Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It comprises a group of autosomal recessive disorders caused by the mutations in the genes encoding for steroidogenic enzymes that involved cortisol synthesis. More than 90% of cases are caused by a defect in the enzyme 21-hydroxylase. Four other enzyme deficiencies (cholesterol side-chain cleavage, 17alpha-hydroxylase [P450c17], 11beta-hydroxylase [P450c11beta], 3beta-hydroxysteroid dehydrogenase) in the steroid biosynthesis pathway, along with one cholesterol transport protein defect (steroidogenic acute regulatory protein), and one electrontransfer protein (P450 oxidoreductase) account for the remaining cases. The clinical symptoms of the different forms of CAH result from the particular hormones that are deficient and those that are produced in excess. A characteristic feature of CAH is genital ambiguity or disordered sex development, and most variants are associated with glucocorticoid deficiency. However, in the rare forms of CAH other than 21-hydroxylase deficiency so-called "atypical CAH", the clinical and hormonal phenotypes can be more complicated, and are not well recognized. This review will focus on the atypical forms of CAH, including the genetic analyses, and phenotypic correlates.
Adrenal Hyperplasia, Congenital* ; Cholesterol ; Disorders of Sex Development ; Genotype ; Hydrocortisone ; Phenotype ; Rare Diseases ; Sexual Development ; Steroid 21-Hydroxylase

Purpose: There is growing global concern about the shift to earlier onset of puberty among girls; however, the prevalences of precocious and normal variant puberty among Thai girls are uncertain. We conducted a study at King Chulalongkorn Memorial Hospital in Bangkok from 2018 to 2022 (amid the coronavirus disease 2019 pandemic) to investigate the prevalence, characteristics, and treatment of early puberty in a large cohort of Thai girls. Methods: The medical records of 583 girls who had been evaluated for early puberty were reviewed. Demographic and clinical characteristics, and treatment approaches were analyzed. Results: The analyses found a significant annual increase in evaluations for early signs of puberty (P-value for trend 0.04). The majority (71.2%) of cases were categorized as gonadotropin-releasing-hormone (GnRH)-dependent or central precocious puberty (CPP), with 16 cases showing abnormal brain magnetic resonance imaging findings. Among girls with normal variant puberty, early normal puberty was the most common category (10.5%), followed by premature thelarche (9.5%), slow-progressive precocious puberty (6.6%), and premature adrenarche (2.2%). Median age at presentation, basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and bone age differed significantly among groups. Importantly, 97% of girls with CPP received GnRH agonists. Girls with CPP exhibited higher body mass index z-scores and basal LH and FSH compared with those with slow-progressive precocious puberty. Conclusion Our analyses of the prevalence, characteristics, and treatment of early puberty in Thai girls highlighted the impact of obesity on pubertal timing. The findings underscore the need for preventive weight management and country-specific guideline updates to enhance healthcare strategies for young girls.

Purpose: There is growing global concern about the shift to earlier onset of puberty among girls; however, the prevalences of precocious and normal variant puberty among Thai girls are uncertain. We conducted a study at King Chulalongkorn Memorial Hospital in Bangkok from 2018 to 2022 (amid the coronavirus disease 2019 pandemic) to investigate the prevalence, characteristics, and treatment of early puberty in a large cohort of Thai girls. Methods: The medical records of 583 girls who had been evaluated for early puberty were reviewed. Demographic and clinical characteristics, and treatment approaches were analyzed. Results: The analyses found a significant annual increase in evaluations for early signs of puberty (P-value for trend 0.04). The majority (71.2%) of cases were categorized as gonadotropin-releasing-hormone (GnRH)-dependent or central precocious puberty (CPP), with 16 cases showing abnormal brain magnetic resonance imaging findings. Among girls with normal variant puberty, early normal puberty was the most common category (10.5%), followed by premature thelarche (9.5%), slow-progressive precocious puberty (6.6%), and premature adrenarche (2.2%). Median age at presentation, basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and bone age differed significantly among groups. Importantly, 97% of girls with CPP received GnRH agonists. Girls with CPP exhibited higher body mass index z-scores and basal LH and FSH compared with those with slow-progressive precocious puberty. Conclusion Our analyses of the prevalence, characteristics, and treatment of early puberty in Thai girls highlighted the impact of obesity on pubertal timing. The findings underscore the need for preventive weight management and country-specific guideline updates to enhance healthcare strategies for young girls.

