Abstract
Aim: To evaluate auxology and metabolic disturbances in children with craniopharyngioma, and to present observational results of treatment of metabolic sequels with metformin and micronized fenofibrate.
Methods: The studied group comprised 22 children [median age at diagnosis 10.5 (0.17–16.75) years; median follow-up 5.1 years]. Assessment included height standard deviations (SDS), body mass index (BMI) SDS, concentrations of lipids, glucose and insulin (fasting or oral glucose tolerance test) and homeostatic model assessment of insulin resistance (HOMA-IR) index. Ten adolescents with hyperinsulinemia and dyslipidemia received therapy with metformin (500–1500 mg/daily) and micronized fenofibrate (160 mg/daily).
Results: At diagnosis, median hSDS was –1.66 (range: –4.08; +0.1). Nine (40.9%) children were growth hormone-treated. There was gradual increase of BMI SDS, 18 (81.8%) patients being overweight at the final assessment. Dyslipidaemia was found in 19 patients (86.4%), hyperinsulinaemia in 11 patients (50%) and elevated HOMA-IR in 15 patients (68.2%). Decrease of triglycerides [median 263.5 (171–362) mg/dL vs. 154 (102–183) mg/dL] and HOMA-IR [8.64 (5.08–12.65) vs. 4.68 (0.7–7.9)] was significant in the group treated with metformin and fenofibrate for 6 months.
Conclusions: Significant auxologic changes and metabolic abnormalities were found in children treated for craniopharyngioma. The use of metformin and fenofibrate seemed to attenuate these disturbances in a short-term observation.
References
1. Haupt R, Magnani C, Pavanello M, Caruso S, Dama E, et al. Epidemiological aspects of craniopharyngioma. J Pediatr Endocrinol Metab 2006;19(Suppl 1):289–93.Search in Google Scholar
2. Müller HL. Craniopharyngioma. Endocr Rev 2014;35:513–43.10.1210/er.2013-1115Search in Google Scholar PubMed
3. Karavitaki N, Cudlip S, Adams CB, Wass JA. Craniopharyngiomas. Endocr Rev 2006;27:371–97.10.1210/er.2006-0002Search in Google Scholar PubMed
4. Halac I, Zimmerman D. Endocrine manifestation of craniopharyngioma. Child Nerv Syst 2005;21:640–8.10.1007/s00381-005-1246-xSearch in Google Scholar PubMed
5. Gungor N, Saad R, Janosky J, Arslanian S. Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J Pediatr 2004;44:47–55.10.1016/j.jpeds.2003.09.045Search in Google Scholar PubMed
6. Kalina MA, Skała-Zamorowska E, Kalina-Faska B, Małecka-Tendera E, Mandera M. Practical approach to childhood craniopharyngioma: a role of an endocrinologist and a general paediatrician. Child Nerv Syst 2009;25:1053–60.10.1007/s00381-009-0931-6Search in Google Scholar PubMed
7. Cizmecioglu FM, Hatun S, Kalaca S. Metabolic syndrome in obese Turkish children and adolescents: comparison of two diagnostic models. Turk J Pediatr 2008;50:359–65.Search in Google Scholar
8. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011;128(Suppl 5):S213–56.10.1542/peds.2009-2107CSearch in Google Scholar PubMed PubMed Central
9. Müller HL, Emser A, Faldum A, Bruhnken G, Etavard-Goris N, et al. Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. J Clin Endocrinol Metab 2004;89:3298–305.10.1210/jc.2003-031751Search in Google Scholar PubMed
10. Phillip M, Moran O, Lazar L. Growth without growth hormone. J Pediatr Endocrinol Metab 2002;15(Suppl 5):1267–72.Search in Google Scholar
11. Pinto G, Bussieres L, Recasens C, Souberbielle JC, Zerah M, et al. Hormopnal factors influencing weight and growth pattern in craniopharyngioma. Horm Res 2000;53:163–9.Search in Google Scholar
12. Srinivasan S, Ogle GD, Garnett SP, Briody JN, Lee JW, et al. Features of the metabolic syndrome after childhood craniopharyngioma. J Clin Endocrinol Metab 2004;89:81–6.10.1210/jc.2003-030442Search in Google Scholar PubMed
13. Müller HL, Gebhardt U, Teske C, Faldum A, Zwiener I, et al. Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up. Eur J Endocrinol 2011;165:17–24.10.1530/EJE-11-0158Search in Google Scholar PubMed
14. Lustig RH, Post SR, Srivannaboon K, Rose SR, Danish RK, et al. Risk factors for development of obesity in children surviving brain tumors. J Clin Endocrinol Metab 2003;88:611–6.10.1210/jc.2002-021180Search in Google Scholar PubMed
15. Lustig RH. Hypothalamic obesity after craniopharyngioma: mechanism, diagnosis, and treatment. Front Endocrinol (Lausanne) 2011;2:60.10.3389/fendo.2011.00060Search in Google Scholar PubMed PubMed Central
16. Poretti A, Grotzer MA, Ribi K, Schönle E, Boltshauser E. Outcome of craniopharyngioma in children: long-term complications and quality of life. Dev Med Child Neurolol 2004;46:220–9.10.1111/j.1469-8749.2004.tb00476.xSearch in Google Scholar
17. Harz KJ, Müller HL, Waldeck E, Pudel V, Roth C. Obesity in patients with craniopharyngioma: assessment of food intake and movement counts indicating physical activity. J Clin Endocrinol Metab 2003;88:5227–31.10.1210/jc.2002-021797Search in Google Scholar PubMed
