Background: Lipoid congenital adrenal hyperplasia (LCAH) is a rare and severe disorder that is caused by mutations in the steroidogenic acute regulatory protein (StAR). Non-classic LCAH is defined as late-onset glucocorticoid deficiency and even complete male external genitalia in 46,XY individuals. However, to date, few cases of non-classic LCAH have been reported.Methods: It was attempted to describe the clinical characteristics of a male child with complete male external genitalia in terms of age of onset, adrenal function, and biochemical indicators. Previously reported cases were also reviewed to investigate the relationship of age of onset with enzymatic activity in non-classic LCAH.Results: The patient with complete male external genitalia was diagnosed with non-classic LCAH, in which the reason for his referral to a local hospital at the of age 1.25 years was progressive skin hyperpigmentation, and plasma adrenocorticotropic hormone (ACTH) level was elevated to higher than 1,250 pg/ml. The compound heterozygous mutations c.772C>T/c.562C>T in STAR gene were identified via genetic testing. The literature review resulted in identification of 47 patients with non-classic LCAH from 36 families. The mutational analysis showed that c.562C>T mutation was prevalent in patients with non-classic LCAH, accounting for 37.2% of the total mutant alleles, which could reflect the founder effect on the non-classic LCAH population. In total, 28 46,XY patients were reported, including 22 (78.5%) cases with complete male external genitalia and six (21.5%) cases with different degrees of hypospadias.Conclusion: The clinical phenotypes of non-classic LCAH are highly variable. Routine physical examination, laboratory measurement, genetic testing, and, importantly, enzymatic activity assay may facilitate the early diagnosis of non-classic LCAH. The age of primary adrenal insufficiency (PAI) onset may not be a diagnostic basis for non-classic LCAH, and enzymatic activity assay determination may be more effective.

Original Article Retrospective analysis and literature review of four cases of thyroid hormone resistance syndrome caused by THRB gene mutation Lidan Zhang, Caiping Zhang, Xiaoyan Chen, Lei Ye, Wenli Lu, Zhiya Dong, Wei Wang, Xiaoyu Ma, Yuan Xiao

Objective: To assess the therapeutic effects of gonadotropin‐releasing hormone agonist (GnRHa) on children with familial central precocious puberty (FCPP) due to Makorin ring finger Protein 3 ( MKRN3 ) gene mutations. Methods: Children with central precocious puberty (CPP) who were admitted to the Pediatric Endocrinology Department of Shanghai Ruijin Hospital from 2014 to 2021 were enrolled, of whom 4 FCPP children with MKRN3 gene mutations, including 3 girls and 1 boy, were selected as research subjects. Their height, weight, body mass index (BMI), predicted adult height (PAH), bone age, bone age advance (BAA, bone age minus chronological age), height‐based standard deviation scores (Ht‐SDS) corresponding to the chronological age, concentrations of sex hormones (luteinizing hormone [LH] and follicle‐stimulating hormone [FSH]), and development of sexual organs were compared before and after at least 2 years of GnRHa treatment. Results: After at least 2‐year GnRHa treatment, mean volume of uterus of three girls decreased from 5.72 ± 2.58 to 2.12 ± 1.62 mL ( p < 0.05) and mean volume of ovaries decreased from 3.61 ± 1.67 to 0.62 ± 0.22 mL ( p < 0.05) as well, indicating that the gonadal development was effectively inhibited. Basal concentrations of LH and FSH in serum decreased, indicating that the secretion of gonadotropin in the anterior pituitary is inhibited. BAA and Ht‐SDS decreased, suggesting that the bone age was restrained, and the growth rate was slowed down to some extent. Both average BMI and obesity prevalence ( X ² = 7.188, p = 0.029) decreased during the treatment. No obvious adverse reaction was found. Conclusion: Long‐term GnRHa treatment could effectively inhibit the gonadal development and FSH secretion in FCPP children with MKRN3 gene mutations, while this inhibitory effect on the bone age and growth rate was not obvious. Adverse reactions such as increased prevalence of obesity were not found. A large‐scale, long‐term follow‐up study is required to indicate whether patients’ final height (FH) could reach PAH or target height (TH).

Central precocious puberty (CPP) requires long-term treatment and follow-up, during which caregivers play a central role in treatment adherence and family decision-making. This multicenter, cross-sectional, internet-based survey aimed to characterize knowledge, attitudes, and practices (KAP) among caregivers of children with CPP and to examine determinants and pathway relationships among these domains. Caregivers of children aged 2–16 years with CPP were recruited from eight pediatric endocrinology centers in China. An anonymous online questionnaire based on the disease-specific PRO-CaregiverCPP scale was administered. Knowledge scores, positive attitudes, and good practices were assessed using predefined criteria. Internal consistency was evaluated using Cronbach’s alpha. Multivariable linear and logistic regression models were used to identify factors associated with knowledge scores, positive attitudes, and good practices. Observed-variable path analysis was performed to estimate direct and indirect associations among KAP domains. A total of 1,471 caregivers were included. The mean knowledge score was 6.31 ± 2.25; 72.5 and 58.8% of caregivers demonstrated positive attitudes and good practices, respectively. Higher knowledge scores were independently associated with greater odds of positive attitudes and good practices. Among caregivers of treated children, 3-monthly injections were associated with higher knowledge scores and higher proportions of positive attitudes and good practices than monthly injections. Path analysis showed that knowledge was directly associated with practices and indirectly associated with practices through positive attitudes. These findings indicate a structured KAP pattern in CPP caregiving and support physician-led education and follow-up strategies to improve caregiver engagement and long-term disease management.

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary disease involving multiple endocrine glands. However, early diagnosis and precise treatment remain challenging. This study aimed to explore the pathogenicity and function of a novel MEN1 gene mutation (c.583G>T, p.E195*) found in a 4-year-old boy presenting with recurrent hypoglycemic episodes. Functional assays were conducted, including the construction of a plasmid containing the MEN1 mutation, co-transfection and luciferase reporter gene assays to assess the impact of the MEN1 mutation on JunD-mediated transcription levels. Empty plasmid vector, wild-type (WT), and mutant MEN1 plasmids were transfected, and the proliferation of tumor cells was assessed using the CCK-8 assay. Statistical analysis was performed using one-way ANOVA with Tukey's post hoc test. The patient was diagnosed with MEN1 and insulinoma via clinical, imaging, pathological, and genetic findings. Hypoglycemia resolved after robotic resection. Genetic testing detected a heterozygous mutation (c.583G>T, p.E195*) in the MEN1 gene. This variation is a de novo mutation. Functional experiments in vitro demonstrated that the MEN1 mutation caused a loss of inhibition on transcriptional activity mediated by the transcription factor JunD. This loss promoted tumor cell proliferation, which led to hypoglycemia caused by the insulinoma. The novel mutation (c.583G>T, p.E195*) in the MEN1 gene was the causative genetic lesion in this MEN1 patient with insulinoma, and its pathogenicity might partially result from the loss of inhibition of JunD-mediated transcriptional activation caused by the MEN1 mutation.