MON-156 - An Unusual Case of Hypergonadotropic Hypergonadism

Background

Hypergonadotropic hyperandrogenism is an endocrinopathy in which both gonadotropins and gonadal function are abnormally high. This condition is most commonly associated with either a functional gonadotroph adenoma, ectopic luteinizing hormone (LH) production, or an hCG-producing tumor. Rare causes include enzymatic deficiencies in the canonical androgen pathway such as 5-alpha reductase deficiency, estrogen insensitivity syndrome, aromatase deficiency, or in genetic mutations with the androgen receptor gene (AR) at chromosome Xq11-12 leading to androgen insensitivity syndrome. We present a case of biochemical hypergonadotropic hypergonadism in a phenotypic male.

Case summary

A 62-year-old man with apparent normal puberty and 2 biological children was evaluated for decreased libido and diminished morning erections. He denied use of anabolic steroids, supplements, or medications known to affect androgen levels. Laboratory evaluation demonstrated hematocrit 32.1%, elevated total testosterone >1500 ng/dL and free testosterone 25 pg/mL with elevated LH 13.5 mIU/mL and normal FSH 7.5 mIU/mL Repeat laboratory assessment showed total testosterone 2346 ng/dL, sex-hormone binding globulin (SHBG) 123 nmol/L, LH 17.4 mIU/mL, bioavailable testosterone 623 ng/dL, prolactin 29.9 ng/mL, 17-hydroxyprogesterone 138 ng/dL, androstenedione 188 ng/dL, beta-hCG < 5 mIU/mL, and DHEA-S 403 mcg/dL. Pituitary MRI showed a normal sized pituitary gland with homogeneous signal intensity with no sellar or suprasellar lesions. The patient had experienced a transient ischemic attack several months prior. A CT scan of the chest, abdomen, and pelvis showed no evidence of a primary malignancy. However, scrotal ultrasound revealed a hypoechoic lesion 0.6 × 0.5 × 0.4 cm in the left testicle. Patient was referred to genetic testing with high suspicion of mild androgen insensitivity syndrome.

Discussion

Mild androgen insensitivity syndrome (MAIS) is a form of AIS that is characterized by external genitalia that is phenotypically male. Most patients with MAIS present with male infertility factor, which highlights how unusual our case is given that he fathered 2 children. Unlike other AIS phenotypes, AR mutations in MAIS are most commonly missense mutations of the N-terminal domain. Our case highlights the importance of considering MAIS in the differential diagnosis of phenotypic males with biochemical hypergonadotropic hypergonadism who clinically are not hyperandrogenic.

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