18. Roth CL, Hunneman DH, Gebhardt U, Stoffel-Wagner B, Reinehr T, et al. Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. Pediatr Res 2007;61:496–501.10.1203/pdr.0b013e3180332cd6Search in Google Scholar PubMed
19. Coutant R, Maurey H, Rouleau S, Mathieu E, Mercier P, et al. A defect in epinephrine production in children with craniopharyngioma, functional or organic origin? J Clin Endocrinol Metab 2003;88:5969–75.10.1210/jc.2003-030552Search in Google Scholar PubMed
20. Kreier F, Fliers E, Voshol PJ, van Eden CG, Havekes LM, et al. Selective parasympathetic innervations of subcutaneous and intra-abdominal fat-functional implications. J Clin Invest 2002;110:1243–50.10.1172/JCI0215736Search in Google Scholar
21. Bramnert M, Segerlanz M, Laurila E, Daugaard JR, Manhem P, et al. Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle. J Clin Endocrinol Metab 2003;88:1455–63.10.1210/jc.2002-020542Search in Google Scholar PubMed
22. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modelling. Diabetes Care 2004;27:1487–95.10.2337/diacare.27.6.1487Search in Google Scholar PubMed
23. Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, et al. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab 2004;89:1096–101.10.1210/jc.2003-031503Search in Google Scholar PubMed
24. Trivin C, Busiah K, Mahlaoui N, Recasens C, Souberbielle JC, et al. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index. BMC Pediatr 2009;9:24.10.1186/1471-2431-9-24Search in Google Scholar PubMed PubMed Central
25. Sahakitrungruang T, Klomchan T, Supornsilchai V, Wacharasindhu S. Obesity, metabolic syndrome, and insulin dynamics in children after craniopharyngioma surgery. Eur J Pediatr 2011;170:763–9.10.1007/s00431-010-1347-8Search in Google Scholar PubMed
26. Simoneau-Roy J, O’Gorman C, Pencharz P, Adeli K, Daneman D, et al. Insulin sensitivity and secretion in children and adolescents with hypothalamic obesity following treatment for craniopharyngioma. Clin Endocrinol (Oxf) 2010;72:364–70.10.1111/j.1365-2265.2009.03639.xSearch in Google Scholar PubMed
27. Adachi M, Tsuchiya T, Muroya K, Asakura Y, Sekido K, et al. Prevalence of obesity, hyperlipemia and insulin resistance in children with suprasellar brain tumors. Clin Pediatr Endocrinol 2007;16:1–9.10.1297/cpe.16.1Search in Google Scholar PubMed PubMed Central
28. Crowley RK, Hamnvik OP, O’Sullivan EP, Behan LA, Smith D, et al. Morbidity and mortality in patients with craniopharyngioma after surgery. Clin Endocrinol (Oxf) 2010;73:516–21.10.1111/j.1365-2265.2010.03838.xSearch in Google Scholar PubMed
29. Mason PW, Krawiecki N, Meacham LR. The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma. Arch Pediatr Adolesc Med 2002;156:887–92.10.1001/archpedi.156.9.887Search in Google Scholar PubMed
30. Miller BS, Aydin F, Lundgren A, Geffner ME. Stimulant use and its impact on growth in children receiving growth hormone therapy: an analysis of the KIGS International Growth database. Horm Res Pediatr 2014;82:31–7.10.1159/000360005Search in Google Scholar PubMed
31. Danielsson P, Janson A, Norgren S, Marcus C. Impact sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes. J Clin Endocrinol Metab 2007;92:4101–6.10.1210/jc.2007-0826Search in Google Scholar PubMed
32. Lustig RH, Hinds PS, Ringwald-Smith K, Christensen RK, Kaste SC, et al. Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab 2003;88:2586–92.10.1210/jc.2002-030003Search in Google Scholar PubMed
33. Hamilton JK, Conwell LS, Syme C, Ahmet A, Jeffery A, et al. Hypothalamic obesity following craniopharyngioma surgery: results of a pilot trial of combined diazoxide and metformin therapy. Int J Pediatr Endocrinol 2011;2011:417949.10.1155/2011/417949Search in Google Scholar PubMed PubMed Central
34. Elijah IE, Børsheim E, Maybauer DM, Finnerty CC, Herndon DN, et al. Role of the PPAR-α agonist fenofibrate in severe pediatric burn. Burns 2012:38:481–6.10.1016/j.burns.2011.12.004Search in Google Scholar PubMed PubMed Central
35. Wysocki J, Belowski D, Kalina M, Kochański L, Okopien B, et al. Effects of micronized fenofibrate on insulin resistance in patients with metabolic syndrome. Int J Clin Pharmacol Ther 2004;42:212–7.10.5414/CPP42212Search in Google Scholar
36. Robinson NJ, Campigotto F, Chi SN, Manley PE, Turner CD, et al. A phase II trial of a multiagent oral antiangiogenic (metrnomic) regimen in children with recurrent or progressive cancer. Pediatr Blood Cancer 2014;61:636–42.10.1002/pbc.24794Search in Google Scholar PubMed PubMed Central
37. Kostapanos MS, Kei A, Elisaf MS. Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease. World J Hepatol 2013;5:470–8.10.4254/wjh.v5.i9.470Search in Google Scholar PubMed PubMed Central
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