Pediatric Cushing’s syndrome: greater risk of being overweight or obese after long-term remission and its predictive factors

in European Journal of Endocrinology
View More View Less
  • 1 Section on Endocrinology and Genetics, Developmental Endocrinology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
  • 2 Section on Endocrinology and Nutrition, Hospital Universitario de Cabueñes, Gijón, Spain
  • 3 Neuroendocrine Tumors Service, Division of Endocrinology, Metabolism and Diabetes, Chaim Sheba Medical Center, Tel Aviv, Israel
  • 4 University of California, San Francisco, California, USA

Correspondence should be addressed to N Valdés; Email: nuria.valdesg@sespa.es
Restricted access

Objective

Due to the rarity of Cushing’s syndrome (CS) in children and adolescents, data are scarce about BMI during active disease and following remission. Therefore, our aim was to analyze BMI after long-term remission and determine predictive factors for promptly identifying patients at risk of being overweight or obese after remission for CS.

Design

Retrospective cohort study.

Patients

73 patients: 58 (79.4%) had Cushing disease, 40 males (58%), median age of 12 years (IQR: 9–15). The mean follow-up time was 22.4 ± 18.2 months (range: 4–98).

Methods

Main outcome measures: BMI, lipid profile, blood pressure, HOMA-IR.

Results

At diagnosis, only eight (11%) patients had a normal weight. Although the BMI z-score at the last follow-up improved (2.0 ± 0.7 to 1.0 ± 1.2, P < 0.001), 44% remained overweight or obese after 2 years of remission according to the Kaplan-Meier curves. The BMI z-scores at the last follow-up correlated only with HOMA-IR levels (r: 0.49, P = 0.027). We found two independent factors related to reaching a normal weight: BMI z-score at diagnosis (HR: 0.156, 95% CI: 0.038–0.644; P = 0.01) and BMI z-score change at 6 ± 2 months (HR: 2.980, 95% CI:1.473–6.028; P = 0.002), which had high accuracy when a cut-off of 0.5 was used for ROC analysis (AUC = 0.828 (0.67–0.97); P < 0.001).

Conclusions

Children and adolescents with CS have a high risk of being overweight or obese after successful treatment for their disease. At risk patients can be identified quickly based on their baseline BMI and initial weight loss after surgery. Efforts should focus on adopting healthy diet and lifestyle in the immediate postoperative period.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 362 362 141
Full Text Views 88 88 62
PDF Downloads 56 56 35
  • 1

    Hales CM, Carroll MD, Fryar CD & Ogden CL Prevalence of obesity among adults and youth: United States, 2015–2016. NCHS Data Brief 2017 288 18.

  • 2

    Freedman DS, Mei Z, Srinivasan SR, Berenson GS & Dietz WH Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa heart study. Journal of Pediatrics 2007 150 12 .e217.e2. (https://doi.org/10.1016/j.jpeds.2006.08.042)

    • Search Google Scholar
    • Export Citation
  • 3

    Amin R & Daniels S Relationship between obesity and sleep-disordered breathing in children: is it a closed loop? Journal of Pediatrics 2002 140 641643. (https://doi.org/10.1067/mpd.2002.125255)

    • Search Google Scholar
    • Export Citation
  • 4

    Freedman DS, Kettel Khan LK, Serdula MK, Dietz WH, Srinivasan SR & Berenson GS The relation of childhood BMI to adult adiposity: the Bogalusa heart study. Pediatrics 2005 115 2227. (https://doi.org/10.1542/peds.2004-0220)

    • Search Google Scholar
    • Export Citation
  • 5

    Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH & Looker HC Childhood obesity, other cardiovascular risk factors, and premature death. New England Journal of Medicine 2010 362 4854 93. (https://doi.org/10.1056/NEJMoa0904130)

    • Search Google Scholar
    • Export Citation
  • 6

    Lupoli R, Ambrosino P, Tortora A, Barba L, Lupoli GA & Di Minno MN Markers of atherosclerosis in patients with Cushing’s syndrome: a meta‐analysis of literature studies. Annals of Medicine 2017 49 206216. (https://doi.org/10.1080/07853890.2016.1252055)

