First Morning Voided Urinary Gonadotropin Measurements as an Alternative to the GnRH Test

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Abstract

Aims: We studied whether first morning voided (FMV) urinary gonadotropin measurements could be used as a noninvasive alternative to the GnRH test in the assessment of the hypothalamic-pituitary-gonadal function in children. Methods: In a single-center study, we compared FMV urinary gonadotropin concentrations with basal and GnRH-stimulated serum gonadotropin levels in 274 children and adolescents (78 girls, 196 boys) aged 5-17 years referred for growth and pubertal disorders. The concordance between FMV urinary gonadotropin concentrations and GnRH test results was assessed. Results: FMV urinary LH (U-LH), urinary FSH (U-FSH) and their ratios correlated well with the corresponding basal and GnRH-stimulated serum parameters (r ≥ 0.66, p < 0.001). Receiver operating characteristic curve analyses using urinary and serum LH and FSH concentrations showed that FMV U-LH and U-LH/U-FSH performed equally well as the GnRH test in the differentiation of early puberty (Tanner stage 2) from prepuberty (Tanner stage 1) (area under the curve 0.768-0.890 vs. 0.712-0.858). FMV U-LH and U-LH/U-FSH performed equally well as basal serum LH in predicting a pubertal GnRH test result (area under the curve 0.90-0.93). Conclusion: FMV U-LH determination can be used for the evaluation of pubertal development and its disorders, reducing the need for invasive GnRH stimulation tests.

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Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children.

Paola B Lara, Tiago B Ferreira, Samuel A R Pereira … (2007)

Recently, new methodologies have been applied to commercial immunofluorometric (IFMA) and immunochemiluminometric (ICMA) LH and FSH assays. The objective of the study was to use ICMA to establish basal and GnRH-stimulated LH and FSH reference values in normal subjects of different ages and sexual development, compared with IFMA. We established basal and GnRH-stimulated LH and FSH levels of 315 prepubertal and pubertal children (170 males and 145 females) divided into five groups according to Tanner stage. Of these, 106 subjects (59 males and 47 females) were submitted to GnRH test. The prepubertal upper limit of normal for basal LH, determined by the 95th percentiles of the prepubertal population, were 0.2 IU/liter (ICMA) and 0.6 IU/liter (IFMA) in both genders. No overlap of basal LH levels determined by ICMA was observed between prepubertal and pubertal males, but basal LH determined by IFMA overlapped in 11.8% of subjects. In girls, both methods yielded overlapping values (10.4%, ICMA; and 84.6%, IFMA). The LH peak after GnRH stimulation that defined puberty was 4.1 IU/liter (ICMA) and 3.3 IU/liter (IFMA) in boys and 3.3 IU/liter (ICMA) and 4.2 IU/liter (IFMA) in girls. After GnRH stimulation, values determined by the two methods overlapped in both genders. We conclude that ICMA is more sensitive and precise than IFMA, permitting differentiation of pubertal and prepubertal stage in boys under basal conditions. However, in girls the overlap of basal values was marked, indicating the need for the GnRH test to establish maturity of the hypothalamus-pituitary-gonadal axis.

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Sexual precocity: sex incidence and aetiology.

Kathleen A. Bridges, P. Hindmarsh, C. Brook … (1994)

The aetiology of 197 girls and 16 boys presenting with sexual precocity was reviewed. Ninety one girls and four boys had central precocious puberty (M:F 23:1); a cause was identified in all the boys but in only six girls. All boys with precocious puberty need detailed investigation; in girls investigation should be based on clinical findings, particularly the consonance of puberty.

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Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone.

K Barnes, Horace G. Cutler, D Lynn Loriaux … (1988)

Premature thelarche is a benign condition that affects young girls. In contrast, central precocious puberty is considered a more serious disorder that causes progressive secondary sexual development, accelerated growth and skeletal maturation, early epiphyseal fusion, and short adult stature. Differentiation between these 2 conditions is important, but may be difficult on clinical grounds, since patients with both disorders may present initially as isolated breast development. To examine the potential usefulness of gonadotropin measurements in distinguishing early central precocious puberty from premature thelarche, we measured basal and LHRH-stimulated plasma gonadotropin levels in 58 girls with idiopathic premature breast development. The girls were divided into six clinically distinct groups, based on the severity of clinical presentation, ranging from isolated breast development (group A) to complete secondary sexual development and accelerated growth and skeletal maturation (group F). The mean basal plasma LH levels and the peak LH response to LHRH stimulation were significantly less in girls with isolated thelarche (group A) than in girls with complete sexual development (group F). The mean basal plasma FSH levels did not differ between these groups, but the peak FSH response to LHRH was greater in girls with isolated thelarche than in girls with complete sexual development. Thus, girls with isolated premature thelarche had a FSH-predominant response to LHRH [mean ratio of peak LH to peak FSH, 0.29 +/- 0.10 (+/- SD)], while girls with complete sexual development had a LH-predominant response (peak LH/FSH, 4.16 +/- 1.80). All girls with isolated thelarche had peak LH/FSH ratios less than 1, and all girls with complete sexual development had a ratio greater than 1. Girls with early or intermediate manifestations of central precocious puberty, who had features of puberty in addition to breast development but lacked all of the features of group F, comprised groups B-E. These girls also had intermediate peak LH/FSH ratios, ranging from 0.29 +/- 0.10 (group B) to 3.35 +/- 2.66 (group E). We conclude that girls with early central precocious puberty frequently have LH and FSH responses to LHRH that are indistinguishable from the FSH-predominant responses of girls with isolated thelarche. These data are consistent with the hypothesis that premature thelarche and central precocious puberty may represent different positions along a continuum of hypothalamic LHRH neuron activation.

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Journal

Journal ID (publisher-id): HRP

Journal ID (nlm-ta): Horm Res Paediatr

Journal ID (doi): 10.1159/issn.1663-2818

Title: Hormone Research in Paediatrics

Publisher: S. Karger AG

ISSN (Print): 1663-2818

ISSN (Electronic): 1663-2826

Publication date Subscription-year: 2016

Publication date (Print): June 2016

Publication date (Electronic): 25 March 2016

Volume: 85

Issue: 5

Pages: 301-308

Affiliations

^aChildren's Hospital and ^bDepartment of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, and ^cDepartment of Pediatrics, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland; ^dWilliam Harvey Research Institute, Barts and the London, Queen Mary University of London, London, UK; ^eDepartment of Pediatrics, Institute of Clinical Sciences, Gothenburg Pediatric Growth Research Center, and ^fSahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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*And Demir, MD, PhD, MBA, Children's Hospital, Stenbäckinkatu 11, FI-00029 HUS Helsinki (Finland), E-Mail drand@demir.net

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And Demir https://orcid.org/0000-0002-0811-8834

Article

Publisher ID: 440955 Other ID: Horm Res Paediatr 2016;85:301-308

DOI: 10.1159/000440955

PubMed ID: 27011314

SO-VID: 3fb4dea2-7786-439b-a292-172cbd505096

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History

Date received : 27 May 2015

Date accepted : 08 September 2015

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Figures: 1, Tables: 4, References: 33, Pages: 8

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First Morning Voided Urinary Gonadotropin Measurements as an Alternative to the GnRH Test

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Karger: Endocrinology

Most cited references 26

Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children.

Sexual precocity: sex incidence and aetiology.

Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone.

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