A male patient with small testes, normal male pattern facial and pubic hair, decreased sperm count, and normal serum testosterone level - what is the most likely cause of these findings?

Klinefelter Syndrome is the Most Likely Diagnosis

The clinical presentation of small testes with normal virilization (normal facial and pubic hair), decreased sperm count, and normal serum testosterone is most consistent with Klinefelter syndrome (47,XXY).

Key Diagnostic Features That Point to Klinefelter Syndrome

The hallmark finding that distinguishes this case is small, firm testes despite normal testosterone levels and normal secondary sexual characteristics 1, 2. This specific combination is pathognomonic for Klinefelter syndrome because:

• Small testicular volume (<12 mL) with normal virilization indicates primary testicular dysfunction affecting the seminiferous tubules while Leydig cell function remains relatively preserved 3, 4
• Normal serum testosterone excludes severe primary testicular failure and secondary hypogonadism, which would present with low testosterone 2, 5
• Decreased sperm count (oligospermia or azoospermia) with elevated FSH is the classic pattern, as FSH levels are negatively correlated with spermatogonia number 3, 4
• Normal male pattern hair distribution confirms adequate androgen exposure, distinguishing this from androgen deficiency states 1, 2

Why Other Options Are Incorrect

Kallmann Syndrome (Option A) - Excluded

• Kallmann syndrome presents with hypogonadotropic hypogonadism with LOW testosterone and LOW/normal FSH and LH, not normal testosterone 6
• Patients would have absent or incomplete pubertal development with sparse facial and pubic hair, contradicting the normal virilization described 6
• Small testes would be prepubertal in size with soft consistency, not the firm small testes characteristic of Klinefelter syndrome 6

5-Alpha Reductase Deficiency (Option B) - Excluded

• This condition presents with ambiguous genitalia at birth and virilization at puberty, not the phenotypically normal male presentation described 4
• External genitalia abnormalities would be present, which is inconsistent with normal male pattern development 4

Androgen Use (Option D) - Excluded

• Exogenous testosterone suppresses FSH and LH through negative feedback, causing azoospermia 4, 6
• However, serum testosterone would be elevated or high-normal, not normal, and testicular size would show progressive atrophy from baseline, not congenitally small testes 4, 6
• The patient would have history of testosterone or anabolic steroid use, which is not mentioned 4

Hyperprolactinemia (Option E) - Excluded

• Hyperprolactinemia causes secondary hypogonadism with LOW testosterone and suppressed LH/FSH 6
• Patients present with decreased libido, erectile dysfunction, and gynecomastia, along with reduced secondary sexual characteristics 6
• Normal testosterone and normal virilization exclude this diagnosis 6

Confirming the Diagnosis of Klinefelter Syndrome

Karyotype analysis revealing 47,XXY is diagnostic and should be performed in all males with azoospermia or severe oligospermia (<5 million/mL) with small testes 3, 4. The clinical presentation described is so characteristic that:

• Klinefelter syndrome affects 1 in 500 males but remains underdiagnosed due to phenotypic variability 1, 5
• Only 21.2% of cases are diagnosed before age 20, and 6.1% before age 10, despite the condition being present from birth 5
• The testosterone/LH ratio peaks during Tanner stages 2-3 and declines from stage 4 onward, explaining why some patients maintain normal testosterone levels into adulthood 7
• Testicular volume progressively decreases after Tanner stage 4, with inhibin B falling and FSH rising, reflecting ongoing seminiferous tubule dysfunction 7

Clinical Implications

Genetic testing including karyotype analysis is mandatory for this patient 3, 4. Additional evaluation should include:

• Measurement of FSH, LH, and testosterone to confirm the hypergonadotropic pattern (elevated FSH with normal/low-normal testosterone) 3, 4
• Semen analysis to document the degree of oligospermia or azoospermia 3, 6
• Counseling regarding fertility options, as microsurgical testicular sperm extraction (micro-TESE) can retrieve sperm in 20-50% of Klinefelter patients 3, 4

The answer is C: Klinefelter syndrome.