for months until the diagnosis were confirmed 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9

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1 ACTA ACADEMIAE MEDICINAE SINICAE LHRH IHH CDP 133 IHH 86 CDP ~ 48 9 IHH 13 CDP LH LH IHH CDP IHH LH 1. 9 ± 1. 2 U /L CDP LH ± 8. 3 U /L P < % IHH LH < 4 U /L CDP % LH < 4 U /L LH < 4 U /L IHH 87. 2% 95. 7% 97. 4% IHH LH 4. 7 ± 2. 5 U /L 5. 1 ± 3. 3 U /L P = CDP LH ± 3. 3 U /L ± 5. 7 U /L P < % IHH CDP IHH CDP - - R DOI /j. issn X A X Clinical Values of Single or Repeated Triptorelin Stimulating Test in the Differential Diagnosis between Idiopathic Hypogonadotropic Hypogonadism and Constitutional Delayed Puberty MAO Jiang-fengWU Xue-yanLU Shuang-yuNIE Min Department of EndocrinologyKey Laboratory of Ministry of HealthPUMC Hospital CAMS and PUMCBeijing China Corresponding author WU Xue-yan Tel wsheyan@vip.sina.com ABSTRACT Objective To investigate the values of single or repeated luteinizing hormone LH releasing hormone analogue triptorelin stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism IHH and constitutional delayed puberty CDP. Methods Male patients n = 133 without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up 566 October2011

2 for months until the diagnosis were confirmed 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value LHmax and the changes of repeated LHmax were investigated. Results In the single triptorelin stimulating testlhmax was 1. 9 ± 1. 2 U /L in IHH groupwhich was significantly lower than that in CDP group ± 8. 3 U /L P < IHH patients 87. 2% had a LHmax lower than 4 U /Lwhile only 2 CDP patients 4. 3% had a LHmax lower than 4 U /L. When LHmax < 4U /L was used as a criteria for the diagnosis of IHH the single triptorelin stimulating test had a sensitivity of 87. 2% a specificity of 95. 7% and a positive predictive value of 97. 4%. The repeated triptorelin stimulating tests performed one year later showed that the LHmax in the 9 IHH patients increased from 4. 7 ± 2. 5 U /L to 5. 1 ± 3. 3 U /L P = while that in the 13 CDP patients increased from ± 3. 3 U /L to ± 5. 7 U /L P < Conclusions A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosisa repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function. Key words triptorelin stimulating test idiopathic hypogonadotropic hypogonadism constitutional delayed puberty hypothalamus-pituitary-gonad axis function Acta Acad Med Sin idiopathic hypogonadotropic hypogonadismihh consti- 133 tutional delayed pubertycdp IHH IHH 24 ~ 48 IHH 9 IHH CDP ~ ± 5. 7 CDP 2 ~ 4 CDP 14 > 3. 5 nmol /L 1 47 IHH luteinizing hormone releasing hormonelhrh LHRH < 3. 5 nmol /LFSH LH 1 86 luteinizing hormonelh 10 follicular stimulating hormonefsh 8 am LHRH 100 μg 0 60 min 2 ml 100 μg LHRH FSH LH 3 ~ 6 1 CDP μg Vol. 33 No

3 Prader Tanner 3 FSH LH E2 T 2 LH FSH uiu /ml FSH LH T LH T 3. 5% 3. 6% 3. 5% 3. 7% 2. 8% 3. 2% x ± s 1 t Gruelich-Pyle t P < Diagnosis Table 1 1 IHH CDP CDP IHH P < IHH CDP LH x ± s The clinical characteristics and the LHmax in triptorelin stimulating test in patients with IHH and CDP x ± s Age year Height cm Weight kg LH Testes volume ml Basic LH FSH FSH LH Basic testosterone LHmax in triptorelin test nmol /L IHH n = ± ± ± ± ± ± ± ± 1. 2 CDP n = ± ± ± ± 0. 6 a 0. 7 ± 0. 3 a 1. 4 ± ± 0. 9 a ± 8. 3 b IHH CDP LH FSH IHH a P < b P < IHH idiopathic hypogonadotropic hypogonadism CDP constitutional delayed puberty LH luteinizing hormone FSH follicular stimulating hormone a P < b P < compared with IHH group LH 87. 2% IHH LH 4 U /L 96% CDP LH 4 U /L 1 LH < 4 U /L IHH 87. 2% 95. 7% 90. 2% 97. 4% 80. 4% 90. 2% LH 1 2 IHH n = 9 LH LHmax 60 min P = 0. 78CDP n = LHmax the level of LH at 60 minutes in triptorelin stimulating test 13 LH 1 P < Diagnosis 1 Fig 1 LH The peak level of LH in triptorelin stimulating test 2 IHH CDP 1 LH x ± s Table 2 Repeated triptorelin stimulating tests showed the change of LHmax in IHH and CDP patients x ± s LH LH Testis volume ml Basic LH Basic testosterone nmol /L LHmax in triptorelin test First visit After 1 year First visit After 1 year First visit After 1 year First visit After 1 year IHH n = ± ± ± ± ± ± ± ± 3. 3 CDP n = ± 0. 6 a 5. 1 ± 1. 6 b 0. 7 ± 0. 3 a 1. 2 ± 0. 4 b 1. 4 ± ± 1. 2 b ± 3. 3 a ± 5. 7 b IHH a P < b P < a P < compared with IHH group b P < compared with first triptorelin stimulating test 568 October2011

4 LH - 95% 9 ~ 12 IHH 2 IHH LH FSH 14 3 ~ 4 ml CDP 18 LH IHH IHH CDP 2 LH IHH LH IHH 3 ~ IHH reversal 1 LHRH CDP IHH 3 LHRH LH 8 IU /L LH LH IHH 12 - LH 5 IU /L IHH % 93. 3% 3 PROKR2 Kisspeptin /Kiss1R TAC3 /TACR3 LHRH LHRH 8 70% IHH 4-5 LHRH LHRH 8 IHH 12 h 6 IHH FSH LH 1 IHH 8 LH 60 min CDP - - IHH 7 IHH CDP - - LH LH IHH 3 ~ 4 ml LH % IHH LHmax < 4 U /L 95. 7% 90. 2% CDP LHmax > 4 U /L LH < 4 U /L LH < 4 IHH 97. 4% U /L IHH CDP 20 ~ LH - Vol. 33 No

5 1Raivio TFalardeau JDwyer Aet al. Reversal of idiopathic hypogonadotropic hypogonadism J. New Engl J Med J. J Semple RKTopaloglu AK. The recent genetics of hypogonadotrophic hypogonadism-novel insights and new questions 3. LHRH J. Clin Endocrinol Oxf David WGenevieve DPharm Det al. A combined analysis of data to identify predictive factors for spermatogenesis in J men with hypogonadotropic hypogonadism treated with recom- 4. binant human follicle-stimulating hormone and human chorionic gonadotropin J. Fertil Steril J Kanika GCara FRobert Let al. Gonadotropin releasing hormone agonist nafarelin test to differentiate gonadotropin deficiency from constitutionally delayed puberty in teen-age boys-a clinical research center study J. Clin Endocrinol Metab M October2011