AA May Increase Risk of Hypothyroidism, AG Needs Further Investigation

Physician diagnoses hair loss, alopecia | Image Credit: buravleva_stock - stock.adobe.com

Patients with alopecia areata (AA) and androgenetic alopecia (AG) expressed positive casual effects of hypothyroidism, which had strong correlations to an increase in the risk of AA, but additional evidence is necessary to understand relationships between non-scarring alopecia and hypothyroidism.

In a Mendelian randomization analysis published in Frontiers in Endocrinology, patients with non-scarring AA and AG were investigated in associations with hypothyroidism, a common thyroid dysfunction defined as elevated serum thyroid-stimulating hormone levels and a reduction in thyroxine levels. Statistics were from genome-wide association studies (GWASs).

The study design utilizes genetic variants as instrumental variables (IVs) to represent potential risk factors. To maintain a reliable estimation of casual outcomes, single nucleotide polymorphisms (SNPs) applied IVs into the analysis and required them to meet relevance, independence, and exclusion restriction.

A total of 4 methods were used in the bidirectional 2-sample Mendelian randomization study. These included MR-Egger, weighted median (WM), inverse variance weighted (IVW), and robust adjusted profile scores (RAPS). The predominant approach was mainly IVW.

Results for the casual effect of non-scarring alopecia on hypothyroidism were observed, recorded, and analyzed. There were 8 SNPs for AA and 23 SNPs for AGA as IVs. Based on the IVW results, there is weak evidence for the potential casual effect of AA on the risk of hypothyroidism, including borderline statistical significance (OR, 1.0017; 95% CI, 1.004-1.0029; P = .0101). The IVW results were then confirmed using the RAPS method (OR 1.0017; 95% CI 1.0003-1.0031; P = .0167).

Similarly, the MR-Egger and WM estimations were consistent with IVW but without statistical significance. Casual associations of AGA failed to show links to hypothyroidism in RAPS, WM, and MR-Egger methods. No evidence of heterogeneity was revealed through the examination of funnel plots from the researchers that used the Cochran Q test conducted on IVW and MR-Egger. There were also no identifiable SNPs revealed in the leave-one-out analysis.

Casual effects of hypothyroidism on non-scarring alopecia were analyzed among 95 and 112 independent SNPs as IVs for AA and AG, respectively. All SNPs had a ratio of variances greater than 10 and were deemed strong IVs. Both the IVW (OR 45.6839; 95% CI 1.8446-1131.4271; P = .0196) and RAPS (OR 58.8579; 95% CI 2.3497-1474.344; P = .0131) methods displayed positive outcomes of hypothyroidism on AA. Despite no significance, the MR-Egger and WM methods estimated similar directions as the IVW method.

There were no observations of directional pleiotropy, horizontal pleiotropy, or heterogeneity. Ultimately, casual effect of hypothyroidism on AGA was not implicated directly.

Since AA is an autoimmune disease, patients have a higher risk of thyroid issues, especially hypothyroidism. Both AA and hypothyroidism share common pathogenesis, genetic backgrounds, and inflammatory processes. It is also significant to note both conditions have psychiatric comorbidities as a result to their condition.

Limitations in the study comprised of constrained abilities to analyze the effects of other variables like age, race, and sex. Additionally, data for AA and AG was from a relatively small sample size from Finland’s electronic health records. In turn, the level of accuracy in the study may be skewed.

Through management of hypothyroidism, patients could reduce their chance of developing hair loss symptoms. However, the study suggests the integration of thyroid function tests into clinical assessments of patients with alopecia to achieve further clarity on the relationships between the autoimmune conditions.

"Meanwhile, physicians should to be aware that patients with hypothyroidism are at an increased risk of developing AA and should be vigilant in recognizing it," the authors concluded. "Optimal management of hypothyroidism could potentially reduce the frequency and severity of AA. Similarly, appropriate treatment of AA may decrease the occurrence of hypothyroidism."

Reference

Yang J, Zhu Z, Zhang C, Guo Y, Wang G, Fu M. Association between non-scarring alopecia and hypothyroidism: a bidirectional two-sample Mendelian randomization study. Front. Endocrinol. 2024;15:1-8. doi:10.3389/fendo.2024.1356832