Primary and Secondary Hyperparathyroidism in Patients with Primary Aldosteronism – Findings From the German Conn’s Registry

Abstract

Context Recent studies support a bidirectional interaction between aldosterone and parathyroid hormone (PTH), possibly increasing the individual cardiovascular risk. Primary aldosteronism (PA) and primary hyperparathyroidism can occur simultaneously.

Objective Our aim was to investigate the prevalence of hyperparathyroidism in PA.

Patients We performed a case finding of primary hyperparathyroidism in a retrospective series of 503 patients with PA (cohort 1). We analysed primary and secondary hyperparathyroidism in 141 prospective PA patients who underwent PTH, serum calcium and phosphate measurements at time of diagnosis of PA (cohort 2).

Results The prevalence for primary hyperparathyroidism was 1.2% in cohort 1, and 2.1% in cohort 2. Secondary hyperparathyroidism was found in 54.6% of the patients. Patients with secondary hyperparathyroidism had significantly higher aldosterone and lower potassium levels and took more antihypertensive medications compared to those with normal PTH levels. In multivariate analysis, aldosterone and 25-hydroxyvitamin D levels were significantly correlated with serum PTH levels. There was a nonsignificant trend to a higher cardiovascular morbidity in patients with secondary hyperparathyroidism. Patients with aldosterone producing adenoma had significantly higher PTH levels compared to patients with bilateral adrenal hyperplasia. After treatment, there was a significant decrease of PTH levels in both groups.

Conclusion Patients with PA frequently have primary or secondary hyperparathyroidism, which is alleviated by correction of PA by surgical or medical means. Patients affected by secondary hyperparathyroidism seem to have a more severe phenotype of PA and have a trend towards more cardiovascular co-morbidities.

Key words

primary aldosteronism - aldosterone - vitamin D - primary hyperparathyroidism - secondary hyperparathyroidism

