Diagnostic Utility of Testosterone Priming Prior to Dynamic Tests to Differentiate Constitutional Delay in Puberty from Isolated Hypogonadotropic Hypogonadism

Abstract

Context

Differentiation between constitutional delay in puberty (CDP) and isolated hypogonadotropic hypogonadism (IHH) during adolescence is a great clinical challenge and the available diagnostic tests are of limited value.

Objective

To study the effect of withdrawal of short term, low dose testosterone therapy (testosterone priming) on the discriminatory power of dynamic tests for hypothalamo-pituitary-testicular axis to differentiate CDP from IHH.

Design

A prospective study (n=30) consisting of 20 boys with delayed puberty (Group A) and 10 patients with IHH (Group B).

Intervention

Patients in groups A and B underwent Triptorelin and hCG stimulation tests, prior to and 2 months after withdrawal of 'testosterone priming' (100 mg intramuscularly 4 weekly for 3 months) and were followed up until onset of puberty or 18 years of age, whichever was earlier.

Results

At baseline, Triptorelin-stimulated 4h LH, with a cut-off of 2.8 IU/l, and hCG-stimulated day 7 testosterone with a cut-off of 3.8 nmol/L had sensitivities of 80% each, and specificities of 93% and 87%, respectively, to diagnose CDP. After withdrawal of testosterone,a 4h LH cut-off of 14.7IU/l and day 7 testosterone cut-off of 10.3nmol/L had sensitivities of 93% and 88% respectively, and specificity and positive predictive value of 100% each. A basal inhibin B >94.7ng/l was discriminatory for diagnosing CDP after withdrawal of testosterone priming.

Conclusions

Inhibin B levels or 4 h LH after Triptorelin stimulation are the best discriminatory tests to differentiate CDP from IHH, when performed after withdrawal of 'testosterone priming'.

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