RESUMO
OBJECTIVE: To improve understanding of the biochemical events in vitamin D-deficiency rickets (VDR). METHODS: We investigated 51 untreated patients, 2 to 36 months of age, during three stages of VDR. Nineteen of these patients were also studied during therapy with 5000 to 10,000 U vitamin D3 (cholecalciferol) and 0.5 to 1 gm calcium. Together with calcium and inorganic phosphate in serum and urine, we measured (1) parathyroid hormone (PTH) secretion (intact serum PTH) and action on the kidney (urinary adenosine 3',5'-cyclic monophosphate (cAMP)/creatinine ratio; (2) serum alkaline phosphatase level; (3) urinary hydroxyproline/creatinine ratio; and (4) serum 1,25-dihydroxyvitamin D (1,25(OH)2D) level. RESULTS: The untreated patients had secondary hyperparathyroidism (high serum PTH and urinary cAMP/creatinine ratio), low calcium and phosphate concentrations in serum, and increased bone turnover (elevated serum alkaline phosphatase and OHP/creatinine ratio), whereas serum 1,25(OH)2D was low, normal, or even slightly elevated. Serum calcium level was positively correlated to serum 1,25(OH)2D and to OHP/creatinine ratio, indicating that normocalcemia in untreated rickets (stage 2) is at least partially maintained by 1,25(OH)2D-induced calcium mobilization from bone. There was no correlation between serum calcium and serum PTH, or between serum PTH and urinary cAMP/creatinine ratio or serum phosphate, indicating disturbed regulation and action of PTH. During vitamin D treatment, serum 1,25(OH)2D values increased to supranormal concentrations in association with the restoration of the physiologic relationship of PTH to serum calcium and phosphate concentrations and urinary cAMP/creatinine ratio. CONCLUSION: Circulating 1,25(OH)2D has an important role in the pathophysiology of VDR before and during treatment, mainly by influencing the bone and kidney response to endogenous PTH.
Assuntos
Cálcio/metabolismo , Raquitismo/metabolismo , Fosfatase Alcalina/sangue , Cálcio da Dieta/administração & dosagem , Pré-Escolar , Colecalciferol/uso terapêutico , Creatinina/sangue , AMP Cíclico/metabolismo , Di-Hidroxicolecalciferóis/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Hidroxiprolina/urina , Lactente , Masculino , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Raquitismo/tratamento farmacológico , Raquitismo/etiologia , Raquitismo/fisiopatologia , Fatores de TempoRESUMO
Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25-dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King-Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cálcio/metabolismo , Hanseníase Dimorfa/metabolismo , Hanseníase Virchowiana/metabolismo , Hormônio Paratireóideo/sangue , Adulto , Idoso , Fosfatase Alcalina/sangue , Di-Hidroxicolecalciferóis/sangue , Feminino , Humanos , Hidroxicolecalciferóis/sangue , Hidroxiprolina/urina , Masculino , Pessoa de Meia-IdadeRESUMO
STUDY OBJECTIVE: To examine (1) the effect of vitamin D intake (380 to 480 IU daily) on plasma 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations and (2) the relationship of 1,25-(OH)2D to calcium and phosphorus absorption and retention in the very low birth weight infant receiving a preterm infant formula. SUBJECTS: Eleven "well" infants with a birth weight and gestational age (mean +/- SD) of 1078 +/- 128 gm and 29 +/- 1.9 weeks, respectively, were studied for a 3-week period. Weight and postnatal age (mean +/- SD) at the beginning of the study were 1132 +/- 56 gm and 16 +/- 6 days, respectively. All infants were fed a preterm infant formula and tolerated a full enteral intake (120 kcal/kg/day) for the duration of the study. INTERVENTIONS: Plasma 25-OHD and 1,25-(OH)2D concentrations were measured at the beginning of the study and at the beginning of each 48-hour balance period. Calcium and phosphorus balance studies (n = 33) were performed weekly. MAIN RESULTS: Plasma 25-OHD (30 +/- 10 ng/ml) and 1,25-(OH)2D (54 +/- 14 pg/ml) concentrations were normal at the beginning of the study. Plasma 25-OHD values did not change, but 1,25-(OH)2D values increased (p less than 0.001) throughout the study. Plasma 1,25-(OH)2D concentrations were not related to calcium or phosphorus absorption and retention, but were a linear function of postconceptional age. CONCLUSIONS: Normal vitamin D status and activity are maintained in the very low birth weight infant fed a high calcium formula (380 to 480 IU of vitamin D daily). Plasma 1,25-(OH)2D concentrations are not related to calcium absorption but are linearly related to maturity.
