Secondary narcolepsy may be a causative factor of increased daytime sleepiness in obese childhood craniopharyngioma patients.

Prognosis in childhood craniopharyngioma survivors hinges upon late effects such as pituitary deficiency and obesity. Observations indicate that reduced physical activity and increased daytime sleepiness might be risk factors for obesity. We analyzed the degree of daytime sleepiness in 115 childhood craniopharyngioma patients (47% obese) using the Epworth Sleepiness Scale (ESS). Thirty-five (30%) displayed increased daytime sleepiness (ESS score > 10) of whom 14 were obese (26% of obese cohort). Polysomnography (PSG) and Multiple Sleep Latency Tests (MSLT) were conducted with 10 obese patients presenting increased daytime sleepiness, with only two craniopharyngioma patients revealing a sleep related breathing disorder. Four patients had repeated episodes of SOREM (sleep onset rapid eye movement), the classic PSG criterion for narcolepsy. Three patients displayed hypersomnia. All but one patient qualified as acutely obese. We speculate that secondary narcolepsy is an exacerbating condition of childhood craniopharyngioma obesity, supported by recent reports on orexin and narcolepsy which suggest hypothalamic failure in idiopathic narcolepsy.

Melatonin treatment in obese patients with childhood craniopharyngioma and increased daytime sleepiness.

Craniopharyngioma is a rare dysontogenetic benign tumor. Patients frequently suffer from endocrine deficiencies, sleep disturbances and obesity due to pituitary and hypothalamic lesions. A self-assessment daytime sleepiness questionnaire (German version of the Epworth Sleepiness Scale [ESS]) was used to evaluate 79 patients with childhood craniopharyngioma. Because hypothalamic lesions may explain daytime sleepiness in craniopharyngioma patients, salivary melatonin and cortisol concentrations were examined in severely obese (BMI>or=4SD) and non severely obese (BMI<4SD) craniopharyngioma patients (n=79), patients with hypothalamic pilocytic astrocytoma (n=19), and control subjects (n=30). Using a general linear model procedure analyzing the influence of BMI and tumor diagnosis on diurnal salivary melatonin we found that morning salivary melatonin levels were related to BMI (F test: p-value=0.004) and tumor diagnosis (F-test: p-value=0.032). Also for nighttime salivary melatonin levels significant relations with BMI (p-value in F-test: <0.001) and tumor diagnosis (p-value in F-test: 0.025) were detectable. Melatonin concentrations in saliva of craniopharyngioma patients collected at nighttime or in the morning showed a negative correlation (Spearman's rho: -0.42; p=0.001; Spearman's rho: -0.31; p=0.020) with the patient's ESS score. Severely obese craniopharyngioma patients and severely obese hypothalamic tumor patients had similar patterns of melatonin secretion. Differences in terms of diurnal salivary cortisol concentrations were not detectable when patient groups and controls were compared. As decreased nocturnal melatonin levels were associated with increased daytime sleepiness, BMI and hypothalamic tumor diagnosis, we initiated an experimental melatonin substitution in 10 adult obese patients (5f/5m) with childhood craniopharyngioma. In all 10 patients with childhood craniopharyngioma the degree of daytime sleepiness significantly improved based on activity diaries, ESS, self assessment questionnaires and actimetry. We speculate that hypothalamic lesions might be responsible for both obesity and daytime sleepiness. As first experiences with experimental melatonin substitution were promising, further randomized double-blinded studies on the beneficial effects of melatonin substitution on daytime sleepiness and weight control in these patients are warranted.

Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients.

Craniopharyngioma is a rare dysontogenetic benign tumor. Patients frequently suffer from endocrine deficiencies, sleep disturbances, and obesity due to pituitary and hypothalamic lesions. A self-assessment daytime sleepiness questionnaire (German version of the Epworth Sleepiness Scale) was used to evaluate 79 patients with childhood craniopharyngioma. Because hypothalamic lesions may explain daytime sleepiness in craniopharyngioma patients, salivary melatonin and cortisol concentrations were examined in obese and nonobese craniopharyngioma patients (n = 79), patients with hypothalamic pilocytic astrocytoma (n = 19), and control subjects (n = 30). Using a general linear model procedure analyzing the influence of body mass index (BMI) and tumor diagnosis on diurnal salivary melatonin, we found that morning salivary melatonin levels were related to BMI (by F test, P = 0.004) and tumor diagnosis (by F test, P = 0.032). Also for nighttime salivary melatonin levels significant relations with BMI (by F test, P < 0.001) and tumor diagnosis (by F test, P = 0.025) were detectable. Melatonin concentrations in saliva of craniopharyngioma patients collected at night or in the morning showed a negative correlation (night: Spearman's rho = -0.42; P = 0.001; morning: Spearman's rho = -0.31; P = 0.020) with the patient's Epworth Sleepiness Scale score. Severely obese craniopharyngioma patients and severely obese hypothalamic tumor patients had similar patterns of melatonin secretion. Differences in terms of diurnal salivary cortisol concentrations were not detectable when patient groups and controls were compared. We speculate that hypothalamic lesions might be responsible for both obesity and daytime sleepiness. As decreased nocturnal melatonin levels were associated with increased daytime sleepiness, BMI, and hypothalamic tumor diagnosis, further studies on the beneficial effects of melatonin substitution on daytime sleepiness and weight control in these patients are warranted.