Chrousos Syndrome: From Molecular Pathogenesis to Therapeutic Management

The document is a systematic review of literature on Chrousos syndrome, a rare genetic disorder caused by mutations in the NR3C1 gene, leading to glucocorticoid resistance. The syndrome's clinical manifestations range from asymptomatic to severe and can include hyperandrogenism, hypertension, and features of mineralocorticoid and/or androgen excess. The review covers the molecular pathogenesis of the syndrome, including the functional characterization of two recently described NR3C1 mutations, and outlines the diagnostic and therapeutic approaches. It emphasizes the importance of a comprehensive evaluation, including 24-hour urinary free cortisol excretion and NR3C1 gene sequencing, for patients with unexplained symptoms. The paper also discusses the role of glucocorticoids in homeostasis, the glucocorticoid receptor, and the signal transduction pathway, highlighting the complexity of glucocorticoid responses.