Navigating Congenital Adrenal Hyperplasia in Adolescence: Diagnostic, Therapeutic, and Psychosocial Challenges

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by defects in enzymes involved in adrenal steroid hormone biosynthesis. The most common cause of CAH is 21-hydroxylase deficiency (21OHD), which results from mutations in the CYP21A2 gene and accounts for approximately 90% of cases. 21OHD encompasses a spectrum of severity based on the residual enzymatic activity. The most severe form without any residual enzymatic activity is the classic salt-wasting form(s) of CAH usually diagnosed after birth or in the first months of life because they are associated with abnormal genitalia in female infants and severe salt wasting in both sexes. C-CAH may be life-threatening due to salt crises, hypoglycemia, and cortisol deficiency. The classic simple virilizing form with a residual enzymatic activity of about 1–2% also presents with androgen-excess symptoms in early life but without features of salt wasting.

NC-CAH is due to pathogenic variants in the CYP21A2 gene with 20–70% residual 21-hydroxylase activity and is considered one of the most common inherited endocrine diseases (estimated prevalence of 1 case per 100-1,000 individuals). NC-CAH has a less severe phenotype than the classic CAH and the symptom spectrum is age-related. In children younger than 10 years, premature adrenarche is the most common feature. Adolescent females may present with severe acne, hirsutism, androgenic alopecia, mild clitoromegaly, irregular menses, or primary amenorrhea. In adolescent males, the symptomatology is nuanced and the disease may be clinically difficult to identify. Some individuals in both sexes may remain undiagnosed or late diagnosed.

The treatment objectives in CAH differ from those in other adrenal insufficiency conditions. In addition to preventing adrenal crises through glucocorticoid and mineralocorticoid replacement, we also aim to suppress ACTH and androgen overproduction. This often requires supraphysiological doses of glucocorticoids, which poses long-term risks. Specific Treatment treatment goals in adolescence include: achieving normal growth and final height, maintaining maintaining a healthy weight, ensuring ensuring normal pubertal and psychosocial development, avoiding avoiding long-term complications, including cardiovascular and metabolic effects and gonadal dysfunction.

While undertreatment in girls will lead to clinical undesired symptoms of hirsutism, acne and menstrual disturbances male adolescents seem to have no serious problem when not regularly taken their medication. Boys are often less amenable to medication because they experience no symptoms and have also developed little sense of illness even in childhood.

This Research Topic aims to address the multifaceted challenges associated with the management of CAH during adolescence. Issues such as optimizing treatment regimens, improving adherence, and ensuring effective transition from pediatric to adult endocrine care are of central concern. We especially encourage submissions that provide new insights into the genetics, clinical manifestations, and long-term outcomes of CAH in this age group. We also seek to facilitate discussion on emerging therapeutic options, fertility preservation, and psychosocial support, aiming to integrate latest research findings with practical clinical approaches.

We invite original research articles, reviews, systematic reviews, mini reviews, brief research reports, case reports, and perspectives that cover a broad range of topics concerning CAH in adolescence.

Themes of interest include, but are not limited to:

- Genetic advances and genotype-phenotype correlations
- Challenges in diagnosis of non-classical forms
- Endocrine and metabolic management
- Patient adherence
- Transition of care
- Fertility issues
- Psychological and quality of life outcomes

Contributions that provide data on treatment innovations, multidisciplinary care models, and long-term follow-up are also highly encouraged. Submissions should present clear clinical implications or highlight gaps in current knowledge to foster improved patient outcomes in adolescent CAH management.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Curriculum, Instruction, and Pedagogy
• Data Report
• Editorial
• FAIR² Data
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Curriculum, Instruction, and Pedagogy
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Congenital adrenal hyperplasia, Premature adrenarche, Adolescent endocrinology, Precocious puberty, Adolescence, Virilization, Hyperandrogenism, Fertility, 21-hydroxylase deficiency, Classical CAH, Non-classical CAH

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.