What is the best course of action for a patient presenting with fatigue, testicular atrophy, throbbing pain, hair loss, and insomnia, but normal erectile function, and no history of hypogonadism (low sex hormone production)?

Evaluation and Management Approach

Order two separate early morning (8-10 AM) total testosterone measurements along with luteinizing hormone (LH), and conduct a focused physical examination of the testes to evaluate for testicular pathology given the concerning symptoms of testicular pain and atrophy. 1

Immediate Diagnostic Workup

The patient's constellation of symptoms—fatigue, testicular atrophy with daily throbbing pain, and hair loss—warrants a comprehensive hypogonadism evaluation, even though erectile function remains normal. 1, 2

Required Laboratory Testing

• Two morning total testosterone levels (drawn between 8-10 AM on separate occasions using the same laboratory): Diagnosis requires levels consistently <300 ng/dL 1, 2
• Serum LH measurement: This distinguishes primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism and is mandatory in all patients with low testosterone 1, 2
• Free testosterone or sex hormone-binding globulin (SHBG): Consider measuring these, particularly if total testosterone is borderline or the patient has obesity or other conditions affecting SHBG 1, 3
• Serum prolactin: Measure if LH is low or low-normal, as this screens for hyperprolactinemia and possible pituitary tumors 1, 2

Critical Physical Examination Components

The physical exam must specifically assess: 1, 2

• Testicular size, consistency, and presence of masses: Small or soft testes indicate testosterone deficiency
• Body hair patterns in androgen-dependent areas (chest, face, pubic region)
• Body mass index or waist circumference
• Presence of gynecomastia
• Varicocele presence

Why This Patient Requires Urgent Evaluation

The testicular atrophy with daily throbbing pain is particularly concerning and requires urgent assessment to rule out testicular pathology beyond simple hypogonadism. 1 This symptom pattern is not typical of uncomplicated testosterone deficiency and may indicate:

• Primary testicular failure
• Testicular torsion (though chronic pain makes this less likely)
• Testicular mass or malignancy
• Orchitis or epididymitis
• Varicocele

Interpretation Algorithm Based on Results

If Both Testosterone Levels Are Low (<300 ng/dL):

With Low or Low-Normal LH (Secondary Hypogonadism): 1, 2

• Measure prolactin immediately
• If prolactin is elevated, evaluate for pituitary adenoma or other endocrine disorders
• Consider MRI of the sella turcica if prolactin persistently elevated
• These patients are candidates for selective estrogen receptor modulator therapy if fertility preservation is desired 1

With Elevated LH (Primary Hypogonadism): 1, 2

• Indicates testicular failure
• Correlates with the patient's reported testicular atrophy
• Testosterone replacement therapy is the primary treatment option
• Further workup for etiology of testicular dysfunction is warranted given the pain symptoms

If Testosterone Levels Are Normal:

Do not stop here. Normal total testosterone does not exclude hypogonadism, particularly in older patients or those with elevated SHBG. 3 In one study of men with erectile dysfunction, 17.2% had normal total testosterone but low free testosterone, with 74.2% of these patients being over 60 years old. 3

• Measure free testosterone by equilibrium dialysis or calculate it using total testosterone and SHBG 1, 3
• Low free testosterone (<6.5 ng/dL) with normal total testosterone still represents biochemical hypogonadism requiring treatment 3

Common Pitfalls to Avoid

• Do not diagnose or exclude hypogonadism based on a single testosterone measurement 1, 2
• Do not measure testosterone at random times of day: Diurnal variation makes afternoon/evening measurements unreliable 1, 2
• Do not rely on screening questionnaires: They have poor sensitivity and specificity and should never replace laboratory testing 1, 2
• Do not overlook free testosterone in patients with borderline total testosterone: This is especially critical as total testosterone alone can miss 17% of hypogonadal cases 3
• Do not ignore the testicular pain and atrophy: These physical findings require direct evaluation and may indicate pathology requiring urgent intervention beyond hormone replacement 1

Additional Considerations

The patient's symptoms of fatigue, hair loss, and poor sleep are consistent with hypogonadism, but normal erectile function is somewhat atypical. 1, 2 However, erectile function can be preserved in early or partial hypogonadism, and libido changes typically precede erectile dysfunction. 4

The testicular pain requires specific attention: If physical examination reveals masses, significant asymmetry, or other concerning findings, urgent urological referral is indicated regardless of testosterone levels. 1