We compared the utility of measurements of serum intact human PTH-(1-84) and midregion human PTH-(44-68) in patients with disorders of extracellular calcium metabolism. Serum midregion PTH was determined by RIA, and serum intact PTH was measured by a sensitive and specific immunoradiometric two-site assay. The serum intact PTH concentrations in 70 patients with primary hyperparathyroidism were above the normal range in 69, and thus widely separated from the levels in 40 patients with hypercalcemia of malignancy, in whom serum intact PTH values were usually below normal. In contrast, both groups had overlapping serum midregion PTH values. In patients after renal transplantation and those with chronic renal failure, serum intact PTH levels were in the normal range twice as often as were serum midregion PTH values. The intact PTH assay was also superior in detecting venous gradients of the hormone and changes in PTH secretion caused by altered serum calcium concentrations, and serum intact PTH was remarkably low in hepatic venous effluent. We conclude that this new assay for serum intact PTH is superior to the midregion RIA in investigating parathyroid function in several different clinical conditions.

In 49 patients with primary hyperparathyroidism, intact parathyroid hormone (PTH) was measured with a recently developed immunoradiometric assay, and midregional PTH fragments (sequence 44-68) were measured with an established radioimmunoassay technique. In 47 normal subjects, the concentration of intact PTH ranged from 2.0 to 6.8 pmol/l, and in 49 patients with primary hyperparathyroidism it ranged from 6.4 to 80.0 pmol/l. In contrast, midregional PTH fragments were normal in seven of 49 patients with primary hyperparathyroidism. In five healthy controls and in 12 patients with surgically confirmed primary hyperparathyroidism and serum calcium levels below 3.0 mmol/l, a rapid calcium loading test was performed. In healthy controls, intact PTH was in the low normal to subnormal range within 2.5-5.0 min, and had recovered within 15 min of calcium infusion. In patients with primary hyperparathyroidism, the calcium infusion also led to a 30-50 per cent decrease in intact PTH levels within 5.0-7.5 min after injection, with a slow recovery after 10-15 min. In six of the patients with only slightly elevated basal intact PTH, a suppression to the normal range was observed. In 24 patients (16 patients with a solitary adenoma and eight patients with four-gland hyperplasia) the intact PTH levels were followed intraoperatively during parathyroidectomy, revealing a significantly different rate of decline for single adenomas compared with hyperplasia during the first 15 min after removal of the primary enlarged gland. Intact PTH values remained constantly elevated in one patient with primary hyperparathyroidism and an unsuccessful neck exploration. These results confirm that (a) the measurement of intact PTH in patients with primary hyperparathyroidism is superior to the measurement of midregional fragments; (b) PTH secretion in primary hyperparathyroidism is not totally autonomous; and (c) intraoperative monitoring of intact PTH values could be used to monitor the success of surgery.

The development of a sensitive 2-site immunoradiometric assay which detects only intact human PTH (1-84) enabled us to study kinetics of PTH secretion intraoperatively. In a prospective study, we assessed the PTH (1-84) secretion mode intraoperatively in 54 patients with adenomas, in 14 patients with tertiary hyperparathyroidism (HPT), and in 2 patients with persistent HPT. After the removal of adenomatous or hyperplastic tissue, a significant drop of PTH (1-84) concentration was seen. A 50% decrease in the basal PTH concentration was reached significantly earlier for adenomas than for hyperplasias. In the 2 cases with unrevealing neck exploration, the PTH (1-84) concentrations showed hardly any change. The recovery of PTH secretion was studied in 23 patients, 20 of whom had a single adenoma; in 2 cases, a hyperplasia was present and 1 patient showed the clinical signs of a toxic HPT. We found an initial drop of PTH concentration 4 hours postoperatively below the limit of detection and a rapid recovery within 24 hours postoperatively. The PTH concentration values were well within the normal range after 48-72 hours.

The ability of amphotericin B (AmB) to potentiate the cytotoxicity of several different anticancer agents against two murine tumor models was examined. A spleen colony assay was used to quantitate the cytotoxicity of BCNU, CCNU, and L-PAM, either alone or in combination with AmB against the MOPC-315 plasmacytoma. A high level of potentiation of the effects of CCNU and L-PAM by AmB occurred, but AmB did not increase the cytotoxicity of BCNU. Tumor growth curves and calculation of cell survival demonstrated significant potentiation of the cytotoxicity of CCNU by AmB against SC Lewis lung carcinoma.