What hormone levels should be checked in a male infant with micropenis?

Hormonal Evaluation in Male Infants with Micropenis

In a male infant with micropenis, you must immediately check serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to distinguish between hypogonadotropic hypogonadism (hypothalamic/pituitary failure) and hypergonadotropic hypogonadism (testicular failure), as this determines both prognosis and treatment approach. 1, 2

Initial Hormonal Assessment

The core hormonal panel should include:

• Serum testosterone: Essential to document testosterone deficiency, which is the most common cause of micropenis 3, 1
• Luteinizing hormone (LH): Distinguishes central (low/normal LH) from primary testicular failure (elevated LH) 4, 1
• Follicle-stimulating hormone (FSH): Helps assess testicular function and Sertoli cell integrity 4, 1

The optimal timing for this evaluation is during the "mini-puberty" period (first 2-3 months of life) when gonadotropins and testosterone are physiologically elevated, making interpretation more reliable. 2

Additional Hormonal Testing Based on Initial Results

If LH and FSH are Low or Low-Normal with Low Testosterone:

• Serum prolactin: Must be measured to screen for hyperprolactinemia, which can indicate pituitary pathology such as prolactinomas 4
• Growth hormone assessment: Growth velocity should be monitored, as associated hypothalamic or pituitary pathology is common in hypogonadotropic hypogonadism 1
• Consider pituitary MRI: If testosterone is severely low (<150 ng/dL equivalent for age) with low/normal LH, imaging may identify non-secreting adenomas or structural abnormalities 4

If LH and FSH are Elevated with Low Testosterone:

This indicates primary testicular failure (hypergonadotropic hypogonadism). Consider:

• Karyotype analysis: To evaluate for chromosomal abnormalities, particularly if bilateral testicular abnormalities are present 4, 1
• Anti-Müllerian hormone (AMH): May help assess Sertoli cell function in cases of suspected testicular dysgenesis 5

Critical Situations Requiring Immediate Specialist Consultation

If bilateral nonpalpable testes are present with micropenis, this is a medical emergency requiring immediate endocrinology consultation to rule out congenital adrenal hyperplasia (CAH) in a 46,XX individual with severe virilization. 4, 6 A phenotypic male newborn with bilateral nonpalpable testes could be a genetic female with life-threatening CAH that can cause shock, hyponatremia, and hyperkalemia if undiagnosed. 4, 6

In this scenario, additional urgent testing includes:

• 17-hydroxyprogesterone: To screen for CAH 4
• Serum electrolytes: To detect life-threatening electrolyte abnormalities 4
• Karyotype: To determine genetic sex 4

Functional Testing

GnRH stimulation test and/or hCG stimulation test: These are often helpful in evaluating the etiology when baseline hormones are equivocal, particularly to assess the capacity of the hypothalamic-pituitary-gonadal axis to respond 1, 2, 7

The hCG stimulation test specifically evaluates Leydig cell function and the penis's ability to respond to testosterone, which is prognostically important. 1, 7

Common Pitfalls to Avoid

• Do not delay hormonal evaluation: The mini-puberty window (first 2-3 months) provides the most reliable hormonal assessment; after this period, gonadotropins and testosterone naturally decline, making interpretation difficult 2
• Do not assume idiopathic micropenis without complete evaluation: Many cases have identifiable endocrine causes that require specific treatment 1, 2
• Do not order imaging before hormonal assessment: Ultrasound or other imaging of the genitalia rarely assists in decision-making and should not delay hormonal evaluation 4, 6
• Do not circumcise the infant until evaluation is complete: Particularly if bilateral nonpalpable testes are present, as this may represent a disorder of sex development 4

Algorithmic Approach

1. Measure stretched penile length using standard technique and compare to age-specific nomograms (micropenis = <2.5 SD below mean) 1, 2

2. Examine for testicular position: Palpable vs. nonpalpable, bilateral vs. unilateral 4, 1

3. If bilateral nonpalpable testes: Emergency endocrinology referral, check 17-hydroxyprogesterone, electrolytes, and karyotype immediately 4, 6

4. If testes palpable or unilateral nonpalpable: Check testosterone, LH, FSH during mini-puberty (ideally 2-3 months of age) 1, 2

5. Based on LH/FSH results:

   • Low/normal LH+FSH → Check prolactin, assess growth, consider pituitary pathology 4, 1
   • Elevated LH+FSH → Consider karyotype, evaluate for testicular failure 4, 1

6. Consider functional testing (GnRH or hCG stimulation) if baseline results are equivocal 1, 7

7. Initiate testosterone trial (25-50 mg testosterone enanthate intramuscularly) to assess penile response, regardless of etiology 3, 1, 2, 8