Influence on parathyroid hormone storage in normal and adenomatous parathyroid tissue by stimulation and inhibition in vitro.

Abstract

The aim of the study was to elucidate morphological and secretory differences between normal and adenomatous human parathyroid tissue after incubations with neutral, stimulatory, and inhibitory culture medium for 2, 6, and 24 h. The glandular response was determined immunohistochemically by revealing alterations of the parathyroid hormone (PTH) distribution pattern, and radioimmunologically by measuring the amounts of PTH secreted into the medium. Normal parathyroids contained varying amounts of intracellular PTH, even in adjacent cells. Before incubation, 35% of the parathyroid cells displayed high, 25% medium, and 40% low amounts of PTH. Hypocalcemic stimulation reduced the intracellular PTH content in normal tissue markedly within 2 h, indicating rapid depletion of the PTH stores. Simultaneously, the PTH secretion into the culture medium was enhanced by a factor of 2.9. Hypercalcemic inhibition induced an increase of the intracellular PTH within 2 h; this increase continued during incubation for up to 6 h. The elevated storage of the hormone is interpreted as the result of the reduction by 40% of the PTH secretion, and of the apparently unimpaired hormone synthesis in parathyroid tissue kept in hypercalcemic medium during short-term incubation. Parathyroid adenomas contained lower amounts of PTH than normal glands, corresponding to lower storage capacity with higher rates of hormone release. Histological cosections of adenoma with the adjacent normal gland showed the tumor cells slightly immunostained, whereas the normal tissue was highly immunoactive, suggesting a difference of in vivo Ca2+ sensitivity. In response to in vitro stimulation or inhibition, adenomatous parathyroid tissue showed alterations of immunostaining and PTH secretion similar to that of normal cells, although the intensity of the immunostaining was lower. This indicates a lower Ca2+ sensitivity of parathyroid adenomas, as compared to normal glands. Based on the results obtained, a working hypothesis on the pathogenesis of primary hyperparathyroidism is proposed.