Gastric Bypass Surgery for Treatment of Hypothalamic Obesity after Craniopharyngioma Therapy

Thomas H Inge; * Paul Pfluger; Meg Zeller; Susan R Rose; Lukas Burget; Sumana Sundararajan; Stephen R Daniels; Matthias H Tschöp

Disclosures

Nat Clin Pract Endocrinol Metab. 2007;3(8):606-609. 

In This Article

Summary and The Case

Summary

Background A 14-year-old boy presented with daytime somnolence, intermittent emesis and hypothyroidism. Neuroimaging revealed a calcified suprasellar intracranial mass, suspected to be a craniopharyngioma. Subtotal resection of the tumor confirmed the diagnosis. Extreme obesity (BMI >60 kg/m2) and hyperinsulinemia followed tumor resection and cranial irradiation. Dietary interventions were unsuccessful, and pharmacologic intervention (i.e. octreotide) only slowed the rate of weight gain.
Investigations Radiography documented the suprasellar mass. Following surgical resection and radiotherapy, hypothalamic–pituitary deficiencies were found. Preprandial and postprandial excursions of insulin, active ghrelin and leptin were measured before and after gastric bypass surgery.
Diagnosis Panhypopituitarism, hypothalamic obesity and hyperinsulinemia following craniopharyngioma therapy.
Management Severe caloric restriction, octreotide, and pituitary hormone replacement did not produce weight loss. Gastric bypass surgery led to reduced food cravings, significant weight loss, and amelioration of obesity-related comorbidities. Correction of fasting hyperinsulinemia, normalization of postprandial insulin responses, and reductions in active ghrelin and leptin concentrations were also observed.

The Case

A previously healthy 14-year-old boy presented to the primary care physician with fatigue, daytime somnolence, intermittent emesis, and hypothyroidism. The patient did not suffer from headache or visual impairment. A CT of the head revealed a large (3 x 4.5 x 4 cm) midline suprasellar mass arising from the sella turcica with amorphous calcification compressing the third ventricle (Figure 1). At diagnosis, the patient's height was 170 cm (50th percentile for his age), his weight was 70.9 kg (85th percentile), and his BMI was 25 kg/m2(92nd percentile; Figure 2). The patient underwent subtotal resection of the lesion through a right-sided orbitozygomatic craniotomy. Histological findings were typical for an adamantinomatous craniopharyngioma (i.e. a slow growing, extra-axial, epithelial-squamous, calcified cystic tumor arising from remnants of the craniopharyngeal duct and/or Rathke cleft).

Figure 1.

MRI scan of the patient´s brain before craniotomy; posterior view (A) and lateral view (B). An hourglass shaped, predominantly cystic mass with peripheral enhancement is seen in the sella turcica and suprasellar cistern in this gadolinium-enhanced, T1-weighted MRI scan of the brain. The lesion was causing a mass effect on the third ventricle.

Figure 2.

BMI changes of the patient and clinical events over time. At the time of gastric bypass surgery, the patient´s BMI was 67 kg/m2, his weight was 223.5 kg, and his excess weight was 150 kg, representing 204% over ideal weight for his gender and age. At the longest available follow-up (2.5 years following operation) the patient had a weight loss of 49 kg; that represents 22% of his initial weight or 33% of his initial excess weight.

An hourglass shaped, predominantly cystic mass with peripheral enhancement is seen in the sella turcica and suprasellar cistern in this gadolinium-enhanced, T1-weighted MRI scan of the brain. The lesion was causing a mass effect on the third ventricle.

At the time of gastric bypass surgery, the patient's BMI was 67 kg/m2, his weight was 223.5 kg, and his excess weight was 150 kg, representing 204% over ideal weight for his gender and age. At the longest available follow-up (2.5 years following operation) the patient had a weight loss of 49 kg; that represents 22% of his initial weight or 33% of his initial excess weight.

The patient was treated with radiation therapy of 54 Gy over the following 3 months. He subsequently developed panhypopituitarism and diabetes insipidus. Hormonal replacement therapy was initiated at the following doses (titrated to the targets shown): levothyroxine 100 μg/m2 per day, orally (target: free T4 level in the highest third of the normal range [23-28 pmol/l]), desmopressin 0.2 mg twice daily, orally (target: pre-dose serum sodium level in the normal range [135-145 mmol/l], no nocturia, daily diuresis), growth hormone (started at age 16 years) 0.1 mg subcutaneous injection daily (target: level of insulin-like growth factor 1 in the mid-normal range [400-500 ng/ml]), prednisone 5 mg/m2 (triple usual dose), and depot intramuscular testosterone, 200 mg every 2 weeks (started at age 17 years).

During the 24 months following tumor resection, the patient's appetite markedly increased and he gained weight at an extreme rate of 70 kg per year (Figure 2), despite outpatient and inpatient dietary and physical activity interventions. His height increased from 173 cm at 15 years of age to a plateau of about 180 cm at 17 years. He developed hyperinsulinemia associated with the extreme rate of weight gain, and octreotide therapy was initiated. The initial octreotide dose was 5 μg/kg/day (350 μg/day), it was increased to 1,000 μg/day over 5 months[1] and continued at this daily dose for another 14 months. Octreotide markedly attenuated serum insulin excursions in response to oral glucose loading, and no evidence of hyperglycemia was observed (data not shown).

Over the entire 19-month octreotide therapy, the patient's weight gain markedly slowed (from 70.0 kg/year to 9.5 kg/year) but no weight loss was observed. After gaining approximately 150 kg, he developed obstructive sleep apnea (which required treatment with nocturnal continuous positive airway pressure); concentric left ventricular hypertrophy (left ventricular mass index of 68.5 g/m2.7 [normal value: <50 g/m2.7]), and hypertriglyceridemia (3.12 mmol/l, normal range 0.34-2.26 mmol/l).

The patient was referred for an evaluation at the Comprehensive Weight Management Center that included consultation with a bariatric surgeon, a pediatric weight management specialist, a psychologist, and an endocrinologist. In view of his extreme obesity, comorbidities, and lack of weight loss with prior interventions, laparoscopic Roux-en-Y gastric bypass surgery was offered. Octreotide therapy was discontinued. To reduce vagal contribution to hyperinsulinemia,[2,3] a truncal anterior vagotomy was also performed. The procedure was performed at the age of 18 years (approximately 3 years following craniopharyngioma resection and irradiation), with no postoperative complications.

After the operation, the patient's weight gain ceased (Figure 2), followed by 49 kg weight loss over the ensuing 2.5 years, while his height remained 182 cm (79th percentile). Over the first postoperative year, standard hormone replacement for hypopituitarism was continued. There was no macronutrient or vitamin deficiency (albumin, vitamin B1 and vitamin B12 levels were normal). Mild iron-deficiency anemia developed (hemoglobin level was 123 g/l [normal range 133-177 g/l], serum iron concentration was 7.34 μmol/l [normal range 8.77-32.40 μmol/l], and ferritin concentration 10 μg/l [normal range 5-244 μg/l]). The patient was therefore given iron supplementation. After maximal weight loss, reassessment showed that the patient's serum triglyceride level (1.85 mmol/l), left ventricular mass index (46 g/m2.7), and snoring had markedly improved. His food cravings also diminished considerably ( Table 1 ). He has maintained his weight loss for 2.5 years after Roux-en-Y gastric bypass and returns annually for clinical visits.

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