Brenden E. Hursh

Adrenal Suppression in Children Treated With Oral Viscous Budesonide for Eosinophilic Esophagitis.

ABSTRACT We sought to determine the prevalence of adrenal suppression (AS) in children with eosinophilic esophagitis treated with oral viscous budesonide (OVB). This was a retrospective review of a quality assurance initiative, whereby all children in our center treated with OVB for ≥3 months were referred over an 18-month time frame for endocrine assessment including 1 &mgr;g adrenocorticotropic hormone stimulation test. Fourteen of 19 children complied with the referral; of these 14 children, 6 (43%) had suboptimal stimulated cortisol (range 343–497 nmol/L, mean [±SD] 424.7 nmol/L [±52.4], normal ≥500 nmol/L). There was no significant association to treatment duration, dose, or concomitant use of inhaled/nasal corticosteroids. This study suggests that children treated with OVB may be at risk for AS.

Acute Kidney Injury in Children With Type 1 Diabetes Hospitalized for Diabetic Ketoacidosis

Importance Acute kidney injury (AKI) in children is associated with poor short-term and long-term health outcomes; however, the frequency of AKI in children hospitalized for diabetic ketoacidosis (DKA) has not been previously examined. Objectives To determine the proportion of children hospitalized for DKA who develop AKI and to identify the associated clinical and biochemical markers of AKI. Design, Setting, and Participants This medical record review of all DKA admissions from September 1, 2008, through December 31, 2013, was conducted at British Columbia Children’s Hospital, the tertiary pediatric hospital in British Columbia, Canada. Children aged 18 years or younger with type 1 diabetes and DKA and with complete medical records available for data analysis were included (n = 165). All data collection occurred between September 8, 2014, and June 26, 2015. Data analysis took place from August 25, 2015, to June 8, 2016. Main Outcomes and Measures Acute kidney injury was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. Multinomial logistic regression was used to identify potential factors associated with AKI. Results Of the 165 children hospitalized for DKA, 106 (64.2%) developed AKI (AKI stage 1, 37 [34.9%]; AKI stage 2, 48 [45.3%]; and AKI stage 3, 21 [19.8%]). Two children required hemodialysis. In the adjusted multinomial logistic regression model, a serum bicarbonate level less than 10 mEq/L (compared with ≥10 mEq/L) was associated with a 5-fold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio [aOR], 5.22; 95% CI, 1.35-20.22). Each increase of 5 beats/min in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39). Initial corrected sodium level of 145 mEq/L or greater (compared with 135-144 mEq/L) was associated with a 3-fold increase in the odds of mild (stage 1) AKI (aOR, 3.29; 95% CI, 1.25-8.66). There were no cases of mortality in patients with or without AKI. Conclusions and Relevance This study is the first to date to document that a high proportion of children hospitalized for DKA develop AKI. Acute kidney injury was associated with markers of volume depletion and severe acidosis. Acute kidney injury is concerning because it is associated with increased morbidity and mortality as well as increased risk of chronic renal disease, a finding that is especially relevant among children who are already at risk for diabetic nephropathy. Strategies are needed to improve the diagnosis, management, and follow-up of AKI in children with type 1 diabetes.

Assessing resting energy expenditure in overweight and obese adolescents in a clinical setting: validity of a handheld indirect calorimeter

Background:Accurately determining energy requirements is key for nutritional management of pediatric obesity. Recently, a portable handheld indirect calorimeter, MedGem (MG) has become available to measure resting energy expenditure (REE). Our work aims to determine the clinical validity and usefulness of MG to measure REE in overweight and obese adolescents.Methods:Thirty-nine overweight and obese adolescents (16 male (M): 23 female (F), 15.2 ± 1.9 y, BMI percentile: 98.6 ± 2.2%) and 15 normal weight adolescents (7M: 8F, age 15.2 ± 2.0 y, BMI percentile: 39.2 ± 20.9%) participated. REE was measured with both MG and standard indirect calorimeter (VMax) in random order.Results:MG REE (1,600 ± 372 kcal/d) was lower than VMax REE (1,727 ± 327 kcal/) in the overweight and obese adolescents. Bland Altman analysis (MG –VMax) showed a mean bias of −127 kcal/d (95% CI = −72 to −182 kcal/d, P < 0.001), and a proportional bias existed such that lower measured REE by VMax was underestimated by MG, and higher measured REE by VMax were overestimated by MG.Conclusion:MG systematically underestimates REE in the overweight and adolescent population, thus the MG portable indirect calorimeter is not recommended for routine use. Considering that it is a systematic underestimation of REE, MG may be clinically acceptable, only if used with caution.

