Impact of systemic treatments for advanced thyroid cancer on the adrenal cortex.

BACKGROUND:Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI). AIM:To assess the entire adrenal function in patients on systemic treatments. METHODS:ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, 6 on vandetanib, and 5 on selpercatinib). ACTH stimulation test was performed in 26 cases. RESULTS:After a median treatment period of 7 months, we observed an increase in ACTH values in 80-100% of patients, and an impaired cortisol response to ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-Androstenedione and 17-OH progesterone levels were below the median of normal values (n.v.) in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of n.v. in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the n.v. in most cases, while renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI. CONCLUSIONS:Our data confirm that systemic treatments for advanced thyroid cancer can lead to an impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been firstly reported and should be considered in the more appropriate management of these fragile patients.