SNARE-ing the Reason for Post-Cardiac Surgery Critical Illness-Related Corticosteroid Insufficiency.

Critical illness-related corticosteroid insufficiency (CIRCI) can cause hemodynamic instability in neonates after congenital heart surgery with manifestations that increase morbidity and potential mortality. We retrospectively reviewed neonates who underwent cardiac surgery between August 2018 and July 2020 at a freestanding children's hospital, had next-generation sequencing performed, and had their cortisol levels drawn as standard clinical care after cardiac surgery. The groups were defined as CIRCI (with a cortisol level ≤ 4.5 mcg/dL) and non-CIRCI (level > 4.5 mcg/dL). The CIRCI group (n = 8) had a 100% incidence of heterozygous gene mutation on STX1A with splicing or loss of function, and this mutation was not found in the non-CIRCI group (n = 8). Additional gene mutations were found in the CIRCI group on RAB6A, ABCA3, SIDT2, and LILRB3, with no incidence in the non-CIRCI group. Three additional mutations were found across the CIRCI group in INPPL1 and FAM189A2 (both splicing and missense), with 12-25% of patients in the non-CIRCI group also displaying these mutations. Novel genetic abnormalities were seen in neonates with symptoms of CIRCI with potential cardiac implications from a gene mutation for STX1A. Compounding effects of additional gene mutations need to be confirmed and explored for potential predisposition to hemodynamic instability during times of stress.

Morning cortisol levels affected by sex and pubertal status in children and young adults.

OBJECTIVE: Morning cortisol levels are frequently used as screening tests for adrenal insufficiency in both adults and children. Reports differ on the specificity of this measurement. The present study was undertaken to determine whether sex or pubertal status affected morning cortisol values. METHODS: We measured morning cortisol levels and performed low-dose adrenocorticotropic hormone stimulation test in 35 healthy male and female subjects (ages 6-34) ranging in Tanner stage (TS) from TS 1 to TS 5. Testing was initiated at 08:00 after an overnight fast. Morning serum total cortisol, free cortisol, cortisol-binding globulin, estradiol (males and females), and testosterone (males) were obtained. RESULTS: Morning total and free cortisol levels were significantly higher in TS 5 participants than in prepubertal children. Using a morning cortisol of 248 nmol/L to define a normal value, 19/21(90%) of healthy TS 5 subjects exhibit normal values. In contrast, 0/8 TS 1 healthy subjects exhibited a value greater than 248 nmol/L (p=0.0005). We also observed sex differences in morning cortisol levels in pubertal but not in prepubertal subjects. We observed sex differences in morning cortisol levels in TS 5 individuals. CONCLUSIONS: Morning cortisol measurements may be more useful as screening tests for adrenal function in adults than in children. TS and sex may be considered in the decision to screen for adrenal insufficiency using morning cortisol or whether to proceed directly to stimulation testing.

A retrospective review of pituitary MRI findings in children on growth hormone therapy.

BACKGROUND: Patients with congenital hypopituitarism might have the classic triad of pituitary stalk interruption syndrome, which consists of: (1) an interrupted or thin pituitarys talk, (2) an absent or ectopic posterior pituitary (EPP), and (3) anterior pituitary hypoplasia or aplasia. OBJECTIVE: To examine the relationship between pituitary anatomy and the degree of hormonal dysfunction. MATERIALS AND METHODS: This study involved a retrospective review of MRI findings in all children diagnosed with congenital growth hormone deficiency from 1988 to 2010 at a tertiary-level pediatric hospital. RESULTS: Of the 52 MRIs reviewed in 52 children, 26 children had normal pituitary anatomy and 26 had one or more elements of the classic triad. Fourteen of fifteen children with multiple pituitary hormone deficiencies had structural anomalies on MRI. Twelve of 37 children with isolated growth hormone deficiency had an abnormal MRI. CONCLUSION: Children with multiple pituitary hormone deficiencies were more likely to have the classic triad than children with isolated growth hormone deficiency. A normal MRI was the most common finding in children with isolated growth hormone deficiency.

Central nervous system vasculitis with positive antithyroid antibodies in an adolescent boy.

Hashimoto's encephalopathy is diagnosed when patients exhibit features of corticosteroid-responsive encephalopathy and positive antithyroid antibodies. The relationship between antithyroid antibodies and encephalopathy is subject to considerable debate. We describe corticosteroid-responsive encephalopathy in a 14-year-old boy with positive antimicrosomal antibodies. His history included subtle neurocognitive decline. He presented with seizures. He underwent a brain biopsy before initiating treatment after his third episode. That biopsy was consistent with central nervous system vasculitis. This report is unique because, to our knowledge, it describes the first pretreatment brain biopsy of a pediatric patient who fits the criteria for Hashimoto's encephalopathy.