副甲状腺機能異常症における尿中Cyclic AMP及びNephrogenous Cyclic AMPの診断的意義

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Urinary excretion of cyclic 3′, 5′-adenosine monophosphate (UcAMP) has been studied by several researchers in an attempt to diagnose primary hyperparathyroidism (1°CHPT), but the results have been conflicting. In secondary hyperparathyroidism, little is known about the behavior of UcAMP. 14 patients with 1°CHPT, 12 patients with hypoparathyroidism (including 2 with pseudohypoparathyroidism), 6 patients with nonparathyroid neoplasms, 44 patients with other normocalcemic diseases including secondary hyperparathyroidism and 16 control subjects were studied with regard to their UcAMP. Nephrogenous cyclic AMP (NcAMP) was calculated as the difference between total UcAMP and cAMP derived from circulating plasma (plasma cAMP × creatinine clearance). 1) UcAMP, expressed as a function of creatinine excretion (μ mol/g.creatinine), was a good index discriminating 1°CHPT from other diseases. Absolute amounts of cAMP in 24-hour urine were less valuable in this respect. But the patients with a relatively low excretion of creatinine, for instance those with hyperthyroidism, were sometimes difficult to differentiate from 1°CHPT by the ratio UcAMP/g.creatinine. The following results were obtained : CAMP was measured by radioimmunoassay employing a YAMASA Kit (YAMASA, Choshi, Japan), and creatinine by Brod & Sirota's method. 2) UcAMP, either expressed in terms of 24-hour excretion or of the ratio to creatinine, was very low in patients with advanced renal diseases. Even in patients with 1°CHPT, UcAMP was not elevated when their renal function had been impaired, rendering the differential diagnosis by the UcAMP less clear cut. 3) UcAMP, expressed as a function of GFR (n mol/100ml GF, GF=glomerular filtrate), reflected parathyroid function more correctly than other expressions : GFR-corrected UcAMP (n mol/100ml GF, mean ± S.D.) was 3.50 ± 0.47 in control subjects, 2.29 ± 0.63 in hypoparathyroidism and 11.25 ± 5.57 in 1°HPT. 4) Two out of three patients with 1°CHPT, whose UcAMP per g.creatinine or per 24-hour urine was within normal limits because of renal damage, showed a definite increase in urinary cAMP when it was expressed as a function of GFR. 5) NcAMP was raised in all 9 patients with 1°CHPT (>2.81 n mol/100ml GF; normal range of values was 0.54-2.42) including a case of chemical type (plasma iPTH=0.43 ng/ml, normal value : <0.5 ng/ml) in whom UcAMP was within the normal range. 6) NcAMP (n mol/100ml GF) was also raised in several examples of normocalcemic patients with Cushing's syndrome, chronic pancreatitis and hypothyroidism in whom plasma iPTH was elevated (indicating secondary hyperparathyroidism). On the other hand, an increase in NcAMP (n mol/100ml GF) was found without elevated iPTH levels in a few examples of patients with pheochromocytoma and hyperthyroidism (indicating false positive). 7) When NcAMP was estimated as a function of the plasma calcium concentration, however, patients with various diseases in whom NcAMP overlapped with that of patients with 1°CHPT could be separated. 8) NcAMP was decreased in one patient with multiple myeloma with bone lesions (0.61 n mol/100ml GF), and increased in another with renal carcinoma without apparent bone metastases (4.71 n mol/100ml GF); the latter was highly suggestive of "ectopic hyperparathyroidism". From these results, it may be concluded that UcAMP or NcAMP, expressed as a function of GFR, reflects the parathyroid function not only in patients with hypoparathyroidism and 1°CHPT but also in secondary hyperparathyroidism. The determination of UcAMP, and especially NcAMP, is extremely useful in the diagnosis of 1°CHPT when interpreted as a function of serum calcium level and is useful in differentiating patients with hypercalcemia, either PTH mediated or not.
日本内分泌学会の論文

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孫孝義
東北大学医学部第二内科

副甲状腺機能異常症における尿中Cyclic AMP及びNephrogenous Cyclic AMPの診断的意義

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