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Infants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for morbidity/mortality arising from life-threatening adrenal crisis. Management of acute illnesses in CAH requires an understanding of factors leading to emergency department (ED) visits and hospitalizations in the first few years of life. We, therefore, examined adrenal crisis at pre-hospital and ED stages of illness in young children with CAH as they related to medical outcomes.Retrospective cohort study of 39 children with CAH due to 21-hydroxylase deficiency (0-4 years of age) and 27 age-matched controls.ED visit, acute illness symptoms (fever, vomiting, diarrhea) and other characteristics (hospitalizations, administration of stress-dose hydrocortisone, electrolyte abnormalities).CAH infants and toddlers had significantly higher rates of ED visits [0.50 (0.25-0.88) per person-year] than controls [0 (0-0) per person-year; P0.001]. Moreover, CAH children under 6 months old had significantly higher rates of ED visits compared to older ages. Only 50% (51/102) of illness-related ED visits in CAH children were preceded by administration of either oral (46/51) or intramuscular (11/51) stress-dosing by parents. 10.8% of ED visits resulted in hospital admission. Controlling for age and 17-hydroxyprogesterone at diagnosis, electrolyte abnormalities and administration of parenteral hydrocortisone in the ED significantly predicted hospital admission. Receiving a hydrocortisone injection prior to the ED was a significant predictor for having electrolyte abnormalities.Infants and toddlers with classical CAH are at high risk for acute illness and hospitalizations and often do not receive adequate stress-dosing prior to the ED. This article is protected by copyright. All rights reserved.

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: β = −0.001 (−0.008, 0.006)]; females: β = −0.004 [−0.015, 0.007]; males: β = 0.001, [−0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine serial radiographs of the left hand obtained clinically in 91 youth with classical CAH (49.5% female) and 70 control youth (44.3% female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males), age (increase of 2D:4D through development) and ethnicity (lower 2D:4D in Hispanic individuals). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: □ = 0.0003 [-0.007, 0.008]; females: □ = −0.004 [-0.015, 0.007]; males: □ = 0.003, [-0.007, 0.013]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.

INTRODUCTIONTesticular adrenal rest tumors (TART) are a known consequence for males with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. TART are associated with potential infertility in adults. However, little is known about TART in very young males with CAH.OBJECTIVEWe assessed the prevalence of TART in newborn, infant, and toddler males with classical CAH via scrotal ultrasound.METHODSMales with CAH had scrotal ultrasounds during the first 4 years of life, evaluating testes for morphology, blood flow, and presence of TART. Newborn screen 17-hydroxyprogesterone (17-OHP) and serum 17-OHP at the time of ultrasound were recorded. Bone ages were considered very advanced if ≥ 2SD above chronological age.RESULTSThirty-one ultrasounds in 16 males were performed. An initial ultrasound was obtained in four newborns at diagnosis (6.8 ±2.1 days), six infants (2.2 ±0.9 months), and six toddlers (2.4 ±0.9 years). Eleven males had at least one repeat ultrasound. A large proportion (11/16) were in poor hormonal control with an elevated 17-OHP (325 ±298 nmol/L). One infant was in very poor hormonal control (17-OHP 447 nmol/L) at initial ultrasound, and two toddlers had advanced bone ages (+3.2 and +4.5 SD) representing exposure to postnatal androgens. However, no TART were detected in any subjects.CONCLUSIONSTART were not found in males up to 4 years of age with classical CAH despite settings with expected high ACTH drive. Further research into the occurrence of TART in CAH may elucidate factors which contribute to the detection and individual predisposition to TART.

