Pituitary Evaluation in Patients With Low Prostate-Specific Antigen

Andjela Drincic, MD; Anh-Thu Nguyen, MD; Shilpi Singh, MBBS; Mohsen Zena, MD; Ryan Walters, PhD; Kathryn Friedman, RN; Robert J. Anderson, MD


Endocr Pract. 2018;24(12):1030-1037. 

In This Article


Serum prostate-specific antigen (PSA) is a tool to screen for or to follow-up patients with prostate cancer.[1] In the absence of prostate cancer, serum PSA concentrations positively correlate with age and prostate volume.[2,3] The lower reference range for serum PSA is <0.08 ng/mL. However, a PSA <0.1 ng/mL is unusual for any man above age 40 years.[2,3] An interesting question is whether a very low PSA value may be of clinical significance by indicating an abnormally small prostate volume that may be associated with clinically relevant hormonal deficiencies. Namely, the physiologic development and growth of the prostate depend primarily on testosterone.[4] Prostate volume and PSA are significantly lower in untreated hypogonadal men compared with both normal men and testosterone-treated hypogonadal men.[5] Growth hormone (GH) and insulin like growth factor-1 (IGF-1) also influence development and growth of the prostate. In addition, there is evidence for crosstalk between the androgen receptor and growth factor signaling pathways.[6] There is a positive association between IGF-1 and serum PSA values in healthy middle-aged men.[7] Pituitary dysfunction affects prostate volume. The prostate is enlarged in young acromegaly patients, despite concurrent hypogonadism,[8–10] whereas GH-deficient patients have a decreased prostate volume,[11] especially if hypogonadal.[11] GH replacement increases the prostate volume in patients with GH deficiency, more so if given concomitantly with testosterone.[12] We have reported a case series of 4 patients with low or undetectable PSA and associated panhypopituitarism.[13]

We hypothesized that hypogonadism and/or GH deficiency would lead to a state of abnormally low prostate volume and abnormally low PSA (i.e., <5th percentile of a normal population). As such, a very low PSA obtained for prostate cancer screening may be a sign of profound GH and testosterone deficiency that may be present in an otherwise asymptomatic patient with hypopituitarism. The purpose of this study was to prospectively evaluate the hypothesis that low PSA may be associated with hormonal deficiencies.