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


METHODS
We conducted a cross-sectional cohort study.


METHODS
The study was performed at the Endocrinology Unit of the Second University of Naples.


METHODS
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.


METHODS
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.
De Bellis
Annamaria
A
Department of Clinical and Experimental Medicine and Surgery F Magrassi, A Lanzara, Second University of Naples, Naples, Italy. annamaria.debellis@unina2.it
Sinisi
Antonio Agostino
AA
Conte
Marisa
M
Coronella
Concetta
C
Bellastella
Giuseppe
G
Esposito
Dario
D
Pasquali
Daniela
D
Ruocco
Giuseppe
G
Bizzarro
Antonio
A
Bellastella
Antonio
A
D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D019084:Fluorescent Antibody Technique, Indirect; D006065:Gonadotropins, Pituitary / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D017436:Kallmann Syndrome / Q000453:epidemiology* / Q000276:immunology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D000857:Olfaction Disorders / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D009830:Olfactory Bulb / Q000276:immunology / Q000473:pathology; D010215:Papio; D010902:Pituitary Gland / Q000276:immunology* / Q000473:pathology; D016036:Seroepidemiologic Studies
D001323:Autoantibodies; D006065:Gonadotropins, Pituitary