TY - JOUR
T1 - A subset of men with age-related decline in testosterone have gonadotroph autoantibodies
AU - Ricciuti, Adriana
AU - Travison, Thomas G.
AU - Di Dalmazi, Giulia
AU - Talor, Monica V.
AU - DeVincentiis, Ludovica
AU - Manley, Robert W.
AU - Bhasin, Shalender
AU - Caturegli, Patrizio
AU - Basaria, Shehzad
N1 - Funding Information:
The authors thank the staff of the General Clinical Research Center of the Boston University Medical Center. This work was supported in part by patient donations to the Johns Hopkins Hypophysitis Research Center. The 5-AR trial was funded by the National Institute of Child Health and Human Development, National Institutes of Health (NIH). The TOM trial was funded by the National Institute on Aging, NIH. The PCa study was funded by the National Cancer Institute, NIH. Disclosure Summary: S.Ba. has previously received a research grant from Abbvie Pharmaceuticals on an investigatorinitiated clinical trial and previously consulted for Eli Lilly and Takeda. S.Bh. has previously received a research grant from Abbvie Pharmaceuticals. None of the other authors have anything to disclose.
Publisher Copyright:
Copyright © 2016 by the Endocrine Society.
PY - 2016/4
Y1 - 2016/4
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2016-1016
DO - 10.1210/jc.2016-1016
M3 - Article
C2 - 26963952
AN - SCOPUS:85011310424
SN - 0021-972X
VL - 101
SP - 1535
EP - 1541
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -