Abstract Background: Artificial intelligence (AI) use by early-career paediatric endocrinologists has started without waiting for the training and governance structures to develop. Since early-career physicians and researchers of today hold no pre-AI performance baseline against which to appraise the AI outputs, career stage-specific concerns regarding rapid adoption of AI use in the field have emerged. The goal of this review was to examine AI use in paediatric endocrinology from the early-career perspective. Summary: A narrative, non-systematic literature review regarding the AI use in paediatric endocrinology across the four professional domains (curricular coverage, clinical practice, teaching, and research) was conducted in January 2026 and updated through July 2026. 57 relevant publications were identified, with level of evidence differing significantly between domains, and inversely with how freely the AI tools are used: from randomised-trials data regarding specific clinical applications like closed-loop insulin delivery and automated bone age assessment, to no published data regarding use of large language models in the research domain. Greatest benefit of automated bone age assessment in the early career stage was reported, while no published studies examining AI use by early-career paediatric endocrinologists were found. Key Messages: While being most exposed to unsupervised AI use, early-career physicians are also the least studied group. Having in mind the lack of pre-AI baseline in this population, findings of this review emphasize the potential career stage-dependent risks regarding the AI use, and the need for subspecialty-specific AI competency frameworks.
Abstract Background: 17-hydroxylase deficiency (17OHD) is a very rare form of congenital adrenal hyperplasia (CAH) caused by autosomal recessive mutations in the cytochrome P450 family (CYP17A1). Despite low cortisol, adrenal insufficiency does not typically manifest because elevated corticosterone, a weaker glucocorticoid (GC), exerts GC effects. Exogenous GC are the foundation of treatment but can be associated with significant side effects. Published literature regarding management strategies is limited. Case Presentations: We describe three female adolescents treated for 17OHD with different GC regimens. All patients presented at age 14 with delayed puberty, hypertension, and primary ovarian insufficiency. Patient 1 was initially treated with physiological hydrocortisone divided three times daily (10 mg/m2/d) and spironolactone 100 mg/d, separately and combined, which did not lower her blood pressure (BP). Eventually, a combination of physiological hydrocortisone once daily (8.8 mg/m2/d) and gradual titration to a higher spironolactone dose (100 mg bid) normalized her BP (115/75 mmHg) with no side effects. Patient 2 was treated with dexamethasone 0.25 mg daily for 10 years with poor follow-up and developed multiple complications related to supraphysiological GC use. She was transitioned and successfully treated with hydrocortisone 10 mg every morning and 5 mg every afternoon with a normal BP and potassium for over a year. Patient 3 was treated with cortisone acetate for 2.6 years and then with dexamethasone for about 10 months before discontinuation of GC and transition to spironolactone monotherapy. Her potassium and BP remained normal. Conclusion: In conclusion, 17OHD is a rare form of CAH, with about 500 published cases and limited established management guidance. Our cases highlight the importance of considering the pathophysiology of 17OHD when developing a management plan; a supraphysiological GC therapy may not be necessary to manage the hypertension and hypokalemia. Physiological hydrocortisone dosing lowers but does not normalize DOC production allowing DOC to exert GC effects. Physiological hydrocortisone and/or monotherapy with mineralocorticoid receptor antagonists both mitigate GC-related side effects, avoid adrenal suppression, and minimize risk for adrenal crisis in patients with 17OHD.
Abstract Introduction E3 ubiquitin protein ligase zinc and ring finger 3 (ZNRF3) negatively regulates Wnt/β-catenin signaling, which is essential for the development and maintenance of the adrenal gland, particularly the zona glomerulosa. Heterozygous ZNRF3 exon 2 deletions cause adrenal hypoplasia congenita (AHC). However, as only a few patients with ZNRF3-related AHC have been reported, the clinical spectrum remains unclear. Case Presentation A girl presented at age 27 days with severe salt-wasting. Endocrinological evaluation revealed elevated ACTH and renin levels. Abdominal ultrasonography failed to detect the adrenal glands. After treatment with hydrocortisone and fludrocortisone, she had no adrenal crises and normal growth and puberty. At age 15 years, hydrocortisone was discontinued, while fludrocortisone was continued. ACTH levels remained within clinically acceptable limits, whereas renin levels remained elevated. Whole-genome sequencing identified a ZNRF3 exon 2 deletion. Conclusion This is the first report of longitudinal endocrine findings in ZNRF3-related AHC, demonstrating predominant and persistent zona glomerulosa dysfunction with age-dependent improvement of zona fasciculata function. Our findings support the proposed role of the ZNRF3–Wnt/β-catenin signaling axis in adrenal development, expand the phenotypic spectrum of ZNRF3-related AHC, and suggest the value of genetic screening for ZNRF3 exon 2 deletions in patients with genetically unresolved mineralocorticoid deficiency.
Conventional thinking suggests that fasting free fatty acids are positively correlated with adiposity. However, there are adiposity differences by sex and ancestry. We evaluated the relationship between fasting free fatty acids and adiposity in in South Asian adolescents and young adults compared with White and African American peers. We measured fasting free fatty acids and total fat mass (Hologic DXA scan) among South Asian, White, and African American adolescents and young adults with BMI ≥ 80%ile (≥ 23kg/m2 if ≥ 18y) without diabetes. Ancestry differences in the fasting free fatty acid - fat mass association were tested using generalized linear models with interaction analysis between ancestry groups, sex, and fasting free fatty acids adjusted for age, pubertal stage, and height-squared. Adolescents and young adults [51 South Asian, mean age: 19.8y, 54 White: 18.9y, 49 African American: 18.8y, p=0.02] did not differ by sex, BMI, pubertal stage, or fat mass [mean: South Asian 31219g, African American 31964g, White 29733g, p=0.5]. In males, White adolescents and young adults had a positive relationship between fasting free fatty acids and fat mass (β=0.07%, p<0.001), but differed by ancestry: South Asian vs White, -0.08%, p<0.000; African American vs White, -0.12%, p<0.001 (See Figure). Among females, there were no significant differences. In our cohort, the fasting free fatty acid - fat mass relationship varied by sex and ancestry. Among males, fasting free fatty acids were positive correlated with fat mass only in the White group. Thus, a positive relationship between fasting free fatty acids and fat mass may be specific to White males.
