Body Mass Index and Cardiovascular Risk Factors in Children with Cushing Syndrome before and after Surgical Treatment

Presentation Number: SAT 405
Date of Presentation: April 1st, 2017

Nuria Valdés*1, Amit Tirosh2, Lyssikatos Charalampos1, Margaret Farmar Keil3, Elena Belyavskaya1, Constantine A Stratakis1 and Maya Beth Lodish1
1Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 2Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH, Bethesda, MD, 3Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)., Bethesda, MD

Abstract

Introduction: Due to the rarity of Cushing syndrome (CS) in pediatric patients data are scarce about body mass index (BMI) and cardiovascular risk factors during active disease and following remission and/or cure.

Objective: The purpose of our study was to study BMI and its relationship with cardiovascular risk factors before and after surgical treatment in pediatric patients with CS.

Patients and methods: We selected patients biochemically cured after surgery of CS and with at least 1 visit following cure. Data were collected from 73 patients, 40 males (58%), median age of 12 years (IQR: 9-15 years) and median follow up time of 14 months (IQR: 11-27 months). Cushing disease was diagnosed in 58 patients and primary adrenal CS in 15 patients according to pathological diagnosis.

Results: Mean BMI z-score at diagnosis was 2.0±0.7 (range: -0.4-3.1), 8 (11%) patients had a normal weight, 23 (31.5%) were overweight and 42 (57.5%) were obese. Hypertension (HTN) was diagnosed in 68.5% patients, dyslipidemia in 41.4% and DM2 in 4%. BMI z-score correlated positively with the duration of disease (r: 0.23, P=0.04), HOMA-IR (r:0.58, P<0.001), and negatively with age (r:-0.39, P=0.03). At the last follow up after cure HTN was present in 3.3%, dyslipidemia in 18.8%, whereas no patient had DM2. BMI z-score at last follow up was 1.2±1.1 (range:-1.5-2.8) and positively correlated with HOMA-IR (r: 0.54, P=0.01).Importantly, while overall the BMI z-score improved from pre-operative to post-cure values (2.0±0.7 to 1.2±1.1, P<0.001) a large percentage of patients remained overweight (24.6%) or obese (28.7%).

There were no differences in BMI, HTN, dyslipidemia and DM2 according to the etiology of CS or gender. The estimated cumulative frequency of achieving a normal weight by Kaplan-Meier curve reached 50% of patients at 16 months (95% CI: 3.93-28.06) and 62% at 25 months. Patients with normal weight at final follow up compared with those without it had shorter duration of hypercortisolism (2.1±2.2 vs 3.6±2.6 years, P=0.03), lower BMI z-score at diagnosis (2.0±0.4 vs 2.6±0.2, P<0.001), lower HOMA-IR (4.9±3.4 vs 36.6±9.7, P<0.006) and higher mean BMI z-score change at 6 months (0.8±0.7 vs 0.2±0.09, P<0.001) and at first visit after cure (1±0.6 vs 0.1±0.1, P<0.001). Cox regression analysis demonstrated that only the change of BMI z-score at 6 months was an independent predictor factor for reaching normal weight (HR: 3.73, 95% CI: 1.02- 12.85; P=0.03) with high accuracy when using a cutoff of 0.5 on ROC analysis (AUC= 0.87 (0.72-1, P<0.001).

Conclusions: Pediatric patients with CS had a great risk of remaining obese or overweight associated with an increase of insulin resistance despite improvements after cure of their CS. A decrease in BMI z-score of – 0.5 by 6 months post-operatively is highly predictive of reaching a normal BMI; thus, efforts should be focused in these early phases post surgery for healthy diet and lifestyle.

 

Nothing to Disclose: NV, AT, LC, MFK, EB, CAS, MBL