Pulsatile parathyroid hormone secretion in health and disease.

In humans plasma parathyroid hormone (PTH) fluctuates episodically at a frequency of 6-7 bursts per hour. Approximately 30% of circulating PTH is attributable to pulsatile secretion and 70% to tonic secretion. PTH release is tightly controlled by Ca2+. Acute hypocalcaemia elicits a biphasic wave of PTH release, with an initial selective amplification and acceleration of the pulsatile component followed by proportionate stimulation of pulsatile and tonic secretion. Acute hypercalcaemia submaximally suppresses the frequency and mass of PTH bursts as well as tonic PTH release. Patients with primary hyperparathyroidism exhibit proportionate increases in pulsatile and tonic secretion, with no change in pulse frequency. In secondary hyperparathyroidism due to renal insufficiency, tonic secretion and pulsatile burst mass are also proportionately amplified, and burst frequency is increased. Moreover, the hypocalcaemia-induced increase in burst frequency and mass as well as their suppression during hypercalcaemia is diminished, suggesting partial uncoupling of hyperplastic parathyroids from physiological regulatory mechanisms. While the secretory pattern of PTH and its dysregulation in disease states is now well defined, the functional significance of pulsatile PTH signalling for target tissues is still largely unexplored. Preliminary work indicates that intermittent, in contrast to continuous, PTH administration stimulates bone formation. Cell culture studies suggest PTH receptor down-regulation with tonic exposure.