What is the recommended evaluation and management for an 11‑year‑old boy with absent erections and low testosterone?

Evaluation and Management of an 11-Year-Old Boy with Absent Erections and Low Testosterone

Immediate Diagnostic Workup

This 11-year-old boy requires urgent hormonal evaluation to differentiate between constitutional delay of puberty, congenital hypogonadotropic hypogonadism, and primary testicular failure—the diagnosis will fundamentally determine whether he needs lifelong testosterone replacement or will undergo spontaneous puberty. 1, 2

Essential Laboratory Tests

Obtain the following blood tests (morning samples):

• Serum LH and FSH: This is the single most critical test to differentiate primary testicular failure (elevated LH/FSH) from central hypogonadism (low or low-normal LH/FSH) 1, 2
• Total testosterone: Confirm the low testosterone with repeat morning measurement 1
• Prolactin: Measure only if LH is low or low-normal, as elevated prolactin suggests a pituitary tumor requiring immediate endocrinology referral 1, 2
• Inhibin B and Anti-Müllerian Hormone (AMH): If bilateral cryptorchidism or anorchia is suspected, these markers assess Sertoli cell function 3

Physical Examination Priorities

Perform a focused examination looking for:

• Testicular examination: Assess testicular size, consistency, and location (palpable vs. nonpalpable) 3, 4
• Olfactory testing: Ask specifically about sense of smell—anosmia indicates Kallmann syndrome, a form of congenital hypogonadotropic hypogonadism 2
• Body proportions: Measure arm span and height to detect eunuchoid proportions (arm span >5 cm greater than height suggests longstanding hypogonadism) 5
• Gynecomastia: Examine breast tissue 3
• Cryptorchidism: Document if testes are undescended 3

Do not order scrotal ultrasound unless the physical examination is inadequate (obesity, scrotal edema) or a testicular mass is suspected—ultrasound is not indicated for routine evaluation of low testosterone. 4

Diagnostic Algorithm Based on Laboratory Results

If LH/FSH are Low or Low-Normal (Central Hypogonadism)

This indicates hypogonadotropic hypogonadism. The differential diagnosis includes:

• Constitutional delay of puberty (most common, 63% of delayed puberty cases): Family history of late puberty, bone age delayed but consistent with pubertal stage 5, 6
• Congenital hypogonadotropic hypogonadism: Anosmia (Kallmann syndrome) or normosmia, may have micropenis or cryptorchidism history 2, 7
• Pituitary tumor or infiltration: Requires brain MRI, especially if testosterone <150 ng/dL 1

Obtain pituitary MRI if testosterone is severely low (<150 ng/dL), prolactin is elevated, or there are other pituitary hormone deficiencies to rule out a tumor. 1, 2

If LH/FSH are Elevated (Primary Testicular Failure)

This indicates primary hypogonadism. Causes include:

• Anorchia (vanishing testis syndrome): Undetectable AMH and inhibin B with elevated FSH/LH confirms absent testicular tissue 3
• Klinefelter syndrome: Consider karyotype testing 8
• Testicular damage: History of torsion, orchitis, chemotherapy, or cryptorchidism 9, 8

If bilateral nonpalpable testes with elevated LH/FSH and undetectable AMH/inhibin B, diagnose anorchia without need for surgical exploration. 3

Treatment Approach

For Constitutional Delay of Puberty

• Short-term low-dose testosterone therapy: Use testosterone enanthate 50 mg IM monthly for 3-6 months to induce secondary sexual characteristics and alleviate psychological distress 10, 6
• Expectant management: After discontinuation, spontaneous puberty should progress normally 6
• Monitor bone age every 6 months to assess epiphyseal maturation 9

For Congenital Hypogonadotropic Hypogonadism

Gonadotropin therapy (hCG with or without FSH) or pulsatile GnRH is preferred over testosterone alone in adolescents with central hypogonadism because these treatments induce testicular growth and preserve future fertility potential. 7, 6

• hCG therapy: Induces testosterone production and testicular enlargement 7
• FSH priming prior to hCG: Enhances testicular response 7
• Alternative: Testosterone replacement if fertility is not an immediate concern, but this will suppress spermatogenesis 9, 10

For Primary Testicular Failure (Anorchia, Klinefelter)

Lifelong testosterone replacement therapy is required, starting with low doses during adolescence and gradually increasing to adult replacement doses. 9, 10

• Testosterone enanthate: Starting dose 50-75 mg IM every 2-4 weeks, gradually increasing over 2-3 years to adult dose of 150-200 mg every 2 weeks 9, 10
• Testosterone gel: Not typically first-line in adolescents due to risk of secondary exposure to family members 8

Critical Pitfalls to Avoid

• Do not skip LH/FSH measurement: This is the only way to differentiate primary from secondary hypogonadism 1
• Do not start testosterone therapy before confirming the diagnosis: Constitutional delay requires only short-term treatment, while permanent hypogonadism requires lifelong therapy 5, 6
• Do not use testosterone in boys with central hypogonadism who desire future fertility: Gonadotropins or GnRH preserve fertility potential 7, 6
• Do not order scrotal ultrasound reflexively: Physical examination is sufficient unless a mass is suspected or examination is inadequate 4
• Do not miss Kallmann syndrome: Always assess sense of smell, as this diagnosis has genetic counseling implications 2