Characterization and management of testicular pathology in McCune-Albright syndrome.

CONTEXT

The testicular phenotype in McCune-Albright syndrome (MAS) has not been well characterized. Boys present with a relatively low incidence of precocious puberty in comparison with girls. Radiographic and histological studies are limited to small series and case reports, which report testicular microlithiasis and Sertoli cell hyperplasia.

OBJECTIVE

Our objective was to characterize the biochemical, radiological, and histological spectrum and clinical management of testicular pathology in males with MAS.

PATIENTS, DESIGN, AND SETTING: Fifty-four males with MAS participated in this prospective cohort study at a clinical research center.

INTERVENTION

Evaluation included testicular exam, pubertal staging, testicular ultrasound, measurement of LH, FSH, and testosterone. Orchiectomies were performed when considered clinically indicated.

MAIN OUTCOME MEASURE

Prevalence and characterization of ultrasound lesions with correlation to histology were evaluated.

RESULTS

Of 54 males, 44 (81%) presented with ultrasound abnormalities including hyperechoic lesions (49%), hypoechoic lesions (30%), microlithiasis (30%), heterogeneity (47%), and focal calcifications (11%). Eight subjects underwent orchiectomy revealing large foci of Leydig cell hyperplasia, which could not be definitively distinguished from Leydig cell tumor. After no subjects developed clinical malignancy, a conservative approach was instituted, and subsequent subjects were followed with serial imaging. Testosterone and gonadotropins were normal in subjects without precocious puberty or pituitary disease. Eleven (21%) presented with precocious puberty, and a combination of aromatase inhibitors, androgen receptor blockers, and leuprolide resulted in improved predicted adult height. In addition, the first cases of testicular adrenal rest and bilateral germ cell tumors in association with MAS are presented.

CONCLUSIONS

Contrary to prevailing thinking, the incidence of gonadal pathology in MAS is equal in males and females. The predominant histopathological finding was Leydig cell hyperplasia, which carries a low risk of malignant transformation and can be managed conservatively.