First-Voided Urinary LH vs. GnRH-stimulation in Differentiating Slowly- From Rapidly Progressive-Precocious Puberty

This study is currently recruiting participants.
Verified February 2013 by Kaplan Medical Center
Sponsor:
Information provided by (Responsible Party):
Amnon Zung, Kaplan Medical Center
ClinicalTrials.gov Identifier:
NCT01800565
First received: February 21, 2013
Last updated: February 25, 2013
Last verified: February 2013
  Purpose

Precocious puberty (PP) in girls is classically defined by the onset of secondary sexual characteristics before eight years of age, but subsequent pubertal maturation can be quite varied. In many girls, PP takes a rapid course of progression (rapidly progressive precocious puberty; RP-PP) with an early menarche and fusion of the epiphyseal growth plates, leading eventually to a reduced final height if not treated. In a subset of girls with PP however, the growth rate slows to normal for age, skeletal maturation progresses in accordance with chronological age and there is little to no risk of impairment of final height (slowly progressive precocious puberty; SP-PP). Other conditions of non-progressive PP include premature breast budding and unsustained PP that is characterized by a spontaneous regression of sexual precocity. Due to their benign course, slowly progressive (SP) PP and other non-progressive forms of PP do not warrant therapy with GnRH agonists. Differentiating these forms from RP-PP is therefore essential to prevent unnecessary intervention in a population that accounts for at least 50% of girls with PP. A distinction between these forms of PP may be difficult on clinical grounds however, since all these patients may present initially as isolated breast development.

The gold standard for the diagnosis of true (central) PP is the measurement of gonadotropins following GnRH stimulation test. There is however an overlap between prepubertal and early pubertal values and between girls with premature breast budding and progressive PP. It was suggested therefore that progressive pubertal development and growth acceleration should be documented over a 3- to 6-months period before GnRHa therapy in initiated.

More than a decade ago several studies demonstrated that urinary gonadotropins are age related and significantly increased during puberty. It has been suggested that urinary gonadotropins measurements can be used for differential diagnosis of pubertal disorders. This is based on the assumption that gradual elevation of nocturnal LH secretion prior to and at the onset of puberty can be reflected by first-voided urinary LH (ULH). In this prospective study, the investigators aimed to evaluate the value of first-voided ULH measurements in predicting pubertal course and differentiating SP-PP from RP-PP, by comparison to GnRH-stimulated gonadotropins.


Condition Intervention
Precocious Puberty, Gonadotropin-dependent
Other: Measurement of LH in first-voided urine
Other: collection of first-voided urine sample for LH level

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Single Blind (Caregiver)
Primary Purpose: Diagnostic
Official Title: Urinary LH in the Diagnosis of Precocious Puberty

Resource links provided by NLM:


Further study details as provided by Kaplan Medical Center:

Primary Outcome Measures:
  • Identification of first-voided urinary LH cutoff for the detection of pubertal advancement by comparison with GnRH stimulated gonadotropins [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Levels first-voided urinary LH measurements in monitoring gonadotropin suppression during GnRHa therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Identification of first-voided urinary LH cutoff for differentiating pseudothelarche from true breast budding, compared with GnRH stimulated gonadotropins [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: June 2006
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
pubertal progression
A collection of first voided urine sample for the measurement of LH.
Other: Measurement of LH in first-voided urine
participants in this study will be studied by the standard GnRH stimulation test. In addition, they will provide first voided urine sample (the experimental part)for the measurement of LH.
Other: collection of first-voided urine sample for LH level
participants in this study will be studied by the standard GnRH stimulation test. In addition, they will provide first voided urine sample (the experimental part)for the measurement of LH.

Detailed Description:

Precocious puberty (PP) in girls is classically defined by the onset of secondary sexual characteristics before eight years of age, but subsequent pubertal maturation can be quite varied. In many girls, PP takes a rapid course of progression (rapidly progressive precocious puberty; RP-PP) with an early menarche and fusion of the epiphyseal growth plates, leading eventually to a reduced final height if not treated. In a subset of girls with PP however, the growth rate slows to normal for age, skeletal maturation progresses in accordance with chronological age and there is little to no risk of impairment of final height (slowly progressive precocious puberty; SP-PP). Other conditions of non-progressive PP include premature thelarche and unsustained PP that is characterized by a regression of sexual precocity. Due to their benign course, slowly progressive (SP) PP and other non-progressive forms of PP do not warrant therapy with GnRH agonists. Differentiating these forms from RP-PP is therefore essential to prevent unnecessary intervention in a population that accounts for at least 50% of girls with PP. A distinction between these forms of PP may be difficult on clinical grounds however, since all these patients may present initially as isolated breast development.

The gold standard for the diagnosis of true (central) PP is the measurement of gonadotropins following GnRH stimulation test , where peak LH and peak LH/FSH ratio are the most valuable diagnostic parameters. There is however an overlap between prepubertal and early pubertal values and between girls with premature thelarche and progressive PP. It was suggested therefore that progressive pubertal development and growth acceleration should be documented over a 3- to 6-months period before GnRHa therapy in initiated.

More than a decade ago, along with the development of high-sensitive immunoassay for gonadotropins that replaced the RIA, Demir and colleagues have shown that urinary gonadotropins are age related and significantly increased during puberty. It has been suggested by others that urinary gonadotropins measurements can be used for differential diagnosis of pubertal disorders. This is based on the assumption that gradual elevation of nocturnal LH secretion prior to and at the onset of puberty can be reflected by first-voided urinary LH (ULH). In this prospective study, the investigators aimed to evaluate the value of first-voided ULH measurements in predicting pubertal course and differentiating SP-PP from RP-PP, by comparison to GnRH-stimulated gonadotropins.

  Eligibility

Ages Eligible for Study:   3 Years to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Onset of puberty after 3 years of age in boys and girls
  • Onset of puberty before 8 years in girls and 9 years in boys

Exclusion Criteria:

  • Non-central precocious puberty
  • Congenital adrenal hyperplasia
  • Enuresis nocturne
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01800565

Contacts
Contact: Amnon Zung, MD 972-8-9441260 amzung2@bezeqint.net

Locations
Israel
Peditaric Endocrinology Unit, Kaplan Medical Center Recruiting
Rehovot, Israel, 76100
Contact: Amnon Zung, MD    972-8-9441260    amzung2@bezeqint.net   
Principal Investigator: Amnon Zung, MD         
Sponsors and Collaborators
Amnon Zung
Investigators
Principal Investigator: Amnon Zung, MD Pediatirc Endocrinology Unit, Kaplan Medical Center, affiliated with the Hebrew University of Jerusalem, Israel
  More Information

No publications provided

Responsible Party: Amnon Zung, MD, Kaplan Medical Center
ClinicalTrials.gov Identifier: NCT01800565     History of Changes
Other Study ID Numbers: ULH
Study First Received: February 21, 2013
Last Updated: February 25, 2013
Health Authority: Israel: Ethics Commission

Keywords provided by Kaplan Medical Center:
precocious puberty
urinary LH
GnRH stimulation test
gonadotropins

Additional relevant MeSH terms:
Puberty, Precocious
Gonadal Disorders
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 15, 2014