PEDIATRICS Vol. 107 No. 3 March 2001, pp. 609-610

Early Puberty: A Cautionary Tale

To the Editor.

Drs Pathomvanich, Merke, and Chrousos have presented their experience with an instructive patienta white girl whose pubic hair growth began shortly after her sixth birthday and breast development approximately a year and a half later. An evaluation did not occur until she was age 8.5, when significant insulin resistance was found. The authors go on to state that the child "fell within the normal range according to the data presented by Herman-Giddens et al."¹ We disagree. At least 3 factors about this girl's findings should have alerted her pediatrician to the need for an endocrine referral. First, the age at which her pubic hair growth began was 2.5 standards deviations (SDs) below the mean according to the data presented in our study. Second, it is less common for white girls to begin pubic hair growth before breast development. Third, the long delay between the onset of pubic hair growth and breast growth (greater than a year) is not typical of the normal pubertal sequence of growth. To summarize, this child exhibited premature breast development (not falling into the normal range of our data) and also displayed an abnormal pattern of maturation.

We are concerned that our study² may be used inappropriately to deter clinicians from referring girls with very early puberty if the findings of our study are not carefully reviewed. The article by Drs Kaplowitz and Oberfield with the Lawson Wilkins Pediatric Endocrine Society³ will help clarify when to refer girls for an endocrine evaluation. By the guidelines of their article, this young girl should have been referred when her pubic hair growth first started.

The data and conclusions provided by our study help redefine and update general population standards for the average onset of puberty in American girls. We hope that the findings will not be misinterpreted and deter clinicians from using their best judgment in evaluating specific individuals who may have a pathologic cause for their premature onset of puberty.

Marcia E. Herman and Giddens, PA, DrPH
School of Public Health
Department of Maternal and Child Health
University of North Carolina
Chapel Hill, NC

Carlos Bourdony
School of Medicine
Department of Pediatrics
University of Puerto Rico
San Juan, Puerto Rico

Eric Slora
Pediatric Research in Office Settings
Department of Research
American Academy of Pediatrics
Elk Grove Village, IL

Richard Wasserman
Pediatric Research in Office Settings
Department of Research
American Academy of Pediatrics
Elk Grove Village, IL and
Department of Pediatrics
University of Vermont College of Medicine
Burlington, VT

REFERENCES

1. Pathomvanich A, Merke DP, Chrousos GP Early puberty: a cautionary tale. Pediatrics. 2000; 105:115-116 [Free Full Text]
2. Herman Giddens ME, Slora EJ, Wasserman RC, Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research and Office Settings Network. Pediatrics. 1997; 99:505-512 [Abstract/Free Full Text]
3. Kaplowitz PB, Oberfield SE, Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Pediatrics. 1999; 104:936-941 [Abstract/Free Full Text]

In Reply.

We appreciate the opportunity to respond to the letter regarding our commentary.¹ Drs Herman-Giddens, Bourdony, Slora, and Wasserman² share our concern that the recent findings of earlier than expected breast and pubic hair development in a large cross-sectional study may deter clinicians from evaluating girls with pathologic precocious puberty. This was in fact the impetus for writing our commentary, which emphasized the importance of performing a medical evaluation of girls with early signs of puberty, including an evaluation for insulin resistance.

The patient we reported was a white girl who began pubic hair development shortly after her sixth birthday and breast development at 7.5 years of age. She had normal breast development (within 2 SDs from the population mean) according to the data presented by Herman-Giddens et al² in their epidemiologic study of secondary sexual characteristics (mean Tanner 2 breast development for white females ± SD, 9.96 ± 1.82 years). Her adrenarche occurred at approximately 2.5 SDs below the population mean for white females (mean age Tanner 2 pubic hair for white females ± SD, 10.51 ± 1.67 years). By the past conventional definition, when both breast and pubic hair appear before the age of 8 years, the diagnosis of precocious puberty is made. The Herman-Giddens data, however, would place our patient in the premature adrenarche rather than precocious puberty category.

Premature adrenarche, the early appearance of pubic hair, has long been considered a benign condition. Often medical evaluation is restricted to evaluation of the hypothalamic-pituitary-adrenal axis to rule out late-onset congenital adrenal hyperplasia. Our patient had significant insulin resistance and was presented as an example of the importance of including an evaluation for insulin resistance in girls with premature adrenarche. This is supported by the mounting evidence that girls with premature adrenarche are at risk for polycystic ovarian syndrome and its long-term sequelae.³

Reexamination of the definition of precocious puberty is an important issue. Subsequent to the submission of our commentary, the Lawson Wilkins Pediatric Endocrine Society undertook a comprehensive review of this topic.⁴ New guidelines proposed that girls with either breast development or pubic hair should be evaluated if this occurs before age 7 in white girls and before age 6 in African-American girls. According to this guideline, our patient should have been evaluated for premature adrenarche. However, this review states: "Girls with pubic hair but no breast development appearing before age 8 usually are diagnosed with premature adrenarche, a benign normal variant. However, those with other evidence of increased androgen production such as linear growth acceleration, clitoral enlargement, or acne require evaluation to exclude a more serious virilizing disorder."⁴

We would like to emphasize that the evaluation of girls with premature adrenarche should include an evaluation for insulin resistance. This is particularly important in light of the fact that the prevalence of overweight and obesity in children in the United States has dramatically increased during the past 20 years, and there has been a rise in the incidence of type 2 diabetes in youth.⁵ The association between this increase in obesity and the population trend toward the development of pubertal characteristics at a younger age is unknown. Similarly, whether the higher degree of insulin resistance in African-Americans than in whites contributes to the earlier puberty of African-American than in white girls is unclear but possible. Nevertheless, early identification of insulin resistance allows the pediatrician to implement improved dietary and physical activity behaviors and promote prevention of the complications of metabolic syndrome X.

Deborah P. Merke
Anuttara Pathomvanich
George P. Chrousos
Pediatric and Reproductive Endocrinology Branch
National Institute of Child Health and Human Development
Bethesda, MD 20892

REFERENCES

1. Pathomvanich A, Merke DP, Chrousos GP Early puberty: a cautionary tale. Pediatrics. 2000; 105:115-116
2. Herman-Giddens ME, Slora EJ, Wasserman RC, Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network [see comments]. Pediatrics. 1997; 99:505-512
3. Ibanez L, Potau N, Virdis R, Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1993; 76:1599-1603 [Abstract]
4. Kaplowitz PB, Oberfield SE, Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Pediatrics. 1999; 104:936-941
5. American Diabetes Association Type 2 diabetes in children and adolescents. Pediatrics. 2000; 105:671-680 [Free Full Text]