Bilateral para-overian Adrenal Rest Tumor in a 15-year-old girl with adrenal failure due to the G200S NNT Mutation

Background: NNT gene mutations are rare cause of glucocorticoid and mineralocorticoid deficiency. Adrenal Rest Tumor (ART) in females is very rare (<20 cases world-wide) and was reported only in noncompliant patients with congenital adrenal hyperplasia having extremely elevated ACTH levels. This study characterizes the clinical characteristics, the pathophysiology and the molecular ontogeny of a unique ART in a female with adrenal failure due to NNT mutation.

Clinical presentation: A 15-year-old girl, with homozygous NNT-mutation reappeared to follow-up with severe virilization and elevated serum testosterone and ACTH levels. Pelvic MRI and Ultrasound demonstrated one sided para-ovarian round tumor. Laparoscopic exploration revealed bilateral para-ovarian masses; the testosterone level normalized within one day after removal of those masses.

Results: Histopathology demonstrated a pattern of adrenal rest tissue with strong intracellular positive staining for adrenal markers such as SF-1, calretinin, MART1, inhibin and ACTH. The staining for ovarian characteristic markers such as PAX 8 was negative. Studying mRNA extracted from the tissue condirmed a typical adrenocortical transcriptional pattern. cDNA of POMC was not detected. Methylome studies to further characterise the tissue are underway.

Conclusion: This study exemplifies severe virilization that resulted from a unique and rare type of ART. This study may indicate timely testosterone screening in noncompliant patients with adrenal failure due to NNT mutation and when increased they should probably be laparoscopically surveyed for ART even when not detected by imaging. How NNT mutation damages mineralo and glucocorticoid secreting cells while androgen secreting cells are rescued is a theme for further studies.