What is the expected pattern of blood hormone levels, including testosterone, inhibin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), in a 16-year-old male with a history of micropenis at birth due to a mutation in the nuclear receptor subfamily 5 group A member 1 (NR5A1)/steroidogenic factor 1 (SF-1) gene affecting Sertoli cell function, who has undergone normal pubertal development?

Hormone Pattern in SF-1 Mutation with Selective Sertoli Cell Dysfunction

The most likely hormone pattern is Option C: Normal Testosterone, Decreased Inhibin, Increased FSH, Normal LH.

Understanding SF-1 Mutations and Selective Sertoli Cell Impairment

The clinical scenario describes a specific NR5A1/SF-1 mutation causing selective Sertoli cell dysfunction while the remainder of the hypothalamic-pituitary-gonadal axis remains unaffected. This creates a distinctive hormonal signature that differs from typical gonadal dysgenesis patterns 1.

Why Testosterone Remains Normal

• Leydig cells are functioning normally in this patient, as evidenced by normal childhood and pubertal development 1
• SF-1 mutations can cause predominant Sertoli cell deficiency while preserving Leydig cell function, allowing spontaneous virilization during puberty 2, 1
• The patient achieved normal pubertal development, which requires adequate testosterone production from functional Leydig cells 2
• Studies demonstrate that 46,XY patients with NR5A1 mutations can produce sufficient testosterone for spontaneous virilization during puberty, with normal testosterone levels documented at age 16 2

Why Inhibin B is Decreased

• Inhibin B is produced exclusively by Sertoli cells and serves as the most sensitive marker of Sertoli cell function 1, 3
• The mutation specifically impairs Sertoli cell function, resulting in low inhibin B concentrations 1, 4
• This selective Sertoli cell defect becomes more apparent during puberty, with progressively declining inhibin B levels 1
• Low inhibin B is the hallmark finding in SF-1 mutations with predominant Sertoli cell dysfunction 1, 3

Why FSH is Increased

• FSH elevation occurs through negative feedback from decreased inhibin B 1
• Inhibin B normally provides negative feedback on FSH secretion at the pituitary level 5
• When Sertoli cells are dysfunctional and inhibin B is low, the pituitary compensates by increasing FSH secretion 1
• Studies show high FSH levels contrasting with normal LH in patients with SF-1 mutations causing selective Sertoli cell defects 1
• This pattern reveals isolated Sertoli cell dysfunction rather than global testicular failure 1

Why LH Remains Normal

• LH is regulated by testosterone through negative feedback, not by inhibin B 1
• Since Leydig cells are functioning normally and producing adequate testosterone, LH remains in the normal range 1
• The normal LH concentration contrasts with elevated FSH, creating the distinctive pattern of selective Sertoli cell dysfunction 1
• This dissociation between FSH and LH distinguishes selective Sertoli cell defects from primary testicular failure, where both gonadotropins would be elevated 6

Critical Distinction from Other Patterns

Why Not Pattern A (All Decreased)?

• This pattern suggests hypogonadotropic hypogonadism (secondary hypogonadism), which contradicts the scenario stating the hypothalamic-pituitary axis is unaffected 6
• The patient had normal pubertal development, which would not occur with persistently low testosterone and gonadotropins 2

Why Not Pattern B (Decreased Testosterone, Normal Inhibin, Increased LH)?

• This suggests primary Leydig cell failure, but the patient achieved normal pubertal development, proving Leydig cells function normally 2, 1
• Inhibin B would not be normal with Sertoli cell dysfunction 1

Why Not Pattern D (Normal Testosterone, Increased Inhibin)?

• Increased inhibin B is physiologically impossible with Sertoli cell dysfunction 1
• Inhibin B is the most sensitive marker of Sertoli cell function and must be decreased when these cells are impaired 1, 3

Why Not Pattern E (Normal Testosterone, Normal Inhibin, Increased FSH)?

• Normal inhibin B cannot coexist with elevated FSH in the absence of exogenous FSH administration 1
• FSH elevation occurs specifically because inhibin B is low, creating the negative feedback signal for increased FSH secretion 1

Clinical Implications and Monitoring

This patient requires long-term surveillance because SF-1 mutations can cause progressive gonadal dysgenesis 2:

• Fertility potential is compromised due to Sertoli cell dysfunction, even with normal testosterone 1
• Early sperm cryopreservation should be considered if any sperm production is detected, as progressive deterioration is likely 2
• Gonadal function should be monitored in adolescence and adulthood with serial measurements of FSH, LH, testosterone, and inhibin B 2
• The Sertoli cell deficiency may become more apparent over time, with progressive elevation of FSH and decline in inhibin B 1