Congenital Hypothyroidism and Hyperthyroidism Alters Adrenal Gene Expression, Development, and Function.

Area of Science:

• Endocrinology
• Adrenal Gland Physiology
• Thyroid Hormone Action

Background:

• The human adrenal cortex remodels throughout life, with rodent X-zone remodeling occurring postnatally via unknown mechanisms.
• The influence of thyroid hormone (TH) on human adrenal glands remains poorly understood.

Purpose of the Study:

• To investigate the impact of TH on adrenal pathophysiology using genetic mouse models and human patient data.
• To explore TH's role in adrenal gland development, steroidogenesis, and medullary function.

Main Methods:

• Created genetic mouse models simulating human hypothyroidism and hyperthyroidism.
• Analyzed serum thyrotropin (TSH) and steroid hormone levels in pediatric patients with congenital hypothyroidism and premature adrenarche (PA).

Main Results:

• TH receptor beta-mediated X-zone hypertrophy increased adrenal weights in hyperthyroid models; X-zone was poorly developed in hypothyroid models.
• Significant reciprocal changes in adrenal cortical function genes were observed in both models.
• Unexpectedly altered gene expression for catecholamine synthesis in adrenal glands of both models; positive correlation between TSH and adrenal steroids in pediatric patients.

Conclusions:

• Congenital hypothyroidism and hyperthyroidism functionally impact adrenal gland development and steroidogenic activity.
• TH influences not only the adrenal cortex but also the adrenal medulla.
• Findings highlight the interconnectedness of thyroid and adrenal function across the lifespan.