Studies on in vivo and in vitro release of intact parathyroid hormone using a new two‐site immunochemiluminometric assay

Abstract

Basal parathyroid hormone (PTH) levels measured by a chemiluminescent immunoassay for intact PTH showed good discrimination between normal, n=82 (1.2–9.4 pmol/l), and hyperparathyroid subjects, n=55 (9–200 pmol/l). In malignant hypercalcemia, all PTH levels were within the normal range or suppressed (0.8–5.2 pmol/l). Dynamic studies of PTH release in response to intramuscular salmon calcitonin (100 u) showed no significant rise out of the normal range in controls, but adenoma patients demonstrated a mean rise at 120, 180, and 240 minutes of 22%, 22%, and 35%, respectively, and hyperplasia patients a mean rise of 44%, 63%, and 46%, respectively. The mean absolute rise in PTH concentration was 10.6±7.2 pmol/g parathyroid adenoma and 26.6±19.2 pmol/g hyperplastic parathyroid tissue; this difference being significant (p <0.01). In vitro studies were performed in which dispersed cells prepared from both parathyroid adenomas and hyperplastic tissue were exposed to low (0.5 mM) and high (2.5 mM) extracellular calcium. Intact PTH secretion was measured under these conditions and compared with the results obtained by a mid‐region (44–68) specific immunoassay for PTH. There was parallel secretion of intact and mid‐region hormone under all conditions, the secretion rate of hyperplastic cells being greater than that of adenomas. Suppressibility of PTH release by high extracellular calcium was significantly greater in hyperplasia than in adenomas. These differences in the behavior of adenomatous and hyperplastic tissues both in vivo, in response to calcitonin, and in vitro, in response to changes in extracellular calcium concentration, suggest that the underlying pathogenesis of hyperparathyroidism may be heterogenous at the cellular level.

Invited commentary

“…These in Vivo and DNA analyses can be correlated with a higher mitotic index [10,11] and agree with earlier in vitro studies [8] as well as With studies of others [6,12], who found functionally less suppressibility of PTH secretion in nodular hyperplastic com-Pared to diffuse hyperplastic glands. The differentiation of diffuse and nodular hyperplasia alone as .~entioned by the authors and earlier by Wallfelt and coworkers 6] and Aston and associates [12] seems insufficient [7]. Also, it ~s quite important to differentiate within diffuse enlarged glands on the basis of the fat cell content [8].…”

“…With cytometric DNA analysis they ex-Plained these findings by a significantly higher number of Scattered cells displaying cytometric nuclear DNA values out-Side the main diploid histogram peak in nodular tissue. These in Vivo and DNA analyses can be correlated with a higher mitotic index [10,11] and agree with earlier in vitro studies [8] as well as With studies of others [6,12], who found functionally less suppressibility of PTH secretion in nodular hyperplastic com-Pared to diffuse hyperplastic glands. The differentiation of diffuse and nodular hyperplasia alone as .~entioned by the authors and earlier by Wallfelt and coworkers 6] and Aston and associates [12] seems insufficient [7].…”

99mTc‐sestamibi Scintigraphy and Cell Cycle in Parathyroid Glands of Secondary Hyperparathyroidism

“…Nodular hyperplasia exhibits more severely disturbed suppression of PTH secretion and more decrease in the density of vitamin D 3 receptors [14,16]. Functional in vitro studies demonstrated a so-called autonomous secretory disorder in these nodules [17,18]. The clonal analyses of diffuse and nodular hyperplasia by Tominaga et al [14] demonstrated that diffuse hyperplastic glands were polyclonal in origin, whereas nodules in nodular hyperplasia were monoclonal; therefore in each case polyclonal diffuse hyperplasia and monoclonal nodular hyperplasia coexist.…”

Thallium-Technetium Subtraction Scintigraphy of Enlarged Parathyroid Glands after Calcitonin Stimulation of Parathyroid Hormone Secretion

“…We stimulated PTH secretion in 14 consecutive pa tients with pHPT before the thallium-technetium subtraction scintigraphy. We selected calcitonin as the stimulus, since pre vious studies have shown that calcitonin decreases serum calcium with a prompt increase of PTH secretion (1,2).…”