Adriana Ricciuti1, Thomas G Travison1, Giulia Di Dalmazi1, Monica V Talor1, Ludovica DeVincentiis1, Robert W Manley1, Shalender Bhasin1, Patrizio Caturegli1, Shehzad Basaria1. 1. Department of Pathology (A.R., G.D.D., M.V.T., L.D.V., P.C.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pharmacy (A.R., G.D.D.), Gabriele d'Annunzio University, Chieti, Italy; The Research Program in Men's Health: Aging and Metabolism (T.G.T., R.W.M., S.B., S.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Institute for Aging Research (T.G.T.), Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts; Feinstone Department of Molecular Microbiology and Immunology (P.C.), The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Abstract
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.
RCT Entities:
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.
Authors: C F Verge; R Gianani; E Kawasaki; L Yu; M Pietropaolo; R A Jackson; H P Chase; G S Eisenbarth Journal: Diabetes Date: 1996-07 Impact factor: 9.461
Authors: N Morel; S Georgin-Lavialle; K Levesque; G Guettrot-Imbert; V Le Guern; J Le Bidois; B Bessières; C Brouzes; D Le Mercier; E Villain; A Maltret; N Costedoat-Chalumeau Journal: Rev Med Interne Date: 2014-09-17 Impact factor: 0.728