Background: Rare cases of human glucocorticoid receptor (hGRalpha) (NR3C1) gene mutations have been described in the gemline or somatic state in Cushing's disease (CD).
Aim: We describe a pediatric patient with CD with clinical evidence of partial glucocorticoid resistance (GR) due to the relative absence of stigmata of Cushing's syndrome (CS).
Case description: A 14-year-old boy with slow growth and hypertension, but no other signs of CS was admitted for CD evaluation. Urinary free cortisol levels (UFC) were consistently 2-3-fold the upper normal range. Pituitary magnetic resonance imaging (MRI) revealed a 3x4 mm hypoenhancing lesion in the right side of the pituitary gland anteriorly (microadenoma). A graded dexamethasone suppression test indicated that the patient had partial GR. Histology confirmed an adrenocorticotrophin (ACTH)-producing pituitary adenoma. We hypothesized that a NR3C1 mutation was present. Sequencing of the entire coding region of the gene produced normal results in both peripheral and tumor DNA.
Conclusion: We present the case of a pediatric patient with an ACTH-producing tumor but little evidence of CS. No mutations in the coding sequence of NR3C1 were detected. We conclude that low level somatic mosaicism for NR3C1 mutations or a mutation in another molecule participating in hGRalpha-signaling may account for this case.