, n = 7), pseudohypoparathyroidism (PHP, n = 4) and normal controls (n = 21). Plasma 25-hydroxyvitamin D (25-OH-D) in 1 degree HPT (9.0 +/0 7.3 ng/ml, mean SD) was significantly lower than that of normal controls (17.9 +/- 5.5ng/ml)(p less than 0.001), and in particular 1 degree HPT classified as the skeletal type showed extremely low value (4.7 +/- 4.6 ng/ml). Plasma 1, 25-dihydroxyvitamin D [1, 25-(OH)2D] was significantly higher in 1 degree HPT (69.1 +/- 31.4pg/ml)(p less than 0.001) and significantly lower in Hp (15.2 +/- 11.0 pg/ml) (p less than 0.001) compared to normal controls (37.2 +/- 13.8pg/ml), although there was no significant difference in PHP (22.3 +/- 17.5 pg/ml). Plasma 24, 25-dihydroxyvitamin D [24,, 25-(OH)2D] in 1 degree HPT (1.06 +/- 0.55 ng/ml) was significantly lower than that of normal controls (1.73 +/- 0.62 ng/ml) (p less than 0.05), and particularly 1 degree HPT classified as the skeletal type showed a marked low value (0.85 +/- 0.27 ng/ml), whereas no significant differences were seen in HP (1.84 +/- 0.46 ng/ml) or PHP (1.34 +/- 0.22 ng/ml). There were slight but significant correlations between either plasma 25-OH-D and 1, 25-(OH)2D (r = -0.350, p less than 0.05), or plasma 25-OH-D and 24, 25-(OH)2D (r = 0.356, p less than 0.05), or plasma 1, 25-(OH)2D and 24, 25-(OH)2D (r = -0.444, p less than 0.01) in all subjects. In addition, relationships between plasma vitamin D metabolites and other indicators of parathyroid function in all subjects were analyzed. There were positive correlations between plasma 1, 25-(OH)2D and serum Ca (r = -0.621, p less than 0.001) or urinary cAMP (r = -0.671, p less than 0.001) or nephrogenous cAMP (r = -0.689, p less than 0.001), while negative correlations were seen between plasma 1, 25-(OH)2D and serum P (r = -0.680, p less than 0.001) or %TRP (r = -0.663, p less than 0.001). On the other hand, there were negative correlations between plasma 24, 25-(OH)2D and serum Ca (r = -0.457, p less than 0.01) or urinary cAMP (r = -0.562, p less than 0.005) or nephrogenous cAMp (r = -0.561, p less than 0.005), and a positive correlation was seen between plasma 24, 25-(OH)2D and %TRP (r = 0.519, p less than 0.005). After parathyroidectomy, a distinct depression of plasma 1, 25-(OH)2D and reciprocal elevation of plasma 24, 25-(OH)2D were observed in 1 degree

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Calcium; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Male; Middle Aged; Phosphorus; Pseudohypoparathyroidism

Topics: Adolescent; Adult; Dihydrotachysterol; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Male; Middle Aged; Pseudohypoparathyroidism

Topics: Adult; Child; Dihydrotachysterol; Dihydroxycholecalciferols; Ergocalciferols; Humans; Male; Pseudohypoparathyroidism; Vitamin D

The aims of this study were to determine the dose of vitamin D2 that maintains the serum calcium level within the normal range in hypoparathyroid and pseudohypoparathyroid children and to establish a safe and quickly acting dose for initiating therapy in symptomatic patients. The dose requirement for maintenance therapy was studied in 11 patients and initiation therapy was studied in five newly diagnosed hypocalcemic patients. The results show that (1) the maintenance requirement of vitamin D2 is proportional to body weight and averages 2,000 IU (50 microgram)/kg/day for children of all ages and with all types of hypoparathyroid disorders and the (2) in newly diagnosed symptomatic patients, carefully controlled administration of 8,000 IU (200 microgram) vitamin D2/kg/day for the first one to two weeks corrects hypocalcemia quickly and safely.

Topics: Adolescent; Adult; Body Weight; Calcium; Child; Child, Preschool; Drug Administration Schedule; Ergocalciferols; Female; Humans; Hypocalcemia; Hypoparathyroidism; Male; Pseudohypoparathyroidism; Vitamin D

Pseudohypoparathyroidism (PsH) is a genetic disease characterized by hypocalcemia, hyperphosphatemia, and metabolic unresponsiveness to parathyroid hormone (PTH). The administration of PTH elicits neither a significant rise in serum calcium (calcemic response) nor a decrease in the renal tubule reabsorption of phosphorus (phosphaturic response). The diminished phosphaturic response is due to an inability of PTH to generate cyclic AMP in renal tubule cells. We investigated the question of whether hypocalcemia and deficient calcemic response to PTH are due to a similar cyclic AMP defect in bone or to an acquired vitamin D deficiency. Four patients were studied. The active form of vitamin D (1,25-dihydroxycholecalciferol) was measured in 3 and was low. Treatment with vitamin D2 restored the serum calcium and the calcemic response to PTH to normal without changing the impaired renal response. Bone biopsy was performed in 2 patients and showed morphologic evidence of increased osteoclastic activity and osteomalacia. The data indicate that the hypocalcemia and bone disease in PsH are due to active vitamin D deficiency, possibly resulting from the genetic renal lesion.

Topics: Adult; Alkaline Phosphatase; Bone Diseases; Calcium; Creatine; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hydroxycholecalciferols; Hypocalcemia; Middle Aged; Parathyroid Hormone; Phosphorus; Pseudohypoparathyroidism

Topics: Adolescent; Dihydrotachysterol; Ergocalciferols; Female; Humans; Hypocalcemia; Hypoparathyroidism; Hypophosphatemia, Familial; Infant; Male; Protein-Losing Enteropathies; Pseudohypoparathyroidism

Topics: Adolescent; Alkaline Phosphatase; Bone and Bones; Calcium; Ergocalciferols; Humans; Kidney; Male; Osteitis Fibrosa Cystica; Parathyroid Hormone; Phosphorus; Pseudohypoparathyroidism; Radiography

Topics: Child, Preschool; Electroencephalography; Ergocalciferols; Humans; Male; Parathyroid Hormone; Phosphates; Pseudohypoparathyroidism; Time Factors

Topics: Calcium; Calcium, Dietary; Diet; Diet Therapy; Ergocalciferols; Humans; Hypoparathyroidism; Pseudohypoparathyroidism

Topics: Alkaline Phosphatase; Calcium; Calcium Metabolism Disorders; Calcium, Dietary; Ergocalciferols; Hypoparathyroidism; Inulin; Kidney Tubules; Osteitis Fibrosa Cystica; Parathyroid Hormone; Pharmacology; Phosphorus; Pseudohypoparathyroidism; Rats; Urine

Topics: Calcium; Child; Diagnosis, Differential; Dihydrotachysterol; Ergocalciferols; Exostoses; Humans; Hyperparathyroidism; Myositis Ossificans; Osteitis Fibrosa Cystica; Parathyroid Glands; Pathology; Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism; Turner Syndrome