Long COVID and pituitary dysfunctions: a bidirectional relationship?

Long COVID is a novel emerging syndrome known to affect multiple health areas in patients previously infected by SARS-CoV-2 markedly impairing their quality of life. The pathophysiology of Long COVID is still largely poorly understood and multiple mechanisms were proposed to underlie its occurrence, including alterations in the hormonal hypothalamic-pituitary axes. Aim of this review is to present and discuss the potential negative implications of these hormonal dysfunctions in promoting and influencing the Long COVID syndrome. To date, the hypothalamic-pituitary-adrenal axis is the mostly investigated and several studies have reported a prolonged impairment leading to mild and subclinical forms of central adrenal insufficiency. Few data are also available regarding central hypogonadism, central hypothyroidism and growth hormone (GH) deficiency. A high prevalence of central hypogonadism in COVID-19 survivors several months after recovery was consistently reported in different cohorts. Conversely, very few data are available on the hypothalamic-pituitary-thyroid axis function that was mainly shown to be preserved in COVID-19 survivors. Finally, a potential impairment of the hypothalamic-GH axis in Long COVID has also been reported. These data altogether may suggest a novel possible pituitary-centred pathophysiological view of Long COVID syndrome which if confirmed by large clinical studies may have relevant implication for the diagnostic and therapeutic approach at least in a subset of patients with the syndrome.