Evaluation and Management of Elevated Testosterone in Adults
Elevated testosterone in adults is exceedingly rare and requires immediate systematic evaluation to exclude androgen-secreting tumors, exogenous steroid use, or laboratory error before considering other etiologies.
Initial Diagnostic Approach
Confirm the Elevation
- Repeat morning total testosterone (8–10 AM) on at least two separate occasions using a highly accurate assay (LC-MS/MS certified by the CDC Hormone Standardization Program) to exclude laboratory error and account for diurnal variation 1, 2, 3.
- A single elevated measurement is insufficient for diagnosis due to significant intra-individual variability and potential assay inaccuracy 2, 3.
- Normal adult male testosterone ranges from approximately 264–916 ng/dL, with mean values around 500–600 ng/dL; values consistently above the upper limit warrant investigation 1.
Obtain Detailed Clinical History
- Screen for exogenous testosterone or anabolic steroid use (prescribed, over-the-counter supplements, or illicit sources), as this is the most common cause of elevated testosterone in clinical practice 4.
- Ask specifically about testosterone replacement therapy, bodybuilding supplements, performance-enhancing drugs, and DHEA supplementation 4.
- Assess for symptoms of androgen excess: severe acne, aggressive behavior, rapid muscle gain, testicular atrophy (in exogenous use), or virilization 4.
Essential Laboratory Workup
Core Hormone Panel
Measure serum LH and FSH to differentiate the mechanism of testosterone elevation 5, 4:
- Suppressed LH/FSH with elevated testosterone → exogenous androgen use or androgen-secreting tumor
- Elevated LH/FSH with elevated testosterone → rare primary testicular disorders (e.g., hCG-secreting tumors)
- Normal LH/FSH with elevated testosterone → consider laboratory error or repeat testing
Measure DHEA and DHEA-S to assess adrenal androgen contribution 4:
- Markedly elevated DHEA-S suggests adrenal source (adenoma, carcinoma, or congenital adrenal hyperplasia)
- DHEA-S is produced exclusively by the adrenal glands and does not aid in diagnosing testicular sources 4
Measure 17-hydroxyprogesterone (17-OHP) early morning levels to screen for late-onset congenital adrenal hyperplasia (21-hydroxylase deficiency), which can present with elevated androgens in adulthood 4.
Measure serum prolactin if LH is low or low-normal, as pituitary tumors can cause secondary hormonal dysregulation 4.
Measure estradiol to evaluate for aromatization of excess androgens and assess gynecomastia risk 4.
Additional Assessments
- Check hematocrit/hemoglobin because elevated androgens stimulate erythropoiesis and can cause polycythemia 4, 6.
- Obtain lipid profile and blood pressure to assess cardiovascular risk, particularly if androgen excess has been prolonged 4.
- Measure liver function tests if pharmacologic therapy or tumor is suspected 4.
Imaging Studies
When to Order Imaging
Obtain testicular ultrasound if testosterone is severely elevated (>1,200 ng/dL) with suppressed LH/FSH to exclude Leydig cell tumor or other testicular masses 4.
Obtain adrenal CT or MRI if DHEA-S is markedly elevated or if 17-OHP suggests adrenal pathology 4:
Obtain pituitary MRI if prolactin is elevated or if clinical features suggest pituitary pathology 4.
Differential Diagnosis and Management
Exogenous Androgen Use (Most Common)
- Immediately discontinue all exogenous testosterone or anabolic steroids with gradual tapering to prevent withdrawal symptoms 4.
- Counsel on cardiovascular risks, including myocardial infarction, stroke, and thromboembolism associated with supraphysiologic androgen levels 4, 6.
- Repeat testosterone, LH, and FSH at 1–2 months after cessation to confirm normalization 4.
Androgen-Secreting Tumors
Testicular tumors (Leydig cell, Sertoli cell):
Adrenal tumors:
Congenital Adrenal Hyperplasia (Late-Onset)
- Initiate glucocorticoid therapy (hydrocortisone 15–25 mg/day in divided doses or equivalent) to suppress excessive ACTH-driven androgen production 4.
- Refer to endocrinology for long-term management and genetic counseling 4.
Laboratory Error
- If repeat testing with LC-MS/MS shows normal testosterone and the clinical picture does not support androgen excess, no further workup is needed 2, 3.
Monitoring and Follow-Up
- Recheck testosterone, DHEA, and DHEA-S at 1–2 months after intervention to assess treatment efficacy 4.
- Monitor hematocrit for polycythemia; withhold therapy if hematocrit >54% 4, 6.
- Assess lipid profile and blood pressure regularly for cardiovascular risk 4.
- Repeat imaging (testicular or adrenal) at 3–6 months if tumor was identified and managed conservatively 4.
Critical Pitfalls to Avoid
- Do not overlook exogenous androgen use; directly ask about all supplements, over-the-counter products, and illicit substances 4.
- Do not rely on a single elevated testosterone measurement; always confirm with repeat testing using an accurate assay 2, 3.
- Do not delay imaging if testosterone is severely elevated (>1,200 ng/dL) with suppressed gonadotropins, as this suggests tumor 4.
- Do not miss late-onset congenital adrenal hyperplasia; always measure 17-OHP in young adults with elevated androgens 4.
- Do not ignore cardiovascular risk; elevated androgens increase risk of myocardial infarction, stroke, and thromboembolism 4, 6.