Biochemical and Radiological Indicators of Cardiovascular Morbidity in Children With Premature Pubarche (PP)

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00581490
First received: December 20, 2007
Last updated: June 24, 2011
Last verified: June 2011
  Purpose

Children with premature pubarche will have radiological and radial artery tonometry evidence of cardiovascular morbidity at diagnosis when compared to matched controls.


Condition
Evidence of Cardiovascular Morbidity

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Biochemical and Radiological Indicators of Cardiovascular Morbidity in Children With Premature Pubarche

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Changes in biometric and radiological features between subjects and matched controls [ Time Frame: 6 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

DNA sample from consented subjects and controls


Estimated Enrollment: 24
Study Start Date: August 2003
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Idiopathic premature pubarche
Children with premature pubarche without precious puberty, adrenal hyperplasia or androgen secreting tumors

Detailed Description:

Premature pubarche (PP), also called premature adrenarche (PA), is the early appearance of pubic hair before the age of 8 in girls and before 9 in boys. It had been shown that PP results from excess adrenal androgens. The terms PP and PA are used synonymously and differ from premature (precocious) puberty, the early activation of hypothalamic-pituitary gonadal axis. The incidence of PP is almost tenfold higher in girls than in boys. PP in the absence of congenital adrenal hyperplasia, virilizing ovarian or adrenal tumors has been regarded in the past as a benign phenomenon that may be associated with transient acceleration of growth and bone maturation and was not thought to have an adverse effect on the onset and progression of puberty and on final height in most patients. However, recent evidence suggests that hyperinsulinemia and obesity are common features in prepubertal and pubertal girls with a history of PP. Peri- and post-pubertal girls with PP exhibit an increase in incidence of hirsutism and polycystic ovary syndrome (PCOS). PCOS, a common hyperandrogenic disorder of women, is characterized by functional ovarian hyperandrogenism (FOH). FOH is defined as a 17-hydroxyprogesterone and/or androstenedione level >2 SD above that of the mean for control subjects after subcutaneous gonadotropin-releasing hormone agonist (GnRHa) stimulation during dexamethasone suppression of the adrenal glands. An increased risk of ovulatory dysfunction and FOH in adolescence detectable 3 years after menarche has also been reported in children diagnosed with PP. Serum triglyceride levels in premature adrenarche patients are higher when compared to controls throughout all stages of pubertal development. Boys with PP show reduced insulin sensitivity, independent of obesity, as observed in girls with PP. In Hispanic and Caribbean girls studies have shown prenatal influence on the development of PP. The lowest birth weights are found in this group of girls with PP who also have pronounced hyperinsulinism. Also, the presence of dyslipidemia in girls with PP depends on weight gain after birth. It has been shown that prepubertal girls are inherently more insulin resistant than boys which has been suggested to be related to the intrinsic difference in sex linked genes. Early metformin therapy prevents progression from PP to PCOS in a high risk group of former low birth weight girls, supporting the key role of insulin resistance in the ontogeny of PCOS.

Early intervention in PP can be initiated before marked obesity, diabetes, hypertension and increased cardiovascular morbidity related to insulin resistance become associated with endothelial dysfunction and abnormal vascular structure. Any intervention to decrease cardiovascular morbidity and mortality related to obesity and insulin resistance optimally begins in childhood. The short term goal of this proposal is to collect non-invasive evidence of cardiovascular disease morbidity risk factors at the time of PP diagnosis and to determine how they progress. Symptomatic endpoints used in most adult intervention trials, i.e. cardiac events and death, are not applicable in the setting of childhood disease.

  Eligibility

Ages Eligible for Study:   3 Years to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Boys below the age of 9; girls below the age of 8 if Caucasian and below age 6 if African American

Criteria

Inclusion Criteria:

  • Boys and girls with isolated premature pubarche

Exclusion Criteria:

  • Congenital adrenal hyperplasia
  • Precocious puberty
  • Androgen producing tumors
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00581490

Locations
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Pfizer
Investigators
Principal Investigator: Revi P. Mathew, M.D. Vanderbilt University
  More Information

No publications provided

Responsible Party: Revi P. Mathew, M.D., Vanderbilt University Medical School
ClinicalTrials.gov Identifier: NCT00581490     History of Changes
Other Study ID Numbers: 030292
Study First Received: December 20, 2007
Last Updated: June 24, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Premature pubarche
Adrenal hyperandrogenism
Metabolic syndrome

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

ClinicalTrials.gov processed this record on October 20, 2014