New treatments for primary brain tumors have improved survival but quality of life may be impaired by neuroendocrine dysfunction. We performed a controlled, cross-sectional study to assess frequency and clinical impact of endocrine dysfunction in adult long-term survivors of primary brain tumors outside the hypothalamic-pituitary region. Thirty-one patients (19 males and 12 females; age, 25 to 66 years) and 31 sex- and age-matched controls were studied 1.5 to 11 years after radiotherapy with a mean total dose of 62.3 +/- 2.8 Gy (mean local doses pituitary, 51.1 +/- 12.1 Gy; hypothalamus, 57.0 +/- 7.8 Gy). Structured clinical assessment included a standardized questionnaire. Thyroid, adrenal, and gonadal hormones were measured at baseline and, in the patients, also after stimulation. Sixteen patients (52%) reported two or more symptoms suggestive of hypothyroidism; eight patients (26%) showed evidence of hypothalamic hypothyroidism. Patients had significantly lower serum baseline concentrations of cortisol and dehydroepiandrosterone sulfate than controls, but no manifest hypoadrenalism was noticed except in one patient with panhypopituitarism. Forty-seven percent of the male patients, but only six percent of the controls, suffered from erectile dysfunction; 42% of the male patients showed either evidence of hypothalamic hypogonadism (32%) or primary gonadal damage (10%). Nine patients (29%) presented with hyperprolactinemia and four women concurrently suffered from oligo-amenorrhea. In adult patients treated for primary brain tumors, endocrine dysfunction due to radiation-induced hypothalamic damage is common and has a significant impact on well being. Endocrinologic evaluation should be performed periodically in these patients.