PROTOCOL FOR DIAGNOSIS OF PRECOCIOUS PUBERTY?

PROTOCOL FOR DIAGNOSIS OF PRECOCIOUS PUBERTY?

QUESTION-hi ,and thank you for your exciting site. i have a question concerning confirmation diagnosis of  precocious puberty with GnRH anlogs  here in algeria where i am parcticing , GnRH are no longer available.  So what i wanted to know , is there any consensus on  a protocol to do this test  and what are protocols  you use?  Can  DECAPEPTYL RETARD prép inj 3.75 mg( triptoréline ), we use to treat CPP be used to perform this test ? thank you very much. mr nadjib kaouache , fellow in training .endocrinology and metabolism ,universitary hospital of constantine .algeria
RESPONSE--Provocative testing using GnRHa for either diagnosis or treatment monitoring has become popular in the U.S. because of the absence of GnRH.  This approach was initiated by Rosenfield et al (1) using nafarelin, but the favored diagnostic agent is the aqueous form of leuprolide, using 10-20 mcg/kg or a fixed dose of 500 mcg, with a serum sample by 60 min (2,3).  Normative data are scarce, and limited comparisons of GnRH- and leuprolide-stimulated LH peaks in prepubertal and pubertal children are unclear about whether the latter are higher.  Most studies have employed longer time courses than that after GnRHa injection, so that the data are not directly comparable. The data of Ibanez et al (3) suggest that the peak levels by the two methods are equal in prepubertal children but that agonist-stimulated levels are higher when pubertal children are assessed.  Other studies do not show a clear difference.

An additional adaptation of the GnRHa stimulation test is measurement of estradiol at 16-24 hours (1-3), again without substantial normative data.  GnRHa stimulation of gonadal response overcomes the limitations of basal estradiol measurement, and the level achieved appears to be predictive of pubertal onset, but with variable thresholds (17-41 pg/ml, or 63-150 pMol/l) among studies. The pubertal estradiol response in the face of a relatively low LH increase in some girls raises the question of the true physiologic significance of this test.

  • Data on the use of triptorelin for diagnosis of precocious puberty are even more scanty. One study (4) has employed subcutaneous Triptorelin acetate (0,1 mg/m2, to a maximum of 0,1 mg) with blood sampling at 0, 3 and 24 h for LH, FSH and estradiol ascertainment.  LH-3 h levels >7 IU/l by immunofluorometric assay or >8 IU/l by electrochemiluminescence immunoassay confirmed the activation of the hypothalamic–pituitary–ovarian axis in central precocious puberty girls and allowed to exclude the precocious thelarche diagnosis. When LH-3 h levels were below cut-off, taking into consideration the estradiol 24 h levels, if rising above 295 pM (80 pg/ml) after the Triptorelin administration, was a very useful tool to confirm the diagnosis of CPP.
  • Another study (5) utilized 100 µg of triptorelin injected sc with blood samples taken at 30, 60, 90, and 120 min after GnRHa injection. Peak LH was achieved within 60 min following GnRHa injection. Peak LH of 6 IU/l provided the most appropriate cutoff level with a sensitivity of 89.1% and specificity of 91.3%.

    1. Rosenfield RL, Garibaldi LR, Moll Jr GW, Watson AC, Burstein S. 1986 The rapid ovarian secretory response to pituitary stimulation by the gonadotropin-releasing hormone agonist Nafarelin in sexual precocity. J Clin Endocrinol Metab. 63:1386-1389.

    2. Garibaldi LR, Aceto T Jr, Weber C, Pang S. 1993 The relationship between luteinizing hormone and estradiol secretion in female precocious puberty: evaluation by sensitive gonadotropin assays and the leuprolide stimulation test. J Clin Endocrinol Metab. 76:851– 856.

    3. Ibanez L, Potau N, Zampolli M, et al. 1994 Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test. J Clin Endocrinol Metab. 78:30-35.

    4. Freire AV, Escobar ME, Gryngarten MG, Arcari AJ, Ballerini MG, Bergada´ I, and Ropelato MG. 2013 High diagnostic accuracy of subcutaneous Triptorelin test compared with GnRH test for diagnosing central precocious puberty in girls. Clinical Endocrinology 78, 398–404.

    5. Poomthavorn P, Khlairit P, Mahachoklertwattana P. 2009 Subcutaneous Gonadotropin-Releasing Hormone Agonist (Triptorelin) Test for Diagnosing Precocious Puberty. Horm Res 2009;72:114–119

    I hope this has been useful to you. I also attach, for your convenience, the last 2 references. Do not hesitate to contact me in case you need more information. Lucia Ghizzoni, M.D., Ph.D, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy