PA is Under-Diagnosed
Less Than 2.5% of Those Who Have Resistant Hypertension Are Ever Tested for Primary Aldosteronism
With regard to primary aldosteronism, belated diagnosis — if any — is the norm throughout the world:
- A survey of 500 general practitioners in Italy and Germany showed that case detection was performed in only 7 to 8% of 3,135 patients with hypertension.
- In a retrospective cohort study of 4,660 patients with resistant hypertension in California, the screening rate for primary aldosteronism was 2.1%.
- An Australian study found that in a group of 87 hypertensives, 69.2% had indications for primary aldosteronism, but only 3.2% were actually screened. At the time of referral to the country’s national health service, 61% of the patients had had hypertension for over 10 years, and 42% of the patients had developed end-organ damage.
Primary Aldosteronism is Not Rare
Until recently, it was estimated that up to 10% of hypertensives may have primary aldosteronism. Since nearly a third of the population has hypertension, the prevalence of the disease would’ve been around 3.3%, with 10.7 million people affected in the US alone (the equivalent of the population of the states of Wyoming, Montana, Idaho, North and South Dakota, Nebraska, and Utah combined), and 250 million worldwide (the equivalent of the population of the UK, France, Italy, and Spain combined).
US Population Equivalent
under 3.3% Prevalence
Worldwide Population Equivalent
under 3.3% Prevalence
In 2020, a groundbreaking study – The Unrecognized Prevalence of Primary Aldosteronism – showed that excess aldosterone is an even more significant issue than was understood earlier. Biochemically overt primary aldosteronism was found in 11.3% of adults without hypertension. This finding not only posits a syndrome ranging from mild to very severe, it reveals a prevalence so high that the disease should be considered a major public health issue. If data indicates such high prevalence, how can a near-absence of diagnosis be explained?
Why Primary Aldosteronism is Under-Diagnosed
Primary aldosteronism is mistakenly considered rare. The definition of “rare disease” varies across countries. In the US, a disease is considered rare when it affects less than 200,000 people. In Europe, a condition is defined as rare when fewer than 2,000 individuals are affected. In all evidence, primary aldosteronism does not meet the criteria of these definitions. The disease is “believed” to be rare while, in fact, it is widespread.
Inadequate physician training. The common misbelief that primary aldosteronism is rare is embedded in medical education. It particularly affects primary care and internal medicine physicians who are not cautioned that primary aldosteronism is widespread, and must be promptly and adequately diagnosed.
Lack of research. Understanding of excess aldosterone remains fragmented, and its measurement threshold (12.0 g per 24 hours) arbitrary. While a cut-off value is needed to enable case detection, this value is currently so high that even systematic screening would miss a significant number of patients.
Lack of standardization. Fragmented understanding of the disease equally affects diagnostic protocols. Among others:
- While Aldosterone Renin Ratios are widely available, assays vary across laboratories, thereby rendering their accuracy and reliability questionable.
- The modalities of confirmatory testing range from the ingestion of salt tablets at home to a saline infusion done under medical supervision.
- Some medical centers use ACTH stimulation to determine the disease subtype, while others do not.
Testing cost and complexity. Workup is not complete without adrenal venous sampling, a procedure few medical centers can successfully offer to their patients since it can only be performed by experienced interventional radiologists. Not only is the procedure costly, its low success rate outside of expert centers leads to repeat testing, and in extreme cases, erroneous surgical recommendations.
- Jenifer M. Brown, Mohammed Siddiqui, David A. Calhoun, Robert M. Carey, Paul N. Hopkins, Gordon H. Williams, Anand Vaidya. The Unrecognized Prevalence of Primary Aldosteronism: A Cross-Sectional Study, Annals of Internal Medicine, 26 Mar 2020. DOI: 10.7326/M20-0065
- James W. Funder, Primary Aldosteronism: At the Tipping Point, Annals of Internal Medicine, 26 Mar 2020. DOI: 10.7326/M20-1758
- Reincke M, Beuschlein F, Williams TA. Progress in Primary Aldosteronism 2019: New Players on the Block?. Horm Metab Res. 2020;52(6):345-346. DOI: 10.1055/a-1156-9926
- Silvi Monticone,Jacopo Burrello, Davide Tizzani, Chiara Bertello, Andrea Violo, Fabricio Buffolo, Luisa Gabetti, Giulio Mengozzi, Tracy A. Williams, Franco Rabbia, Franco Veglio, Paolo Mulatero, Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice, Journal of the American College of Cardiology, Volume 69, Issue 14, 11 April 2017, Pages 1811-1820, DOI: 10.1016/j.jacc.2017.01.052
- Yin Yu Lim, Jimmy Shen, Peter J Fuller, Jun Yang, Current pattern of primary aldosteronism diagnosis: Delayed and complicated, Australian Journal of General Practice, Volume 47, Issue 10, October 2018, DOI: 10.31128/AJGP-05-18-4587
- Hannemann A, Wallaschofski H. Prevalence of primary aldosteronism in patient’s cohorts and in population-based studies – A review of the current literature. Horm Metab Res 2012;44(3):157–62. DOI: 10.1055/s-0031-1295438
- Diagnostic rate of primary aldosteronism in Emilia‐Romagna, Northern Italy, during 16 years (2000–2015). J Hypertens 2017; 35: 1691–7, DOI: 10.1097/HJH.0000000000001384 , , , .