Infertility and hypergonadotropic hypogonadism as first evidence of hereditary apolipoprotein A-I amyloidosis.
OBJECTIVE
We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein.


METHODS
Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene.


RESULTS
All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels.


CONCLUSIONS
Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary.
Scalvini
Tiziano
T
Department of Endocrinology and Andrology, Spedali Civili, Brescia, Italy.
Martini
Paola Rossana
PR
Obici
Laura
L
Tardanico
Regina
R
Biasi
Luciano
L
Gregorini
Gina
G
Scolari
Francesco
F
Merlini
Giampaolo
G
D000328:Adult; D028226:Amyloidosis, Familial / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016632:Apolipoprotein A-I / Q000235:genetics*; D053713:Azoospermia / Q000209:etiology; D006801:Humans; D007006:Hypogonadism / Q000209:etiology* / Q000473:pathology; D007248:Infertility, Male / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013733:Testicular Diseases / Q000209:etiology* / Q000473:pathology; D013737:Testis / Q000473:pathology
D016632:Apolipoprotein A-I