Adrenal insufficiency exists for both swallowed budesonide and fluticasone propionate in the treatment of eosinophilic esophagitis

To the Editor: The report by Golekoh et al examined the prevalence of adrenal insufficiency in children with eosinophilic esophagitis treated with swallowed fluticasone propionate (FP) or budesonide and found that all patients on budesonide had normal testing. This contrasts with our study, in which we documented an adrenal insufficiency prevalence of 43% with budesonide. They consequently explain these contrasting results by suggesting that our study population was treated concomitantly with inhaled corticosteroids for asthma. However, this misinterprets our findings because 3 of the 6 patients with adrenal insufficiency were treated solely with budesonide. Additionally, being on concomitant corticosteroid therapy for asthma and for eosinophilic esophagitis is representative of the average patient with this condition and, if anything, should increase the concern for adrenal insufficiency. The authors also state that our study was limited by a small population (n = 14 on budesonide); however, one should take into account that their study included 19 patients on budesonide, a similar number to our sample. The authors’ remarks in the Abstract and Discussion are that they found evidence of adrenal insufficiency only in children on FP and therefore recommend testing in those children. We are concerned that readers may be left with an impression that only patients on FP need screening, and that those on budesonide do not require screening. Given our study found that some patients developed adrenal insufficiency only on budesonide (and no other corticosteroid medications), we would suggest caution is necessary in at least some patients on budesonide, until further prospective studies are available.

Cardiac Autonomic Function at Baseline and under Stress and Its Relationship to Circulatory Markers of Inflammation in Obese Compared to Nonobese Children: A Pilot Study

Background/Aims: The autonomic nervous system (ANS) provides neurogenic control of inflammatory reactions. ANS changes in obesity may result in inflammation. This study sought to gain insight into cardiac autonomic dysfunction and inflammation in childhood obesity, and to gather pilot data on the potential relationship between altered ANS and inflammation. Methods: Fifteen obese children and adolescents without metabolic complications and 15 nonobese controls underwent heart rate variability and impedance cardiography testing during rest, mental stress, and physical stress. Inflammatory cytokines and immune reactivity were measured. Results: There was no statistically significant difference between groups in cardiac ANS testing at rest or in response to stress. Median high-sensitivity C-reactive protein (hsCRP) was higher in the obese group [obese 2.6 mg/l (IQR 1.6-11.9); nonobese 0.3 mg/l (IQR 0.2-0.7); p < 0.001]. Interleukin-6 and tumour necrosis factor-α were similar between groups. Immune reactivity testing (in vitro Toll-like receptor stimulation) revealed a strong, but comparable, inflammatory response in both groups. Conclusions: Obese children and adolescents without metabolic complications did not have cardiac ANS dysfunction. While hsCRP was elevated, systemic cytokines were not raised. Compared to prior studies, which often focused on children with obesity and its complications, it is encouraging that obese children without metabolic complications may not yet have autonomic dysfunction.

