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Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal features in comparison with non-tumoral causes of androgen excess

¹ Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service d'Endocrinologie, Paris, France² Université Paris Descartes, Paris, France³ Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Biostatistiques, Paris, France⁴ INSERM U 567, CNRS UMR 8104, Institut Cochin, Paris, France⁵ Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service d'Hormonologie, Paris, France⁶ Adrenal Cancer INCa-COMETE Network, Paris, France⁷ Center for Rare Adrenal Diseases, Hôpital Cochin, Paris, France

(Correspondence should be addressed to J Bertherat at Service d'Endocrinologie, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Email: jerome.bertherat{at}cch.ap-hop-paris.fr)

Objective: Adrenocortical tumors (ACT) account for no more than 0.2% of the causes of androgen excess (AE). Conversely, these rare tumors have a very poor prognosis. It is difficult and important to exclude this diagnosis whenever there is AE.

Design: Retrospective investigation of androgen profiles in a large consecutive series of androgen-secreting (AS) ACT to assess their relative diagnostic value.

Methods: A total of 44 consecutive female patients with ACT-AS and a comparison group of 102 women with non-tumor causes of AE (NTAE).

Results: Patients with ACT-AS were older than the ones with NTAE (37.7 vs 24.8 years; P<0.001) and the prevalence of hirsutism, acne, and oligo/amenorrhea were not different. Free testosterone was the most commonly elevated androgen in ACT-AS (94%), followed by androstenedione (90%), DHEAS (82%), and total testosterone (76%), and all three androgens were simultaneously elevated in 56% of the cases. Androgen serum levels became subnormal in all ACT-AS patients after complete tumor removal. In NTAE, the most commonly elevated androgen was androstenedione (93%), while all three androgens were elevated in only 22% of the cases. Free testosterone values above 6.85 pg/ml (23.6 pmol/l) had the best diagnostic value for ACT-AS (sensitivity 82%, confidence interval (CI): 57–96%; specificity 97%, CI: 91–100%). Basal LH and FSH levels were significantly lower in the ACT-AS group.

Conclusion: Free testosterone was the most reliable marker of ACT-AS. However, the large overlap of androgen levels between ACT-AS and NTAE groups suggests that additional hormonal and/or imaging investigations are required to rule out ACT-AS in case of increased androgens.

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