Diagnosis and Management of Precocious Puberty with Testicular Mass in a 5-Year-Old Male
a) Most Probable Diagnosis
The most probable diagnosis is a Leydig cell tumor of the left testis causing gonadotropin-independent (peripheral) precocious pseudopuberty. 1
The clinical presentation is highly characteristic:
- Asymmetric testicular enlargement (left testis 4ml with nodular mass, right testis smaller) is pathognomonic for a testicular tumor rather than central precocious puberty, where both testes enlarge symmetrically 1
- Signs of virilization (acne, facial hair, axillary hair, deep voice, penile enlargement) indicate excessive androgen production 1
- Age of presentation (5 years) with Tanner stage 2 pubic hair represents true precocious development (before age 9 in boys) 2, 3
- Palpable nodular mass in the upper pole of the left testis is the key distinguishing feature 1
Leydig cell tumors are the most common hormone-secreting testicular tumors in prepubertal boys and secrete high amounts of testosterone, causing precocious pseudopuberty 1. The asymmetric, firm, painless testicular enlargement with virilization signs is classic for this diagnosis 1.
b) Investigation and Interpretation
Laboratory Testing
Hormonal Profile:
- Measure testosterone, LH, FSH, and estradiol - In Leydig cell tumors, expect markedly elevated testosterone with suppressed gonadotropins (LH and FSH), confirming gonadotropin-independent precocious puberty 4
- Tumor markers - Measure alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (β-hCG) to exclude germ cell tumors, though these are typically negative in Leydig cell tumors 1, 4
- DHEA-S and 17-hydroxyprogesterone - Should be normal, helping exclude adrenal causes of virilization 3
Interpretation: Suppressed gonadotropins with elevated testosterone confirms peripheral (gonadotropin-independent) precocious puberty from autonomous androgen production by the testicular mass 4.
Radiologic Assessment
Testicular Ultrasound:
- Characterize the testicular mass - Leydig cell tumors typically appear as homogenous, hypoechoic masses, sometimes with calcification 1
- Assess both testes - Document size, echogenicity, and presence of any masses 1
Bone Age X-ray (Left Hand and Wrist):
- Assess skeletal maturation - Expect advanced bone age due to prolonged androgen exposure, which predicts compromised final adult height 2, 1
Brain MRI:
- Not indicated initially since the asymmetric testicular enlargement with palpable mass clearly indicates a peripheral cause 2
- Reserve for later if central precocious puberty develops post-operatively (see below) 5
Additional Considerations
Contralateral testis evaluation - The American Academy of Pediatrics recommends assessing the contralateral testis, as unilateral pathology may affect the opposite testis 6
c) Management and Justification
Surgical Management
Perform radical inguinal orchiectomy of the left testis as the definitive treatment. 1
Justification:
- Radical orchiectomy is the treatment of choice for Leydig cell tumors in prepubertal boys, performed through an inguinal approach to avoid scrotal violation 6, 1
- Histopathological examination is mandatory to confirm the diagnosis and determine if the tumor is benign or malignant (90-95% are benign in children, but malignant variants exist) 1
- Testis-sparing surgery may be considered only in highly experienced centers for small tumors with frozen section confirmation, but radical orchiectomy remains standard given the young age and need for definitive diagnosis 6
- The contralateral testis is preserved for future fertility and hormone production 6
Post-Operative Monitoring
Critical: Monitor for development of central precocious puberty after tumor removal. 5
Rationale:
- Up to 8 reported cases have developed gonadotropin-dependent (central) precocious puberty following successful treatment of Leydig cell tumors 5
- Mechanism: Prolonged exposure to sex steroids from the tumor may prime the hypothalamic-pituitary-gonadal axis, leading to its premature activation after tumor removal 5
- Clinical presentation: After initial regression of pubertal signs post-surgery, patients may develop persistent or recurrent signs of puberty with elevated gonadotropins 5
Monitoring Protocol:
- Measure LH, FSH, and testosterone at 1,3,6, and 12 months post-operatively 5
- Assess Tanner staging at each visit 2
- Repeat bone age at 6-12 months to assess progression 2
- If central precocious puberty develops: Initiate GnRH analog therapy (e.g., leuprolide depot) to suppress the gonadotropic axis and preserve final adult height 5, 7
Psychosocial Support
Provide psychological counseling for the child and family. 8
Early puberty is associated with increased risk of behavioral problems, anxiety, and social difficulties 8. The American Academy of Child and Adolescent Psychiatry recommends early psychosocial intervention before psychiatric disorders develop 8.
Long-Term Follow-Up
Annual surveillance is required:
- Monitor growth parameters and final adult height, as GnRH agonist treatment (if needed) can restore height compromised by precocious puberty 7
- Testicular self-examination education when age-appropriate, as patients with testicular tumors have increased risk of contralateral pathology 6
- Fertility counseling in adolescence, as unilateral orchiectomy typically preserves fertility but the contralateral testis may have subtle abnormalities 6
Common Pitfalls to Avoid
- Do not assume central precocious puberty based solely on virilization signs - the asymmetric testicular enlargement is the critical distinguishing feature 1
- Do not perform scrotal biopsy or scrotal surgery - always use an inguinal approach to avoid tumor seeding 6
- Do not discontinue follow-up after successful tumor removal - central precocious puberty can develop months to years later 5
- Do not delay surgery - prolonged androgen exposure further advances bone age and compromises final height 7