Assuntos
Cálcio/metabolismo , Di-Hidroxicolecalciferóis/sangue , Hidroxicolecalciferóis/sangue , Recém-Nascido de Baixo Peso/metabolismo , Fósforo/metabolismo , Vitamina D/administração & dosagem , Humanos , Recém-Nascido , Necessidades NutricionaisRESUMO
Inappropriately elevated concentrations of 1,25(OH)2 vitamin D in serum appear to be responsible for excessive gastrointestinal absorption of dietary calcium in patients with absorptive hypercalciuria. We have examined serum 1,25(OH)2 vitamin D concentrations in another group of children with hypercalciuria in whom urinary calcium excretion was excessive after an overnight fast. Eleven children with idiopathic fasting hypercalciuria (IH) (urinary calcium excretion greater than 4 mg/kg/24 hr and fasting urinary calcium/urinary creatinine ratio greater than 0.21) and seven healthy children were observed while they were eating a diet containing 1 gm calcium per day. Fasting serum 1,25(OH)2 vitamin D concentrations were elevated in children with IH compared with control values (35.3 +/- 3.2 vs 21 +/- 2 pg/ml, P = 0.003), whereas fasting serum parathyroid hormone, 25-OH vitamin D, phosphorus, and ionized calcium concentrations were similar in the two groups. These data suggest that disordered 1,25(OH)2 vitamin D metabolism occurs in children with fasting IH. Absorptive and fasting IH may represent a spectrum of a single disorder characterized by excessive urinary calcium excretion and inappropriately elevated serum concentrations of 1,25(OH)2 vitamin D.
Assuntos
Cálcio/urina , Di-Hidroxicolecalciferóis/sangue , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
The circulating concentrations of calcium, phosphorus, and vitamin D metabolites were measured in 25 infants (fifteen to 30 days of age) with congenital hypothyroidism before treatment or during the first 6 months of thyroxine therapy. Five of the children before treatment and four during the early 3 months of treatment had mild hypercalcemia (10.8 to 12.4 mg/dl). Hypercalcemia before treatment did not appear to be related to the vitamin D status of the infant nor to an alteration in vitamin D metabolism, but to the presence of a residual thyroid secretion. In contrast, hypercalcemia during thyroxine therapy was related to vitamin D supplementation, even though the serum calcium concentration could not be correlated with the circulating concentration of any of the vitamin D metabolites assayed and obvious changes in vitamin D metabolism could not be demonstrated.
