A subset of men with age-related decline in testosterone have gonadotroph autoantibodies

Context: Age-related decline in serum testosterone (T) is being increasingly diagnosed. In most men, it associates with low or inappropriately normal gonadotropin levels, which suggests a hypothalamic-pituitary etiology. Autoantibodies against adenohypophyseal cells have been associated with pituitary dysfunction; however, the prevalence of pituitary autoimmunity in this age-related T decline has not been assessed. Objectives: This is a proof-of-concept study with the objective of determining the prevalence of antibodies to gonadotrophs in older men with age-related low T and compare it with healthy young and older eugonadal men. Study Design: This is a cross-sectional case-control study of 182 men. Cases included 100 older men (≥65 years) with age-related low T levels; the control groups were composed of 50 young and 32 older healthy eugonadal men. Serum antibodies against the anterior pituitary gland were measured using a two-step approach: 1) single indirect immunofluorescence (ie, participant serum only) to determine the pattern of cytosolic staining; and 2) double indirect immunofluorescence (ie, participant serum plus a commercial adenohypophyseal hormone antibody) to identify the anterior pituitary cell type recognized by the patient's antibodies). Results: In participants with positive antipituitary antibodies, the granular cytosolic pattern (highly predictive of pituitary autoimmunity) was only seen in older men with age-related low T (4%) and none in control groups (0%, P = .001). Double indirect immunofluorescence confirmed that pituitary antibodies were exclusively directed against the gonadotrophs. Conclusion: A subset of older men with age-related low T levels have specific antibodies against the gonadotrophs. Whether these antibodies are pathogenic and contributory to the age-related decline in T remains to be established.