Absence of Testicular Adrenal Rest Tumors in Newborns, Infants, and Toddlers with Classical Congenital Adrenal Hyperplasia

Abstract

<b><i>Introduction:</i></b> Testicular adrenal rest tumors (TART) are a known consequence for males with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. TART are associated with potential infertility in adults. However, little is known about TART in very young males with CAH. <b><i>Objective:</i></b> We assessed the presence of TART in newborn, infant, and toddler males with classical CAH via scrotal ultrasound. <b><i>Methods:</i></b> Males with CAH had scrotal ultrasounds during the first 4 years of life, evaluating testes for morphology, blood flow, and presence of TART. Newborn screen 17-hydroxyprogesterone (17-OHP) and serum 17-OHP at the time of ultrasound were recorded. Bone ages were considered very advanced if ≥2 SD above chronological age. <b><i>Results:</i></b> Thirty-one ultrasounds in 16 males were performed. An initial ultrasound was obtained in four newborns at diagnosis (6.8 ± 2.1 days), six infants (2.2 ± 0.9 months), and six toddlers (2.4 ± 0.9 years). Eleven males had at least one repeat ultrasound. A large proportion (11/16) were in poor hormonal control with an elevated 17-OHP (325 ± 298 nmol/L). One infant was in very poor hormonal control (17-OHP 447 nmol/L) at initial ultrasound, and two toddlers had advanced bone ages (+3.2 and +4.5 SD) representing exposure to postnatal androgens. However, no TART were detected in any subjects. <b><i>Conclusions:</i></b> TART were not found by scrotal ultrasound in males up to 4 years of age with classical CAH despite settings with expected high ACTH drive. Further research into the occurrence of TART in CAH may elucidate factors that contribute to the detection and individual predisposition to TART.

Patient and Parent Perspectives on Testicular Adrenal Rest Tumors in Congenital Adrenal Hyperplasia

“…TARTs occur in up to 86% of males with classic CAH [3]. In children, the reported prevalence is 21–24% [7, 8] and though rare [9, 10], TARTs have been documented in boys as young as age 4 [11]. TARTs arise at the rete testis (stage 1) and are not palpable until stages 3 or 4 when fibrosis and lymphocytic infiltration are present [3].…”

Testicular adrenal rest tumors in children with congenital adrenal hyperplasia

“… 3 - 7 Although, TART was not detected in neonates or toddlers, a single study reported the presence of TART in young children with CAH as the youngest affected patient was 1.8 year old. 9 , 21 …”

“…[3][4][5][6][7] Although, TART was not detected in neonates or toddlers, a single study reported the presence of TART in young children with CAH as the youngest affected patient was 1.8 year old. 9,21 It was suggested that TART prevalence increases with age, as the nature of the disease would require time to develop. 22 In a 6-year follow-up study of patients with CAH aged 3-23 years, the prevalence of TARTs increased from 41% to 66% in those patients during the follow up, with 16 times greater chance of TART development due to poor control mostly at pubertal age.…”

A spontaneous pregnancy and live birth in a woman with primary infertility following the excision of an ovarian adrenal rest tumor: A rare case

“…The mechanism of ART formation still has not yet been fully elucidated. Kim et al [ 4 ] mentioned that these tumors may arise from ectopic migration of residual adrenal cortex cells into the developing gonads because of the connection between the adrenal glands and gonads during embryonic development. Claahsen-van der Grinten et al [ 5 ] suggested that defective primary sex cord regression, including all aberrant adrenal cells, during gonad development may be a causative factor in OART development.…”