Assuntos
Hipotireoidismo Congênito , Hipercalcemia/complicações , Hormônios Tireóideos/sangue , Vitamina D/metabolismo , 24,25-Di-Hidroxivitamina D 3 , 25-Hidroxivitamina D 2 , Fosfatase Alcalina/sangue , Calcitriol/sangue , Cálcio/sangue , Di-Hidroxicolecalciferóis/sangue , Ergocalciferóis/administração & dosagem , Ergocalciferóis/análogos & derivados , Ergocalciferóis/sangue , Ergocalciferóis/uso terapêutico , Humanos , Hipercalcemia/sangue , Hipotireoidismo/sangue , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Recém-Nascido , Fósforo/sangue , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/uso terapêutico , Fatores de TempoRESUMO
This study was designed to evaluate the role of vitamin D sufficiency, as reflected in serum 25-hydroxyvitamin D (25-OHD) concentrations, on serum minerals and bone mineralization in very premature infants. Seventy-two infants (mean +/- SD gestation 30.1 +/- 2.5 weeks, mean +/- SD birth weight 1178 +/- 278 gm) were observed serially for the first 3 months of life. Mean serum calcium and phosphorus values, but not magnesium, remained low prior to 12 weeks. The percentage of infants with moderate to severe hypomineralization was 75% at 3 weeks, 55% at 6 weeks, 54% at 9 weeks, and 15% at twelve weeks. Low serum calcium and phosphorus values, high alkaline phosphatase activity, and moderate-severe hypomineralization were more frequent in infants weighing less than 1000 gm and in those with lower mineral intake. With a 400 IU vitamin D supplement, 45% of infants could maintain an initially normal serum 25-OHD concentration or increase low concentrations, whereas 55% had falling or persistently low (less than or equal to 15 ng/ml) 25-OHD concentrations. Birth weight and mineral intakes were comparable in these two groups, yet the group with the lower serum 25-OHD concentration had lower serum calcium and higher alkaline phosphatase values, and a higher percentage of moderate to severe hypomineralization. Regardless of birth weight, mineral intake, or 25-OHD concentration, increases in serum calcium and phosphorus values and in mineralization were seen at postconception term (12 weeks in most infants, nine weeks in those weighing 1250 to 1600 gm). At 12 weeks of age, but not before, serum 25-OHD concentration was directly correlated with serum calcium (r = 0.47, P less than 0.01) and serum phosphorus (r = 0.47, P less than 0.01) and inversely correlated with alkaline phosphatase values (r = -0.71, P less than 0.01). Mineral availability and 25-OHD sufficiency both appear to be important and to act synergistically, with neither totally compensating for the other.
Assuntos
Osso e Ossos/metabolismo , Calcifediol/sangue , Homeostase , Recém-Nascido Prematuro , Minerais/sangue , Fosfatase Alcalina/sangue , Peso ao Nascer , Cálcio/sangue , Di-Hidroxicolecalciferóis/sangue , Humanos , Recém-Nascido , Assistência de Longa Duração , Minerais/metabolismo , Fósforo/sangue , Raquitismo/metabolismo , Vitamina D/sangueRESUMO
Elevated 1,25 dihydroxyvitamin D concentrations were found in five VLBW infants who developed rickets at two to three months postnatal age or term postconceptual age; 25 hydroxyvitamin D concentrations were low. Bone mineralization was found to be extremely low as measured by infant-adapted direct photon absorptiometry. After treatment with a formula supplemented with additional Ca and P, there was a rapid improvement in bone mineralization with a concomitant decrease of 1,25(OH)2D to normal adult values, whereas 250HD values increased and parathyroid hormone values decreased. In the VLBW infants studied, we suggest that rickets may be caused by Ca and P deficiency rather than by a deficiency of vitamin D metabolism.
