Endocrine, cardiac and neuropsychological aspects of adult congenital adrenal hyperplasia.

OBJECTIVE: To investigate the metabolic, cardiovascular, and neuropsychological phenotype, quality of life (QoL), and hormonal regulation in individuals with congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired synthesis of cortisol in the adrenal cortex and, if untreated compensatory hyperandrogenism. CAH is associated with an increased cardiovascular and metabolic morbidity, possibly due to overtreatment with glucocorticoids, leading to weight gain, insulin resistance, and metabolic syndrome. DESIGN, PARTICIPANTS, MEASUREMENTS: Thirty-seven individuals with CAH and 33 age- and sex-matched controls were evaluated at a single centre at Aarhus University Hospital with echocardiography, electrocardiogram, 24-h blood pressure, biochemistry, anthropometrics, and autism spectrum, anxiety, depression, personality, cognitive failures, and QoL were assessed using questionnaires. RESULTS: CAH individuals had lower height than controls (170.5 vs. 182.9 cm in males and 160.2 vs. 170.1 cm in females, p < 0.01). Compared with female controls, females with CAH had higher haemoglobin (8.8 vs. 8.2 mmol/L, p = 0.003) and BMI (29.7 vs. 25.5 kg/m2, p = 0.006), reduced insulin sensitivity (HOMA-IR): 2.7 vs. 1.9, p = 0.018), prolonged E-wave deceleration time (193 vs. 174 cm, p = 0.015), and E/é ratios (5.4 vs. 4.5, p = 0.017), and lower self-reported QoL. Males with CAH had more cognitive complaints (p = 0.034) and higher autistic scores (19.9 vs. 14.9; p = 0.068) compared with male controls. More individuals with CAH than controls reported writing problems. CONCLUSION: A sex-specific comorbidity profile is evident in CAH, with females presenting with decreased metabolic and overall self-reported health, whereas males with CAH presented with increased cognitive complaints and autistic traits.

Epidemiology and diagnostic trends of congenital adrenal hyperplasia in Denmark: a retrospective, population-based study.

Background: The prevalence of newborns with congenital adrenal hyperplasia (CAH) detected by neonatal screening is well-described, but data including patients diagnosed later in life are extremely limited. This study aimed to describe diagnostic trends for all patients with CAH in Denmark. Methods: A nationwide population-based registry study including medical record review. Findings: We identified 462 patients (290 females) with any form of CAH. The prevalence of CAH combined was 15.1 (95% confidence interval [CI]: 12.3-16.1) and 9.0 (CI: 7.6-10.4) per 100,000 newborn females and males. There was a prevalence of salt-wasting (SW), simple-virilizing (SV), and non-classic (NC) CAH due to 21-hydroxylase deficiency of: SW-CAH: 6.4 (CI: 5.3-7.6) and 5.6 (CI: 4.6-6.8); SV-CAH: 2.0 (CI: 1.4-2.8) and 1.6 (CI: 1.0-2.7); and NC-CAH: 5.5 (CI: 4.4-6.9) and 2.5 (CI: 1.7-3.7) per 100,000 newborn females and males, respectively. Diagnosis of NC-CAH increased significantly during the course of the study. There was a female preponderance for SV-CAH (ratio: 1.8) and NC-CAH (ratio: 3.2). Median age at diagnosis, females and males respectively: SW-CAH: 4 (interquartile range [IQR]: 0-11) and 14 (IQR: 8-24) days, SV-CAH: 3.1 (IQR: 1.2-6.6) and 4.8 (IQR: 3.2-6.9) years, and NC-CAH: 15.5 (IQR: 7.9-22.5) and 9.4 (IQR: 7.2-23.2) years. Interpretation: The combined prevalence of CAH was 15.1 and 9.0 per 100,000 newborn females and males, respectively. The female preponderance was primarily due to diagnosis of more females than males with NC-CAH. Funding: International Fund of Congenital Adrenal Hyperplasia, Health Research Fund of Central Denmark Region, Aase and Einar Danielsen Fund, and "Fonden til Lægevidenskabens Fremme".

Neonatal Screening for Congenital Adrenal Hyperplasia in Denmark: 10 Years of Experience.

INTRODUCTION: Early detection of salt-wasting congenital adrenal hyperplasia (SW-CAH) is important to reduce CAH-related morbidity. However, neonatal screening has shown to have a low positive predictive value (PPV), especially among preterm newborns. Here, the Danish CAH screening is evaluated by comparing incidence and morbidity of SW-CAH 10 years before and after introduction of screening. Furthermore, sensitivity, specificity, and PPV are determined. METHODS: All newborns in Denmark born during 1999-2018 and diagnosed with SW-CAH were identified in the Danish National Patient Registry and/or at the Department of Clinical Genetics, Rigshospitalet. Newborns with a positive neonatal CAH screening were identified at Statens Serum Institut. Correct diagnosis was evaluated by medical record review. RESULTS: A total of 65 newborns with SW-CAH were identified. The incidence of SW-CAH was 5:100,000 both before and after introduction of screening. Performance of sensitivity and specificity of the screening were 97% and 100%, respectively, and the PPV was 55% for the given period. Stratified according to gestational age, the PPV was 33% and 61% for pre -and fullterm newborns, respectively. Though not significant, the proportion of newborns presenting with SW-crisis decreased after introduction of screening from 29% versus 10% (p = 0.07). DISCUSSION AND CONCLUSION: Neonatal screening for SW-CAH has not led to an increase in the incidence of newborns diagnosed with SW-CAH. The screening algorithm has effectively identified newborns with SW-CAH. After 2009, there was a tendency toward a lower proportion of newborns with SW-crisis at diagnosis. Finally, the study emphasizes the benefits of using second-tier screening as well as repeated screening of premature newborns.

High-dose anakinra as treatment for macrophage activation syndrome caused by refractory Kawasaki disease in an infant.

We report a 12-week-old boy presenting with incomplete refractory Kawasaki disease (KD) complicated with macrophage activation syndrome (MAS). The infant presented with cerebral irritability, pain, tachypnoea and vomiting for 10 days. He did not fulfil any of the classic diagnostic criteria for KD. Pericardial effusion on echocardiography in addition to severe dilatation of the coronary arteries in combination with leucocytosis and raised acute phase reactants led to the diagnosis of incomplete KD. Treatment with intravenous immunoglobulin and aspirin was initiated but without any response. The condition was subsequently refractory to additional treatment with infliximab and high-dose methylprednisolone. His condition worsened, fulfilling the criteria for MAS. High-dose anakinra was initiated, and remission of the inflammation was achieved.