Improved differential diagnosis of hypercalcemia by hypocalcemic stimulation of parathyroid hormone secretion

Abstract

In vitro experiments have indicated that in primary hyperparathyroidism (HPT) the hyperfunctioning glands have a set point error, i.e., they are not autonomous but regulate serum calcium around a hypercalcémie value. In contrast, parathyroid function is suppressed in patients with hypercalcemia of causes other than HPT (e.g., malignancy or sarcoidosis). The basal measurements of serum parathyroid hormone (PTH) levels, however, cannot, alone, separate with precision HPT from other causes of hypercalcemia. Lowering of calcium, in order to stimulate secretion of PTH, was, therefore, achieved by either infusion of Na2 EDTA (24 mg/kg per hr) for 1 hour, or intramuscular injection of 100 IU salmon calcitonin. All 35 patients with primary HPT displayed a significant increase of serum PTH concentrations, evaluated by a midregion/intact hormone assay, during the EDTA infusion, which lowered plasma ionized calcium by an average of 0.16 mmol/l. The injection with calcitonin reduced the calcium concentrations by 0.10 mmol/l after 8 hours and caused a rise in PTH in 80% of HPT patients. With both tests, the secretory response by PTH to the reduction of plasma calcium was generally evident while the patients were still hypercalcemic. In 32 patients with other causes for hypercalcemia, primarily malignancy and sarcoidosis, similar reductions of plasma ionized calcium were obtained. In contrast to the HPT patients, none of them raised their serum PTH values during the test. Thus, stimulation of PTH secretion by a moderate reduction of serum calcium considerably improves the differential diagnosis of hypercalcemia since a significant secretory response appears to be exclusive for HPT.

Primary hyperparathyroidism: Epidemiology, diagnosis and clinical picture

“…In the few cases of HPT with PTH values in the normal range, the fact that PTH secretion in HPT maintains sensitivity to extracellular calcium can be used to diagnostic advantage [27][28][29][30][31]. Lowering of serum calcium, even within the hypercalcemic range, thus yields a compensatory increased secretion of PTH in patients with HPT whereas those with other causes of hypercalcemia will not change their (relatively suppressed) PTH value until serum calcium is lowered well into the normal range [32][33][34][35]. Such a reduction of serum calcium can easily be accomplished by either a short-term (30-60 min) infusion of EDTA or by a subcutaneous injection of calcitonin [32][33][34][35].…”

“…Lowering of serum calcium, even within the hypercalcemic range, thus yields a compensatory increased secretion of PTH in patients with HPT whereas those with other causes of hypercalcemia will not change their (relatively suppressed) PTH value until serum calcium is lowered well into the normal range [32][33][34][35]. Such a reduction of serum calcium can easily be accomplished by either a short-term (30-60 min) infusion of EDTA or by a subcutaneous injection of calcitonin [32][33][34][35]. A clear increase of serum PTH during a modest reduction of serum calcium within the hypercalcemic range seems to exclude causes of hypercalcemia other than HPT [35].…”

“…Such a reduction of serum calcium can easily be accomplished by either a short-term (30-60 min) infusion of EDTA or by a subcutaneous injection of calcitonin [32][33][34][35]. A clear increase of serum PTH during a modest reduction of serum calcium within the hypercalcemic range seems to exclude causes of hypercalcemia other than HPT [35].…”

Heterotransplantation of Human Parathyroid Glands into Nude Mice.

“…Many studies have been conducted on PTH synthesis by parathyroid cells by evaluating the expression of PTH mRNA, and secretion by both in vivo study with dogs or rats and in vitro study of cell cultures [9][10][11][12][13][14][15][16][17][18][19] …”