Context There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. Objective This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. Methods Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography–mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. Results A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. Conclusion Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.

Journal of Clinical Research in Pediatric Endocrinology

Iatrogenic Cushing’s syndrome in children may occur as a result of the application of exogenous steroids. Prolonged use of powerful corticosteroids suppresses adrenal functions and iatrogenic Cushing’s syndrome may develop particularly in infants who are given topical corticosteroids. We report here a case on three infants having Cushing’s syndrome with similar clinical presentations due to overuse of topical steroids for diaper dermatitis. The importance of exercising caution during the use of topical steroids is underlined in this study.

Background: Thyroid hormones are essential for growth and brain development in childhood. Although congenital hypothyroidism (CH) is the most common reason for mental retardation, normal neurological development can be achieved through early and effective treatment. The aim of the present study was to evaluate the neurological development of CH patients aged 24–56 months.Methods: The study included a total of 116 healthy control subjects and 112 patients aged 24–56 months who were diagnosed with CH during the neonatal period and were being followed up at the Pediatric Endocrinology Department, Keçiören Training and Research Hospital, between 2012 and 2015. Demographics and clinical data of interventions and outcomes were retrieved for each patient. Statistical analysis was performed using an unpaired Student’s t-test to compare means and χResults: There were no significant differences between the CH and control groups with respect to gestational age, birth weight, height standard deviation scores (HSDS) and body weight standard deviation scores (BWSDS) (p>0.05). When the groups were compared according to the Denver Developmental Screening Test (DDST), no significant differences were found in terms of personal-social, fine motor skills, or language development (p=0.325, p=0.087 and p=0.636, respectively). However, a significant difference was found between the two groups with respect to gross motor development and the result of the DDST (p=0.001). No statistical difference was found between the control and patient groups on the day of starting treatment but the number of patients with an abnormal result in the DDST starting treatment at >15 days was found to be significantly higher than the number of patients starting treatment ≤15 days. No associations were found between the DDST results of the CH group and the following factors: initial L-thyroxine (LT4) level, initial LT4 dose and the onset of treatment.Conclusions: The findings of this study indicate that the DDST results in patients with CH are generally good. Initiating treatment immediately after diagnosis and during the first days of life is absolutely imperative. However, in contrast to timing, we could not find strong evidence for determining the precise optimal dosage of LT4 to initiate treatment in children diagnosed with CH. Both the American Academy of Pediatrics and the European Society for Pediatric Endocrinology recommend 10–15 μg/kg/day as the initial dose.

Keywords: Type 1 Diabetes; Insulin; Hypoglycemia

Journal of Clinical Research in Pediatric Endocrinology