What is the management approach for a 14-year-old with elevated testosterone and Dehydroepiandrosterone (DHEA) levels?

Management of a 14-Year-Old with Elevated Testosterone and DHEA

A 14-year-old with elevated testosterone and DHEA requires immediate comprehensive hormonal evaluation to exclude androgen-secreting tumors, congenital adrenal hyperplasia, and other serious endocrine disorders before considering physiologic pubertal variation. 1

Immediate Diagnostic Workup

Essential Laboratory Tests

• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish between primary gonadal disorders versus central causes of androgen excess 1, 2
• Obtain serum prolactin levels, particularly if LH is low or low-normal, as this may indicate a pituitary tumor causing secondary hormonal dysregulation 1, 2
• Measure 17-hydroxyprogesterone (17-OHP) early morning levels to screen for congenital adrenal hyperplasia, specifically 21-hydroxylase deficiency, which commonly presents with elevated androgens in adolescence 3
• Check ACTH levels to determine if excess cortisol or androgen production originates from the adrenal gland versus ectopic sources 3
• Assess estradiol levels to evaluate for aromatization of excess androgens and potential gynecomastia risk 1, 2

Critical Imaging Studies

• Obtain adrenal imaging (CT or MRI) if DHEA-S is markedly elevated (>16.3 μmol/L or 6000 ng/mL), as this suggests adrenal pathology including androgen-secreting tumors 4
  • Malignancy should be suspected if tumors are >3 cm, have irregular morphology, are lipid-poor, or secrete multiple hormones 3
• Consider pelvic ultrasound if testosterone is severely elevated (>8.7 nmol/L or 250 ng/dL) to evaluate for gonadal tumors, though this threshold has low positive predictive value (9%) 4
• Obtain pituitary MRI if testosterone is low with low/normal LH levels and elevated prolactin, or if clinical features suggest central pathology 1, 2

Differential Diagnosis Priority

High-Risk Conditions Requiring Urgent Evaluation

• Androgen-secreting tumors (ovarian or adrenal): Suspect if testosterone >8.7 nmol/L (250 ng/dL) with rapid virilization, though sensitivity is only 100% because these are rare 4
• Congenital adrenal hyperplasia: Elevated 17-OHP with decreased androstenedione and testosterone relative to DHEA suggests enzyme deficiencies like 11β-hydroxylase or 17α-hydroxylase deficiency 3
• Cushing syndrome: Check 24-hour urinary free cortisol if clinical features of hypercortisolism are present (hypertension, hyperglycemia, muscle atrophy) 3

Common Physiologic Considerations

• Normal pubertal progression: In healthy adolescents, DHEA rises significantly between ages 7-14, with levels increasing from 52.7 ng/100 mL at age 7 to 188 ng/100 mL at age 12 in boys 5
• In girls, DHEA increases from 44.7 ng/100 mL at age 6 to 80.9 ng/100 mL at age 8, with the first significant testosterone rise occurring at bone age 10 years 5
• DHEA elevation precedes gonadotropin increases and may play a role in hypothalamic-pituitary-gonadal axis maturation, so isolated mild DHEA elevation may be physiologic 5

Management Algorithm

If Tumor Suspected

• Refer immediately to pediatric endocrinology and surgical oncology for tumors >5 cm, inhomogeneous appearance, irregular margins, or local invasion 3
• Open adrenalectomy is recommended for suspected malignant hyperaldosteronism or androgen-secreting tumors prone to rupture 3
• Laparoscopic adrenalectomy is appropriate for benign adenomas when feasible, with postoperative corticosteroid supplementation required until HPA axis recovery 3

If Congenital Adrenal Hyperplasia Confirmed

• Initiate glucocorticoid therapy (typically hydrocortisone or prednisone) to suppress excessive ACTH-driven androgen production 3, 6
• Chronic low-dose prednisone therapy has demonstrated suppression of testosterone, DHEA, and DHEA-S in 75-80% of hyperandrogenic patients 6
• Monitor treatment response with repeat androgen levels; a 2-day dexamethasone suppression test quantitatively predicts degree of testosterone suppression better than overnight testing 6

If Exogenous Androgen Use Identified

• Immediately discontinue all exogenous testosterone or anabolic steroids with gradual tapering to prevent withdrawal symptoms 1
• Counsel on cardiovascular risks including atherosclerosis, adverse lipid changes, and thrombotic events from supraphysiologic androgen levels 1
• Discuss fertility implications, as elevated testosterone suppresses spermatogenesis through FSH feedback inhibition 1, 2

Monitoring and Follow-Up

Regular Laboratory Surveillance

• Recheck testosterone, DHEA, and DHEA-S levels at 1-2 months after intervention to assess treatment efficacy 1
• Monitor complete blood count for polycythemia, as elevated androgens increase hemoglobin/hematocrit 1
• Assess lipid profile and blood pressure regularly for cardiovascular risk, particularly in adolescents with prolonged androgen excess 1
• Measure liver function tests if pharmacologic therapy is initiated 1

Bone Age Assessment

• Obtain bone age radiograph to correlate hormonal levels with skeletal maturation, as DHEA and testosterone rise predictably with advancing bone age 5
• In boys, DHEA increases from 31.1 ng/100 mL at bone age 5 years to 221.2 ng/100 mL at bone age 12 years, with testosterone rising significantly at bone age 12 years 5

Critical Pitfalls to Avoid

• Do not assume physiologic puberty without excluding pathology: While DHEA naturally rises during adolescence, markedly elevated levels (>2-3 times upper normal for age) warrant investigation 5
• Testosterone and DHEA-S screening has poor positive predictive value (9% and unmeasurable respectively) for tumors due to low disease prevalence, but clinical evaluation with rapid virilization mandates imaging regardless 4
• Measure conjugated DHT metabolites (androsterone glucuronide, androstane-3α,17β-diol-G) as better markers of total androgenic activity than serum testosterone alone, which may remain normal despite significant tissue androgen exposure 7
• Avoid measuring random testosterone levels: Obtain early morning samples on at least two separate occasions for accuracy 8
• Do not overlook secondary hypertension: Children <6 years with hypertension or those with suggestive history/physical findings require extensive evaluation for secondary causes including androgen-secreting tumors 3