Skip to main content
Erschienen in:

26.11.2021 | Original Article

Triptorelin stimulated luteinizing hormone concentrations for diagnosing central precocious puberty: study of diagnostic accuracy

verfasst von: Rade Vukovic, Tatjana Milenkovic, Ivan Soldatovic, Sandra Pekic, Katarina Mitrovic, Sladjana Todorovic

Erschienen in: Endocrine | Ausgabe 3/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always readily available. The aim of the present study was to evaluate the diagnostic accuracy of triptorelin-stimulated luteinizing hormone (LH) concentrations in the diagnosis of CPP among girls presenting with premature thelarche compared to the gold standard GnRH test.

Methods

A prospective, case–control (CPP vs isolated premature thelarche), clinical study evaluating the diagnostic accuracy of triptorelin-stimulated LH concentrations in 60 girls with premature thelarche was performed. All girls underwent stimulation with subcutaneous triptorelin injection and intravenous GnRH in a randomized order. During the stimulation test with triptorelin, LH and FSH were measured at time 0, 30, 60, 90, 120, and 180 min after the injection. Estradiol was sampled 24 h after the injection. During the GnRH test, LH and FSH were measured at time 0, 30, 45, and 60 min. Girls with peak GnRH-stimulated LH concentrations ≥5.0 IU/L were classified as having CPP. Area under the curve (AUC) for triptorelin-stimulated LH concentrations was assessed using the receiver operating characteristic (ROC) analysis.

Results

Triptorelin-stimulated LH concentrations were significantly higher in girls who had CPP according to the GnRH test (53.3%). LH peaked at 180 min after the triptorelin injection. The highest diagnostic accuracy for CPP (AUC = 0.973, sensitivity 96.9%, specificity 89.3%) at 180 min was at a LH concentration ≥3.4 IU/L. The 24 h estradiol concentration did not improve the predictive model.

