Clinical Studies Using a Highly Sensitive Radioimmunoassay for Mid-Region and Carboxy Terminus of Parathyroid Hormone in Normal, Hypo-and Hypercalcemic States

Abstract

Parathyroid hormone radioimmunoassay (RIA), specific for mid-region of the PTH molecule, has been proven to be extremely useful for the differential diagnosis of abnormal calcium metabolism. Recently, we developed a highly sensitive RIA for PTH, consisting of PTH antiserum (CH9), 125I labelled Tyr42 hPTH (43-68) and synthetic hPTH (1-84) as standard. This RIA cross-reacted with mid-region and carboxyl terminals of PTH. The within-assay and between-assay coefficients of variation were less than 4.6% and less than 8.6%, respectively. The limit of detection was 50pg/ml. The levels of serum calcium, serum phosphate, serum creatinine, Tmpo4/GFR and creatinine clearance (Ccr) in normal healthy volunteers aged 20 to 50 years remained almost constant and showed 9.24 +/- 0.34mg/dl (mean +/- SD, n = 242), 3.34 +/- 0.38mg/dl (n = 242), 0.870 +/- 0.121mg/dl (n = 242), 3.20 +/- 0.54mg/dl GF (n = 189) and 103 +/- 17ml/min (n = 137), respectively. All healthy volunteers (n = 326) had measurements of PTH in the blood. From 20 to 50 years, normal PTH mean was 374 +/- 97pg/ml (+/- SD, n = 237) and ranged from 180-568pg/ml, and from 60 to 80 years it was 471 +/- 133pg/ml (n = 34) and ranged from 205-737pg/ml. Since we found that PTH was markedly elevated above normal when Ccr was below 40ml/min, and PTH was very significantly correlated with the reciprocal of Ccr (r = 0.8996, P less than 0.001) using a multivariate analysis, all of the patients whose Ccr was higher than 40ml/min were selected and examined in the following studies. Serum PTH values completely separated patients with surgically proven primary hyperparathyroidism (1 degree HPT) from malignant associated hypercalcemia (MAH), and patients with idiopathic hypoparathyroidism (IHP) from pseudohypoparathyroidism (PHP), both of which were diagnosed by Ellsworth-Howard test. PTH values in all of the patients with 1 degree HPT (n = 23) were above normal, but those with MAH (n = 6) were below the normal or lower normal range. PTH values in patients with PHP (n = 7) showed above normal, while those with IHP (n = 5) were below the normal range. PTH was normalized in post operative status in all patients after parathyroidectomy (n = 6). These results indicate that this PTH RIA is extremely useful for the differential diagnosis in diseases with calcium abnormalities.