    • Search Google Scholar
    • Export Citation
  • 7

    Ferraù F & Korbonits M Metabolic comorbidities in Cushing’s syndrome. European Journal of Endocrinology 2015 173 M133M157. (https://doi.org/10.1530/EJE-15-0354)

    • Search Google Scholar
    • Export Citation
  • 8

    Lodish MB, Sinaii N, Patronas N, Batista DL, Keil M, Samuel J, Moran J, Verma S, Popovic J & Stratakis CA Blood pressure in paediatric patients with Cushing syndrome. Journal of Clinical Endocrinology and Metabolism 2009 94 2002200 8. (https://doi.org/10.1210/jc.2008-2694)

    • Search Google Scholar
    • Export Citation
  • 9

    Libuit LG, Karageorgiadis AS, Sinaii N, Nguyen N, Keil MF, Lodish MB & Stratakis CA A gender-dependent analysis of Cushing’s disease in childhood: pre- and postoperative follow-up. Clinical Endocrinology 2015 83 7277.

    • Search Google Scholar
    • Export Citation
  • 10

    Leong GM, Abad V, Charmandari E, Reynolds JC, Hill S, Chrousos GP & Nieman LK Effects of child- and adolescent-onset: endogenous Cushing syndrome on bone mass, body composition, and growth: a 7-year prospective study Into young adulthood. Journal of Bone and Mineral Research 2006 22 11011 8. (https://doi.org/10.1359/jbmr.061010)

    • Search Google Scholar
    • Export Citation
  • 11

    Güemes M, Murray PG, Brain CE, Spoudeas HA, Peters CJ, Hindmarsh PC & Dattani MT Management of Cushing syndrome in children and adolescents: experience of a single tertiary centre. European Journal of Pediatrics 2016 175 9679 76. (https://doi.org/10.1007/s00431-016-2727-5)

    • Search Google Scholar
    • Export Citation
  • 12

    Davies JH, Storr HL, Davies K, Monson JP, Besser GM, Afshar F, Plowman PN, Grossman AB & Savage MO Final adult height and body mass index after cure of paediatric Cushing’s disease. Clinical Endocrinology 2005 62 4664 72. (https://doi.org/10.1111/j.1365-2265.2005.02244.x)

    • Search Google Scholar
    • Export Citation
  • 13

    Keil MF, Graf J, Gokarn N & Stratakis CA Anthropometric measures and fasting insulin levels in children before and after cure of Cushing syndrome. Clinical Nutrition 2012 31 3593 63. (https://doi.org/10.1016/j.clnu.2011.11.007)

    • Search Google Scholar
    • Export Citation
  • 14

    Holst JM, Horváth-Puhó E, Jensen RB, Rix M, Kristensen K, Herte NT, Dekkers OM, Sørensen HT, Juul A & Jørgensen JOL Cushing’s syndrome in children and adolescents: a Danish nationwide population-based cohort study. European Journal of Endocrinology 2017 176 5675 74. (https://doi.org/10.1530/EJE-16-0843)

    • Search Google Scholar
    • Export Citation
  • 15

    Batista DL, Riar J, Keil M & Stratakis CA Diagnostic tests for children who are referred for the investigation of Cushing syndrome. Pediatrics 2007 120 e575e586. (https://doi.org/10.1542/peds.2006-2402)

    • Search Google Scholar
    • Export Citation
  • 16

    Lodish M, Dunn SV, Sinaii N, Keil MF & Stratakis CA Recovery of the hypothalamic-pituitary-adrenal axis in children and adolescents after surgical cure of Cushing’s disease. Journal of Clinical Endocrinology and Metabolism 2012 97 148314 91. (https://doi.org/10.1210/jc.2011-2325)

    • Search Google Scholar
    • Export Citation
  • 17

    Centers for Disease Control and Prevention. National Center for Health Statistics. (available at: http://www.cdc.gov/growthcharts/). Accessed on 13 September 2016.

