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MELATONIN DEFICIENCY AND DISRUPTED CIRCADIAN RHYTHMS IN PEDIATRIC SURVIVORS OF CRANIOPHARYNGIOMA

Craniopharyngiomas are the most common extraneural tumors of the CNS in children.1 Because craniopharyngiomas usually grow along the anatomic midline, the tumors or their treatments (surgical excision and radiation) frequently lead to hypopituitarism, visual field defects, obesity, sleep abnormalities, and daytime hypersomnolence (DH).2,3 DH persists despite hormone replacement or treatment of commonly associated obstructive sleep apnea (OSA). We hypothesized that disrupted sleep patterns in patients with craniopharyngioma result from dysfunction of the hypothalamic circadian pacemaker located in the suprachiasmatic nucleus, which controls the timing of the daily sleep propensity rhythm. Daily variations in levels of the pineal hormone melatonin serve as a marker of the function of this system. Low salivary melatonin has been documented in obese craniopharyngioma survivors and melatonin supplementation has proved beneficial in some cases; however, a detailed analysis of circadian rhythms in this patient population had not been performed.4

### Methods.

Subjects older than 8 years of age with self-reported DH requiring daytime stimulant medication were recruited from a pool of 42 craniopharyngioma survivors treated at the Children’s Hospital Boston (CHB)/Dana-Farber Cancer Institute Brain Tumor Program between 1990 and 2002 by a single neurologist (S.L.P.). Four subjects were enrolled after informed consent was obtained in accordance with the Committee on Clinical Research. Three subjects (2 female, 1 male) ages 15, 15, and 22 completed the study. All had undergone both surgical extirpation and radiotherapy, were morbidly obese (BMI 41–54; normal 17–25), had panhypopituitarism requiring hormone supplementation, and had mild REM-related OSA, and 1 had a seizure disorder. Wrist actigraphy was obtained for 2 to 3 weeks prior to admission …