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



This was a case-control study of anterior pituitary hormone function in asymptomatic patients receiving a screening PSA. The results of the group of patients with screening PSA value of ≤0.1 ng/mL was compared to the control group with a screening PSA value of 1 to 4 ng/mL. The VA-Nebraska Western Iowa Health Care System (VA-NWIHCS) Institutional Review Board and the Research and Development Committee approved this project.

Subjects and Setting

All men presenting to their primary care doctor at the Omaha VA-NWIHCS for routine screening for prostate disease and who were identified to have a PSA level of ≤0.1 ng/mL were considered for the recruitment for the low-PSA case group. Subsequently, 20 subjects with a screening PSA 1 to 4 ng/mL were recruited for the control group. Exclusion criteria included any acute illness, known history of treated prostate cancer or medical/surgical treatment of benign prostate hyperplasia, and history of intake of medications that directly lower the PSA level, such as the 5-alpha-reductase inhibitors finasteride and dutasteride. Subjects were also evaluated for use of other over-the-counter supplements which could have lowered their testosterone, such as estrogen-containing compounds, and excluded if they were using any such supplements.


Potential study participants were identified through computer-generated lists of all VA-NWIHCS male patients with PSA ≤0.1 ng/mL. The study participants were prescreened through chart review, mailed an invite letter, and followed up with a phone call offering the opportunity to participate in the study. Subjects underwent clinical and hormonal evaluation after providing informed consent and meeting inclusion and exclusion criteria. Hormonal testing included morning fasting measurement of total and free testosterone, luteinizing hormone, follicle-stimulating hormone, IGF-1, GH, prolactin, free thyroxine (FT4), thyroid-stimulating hormone, cortisol, and adrenocorticotropic hormone levels. Using the recommendations of the Endocrine Society,[14] patients who had central (hypogonadotropic) hypogonadism also received follow-up evaluation by pituitary magnetic resonance imaging (MRI). Twenty additional subjects were enrolled in the normal-PSA control group (PSA ranging from 1 to 4 ng/mL). The normal-PSA control group completed the same hormonal testing utilizing the same assays as the low-PSA group.

Hormonal Assays

PSA was measured by Access Immunoassay Systems (Beckman Coulter, Fullerton, CA) using the Hybritech PSA method, a 2-site immunoenzymatic ("sandwich") assay. The lowest detectable level of PSA distinguishable from zero (with the Access Hybritech PSA calibrator) with 95% confidence is <0.08 ng/mL (reference range, 0 to 4 ng/mL).

A single fasting morning (before 10:00 AM) venous blood sample was obtained from each subject. Testosterone was measured using a Beckman Coulter Access Testosterone paramagnetic particle chemiluminescent immunoenzymatic assay with a normal range of 170 to 720 ng/dL (conversion factor of 0.0347 to SI units, nmol/L). Standard clinical assays were used to measure hormonal values, and standard reference ranges were used to interpret the data.

Statistical Analysis

PASW Statistics 19.0 (SPSS Inc, Chicago, IL) was used to generate the descriptive statistics. All values are expressed as the mean ± standard deviation. Paired t test was used to compare all hormonal values (except for IGF-1) in the low- and normal-PSA groups. Given the age-dependent reference range for IGF-1, in addition to the mean value, we calculated the difference between each patient's observed IGF-1 and the IGF-1 age-specific lower limit. The odds ratios (ORs) for having hypogonadism and associated 95% confidence intervals (CIs) were calculated using the Cochran-Mantel-Haenszel test.