title: Pathogenesis of hypocalcemia in primary hypomagnesemia: normal end-organ responsiveness to parathyroid hormone, impaired parathyroid gland function.
abstract: Hypocalcemia is a frequent feature of hypomagnesemia in man and several other species. To elucidate the cause of this hypocalcemia, we have studied a child with primary hypomagnesemia and secondary hypocalcemia during magnesium supplementation when he was normomagnesemic and normocalcemic and after magnesium restriction for 16 days when he quickly became hypomagnesemic (0.5 meq/liter) and hypocalcemic (3.4 meq/liter) and had positive Chvostek's and Trousseau's signs. Whether in the normomagnesemic or hypomagnesemic state, intravenous bovine parathyroid extract (PTE) 8 U. S. P. U/kg promptly caused transient increases in the urinary phosphate excretion, renal phosphate clearance and cyclic AMP excretion. The magnitudes of these responses were similar in the two states, and similar to those observed in a hypoparathyroid patient. When the patient was hypomagnesemic and hypocalcemic, intramuscular PTE, 8 U/kg at 8-h intervals for four doses promptly caused hypercalcemia. The findings indicate that the end-organs were responsive to parathyroid hormone. The concentrations of serum parathyroid hormone (PTH) were normal in the normomagnesemic state ranging from 0.15 ng/ml to 0.40 ng/ml. Serum PTH did not increase in the hypomagnesemic state in spite of hypocalcemia. Indeed, PTH became unmeasurable in four consecutive samples at the end of the period of magnesium restriction. The concentrations of serum calcitonin remained unmeasurable (< 0.10 ng/ml) throughout the study, implying that excess calcitonin was not the cause of hypocalcemia in magnesium depletion. The findings in this study support our thesis that magnesium depletion causes impaired synthesis or secretion of parathyroid hormone. This impairment would account for the hypocalcemia observed in the hypomagnesemic state.
mesh_terms: D002116:Calcitonin / Q000097:blood; D002118:Calcium / Q000097:blood; D002648:Child; D003404:Creatinine / Q000097:blood / Q000652:urine; D000242:Cyclic AMP / Q000652:urine; D006801:Humans; D006996:Hypocalcemia / Q000097:blood / Q000209:etiology*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D008274:Magnesium / Q000097:blood / Q000627:therapeutic use; D008275:Magnesium Deficiency / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010710:Phosphates / Q000097:blood / Q000652:urine; D011863:Radioimmunoassay
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D002116:Calcitonin; D003404:Creatinine; D000242:Cyclic AMP; D008274:Magnesium; D002118:Calcium