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It takes a careful stepwise approach to diagnose and treat patients withlow testosterone, says Cully C. Carson, MD, chair of urology at University ofNorth Carolina at Chapel Hill School of Medicine.
Once a dialogue has been established and causes of hypogonadism such ascurrent medications have been ruled out, a thorough diagnosis is vital toensure that hypogonadism is not a symptom of a serious health issue, such as apituitary tumor. Prolactin and thyrotropin levels in particular could indicatea pituitary cause of low testosterone.
CHECKING IT TWICE
When a first test finds that somebody's testosterone level is low, there isenough variation in test levels in normal people that the results need to beconfirmed, says andrologist Bradley Anawalt, MD, associate professor atUniversity of Washington in Seattle and associate chief of medicine at theVeterans Affairs Puget Sound Health Care System.
Check testosterone a second time before 10 a.m., since circadian rhythmsnormally cause testosterone levels to be highest in the morning, Anawaltsays.
Patients may have symptoms of hypogonadism while total testosterone levelsremain in the normal range. But because levels of sex hormone–bindingglobulin (SHBG) rise with age, and SHBG binds with testosterone, there may beless unbound testosterone available to do its work.
"I think primary care providers should confirm it if they can with anaccurate assessment of calculated free and weakly bound testosterone,"Anawalt says. Carson suggests testing for total testosterone first, and usingthe more costly and time-consuming test of free testosterone only if thepatient's symptoms warrant.
WHEN TO TEST GONADOTROPINS
For every man whose low testosterone is confirmed, the next step is tocheck the gonadotropins leutinizing hormone (LH) and follicle-stimulatinghormone (FSH). Although levels may vary from lab to lab, in general theyshould fall between 1–11 mIU/ml. If the gonadotropins are elevated, theclinician does not need to perform any more tests because it means the problemstems from the testicles not working. In that setting, tests for prolactin andthyroid-stimulating hormone (TSH) are not necessary, and testosteronereplacement could be considered.
If LH and FSH levels are low or "inappropriately" normal, thenthe clinician also should look for low thyroid hormone and TSH levels andelevated prolactin levels, because the pituitary could be involved.
Anawalt says most experts recommend assessment for hemochromatosis (ironoverload), which can occur if someone is receiving numerous bloodtransfusions. He also suggests assessment for excess corticosteroids(Cushing's syndrome) as well as any exogenous steroid use (either estrogen orandrogens), particularly in younger men. Anabolic steroids can result in lowtestosterone and low LH and FSH by turning off thepituitary.
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Checking thyroid function with both thyroxine (T4) and TSH levels generallycan be helpful, too, Anawalt says. For those whose thyroid function andprolactin levels are okay, pituitary imaging may not be necessary. But all men<50 years of age with a very low testosterone level (<200 ng/dl) and lowor normal gonadotropins should have pituitary testing with a CT or MRI scan,says Richard J. Santen, MD, professor of medicine in the division ofendocrinology and metabolism at the University of Virginia inCharlottesville.
"There is some debate about this, but I think the majority ofendocrinologists would agree this is probably the cutoff," Santen says."The primary care practitioner would probably refer if testosterone islow and LH and FSH are low. Testosterone <200 ng/dl and high LH and FSHprobably also merit a referral, because that indicates clear-cut endocrinedisease." 
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