Category: Reproductive Endocrinology

Monitor: 13


Saturday, Apr 27
10:00 AM – 10:30 AM

Objective :

46,XX disorder of sex development (DSD) is a rare chromosomal abnormality occurring that occurs in about 1:20,000 males. These patients can be classified into two groups according to presence or absence of the sex-determining region Y gene (SRY) and typically present with ambiguous genitalia or infertility with small testes and hypergonadotropic hypogonadism.

Methods :

Case report of a 46,XX phenotypic male presenting at age 66 with hypogonadism and gynecomastia.

Results :

A 66-year-old phenotypic male presents with hypogonadism and bilateral gynecomastia. Patient reports a long history of nontender gynecomastia, low libido, scant pubic hair, small testes, and infertility. Puberty occurred around age 16. Due to embarrassment the patient never sought medical attention, but was previously told testosterone levels were low. Denies history of testicular trauma or infection. Exam notable for height of 69 inches, 5cm bilateral non-tender gynecomastia, bilateral testicular volume of 4mL and scant pubic hair. Biochemical assessment was consistent with hypergonadotropic hypogonadism. Testicular ultrasound and abdominal MRI confirmed bilateral testicles in the scrotum. Chromosomal analysis revealed an SRY-positive 46,XX karyotype. Patient was started on testosterone replacement therapy and reported improvement of libido, energy and muscle mass.

Discussion :

This is a case of a 46,XX phenotypic male. The main factor influencing the sex determination of an embryo is the presence or absence of a Y chromosome. Some individuals, however, have a female karyotype but are phenotypically male. Chromosomal abnormalities occur in less than 1% of the population, but rise to 15% in men with infertility. 46,XX DSD occurs in about 1:20,000 phenotypic males. Patients typically present at an early age with ambiguous genitalia or with normal male genitalia reporting infertility. Translocation of the SRY gene preserves a male phenotype in about 80% of cases. Those who are SRY-negative present with genital ambiguity. About 40% of patients have some form of reduced virilization. Testicular atrophy, azoospermia and hypergonadotropic hypogonadism are always present. Hypogonadism should be managed with testosterone replacement.

Conclusion :

This is an atypical case of 46,XX phenotypic male as he presented at age 66. Typically these patients are identified much earlier; infertility or the severity of hypogonadism brings them to medical attention. This unique case highlights the need for medical providers to consider rare disorders of sex development in their differential for hypogonadism and gynecomastia.


David LaChance

Walter Reed National Military Medical Center
North Bethesda, Maryland

First year Endocrine Fellow at Walter Reed National Military Medical Center

Nicole Vietor

Associate Program Director
Walter Reed National Military Medical Center

Associate Program Director for Endocrinology Fellowship at Walter Reed National Military Medical Center

Thanh Hoang

Program Director
Walter Reed National Military Medical Center

Current Program Director for Endocrinology Fellowship at Walter Reed National Military Medical Center