先天性副腎皮質酵素欠損症

UNLABELLED: Serum sclerostin levels as a negative regulator of bone formation in children with congenital adrenal hyperplasia (CAH) have not been evaluated to date. The study aimed to investigate serum sclerostin and osteoprotegerin levels in children with CAH. Thirty-one patients with CAH (mean age 11.6 ± 3.7 years) taking glucocorticoids for at least 5 years, and age- and gender-matched controls were included in this cross-sectional study. Serum levels of sclerostin, osteoprotegerin, and standard bone markers were assessed. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. The factors influencing serum sclerostin and osteoprotegerin levels were identified using generalized linear modeling. In healthy controls, being pubertal was associated with lower serum sclerostin levels, whereas pubertal patients did not demonstrate the expected decline in sclerostin levels. Osteoprotegerin levels were higher in patients than in controls (p < 0.001). Serum 17-hydroxy progesterone exerted a significant negative effect on osteoprotegerin and a positive effect on sclerostin. Cumulative glucocorticoid dose, vitamin D, pubertal status, and sex had no significant effect on sclerostin or osteoprotegerin levels in patients. The BMD Z-scores exceeded - 1 in 80% of both patient and controls. CONCLUSIONS: The present study is the first to investigate the role of sclerostin in bone metabolism in patients with CAH, revealing sclerostin- and osteoprotegerin-mediated alterations in bone metabolism in this population. These alterations, along with their associations with serum 17-hydroxy progesterone levels, may be related to disease control status. Furthermore, the absence of the expected pubertal decline in sclerostin levels may adversely affect peak bone mass acquisition during growth. WHAT IS KNOWN: • Promoting bone mass accumulation during puberty is important for lifelong skeletal health. The long-term effect of glucocorticoid treatment on bone health in CAH patients is still unclear. WHAT IS NEW: • The present study provides evidence for sclerostin- and osteoprotegerin-mediated alterations in bone metabolism in children with CAH, potentially influenced by 17-OHP, and these findings may inform future research in this field.

UNLABELLED: Congenital adrenal hyperplasia (CAH) is a chronic endocrine disorder requiring lifelong management that may significantly impact health-related quality of life (HRQoL) in pediatric patients. Despite growing recognition of psychosocial outcomes in CAH, data from diverse populations remain limited. This cross-sectional study evaluated HRQoL in 40 children and adolescents with CAH (aged 2-18 years) followed at our pediatric endocrinology clinic, compared with 82 healthy controls. The Pediatric Quality of Life Inventory (PedsQL) was administered to assess physical, emotional, social, and school functioning domains. Clinical data including 17-hydroxyprogesterone (17-OHP), adrenocorticotropic hormone (ACTH), androstenedione levels, bone age, treatment regimens, and surgical history were collected. Statistical analyses included Mann-Whitney U test, chi-square test, and Spearman correlation. The mean age of patients with CAH was 11.85 ± 4.3 years. Based on child self-reports, total HRQoL scores were significantly lower in the CAH group compared with controls (81.69 ± 11.6 vs. 87.95 ± 6.0, p = 0.007). Emotional functioning (p = 0.001), social functioning (p = 0.039), school functioning (p = 0.048), and psychosocial health scores (p = 0.002) were also significantly lower in patients, whereas physical functioning scores were comparable between groups (p = 0.117). Parent proxy-reports similarly demonstrated significantly lower total HRQoL (p = 0.001), social functioning (p < 0.001), school functioning (p = 0.010), and psychosocial health scores (p = 0.001) in the CAH group. No significant differences were observed between child and parent assessments. Disease duration showed positive correlations with child-reported physical functioning (r = 0.402, p = 0.012), emotional functioning (r = 0.595, p < 0.001), psychosocial health (r = 0.394, p = 0.014), and total HRQoL scores (r = 0.393, p = 0.015). No consistent associations were identified between HRQoL scores and glucocorticoid dose, BMI SDS, height SDS, biochemical control, or history of surgery. CONCLUSIONS: Children and adolescents with CAH experience substantial impairments in HRQoL across all functional domains, particularly in psychosocial functioning.These findings should be interpreted with caution given the relatively small sample size of this study. Nevertheless, they suggest.Nevertheless, they suggest the need for comprehensive, multidisciplinary care approaches that address not only biochemical control but also psychological and social well-being in pediatric CAH management. WHAT IS KNOWN: • Congenital adrenal hyperplasia requires lifelong glucocorticoid therapy. Its potential to impair health-related quality of life in affected children is increasingly recognized. WHAT IS NEW: • Children and adolescents with CAH had significantly lower HRQoL than healthy controls on both self- and parent proxy-reports, with impairment concentrated in the psychosocial (emotional, social, and school) domains rather than physical functioning. • HRQoL scores were unrelated to glucocorticoid dose, biochemical control, anthropometry, or surgical history.

