Skip to main content
Top
Published in: Italian Journal of Pediatrics 1/2023

Open Access 01-12-2023 | Research

Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty

Authors: Ilaria Brambilla, Carmen Guarracino, Carmelo Pistone, Catherine Klersy, Amelia Licari, Gian Luigi Marseglia, Enrico Tondina

Published in: Italian Journal of Pediatrics | Issue 1/2023

Login to get access

Abstract

Background

Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation.

Methods

The study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up).

Results

Two uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23–0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 − 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (pU < 0.05), and uLH collected in prepubertal group control.

Conclusions

uLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.
Literature
2.
go back to reference Maione L, Bouvattier C, Kaiser UB. Central precocious puberty: recent advances in understanding the aetiology and in the clinical approach. Clin Endocrinol. 2021;95(4):542–55.CrossRef Maione L, Bouvattier C, Kaiser UB. Central precocious puberty: recent advances in understanding the aetiology and in the clinical approach. Clin Endocrinol. 2021;95(4):542–55.CrossRef
3.
go back to reference Bruzzi P, Bizzarri C, Bozzola M, Cassio A. Central precocious Puberty Diagnostic Therapeutic Care Programme. Italian Soc Pediatr Endocrinol Diabetol 2017; 1–17. Bruzzi P, Bizzarri C, Bozzola M, Cassio A. Central precocious Puberty Diagnostic Therapeutic Care Programme. Italian Soc Pediatr Endocrinol Diabetol 2017; 1–17.
4.
go back to reference Cheuiche AV, da Silveira LG, de Paula LCP, Lucena IRS, Silveiro SP. Diagnosis and management of precocious sexual maturation: an updated review. Eur J Pediatrics. 2021;180(10):3073–87.CrossRef Cheuiche AV, da Silveira LG, de Paula LCP, Lucena IRS, Silveiro SP. Diagnosis and management of precocious sexual maturation: an updated review. Eur J Pediatrics. 2021;180(10):3073–87.CrossRef
5.
go back to reference Zhan S, Huang K, Wu W, Zhang D, Liu A, Dorazio RM, Shi J, Ullah R, Zhang L, Wang J, Dong G, Ni Y, Fu J. The use of morning urinary gonadotropins and sex hormones in the management of early puberty in chinese girls. J Clin Endocrinol Metab. 2021;106(11). Zhan S, Huang K, Wu W, Zhang D, Liu A, Dorazio RM, Shi J, Ullah R, Zhang L, Wang J, Dong G, Ni Y, Fu J. The use of morning urinary gonadotropins and sex hormones in the management of early puberty in chinese girls. J Clin Endocrinol Metab. 2021;106(11).
6.
go back to reference Xu D, Zhou X, Wang J, Cao X, Liu T. The value of urinary gonadotropins in the diagnosis of central precocious puberty: a meta-analysis. BMC Pediatr. 2022;22(1):453.CrossRefPubMedPubMedCentral Xu D, Zhou X, Wang J, Cao X, Liu T. The value of urinary gonadotropins in the diagnosis of central precocious puberty: a meta-analysis. BMC Pediatr. 2022;22(1):453.CrossRefPubMedPubMedCentral
7.
go back to reference Lee SY, Kim JM, Kim YM, Lim HH. Single random measurement of urinary gonadotropin concentration for screening and monitoring girls with central precocious puberty. Annals of Pediatric Endocrinology & Metabolism. 2021;26(3):178–84.CrossRef Lee SY, Kim JM, Kim YM, Lim HH. Single random measurement of urinary gonadotropin concentration for screening and monitoring girls with central precocious puberty. Annals of Pediatric Endocrinology & Metabolism. 2021;26(3):178–84.CrossRef
8.
go back to reference Oerter KE, Uriarte MM, Rose SR, Barnes KM, Cutler GB Jr. Gonadotropin secretory dynamics during puberty in normal girls and boys. J Clin Endocrinol Metab. 1990;7:1251–8.CrossRef Oerter KE, Uriarte MM, Rose SR, Barnes KM, Cutler GB Jr. Gonadotropin secretory dynamics during puberty in normal girls and boys. J Clin Endocrinol Metab. 1990;7:1251–8.CrossRef
10.
go back to reference Carel JC, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatr April. 2009;123(4):e752–62.CrossRef Carel JC, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatr April. 2009;123(4):e752–62.CrossRef
11.
go back to reference Kolby, et al. Nocturnal urinary excretion of FSH and LH in children and adolescents with normal and early puberty. J Clin Endocrinol Metab October. 2017;102(10):3830–8.CrossRef Kolby, et al. Nocturnal urinary excretion of FSH and LH in children and adolescents with normal and early puberty. J Clin Endocrinol Metab October. 2017;102(10):3830–8.CrossRef
12.
go back to reference Bourguignon JP, et al. Radioimmunoassays of unextracted gonadotrophins in timed fractions of 24-hour urine: morning increase of gonadotrophin excretion, a circadian pattern in relation to puberty. Hormone Res Paediatrics. 1980;13(6):367–84.CrossRef Bourguignon JP, et al. Radioimmunoassays of unextracted gonadotrophins in timed fractions of 24-hour urine: morning increase of gonadotrophin excretion, a circadian pattern in relation to puberty. Hormone Res Paediatrics. 1980;13(6):367–84.CrossRef
13.