Conclusions

Measuring LH concentrations 180 min after triptorelin injection with a cut-off value of ≥3.4 IU/L demonstrated a high diagnostic accuracy compared to the GnRH test. Thus, stimulation with triptorelin can be used as a reliable alternative for diagnosing CPP in girls with premature thelarche.
Literatur
1.
Zurück zum Zitat L. Aksglaede, K. Sorensen, J.H. Petersen, N.E. Skakkebaek, A. Juul, Recent decline in age at breast development: the Copenhagen Puberty Study. Pediatrics. 123(5), e932–e939 (2009)CrossRef L. Aksglaede, K. Sorensen, J.H. Petersen, N.E. Skakkebaek, A. Juul, Recent decline in age at breast development: the Copenhagen Puberty Study. Pediatrics. 123(5), e932–e939 (2009)CrossRef
2.
Zurück zum Zitat F.M. Biro, L.C. Greenspan, M.P. Galvez, S.M. Pinney, S. Teitelbaum, G.C. Windham et al. Onset of breast development in a longitudinal cohort. Pediatrics. 132(6), 1019–1027 (2013)CrossRef F.M. Biro, L.C. Greenspan, M.P. Galvez, S.M. Pinney, S. Teitelbaum, G.C. Windham et al. Onset of breast development in a longitudinal cohort. Pediatrics. 132(6), 1019–1027 (2013)CrossRef
3.
Zurück zum Zitat K. Bangalore Krishna, J.S. Fuqua, A.D. Rogol, K.O. Klein, J. Popovic, C.P. Houk et al. Use of gonadotropin-releasing hormone analogs in children: update by an international consortium. Horm. Res. Paediatr. 91(6), 357–372 (2019)CrossRef K. Bangalore Krishna, J.S. Fuqua, A.D. Rogol, K.O. Klein, J. Popovic, C.P. Houk et al. Use of gonadotropin-releasing hormone analogs in children: update by an international consortium. Horm. Res. Paediatr. 91(6), 357–372 (2019)CrossRef
4.
Zurück zum Zitat F.M. Biro, A. Pajak, M.S. Wolff, S.M. Pinney, G.C. Windham, M.P. Galvez et al. Age of menarche in a longitudinal US cohort. J. Pediatr. Adolesc. Gynecol. 31(4), 339–45 (2018)CrossRef F.M. Biro, A. Pajak, M.S. Wolff, S.M. Pinney, G.C. Windham, M.P. Galvez et al. Age of menarche in a longitudinal US cohort. J. Pediatr. Adolesc. Gynecol. 31(4), 339–45 (2018)CrossRef
5.
Zurück zum Zitat S.Y. Zhu, M.L. Du, T.T. Huang, An analysis of predictive factors for the conversion from premature thelarche into complete central precocious puberty. J. Pediatr. Endocrinol. Metab. 21(6), 533–538 (2008)CrossRef S.Y. Zhu, M.L. Du, T.T. Huang, An analysis of predictive factors for the conversion from premature thelarche into complete central precocious puberty. J. Pediatr. Endocrinol. Metab. 21(6), 533–538 (2008)CrossRef
6.
Zurück zum Zitat J.S. Fuqua, Treatment and outcomes of precocious puberty: an update. J. Clin. Endocrinol. Metab. 98(6), 2198–2207 (2013)CrossRef J.S. Fuqua, Treatment and outcomes of precocious puberty: an update. J. Clin. Endocrinol. Metab. 98(6), 2198–2207 (2013)CrossRef
7.
Zurück zum Zitat T. Varimo, H. Huttunen, P.J. Miettinen, L. Kariola, J. Hietamaki, A. Tarkkanen et al. Precocious puberty or premature thelarche: analysis of a large patient series in a single tertiary center with special emphasis on 6- to 8-year-old girls. Front. Endocrinol. (Lausanne) 8, 213 (2017)CrossRef T. Varimo, H. Huttunen, P.J. Miettinen, L. Kariola, J. Hietamaki, A. Tarkkanen et al. Precocious puberty or premature thelarche: analysis of a large patient series in a single tertiary center with special emphasis on 6- to 8-year-old girls. Front. Endocrinol. (Lausanne) 8, 213 (2017)CrossRef
8.
Zurück zum Zitat E.A. Eugster, Treatment of central precocious puberty. J. Endocr. Soc. 3(5), 965–972 (2019)CrossRef E.A. Eugster, Treatment of central precocious puberty. J. Endocr. Soc. 3(5), 965–972 (2019)CrossRef
9.
Zurück zum Zitat E.A. Resende, B.H. Lara, J.D. Reis, B.P. Ferreira, G.A. Pereira, M.F. Borges, Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J. Clin. Endocrinol. Metab. 92(4), 1424–1429 (2007)CrossRef E.A. Resende, B.H. Lara, J.D. Reis, B.P. Ferreira, G.A. Pereira, M.F. Borges, Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J. Clin. Endocrinol. Metab. 92(4), 1424–1429 (2007)CrossRef
10.
Zurück zum Zitat J.C. Carel, J. Leger, Clinical practice. Precocious puberty. N Engl J Med 358(22), 2366–2377 (2008)CrossRef J.C. Carel, J. Leger, Clinical practice. Precocious puberty. N Engl J Med 358(22), 2366–2377 (2008)CrossRef
11.
Zurück zum Zitat P. Poomthavorn, P. Khlairit, P. Mahachoklertwattana, Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty. Horm. Res. 72(2), 114–119 (2009)CrossRef P. Poomthavorn, P. Khlairit, P. Mahachoklertwattana, Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty. Horm. Res. 72(2), 114–119 (2009)CrossRef
12.
Zurück zum Zitat A.V. Freire, M.E. Escobar, M.G. Gryngarten, A.J. Arcari, M.G. Ballerini, I. Bergada et al. High diagnostic accuracy of subcutaneous Triptorelin test compared with GnRH test for diagnosing central precocious puberty in girls. Clin. Endocrinol. (Oxf) 78(3), 398–404 (2013)CrossRef A.V. Freire, M.E. Escobar, M.G. Gryngarten, A.J. Arcari, M.G. Ballerini, I. Bergada et al. High diagnostic accuracy of subcutaneous Triptorelin test compared with GnRH test for diagnosing central precocious puberty in girls. Clin. Endocrinol. (Oxf) 78(3), 398–404 (2013)CrossRef
13.
