Effects of synthetic human parathyroid hormone (1-34) on plasma and urinary adenosine 3',5'-monophosphate and urinary phosphate and calcium in patients with hypoparathyroidism and pseudohypoparathyroidism (author's transl)

Abstract

According to recent advances in biochemistry, it is believed that the biologically active site of the parathyroid hormone (PTH) is the amino-terminal portion. Recently human PTH (1-34) (hPTH (1-34)) was synthesized in this country and has been used at a few laboratories. However, the clinical usefulness of this synthetic hPTH (1-34) remains uncertain. In this paper, whether or not hPTH (1-34) can be used for diagnostic evaluation of hypoparathyroidism and pseudohypoparathyroidism as well as native bovine PTH is investigated. The subjects were 5 patients with untreated idiopathic hypoparathyroidism (group Al), 10 patients with treated idiopathic or post-operative hypoparathyroidism (group A2), 3 patients with treated pseudohypoparathyroidism (group B) and 6 normal controls (group N). 5, 10, 20 or 30μg of hPTH (1-34) (Niall sequence, Toyo Jozo Inst.) or 200 units of bovine PTH (Parathormone, Eli Lilly) were injected intravenously with saline at 10 : 00 a.m. Urine was collected at 9 : 00, 10 : 00, 10 : 30, 11 : 00, 11 : 30, 12 : 00 and 13 : 00 and blood was driven at 9 : 30, 10 : 15, 10 : 30, 11 : 00, 11 : 30 and 12 : 00. Urine, serum phosphate, calcium and creatinine were measured by Technicon Autoanalizer. Urine and plasma adenosine 3', 5'-monophosphate (cAMP) were measured by radioimmunoassay using YAMASA cAMP kits. The results were as follows : 1) 5, 10 and 20μg of hPTH (1-34) were given to 2 patients in group Al. The doseresponse relationship was observed as to the maximum increase in the urinary cAMP excretion after hPTH (1-34) administration in both patients. The phosphaturic response to 5μg of hPTH (1-34) was lower than that to 10 or 20μg in one patient. In another, 5, 10 and 20μg of hPTH (1-34) had almost the same phosphaturic effect. 2) The basal excretion of urinary cAMP was significantly lower in groups Al, A2 and B than group N. In groups Al and A2, 20μg of hPTH (1-34) caused an 82.7 or 97.7 fold in-crease in urinary cAMP excretion. In group B, however, it caused only several fold increase. 3) The basal excretion of urinary phosphate was significantly lower in groups A1, A2 and B than in group N. Phosphaturic response to hPTH (1-34) was more than 5 times in groups Al and A2 but very low in groups B and N. 4) The basal excretion of urinary calcium was significantly low in group Al, but almost the same level of excretion was observed in groups A2, B and N. Urinary excretion of calcium after hPTH (1-34) administration decreased in groups A1 A2 and N, while it slightly elevated in group B. 5) The basal plasma cAMP levels were higher in groups A2 and B than in group N, and were not significantly different in groups Al and N. The responsiveness to hPTH (1-34) showed the same tendency to urinary cAMP. 6) Renal responses of cAMP and phosphate to 30pg of hPTH (1-34) were not so different from those to 20pg of hPTH (1-34) in patients with idiopathic hypoparathyroidism and pseudohypoparathyroidism. 7) There was a significant positive correlation between basal urinary phosphate and cAMP excretion. 8) 20μg of hPTH (1-34) and 200 units of Parathormone had almost identical effects on urinary cAMP excretion in patients with idiopathic hypoparathyroidism and pseudohypoparathyroidism, but hPTH (1-34) had less effect on urinary phosphate excretion than Parathormone. From these results, it is suggested that synthetic human PTH (1-34) can be used for diagnostic evaluation of patients with hypoparathyroidism and pseudohypoparathyroidism as well as native bovine PTH.