title: The acute effect of chlorothiazide on serum-ionized calcium. Evidence for a parathyroid hormone-dependent mechanism.
abstract: The acute effects of chlorothiazide (CTZ) on total (TSCA) and ionized (SCA-plus 2) serum calcium concentrations were studied in three groups of people: (a) eight subjects with normal parathyroid function; (b) six patients with hypoparathyroidism; and (c) two patients with hyperparathyroidism. Most subjects were studied on four occasions; at least 3 days intervened between studies on an individual subject. During each experiment the subject received an i.v. influsion of 5% dextrose in water at 1 ml/min from 8 a.m. to 4 p.m. Additions to the infusions were (a) none; (b) CTZ to deliver 3.33 mg/kg/h; (c) parathyroid extract to deliver 1 U/kg/h; or (d) both CTZ and parathyroid extract at the rates previously indicated. CTZ, when used, was added to the infusion at 10 a.m., parathyroid extract at 8 a.m. When CTZ was infused, the diuretic-induced losses of Na and water were replaced by i.v. infusion. In normal subjects 2 h after the start of CTZ infusion, there was a transient increase in SCA-plus 2 which coincided in time of day with a transient decrease in SCA-plus 2 in control experiments. At that time of day SCA-plus 2 was 4.18 plus or minus 0.12 mg/100 ml in control experiments and 4.56 plus or minus 0.08 in experiments with CTZ, P smaller than 0.025. The corresponding values for (TSCA) were 9.32 plus or minus 0.15 and 9.80 plus or minus 0.30, P smaller than 0.01. Such differences were not observed in the group with hypoparathyroidism. In the two patients with hyperparathyroidism, CTZ produced sustained increases in TSCA and SCA-plus 2. In normal subjects and those with hypoparathyroidism, CTZ plus parathyroid extract infusion resulted in sustained increases in both SCA-plus 2 and TSCA throughout the periods of observation when compared to experiments in which only parathyroid extract was infused, P smaller than 0.01 in all instances. The results suggest that the acute hypercalcemic action of CTZ requires the presence of circulating parathyroid hormone.
mesh_terms: D000328:Adult; D002118:Calcium / Q000097:blood* / Q000652:urine; D002740:Chlorothiazide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood / Q000652:urine; D007011:Hypoparathyroidism / Q000097:blood / Q000652:urine; D007263:Infusions, Parenteral; D008274:Magnesium / Q000652:urine; D008297:Male; D008875:Middle Aged; D010279:Parathyroid Diseases / Q000097:blood / Q000378:metabolism* / Q000652:urine; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010758:Phosphorus / Q000652:urine; D012964:Sodium / Q000008:administration & dosage / Q000652:urine; D014867:Water / Q000008:administration & dosage
chemical_list: D010281:Parathyroid Hormone; D014867:Water; D010758:Phosphorus; D002740:Chlorothiazide; D012964:Sodium; D008274:Magnesium; D002118:Calcium