Zurück zum Zitat L. Soriano-Guillen, J. Argente, Central precocious puberty, functional and tumor-related. Best. Pract. Res. Clin. Endocrinol. Metab. 33(3), 101262 (2019)CrossRef L. Soriano-Guillen, J. Argente, Central precocious puberty, functional and tumor-related. Best. Pract. Res. Clin. Endocrinol. Metab. 33(3), 101262 (2019)CrossRef
14.
Zurück zum Zitat E.K. Neely, R.L. Hintz, D.M. Wilson, P.A. Lee, T. Gautier, J. Argente et al. Normal ranges for immunochemiluminometric gonadotropin assays. J. Pediatr. 127(1), 40–46 (1995)CrossRef E.K. Neely, R.L. Hintz, D.M. Wilson, P.A. Lee, T. Gautier, J. Argente et al. Normal ranges for immunochemiluminometric gonadotropin assays. J. Pediatr. 127(1), 40–46 (1995)CrossRef
15.
Zurück zum Zitat Y. Pasternak, M. Friger, N. Loewenthal, A. Haim, E. Hershkovitz, The utility of basal serum LH in prediction of central precocious puberty in girls. Eur. J. Endocrinol. 166(2), 295–299 (2012)CrossRef Y. Pasternak, M. Friger, N. Loewenthal, A. Haim, E. Hershkovitz, The utility of basal serum LH in prediction of central precocious puberty in girls. Eur. J. Endocrinol. 166(2), 295–299 (2012)CrossRef
16.
Zurück zum Zitat M. Kumar, S. Mukhopadhyay, D. Dutta, Challenges and controversies in diagnosis and management of gonadotropin dependent precocious puberty: an Indian perspective. Indian J. Endocrinol. Metab. 19(2), 228–235 (2015)CrossRef M. Kumar, S. Mukhopadhyay, D. Dutta, Challenges and controversies in diagnosis and management of gonadotropin dependent precocious puberty: an Indian perspective. Indian J. Endocrinol. Metab. 19(2), 228–235 (2015)CrossRef
17.
Zurück zum Zitat V.N. Brito, A.M. Spinola-Castro, C. Kochi, C. Kopacek, P.C. Silva, G. Guerra-Junior, Central precocious puberty: revisiting the diagnosis and therapeutic management. Arch. Endocrinol. Metab. 60(2), 163–172 (2016)CrossRef V.N. Brito, A.M. Spinola-Castro, C. Kochi, C. Kopacek, P.C. Silva, G. Guerra-Junior, Central precocious puberty: revisiting the diagnosis and therapeutic management. Arch. Endocrinol. Metab. 60(2), 163–172 (2016)CrossRef
18.
Zurück zum Zitat L.G.A. Fujita, H. Palhares, A.P. da Silva, J.M. Tome, M.F. Borges, Clinical and laboratory parameters of gonadotropin-releasing hormone analog treatment effectiveness in children with precocious puberty. Clinics (Sao Paulo) 74, e1205 (2019)CrossRef L.G.A. Fujita, H. Palhares, A.P. da Silva, J.M. Tome, M.F. Borges, Clinical and laboratory parameters of gonadotropin-releasing hormone analog treatment effectiveness in children with precocious puberty. Clinics (Sao Paulo) 74, e1205 (2019)CrossRef
19.
Zurück zum Zitat K. Hari Kumar, “Make in India”—time for Indian protocols. Indian J. Endocrinol. Metab. 23(6), 591–592 (2019)CrossRef K. Hari Kumar, “Make in India”—time for Indian protocols. Indian J. Endocrinol. Metab. 23(6), 591–592 (2019)CrossRef
20.
Zurück zum Zitat C.P. Houk, A.R. Kunselman, P.A. Lee, The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-minute post-stimulation LH sample is adequate. J. Pediatr. Endocrinol. Metab. 21(12), 1113–1118 (2008)CrossRef C.P. Houk, A.R. Kunselman, P.A. Lee, The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-minute post-stimulation LH sample is adequate. J. Pediatr. Endocrinol. Metab. 21(12), 1113–1118 (2008)CrossRef
21.
Zurück zum Zitat G. Binder, R. Schweizer, G. Blumenstock, R. Braun, Inhibin B plus LH vs GnRH agonist test for distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism in boys. Clin. Endocrinol. (Oxf) 82(1), 100–105 (2015)CrossRef G. Binder, R. Schweizer, G. Blumenstock, R. Braun, Inhibin B plus LH vs GnRH agonist test for distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism in boys. Clin. Endocrinol. (Oxf) 82(1), 100–105 (2015)CrossRef
22.
Zurück zum Zitat P.M. Bossuyt, J.B. Reitsma, D.E. Bruns, C.A. Gatsonis, P.P. Glasziou, L. Irwig et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ 351, h5527 (2015)CrossRef P.M. Bossuyt, J.B. Reitsma, D.E. Bruns, C.A. Gatsonis, P.P. Glasziou, L. Irwig et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ 351, h5527 (2015)CrossRef
23.
Zurück zum Zitat M. de Onis, A.W. Onyango, E. Borghi, A. Siyam, C. Nishida, J. Siekmann, Development of a WHO growth reference for school-aged children and adolescents. Bull. World Health Organ. 85(9), 660–667 (2007)CrossRef M. de Onis, A.W. Onyango, E. Borghi, A. Siyam, C. Nishida, J. Siekmann, Development of a WHO growth reference for school-aged children and adolescents. Bull. World Health Organ. 85(9), 660–667 (2007)CrossRef
24.
Zurück zum Zitat WHO (2009). WHO AnthroPlus for personal computers: software for assessing growth of the world’s children and adolescents (World Health Organization, Geneva, 2009), http://www.who.int/growthref. Accessed Feb 18, 2021. WHO (2009). WHO AnthroPlus for personal computers: software for assessing growth of the world’s children and adolescents (World Health Organization, Geneva, 2009), http://​www.​who.​int/​growthref. Accessed Feb 18, 2021.
25.
Zurück zum Zitat W.A. Marshall, J.M. Tanner, Variations in pattern of pubertal changes in girls. Arch Dis Child 44(235), 291–303 (1969)CrossRef W.A. Marshall, J.M. Tanner, Variations in pattern of pubertal changes in girls. Arch Dis Child 44(235), 291–303 (1969)CrossRef
