Basal follicle-stimulating hormone and peak gonadotropin levels after gonadotropin-releasing hormone infusion show high diagnostic accuracy in boys with suspicion of hypogonadotropic hypogonadism.

CONTEXT

Differential diagnosis between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty in boys is challenging. Most tests use an acute GnRH stimulus, allowing only the release of previously synthesized gonadotropins. A constant GnRH infusion, inducing de novo gonadotropin synthesis, may allow a better discrimination.

OBJECTIVE

We evaluated the diagnostic accuracy of basal and peak gonadotropins after GnRH infusion, measured by ultrasensitive assays, to confirm the diagnosis in boys with suspected HH.

DESIGN AND SETTING

We conducted a validation study following Standards for Reporting of Diagnostic Accuracy criteria at a tertiary public hospital.

PATIENTS AND METHODS

A GnRH i.v. infusion test was performed in 32 boys. LH and FSH were determined by immunofluorometric assay at 0-120 min. DIAGNOSIS ASCERTAINMENT: The following diagnoses were ascertained: complete HH (n = 19; testes < 4 ml at 18 yr), partial HH (n = 6; testes enlargement remained arrested for > or = 1 yr or did not reach 15 ml), and constitutional delay of puberty (n = 7; testes > or = 15 ml at 18 yr).

MAIN OUTCOME MEASURES

Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were assessed.

RESULTS

Basal FSH less than 1.2 IU/liter confirmed HH with specificity of 1.00 (95% confidence interval = 0.59-1.00), rendering GnRH infusion unnecessary. In patients with basal FSH of at least 1.2 IU/liter, the coexistence of peak FSH less than 4.6 IU/liter and peak LH less than 5.8 IU/liter after GnRH infusion had high specificity (1.00; 95% confidence interval = 0.59-1.00) and diagnostic efficiency (76.9%) for HH.

CONCLUSIONS

Basal FSH less than 1.2 IU/liter confirms HH, which precludes from further testing, reducing patient discomfort and healthcare system costs. In patients with basal FSH of at least 1.2 IU/liter, a GnRH infusion test has a high diagnostic efficiency.