Relationship between COVID-19 and hypopituitarism: A two-sample Mendelian randomization study

COVID-19 has been identified as causing damage to the nervous and endocrine systems, with observed effects on hypopituitarism. However, the effects of COVID-19 on hypopituitarism are controversial. In this study, we conducted MR analysis to investigate the relationship between COVID-19 and hypopituitarism.

The MR study utilized publicly available summary statistics from an independent European cohort. Data were sourced from the EBI database for COVID-19(case N = 8316 and control N = 1549,095) and from the FinnGen database for hypopituitarism (case N = 910 and control N = 211,123). Independent genetic variants significantly associated with each exposure(P < 5 ×10-8) were considered as instrumental variables. The MR analysis and colocalisation analysis were underwent.

Four methods were employed: IVW, MR-Egger regression, weighted median and weighted mode with sensitivity analyses conducted. Finally, colocalisation analysis was also conducted.

MR study analyses were performed using the IVW fixation method, and we found a significant causal association between COVID-19 and hypopituitarism. IVW OR= 1.283, 95 %CI(1.017, 1.617), p = 0.035; MR-Egger OR= 1.355, 95 % CI(0.850, 2.160), p = 0.291; OR= 1.327, 95 %CI(1.017, 1.732), p = 0.037 in the weighted median approach and OR= 1.330, 95 % CI(0.993, 1.782), p = 0.128 in the weighted modal approach, with the results of the sensitivity analysis showing a stable and suggestive of a causality that COVID-19 increases the risk of developing hypopituitarism. The probability of colocalization of COVID-19 and hypopituitarism was PP.H4.abf= 9.55 %.

In this study, we have established a causal relationship between COVID-19 and the risk of hypopituitarism. This suggests that vigilance against the development of hypopituitarism is warranted following SARS-CoV-2 infection, and underscores the potential for long-term autonomic dysfunction in post-COVID-19 clinical management.