PTH Modulation by Aldosterone and Angiotensin II is Blunted in Hyperaldosteronism and Rescued by Adrenalectomy
Open accessAbstract
Context: Accumulating evidence suggests a link between adrenocortical zona glomerulosa and parathyroid gland through mechanisms that remain unexplored. Objectives: 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. Design and Setting: 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). Results: 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. Conclusion: 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.
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- Authors
- Lenzini, L., Prisco, S., Vanderriele, P. E., Lerco, S., Torresan, F., Maiolino, G., Seccia, T. M., Iacobone, M., & Rossi, G. P.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Rossi, Gian Paolo
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-03-13
- Volume
- 104
- Issue
- 9
- Pages
- 3726-3734
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2922413362
- Cited by
- 33
- References
- 26
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 3
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Università degli Studi di Padova
- Foundation for Advanced Research In Hypertension and Cardiovascular Diseases (FORICA)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- parathyroid hormone, aldosterone, angiotensin II, renin-angiotensin-aldosterone system, primary aldosteronism, aldosterone-producing adenoma, bilateral adrenal hyperplasia, adrenalectomy, captopril, mineralocorticoid receptor, angiotensin II type 1 receptor, parathyroid cells, primary hyperparathyroidism, essential hypertension, parathyroid hormone regulation
- MeSH terms
- Essential Hypertension, Adenoma, Adrenal Hyperplasia, Congenital, Adrenalectomy, Aldosterone, Angiotensin II, Antihypertensive Agents, Captopril, Cells, Cultured, Female, Follow-Up Studies, Humans, Hyperaldosteronism, Male, Middle Aged, Parathyroid Hormone, Prognosis, Prospective Studies, Vasoconstrictor Agents, Biomarkers, Disorder of Sex Development, 46,XY
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