Estrogen-secreting testicular tumors in 46,XY females with 17α- hydroxylase/17,20-lyase deficiency: two unusual case reports and review of the literature

Julio Americo Pereira Batatinha ^1,2 Sorahia Domenice ^1,2* Miriam Yumie Nishi ^1,2 Rafael Loch Batista ^1,2 José Antônio Diniz Faria Júnior ^1,2 Maria Helena Palma Sircilli ^1,2 Francisco Tibor Dénes ^1,2 Maria Jimena Chafloque Mesia ^1,2 Laura da Silva Salvanini ² Elaine Maria Frade Costa ^1,2 Filomena Carvalho ^1,2 Berenice Bilharinho Mendonca ^1,2

• ¹ University of São Paulo, São Paulo, Brazil
• ² Hospital das Clinicas da FMUSP, SAO PAULO, Brazil

Context: 17α-hydroxylase/17,20-lyase deficiency is a rare autosomal recessive condition. Women who have the complete form of 17α-hydroxylase/17,20-lyase deficiency typically presents a female phenotype, with an absence of secondary sexual characteristics, primary amenorrhea, and hypertension, which is usually detected in adolescence. Generally, 46,XY patients with a partial form of 17α-hydroxylase/17,20-lyase deficiency have atypical genitalia and intra-abdominal or inguinal testes. The risk of developing malignant testicular tumors or testicular adrenal rest tumors in 21-hydroxylase deficiency congenital adrenal hyperplasia is reported in 46,XY patients. Differently, these conditions are rarely described in patients with 17α-hydroxylase/17,20-lyase deficiency. Objective: To investigate patients with 17α-hydroxylase/17,20-lyase deficiency who present testicular tumors and spontaneous pubertal development. Patients and Results: Two unrelated 46,XY women with 17α-hydroxylase/17,20-lyase deficiency who presented with unexpected spontaneous development of secondary sexual characteristics and testicular tumors were described. Pathogenic allelic variants in CYP17A1 were identified in the compound heterozygous state in both patients. The variants p.Trp406Arg and p.Pro428Leu were identified in the patient with Leydig cell neoplasia plus germ cell neoplasia in situ, and the p.Arg358Gln and p.Trp406Arg variants were identified in the patient with intratubular seminoma associated with invasive classic seminoma. Conclusion: Our findings reinforce the risk of testicular tumor development among 46,XY patients with 17α-hydroxylase/17,20-lyase deficiency, and add data to the discussion of the risk/benefit ratio of prophylactic gonadectomy in the therapeutic approach of patients with this condition of 46,XY DSD.