Endocrine Abstracts

Objective: To assess the usefulness of the GnRH analogue Diphereline (Triptoreline) in the evaluation of central gonadal dysfunction in children and adults.

Methods: A 18-month retrospective study of dynamic testing of the hypothalamic pituitary gonadal axis in 36 patients, 10 prepubescent children (<13 years for girls and 14 years for boys) and 26 postpubescent subjects. The children were investigated for disorders of sexual development while the adults presented with clinical hypogonadism. In order to assess the response of the gonadal axis to the GnRH analogue Diphereline, 100 μg were subcutaneously injected. FSH, LH were sampled basally and after 4 h, while testosterone/ estradiol were sampled after 24 h.

Results: Of the 26 postpubescent patients, 3 men presenting pituitary adenomas were shown to have hypergonadotropic hypogonadism, 15 patients had hypogonadotropic hypogonadism of probable pituitary origin and 8 had hypothalamic disorders. In the pituitary group the results showed a diminished response to the GnRH test in FSH, LH and the periphery, significant only for FSH (1.31±1.46 to 2.72±3.04 IU/l, P=0.02). In the group with hypothalamic hypogonadism there was a significant FSH increase from an average value of 2.07±1.10 to 12.62±10.75 IU/l (P=0.02), LH from 0.97±0.93 to 17.68±16.62 IU/l (P=0.02), while the peripheral answer was an increase in testosterone from 2.24±1.84 to 3.10±1.61 ng/ml and an increase in estradiol from 14.68±3.45 to 19.36±13.51 pg/ml (P=NS). The response to GnRH was significantly higher for the hypothalamic then the pituitary group for both LH (P=0.03) and FSH (P=0.04), consistent with the original etiological hypothesis and pathophysiological mechanism. All three patients with hypergonadotropic hypogonadism had high basal LH or FSH levels, with further increase after stimulation, without reaching statistical significance. In the prepubescent group, aged 4–13 years, the subgroup aged <10 had an increase in LH and FSH only, while the older children had both central and peripheral responses, consistent with gonadal maturation. A similar response in a 7-year-old girl helped establish the diagnosis of precocious puberty. There was no response in a 13-year-old boy with Prader Willi syndrome.

Conclusion: Although not diagnostic in itself, GnRH testing can help shed light on the aetiology of hypogonadotropic hypogonadism syndromes in complex clinical settings. Diphereline can be used as a surrogate test.