Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients – First experiences in therapeutic melatonin substitution

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 obese and non-obese craniopharyngioma patients (n=79), patients with hypothalamic pilocytic astrocytoma (n=19), and control subjects (n=30). Using a linear prediction model analyzing the influence of BMI and tumor diagnosis on diurnal salivary melatonin and cortisol levels we found that morning salivary melatonin levels were significantly and independently related to BMI (p-value in F-test: 0.004) and tumor diagnosis (p-value in F-test: 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 significant (p<0.01; p<0.05) inverse correlation (Spearman r: –0.42; –0.31) 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 morning and nighttime salivary melatonin concentrations were not detectable between normal weight controls and normal weight patients with craniopharyngioma or hypothalamic tumor. Differences in salivary cortisol concentrations were not related to impaired melatonin secretion in patients with childhood craniopharyngioma. A pilot study on efficacy of melatonin substitution (6mg/d) in childhood craniopharyngioma patients with severe daytime sleepiness (n=12) showed a significant improvement based on ESS and activity protocols. 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. (www.kraniopharyngeom.com)