[Primary Generalized Glucocorticoid Resistance: a case report]

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Primary glucocorticoid resistance (PGR) is a rare disorder characterized by target organ insensitivity to glucocorticoids (GC).
• It stems from defects in the human glucocorticoid receptor (hGR), leading to compensatory hypothalamic-pituitary-adrenal (HPA) axis activation.
• Clinical manifestations vary, from asymptomatic cases to mineralocorticoid and/or androgen excess.

Observation:

• This report details an adolescent patient presenting with clinical signs of glucocorticoid resistance.
• Endocrinologic evaluations confirmed the patient's insensitivity to glucocorticoids.
• Genetic analysis did not reveal mutations in the NR3C1 gene, the commonly associated gene for PGR.

Findings:

• The patient exhibited features of glucocorticoid resistance.
• No mutations were identified in the NR3C1 gene, challenging the established genetic basis for PGR.
• This suggests potential novel genetic or epigenetic factors contributing to glucocorticoid resistance.

Implications:

• The findings broaden the understanding of the genetic heterogeneity of primary glucocorticoid resistance.
• This case underscores the need for comprehensive genetic screening beyond NR3C1 in suspected PGR cases.
• Further research is warranted to identify alternative genetic or molecular mechanisms underlying this rare endocrinopathy.