PurposeInfants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for adrenal crisis and associated sequelae. To better understand acute illness at this early age, we determined the frequency and severity of acute illness and hospitalizations between 0-4 years of age, both within CAH and compared to controls. We also evaluated the impact of pre-hospital stress-dose hydrocortisone on Emergency Department (ED) visits and hospitalizations.MethodsWe performed a retrospective study of 40 CAH youth and 27 age-matched controls at a tertiary center. Characteristics of acute illnesses during the first 4 years of life were recorded, including fever, vomiting, diarrhea, ED visits, hospitalizations, abnormal electrolytes, and stress-dose hydrocortisone usage.ResultsCAH youth had more frequent illnesses requiring stress-dosing when they were younger than 2 years old [4.0 (1.0-6.0)] compared to when they were 2-4 years old [3.0 (1.0-4.0), P < 0.05], with the most illnesses during their first year of life. As well, CAH infants and toddlers had more hospitalizations younger than 2 years old compared to 2-4 years old (36 vs 2). 25% (3/12) of CAH youth with abnormal electrolytes in the ED did not receive any stress-dosing (oral/IM) prior to the ED, and only 25% (3/12) had received intramuscular hydrocortisone at home. CAH youth had more frequent ED visits (7.4 times as many) and hospitalizations (38 to 0) compared to controls.ConclusionsVery young children with classical CAH are at high risk for acute illness and hospitalizations during their first 2 years of life, and do not receive adequate stress-dosing prior to the ED despite appropriate education. Our findings underscore the need for earlier recognition of acute illness in this vulnerable population and improved education regarding administration of stress-dose hydrocortisone to prevent morbidity.

Background: Classical congenital adrenal hyperplasia (CAH) is a potentially life-threatening condition, and adrenal crisis is a major cause of morbidity and mortality in affected children. Medical-alert identification (ID) could prevent complications of adrenal crisis by identifying the need for time-sensitive, critical treatment. Our objectives were to evaluate usage of medical-alert IDs by CAH youth, ownership and awareness of IDs amongst their parents, and the effect of an in-clinic educational intervention on ID utilization. Methods: Fifty families of youth with classical CAH secondary to 21-hydroxylase deficiency (11.2±5.0 years old, 58% female) were prospectively studied. An in-clinic needs assessment survey was administered at baseline to parents, paired with an educational intervention, and a follow-up needs assessment phone survey 1 month post-intervention. A quality improvement (QI) framework was utilized with plan-do-study-act (PDSA) process-improvement cycles. Results: At baseline, 20/50 (40%) CAH families owned a medical-alert ID, of which only 10/20 (50%) of ID owners reported usage >3 days per week. Only 26/50 (52%) parents were aware of ID options. Post-intervention, ID ownership doubled to 39/50 (78%; p Conclusions: Only a small percentage of CAH youth frequently wear a medical-alert ID, but utilization can be effectively improved with an in-clinic educational intervention. Further study is merited to assess a potential reduction in morbidity and mortality of adrenal crisis with increased medical-alert ID utilization.

Testicular adrenal rest tumors are a well-known complication in males who have congenital adrenal hyperplasia with potential infertility in adulthood. We assessed the prevalence of testicular adrenal rest tumors in infants to young men presenting to a congenital adrenal hyperplasia Comprehensive Care Center.A total of 35 males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency underwent scrotal ultrasonography, including 7 younger than 5 years, 9 who were 5 to 12 years old and 19 who were older than 12 years. Three and 35 patients had classic and nonclassic congenital adrenal hyperplasia, respectively. Bone age x-ray or advanced bone age x-ray history, glucocorticoid dose, fludrocortisone dose, and serum 17-hydroxyprogesterone, testosterone and androstenedione levels within 3 months of ultrasound were also recorded.Testicular adrenal rest tumors were detected in 5 of 35 patients (14%), including 1 of 9 (11%) who were 5 to 12 years old and 4 of 19 (21%) who were older than 12 years. The tumors were not detected in any patients younger than 5 years, including 1 infant with poor hormonal control. The youngest patient with positive findings was 6.6 years old. All patients with positive findings had bilateral disease and only 1 had suspicious physical findings. The glucocorticoid dose and 17-hydroxyprogesterone did not differ between patients with vs without a testicular adrenal rest tumor. Those with a tumor were more likely to have advanced bone age x-ray results (100% vs 42%, p = 0.04) and higher fludrocortisone dose (p0.01). All males with nonclassic congenital adrenal hyperplasia had negative tumor findings.Testicular adrenal rest tumors were present in young males with classic congenital adrenal hyperplasia but not in infants or toddlers. These tumors were associated with higher fludrocortisone requirements and a history of advanced bone age x-ray results. However, the tumors did not develop in all poorly controlled males. Longitudinal studies are needed to understand the individual predisposition to testicular adrenal rest tumors and the age at which to begin screening patients with congenital adrenal hyperplasia.