Basal Follicle-Stimulating Hormone and Peak

GRINSPON, R.; ROPELATO, M.G.; GOTTLIEB, S; KESELMAN, A.; MART¨ªNEZ, A.; BALLERINI, M.G.; DOMEN¨¦, H.; REY, R

JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM

ENDOCRINE SOC

Año: 2010 vol. 95 p. 2811 - 2818

0021-972X

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 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 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 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 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 novode 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. infusion, measured by ultrasensitive assays, to confirm the diagnosis in boys with suspected HH. infusion, measured by ultrasensitive assays, to confirm the diagnosis in boys with suspected HH. infusion, measured by ultrasensitive assays, to confirm the diagnosis in boys with suspected HH. 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. Diagnostic Accuracy criteria at a tertiary public hospital. Diagnostic Accuracy criteria at a tertiary public hospital. Diagnostic Accuracy criteria at a tertiary public hospital. We conducted a validation study following Standards for Reporting of Diagnostic Accuracy criteria at a tertiary public hospital. Patients and Methods: A GnRH iv infusion test was performed in 32 boys. LH and FSH were determined by immunofluorometric assay at 0–120 min. determined by immunofluorometric assay at 0–120 min. determined by immunofluorometric assay at 0–120 min. determined by immunofluorometric assay at 0–120 min. A GnRH iv 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
1 yr or did not reach 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 4 ml at 18 yr), partial HH (n
6; testes enlargement remained arrested for
1 yr or did not reach 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 4 ml at 18 yr), partial HH (n
6; testes enlargement remained arrested for
1 yr or did not reach 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 4 ml at 18 yr), partial HH (n
6; testes enlargement remained arrested for
1 yr or did not reach 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). The following diagnoses were ascertained: complete HH (n
19; testes 4 ml at 18 yr), partial HH (n
6; testes enlargement remained arrested for
1 yr or did not reach 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr). 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr).
6; testes enlargement remained arrested for
1 yr or did not reach 15 ml), and constitutional delay of puberty (n
7; testes
15 ml at 18 yr).
7; testes
15 ml at 18 yr). Main Outcome Measures: Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were assessed. diagnostic efficiency were assessed. diagnostic efficiency were assessed. diagnostic efficiency were assessed. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH. 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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH.
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. efficiency (76.9%) for HH. efficiency (76.9%) for HH. efficiency (76.9%) for HH.
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. 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. 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. 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. 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.