Is the patient pre- or postpubertal?
Assessment of low testosterone should distinguish between pre- and postpubertal males. In prepubertal males, chromosomal analysis is indicated because hypothalamic-pituitary-gonadal axis defects are common—especially Klinefelter syndrome (1 in 500 males).6,8
Men with very low testosterone levels (<150 ng/dL) or signs and symptoms suggesting pituitary pathology warrant pituitary imaging and measurement of thyroxine, cortisol, and prolactin levels.6 Both pre- and postpubertal males with low testosterone should have FSH, LH, and prolactin levels tested to differentiate primary from secondary hypogonadism.6,9
Be alert for hemochromatosis and low bone density
Order biopsy or ultrasound examination of testicular masses and iron studies if hemochromatosis is suspected. Hemochromatosis is the most common single gene disorder of Caucasian Americans (1 in 250-300 are homozygous; 1 in 10 are heterozygous) and is associated with hypogonadotrophic hypogonadism.5,10 In a series of 3 studies, 30% (26 of 89) of men with hemochromatosis had hypogonadism.11 The prevalence of hemochromatosis in males with hypogonadism hasn’t been reported.
Because chronic hypogonadism leads to low bone density and increased risk of fracture, baseline bone densitometry may be prudent.12 A chart review study of nursing home residents found that 66% of men with hip fractures and 20% of men with vertebral fractures had low testosterone.13 Notably, 50% of men in their 80s have testosterone levels in the hypogonadal range (<300 ng/dL), compared with 12% of men <50 years.1,14
Recommendations
Scant guidance is available concerning what screening tests to order for a male with low testosterone. The United States Preventive Services Task Force and Canadian Task Force on Preventive Health Care make no recommendations; the Cochrane collaboration has no reviews on the topic. The American Association of Clinical Endocrinologists’ (AACE) guidelines are based on expert opinion.3
The AACE consensus guideline used peer review for validation and didn’t specify the method used to assess the quality and strength of the evidence used to write the statement. The AACE guideline recommends a history and physical exam, obtaining repeat morning testosterone levels, prolactin, FSH, LH, bone densitometry, and a semen analysis if fertility is an issue.
In acquired hypogonadism, pituitary imaging is recommended along with thyroid, adrenal, and growth hormone axis testing. Prepubertal males should undergo chromosome analysis, and men with a suspected mass should have a testicular ultrasound examination.