  • 18

    Ogden CL & Flegal KM Changes in terminology for childhood overweight and obesity. National Health Statistics Reports 2010 50 15.

  • 19

    Wright CM, Parker L, Lamont D & Craft AW Implications of childhood obesity for adult health: findings from thousand families cohort study. BMJ 2001 323 128012 84. (https://doi.org/10.1136/bmj.323.7324.1280)

    • Search Google Scholar
    • Export Citation
  • 20

    National Heart Lung and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Paediatrics 2011 128 S213S2 56.

    • Search Google Scholar
    • Export Citation
  • 21

    Standards of Medical Care in Diabetes – 2016. Classification and diagnosis of diabetes. Diabetes Care 2016 39 S13S23.

  • 22

    Ogden CL, Carroll MD, Kit BK & Flegal KM Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 2014 311 8068 14. (https://doi.org/10.1001/jama.2014.732)

    • Search Google Scholar
    • Export Citation
  • 23

    Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK & Flegal KM Trends in obesity prevalence among children and adolescents in the United States, 1988–1994 through 2013–2014. JAMA 2016 315 229222 99. (https://doi.org/10.1001/jama.2016.6361)

    • Search Google Scholar
    • Export Citation
  • 24

    Skinner AC, Perrin EM, Moss LA & Skelton JA Cardiometabolic risks and severity of obesity in children and young adults. New England Journal of Medicine 2015 373 13071317. (https://doi.org/10.1056/NEJMoa1502821)

    • Search Google Scholar
    • Export Citation
  • 25

    Mancini T, Kola B, Mantero F, Boscaro M & Arnaldi G High cardiovascular risk in patients with Cushing’s syndrome according to 1999 WHO/ISH Guidelines. Clinical Endocrinology 2004 61 768777.

    • Search Google Scholar
    • Export Citation
  • 26

    Barahona MJ, Sucunza N, Resmini E, Fernández-Real JM, Ricart W, Moreno-Navarrete JM, Puig T, Farrerons J & Webb SM Persistent body fat mass and inflammatory marker increases after long-term cure of Cushing’s syndrome. Journal of Clinical Endocrinology and Metabolism 2009 94 336533 71. (https://doi.org/10.1210/jc.2009-0766)

    • Search Google Scholar
    • Export Citation
  • 27

    Bacha F, Saad R, Gungor N & Arslanian SA Are obesity-related metabolic risk factors modulated by the degree of insulin resistance in adolescents? Diabetes Care 2006 29 15991604. (https://doi.org/10.2337/dc06-0581)

    • Search Google Scholar
    • Export Citation
  • 28

    Sinaiko AR, Steinberger J, Moran A, Prineas RJ, Vessby B, Basu S, Tracy R & Jacobs DR Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence. Circulation 2005 111 198519 91. (https://doi.org/10.1161/01.CIR.0000161837.23846.57)

    • Search Google Scholar
    • Export Citation
  • 29

    Braet C Patient characteristics as predictors of weight loss after an obesity treatment for children. Obesity 2006 14 1481 55. (https://doi.org/10.1038/oby.2006.18)

    • Search Google Scholar
    • Export Citation
  • 30

    Gow ML, Baur LA, Ho M, Chisholm K, Noakes M, Cowell CT & Garnett SP Can early weight loss, eating behaviors and socioeconomic factors predict successful weight loss at 12- and 24-months in adolescents with obesity and insulin resistance participating in a randomized controlled trial ? International Journal of Behavioral Nutrition and Physical Activity 2016 13 4343. (https://doi.org/10.1186/s12966-016-0367-9)

    • Search Google Scholar
    • Export Citation
  • 31

    Gross AC, Kaizer AM, Kelly AS, Rudser KD, Ryder JR, Borzutzky CR, Santos M, Tucker JM, Yee JK, Fox CKet al. Long and short of it: early response predicts longer-term outcomes in paediatric weight management. Obesity 2019 27 272279. (https://doi.org/10.1002/oby.22367)

    • Search Google Scholar
    • Export Citation