Medical Forum

A Veteran Presenting for Low Testosterone and Lower Urinary Tract Symptoms

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Case Presentation: A 76-year-old patient presented with decreased libido, repeated low testosterone levels, and lower urinary tract symptoms. He had a history of a left nephrectomy approximately 17 years prior for presumed renal cell carcinoma (RCC) subsequently complicated by chronic kidney disease stage 4, benign prostatic hypertrophy, erectile dysfunction, and a 50-pack-year history of smoking. His medications included tadalafil, tamsulosin, oxybutynin, and losartan.



►Anish Bhatnagar, MD, Chief Medical Resident, Veterans Affairs Boston Healthcare System (VABHS) and Beth Israel Deaconess Medical Center (BIDMC): The patient noted erectile dysfunction starting 4 years ago, with accompanied decreased libido. However, until recently, he was able to achieve acceptable erectile capacity with medications. As part of his previous evaluations for erectile dysfunction, the patient had 2 total testosterone levels checked 6 months apart, both low at 150 ng/dL and 38.3 ng/dL (reference range, 220-892). The results of additional hormone studies are shown in the Table. Dr. Ananthakrishnan, can you help us interpret these laboratory results and tell us what tests you might order next?

►Sonia Ananthakrishnan, MD, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center (BMC) and Assistant Professor of Medicine, Boston University School of Medicine (BUSM): When patients present with signs of hypogonadism and an initial low morning testosterone levels, the next test should be a confirmatory repeat morning testosterone level as was done in this case. If this level is also low (for most assays < 300 ng/dL), further evaluation for primary vs secondary hypogonadism should be pursued with measurement of luteinizing hormone and follicle-stimulating hormone levels. Secondary hypogonadism should be suspected when these levels are low or inappropriately normal in the setting of a low testosterone level as in this patient. This patient does not appear to be on any medication or have reversible illnesses that we traditionally think of as possibly causing these hormone irregularities. Key examples include medications such as gonadotropin-releasing hormone analogs, glucocorticoids, and opioids, as well as conditions such as hyperprolactinemia, sleep apnea, diabetes mellitus, anorexia nervosa, or other chronic systemic illnesses, including cirrhosis or lung disease. In this setting, further evaluation of the patient’s anterior pituitary function should be undertaken. Initial screening tests showed mildly elevated prolactin and low normal thyroid-stimulating hormone levels, with a relatively normal free thyroxine. Given these abnormalities in the context of the patient’s total testosterone level < 150 ng/dL, magnetic resonance imaging (MRI) of the anterior pituitary is indicated, and what I would recommend next for evaluation of pituitary and/or hypothalamic tumor or infiltrative disease.1

Laboratory Results

►Dr. Bhatnagar: An MRI of the brain showed a large 2.7-cm sellar mass, with suprasellar extension and mass effect on the optic chiasm and pituitary infundibulum, partial extension into the right sphenoid sinus, and invasion into the right cavernous sinus. These findings were consistent with a pituitary macroadenoma. The patient was subsequently evaluated by a neurosurgeon who felt that because of the extension and compression of the mass, the patient would benefit from surgical resection.

Given his lower urinary tract symptoms, a prostate-specific antigen level was checked and returned elevated at 11.5 ng/mL. In the setting of these abnormalities, the patient underwent MRI of the abdomen, which noted a new 5.6-cm enhancing mass in the upper pole of his solitary right kidney, highly concerning for new RCC. After a multidisciplinary discussion, urology scheduled the patient for partial right nephrectomy first, with plans for pituitary resection only if the patient had adequate recovery following the urologic procedure.

Dr. Rifkin, this patient went straight from imaging to presumed diagnosis to planned surgical intervention without a confirmatory biopsy. In a patient who already has chronic kidney disease stage 4, why would we not want to pursue biopsy prior to this invasive procedure on his solitary kidney? In addition, given his baseline advanced renal disease, why pursue partial nephrectomy to delay initiation of hemodialysis instead of total nephrectomy and beginning hemodialysis?

►Ian Rifkin, MBBCh, PhD, MSc, Chief, Renal Section, VABHS, Section of Nephrology, BMC, and Associate Professor of Medicine, BUSM: In most cases, imaging alone is used to make a presumptive diagnosis of benign vs malignant renal masses. In one study, RCC was identified by MRI with 85% sensitivity and 76% specificity.2 However, as imaging and biopsy techniques have advanced, there are progressing discussions regarding the utility of biopsy. That being said, there are a number of situations in which patients currently undergo biopsy, particularly when there is diagnostic uncertainty.3 In this patient, with a history of RCC and imaging findings concerning for RCC, biopsy is unnecessary given the high clinical suspicion.

Regarding the choice of partial vs total nephrectomy, there are 2 important distinctions to be made. The first is that though it was previously felt that early initiation of dialysis improves survival, newer studies suggest that early initiation based off of glomerular filtration rate (GFR) offers no survival benefits compared to delayed initiation.4 Second, though there is less clinical data to support this, there is a signal toward the use of partial nephrectomy decreasing mortality compared to radical nephrectomy in management of RCC.5 In this patient, partial nephrectomy may not only increase rates of survival, but also delay initiation of dialysis.

►Dr. Bhatnagar: Prior to undergoing partial right nephrectomy, a morning cortisol level was found to be 5.8 μg/dL with an associated corticotropin (ACTH) level of 26 pg/mL. Dr. Ananthakrishnan, how would you interpret these laboratory results and what might you recommend prior to surgery?


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