Spermatogenic and Steroidogenic Impairment of the Testicle Characterizes the Hereditary Leucine-75-Proline Apolipoprotein A-I Amyloidosis

• Published in: The journal of clinical endocrinology and metabolism Vol. 93; no. 5; pp. 1850 - 1853
• Main Authors: Scalvini, Tiziano, Martini, Paola Rossana, Gambera, Alessandro, Tardanico, Regina, Biasi, Luciano, Scolari, Francesco, Gregorini, Gina, Agabiti Rosei, Enrico
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2008
• Subjects: Adult; Aged; Amyloidosis; Amyloidosis, Familial - pathology; Amyloidosis, Familial - physiopathology; Apolipoprotein A; Apolipoprotein A-I; Apolipoprotein A-I - genetics; Apolipoproteins; Biopsy; Endocrinology; Epithelium; Genetic analysis; Gonadotropins; High density lipoprotein; Humans; Hypogonadism; Infertility; Leucine; Leucine - genetics; Leydig cells; Lipids - blood; Male; Middle Aged; Pituitary (anterior); Proline; Proline - genetics; Spermatogenesis; Steroids - biosynthesis; Structure-function relationships; Testes; Testis - pathology; Testis - physiopathology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2007-1656

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.