• References

• 1 Rossi GP, Bernini G, Caliumi C. et al. A prospective study of the prevalence of primary aldosteronism in 1 125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300. DOI: S0735-1097(06)02332-1 [pii]. doi:10.1016/j.jacc.2006.07.059
• 2 Funder JW, Carey RM, Mantero F. et al. The management of primary aldosteronism: Case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016; 101: 1889-1916 doi:10.1210/jc.2015-4061
• 3 Catena C, Colussi G, Nadalini E. et al. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008; 168: 80-85 doi:10.1001/archinternmed.2007.33
• 4 Milliez P, Girerd X, Plouin PF. et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45: 1243-1248. doi:10.1016/j.jacc.2005.01.015
• 5 Reincke M, Fischer E, Gerum S. et al. Observational study mortality in treated primary aldosteronism: The German Connʼs Registry. Hypertension 2012; HYPERTENSIONAHA.112.197111 [pii]
• 6 Tomaschitz A, Ritz E, Pieske B. et al. Aldosterone and parathyroid hormone: A precarious couple for cardiovascular disease. Cardiovasc Res 2012; 94: 10-19. DOI: cvs092 [pii]. doi:10.1093/cvr/cvs092
• 7 Rossi GP. Hyperparathyroidism, arterial hypertension and aortic stiffness: A possible bidirectional link between the adrenal cortex and the parathyroid glands that causes vascular damage?. Hypertens Res 2011; 34: 286-288 doi:10.1038/hr.2010.251
• 8 Lenzini L, Prisco S, Vanderriele PE. et al. PTH Modulation by Aldosterone and Angiotensin II is blunted in hyperaldosteronism and rescued by adrenalectomy. J Clin Endocrinol Metab 2019;
• 9 Pilz S, Kienreich K, Drechsler C. et al. Hyperparathyroidism in patients with primary aldosteronism: Cross-sectional and interventional data from the GECOH study. J Clin Endocrinol Metab 2012; 97: E75-E79 DOI: jc.2011-2183 [pii] doi:10.1210/jc.2011-2183
• 10 Maniero C, Fassina A, Seccia TM. et al. Mild hyperparathyroidism: A novel surgically correctable feature of primary aldosteronism. J Hypertens 2012; 30: 390-395 doi:10.1097/HJH.0b013e32834f0451
• 11 Rossi E, Sani C, Perazzoli F. et al. Alterations of calcium metabolism and of parathyroid function in primary aldosteronism, and their reversal by spironolactone or by surgical removal of aldosterone-producing adenomas. Am J Hypertens 1995; 8: 884-893 DOI: 0895-7061(95)00182-O [pii] doi:10.1016/0895-7061(95)00182-O
• 12 Rossi GP, Ragazzo F, Seccia TM. et al. Hyperparathyroidism can be useful in the identification of primary aldosteronism due to aldosterone-producing adenoma. Hypertension 2012; 60: 431-436. DOI: HYPERTENSIONAHA.112.195891 [pii]. doi:10.1161/HYPERTENSIONAHA.112.195891
• 13 Petramala L, Savoriti C, Zinnamosca L. et al. Primary aldosteronism with concurrent primary hyperparathyroidism in a patient with arrhythmic disorders. Intern Med 2013; 52: 2071-2075
• 14 Concistre A, Petramala L, Zinnamosca L. et al. Primary aldosteronism with concurrent primary hyperparathyroidism: Clinical case load in a single centre. European Review for Medical and Pharmacological Sciences 2015; 19: 971-976
• 15 Maniero C, Fassina A, Guzzardo V. et al. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension 2011; 58: 341-346. DOI: HYPERTENSIONAHA.111.173948 [pii] doi:10.1161/HYPERTENSIONAHA.111.173948
• 16 Funder JW. ACE inhibitors and mineralocorticoid receptor blockade in patients with congestive heart failure. Curr Diab Rep 2005; 5: 36-40
• 17 Fischer E, Adolf C, Pallauf A. et al. Aldosterone excess impairs first phase insulin secretion in primary aldosteronism. J Clin Endocrinol Metab 2013; 98: 2513-2520 doi:10.1210/jc.2012-3934
• 18 Vonend O, Ockenfels N, Gao X. et al. Adrenal venous sampling: evaluation of the German Conn's registry. Hypertension 2011; 57: 990-995 doi:10.1161/HYPERTENSIONAHA.110.168484
• 19 Brown JM, Williams JS, Luther JM. et al. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone. Hypertension 2014; 63: 273-280 doi:10.1161/HYPERTENSIONAHA.113.01910
• 20 Hedback GM, Oden AS. Cardiovascular disease, hypertension and renal function in primary hyperparathyroidism. J Intern Med 2002; 251: 476-483. DOI: 984 [pii]
• 21 Feldstein CA, Akopian M, Pietrobelli D. et al. Long-term effects of parathyroidectomy on hypertension prevalence and circadian blood pressure profile in primary hyperparathyroidism. Clinical and Experimental Hypertension 2010; 32: 154-158 doi:10.3109/10641960903254471
• 22 Brunaud L, Germain A, Zarnegar R. et al. Serum aldosterone is correlated positively to parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism. Surgery 2009; 146: 1035-1041. DOI: S0039-6060(09)00693-X [pii] doi:10.1016/j.surg.2009.09.041
