What initial laboratory tests are recommended for a 14-year-old boy with suspected hypogonadism?

Initial Laboratory Evaluation for Suspected Hypogonadism in a 14-Year-Old Boy

The initial laboratory workup for a 14-year-old boy with suspected hypogonadism should include morning total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and serum prolactin if testosterone and LH are both low. 1

Core Hormonal Assessment

Primary Testosterone Measurement

• Obtain a morning total testosterone level using an accurate and reliable assay, as testosterone exhibits significant diurnal variation with highest levels in the morning 1
• If total testosterone is low or borderline, measure free testosterone either by equilibrium dialysis (gold standard) or calculated from total testosterone, sex hormone-binding globulin (SHBG), and albumin 1
• The free testosterone index (total testosterone/SHBG ratio) can help assess true gonadal status, particularly important in adolescents where SHBG levels may vary 1

Gonadotropin Assessment

• Measure LH and FSH simultaneously with testosterone to distinguish primary (testicular) from secondary (central) hypogonadism 1, 2
• Low testosterone with elevated LH/FSH indicates primary hypogonadism (testicular failure), while low or low-normal LH/FSH suggests secondary hypogonadism (hypothalamic-pituitary dysfunction) 2, 3, 4
• FSH levels are particularly valuable in adolescents as they remain detectable during childhood, unlike LH which is physiologically low until puberty onset 5

Additional Hormonal Testing

• Measure serum prolactin if testosterone and LH are both low or low-normal to screen for hyperprolactinemia 1
• If prolactin is elevated, repeat the measurement to exclude spurious elevation before pursuing further pituitary evaluation 1
• Check inhibin B levels as they correlate with testicular function and spermatogenic capacity; very low levels suggest primary testicular dysfunction 2

Supplementary Laboratory Tests

Anti-Müllerian Hormone (AMH)

• Consider measuring AMH, which remains elevated during childhood and can help diagnose central hypogonadism before puberty when testosterone and LH are physiologically low 1, 5
• AMH assessment may be particularly useful in prepubertal boys (before age 13-14) where traditional markers are less reliable 5

Metabolic and Nutritional Assessment

• Check thyroid function (TSH and free T4) as thyroid disorders can affect pubertal development 1
• Measure 25-hydroxyvitamin D levels, as vitamin D deficiency is common and affects bone health during critical growth periods 1
• Assess for metabolic conditions including fasting glucose and lipid panel, as obesity and metabolic syndrome are associated with functional hypogonadism 1

Critical Diagnostic Considerations

Timing and Interpretation

• At age 14, this patient is at the expected age of pubertal onset, making the distinction between constitutional delay of puberty versus true hypogonadism challenging 2, 6
• Testosterone levels below 8 nmol/L (approximately 230 ng/dL) strongly support hypogonadism, while levels above 12 nmol/L (approximately 350 ng/dL) suggest normal function 6
• The "grey zone" between these values requires assessment of free testosterone and clinical correlation 6

When to Pursue Advanced Testing

• If testosterone is <150 ng/dL with low or low-normal LH, consider pituitary MRI regardless of prolactin levels to exclude non-secreting adenomas 1
• Persistently elevated prolactin warrants endocrinology referral and pituitary imaging to evaluate for prolactinoma 1
• Anosmia or hyposmia should prompt consideration of Kallmann syndrome; formal olfactory testing may be needed as patients may not spontaneously report smell deficits 2

Common Pitfalls to Avoid

• Do not obtain testosterone levels during acute illness, as stress and systemic disease can transiently suppress the hypothalamic-pituitary-gonadal axis 1
• Avoid single measurements for diagnosis; confirm abnormal results with repeat testing given normal physiologic variability 1
• Do not overlook physical examination findings including testicular volume (normally >4 mL at puberty onset), presence of gynecomastia, body proportions (eunuchoid if arm span exceeds height by >5 cm), and Tanner staging 1, 2
• Screen for systemic conditions that can cause functional hypogonadism including chronic illness, malnutrition, excessive exercise, and medications (particularly opioids and corticosteroids) 1, 6

Baseline Assessment Before Any Treatment

• Document baseline hemoglobin/hematocrit before considering any future testosterone therapy 1
• Measure bone mineral density if hypogonadism is confirmed, as adolescence is a critical period for bone mass accrual 1
• Assess fertility potential with testicular examination and consider FSH levels, as this information is crucial for future treatment decisions 1