PTH Modulation by Aldosterone and Angiotensin II is Blunted in Hyperaldosteronism and Rescued by Adrenalectomy

Accumulating evidence suggests a link between adrenocortical zona glomerulosa and parathyroid gland through mechanisms that remain unexplored.

To test the hypothesis that in vivo angiotensin II blockade affects PTH secretion in patients with hypertension and that aldosterone and angiotensim II directly stimulate PTH secretion ex vivo.

We investigated the changes of serum PTH levels induced by oral captopril (50 mg) administration in patients with primary essential hypertension (EH) and with primary aldosteronism (PA) caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenoma (APA), the latter before and after adrenalectomy. We also exposed primary cultures of human parathyroid cells from patients with primary hyperparathyroidism to angiotensin II (10-7 M) and/or aldosterone (10-7 M).

Captopril lowered PTH levels (in nanograms per liter) both in patients with EH (n = 63; 25.9 ± 8.3 baseline vs 24.4 ± 8.0 postcaptopril, P < 0.0001) and in patients with APA after adrenalectomy (n = 27; 26.3 ± 11.6 vs 24.0 ± 9.7 P = 0.021). However, it was ineffective in patients with full-blown PA caused by APA and BAH. In primary culture of human parathyroid cells, both aldosterone (P < 0.001) and angiotensin II (P = 0.002) markedly increased PTH secretion from baseline, by acting through mineralocorticoid receptor and angiotensin type 1 receptor, as these effects were abolished by canrenone and irbesartan, respectively.

These results collectively suggest an implication of the renin-angiotensin-aldosterone system in PTH regulation in humans, at least in PTH-secreting cells obtained from parathyroid tumors. Moreover, they further support the concept that mild hyperparathyroidism is a feature of human PA that is correctable with adrenalectomy.