title: A Subset of Men With Age-Related Decline in Testosterone Have Gonadotroph Autoantibodies.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.affiliation: 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.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ricciuti
authors.affiliation: 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.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.affiliation: 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.
authors.forename: Giulia
authors.initials: G
authors.lastname: Di Dalmazi
authors.affiliation: 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.
authors.forename: Monica V
authors.initials: MV
authors.lastname: Talor
authors.affiliation: 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.
authors.forename: Ludovica
authors.initials: L
authors.lastname: DeVincentiis
authors.affiliation: 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.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Manley
authors.affiliation: 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.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.affiliation: 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.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Caturegli
authors.affiliation: 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.
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005640:Follicle Stimulating Hormone / Q000097:blood; D052681:Gonadotrophs / Q000276:immunology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone