Adrenal steroids in female hypothyroid neonates: Unraveling an association between thyroid hormones & adrenal remodeling

J Clin Endocrinol Metab. 2019 Feb 20;jc.2018-02013. doi: 10.1210/jc.2018-02013. Online ahead of print.


Context: The adrenal gland undergoes significant remodeling during the neonatal period, an essential developmental process that still remains incompletely understood. With respect to control over the remodeling process and, specifically, the role of thyroid hormones (TH), no human studies have been published. The effect of both hypo- and hyper-thyroidism has only been evaluated in adults, focusing on the mature adrenal. Recently, Huang et al identified expression of the TH receptor β1 in the mouse adrenal X-zone and demonstrated that TH administration could alter the postnatal adrenal remodeling process.

Objective: To address whether TH influence adrenal steroid profiles and adrenal remodeling during the neonatal period.

Methods: We compared the adrenal steroid profile of a naturally occurring prototype, female neonates with severe congenital hypothyroidism (CH, n=22, upon diagnosis of CH), with that of euthyroid neonates (n=20).

Results: Significantly higher levels of adrenal steroids (17-OH-progesterone, DHEAS, Δ4- androstenedione and testosterone) were measured in neonates with severe CH compared to euthyroid neonates, returning within normal range after euthyroid state had been established on L-thyroxine replacement therapy whereas cortisol levels did not differ. TSH values in the CH group were positively, while FT4 levels were negatively correlated with circulating adrenal steroids.

Conclusions: The hormonal profile of female neonates with severe CH suggests a more active adrenal fetal zone than controls. These data indirectly associate TH with the adrenal remodeling and maturation process in humans. Based on our results we suggest that severe hypothyroidism decelerates the involution of the adrenal fetal zone that normally occurs postnatally.