What are the guidelines for ordering testosterone testing in teenage boys (14-19 years old) with symptoms of hypogonadism, such as delayed puberty, gynecomastia, or low libido?

Ordering Testosterone Testing for Teenage Boys

When to Order Testosterone Testing

Testosterone testing in teenage boys (14-19 years) should be ordered when specific clinical symptoms or signs of hypogonadism are present, including delayed puberty, gynecomastia with clinical hypogonadism features, diminished libido, erectile dysfunction, or high-risk conditions such as unexplained anemia, bone density loss, diabetes, chemotherapy exposure, testicular radiation, HIV/AIDS, chronic narcotic use, male infertility concerns, pituitary dysfunction, or chronic corticosteroid use. 1, 2, 3

Specific Clinical Indications

Delayed Puberty:

• Absence of testicular enlargement by age 14 years warrants evaluation 4, 5
• Lack of progression of secondary sexual characteristics after puberty has begun 5, 6
• Familial pattern of delayed puberty should be distinguished from pathological hypogonadism 4

Gynecomastia:

• Measure serum estradiol in testosterone-deficient patients who present with breast symptoms or gynecomastia prior to testosterone therapy 1
• Note that gynecomastia incidence in adolescents is approximately 35-36%, similar to typically developing boys, and does not automatically indicate hypogonadism 7

Other Symptoms:

• Low energy and fatigue (common presenting complaint in young men, unlike older men who typically report decreased libido) 3
• Reduced endurance, diminished work/physical performance 2
• Depression, reduced motivation, poor concentration, impaired memory, irritability 2
• Reduced sex drive or erectile dysfunction (less common in adolescents than adults) 2, 3

Proper Testing Protocol

Morning Testosterone Measurement:

• Draw two separate morning total testosterone levels between 8 AM and 10 AM 8, 2
• Low testosterone is defined as consistently <300 ng/dL on both measurements 8, 2
• Single measurements are insufficient due to assay variability and diurnal fluctuation 8

Additional Testing When Testosterone is Low:

• Measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG) levels, especially in boys with obesity 8
• Measure serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1, 8
  • Elevated LH/FSH with low testosterone = primary hypogonadism 8
  • Low or low-normal LH/FSH with low testosterone = secondary hypogonadism 1, 8

For Secondary Hypogonadism:

• Measure serum prolactin levels in patients with low testosterone combined with low or low-normal LH levels 1
• If prolactin is persistently elevated, refer to endocrinology for evaluation of pituitary tumors 1
• Consider pituitary MRI if total testosterone <150 ng/dL with low or low-normal LH, regardless of prolactin levels 1

Fertility Assessment (Critical in Adolescents):

• Perform testicular exam to evaluate testicular size, consistency, and descent 1
• Measure serum FSH to assess reproductive health status 1
• Consider semen analysis if FSH is elevated (hypergonadotropic hypogonadism) 1
• Offer reproductive genetics testing (karyotype and Y-chromosome microdeletion analysis) if severe oligospermia or non-obstructive azoospermia is present 1

Diagnostic Coding

Primary Code:

• Use E29.1 (Testicular hypofunction) when clinical suspicion of testosterone deficiency exists based on symptoms or risk factors 2

Supplementary Codes:

• N52.9 (Male erectile dysfunction, unspecified) if erectile dysfunction is the primary complaint 2
• R53.83 (Other fatigue) if fatigue is the presenting symptom 2
• F32.9 (Major depressive disorder, single episode, unspecified) if depressive symptoms are prominent 2
• D64.9 (Anemia, unspecified) if unexplained anemia is present 2

Critical Pitfalls to Avoid

Do Not:

• Order testosterone testing based on symptoms alone without considering age-appropriate development 2, 3
• Diagnose hypogonadism with a single testosterone measurement 8, 2
• Test testosterone at random times of day—must be morning samples 8, 2
• Assume gynecomastia automatically indicates hypogonadism (35-36% incidence is normal in adolescence) 7
• Start testosterone therapy without confirming the patient does not desire fertility preservation, as testosterone suppresses spermatogenesis 8, 3

Always:

• Distinguish between constitutional delay of growth and puberty (CDGP) versus pathological hypogonadism before initiating treatment 4, 6
• Obtain bone age X-ray (hand and wrist) every 6 months if testosterone therapy is initiated to monitor epiphyseal closure 4
• Consider reversible causes in young men, including obesity, diabetes, anabolic steroid use, or illicit drug use 3
• Refer to pediatric endocrinology for complex cases or when secondary hypogonadism is confirmed 1, 5

Special Considerations for Adolescents

Constitutional Delay vs. Hypogonadism:

• Brief treatment with conservative testosterone doses may be justified in carefully selected males with clearly delayed puberty who have a familial pattern and are expected to undergo spontaneous puberty 4
• Low-dose testosterone enanthate (50 mg monthly) for approximately 1 year can effectively induce puberty without compromising final adult height 9
• Discuss potential adverse effects on bone maturation with patient and parents prior to androgen administration 4

Fertility Preservation:

• For adolescents with secondary hypogonadism who may desire future fertility, gonadotropin therapy (recombinant hCG plus FSH) is mandatory and testosterone is absolutely contraindicated 8, 3
• Alternative agents that increase natural testosterone production without decreasing spermatogenesis include intranasal testosterone, selective estrogen receptor modulators, aromatase inhibitors, or human chorionic gonadotropin 3