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Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency results in severe cortisol and aldosterone deficiency, leading to persistent adrenal stimulation and excess production of ACTH and adrenal androgens. This review examines the clinical considerations and challenges of balancing under- and overtreatment with glucocorticoids in adolescent and adult male individuals with CAH. Adolescents face many unique challenges that can hinder adherence, hormonal control, and transition to independence. Thus, patient education is critical during adolescence, especially in poorly controlled postpubertal males who lack obvious symptoms and may not recognize the long-term consequences of nonadherence, such as reduced final height, reduced reproductive health, poor bone health, obesity, and hypertension. The risk of subfertility/infertility begins early, especially in males with poor hormonal control, who often have reduced sperm counts, small testes, and benign tumors called testicular adrenal rest tumors (TARTs). Even males with good hormonal control can experience subfertility/infertility due to TARTs. In addition, several factors such as hypogonadism and long-term glucocorticoid treatment can predispose males with CAH to poor bone health (eg, low bone mineral density, increased risk of osteoporosis/osteopenia and fractures) and metabolic syndrome (eg, obesity, insulin resistance, dyslipidemia, and hypertension). Regular monitoring is recommended, with glucocorticoid dose optimization and prophylactic treatment to maximize future fertility potential and protect long-term bone health. Early implementation of lifestyle interventions and medical treatment are needed to address cardiometabolic consequences. [ABSTRACT FROM AUTHOR]

Objective Classic androgens such as dehydroepiandrosterone, androstenedione, and testosterone are generally measured for diagnosis and treatment monitoring in children and adolescents with hyperandrogenism, as can occur in congenital adrenal hyperplasia, premature pubarche, or polycystic ovarian syndrome. However, adrenally-derived 11-oxygenated androgens also contribute to the androgen pool and should therefore be considered in clinical management. Nevertheless, paediatric reference intervals are lacking. Therefore, we developed a serum assay to establish reference intervals for four 11-oxygenated androgens in addition to four classic androgens. Design Reference interval study for serum 11-oxygenated androgens in children. Methods We developed and validated a sensitive liquid chromatography-tandem mass spectrometry assay and quantified eight serum androgens, including four 11-oxygenated androgens, in serum of 256 healthy children (aged 0-17 years old). An age-dependency for all androgens was observed, and therefore we divided the cohort based on age (prepubertal [ n = 133; 94 boys, 39 girls] and pubertal [ n = 123; 52 boys, 71 girls]) to compute reference intervals (2.5th-97.5th percentiles). Results In the prepubertal group, there was no significant sex-difference for any of the measured androgens. In the pubertal group, androstenedione, testosterone, and dihydrotestosterone showed a significant difference between boys and girls. In contrast, adrenal androgens dehydroepiandrosterone, 11-hydroxyandrostenedione, 11-ketoandrostenedione, 11-hydroxytestosterone, and 11-ketotestosterone did not. Conclusions We developed and validated an assay for 11-oxygenated androgens, in addition to four classic androgens and established reference intervals. This enables a comprehensive evaluation of serum androgen status in children with clinical symptoms of hyperandrogenism. [ABSTRACT FROM AUTHOR]

Importance: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development.Objective: This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. Design and participants: This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. Results: TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. Conclusions and relevance: A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life. [ABSTRACT FROM AUTHOR]