A rare cause of hypertension in a healthy 2-year-old female: Answers

This patient has 17α-hydroxylase deficiency, a rare form of congenital adrenal hyperplasia (CAH) and one of the rarer forms of monogenic hypertension. This autosomal recessive disorder results from a complete or partial deficiency of the P450c17 enzyme, which has both 17α-hydroxylase and 17,20-lyase activity (see Fig. 1) [1]. The enzymatic defect leads to impaired formation of cortisol and sex hormones, with retained functioning of the mineralocorticoid pathway. The first case of 17α-hydroxylase deficiency was reported in 1966 by Biglieri, who described a 35-year-old woman who was hypertensive and hypokalemic and had not entered puberty [2]. Since that time, more than 200 cases have been reported in the literature [3]. Overall, 17α-hydroxylase deficiency constitutes approximately 1 % of CAH cases [4]. It has been more commonly identified in certain ethnic populations, including Brazilians and Japanese [5, 6]. As in other forms of CAH, cortisol deficiency stimulates adrenocorticotropic hormone (ACTH) production, ultimately resulting in adrenal gland hyperplasia. In 17αhydroxylase deficiency, this leads to an accumulation of deoxycorticosterone (DOC) and corticosterone (see Fig. 1). In this patient, DOC was elevated at 116 ng/dL (normal range 2–34 ng/dL) and corticosterone was also elevated at 14,948 ng/dL (normal range 135–1860 ng/dL). Hypertension, hypokalemia and metabolic alkalosis result from elevated DOC, which has mineralocorticoid activity. The extent of hypertension may vary significantly in this condition. In one of the larger cohorts described, average blood pressure prior to treatment was 146/100 mmHg at a median age of 18 years [5]. Malignant hypertension may also be seen [7]. Interestingly, 17α-hydroxylase deficiency does not present with adrenal crisis despite the lack of cortisol, as the elevated corticosterone provides sufficient glucocorticoid activity. Although one might anticipate that these patients would have elevated aldosterone levels, the opposite is typically true. 17-α-Hydroxylase deficiency causes a non-aldosterone mineralocorticoid hypertension, also known as pseudoaldosteronism. In this condition, high levels of DOC cause volume expansion, leading to suppression of the renin– angiotensin system and subsequent low levels of renin and aldosterone [8]. It is important to note that hypokalemia is not consistently observed, as demonstrated in this case and previously documented in the literature [5]. Thus, a normal serum potassium should not sway one from considering the diagnosis. As with This article refers to the article that can be found at http://dx.doi.org/ 10.1007/s00467-012-2161-5.

A rare cause of hypertension in a healthy 2-year-old female: Questions

A previously healthy 2-year-old Caucasian female was admitted to the hospital for dehydration secondary to a diarrheal illness. In the emergency department, she was noted to be hypertensive, and this persisted throughout her admission, including during sleep. Her average blood pressure was elevated at 140/90 mmHg by Dinamap oscillometric measurements. High blood pressure readings were confirmed by sphygmomanometry. She received intravenous fluids and was discharged home two and a half days later. The elevated blood pressure was not investigated during the admission, but follow-up was arranged with a community pediatrician to reassess her blood pressure in an outpatient setting. Her hypertension persisted at that appointment, prompting a workup for potential causes. This young girl was otherwise healthy with no significant prenatal, perinatal, or past medical history. A review of systems was unremarkable. She was growing and developing appropriately. Her parents did not recall her blood pressure being measured in the past. She was on no medications. There was a family history of hypertension in the maternal grandmother and paternal great-grandmother, both of which were diagnosed in adulthood. She had a healthy, normotensive 4-year-old brother. Parents were also normotensive. Physical examination was unremarkable aside from the elevated blood pressure of 145/90 mmHg by auscultation (>99th percentile for age and height). Measurements were similar in all four extremities. Heart rate was normal at 110 bpm. Weight was 16.1 kg (>95th percentile) and height was 94.5 cm (>95th percentile). BMI was 18 kg/m (85th percentile). She was not dysmorphic. Cardiac examination was normal. There was no abdominal mass or bruit. She had no edema. She had normal female external genitalia. The exam was otherwise normal. The pediatrician’s workup included the following: sodium 140 mmol/l, potassium 3.8mmol/l, total calcium 10mg/dl, bicarbonate 24 mmol/l, creatinine 0.37 mg/dl, and BUN 5.6 mg/dl (all within normal limits). Urinalysis was negative The answers to these questions can be found at doi:10.1007/s00467012-2164-2.