Spermatogenic and steroidogenic impairment of the testicle characterizes the hereditary leucine-75-proline apolipoprotein A-I amyloidosis

Abstract

Context: The leucine-75-proline variant of apolipoprotein A-I leads to a new hereditary systemic amyloidosis involving mostly the liver and kidney. Objective: The objective of the study was to examine the effects of this amyloidosis on testicular structure and function. Design: This was an observational study in which patients with testicular amyloidosis were characterized. Setting: The study was carried out at the Endocrinology Department of Brescia University. Patients or Other Participants: Over a 13-yr period, 25 patients were found to be affected by leucine-75-proline apolipoprotein A-I testicular amyloidosis. Thirteen had the testicle as the first or only organ involved (group 1); in 12 testicular damage followed that of other organs (group 2). Interventions: There were no interventions. Main Outcome Measure: Hormone and lipidic profiles, semen analysis, echographic volume of testicles, testicular histology, and genetic analysis were carried out. Results: Group 1 patients were younger than those of group 2. In group 1, eight had hypergonadotropic hypogonadism and five were normogonadic with high gonadotropins; in group 2 all subjects were hypogonadic. All men had low high-density lipoprotein values. Group 1 patients were macroorchid, whereas the testicular volume was at the highest limit in group 2 (group 1 vs. group 2, P < 0.05). All men in the first group and six in the second group were azoospermic; the remaining had oligoposia. Biopsies showed the germinal epithelium replaced by amyloid. Leydig cells were essentially preserved in normogonadic but not hypogonadic patients. Conclusions: This amyloidosis may determine infertility, macroorchidism, and hypogonadism. Endocrine impairment follows spermatogenic impairment. Copyright © 2008 by The Endocrine Society.