Bariatric Interventions in Craniopharyngioma Patients—Best Choice or Last Option for Treatment of Hypothalamic Obesity?
Hermann L. Müller
Abstract
Although craniopharyngiomas are of low-grade histological quality and have good prognosis in terms of overall survival, long-term survivors frequently suffer from severe morbidity due to hypothalamic lesions (1). Imbalances of thirst and hunger-satiety feelings, problems of psychosocial behavior, disturbed circadian rhythm, reduced energy expenditure, pituitary deficits, and dysregulation of temperature are caused by disease and/or treatment-related hypothalamic lesions. Affected patients are at great risk for developing hypothalamic disorders of body composition such as obesity and cachexia, with comorbidities leading to premature mortality (2). Cachexia and severe weight loss due to diencephalic syndrome can occur as a rare hypothalamic disturbance of body composition in craniopharyngioma patients with hypothalamic damage. Diencephalic syndrome and cachexia at the time of craniopharyngioma diagnosis are rare (4%; ie, 21 of 485 cases recruited in KRANIOPHARYNGEOM 2000/2007). However, also in craniopharyngioma patients with diencephalic syndrome, subsequent weight gain and obesity were observed during long-term follow-up (3). Tumor- and/or treatment-associated lesions of specific posterior hypothalamic areas (ie, the mammillary bodies and the area beyond) are risk factors for the development of severe obesity and reduced long-term quality of life. A combination of hypothalamus-sparing surgical intervention and irradiation, preferably by proton beam therapy, has been shown to be effective in control of residual craniopharyngioma associated with less hypothalamic morbidity. Long-term outcome data after proton beam therapy are rare, due to the restricted availability of proton beam therapy to only few centers. The advantages of proton beam therapy based on physical characteristics of proton beam radiation include improved conformation of dose to the target volume, reduction of integral dose and of secondary neutrons, and lower risk of second malignancies by sparing of critical structures. The morbid obesity in craniopharyngioma patients with hypothalamic involvement/lesion is the result of impairment in satiety regulation, a reduced level of energy expenditure, and a downregulation of sympathetic activity. Due to this, craniopharyngioma patients develop an overactivation of their parasympathetic systems, which leads to increased daytime sleepiness, disturbed temperature regulation, and reduced heart rate. Hypothalamic obesity is mostly unresponsive to conventional interventions, such as lifestyle modifications. Accordingly, pharmacological interventions might have beneficial effects on the degree of obesity. Reported pharmacotherapeutic interventions for hypothalamic obesity include antidiabetic agents (metformin, diazoxide, fenofibrate), central stimulating agents (dextro-amphetamine, methylphenidate), hypothalamic-pituitary substitution therapy (recombinant growth hormone, thyroxine, hydrocortisone), and others, such as oxytocin or somatostatin analogues (octreotide). The reported effects are often transient and generally modest. Due to the lack of randomized controlled trials, there is currently no consensus on pharmacotherapy of hypothalamic obesity in craniopharyngioma patients. Several surgical techniques of bariatric interventions such as sleeve gastrectomy (SG), laparoscopic adjustable gastric banding (LAGB), biliopancreatic diversion, gastric bypass, and Roux-en-Y gastric bypass (RYGB) have been reported for treatment of severe hypothalamic obesity in craniopharyngioma patients. In a review of treatment strategies for hypothalamic obesity, van Iersel et al (4) analyzed the response to different bariatric procedures in craniopharyngioma patients and observed that 19 of 24 (79%) patients achieved a weight loss after bariatric intervention. The specific rate of responders to bariatric procedures was 0% (0 of 4) for LAGB, 100% (6 of 6) for SG, and 93% (13 of 14) for gastric bypass. Two nonresponders to bariatric interventions were observed: 1 patient after SG and 1 patient after RYGB. Van Santen et al (5) recently compared the effects and tolerability of 2 options for bariatric surgery (SG and RYGB) in craniopharyngioma patients suffering from hypothalamic obesity with body mass index–matched controls in a retrospective case-control study. No major changes in endocrine replacement therapy were observed after bariatric surgery. One patient died of unknown cause. One patient had long-term absorptive problems. Obese patients with craniopharyngioma had a substantial mean weight loss of 22% at 5 years after bariatric surgery, independent of type of bariatric surgery procedure. Weight loss was lower than in obese controls after RYGB. The authors conclude that bariatric surgery appears to be effective and relatively safe in the treatment of obese craniopharyngioma patients. This is the first study on the long-term effects of SG and RYGB in craniopharyngioma patients and matched controls. Different degrees of weight loss after various bariatric procedures in craniopharyngioma patients may be related to gastrointestinal hormones, especially glucagon-like peptide 1 (GLP-1). A significant increase in GLP-1 serum concentrations is observed in craniopharyngioma patients after RYGB when compared with other restrictive bariatric procedures (6). The hypothesis that increased GLP-1 levels after bariatric interventions will be associated with weight loss was analyzed in a small cohort of patients with craniopharyngioma (7). Only after RYGB, increased GLP-1 serum concentrations were observed but not after SG. In pediatric craniopharyngioma patients, experiences with bariatric interventions are limited. Accordingly, bariatric procedures in pediatric craniopharyngioma patients—especially irreversible techniques—are controversially discussed for medical, ethical, and legal reasons in this specific age group. In the current Endocrine Society’s Clinical Practice Guideline for treatment of pediatric obesity, only adolescents with morbid obesity and advanced pubertal development, who have reached near final or final height and who demonstrate the ability to adhere to the principles of healthy dietary and activity habits, should be considered for bariatric interventions (8). The decision for bariatric treatment should be made by an experienced multidisciplinary team based on individual patient criteria. Postoperative complications after bariatric surgery include iron-deficiency anemia, diarrhea, abdominal pain, and dumping syndrome after RYGB; folic acid and vitamin D deficiency, impaired effectiveness of oral desmopressin medication after SG; and abdominal discomfort, dysphagia, vomiting, banding readjustment, and device explantation after LAGB. Craniopharyngioma should be considered as a chronic disease due to severe sequelae mainly caused by disease or treatment-related consequences of hypothalamic damage. Prevention of hypothalamic obesity is most effective, thus hypothalamus-sparing therapeutic strategies are the best option in craniopharyngioma patients with regard to long-term quality of life. Bariatric interventions are effective—with highest weight loss after RYGB—and safe. However, similar to other treatment modalities, the decision on bariatric intervention should also be made by an experienced multidisciplinary team in the context of national/international trials. Sufficient and experienced long-term follow-up care is mandatory after bariatric procedures. glucagon-like peptide-1 laparoscopic adjustable gastric banding Roux-en-Y gastric bypass sleeve gastrectomy Disclosures: The author has received reimbursement of participation fees for scientific meetings and continuing medical education events from the following companies: Ferring, Lilly, Pfizer, Sandoz/Hexal, Novo Nordisk, Ipsen, and Merck Serono. He has received reimbursement of travel expenses from Ipsen and lecture honoraria from Pfizer. Hermann L. Müller is supported by the German Childhood Cancer Foundation, Bonn, Germany. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.