The Clinical Value of Salivary Aldosterone in Diagnosis and Follow-Up of Primary Aldosteronism

Abstract

Primary aldosteronism (PA), the most common form of secondary hypertension, causes relevant morbidity. The value of salivary measurements of aldosterone in clinical routine in PA so far has not been assessed. First, we analyzed salivary and plasma aldosterone concentrations of 42 patients with PA and 37 hypertensive controls (HC) during a sodium infusion test prospectively. Second, morning salivary and plasma aldosterone concentrations as well as diurnal saliva aldosterone profiles were analyzed in 115 patients treated for PA (46 adrenalectomy, 56 spironolactone, 13 eplerenone). Salivary aldosterone was substantially elevated in PA patients compared to HC at baseline (106±119 vs. 40±21 ng/l, p=0.01), and after 4-h sodium infusion test (60±36 vs. 23±14, p=0.01). Positive correlation between salivary and plasma aldosterone levels was evident, with exception of concentrations in or below the lower normal range. Applying a salivary aldosterone cutoff of 51.2 ng/l, found by ROC curve analysis, rendered a sensitivity of 81% and a specificity of 73% for PA. The diurnal rhythm of aldosterone was preserved in untreated PA patients, but concentrations were higher in the context of PA, and normalized after surgery (118±57 vs. 31±18 ng/l, p<0.01). Taken together, salivary aldosterone measurements correlate with plasma levels, allowing simple and cost effective assessments of aldosterone secretion in an outpatient setting. Nevertheless, as this method alone cannot replace other plasma parameters, and as aldosterone profiling would not alter diagnostic or treatment strategies, salivary aldosterone measurements in routine practice are of limited clinical value.

Key words

aldosterone - rennin - Conn’s syndrome - hypertension - saliva - aldosterone producing adenoma

• References

• 1 Hannemann A, Bidlingmaier M, Friedrich N, Manolopoulou J, Spyroglou A, Volzke H, Beuschlein F, Seissler J, Rettig R, Felix SB, Biffar R, Doring A, Meisinger C, Peters A, Wichmann HE, Nauck M, Wallaschofski H, Reincke M. Screening for primary aldosteronism in hypertensive subjects: results from two German epidemiological studies. Eur J Endocrinol 2012; 167: 7-15
• 2 Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45: 1243-1248
• 3 Quinkler M, Born-Frontsberg E, Fourkiotis VG. Comorbidities in primary aldosteronism. Horm Metab Res 2010; 42: 429-434
• 4 Reincke M, Fischer E, Gerum S, Merkle K, Schulz S, Pallauf A, Quinkler M, Hanslik G, Lang K, Hahner S, Allolio B, Meisinger C, Holle R, Beuschlein F, Bidlingmaier M, Endres S. German Conn’s Registry-Else Kroner-Fresenius-Hyperaldosteronism R . Observational study mortality in treated primary aldosteronism: the German Conn’s registry. Hypertension 2012; 60: 618-624
• 5 Zennaro MC, Fernandes-Rosa F, Boulkroun S, Jeunemaitre X. Bilateral Idiopathic Adrenal Hyperplasia: Genetics and Beyond. Horm Metab Res 2015; 47: 947-952
• 6 Rossi GP, Dalla CA. Italian Society of H . Clinical management of primary aldosteronism: 2013 Practical Recommendations of the Italian Society of Hypertension (SIIA). High Blood Press Cardiovasc Prev 2014; 21: 71-75
• 7 Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young Jr. WF, Montori VM. Endocrine S. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 3266-3281
• 8 Riester A, Reincke M, Beuschlein F. Primary hyperaldosteronism: boundaries of diagnostics and therapy. Dtsch Med Wochenschr 2014; 139: 1982-1984
• 9 Quinkler M, Stewart PM. Treatment of primary aldosteronism. Best Pract Res Clin Endocrinol Metab 2010; 24: 923-932
• 10 Manolopoulou J, Gerum S, Mulatero P, Rossignol P, Plouin PF, Reincke M, Bidlingmaier M. Salivary aldosterone as a diagnostic aid in primary aldosteronism. Horm Metab Res 2010; 42: 400-405
• 11 Manolopoulou J, Mulatero P, Maser-Gluth C, Rossignol P, Spyroglou A, Vakrilova Y, Petersenn S, Zwermann O, Plouin PF, Reincke M, Bidlingmaier M. Saliva as a medium for aldosterone measurement in repeated sampling studies. Steroids 2009; 74: 853-858
• 12 Atherden SM, Corrie JE, Jones DB, Al-Dujaili EA, Edwards CR. Development and application of a direct radioimmunoassay for aldosterone in saliva. Steroids 1985; 46: 845-855
• 13 Lewis JG. Steroid analysis in saliva: an overview. Clin Biochem Rev 2006; 27: 139-146
• 14 Hofman LF. Human saliva as a diagnostic specimen. J Nutr 2001; 131: 1621S-1625S
• 15 Kem DC, Weinberger MH, Gomez-Sanchez C, Kramer NJ, Lerman R, Furuyama S, Nugent CA. Circadian rhythm of plasma aldosterone concentration in patients with primary aldosteronism. J Clin Invest 1973; 52: 2272-2277
• 16 Sonoyama T, Sone M, Tamura N, Honda K, Taura D, Kojima K, Fukuda Y, Kanamoto N, Miura M, Yasoda A, Arai H, Itoh H, Nakao K. Role of endogenous ACTH on circadian aldosterone rhythm in patients with primary aldosteronism. Endocr Connect 2014; 3: 173-179
• 17 Schirpenbach C, Seiler L, Maser-Gluth C, Beuschlein F, Reincke M, Bidlingmaier M. Automated chemiluminescence-immunoassay for aldosterone during dynamic testing: comparison to radioimmunoassays with and without extraction steps. Clin Chem 2006; 52: 1749-1755