RESUMEN
Hypocalcemia is a major stimulus for parathyroid hormone secretion and presumably the major cause of parathyroid hyperplasia in chronic hypocalcemic syndromes. We could find no data to indicate what degree, duration, or frequency of hypocalcemia is needed to produce parathyroid hyperplasia in humans. We have monitored the effects of thrice weekly hypocalcemic parathyroid stimulation for 10 weeks. Measurements were made during a study designed to test the feasibility of carrying out a randomized, blinded trial of "chelation therapy," a widely used but unproven method to treat atherosclerotic symptoms. Eight patients received infusions of disodium ethylenediaminetetraacetic acid (EDTA) and six received placebo infusions thrice weekly for ten weeks. The EDTA infusions (50 mg/kg over three hours) lowered serum ionized calcium at two hours by an average of 0.20 mmol/L and trebled the immunoreactive parathyroid hormone (iPTH) value. Basal serum iPTH, ionized calcium and 1,25-dihydroxyvitamin D values, measured just before the infusion, did not change significantly after 10 weeks of treatment with either EDTA or placebo. The increment in serum iPTH produced by the EDTA-induced hypocalcemia was also unchanged. Lowering ionized serum calcium to values below the normal range three times a week for 10 weeks is not a sufficient stimulus to cause a detectable increase in basal or stimulated parathyroid function.
Asunto(s)
Calcio/sangre , Glándulas Paratiroides/fisiología , Anciano , Arteriosclerosis/tratamiento farmacológico , Ácido Edético/farmacología , Ácido Edético/uso terapéutico , Humanos , Hiperplasia , Hipocalcemia/complicaciones , Persona de Mediana Edad , Glándulas Paratiroides/patología , Hormona Paratiroidea/metabolismo , Factores de TiempoRESUMEN
We have designed a cyclic regimen for the treatment of osteoporosis based on the activate, depress, free, and repeat (ADFR) concept. Osteoclastic bone resorption is activated by 7 days of oral neutral phosphate and inhibited with a brief pulse (5 days) of etidronate disodium at a high dose (20 mg/kg body weight). Patients next take calcium supplements for 48 days before resuming phosphate to enter the next cycle. Osteoporotic women increased the bone mineral density of the lumbar spine at 6 months by 7.2 +/- 5.2% (mean +/- SD, N = 14) and at 12 months by 8.2 +/- 4.0% (N = 8). Control observations in regularly exercising postmenopausal women (N = 30) showed no significant change in spine mineral density after 20 months (0.5 +/- 3.2%), confirming the stability of the measurement technique. The two patients who responded poorly to the cyclic regimen each showed a blunted rise in serum PTH during oral phosphate administration, suggesting that the rise in PTH induced by oral phosphate may be an important component of this cyclic regimen. This preliminary study does not identify which component or components of the regimen are responsible for the increase in bone mass but provides positive encouragement for randomized studies designed to determine the optimum dosage, duration, and timing of each component of the regimen.
Asunto(s)
Ácido Etidrónico/uso terapéutico , Osteoporosis/tratamiento farmacológico , Fosfatos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Resorción Ósea/efectos de los fármacos , Calcio/sangre , Esquema de Medicación , Quimioterapia Combinada , Ácido Etidrónico/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis/metabolismo , Hormona Paratiroidea/sangre , Fosfatos/administración & dosificación , Columna Vertebral/efectos de los fármacos , Columna Vertebral/metabolismoRESUMEN
A patient with pseudoxanthoma elasticum was documented to be hyperphosphatemic and mildly hypercalcemic for six years. Complications included metastatic calcification, absorptive hypercalciuria, and renal insufficiency. The 1,25-dihydroxyvitamin D value was elevated, despite normal serum parathyroid hormone values, high serum phosphate levels, and renal insufficiency. Either increased dietary calcium or prednisone seemed to suppress the 1,25-dihydroxyvitamin D value. Nephrolithiasis or abnormalities suggestive of pseudoxanthoma elasticum occurred in the patient's father, daughter, and several siblings, suggesting a distinct familial syndrome in which connective tissue changes are accompanied by abnormalities of phosphorus and vitamin D metabolism that may resemble those in the syndrome of familial tumoral calcinosis. Nine similar cases were described before 1970.
Asunto(s)
Hipercalcemia/metabolismo , Fósforo/metabolismo , Seudoxantoma Elástico/metabolismo , Vitamina D/metabolismo , Calcitriol/metabolismo , Calcio/metabolismo , Humanos , Cálculos Renales/genética , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/metabolismo , Prednisona/uso terapéutico , Seudoxantoma Elástico/genética , Pruebas de Función de la TiroidesRESUMEN
Eight patients with childhood acute lymphoblastic leukemia (ALL) and hypercalcemia, osteopenia, or vertebral compression fractures seen at our institution during the last 12 years were evaluated for biochemical evidence of bone disease. Five patients were hypercalcemic, three had abnormal phosphorous levels, and four had elevated alkaline phosphatase values. Parathyroid hormone (PTH) was measured by a polyvalent radioimmunoassay in five patients and these levels were abnormally high in three patients. Four of these five patients also had PTH measured by a midregion-specific radioimmunoassay. One patient had a high PTH value. Two patients had low levels and one patient had a normal PTH level. Although these studies suggest diverse biochemical mechanisms may be contributing to the bone changes and hypercalcemia seen in childhood ALL, ectopic PTH production as well as ectopically produced fragments of PTH may have a role in mediating bone resorption and hypercalcemia.
