This systematic review and meta-analysis have been reported with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and has been prospectively registered in PROSPERO (CRD42025629905) (22).

Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched for this systematic literature review and meta-analysis from the inception of the databases through December 1, 2024. The search terms included those related to primary aldosteronism (e.g., hyperaldosteronism, aldosteronism, Conn syndrome) and thyroid diseases (e.g., thyroid function, hypothyroidism, hyperthyroidism, and thyroid cancer). The detailed search strategy is provided in the Supplementary Material . Literature meeting the inclusion criteria were exported to EndNote Desktop version X9, and duplicates were automatically removed. The studies were then screened by title and abstract, followed by full-text review according to the eligibility criteria. Two authors (WH, YW) independently participated in all stages of screening. Disagreements in the screening process were resolved through consensus discussions.

All studies published in English were included as long as they met the following basic eligibility criteria.

Basic eligibility criteria were met:

The following studies were excluded:

Two authors (WH and YW) completed a quality assessment of all included studies using the Newcastle-Ottawa Scale (NOS). The NOS assesses the quality of cohort and case-control studies according to three categories. They are (a) “Selection”, which includes four assessment items with a maximum score of four stars; (b) “Comparability”, which includes one assessment item with a maximum score of two stars; and finally, (c) “Outcome “, consisting of three assessment items with a maximum score of three stars (23). The disagreements were resolved in a consensus meeting.

Two reviewers, WH and YW, extracted data in a pre-designed Excel sheet that included the items: authors, year, country of study, mean age, gender distribution, and data used to calculate prevalence estimates such as the total number of people with PA in the sample and the number of people with thyroid diseases. In the meta-analysis, the prevalence of different thyroid disorders among PA patients and controls was also extracted.

The primary endpoint of this study was the prevalence of thyroid disease in patients with primary aldosteronism. Combined prevalence estimates and 95% confidence intervals (CIs) were calculated using a random-effects model with logit transformations. Random-effects models account for study heterogeneity and provide more conservative estimates of overall effect sizes. For all models, the Cochrane’s Q statistic and I² were calculated to assess heterogeneity. Heterogeneity was categorized as low (<40%), moderate (40-60%), high (70-90%), or substantial (>90%) according to I²values. Each thyroid disorder was analyzed in a separate subgroup, and pooled odds ratios (ORs) were calculated for each subgroup as well as for all subgroups combined. To assess the impact of individual studies on the overall effect, sensitivity analyses were performed by omitting one study at a time. For publication bias, funnel plot inspection and Egger and Begg regression tests were conducted. A p-value <0.05 was considered statistically significant. Statistical analyses were performed using Cochrane Review Manager v5.4 and Stata 18. The results of this meta-analysis were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

To assess the risk of false-positive or false-negative results in the meta-analysis, we conducted trial sequential analyses (TSAs) using TSA software (version 0.9.5.10 beta; Copenhagen Trial Unit, Clinical Intervention Research Center, Rigshospitalet, Copenhagen, Denmark). The required information size (RIS) was calculated with an alpha risk of 5%, a beta risk of 20%, and a two-sided border type. When the cumulative Z-curve enters the null zone or crosses the TSA boundaries, the intervention effect is considered to be sufficiently supported by evidence. If the Z-curve does not cross any boundaries and does not reach the required information size, the evidence is insufficient to draw any conclusions.

A total of 954 records were identified from database and electronic sources. After removing duplicates, 735 records were screened, and 410 studies were excluded based on title and abstract review. The remaining studies were assessed for eligibility according to predefined criteria. Ultimately, five studies were included in the meta-analysis. The study selection flowchart is shown in Figure 1 .

All included studies were assessed for risk of bias by the NOS scale as shown in Table 1 . The results showed that all studies had high quality and low risk of bias. Total score ranged from 7 to 9.

Five studies with a total of 1368 PA and 6774 controls were included (13, 24–27). Four studies were from Europe and one from Asia. All participants were adults, with a mean age between 50 and 55 years. In total, the studies showed that the female PA population was larger than that of women. A detailed description of the population characteristics in each study is presented in the Table 2 below.

A total of five studies were included to compare the combined prevalence of thyroid disorders. Patients with primary aldosteronism had different types of thyroid disease. We divided subgroups by disease and performed stratified analyses. The results of the study are as follows:

Figure 2A shows a forest plot of thyroid disease in patients with PA. The pooled prevalence of any thyroid disease was significantly higher in the PA group than in controls (OR: 3.68, 95% CI: 2.41-5.62, p < 0.00001). However, I² and Galbraith ( Figure 2B ) suggested some heterogeneity in findings, we therefore did further subgroup and sensitivity analyses. Subgroup analysis demonstrated that this overall difference was predominantly attributable to a significantly higher prevalence of thyroid nodules in PA patients (OR: 1.85, 95% CI: 1.23-2.80, p=0.003; Figure 3 ). In contrast, the prevalences of hyperthyroidism, hypothyroidism, thyroiditis, and thyroid cancer did not differ significantly between groups.

In order to assess the impact of individual studies on the overall combined effect size, sensitivity analyses were performed using an exclusion-by-exclusion approach, and the detailed results are shown in Table 3 and Figure 2C . Sensitivity analysis of subgroups was showed in Supplementary Figures 1–5 . Although the pooled ORs were altered in the subgroups of hypothyroidism, hyperthyroidism, thyroiditis, and thyroid cancer, there was no significant change in the ORs in the subgroups of overall thyroid disorders and thyroid nodular disorders, a finding that suggests a consistency of results across studies. Further studies are needed to provide robust evidence. Nonetheless, there does seem to be an association between primary aldosteronism and thyroid disease. This is evidenced by the robustness of the study results.

Funnel plot analysis of thyroid disease in patients with primary aldosteronism is shown in Supplementary Figure 8 , there was no publication bias between the included studies when analyzed for the overall thyroid disease in PA [p-values: Egger’s test:0.280 and Begg’s test:0.086]. Funnel plot analysis of Egger’s test and Begg’s test were showed in Supplementary Figures 6 and 7 .

The results of the TSA analysis are shown in Figure 2D . This analysis tests the stability of the statistical results by calculating the amount of required information size (RIS) and the bounds and null lines for hypothesis testing. The cumulative z-curve shown in the figure crosses the traditional bounds and the TSA bounds, and although the cumulative amount of information did not reach the desired value, no more tests were needed, proving that the results of this study are trustworthy.