Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

Abstract

Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients.

Keywords: brain tumors; craniopharyngioma; hypothalamic obesity; irradiation; neurocognitive; neuroendocrinology; neurosurgery; pituitary; quality of life; recurrence; sleep.

Figure 1

Manifestations before diagnosis of craniopharyngioma in children and adolescents. Frequency of occurrence of each manifestation before diagnosis (blue columns) and frequency of occurrence as the initial manifestation (red columns). The median time (months) from the appearance of each initial manifestation until diagnosis is indicated above each red column. In the overall group, the median time from the initial manifestation of disease until diagnosis was 12 months, with a range of 0.01–96 months. Modified from [20] with kind permission from Springer.

Figure 2

Degree of obesity in relation to the location of childhood-onset craniopharyngioma. In both patients, craniopharyngioma (as indicated by arrow on magnetic resonance imaging before surgery) could be completely resected. Both patients had complete hypopituitarism after surgery requiring endocrine substitution of all hypothalamic-pituitary axes. The patient depicted in (B) developed severe obesity due to hypothalamic lesions of suprasellar parts of craniopharyngioma (C). The patient depicted in (A) presented with a small tumor confined to the sellar region (D). After complete resection, she maintained a normal weight without any eating disorders. Modified from [20], with kind permission of Springer.

Figure 3

Kaplan-Meier analyses of overall (A) and progression-free survival rates (PFS) (B) depending on preoperative hypothalamic involvement in 177 patients with sellar masses (163 childhood-onset craniopharyngiomas, 14 cysts of Rathke’s pouch) recruited in the trial Hit Endo. Modified from [47] with kind permission from Bioscientifica.

Figure 4

BMI and MRI imaging at diagnosis and 36 months after surgery in three cases of childhood-onset craniopharyngioma (CP) with different grades of hypothalamic involvement/lesion. (A,B) CP confined to the intrasellar space (0° no hypothalamic involvement (A)/surgical lesion (B)). BMI at diagnosis: −0.11 S.D.; BMI 36 months after complete resection: −0.41 S.D. (C,D) CP involving the anterior hypothalamus (I° hypothalamic involvement (C)/surgical lesion of the anterior hypothalamic area (D)). BMI at diagnosis: −1.75 S.D.; BMI 36 months after complete resection: −0.43 S.D. (E,F) CP involving the anterior and posterior hypothalamus (II° hypothalamic involvement (E)/surgical lesion of the anterior and posterior hypothalamic area (F)). BMI at diagnosis: +6.08 S.D.; BMI 36 months after complete resection: +6.79 S.D. Modified from [46], with kind permission from Bioscientifica.

Figure 5

Changes in body mass index (BMI SDS) during first 36 months after diagnosis of 117 childhood-onset craniopharyngioma patients recruited inKRANIOPHARYNGEOM 2000 relative to the extent of surgical hypothalamic lesions (grade 0–2). The horizontal line in the middle of the box depicts the median. The edges of the box mark the 25th and 75th percentile. Whiskers indicate the range of values that fall within 1.5 box-lengths. Modified from [46], with kind permission from Bioscientifica.

Figure 6

Study design of KRANIOPHARYNGEOM 2007 (www.kraniopharyngeom.net). Modified from [33], with kind permission from Thieme.