Interplay Between Sodium and Calcium Regulatory Hormones
A Clinically Relevant Research Field
See related article, pp 273–280
Sodium and calcium homeostasis are tightly regulated by endocrine systems. Of particular importance are effects of the renin–angiotensin–aldosterone system (RAAS) on sodium and of parathyroid hormone (PTH) and vitamin D on calcium homeostasis.
Although previous investigations studied the relationship between the RAAS and PTH in the setting of either absolute aldosterone excess, that is, primary aldosteronism (PA), or absolute PTH excess, that is, primary hyperparathyroidism, Brown et al addressed this issue in study participants without autonomous dysregulation of either aldosterone or PTH.1 This post hoc investigation was performed in obese and overweight patients under control of posture, diet, time of day, and medications known to modulate the RAAS.
The research group around Brown identified the expression of the angiotensin II (AngII) type I receptor and of the mineralocorticoid receptor (MR) in normal parathyroid glands and increased 2- to 4-fold in adenomatous parathyroid glands. Although low serum calcium levels are the physiological stimulus for the synthesis and secretion of PTH by the parathyroid glands, the data by Brown et al suggest an additional direct regulatory impact of the RAAS on PTH. This hypothesis was substantiated by an increase of PTH and aldosterone after AngII infusions and a decrease of both hormones after a single dose of the angiotensin-converting enzyme (ACE)–inhibitor captopril.
In view of a lacking effect of aldosterone infusion on PTH levels, Brown et al concluded that AngII might mediate the acute effects of the RAAS on PTH secretion, whereas aldosterone might mediate long-term effects on PTH via genomic MR-related mechanisms. With this in line, MR antagonists by spironolactone treatment for 6 weeks modestly but significantly lowered PTH, as well as serum calcium and …