Biochemical and Radiological Indicators of Cardiovascular Morbidity in Children With Premature Pubarche
Condition: Evidence of Cardiovascular Morbidity
MeSH terms: Premature Birth
Study type: Observational

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

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.
    

Observational model: Case-Control
Time perspective: Prospective
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
      
Biospecimen description: 
      DNA sample from consented subjects and controls
    
Keywords: Premature pubarche; Adrenal hyperandrogenism; Metabolic syndrome