To the Editor,
We thank Dr Pankaj Singhania and Dr Rana Bhattacharjee for their comments (1) on our recently published study (2). In the study we identified patients with primary aldosteronism (PA) by searching for the diagnostic codes for the disease in the national Swedish Patient Registry and not by biochemical screening. Indeed, we agree that screening for PA in all patients with hypertension is probably not cost-effective and should instead be performed in specific subgroups of patients in accordance with the clinical guidelines from the Endocrine Society.
We also agree that the prevalence of hypokalemia in our cohort was surprisingly high (79%). This probably illustrates that most patients diagnosed with PA during the study period had a severe phenotype, and patients with milder disease remain underdiagnosed. This is unfortunate since patients with a severe phenotype are more likely to already have developed secondary cardiovascular disease and/or impaired renal function, that can be prevented by earlier detection and adequate treatment [3].
Between 2007 and 2016, PA was confirmed with a saline infusion test in 87% of our cohort. This is in line with the clinical practice guidelines from the Endocrine Society published in 2008 that recommended a confirmatory test in all patients with a positive aldosterone-renin ratio. However, in the updated version of the guidelines, published in 2016, it was suggested that confirmatory test may not be necessary in patients with plasma aldosterone >550 pmol/L, low plasma renin, and spontaneous hypokalemia. Recently, this recommendation received further support in a study including more than 500 patients with PA, finding that one-third of the patients could bypass a confirmatory test without jeopardizing the diagnostic accuracy (4). Thus, in the future, a substantial number of patients with hypertension and a pathological aldosterone-renin ratio should be able to proceed directly to a subtype classification without a confirmatory test.
A pooled sensitivity and specificity of adrenal imaging for identifying unilateral PA in a recent meta-analysis, including 4669 subjects from 25 studies, was 68% and 57%, respectively (5). In fact, by using adrenal imaging for deciding treatment, 15% of patients would inappropriately be considered to be candidates for adrenalectomy, 19% would not be adequately offered surgical treatment, and in 4% adrenalectomy on the wrong side would be performed (6). Therefore, in our opinion, adrenal vein sampling is necessary to determine laterality in patients with PA, even in patients aged 40 years or younger (7, 8).
Glossary
Abbreviation
- PA
primary aldosteronism
References
- 1. Singhania P, Bhattacharjee R. Letter to the Editor From Singhania et al.: “Increasing Incidence of Primary Aldosteronism in Western Sweden During 3 Decades – Yet an Underdiagnosed Disorder”. J Clin Endocrinol Metab. Published online before print November 3, 2021;dgab804. doi: 10.1210/clinem/dgab804 [DOI] [PubMed] [Google Scholar]
- 2. Gkaniatsa E, Ekerstad E, Gavric M, et al. Increasing incidence of primary aldosteronism in western Sweden during 3 decades - yet an underdiagnosed disorder. J Clin Endocrinol Metab. 2021;106(9):e3603-e3610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Monticone S, D’Ascenzo F, Moretti C, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6(1):41-50. [DOI] [PubMed] [Google Scholar]
- 4. Wang K, Hu J, Yang J, et al. Development and validation of criteria for sparing confirmatory tests in diagnosing primary aldosteronism. J Clin Endocrinol Metab. 2020;105(7):e2449-e2456. [DOI] [PubMed] [Google Scholar]
- 5. Zhou Y, Wang D, Jiang L, et al. Diagnostic accuracy of adrenal imaging for subtype diagnosis in primary aldosteronism: systematic review and meta-analysis. BMJ Open. 2020;10(12):e038489. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Kempers MJ, Lenders JWM, van Outheusden L, et al. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med. 2009;151(5):329-337. [DOI] [PubMed] [Google Scholar]
- 7. Gkaniatsa E, Sakinis A, Palmer M, et al. Adrenal venous sampling in young patients with primary aldosteronism. extravagance or irreplaceable? J Clin Endocrinol Metab. 2021;106(5): e2087-e2095. [DOI] [PubMed] [Google Scholar]
- 8. Riester A, Fischer E, Digenhart E, 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(6):E1035-E1039. [DOI] [PubMed] [Google Scholar]
