TY - JOUR
T1 - Severely deficient binding of 1,25-Dihydroxyvitamin D to its receptors in a patient responsive to high doses of this hormone
AU - Castells, Salvador
AU - Greig, Fenella
AU - Fusi, Maria A.
AU - Finberg, Laurence
AU - Yasumura, Seiichi
AU - Liberman, Uri A.
AU - Eil, Charles
AU - Marx, Stephen J.
PY - 1986/7
Y1 - 1986/7
N2 - A 1.6-yr-old Hispanic boy with sparse hair, muscle weakness, severe growth retardation, and rickets was found to have hypocalcemia, secondary hyperparathyroidism, and high circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. One year of treatment with a high dose of 1,25-(OH)2D3 (20 μg, orally, daily) resulted in marked subjective and radiological improvement; there was a parallel improvement in serum calcium, phosphorus, PTH, alkaline phosphatase, and osteocalcin concentrations. Soluble extracts from cultured skin fibroblasts did not bind [3H]1,25-(OH)2D3 using standard methods. To evaluate the possibility of receptors with abnormally low affinity, we tested for binding with [3H]1,25-(OH)2D3 concentrations higher than those usually used. In one experiment, there was a suggestion of low affinity binding. Hormone receptors with abnormally low affinity for 1,25-(OH)2D may explain this patients resistance to 1,25-(OH)2D. Therapy to maintain extremely high serum 1,25- (OH)2D3 concentrations markedly improved mineral homoeostasis, but did not affect the hair disorder.
AB - A 1.6-yr-old Hispanic boy with sparse hair, muscle weakness, severe growth retardation, and rickets was found to have hypocalcemia, secondary hyperparathyroidism, and high circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. One year of treatment with a high dose of 1,25-(OH)2D3 (20 μg, orally, daily) resulted in marked subjective and radiological improvement; there was a parallel improvement in serum calcium, phosphorus, PTH, alkaline phosphatase, and osteocalcin concentrations. Soluble extracts from cultured skin fibroblasts did not bind [3H]1,25-(OH)2D3 using standard methods. To evaluate the possibility of receptors with abnormally low affinity, we tested for binding with [3H]1,25-(OH)2D3 concentrations higher than those usually used. In one experiment, there was a suggestion of low affinity binding. Hormone receptors with abnormally low affinity for 1,25-(OH)2D may explain this patients resistance to 1,25-(OH)2D. Therapy to maintain extremely high serum 1,25- (OH)2D3 concentrations markedly improved mineral homoeostasis, but did not affect the hair disorder.
UR - http://www.scopus.com/inward/record.url?scp=0022596443&partnerID=8YFLogxK
U2 - 10.1210/jcem-63-1-252
DO - 10.1210/jcem-63-1-252
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AN - SCOPUS:0022596443
SN - 0021-972X
VL - 63
SP - 252
EP - 256
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 1
ER -
