Background: Testicular Adrenal Rest Tumors (TART) in patients with 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) are benign lesions causing testicular damage and infertility. It could be speculated that TART arise from cells that normally regress during the neonatal period but continue to exist in the adult CAH testis due to ACTH exposure and could become hyperplastic during prolonged periods of poor disease control.

Objective: This study aims to examine the relationship between early diagnosis and consequent start of proper treatment (< 1 month vs > 1 month-1 year vs > 1 year) ánd the development of TART as well as the relationship between biochemical disease control during infancy and early childhood and the development of TART.

Methods: In this retrospective open cohort study, data was collected from the I-CAH registry; an international database of pseudonymized information on CAH patients. The study  included 149 male (XY) patients from 19 centers with 21OHD or 11OHD in which at least one testicular ultrasound (US) was performed.

Results: TART was detected by US in 38% male patients. Prevalence varied enormously between centers. Slightly delayed diagnosis and start of treatment (> 1 month-1 year vs < 1 month), but not later-onset (>1 year), were associated with a higher probability of TART development when normalized for differences in age at last US (Odds ratio of 6.4; p<0.001). Neonatal screening resulted in earlier diagnosis and was associated with a lower probability of TART. After initiation of treatment, biochemical disease control, bone age advancement, or height SDS (both covering longer-term disease control) during the first 4 years of life did not explain the probability of TART development.

Conclusion: Slightly delayed diagnosis was associated with a higher prevalence of TART. Analyses are ongoing and will narrate if the association between early diagnosis and TART development may be explained by neonatal ACTH exposure, or whether this association reflects differences in quality of care in general.