go back to reference Demir A, et al. First Morning voided urinary gonadotropin measurements as an alternative to the GnRH Test. Hormone Res Paediatrics. 2016;85(5):301–8.CrossRef Demir A, et al. First Morning voided urinary gonadotropin measurements as an alternative to the GnRH Test. Hormone Res Paediatrics. 2016;85(5):301–8.CrossRef
14.
15.
go back to reference Demir A, et al. Age-related course of urinary gonadotropins in children. J Clin Endocrinol Metab. 1995;80(4):1457–60.PubMed Demir A, et al. Age-related course of urinary gonadotropins in children. J Clin Endocrinol Metab. 1995;80(4):1457–60.PubMed
16.
go back to reference Demir A, et al. Increase in first morning voided urinary luteinizing hormone levels precedes the physical onset of puberty. J Clin Endocrinol Metab. 1996;81(8):2963–7.PubMed Demir A, et al. Increase in first morning voided urinary luteinizing hormone levels precedes the physical onset of puberty. J Clin Endocrinol Metab. 1996;81(8):2963–7.PubMed
17.
go back to reference Yüce O, et al. Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment. Archives of Endocrinology and Metabolism. 2020;64(2):121–7.PubMedPubMedCentral Yüce O, et al. Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment. Archives of Endocrinology and Metabolism. 2020;64(2):121–7.PubMedPubMedCentral
18.
go back to reference Lucaccioni L, et al. The measurement of urinary gonadotropins for assessment and management of pubertal disorder. Hormones. 2016;15(3):377–84.PubMed Lucaccioni L, et al. The measurement of urinary gonadotropins for assessment and management of pubertal disorder. Hormones. 2016;15(3):377–84.PubMed
19.
20.
go back to reference Amnon, Zung, et al. Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods. J Pediatr Endocrinol Metab. 2015;28(7–8):885–93. Amnon, Zung, et al. Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods. J Pediatr Endocrinol Metab. 2015;28(7–8):885–93.
21.
go back to reference Manoranjan, Tripathy, et al. The role of urinary LH and FSH in the diagnosis of Pubertal Disorders. Indian J Endocrinol Metabolism. 2021 Mar-Apr;25(2):110–20. Manoranjan, Tripathy, et al. The role of urinary LH and FSH in the diagnosis of Pubertal Disorders. ​Indian J Endocrinol Metabolism. 2021 Mar-Apr;25(2):110–20.
22.
go back to reference Brito VN, Spinola-Castro AM, Kochi C, Kopacek C, Silva PC, Guerra-Júnior G. Central precocious puberty: revisiting the diagnosis and therapeutic management. Arch Endocrinol Metab. 2016;60(2):163–72.CrossRefPubMed Brito VN, Spinola-Castro AM, Kochi C, Kopacek C, Silva PC, Guerra-Júnior G. Central precocious puberty: revisiting the diagnosis and therapeutic management. Arch Endocrinol Metab. 2016;60(2):163–72.CrossRefPubMed
23.
go back to reference Stagi S, De Masi S, Bencini E, Losi S, Paci S, Parpagnoli M, Ricci F, Ciofi D, Azzari C. Increased incidence of precocious and accelerated puberty in females during and after the italian lockdown for the coronavirus 2019 (COVID-19) pandemic. Ital J Pediatr. 2020;46(1):165.CrossRefPubMedPubMedCentral Stagi S, De Masi S, Bencini E, Losi S, Paci S, Parpagnoli M, Ricci F, Ciofi D, Azzari C. Increased incidence of precocious and accelerated puberty in females during and after the italian lockdown for the coronavirus 2019 (COVID-19) pandemic. Ital J Pediatr. 2020;46(1):165.CrossRefPubMedPubMedCentral
24.
go back to reference Chioma L, Bizzarri C, Verzani M, Fava D, Salerno M, Capalbo D, Guzzetti C, Penta L, Di Luigi L, di Iorgi N, Maghnie M, Loche S, Cappa M. Sedentary lifestyle and precocious puberty in girls during the COVID-19 pandemic: an italian experience. Endocr Connections. 2022;11(2). Chioma L, Bizzarri C, Verzani M, Fava D, Salerno M, Capalbo D, Guzzetti C, Penta L, Di Luigi L, di Iorgi N, Maghnie M, Loche S, Cappa M. Sedentary lifestyle and precocious puberty in girls during the COVID-19 pandemic: an italian experience. Endocr Connections. 2022;11(2).
25.
go back to reference Street ME, Sartori C, Catellani C, Righi B. Precocious puberty and Covid-19 into perspective: potential increased frequency, possible causes, and a potential emergency to be addressed. Front Pead. 2021;9:734899.CrossRef Street ME, Sartori C, Catellani C, Righi B. Precocious puberty and Covid-19 into perspective: potential increased frequency, possible causes, and a potential emergency to be addressed. Front Pead. 2021;9:734899.CrossRef
26.
go back to reference Turriziani Colonna A, Curatola A, Sodero G, Lazzareschi I, Cammisa I, Cipolla C. Central precocious puberty in children after COVID-19 outbreak: a single-center retrospective study. Minerva Pediatr. 2022. Turriziani Colonna A, Curatola A, Sodero G, Lazzareschi I, Cammisa I, Cipolla C. Central precocious puberty in children after COVID-19 outbreak: a single-center retrospective study. Minerva Pediatr. 2022.
Metadata
Title
Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty
Authors
Ilaria Brambilla
Carmen Guarracino
Carmelo Pistone
Catherine Klersy
Amelia Licari
Gian Luigi Marseglia
Enrico Tondina
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Italian Journal of Pediatrics / Issue 1/2023
Electronic ISSN: 1824-7288
DOI
https://doi.org/10.1186/s13052-023-01506-8

Other articles of this Issue 1/2023

Italian Journal of Pediatrics 1/2023 Go to the issue