The Effect of Extracellular Calcium Metabolism on Aldosterone Biosynthesis in Physiological and Pathological Status

Abstract

Primary aldosteronism (PA) was reported to frequently harbor not only cardiovascular diseases but also some metabolic disorders including secondary calcium metabolic diseases. Recently, the potential association between aldosterone producing cells and systemic calcium metabolism has been proposed. For instance, PA is frequently associated with hypercalciuria or hypocalcemia, which subsequently stimulates parathyroid hormone (PTH) secretion. This altered calcium metabolism in PA patients could frequently result in secondary osteoporosis and fracture in some patients. On the other hand, extracellular calcium itself directly acts on adrenal cortex and has been also proposed as an independent regulator of aldosterone biosynthesis in human adrenals. However, it is also true that both PTH and vitamin D pathways stimulate endocrine functions of adrenal cortical adenomas to co-secret both aldosterone and cortisol. Therefore, it has become pivotal to explore the potential crosstalk between aldosterone and systemic calcium metabolism. We herein reviewed recent advances in these fields.

Severe Hypocalcemia and Transient Hypoparathyroidism After Hyperthermic Intraperitoneal Chemotherapy

“…Longterm treatment with calcitriol in postsurgical hypoparathyroidism can lead to renal function decline [15]. Interestingly, hypocalcemia or hypercalciuria has been associated with primary aldosteronism, a frequent cause of endocrine hypertension [16,17].…”

Evaluating the clinical and mechanistic effects of eplerenone and amiloride monotherapy, and combination therapy with cinacalcet, in primary hyperparathyroidism: A placebo‐controlled randomized trial

“…A growing body of research has consistently shown that the RAAS also has complex physiologic interactions with parathyroid hormone (PTH) 4–10 . In populations without primary hyperparathyroidism (P‐HPT), higher circulating aldosterone concentrations and aldosterone‐to‐renin ratios are associated with higher PTH levels 11–15 .…”

“…[1][2][3] A growing body of research has consistently shown that the RAAS also has complex physiologic interactions with parathyroid hormone (PTH). [4][5][6][7][8][9][10] In populations without primary hyperparathyroidism (P-HPT), higher circulating aldosterone concentrations and aldosterone-to-renin ratios are associated with higher PTH levels. [11][12][13][14][15] A continuous relationship between aldosterone and PTH levels has been demonstrated, 12 particularly in hypertension and individuals with a primary aldosteronism-like phenotype; conversely, the use of RAAS inhibitors is associated with lower PTH levels in large human cohort studies.…”

Progress in Primary Aldosteronism 2019: New Players on the Block?

“…In a series of pathophysiologic manuscripts, the role of mast cells [14], expression of aldosterone synthase in adrenalectomy samples [15], the role of aldosterone producing cell clusters [16], and the methodologic advances obtained by tissue mass spectrometry imaging [17] are analyzed. Finally, the study of Gao et al [18] gives a comprehensive overview on calcium metabolism in PA, followed by an in-depth study on clinical determinants of surgical success by Naruse et al [19]. The final word and outlook has the nestor of primary aldosteronism research, John Funder, in his commentary "Primary Aldosteronism: Where Are We Now?…”

“…Finally, the study of Gao et al. 18 gives a comprehensive overview on calcium metabolism in PA, followed by an in-depth study on clinical determinants of surgical success by Naruse et al 19 . The final word and outlook has the nestor of primary aldosteronism research, John Funder, in his commentary “Primary Aldosteronism: Where Are We Now?…”