Original article
Vol. 148 No. 0506 (2018)
A ten-year follow-up study of treatment outcome of craniopharyngiomas
- Lukas Andereggen
- Benjamin Hess
- Robert H. Andres
- Marwan El-Koussy
- Luigi Mariani
- Andreas Raabe
- Rolf W. Seiler
- Emanuel Christ
Summary
PURPOSE
Craniopharyngioma-related hypothalamic obesity is a devastating complication with limited data on whether long-term follow-up should focus on problems other than endocrine deficiencies and weight gain. The primary endpoint was the assessment of predictors of hypothalamic obesity development; the secondary endpoint was the assessment of functional outcome (endocrine deficiencies, visual acuity) at long-term follow-up.
METHODS
This retrospective case-note study examined craniopharyngioma patients with at least 2 years of follow-up. Clinical, radiological and biochemical characteristics were assessed at diagnosis, postoperatively, and at last follow-up.
RESULTS
Thirty-two patients met the inclusion criteria. Median follow-up period was 9.8 years (range 2.2–33 years). Longitudinal changes in body mass index (BMI) were substantial (median ΔBMI/year was +0.48 kg/m2/year, interquartile range 0.28–1.33). The prevalence of patients with hypothalamic obesity had significantly increased at last follow-up (45 vs 4%; p = 0.003). Long-term pituitary deficiencies remained high. Diabetes insipidus was common (66% vs 34%, p<0.001), with postoperative diabetes insipidus but not hypothalamic involvement, being an independent predictor for hypothalamic obesity (odds ratio 15.2, 95% confidence interval 1.3–174.8, p = 0.03). Osteodensitometry in two thirds of patients at last follow-up revealed a pathological bone density in 53% of those tested.
CONCLUSIONS
Rates of hypothalamic obesity and long-term pituitary deficiencies are substantial, with postoperative diabetes insipidus being a potential marker for hypothalamic obesity development. Besides long-term monitoring of endocrine deficiencies with consideration of osteodensitometry, early weight control programmes and continuing multidisciplinary care are mandatory in craniopharyngioma patients.
References
- Hussain I, Eloy JA, Carmel PW, Liu JK. Molecular oncogenesis of craniopharyngioma: current and future strategies for the development of targeted therapies. J Neurosurg. 2013;119(1):106–12. doi:.https://doi.org/10.3171/2013.3.JNS122214
- Mortini P, Gagliardi F, Bailo M, Spina A, Parlangeli A, Falini A, et al. Magnetic resonance imaging as predictor of functional outcome in craniopharyngiomas. Endocrine. 2016;51(1):148–62. doi:.https://doi.org/10.1007/s12020-015-0683-x
- Roth CL, Eslamy H, Werny D, Elfers C, Shaffer ML, Pihoker C, et al. Semiquantitative analysis of hypothalamic damage on MRI predicts risk for hypothalamic obesity. Obesity (Silver Spring). 2015;23(6):1226–33. doi:.https://doi.org/10.1002/oby.21067
- Clark AJ, Cage TA, Aranda D, Parsa AT, Auguste KI, Gupta N. Treatment-related morbidity and the management of pediatric craniopharyngioma: a systematic review. J Neurosurg Pediatr. 2012;10(4):293–301. doi:.https://doi.org/10.3171/2012.7.PEDS11436
- Heymsfield SB, Avena NM, Baier L, Brantley P, Bray GA, Burnett LC, et al. Hyperphagia: current concepts and future directions proceedings of the 2nd international conference on hyperphagia. Obesity (Silver Spring). 2014;22(S1, Suppl 1):S1–17. doi:.https://doi.org/10.1002/oby.20646
- Wijnen M, Olsson DS, van den Heuvel-Eibrink MM, Wallenius V, Janssen JA, Delhanty PJ, et al. Efficacy and safety of bariatric surgery for craniopharyngioma-related hypothalamic obesity: a matched case-control study with 2 years of follow-up. Int J Obes. 2017;41(2):210–6. doi:.https://doi.org/10.1038/ijo.2016.195
- Must A, Anderson SE. Body mass index in children and adolescents: considerations for population-based applications. Int J Obes. 2006;30(4):590–4. doi:.https://doi.org/10.1038/sj.ijo.0803300
- Müller HL. Craniopharyngioma and hypothalamic injury: latest insights into consequent eating disorders and obesity. Curr Opin Endocrinol Diabetes Obes. 2016;23(1):81–9. doi:.https://doi.org/10.1097/MED.0000000000000214
- Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, et al. Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome. Neurosurgery. 1994;35(6):1001–10, discussion 1010–1. doi:.https://doi.org/10.1227/00006123-199412000-00001
- Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code Biol Med. 2008;3(1):17. doi:.https://doi.org/10.1186/1751-0473-3-17
- Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol. 1989;129(1):125–37. doi:.https://doi.org/10.1093/oxfordjournals.aje.a115101
- Khan MJ, Humayun KN, Donaldson M, Ahmed SF, Shaikh MG. Longitudinal changes in body mass index in children with craniopharyngioma. Horm Res Paediatr. 2014;82(6):372–9. doi:.https://doi.org/10.1159/000368798
- Andereggen L, Frey J, Andres RH, El-Koussy M, Beck J, Seiler RW, et al. Long-term follow-up of primary medical versus surgical treatment of prolactinomas in men: Effects on hyperprolactinemia, hypogonadism and bone health. World Neurosurg. 2017;97:595–602. doi:.https://doi.org/10.1016/j.wneu.2016.10.059
- Müller HL, Gebhardt U, Teske C, Faldum A, Zwiener I, Warmuth-Metz M, et al.; Study Committee of KRANIOPHARYNGEOM 2000. 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(1):17–24. doi:.https://doi.org/10.1530/EJE-11-0158
- Bretault M, Boillot A, Muzard L, Poitou C, Oppert JM, Barsamian C, et al. Clinical review: Bariatric surgery following treatment for craniopharyngioma: a systematic review and individual-level data meta-analysis. J Clin Endocrinol Metab. 2013;98(6):2239–46. doi:.https://doi.org/10.1210/jc.2012-4184
- Elowe-Gruau E, Beltrand J, Brauner R, Pinto G, Samara-Boustani D, Thalassinos C, et al. Childhood craniopharyngioma: hypothalamus-sparing surgery decreases the risk of obesity. J Clin Endocrinol Metab. 2013;98(6):2376–82. doi:.https://doi.org/10.1210/jc.2012-3928
- Lustig RH, Post SR, Srivannaboon K, Rose SR, Danish RK, Burghen GA, et al. Risk factors for the development of obesity in children surviving brain tumors. J Clin Endocrinol Metab. 2003;88(2):611–6. doi:.https://doi.org/10.1210/jc.2002-021180
- Sterkenburg AS, Hoffmann A, Gebhardt U, Warmuth-Metz M, Daubenbüchel AM, Müller HL. Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes. Neuro-oncol. 2015;17(7):1029–38. doi:.https://doi.org/10.1093/neuonc/nov044
- Karavitaki N, Brufani C, Warner JT, Adams CB, Richards P, Ansorge O, et al. Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up. Clin Endocrinol (Oxf). 2005;62(4):397–409. doi:.https://doi.org/10.1111/j.1365-2265.2005.02231.x
- Van Effenterre R, Boch AL. Craniopharyngioma in adults and children: a study of 122 surgical cases. J Neurosurg. 2002;97(1):3–11. doi:.https://doi.org/10.3171/jns.2002.97.1.0003
- Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, et al.; West Midlands Prospective Hypopituitary Study Group. Association between premature mortality and hypopituitarism. Lancet. 2001;357(9254):425–31. doi:.https://doi.org/10.1016/S0140-6736(00)04006-X
- Patel KS, Raza SM, McCoul ED, Patrona A, Greenfield JP, Souweidane MM, et al. Long-term quality of life after endonasal endoscopic resection of adult craniopharyngiomas. J Neurosurg. 2015;123(3):571–80. doi:.https://doi.org/10.3171/2014.12.JNS141591
- Lee MJ, Hwang JM. Initial visual field as a predictor of recurrence and postoperative visual outcome in children with craniopharyngioma. J Pediatr Ophthalmol Strabismus. 2012;49(1):38–42. doi:.https://doi.org/10.3928/01913913-20110208-03
- Drimtzias E, Falzon K, Picton S, Jeeva I, Guy D, Nelson O, et al. The ophthalmic natural history of paediatric craniopharyngioma: a long-term review. J Neurooncol. 2014;120(3):651–6. doi:.https://doi.org/10.1007/s11060-014-1600-5
- Kyvernitakis I, Saeger U, Ziller V, Bauer T, Seker-Pektas B, Hadji P. The effect of age, sex hormones, and bone turnover markers on calcaneal quantitative ultrasonometry in healthy German men. J Clin Densitom. 2013;16(3):320–8. doi:.https://doi.org/10.1016/j.jocd.2013.01.009
- Boot AM, van der Sluis IM, Krenning EP, de Muinck Keizer-Schrama SM. Bone mineral density and body composition in adolescents with childhood-onset growth hormone deficiency. Horm Res. 2009;71(6):364–71.