Asunto(s)
Enfermedades Óseas Metabólicas/complicaciones , Leucemia Linfoide/complicaciones , Adolescente , Fosfatasa Alcalina/análisis , Niño , Preescolar , Humanos , Hipercalcemia/complicaciones , Hormona Paratiroidea/análisis , Fósforo/análisis , RadioinmunoensayoRESUMEN
An increase in circulating, 1,25-dihydroxyvitamin D level and net intestinal calcium absorption have been previously demonstrated in pregnant women and have been widely regarded as compensatory mechanisms whereby fetal mineral demands are satisfied. The alternate possibility, that these adjustments might anticipate such demands, has not previously been considered. To examine the effects of pregnancy on the intestinal absorption and renal excretion of calcium, oral calcium tolerance tests were performed and urinary calcium excretion was measured in 16 healthy women receiving a moderate calcium intake during and after pregnancy. Circulating 1,25-dihydroxyvitamin D levels and indexes of parathyroid function were also measured. As expected, 1,25-dihydroxyvitamin D levels were significantly (p less than 0.05) elevated throughout pregnancy (94 +/- 11, 118 +/- 9, and 117 +/- 11 pg/ml in the first, second, and third trimesters, respectively, versus 51 +/- 5 pg/ml after delivery). Twenty-four-hour calcium excretion also increased sharply (247 +/- 54, 316 +/- 42, 300 +/- 61 mg versus 91 +/- 18 mg), often to the point of hypercalciuria. Calcium tolerance test results included significant increases in the calciuric and calcemic responses during each trimester, whereas fasting calcium excretion and parathyroid function remained normal. These findings portray normal pregnancy as a state of physiologic absorptive hypercalciuria and call into question the widespread practice of supplementing calcium intake in otherwise well-nourished women during pregnancy.
Asunto(s)
Calcitriol/sangre , Calcio/metabolismo , Embarazo , Adulto , Calcio de la Dieta/administración & dosificación , Femenino , Tasa de Filtración Glomerular , Humanos , Absorción Intestinal , Factores de TiempoRESUMEN
Recent studies have emphasized the pathophysiological importance of circulating 1,25-dihydroxyvitamin D ((1,25-(OH)2D] in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. Reasoning that phosphate administration might be capable of reducing the plasma concentration of 1,25-(OH)2D in patients with a prominent 1,25-(OH)2D-mediated absorptive component to their disease, 10 carefully selected patients were treated with oral phosphate (1500 mg elemental phosphorus daily) for 1 yr. Phosphate treatment significantly reduced circulating 1,25-(OH)2D levels (84 to 56 pg/ml), the calciuric response to an oral calcium tolerance test (0.30 to 0.21 delta mg calcium/dl GF), and calcium excretion on an unrestricted calcium diet (438-269 mg/day), in essence reversing the absorptive pattern of abnormalities observed before treatment. This response, however, was accompanied by an increase in biochemical hyperparathyroidism, as assessed by circulating immunoreactive PTH and nephrogenous cAMP excretion. In patients with biochemical evidence of an increase in bone resorption before therapy, histomorphometric, radiographic, and biochemical data revealed a trend toward a reduction in bone turnover during phosphorus therapy, with an apparent maintenance of coupled bone resorption and bone formation. This trend, however, was of marginal statistical significance in the patient group as a whole. It is concluded 1) that phosphate therapy represents a viable medical alternative in selected patients with primary hyperparathyroidism, 2) that the net response in treated patients is multifaceted and complex, and 3) that the efficacy of phosphate therapy will ultimately depend upon its long term effects on skeletal homeostasis.
Asunto(s)
Hiperparatiroidismo/tratamiento farmacológico , Fósforo/uso terapéutico , Huesos/fisiopatología , Calcitriol/sangre , Calcio/sangre , Calcio/orina , AMP Cíclico/orina , Evaluación de Medicamentos , Femenino , Humanos , Hiperparatiroidismo/fisiopatología , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangreRESUMEN
The diagnosis of hypoparathyroidism by radioimmunoassay of serum parathyroid hormone (PTH) has been hampered by lack of an assay system sensitive enough to allow discrimination between low and normal values. A new assay for human PTH that has improved sensitivity has been developed. It uses an homologous antiserum (against the human hormone) and uses a carboxy-terminal fragment of bovine PTH as tracer to provide an assay monospecific for the midregion of PTH. Immunoreactive PTH (iPTH) was detectable in 25/27 normal children and borderline detectable in the other two. The pediatric normal range was slightly lower than that previously established in adults. Among patients with secondary hyperparathyroidism and normal renal function, iPTH was 3- to 8-fold elevated in those with rickets, and 1.3- to 2.0-fold above normal in those with more acute forms of hypocalcemia. Twelve patients with hypoparathyroidism were studied. iPTH was undetectable in seven with permanent total hypoparathyroidism, and was borderline detectable in five, including four neonates who proved to have transient hypoparathyroidism. In these four patients, iPTH became detectable as the requirements for supplemental calcium decreased. Measurement of iPTH with an adequately sensitive assay may be useful in the diagnosis and management of pediatric hypocalcemia.