Endocrine Abstracts

Introduction: Amyloidosis due to Apo A-I Leu75Pro mutation is a rare form of hereditary amyloidosis with systemic involvement mainly of testicle, kidney and liver. This disease finds a wide prevalence in the province of Brescia (Northern Italy), which represents a geographic uniqueness for the spread of this amyloidosis form. Somefeatures of this disease have not yet been described.

Purpose: To describe the frequency of organ damages in this amyloidosis form and above all to define the characteristics of testicular involvement for the first time in such a wide range of cases.

Materials and methods: We have retrospectively analyzed 129 male patients >18 years of age with diagnosis of ApoA-I Leu75Pro amyloidosis. Organ involvement was assessed with scrotal ultrasound, gonadal hormone levels, glomerular filtration rate estimate and cholestasis indices evaluation.

Results: Testicular involvement is predominant with respect to liver and kidney involvement, and in younger patients it is often the first and/or only manifestation of disease. The testicle is affected in 88/129 (68.2%) of the patients and considering the younger patients (18–38 years) it turns out to be the only manifestationin 30% of cases. In older age group, gonadal involvement is associated with kidney and liver impairment in 53.3% of patients. Testicular involvement manifests itself as hypogonadism, which it is primary (reduced testosterone and increased LH)in 83% of cases. Considering also FSH-Sertoli cell axis (indirect expression of spermatogenesis function), almost all patients (96.6%) have testicular impairment of both gonadal axes. In addition, an increase in testicular volumes (>253 ml) is often found in this amyloidosis form (48.2% of cases).

Discussion: In Apo A-I Leu75 Proamyloidosis, the testicular involvement is often early and it can compromise endocrine and spermatogenic testicular function. It should be noted that ApoA-I Leu75 Pro amyloidosis manifests itself as primary testicular damage with peculiar characteristics (different from many other known forms of hypogonadism): the macroorchidism and the concomitant global involvement of testicular cell populations. Conclusions: this is the first large description of testicular involvement in this form of amyloidosis. The results of this study may have important clinical implications forearly diagnosis, screening of family membersand clinical-therapeutic follow-up of these patients.