The value of urinary gonadotropins in the diagnosis of central precocious puberty: a meta-analysis

Xu, Dan; Zhou, Xueying; Wang, Junfei; Chen, Xi; Liu, Tao

doi:10.1186/s12887-022-03481-1

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…Although home urinary samples could underlie some limitations concerning the correct collection procedure, as reported by Xu et al [ 19 ], it represents an undoubtedly valid tool as a non-invasive method to diagnose CPP. Concerning the storage of urinary samples, the choice not to freeze but to store urines at a controlled temperature of 4 °C derives from the need to ensure greater stability of the LH molecule, in accordance with what was established by Demir et al[ 13 ].…”

Section: Discussionmentioning

confidence: 99%

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

Brambilla,

Guarracino,

Pistone

et al. 2023

Ital J Pediatr

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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.

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Section: Discussionmentioning

confidence: 99%

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

Brambilla,

Guarracino,

Pistone

et al. 2023

Ital J Pediatr

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“…Studies from last decade reporting data on FMV urines or random urines have shown good usefulness, with sensitivity from 65% to 92% and specificity from 63% to 100% ( Demir et al , 2021 ; Zhan et al , 2021 ). A meta-analysis from Xu et al (2022) that retained six studies, in spite of heterogeneous collecting protocols (collection protocols, sample treatment prior to analysis) and analytical techniques, revealed an overall sensitivity of 79% and specificity of 84%. Comparisons of diagnostic thresholds from different studies must consider these pre-analytical and assay method differences.…”

Section: Discussionmentioning

confidence: 99%

Urinary gonadotropin assay on 24-h collections as a tool to detect early central puberty onset in girls: determination of predictive thresholds

Janot,

Perrin,

Raverot

et al. 2024

Human Reproduction

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STUDY QUESTION Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? SUMMARY ANSWER This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. WHAT IS KNOWN ALREADY Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. STUDY DESIGN, SIZE, DURATION This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. MAIN RESULTS AND THE ROLE OF CHANCE The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. LIMITATIONS, REASONS FOR CAUTION This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was used. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER In-house #23-5214 registered study.

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“…Among the newest laboratory data considered are levels of inhibin B, SHBG, and urinary gonadotropins. However, these tests are not easily accessible in all centers, can be expensive, and do not yet have a well-defined cut-off level [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Does Basal Morning Luteinizing Hormone (bLH) Predict Central Precocious Puberty (CPP) in Girls?

Baronio,

Assirelli,

Deiana

et al. 2024

Medicina

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Background and Objectives: bLH is considered an excellent biochemical predictor of CPP. However, its utilization in clinical practice shows some uncertainties. This study aims to evaluate the diagnostic power of bLH and propose a diagnostic algorithm for CPP. Materials and Methods: We conducted a monocentric cohort retrospective study evaluating all females referred for suspicion of CPP between 1 January 2017 and 31 December 2020 who underwent a GnRH test. Auxological, hormonal, and instrumental data were collected, including pelvic ultrasonography and bone age (BA) assessment. Simple linear regression, t-test, and ROC tests were utilized to study the diagnostic value of basal hormone levels. Two hundred thirteen girls were included in the study. They were subdivided into two groups according to the results of the GnRH test: Group 1, with LH peak > 5 IU/L (pubertal) and 79 patients (37%), and Group 2, with an LH peak ≤ 5 IU/L (prepubertal) and 134 patients (63%). Results: The ROC curve showed that bLH level > 1.5 Ul/L best predicts a pubertal response to the GnRH test (AUC 0.8821, accuracy 82%), with low sensitivity (34%). The multivariate analysis found that bLH > 0.5 IU/L, basal FSH (bFSH) > 3.5 IU/L, bLH/bFSH ratio > 0.16, BA advancement > 1.7 years, uterine volume > 3.6 mL, longitudinal uterine diameter > 41 mm, and the presence of endometrial rhyme were significantly associated with a pubertal response at the GnRH test. An algorithm based on these features was created, and its application would reduce the number of GnRH tests by 34%. Overall, 96.2% of Group 1 patients reached the LH peak at the 30th minute of the GnRH test, supporting the hypothesis that the GnRH test duration could be reduced to 30 min. Conclusions: Morning bLH > 1.5 IU/L could be carefully used as a diagnostic predictor of CPP. The GnRH test, even reduced to 30 min, could be reserved for girls who show low intermediate morning bLH and specific clinical signs of pubertal development.

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The value of urinary gonadotropins in the diagnosis of central precocious puberty: a meta-analysis

Cited by 6 publications

References 26 publications

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

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

Urinary gonadotropin assay on 24-h collections as a tool to detect early central puberty onset in girls: determination of predictive thresholds

Does Basal Morning Luteinizing Hormone (bLH) Predict Central Precocious Puberty (CPP) in Girls?

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