Antipituitary antibodies against gonadotropin-secreting cells in adult male patients with apparently idiopathic hypogonadotropic hypogonadism

Context: Hypogonadotropic hypogonadism (HH) can occur at any stage of life as an isolated congenital or acquired abnormality or within a more generalized pituitary or hypothalamic impairment. However, the defect in patients with idiopathic HH is still unknown. Objective: The aim of this study was to investigate the prevalence of antipituitary antibodies (APA) in a group of HH patients with or without Kallmann's syndrome and to characterize their pituitary target. Design: We conducted a cross-sectional cohort study. Setting: The study was performed at the Endocrinology Unit of the Second University of Naples. Patients: Twenty-one HH patients with normal sense of smell (group 1), 10 patients with Kallmann's syndrome (group 2), 13 patients with HH associated with other pituitary hormone deficiencies (group 3), and 50 normal controls were studied. Main Outcome Measures: APA were evaluated in patients and in controls by indirect immunofluorescence. Moreover, a magnetic resonance imaging (MRI) of the hypothalamic-pituitary region was performed in all three groups of patients. Results: APA were detected at high titer in eight out of 21 patients in group 1 (38%) and in five of 13 in group 3 (38.4%), and at low titers in two out of 10 in group 2 (20%) and in three of 50 controls (6%). In patients of group 1, APA immunostained selectively gonadotropin-secreting cells, whereas in those of group 3, they immunostained other pituitary hormone-secreting cells also. None of patients in group 1 showed alterations on MRI, whereas all patients in group 2 showed aplasia/hypoplasia of the olfactory bulbs/tracts and/or of olfactory sulci. Among the five APA-positive patients in group 3, three had normal MRI, one had findings of empty sella, and one had findings of autoimmune hypophysitis. Conclusions: Our results suggest that some apparently idiopathic cases of HH, both isolated and associated with other pituitary impairment, can be caused by an early autoimmune process involving the gonadotrophs at pituitary level. Future longitudinal studies are needed to clarify the natural history of this process and the possible effect of early corticosteroid therapy.