What are the implications and treatment options for elevated testosterone in an adolescent female?

Elevated Testosterone in a 14-Year-Old Female

In a 14-year-old female with elevated testosterone, immediately measure LH, FSH, prolactin, DHEA-S, and 17-hydroxyprogesterone to differentiate between ovarian, adrenal, and pituitary sources, with imaging (pelvic ultrasound and/or adrenal CT/MRI) indicated for markedly elevated levels (>2-3 SD above normal) to rule out androgen-secreting tumors. 1, 2, 3

Initial Diagnostic Workup

Laboratory Evaluation Priority

• Confirm the elevated testosterone with repeat testing, as laboratory interference from heterophile antibodies can cause falsely elevated results, particularly when clinical findings don't match the laboratory values 3, 4

• Measure comprehensive hormonal panel including:

  • LH and FSH levels to determine if the source is ovarian versus other 1, 2
  • Serum prolactin to screen for hyperprolactinemia and pituitary pathology 1, 2
  • DHEA-S to assess for adrenal source 2
  • 17-hydroxyprogesterone to evaluate for congenital adrenal hyperplasia 2
  • Estradiol levels if breast symptoms or other estrogenic effects are present 1

• Check hemoglobin/hematocrit as elevated testosterone can cause erythrocytosis, with levels above 50% warranting immediate investigation 1, 2

Clinical Assessment Specifics

Look for these key clinical features:

• Virilization signs: hirsutism, acne, clitoromegaly, voice deepening, male-pattern baldness 3, 5
• Menstrual history: primary amenorrhea, secondary amenorrhea, or irregular cycles 3, 6
• Growth patterns: accelerated growth velocity, advanced bone age 7
• PCOS features: obesity, acanthosis nigricans, insulin resistance 2, 6
• Timing and rapidity of symptom onset: rapid virilization suggests tumor 3

Critical caveat: Very high testosterone levels (>2-3 SD above normal) with absent or minimal virilization signs should raise suspicion for either laboratory interference or selective tissue response, requiring diethyl-ether extraction testing or liquid chromatography-mass spectrometry confirmation 3, 4

Imaging Studies

• Pelvic ultrasound is first-line to evaluate for ovarian tumors (steroid cell tumors, Leydig cell tumors) or polycystic ovaries 2, 3

• Adrenal CT or MRI if DHEA-S is elevated or clinical suspicion for adrenal source exists 2

• Pituitary MRI if LH is low or prolactin is elevated, as pituitary adenomas can cause hormonal dysregulation 1, 2

Common Etiologies in Adolescent Females

Most Likely Causes

• Polycystic ovary syndrome (PCOS): most common cause, typically with mild testosterone elevation, irregular menses, and metabolic features 2, 3, 6

• Congenital adrenal hyperplasia: particularly late-onset forms, identified by elevated 17-hydroxyprogesterone 2

• Androgen-secreting tumors: ovarian (steroid cell tumors) or adrenal, suggested by very high testosterone levels and rapid symptom onset 2, 3

• Exogenous androgen exposure: though less common in this age group, inquire about supplements or medications 2

Treatment Approach

If Tumor Identified

• Surgical removal is the primary treatment for ovarian or adrenal androgen-secreting tumors 1, 2

• Monitor testosterone levels 24 hours post-surgery to confirm normalization; levels should return to normal range immediately after successful tumor removal 3

• Follow-up monitoring includes repeat testosterone levels and assessment for menstrual cycle resumption (typically within 1 month post-surgery) 1, 3

If PCOS or Functional Hyperandrogenism

• Combined oral contraceptives are first-line to suppress ovarian androgen production and increase SHBG 6

• Anti-androgenic progestins (such as those containing cyproterone acetate or drospirenone) may be particularly useful 6

• Metformin if insulin resistance is present 6

If Congenital Adrenal Hyperplasia

• Glucocorticoid replacement to suppress ACTH-driven adrenal androgen production 2

Monitoring Parameters

• Testosterone levels every 3-6 months initially, then annually once stable 2

• Hemoglobin/hematocrit regularly, with intervention if hematocrit exceeds 50-54% 1, 2

• Menstrual cycle tracking to assess treatment efficacy 3

• Growth velocity and bone age in younger adolescents 7

Complications of Untreated Hyperandrogenism

• Reproductive effects: anovulation, infertility, menstrual irregularities 2, 3, 6

• Metabolic consequences: insulin resistance, type 2 diabetes risk, adverse lipid profile changes 2, 6

• Psychological impact: depression (testosterone levels correlate with depression in a parabolic curve, with both low and high levels associated with mood disturbances), aggressive behavior 6

• Cardiovascular risk: increased atherosclerosis risk, thrombotic events 2

• Irreversible virilization: voice deepening, male-pattern baldness if left untreated 7, 5

Key Clinical Pitfalls

Beware of laboratory interference: When testosterone levels are markedly elevated but clinical signs are absent or minimal, always confirm with alternative testing methods (liquid chromatography-mass spectrometry or diethyl-ether extraction) before pursuing invasive workup 3, 4

Don't overlook fertility implications: Elevated testosterone suppresses gonadotropins and can impair future fertility; early intervention is crucial for preserving reproductive potential 1, 2

Normal puberty can confound interpretation: Hormone levels fluctuate during adolescence, and confirmation of abnormal results is essential before initiating treatment 1, 2