- Shalet SM, Shavrikova E, Cromer M, Child CJ, Keller E, Zapletalová J, et al. Effect of growth hormone (GH) treatment on bone in postpubertal GH-deficient patients: a 2-year randomized, controlled, dose-ranging study. J Clin Endocrinol Metab. 2003;88(9):4124–9. doi:.https://doi.org/10.1210/jc.2003-030126
- Hamrick MW, Ferrari SL. Leptin and the sympathetic connection of fat to bone. Osteoporos Int. 2008;19(7):905–12. doi:.https://doi.org/10.1007/s00198-007-0487-9
- Roth C, Wilken B, Hanefeld F, Schröter W, Leonhardt U. Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite. Eur J Endocrinol. 1998;138(1):89–91. doi:.https://doi.org/10.1530/eje.0.1380089
- do Prado WL, de Piano A, Lazaretti-Castro M, de Mello MT, Stella SG, Tufik S, et al. Relationship between bone mineral density, leptin and insulin concentration in Brazilian obese adolescents. J Bone Miner Metab. 2009;27(5):613–9. doi:.https://doi.org/10.1007/s00774-009-0082-6
- Fu L, Patel MS, Bradley A, Wagner EF, Karsenty G. The molecular clock mediates leptin-regulated bone formation. Cell. 2005;122(5):803–15. doi:.https://doi.org/10.1016/j.cell.2005.06.028
- Albright AL, Hadjipanayis CG, Lunsford LD, Kondziolka D, Pollack IF, Adelson PD. Individualized treatment of pediatric craniopharyngiomas. Childs Nerv Syst. 2005;21(8-9):649–54. doi:.https://doi.org/10.1007/s00381-005-1185-6
- Puget S, Garnett M, Wray A, Grill J, Habrand JL, Bodaert N, et al. Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg. 2007;106(1, Suppl):3–12.
- Ali ZS, Bailey RL, Daniels LB, Vakhshori V, Lewis DJ, Hossain AT, et al. Comparative effectiveness of treatment options for pediatric craniopharyngiomas. J Neurosurg Pediatr. 2014;13(2):178–88. doi:.https://doi.org/10.3171/2013.11.PEDS1320
- Hoffmann A, Warmth-Metz M, Gebhardt U, Pietsch T, Pohl F, Kortmann RD, et al. Childhood craniopharyngioma - changes of treatment strategies in the trials KRANIOPHARYNGEOM 2000/2007. Klin Padiatr. 2014;226(3):161–8. doi:.https://doi.org/10.1055/s-0034-1368785
- Gautier A, Godbout A, Grosheny C, Tejedor I, Coudert M, Courtillot C, et al.; Craniopharyngioma Study Group. Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients. J Clin Endocrinol Metab. 2012;97(4):1258–67. doi:.https://doi.org/10.1210/jc.2011-2817
- Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, Thorner AR, et al. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet. 2014;46(2):161–5. doi:.https://doi.org/10.1038/ng.2868