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. 2023 Apr 5:14:1128061.
doi: 10.3389/fendo.2023.1128061. eCollection 2023.

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study

Andrea Delbarba  1 , Deborah Cosentini  2 , Paolo Facondo  1 , Marta Laganà  2 , Letizia Chiara Pezzaioli  1 , Valentina Cremaschi  2 , Andrea Alberti  2 , Salvatore Grisanti  2 , Carlo Cappelli  1 , Alberto Ferlin  3 , Alfredo Berruti  2
Affiliations

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study

Andrea Delbarba et al. Front Endocrinol (Lausanne). .

Abstract

Objective: Hypogonadism is common in male patients with adrenocortical carcinoma (ACC) who are under treatment with mitotane, but the phenomenon is underestimated, and its prevalence has been poorly studied. This single-center retrospective longitudinal study was undertaken to assess the frequency of testosterone deficiency before and after mitotane therapy, the possible mechanism involved, and the relationship between hypogonadism with serum mitotane levels and prognosis.

Research design and methods: Consecutive male ACC patients followed at the Medical Oncology of Spedali Civili Hospital in Brescia underwent hormonal assessment to detect testosterone deficiency at baseline and during mitotane therapy.

Results: A total of 24 patients entered the study. Of these patients, 10 (41.7%) already had testosterone deficiency at baseline. During follow-up, total testosterone (TT) showed a biphasic evolution over time with an increase in the first 6 months followed by a subsequent progressive decrease until 36 months. Sex hormone binding globulin (SHBG) progressively increased, and calculated free testosterone (cFT) progressively decreased. Based on cFT evaluation, the proportion of hypogonadic patients progressively increased with a cumulative prevalence of 87.5% over the study course. A negative correlation was observed between serum mitotane levels >14 mg/L and TT and cFT.

Conclusion: Testosterone deficiency is common in men with ACC prior to mitotane treatment. In addition, this therapy exposes these patients to further elevated risk of hypogonadism that should be promptly detected and counteracted, since it might have a negative impact on quality of life.

Keywords: adrenal tumor; androgens; hypogonadism; mitotane; testosterone.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Trend of TT (A), SHBG (B) and cFT (C) levels, during mitotane treatment. Friedman test was used to develop the trend lines. TT, total testosterone; SHBG, sex hormone binding globulin; cFT, calculated free testosterone. Trend lines in dotted.
Figure 2
Figure 2
Impact of testosterone deficiency on PFS and OS. (A) Baseline testosterone deficiency and PFS: cases of metastasis in men with baseline testosterone deficiency (10/10) vs. baseline eugonadal men (11/14); (B) testosterone deficiency developed during treatment and PFS: cases of metastasis in men with developed testosterone deficiency (9/11) vs. eugonadal men also during treatment (2/3); (C) baseline testosterone deficiency and OS: cases of death in men with baseline testosterone deficiency (3/10) vs. baseline eugonadal men (5/14); (D) testosterone deficiency developed during treatment and OS: cases of death in men with developed testosterone deficiency (5/11) vs. eugonadal men also during treatment (0/3). Comparison was performed with chi-square test. Continuous line: testosterone deficiency patients; dotted line: eugonadal men. On the horizontal axis, the months passed. PFS, progression-free survival (as months without metastasis); OS, overall survival (as months without death).
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