副甲状腺機能低下症における血中, 尿中cyclic AMP, 尿中リン, カルシウムに対する合成ヒト副甲状腺ホルモン (1-34) の効果

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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.
日本内分泌学会の論文

副甲状腺機能低下症における血中, 尿中cyclic AMP, 尿中リン, カルシウムに対する合成ヒト副甲状腺ホルモン (1-34) の効果

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