Diagnostic utility of testosterone priming prior to dynamic tests to differentiate constitutional delay in puberty from isolated hypogonadotropic hypogonadism

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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 the onset of puberty or 18 years of age, whichever was earlier.

Results

At baseline, Triptorelin-stimulated 4 h 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 4 h LH cut-off of 14·7 IU/l and day 7 testosterone cut-off of 10·3 nmol/l had sensitivities of 93% and 88% respectively, and specificity and positive predictive value of 100% each. A basal inhibin B > 94·7 ng/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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