Purpose: There is growing global concern about the shift to earlier onset of puberty among girls; however, the prevalences of precocious and normal variant puberty among Thai girls are uncertain. We conducted a study at King Chulalongkorn Memorial Hospital in Bangkok from 2018 to 2022 (amid the coronavirus disease 2019 pandemic) to investigate the prevalence, characteristics, and treatment of early puberty in a large cohort of Thai girls. Methods: The medical records of 583 girls who had been evaluated for early puberty were reviewed. Demographic and clinical characteristics, and treatment approaches were analyzed. Results: The analyses found a significant annual increase in evaluations for early signs of puberty (P-value for trend 0.04). The majority (71.2%) of cases were categorized as gonadotropin-releasing-hormone (GnRH)-dependent or central precocious puberty (CPP), with 16 cases showing abnormal brain magnetic resonance imaging findings. Among girls with normal variant puberty, early normal puberty was the most common category (10.5%), followed by premature thelarche (9.5%), slow-progressive precocious puberty (6.6%), and premature adrenarche (2.2%). Median age at presentation, basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and bone age differed significantly among groups. Importantly, 97% of girls with CPP received GnRH agonists. Girls with CPP exhibited higher body mass index z-scores and basal LH and FSH compared with those with slow-progressive precocious puberty. Conclusion Our analyses of the prevalence, characteristics, and treatment of early puberty in Thai girls highlighted the impact of obesity on pubertal timing. The findings underscore the need for preventive weight management and country-specific guideline updates to enhance healthcare strategies for young girls.

Purpose: Diabetic neuropathy (DN) is a serious complication in diabetes mellitus. We aimed to determine the prevalence of DN in pediatric-onset diabetes in a tertiary care center and to assess the sensitivity and specificity of monofilament testing and noninvasive screening to diagnose DN compared with the gold standard nerve conduction study (NCS). Methods: Sixty-five Thai children and adolescents (39 females) diagnosed with diabetes before 15 years of age were included. All subjects were screened for DN by foot and neurological examinations, light touch sensation by 10 g Semmes-Weinstein monofilaments, and the Michigan Neuropathy Screening Instrument (MNSI). NCSs were used as the gold standard for diagnosis of DN. Results: Fifty-eight patients had type 1 diabetes ( T1D), 5 patients had type 2 diabetes, and 2 patients had other types of diabetes. The mean age was 17.7±4.6 years (8–33 years). The prevalence of DN in this cohort was 12.3% by NCS. All subjects were asymptomatic. Mean diabetes duration did not differ between the groups (with DN 8.0±3.0 years vs. no DN 8.2±5.0 years). Notably, one patient with T1D developed DN within 3 years after diagnosis. Poor glycemic control was a significant risk factor for DN. Glycosylated hemoglobin was higher in the DN group (10.6%±2.3% vs. 8.5%±1.6%, P=0.008). The occurrence of diabetic nephropathy was associated with DN (prevalence rate ratio, 4.97; 95% confidence interval, 1.5–16.46). Foot and neurological examinations, monofilaments, and the MNSI failed to detect DN in all subjects with abnormal NCS. Conclusion The prevalence of DN in pediatric-onset diabetes is not uncommon but mainly is subclinical. Poor glycemic control is the main risk factor. Noninvasive screening tests for DN exhibited poor diagnostic sensitivity in the pediatric population.