26.
Zurück zum Zitat W.W. Greulich, S.I. Pyle, Radiographic atlas of skeletal development of the hand and wrist. 2nd edn. (Stanford University Press, Stanford, CA, 1959). W.W. Greulich, S.I. Pyle, Radiographic atlas of skeletal development of the hand and wrist. 2nd edn. (Stanford University Press, Stanford, CA, 1959).
27.
Zurück zum Zitat C. De Leonibus, M.L. Marcovecchio, F. Chiarelli, Update on statural growth and pubertal development in obese children. Pediatr. Rep. 4(4), e35 (2012)CrossRef C. De Leonibus, M.L. Marcovecchio, F. Chiarelli, Update on statural growth and pubertal development in obese children. Pediatr. Rep. 4(4), e35 (2012)CrossRef
28.
Zurück zum Zitat S. Chung, Growth and puberty in obese children and implications of body composition. J. Obes. Metab. Syndr. 26(4), 243–250 (2017)CrossRef S. Chung, Growth and puberty in obese children and implications of body composition. J. Obes. Metab. Syndr. 26(4), 243–250 (2017)CrossRef
29.
Zurück zum Zitat C. Bizzarri, G.L. Spadoni, G. Bottaro, G. Montanari, G. Giannone, M. Cappa et al. The response to gonadotropin releasing hormone (GnRH) stimulation test does not predict the progression to true precocious puberty in girls with onset of premature thelarche in the first three years of life. J. Clin. Endocrinol. Metab. 99(2), 433–439 (2014)CrossRef C. Bizzarri, G.L. Spadoni, G. Bottaro, G. Montanari, G. Giannone, M. Cappa et al. The response to gonadotropin releasing hormone (GnRH) stimulation test does not predict the progression to true precocious puberty in girls with onset of premature thelarche in the first three years of life. J. Clin. Endocrinol. Metab. 99(2), 433–439 (2014)CrossRef
30.
Zurück zum Zitat S. Schubert, A.H. Hvelplund, A. Handberg, S. Hagstroem, T.L. Leunbach, Elevated pre-injection basal luteinizing hormone concentrations are common in girls treated for central precocious puberty. J. Clin. Res. Pediatr. Endocrinol. 13(2), 204–211 (2021)CrossRef S. Schubert, A.H. Hvelplund, A. Handberg, S. Hagstroem, T.L. Leunbach, Elevated pre-injection basal luteinizing hormone concentrations are common in girls treated for central precocious puberty. J. Clin. Res. Pediatr. Endocrinol. 13(2), 204–211 (2021)CrossRef
31.
Zurück zum Zitat C.P. Houk, A.R. Kunselman, P.A. Lee, Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls. Pediatrics 123(6), e1059–e1063 (2009)CrossRef C.P. Houk, A.R. Kunselman, P.A. Lee, Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls. Pediatrics 123(6), e1059–e1063 (2009)CrossRef
32.
Zurück zum Zitat E.T. Vestergaard, M.E. Schjorring, K. Kamperis, K.K. Petersen, S. Rittig, A. Juul et al. The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response to a gonadotropin-releasing hormone analogue test in healthy prepubertal girls aged 10 months to 6 years. Eur. J. Endocrinol. 176(6), 747–753 (2017)CrossRef E.T. Vestergaard, M.E. Schjorring, K. Kamperis, K.K. Petersen, S. Rittig, A. Juul et al. The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response to a gonadotropin-releasing hormone analogue test in healthy prepubertal girls aged 10 months to 6 years. Eur. J. Endocrinol. 176(6), 747–753 (2017)CrossRef
33.
Zurück zum Zitat H.K. Kim, S.J. Kee, J.Y. Seo, E.M. Yang, H.J. Chae, C.J. Kim, Gonadotropin-releasing hormone stimulation test for precocious puberty. Korean J. Lab. Med. 31(4), 244–249 (2011)PubMedPubMedCentral H.K. Kim, S.J. Kee, J.Y. Seo, E.M. Yang, H.J. Chae, C.J. Kim, Gonadotropin-releasing hormone stimulation test for precocious puberty. Korean J. Lab. Med. 31(4), 244–249 (2011)PubMedPubMedCentral
34.
Zurück zum Zitat D.S. Lee, N.Y. Ryoo, S.H. Lee, S. Kim, J.H. Kim, Basal luteinizing hormone and follicular stimulating hormone: is it sufficient for the diagnosis of precocious puberty in girls? Ann. Pediatr. Endocrinol. Metab. 18(4), 196–201 (2013)CrossRef D.S. Lee, N.Y. Ryoo, S.H. Lee, S. Kim, J.H. Kim, Basal luteinizing hormone and follicular stimulating hormone: is it sufficient for the diagnosis of precocious puberty in girls? Ann. Pediatr. Endocrinol. Metab. 18(4), 196–201 (2013)CrossRef
35.
Zurück zum Zitat E.K. Choo, S.V. Rajkumar, Medication shortages during the COVID-19 crisis: what we must do. Mayo Clin Proc. 95(6), 1112–115 (2020)CrossRef E.K. Choo, S.V. Rajkumar, Medication shortages during the COVID-19 crisis: what we must do. Mayo Clin Proc. 95(6), 1112–115 (2020)CrossRef
36.
Zurück zum Zitat H.A. Badreldin, B. Atallah, Global drug shortages due to COVID-19: impact on patient care and mitigation strategies. Res. Social Adm. Pharm. 17(1),1946–1949 (2021). H.A. Badreldin, B. Atallah, Global drug shortages due to COVID-19: impact on patient care and mitigation strategies. Res. Social Adm. Pharm. 17(1),1946–1949 (2021).
Metadaten
Titel
Triptorelin stimulated luteinizing hormone concentrations for diagnosing central precocious puberty: study of diagnostic accuracy
verfasst von
Rade Vukovic
Tatjana Milenkovic
Ivan Soldatovic
Sandra Pekic
Katarina Mitrovic
Sladjana Todorovic
Publikationsdatum
26.11.2021
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 3/2022
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-021-02947-z

