This issue highlights a case from a free online educational activity for the Testosterone Therapy in Men with Hypogonadism: An Endocrine Society Clinical Practice Guideline. Test your clinical knowledge with more cases by enrolling in this activity.
Clinical Vignette
A 58-year-old moderately obese man is concerned that his erections are weak and insufficient to have satisfactory intercourse despite normal sexual desire. He also feels that his energy level is very low and has been worsening over the last 3 years. He has type 2 diabetes mellitus, coronary artery disease with stable angina, hypertension, and hypercholesterolemia. Current medications include metformin, hydrochlorothiazide, lisinopril, metoprolol, isosorbide mononitrate, and atorvastatin.
On physical examination, he is a plethoric, obese man with a mildly depressed mood. Blood pressure is 138/83 mm Hg. His height is 73.5 in (186.7 cm), and weight is 265 lb (120.2 kg) (BMI = 34.5 kg/m2). He has normal axillary and pubic hair. You palpate 2.5-cm, nontender breast tissue bilaterally. There are no striae on his abdomen, but you observe that he has prominent abdominal adiposity. He has normal-sized testes, 20 mL bilaterally. On examination of his extremities, he has 1+ ankle edema and no dorsalis pedis pulses bilaterally. Neurologic examination shows reduced vibratory sensation, but intact sensation to 10-g monofilament.
Laboratory test results (8 AM):
- Hematocrit = 46% (41%-50%) (SI: 0.46 [0.41-0.51])
- Fasting glucose = 178 mg/dL (70-99 mg/dL) (SI: 9.9 mmol/L [3.9-5.5 mmol/L])
- Creatinine = 1.2 mg/dL (0.7-1.3 mg/dL) (SI: 106.1 µmol/L [61.9-114.9 µmol/L])
- Estimated glomerular filtration rate = 75 mL/min per 1.73 m2 (>60 mL/min per 1.73 m2)
- Hemoglobin A1c = 7.7% (4.0%-5.6%) (61 mmol/mol [20-38 mmol/mol])
- Total testosterone = 250 ng/dL (300-900 ng/dL) (SI: 8.7 nmol/L [10.4-31.2 nmol/L])
Which of the following laboratory tests should you order next?
- Direct free testosterone measurement by immunoassay
- Serum LH measurement
- Calculated free testosterone level by equilibrium dialysis
- Serum prolactin measurement
- No further testing is necessary
SEE CORRECT ANSWER AND EXPLANATION
Correct Answer: C (Calculated free testosterone level by equilibrium dialysis)
Answer Discussion:
This patient has erectile dysfunction with normal libido and low energy, and his initial total testosterone level is low. Erectile dysfunction and low energy may be due to androgen deficiency, although this is less likely in the presence of normal libido. Because of the variability in serum testosterone measurements, the Endocrine Society guidelines recommend that testosterone levels be measured on at least 2 occasions to confirm a diagnosis of hypogonadism. The normal range for testosterone levels is based on peak levels that occur in the early-morning hours of the circadian cycle; confirmation of low testosterone levels should be done on an early-morning blood sample.
Moderate obesity is a common cause of decreased SHBG levels, and, in this obese man, the total testosterone level may be low because of low SHBG. Thus, measuring total testosterone again would not be helpful. If alterations in SHBG are suspected, as in this case, measurement of free testosterone should be performed using an accurate and reliable assay to confirm the diagnosis of hypogonadism. Accurate and reliable methods of free testosterone measurements include calculated free testosterone by equilibrium dialysis (Answer C), and free testosterone by equilibrium dialysis. Calculated free testosterone should be ordered next, as it is more practical than free testosterone by equilibrium dialysis that is more expensive, time-consuming and not always available to clinicians. Direct free testosterone measurements by analogue-based immunoassays (Answer A) are inaccurate and should not be used. Measuring serum LH (Answer B) or prolactin (Answer D) would not be helpful in establishing the diagnosis of hypogonadism (and measuring prolactin is only appropriate in patients with secondary hypogonadism). LH should be measured after the diagnosis of hypogonadism is confirmed to distinguish primary from secondary hypogonadism. Pursuing no further testing (Answer E) is inappropriate.
Educational objective:
When an alteration in the SHBG concentration is suspected, order an accurate and reliable measurement of free testosterone (free testosterone by equilibrium dialysis or calculated free testosterone) to confirm the diagnosis of hypogonadism.
Reference(s):
Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA; Task Force, Endocrine Society 2018 Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab https://doi.org/10.1210/jc.2018-00229
Goldman AL, Bhasin S, Wu FCW, Krishna M, Matsumoto AM, Jasuja R. A reappraisal of testosterone’s binding in circulation: physiological and clinical implications. Endocr Rev. 2017;38(4):302-324. PMID: 2867303928673039
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