Dynamic Tests of Parathyroid Function for Diagnosis of Primary Hyperparathyroidism in Malignancy

Abstract

Hypercalcaemia can be caused by malignant diseases as well as by primary hyperparathyroidism (HPT). The two disorders may occur together and an accurate discrimination between them is sometimes not possible from basal measurements of calcium and parathyroid hormone (PTH) concentrations. In primary HPT the regulation of PTH secretion is maintained, albeit the set-point is shifted to a hypercalcaemic value. Therefore, when serum calcium is lowered by ethylene diamine tetra-acetic acid (EDTA) infusions or calcitonin injections, patients with primary HPT display enhanced secretion of PTH already within the hypercalcaemic range, whereas parathyroid function remains suppressed in malignancy-associated hypercalcaemia. Tests based on this principle enable a specific identification of HPT. The present report describes eight hypercalcaemic patients with disseminated malignancy where HPT could be diagnosed by the use of such stimulatory tests.

Normal pattern of parathyroid response to blood calcium lowering in primary hyperparathyroidism: a citrate clamp study

“…The concentration of PTH( 1-84), which increases 2-10 times in PHPT patients and 4-7 times in normals, subsequently declines to a steady state increase 2-4 times above baseline, which is maintained throughout the 2hour study period. This way of responding is in close harmony with the concept that parathyroid adenomas and normal parathyroid glands are 'set' to maintain blood Ca2+ at different levels (Benson et a/., 1984(Benson et a/., , 1986Ljunghall et al, 1987;Brown et al, 1978;Gardin et al, 1988). The parathyroid responsiveness of some of the controls seems greater than described in a study by Brent et al (1988).…”

“…The introduction of radioimmunoassays for measurements of the Cterminal and mid-region, and later the immunoradiometric assay for PTH( 1-84), have challenged this concept. Increasing serum calcium by calcium infusion, or reducing it by infusions of EDTA or salmon calcitonin, promoted reciprocal changes in PTH, principally identical to those observed in normal man (Reiss & Canterbury, 1969;Murray et al, 1972;Benson et al, 1984Benson et al, , 1986Ljunghall et al, 1987;Paillard et al, 1989;Mazzuoli et al, 1990;Lips et al, 1991). Primarily, such reactivity was claimed specific for patients with chief cell hyperplasia (Reiss & Canterbury, 1969).…”

“…The PTH(1-84) responses in the PHPT group were independent of baseline concentrations and presence or absence of surgical confirmation. Benson et al (1984,1986) and Ljunghall et al (1987) suggested that PTH stimulation tests might be of help in the diagnosis of PHPT, but the clinical value would depend on the PTH assay used. By our use of the PTH(1-84) assay and carefully standardized degree of blood Caz+ lowering, we found that the PTH( 1-84) response was of little value in the differentiation between PHPT and normality.…”

“…Primarily, such reactivity was claimed specific for patients with chief cell hyperplasia (Reiss & Canterbury, 1969). Later studies, however, revealed similar reactivity in almost all patients with PHPT regardless of parathyroid pathology (Murray et al, 1972;Benson et al, 1984Benson et al, , 1986Ljunghall et al, 1987). In the tissue culture studies of Brown et al (1978) parathyroid adenomas and hyperplastic glands from patients with chief cell hyperplasia were also found to respond almost identically to changes in the calcium ion concentration of the surrounding fluid.…”

“…None of these studies paid attention to the early PTH( 1-84) response to blood calcium lowering. Benson et al (1984Benson et al ( , 1986 and Ljunghall et al (1987) have suggested that the PTH response to EDTA or salmon calcitonin infusion might be useful from a diagnostic point of view. Technical improvements using bedside measurements of blood ionized calcium (CaZ+) and laboratory measurements of serum intact parathyroid hormone (PTH( 1-84)), have enabled us to undertake more detailed studies of PTH( 1-84) secretion, using the trisodium citrate clamp technique (citrate clamp) to provoke and maintain a carefully standardized degree of relative hypocalcaemia (Schwarz et al, 1990).…”