OBJECTIVE: Congenital endocrine salt-wasting syndromes unrelated to 21-hydroxylase deficiency are rare disorders with overlapping clinical and biochemical features at presentation. This study described the spectrum, early clinical course, and 36-month outcomes of these conditions in the era of newborn screening, and assessed whether severity at presentation was associated with later treatment requirements and growth. METHODS: Retrospective single-center cohort study including infants diagnosed between 1989 and 2023 with endocrine salt-wasting syndromes unrelated to 21-hydroxylase deficiency. Clinical presentation, biochemical findings, treatment requirements, genetic data, and longitudinal growth outcomes up to 36 months were analysed. RESULTS: Twenty patients were included: eight with aldosterone synthase deficiency, six with renal pseudohypoaldosteronism type 1, four with systemic pseudohypoaldosteronism type 1, and two with congenital adrenal hypoplasia. Systemic pseudohypoaldosteronism type 1 presented earliest and with the most severe biochemical abnormalities, requiring higher sodium supplementation at onset. Aldosterone synthase deficiency and renal pseudohypoaldosteronism type 1 presented later, with less severe, overlapping biochemical profiles. Differences in early management across etiologies were mainly limited to sodium supplementation, whereas time to electrolyte stabilization and mineralocorticoid initiation did not differ significantly. In exploratory analyses, severity at presentation was not associated with later treatment requirements or growth outcomes, whereas growth was largely preserved, with greater auxological vulnerability in systemic pseudohypoaldosteronism type 1. CONCLUSIONS: Congenital endocrine salt-wasting syndromes unrelated to 21-hydroxylase deficiency show substantial overlap at onset, whereas disease-specific features become more recognizable during follow-up. Growth outcomes were generally preserved with appropriate management and did not appear to be influenced by clinical severity at presentation.

17α-hydroxylase deficiency (17-OHD) is a rare autosomal recessive disorder caused by CYP17A1 mutations, and patients with a 46,XY karyotype typically lack a uterus. Here we report a 46,XY 17-OHD case presenting with a hypoplastic uterus and a history of left adrenalectomy, and provide the first in vitro functional characterization of the CYP17A1 c.985_987delTACinsAA mutation. The patient underwent clinical, hormonal, imaging, and genetic evaluations. Wild-type and mutant CYP17A1 were overexpressed in HEK293T cells, and protein expression and 17α-hydroxylase activity were assessed by Western blot and 17-OHP ELISA, respectively. The 46,XY patient had a hypoplastic uterus (35 × 14 × 26 mm) and vaginal structure with no visible gonads on imaging, but serum AMH was 10.71 ng/mL, indicating functional testicular tissue. Genetic testing revealed a homozygous CYP17A1 frameshift mutation (c.985_987delTACinsAA, p.Tyr329fsTer90) and a heterozygous POR variant of no diagnostic significance. Previous in silico structural modeling reports predicted that this mutation would cause protein truncation, but direct in vitro evidence has been lacking. In vitro, the mutant protein was truncated (∼45 kDa vs. 57 kDa for wild-type) and showed complete loss of 17α-hydroxylase activity (17-OHP levels comparable to empty vector control, P < 0.01 for wild-type vs. mutant). This study provides the first in vitro functional evidence that c.985_987delTACinsAA causes protein truncation and complete loss of 17α-hydroxylase activity. The presence of a hypoplastic uterus in this 46,XY patient suggests incomplete Müllerian regression, and for 17-OHD patients with a history of unilateral adrenalectomy, glucocorticoid replacement should be carefully titrated.

Clitoromegaly secondary to congenital adrenal hyperplasia (CAH) poses a significant surgical challenge, requiring preservation of neurovascular integrity alongside satisfactory aesthetic restoration. The optimal timing and operative approach for feminizing genitoplasty remain subjects of ongoing debate. We report a six-year-old girl with classic CAH (Prader stage 3) who underwent nerve-sparing clitoroplasty via a ventral approach. The technique prioritised preservation of the urethral plate, dorsal neurovascular bundle, and clitoral glans. At the six-month follow-up, both the patient and family expressed high satisfaction with cosmetic and functional outcomes. Ventral nerve-sparing clitoroplasty offers reliable aesthetic results with preservation of neurovascular structures. Magnification loupes, meticulous dissection, and intraoperative papaverine irrigation minimise the risk of vasospasm and neurovascular injury. Multidisciplinary care and community-level awareness are essential for timely intervention.