P-40 A rare cause of male infertility: 46, XX testicular disorder of sex development

Abstract

Abstract Introduction 46, XX testicular disorder of sex development (DSD) is a rare condition with an estimated incidence of 1 per 20,000 individuals. The clinical spectrum ranges from ambiguous genitalia that is usually diagnosed at birth, to male infertility that is diagnosed in the adult years. However, the diagnosis of 46, XX DSD in an individual presenting with infertility may be challenging due to occult clinical findings. A thorough physical examination as well as clinical suspicion is required for diagnosis. Clinical Case A 22-year-old male presented to the urology clinic for infertility despite at least 3 years of regular unprotected intercourse. On physical examination, his testicles were palpable bilaterally in the scrotum with small volumes. Laboratory results revealed hypergonadotropic hypogonadism and his spermiogram revealed azoospermia. Abdominopelvic ultrosonagraphy (US) was reported normal except abdominal situs inversus. Tumor markers for a probable testicular tumor were negative. He was referred to medical genetic department. His family history was unremarkable except for parental consanguineouty. The chromosomal analyze revealed a 46, XX karyotype, and fluorescence in situ hybridization (FISH) disclosed that the SRY gene locus was translocated to the X chromosome: 46,x,der(x) t(x;Y) (sry+); SRY + AZF a,b,c microdeletion. The patient was consulted to the endocrinology department for further evaluation of hypogonadism. On physical exam, he had eunuchoid habitus with incomplete virilization, bilateral and symmetric gynecomastia. The height, and body mass index of the patient was 165 cm, and 29.2 kg/m2, respectively. The testicles were bilaterally palpable in the scrotum, with a volume of 4 mL each. His luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone levels were 14 mUI/mL (laboratory reference: 1.5–9 mUI/mL), 42 mUI/mL (1.4–18 mUI/mL), and 140 ng/dl (197-700 ng/dL), respectively. The bone age matched his chronological age. Bone densitometry revealed osteopenia. A direct X-ray of the thorax showed thoracic situs inversus, he diagnosed with situs inversus totalis. Detailed genetic analyses could not be done concerning this diagnosis due to financial constraints. He had no history of lung infections that ruled out Kartagener's syndrome. Treatment was started with monthly intramuscular testosterone injections of 250 mg/ml. The patient and his family received genetic counseling, including advice that assisted reproduction will not work owing to AZFabc deletion. Conclusion 46, XX DSD is an uncommon genetic disorder that is rarely identified during the evaluation of male infertility. Clinical suspicion and a comprehensive physical exam are keys for diagnosis. Genetic analysis is essential for definitive diagnosis. A multidisciplinary is required for treatment and follow-up. Psychological support and genetic counseling are also critical for the management of these patients.