Diagnosis of adrenal insufficiency in eosinophilic esophagitis: The importance of timing of cortisol measurements in interpreting low-dose adrenocorticotropic hormone stimulation testing

Comment on Adrenal Insufficiency after Chronic Swallowed Glucocorticoid Therapy for Eosinophilic Esophagitis. [J Pediatr. 2016

Growth and Reproductive Outcomes in Congenital Adrenal Hyperplasia

The treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is complex. In addition to disease control, important therapeutic goals are the maintenance of normal growth and the acquisition of normal reproductive function. Here, data regarding final adult height (FH) in patients with CAH will be reviewed. Additional difficulties associated with CAH, including risks of obesity and hypertension, will be discussed. Information about fertility and reproductive outcomes in men and women with CAH will also be summarized. Although the treatment of each child with CAH needs to be individualized, close medical followup and laboratory monitoring along with good compliance can often result in positive clinical outcomes

Pediatric toxic polycystic thyroid

Background: Polycystic thyroid disease (PCTD) is a rare condition and has been described in adults in the setting of subclinical and clinical hypothyroidism. We present the first known case of a pediatric patient with diffuse macrocystic degeneration of the thyroid. Clinical presentation: A 6-year-old previously healthy patient was evaluated after presenting with a 16-month history of an enlarging polycystic thyroid and hyperthyroidism. Markers of autoimmune thyroid disease including thyroid stimulating immunoglobulin (TSI), thyroid stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody and thyroglobulin antibody were negative. No family history of benign or malignant thyroid or cystic disease was present. The patient underwent a total thyroidectomy without perioperative complication. She remains euthyroid with thyroid hormone replacement therapy. Summary: To our knowledge, this is the first report of PCTD in the pediatric population associated with hyperthyroidism without evidence of autoimmune disease. Somatic activating thyrotropin-receptor gene mutations are known to cause non-autoimmune hyperthyroidism in children, however it is unknown if similar mechanisms are responsible for pediatric PCTD. Conclusions: Polycystic thyroid degeneration can occur in children and may result in a hyperthyroid state

Endocrine Effects of Inhaled Corticosteroids in Children

Inhaled corticosteroids (ICSs) are widely used as first-line treatment for various chronic respiratory illnesses. Advances in devices and formulations have reduced their local adverse effects. However, as delivery of ICSs to the lungs improves, the systemic absorption increases, and an adverse effect profile similar to, although milder than, oral corticosteroids has emerged. The most serious potential adverse effect is adrenal insufficiency, which can be life threatening. Adrenal insufficiency occurs most in patients taking the highest doses of ICSs but is reported with moderate or even low doses as well. Our recommendations include greater vigilance in testing adrenal function than current standard practice. In patients with diabetes mellitus (types 1 and 2), an increase in glucose levels is likely, and diabetes medication adjustment may be needed when initiating or increasing ICSs. The risk of linear growth attenuation and adverse effects on bone mineral density is generally low but should be considered in the face of additional risk factors. On behalf of the Pediatric Endocrine Society Drugs and Therapeutics Committee, we present a review of the endocrine adverse effects of ICSs in children and offer recommendations relating to testing and referral. Limited data in particular realms diminish the strength of certain recommendations, and clinical judgment continues to be paramount

Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia

BACKGROUND: Little is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics. METHODS: Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI). Single nucleotide polymorphism (SNP) analysis of genes in the glucocorticoid pathway was also performed. RESULTS: Nine prepubertal subjects aged 8.1 ± 2.3 years completed the study. Mean ACTH, androstenedione, and 17-hydroxyprogesterone (17-OHP) values were lower following the DEX arm of the study than after subjects received HC (p ≤ 0.016) or PDN (p ≤ 0.002). 17-OHP was also lower after HC than PDN (p < 0.001). There was no difference in IGF-1, GH, or change in BMI. SNP analysis revealed significant associations between hormone concentrations, pharmacokinetic parameters, and variants in several glucocorticoid pathway genes (ABCB1, NR3C1, IP013, GLCCI1). CONCLUSIONS: DEX resulted in marked adrenal suppression suggesting that its potency relative to hydrocortisone and prednisone was underestimated. SNPs conferred significant differences in responses between subjects. Although preliminary, these pilot data suggest that incorporating pharmacogenetics has the potential to eventually lead to targeted therapy in children with CAH

A brother and sister with the same karyotype: Case report of two siblings with partial 3p duplication and partial 9p deletion and sex reversal

Two siblings with the same male unbalanced karyotype demonstrate sex reversal. The older sib appeared phenotypically female and the younger sib demonstrated a male gender. The female had gonadal dysgenesis with bilateral ovatestes. The male had bilateral testes. The report discusses the phenotypical differences and genes associated with sex reversal

Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency

Inactivating mutations in chromodomain helicase DNA binding protein 7 (CHD7) cause CHARGE syndrome, a severe multiorgan system disorder of which Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a minor feature. Recent reports have described predominantly missense CHD7 alleles in IGD patients, but it is unclear if these alleles are relevant to causality or overall genetic burden of Kallmann syndrome (KS) and normosmic form of IGD. To address this question, we sequenced CHD7 in 783 well-phenotyped IGD patients lacking full CHARGE features; we identified nonsynonymous rare sequence variants in 5.2% of the IGD cohort (73% missense and 27% splice variants). Functional analyses in zebrafish using a surrogate otolith assay of a representative set of these CHD7 alleles showed that rare sequence variants observed in controls showed no altered function. In contrast, 75% of the IGD-associated alleles were deleterious and resulted in both KS and normosmic IGD. In two families, pathogenic mutations in CHD7 coexisted with mutations in other known IGD genes. Taken together, our data suggest that rare deleterious CHD7 alleles contribute to the mutational burden of patients with both KS and normosmic forms of IGD in the absence of full CHARGE syndrome. These findings (i) implicate a unique role or preferential sensitivity for CHD7 in the ontogeny of GnRH neurons, (ii) reiterate the emerging genetic complexity of this family of IGD disorders, and (iii) demonstrate how the coordinated use of well-phenotyped cohorts, families, and functional studies can inform genetic architecture and provide insights into the developmental biology of cellular systems