Assuntos
Di-Hidroxicolecalciferóis/sangue , Hidroxicolecalciferóis/sangue , Recém-Nascido de Baixo Peso , Raquitismo/sangue , Calcitriol , Cálcio/administração & dosagem , Colecalciferol/administração & dosagem , Humanos , Recém-Nascido , Fósforo/administração & dosagem , Raquitismo/dietoterapiaAssuntos
Sangue Fetal/análise , Troca Materno-Fetal , Vitamina D/sangue , 25-Hidroxivitamina D 2 , Transporte Biológico Ativo , Calcitriol , Cálcio/sangue , Cromatografia Líquida de Alta Pressão , Di-Hidroxicolecalciferóis/sangue , Feminino , Humanos , Hidroxicolecalciferóis/sangue , Recém-Nascido , GravidezAssuntos
Di-Hidroxicolecalciferóis/sangue , Sangue Fetal/análise , Hidroxicolecalciferóis/sangue , 25-Hidroxivitamina D 2 , Calcitriol , Cálcio/sangue , Di-Hidroxicolecalciferóis/biossíntese , Feminino , Humanos , Hipocalcemia/sangue , Recém-Nascido , Doenças do Prematuro/sangue , Magnésio/sangue , Troca Materno-Fetal , Hormônio Paratireóideo/sangue , Fósforo/sangue , Gravidez , População UrbanaRESUMO
Rickets with alopecia, an inborn error of vitamin D metabolism, is described in two sisters. The rachitic disorder began during the first year of life and was refractory to 50,000 IU of vitamin D2/day. Surprisingly, both children had marked elevations in serum concentrations of 1,25-(OH)2D. Although the molecular basis for this disorder is not evident to date, intestinal end-organ unresponsiveness to exceedingly high levels of 1,25-(OH)2D was present, in addition to hyporesponsiveness of bone to these high levels of the hormone, since normocalcemia was maintained despite elevated serum levels of PTH. Therapy with oral 1,25-(OH)2D3 failed to reverse the disorder, but oral phosphorus supplements resulted in significant radiographic and clinical improvement.
Assuntos
Alopecia/complicações , Hipofosfatemia Familiar/complicações , Erros Inatos do Metabolismo/complicações , Vitamina D/metabolismo , Alopecia/genética , Alopecia/metabolismo , Cálcio/metabolismo , Criança , Pré-Escolar , Di-Hidroxicolecalciferóis/sangue , Di-Hidroxicolecalciferóis/uso terapêutico , Feminino , Humanos , Hipofosfatemia Familiar/genética , Hipofosfatemia Familiar/metabolismo , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/metabolismo , Fenótipo , Fósforo/metabolismo , Fósforo/uso terapêuticoRESUMO
The mean serum concentration of 24,25(OH)2D determined by competitive protein-binding radioassay was significantly lower in ten uremic children maintained on hemodialysis (0.82 +/- 0.43[SD] ng/ml) than in ten patients with impaired renal function not requiring hemodialysis (1.30 +/- 0.54 ng/ml, P less than 0.05), or in 12 normal children (2.98 +/- 1.57 ng/ml, P less than 0.01). The serum levels of 250HD were similar in all groups. There were significant (P less than 0.01) positive correlations between the serum concentration of 24,25(OH)2D or the ratio 24,25(OH)2D/25OHD and the creatinine clearance. The serum concentration of 24,25(OH)2D was significantly decreased also in six anephric adults relative to normal adult values. The data indicate that production of 24,25(OH)2D is impaired in subjects with compromised renal function. Inasmuch as the major active metabolite of Vitamin D, i.e., 1,25(OH)2D, is requried for renal synthesis of 24,25(OH)2D measurement of the latter metabolite may provide a convenient method for assessment of renal vitamin D metabolism. The role of this metabolite in the pathogenesis of renal osteodystrophy remains speculative.
Assuntos
Di-Hidroxicolecalciferóis/sangue , Hidroxicolecalciferóis/sangue , Rim/metabolismo , Uremia/sangue , Criança , Humanos , Diálise Renal , Uremia/terapiaRESUMO
Serum concentration of 25OHD and 24,25(OH)2D were measured in lipid extracts of serum by competitive radioassay following separation of the metabolits by Sephadex LH-20 column chromatography. The concentration of 24,25(OH)2D in children and adolescents (3.3 +/- 1.3 SD ng/ml) was significantly greater (P less than 0.01) than the levels recorded in neonates (1.8 +/- 0.6 ng/ml), and was approximately one-tenth the concentration of 25OHD in the two populations (children 35.2 +/- 9.2 ng/ml; neonates 14.4 +/- 3.4 ng/ml, P less than 0.01). Although 24,25(OH)2D is present in significant quantities in the sera of children and adolescents, its metabolic function remains unknown at present.