• 23 Bernini G, Moretti A, Lonzi S. et al. Renin-angiotensin-aldosterone system in primary hyperparathyroidism before and after surgery. Metabolism 1999; 48: 298-300
• 24 Mazzocchi G, Aragona F, Malendowicz LK. et al. PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells. Am J Physiol Endocrinol Metab 2001; 280: E209-E213
• 25 Isales CM, Barrett PQ, Brines M. et al. Parathyroid hormone modulates angiotensin II-induced aldosterone secretion from the adrenal glomerulosa cell. Endocrinology 1991; 129: 489-495
• 26 Yeh MW, Ituarte PH, Zhou HC. et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 2013; 98: 1122-1129. doi:10.1210/jc.2012-4022
• 27 Vaidya A, Curhan GC, Paik JM. et al. Hypertension, Antihypertensive Medications, and Risk of Incident Primary Hyperparathyroidism. J Clin Endocrinol Metab 2015; 100: 2396-2404. doi:10.1210/jc.2015-1619
• 28 Pilz S, Tomaschitz A, Drechsler C. et al. Parathyroid hormone level is associated with mortality and cardiovascular events in patients undergoing coronary angiography. Eur Heart J 2010; 31: 1591-1598 DOI: ehq109 [pii] doi:10.1093/eurheartj/ehq109
• 29 Tomaschitz A, Pilz S, Ritz E. et al. Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin Chim Acta 2010; 411: 1354-1360. DOI: S0009-8981(10)00370-0 [pii]. doi:10.1016/j.cca.2010.05.037
• 30 Brown J, de Boer IH, Robinson-Cohen C. et al. Aldosterone, parathyroid hormone, and the use of renin-angiotensin-aldosterone system inhibitors: The multi-ethnic study of atherosclerosis. J Clin Endocrinol Metab 2015; 100: 490-499. doi:10.1210/jc.2014-3949
• 31 Fischer E, Hannemann A, Rettig R. et al. A high aldosterone to renin ratio is associated with high serum parathyroid hormone concentrations in the general population. J Clin Endocrinol Metab 2014; 99: 965-971 doi:10.1210/jc.2013-3214
• 32 Tomaschitz A, Pilz S, Rus-Machan J. et al. Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular mortality risk. International Journal of Cardiology 2015; 184: 710-716 doi:10.1016/j.ijcard.2015.03.062
• 33 Jiang Y, Zhang C, Ye L. et al. Factors affecting parathyroid hormone levels in different types of primary aldosteronism. Clin Endocrinol (Oxf) 2015;
• 34 Ceccoli L, Ronconi V, Giovannini L. et al. Bone health and aldosterone excess. Osteoporosis international : A journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2013; 24: 2801-2807. doi:10.1007/s00198-013-2399-1
• 35 Zhang Y, Feng B. The association of serum parathyriod hormone and calcium levels with primary aldosteronism: A meta-analysis. Minerva Endocrinologica 2016
• 36 Riester A, Fischer E, Degenhart C. et al. Age below 40 or a recently proposed clinical prediction score cannot bypass adrenal venous sampling in primary aldosteronism. J Clin Endocrinol Metab 2014; 99: E1035-E1039 doi:10.1210/jc.2013-3789
• 37 Salcuni AS, Palmieri S, Carnevale V. et al. Bone involvement in aldosteronism. J Bone Miner Res 2012;
• 38 Kamalov G, Bhattacharya SK, Weber KT. Congestive heart failure: Where homeostasis begets dyshomeostasis. Journal of Cardiovascular Pharmacology 2010; 56: 320-328. doi:10.1097/FJC.0b013e3181ed064f
• 39 Rubin MR, Maurer MS, McMahon DJ. et al. Arterial stiffness in mild primary hyperparathyroidism. J Clin Endocrinol Metab 2005; 90: 3326-3330. DOI: jc.2004-1400 [pii]. doi:10.1210/jc.2004-1400
• 40 Vestergaard P, Mollerup CL, Frokjaer VG. et al. Cardiovascular events before and after surgery for primary hyperparathyroidism. World J Surg 2003; 27: 216-222. doi:10.1007/s00268-002-6541-z
• 41 Piovesan A, Molineri N, Casasso F. et al. Left ventricular hypertrophy in primary hyperparathyroidism. Effects of successful parathyroidectomy. Clin Endocrinol (Oxf) 1999; 50: 321-328
• 42 Rosa J, Raska Jr. I, Wichterle D. et al. Pulse wave velocity in primary hyperparathyroidism and effect of surgical therapy. Hypertens Res 2011; 34: 296-300. doi:10.1038/hr.2010.232
• 43 Concistre A, Grillo A, La Torre G. et al. Ambulatory blood pressure monitoring-derived short-term blood pressure variability in primary hyperparathyroidism. Endocrine 2018; 60: 129-137. doi:10.1007/s12020-017-1362-x
• 44 Rutledge MR, Farah V, Adeboye AA. et al. Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in aldosteronism. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy 2013; 27: 161-170. doi:10.1007/s10557-012-6378-0
• 45 Tomaschitz A, Verheyen N, Meinitzer A. et al. Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: Results from the EPATH randomized, placebo-controlled trial. J Hypertens 2016; 34: 1347-1356. 10.1097/HJH.0000000000000927