Kompaktes Leitlinien-Wissen Innere Medizin (Link öffnet in neuem Fenster)

Mit medbee Pocketcards schnell und sicher entscheiden.
Leitlinien-Wissen kostenlos und immer griffbereit auf ihrem Desktop, Handy oder Tablet.

Neu im Fachgebiet Innere Medizin

Studie zur HIFU bei Prostatakrebs lässt viele Fragen offen

Führt eine HIFU-Ablation beim Prostatakarzinom im Vergleich mit einer radikalen Prostatektomie zu ähnlichen onkologischen, aber besseren funktionalen Ergebnissen? Interimsdaten der französischen HIFI-Studie sind uneindeutig. In einem Kommentar zur Studie werden zumindest drei allgemeine Erkenntnisse herausgearbeitet.

Leitlinienkonformes Management thermischer Verletzungen

Thermische Verletzungen gehören zu den schwerwiegendsten Traumen und hinterlassen oft langfristige körperliche und psychische Spuren. Die aktuelle S2k-Leitlinie „Behandlung thermischer Verletzungen im Kindesalter (Verbrennung, Verbrühung)“ bietet eine strukturierte Übersicht über das empfohlene Vorgehen.

Verschlechtert frühe Hyperoxie nach Reanimation die Prognose?

Kommt es sehr früh nach einer kardiopulmonalen Reanimation zu einem Zustand der Hyperoxie, ist dies bei Patienten nach einem Herzstillstand mit schlechteren funktionellen Ergebnissen assoziiert. Das zeigt eine Sekundäranalyse der TTM-2-Studie.

Infektanfälligkeit in früher Kindheit: eine bleibende Last?

Wenn Kinder in den ersten Lebensjahren immer wieder Infekte durchmachen, lässt dies Schlüsse auf die Infektneigung in der weiteren Kindheit zu.

EKG Essentials: EKG befunden mit System (Link öffnet in neuem Fenster)

In diesem CME-Kurs können Sie Ihr Wissen zur EKG-Befundung anhand von zwölf Video-Tutorials auffrischen und 10 CME-Punkte sammeln.
Praxisnah, relevant und mit vielen Tipps & Tricks vom Profi.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.