Workup for Elevated Testosterone (Hyperandrogenism)
The initial workup for elevated testosterone should include comprehensive hormonal testing, imaging studies when indicated, and evaluation for underlying causes, with specific tests determined by the patient's clinical presentation and gender.
Initial Laboratory Assessment
- Measure morning total testosterone concentration between 8 AM and 10 AM, and repeat if elevated to confirm the finding 1
- Obtain free testosterone level by equilibrium dialysis and sex hormone-binding globulin (SHBG) level, especially in patients with obesity 1
- Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary (testicular/ovarian) from secondary (pituitary-hypothalamic) causes 1, 2
- Measure serum prolactin levels, particularly in patients with low or low/normal LH levels 1, 2
- Measure serum estradiol in patients presenting with breast symptoms or gynecomastia 1, 2
- Consider measuring dehydroepiandrosterone sulfate (DHEAS) to evaluate for adrenal causes of hyperandrogenism 3, 4
Additional Testing Based on Initial Results
- If testosterone is markedly elevated (>2x upper limit of normal), obtain DHEAS to rule out androgen-secreting adrenal tumors 4, 5
- If prolactin is elevated, repeat measurement to ensure the elevation is not spurious 1
- For men with total testosterone <150 ng/dL with low/normal LH, obtain pituitary MRI regardless of prolactin levels 1
- For women with signs of androgen excess, consider 17-hydroxyprogesterone test to screen for nonclassic congenital adrenal hyperplasia 6
Imaging Studies When Indicated
- Pituitary MRI for patients with persistently elevated prolactin levels or significantly abnormal hormone patterns 1, 2
- Pelvic ultrasonography in women to evaluate for polycystic ovaries or ovarian tumors 2, 3
- Consider adrenal imaging (CT/MRI) when DHEAS is markedly elevated (>600 mg/dL) 3, 4
Clinical Assessment
- Evaluate for clinical signs of hyperandrogenism:
- Assess for cardiovascular risk factors (dyslipidemia, hypertension, diabetes) 1
- Measure hemoglobin/hematocrit as baseline before any testosterone therapy 1
- In men over 40, measure PSA and perform digital rectal examination 1
Differential Diagnosis Considerations
- For women: polycystic ovary syndrome (PCOS), non-classical congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome 6, 3
- For men: exogenous testosterone use, androgen-producing tumors, congenital adrenal hyperplasia 7
Important Caveats
- Testosterone levels can be affected by obesity, which lowers SHBG and may affect interpretation of total testosterone 1, 4
- Severe hyperandrogenism with rapid onset or virilization should prompt urgent evaluation for androgen-secreting tumors 3, 5
- In men interested in fertility, exogenous testosterone therapy should be avoided as it can suppress spermatogenesis 1
- For men with elevated testosterone who are on testosterone therapy, consider checking levels 2-3 months after treatment initiation or dose changes 1
Follow-up Recommendations
- For confirmed hyperandrogenism, treatment should target the underlying cause 2
- Regular monitoring of hormone levels to assess treatment efficacy 1, 2
- For men on testosterone therapy, monitor testosterone levels, hemoglobin/hematocrit, and PSA at 3-6 month intervals for the first year and yearly thereafter 1