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[Primary Generalized Glucocorticoid Resistance: a case report].

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Primary glucocorticoid resistance, a condition of insensitivity to glucocorticoids (GC), typically involves NR3C1 gene defects. This case highlights an adolescent with GC resistance despite no NR3C1 mutations, expanding the known genetic landscape of this rare disorder.

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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.