A global real-world study assessing total time to adrenalectomy in primary aldosteronism

Abstract

Background: Primary aldosteronism (PA) is a common treatable cause of hypertension. When caused by unilateral adrenal disease, it is potentially curable by adrenalectomy. However, specialized tests and other factors may delay definitive treatment. We assessed the time to adrenalectomy (TTA) for patients worldwide.

Methods: We conducted an international, multicentre retrospective study involving 39 centres from 15 countries to determine the total time taken from the first presentation to adrenalectomy and the intervals between each stage (screening, confirmatory, subtyping, and adrenalectomy). We included patients with PA who underwent adrenalectomy from January 1, 2018, to October 30, 2022. Post-adrenalectomy outcomes were evaluated using the Primary Aldosteronism Surgery Outcome criteria. We performed multivariable quantile and linear regression to identify characteristics associated with longer TTA.

Results: We included 861 patients, mean age 49.3 ± 11.1 years, and 44.5% were women. Overall median TTA was 13.5 months, IQR: 6.6-24.5. Median intervals were 0.1 months (screening), 1.0 months (confirmatory), 4.1 months (subtyping), and 4.3 months (adrenalectomy). On multivariable analysis, median TTA was increased by 5.4 months for each additional adrenal vein sampling (AVS) procedure. Other factors associated with longer TTA included adrenalectomy post-COVID-19, younger age, and additional screening tests. Compared with countries with routine AVS, those without AVS had a shorter TTA (6.1 vs 15.1 months, P < .001), but greater likelihood of absent/partial biochemical success post-adrenalectomy (27.4% vs 12.4%, P < .001).

Conclusion: Primary aldosteronism management is time-consuming worldwide, especially for subtyping tests and adrenalectomy. While omitting AVS reduces overall time, patients are less likely to achieve biochemical cure post-adrenalectomy.

Keywords: adrenal surgery; adrenal vein sampling; diagnostic delay; endocrine hypertension; functional imaging; global health; primary hyperaldosteronism.

Graphical Abstract

Figure 1.

Box plots of TTA, by country of centre where adrenalectomy was performed. Median TTA in months is shown. TTA data more than 1.5 times the interquartile range from the 75th percentile is not shown. “AVS yes” includes countries that routinely perform AVS, while “AVS no” includes countries that do not routinely perform AVS. %”AVS, adrenal vein sampling.

Figure 2.

Horizontal stacked bar charts of median TTA intervals, by country of centre where adrenalectomy was performed. (A) Absolute median no. of months. (B) Relative percentage of the median TTA. The sum of the 4 intervals for each country was not equivalent to the median total TTA as different intervals had different participants with missing data and because the sum of medians of intervals does not equal the total median. TTA, time to adrenalectomy.

Figure 3.

Restricted cubic spline plots of predicted natural log-transformed TTA (line) and 95% CI (area) against the countries’ CHE per capita, by whether country routinely performed AVS. The predicted natural log-transformed TTA values were obtained by fitting a multivariable linear regression. The relationship between natural log-transformed TTA with the countries’ CHE per capita was modelled using restricted cubic splines with 3 knots at the 10th, 50th, and 90th percentiles. We used a linear term only for mean CHE per capita in the “no routine AVS” subgroup as there were only 4 distinct mean CHE per capita values. When plotting splines, all covariates were held constant at their mean or reference level, except the variable of interest. The 95% CIs of predicted natural log-transformed TTA were calculated using the Wald method based on the standard errors of the predictions. AVS, adrenal vein sampling; CHE, current health expenditure; PPP, purchasing power parity; TTA, time to adrenalectomy.