Premature Thelarche and Adrenarche

Definitions

  • Puberty is the developmental stage during which secondary sexual characteristics appear.
    • Precocious puberty is the onset of puberty at an abnormally early age; usually before the age of 8 in girls and 9 in boys. This number may be lower for African American or Hispanic patients. 
  • Thelarche is the onset of female breast development.
  • Pubarche is the appearance of sexual hair.
  • Adrenarche is the onset of androgen-dependent body changes such as growth of axillary and pubic hair, body odor, and acne.
  • Menarche is the onset of menstruation.

 

Normal Puberty

  • Normal puberty begins between ages 8-12 years in girls and 9-14 years in boys.
    • Tanner stage 2 breast development in girls
    • Tanner stage 2 testicular enlargement in boys
  • From a physiologic standpoint, this results when pulsatile secretion of GnRH begins and the hypothalamo-pituitary-gonadal axis is activated.
  • Criteria for defining the stages of puberty, proposed by Marshall and Tanner in 1969 and 1970, remain the standard of practice.

 

Premature Adrenarche

  • Premature adrenarche is the appearance of sexual hair (e.g., pubic, axillary) without other signs of sexual development. In the literature, the age ranges for diagnosis differ, but general practice dictates that the diagnosis be considered if signs develop in girls < 8 years old and boys < 9 years old.   
  • The appearance of pubic hair does not necessarily mean that true puberty has started.
  • Pathophysiology: GnRH secretion is activated early, either because of tumor (central or peripheral), but more commonly due to unexplained causes. This HPA axis dysfunction leads to DHEA and DHEA-S secretion from the adrenal glands that occurs earlier as well. The levels are normal for pubertal stage but elevated for chronologic age. The zona reticularis of the adrenals is responsible for androgen secretion.
  • Labs:
    • Adrenal steroid hormones, sex hormones, and ACTH and GnRH stimulation tests are normal.
    • The serum concentration of DHEA-S is the best marker for the presence of adrenarche. A level over 40 mcg/dl indicates that adrenarche has begun.
  • Differential:
    • Benign premature adrenarche
    • Tumors (e.g., androgen-secreting tumors in the gonads or adrenals)
    • Congenital disorders (e.g., CAH, McCune-Albright syndrome)
    • Central precocious puberty
    • Exogenous androgen exposure
  • Diagnostic Criteria:
    • Sparse to moderate development of pubic hair
    • Sparse or no growth of axillary hair
    • Mild or no acne
    • Minimal or no acceleration in growth rate
    • Mild apocrine body odor
    • No lowering of voice
    • No breast or testicular enlargement
    • No clitoromegaly
  • Management: If the criteria are met for benign premature adrenarche, then management can be limited to reassurance and continued observation every 6 months.
    • GnRH agonists remain the gold standard for central precocious puberty, usually stopped at 11 years to optimize for height outcomes
    • Surgical removal of any tumors that could be leading to precocious puberty (hypothalamic hamartoma, adrenal/gonadal tunors, etc)
  • Prognosis:
    • 50% will undergo puberty appropriately with normal fertility.
    • Final adult height is normal.
    • Some 20% of affected girls develop clinically significant ovarian hyperandrogenism as adults (e.g., PCOS)

 

Premature Thelarche

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  • Breast tissue development, bilateral or unilateral, with no other signs of sexual maturation.
  • Breast enlargement may regress after a few months or persist with little change.
  • 60% of cases are identified between 6-24 months of age and diagnosis after 4 years of age is unusual.
  • Management: If there are no other signs of sexual maturation, this is most likely a benign, self-limiting condition for which reassurance and continued observation every 6 months would be appropriate.
    • Recent studies have shown some indication for brain imaging studies if (1) onset is between 7-8 years of age, and (2) lack of pubic hair at the time of diagnosis
  • Prognosis:
    • Most patients undergo puberty appropriately.
    • About 10% of girls who have typical benign idiopathic thelarche develop true central precocious puberty and require treatment (see above)

 

References

  1. Carel, J and Leger, J. (2008). Precocious pubertyNEJM, 358(22), 2366-2377. 
  2. Chalumeau, M., et. al. (2002). Central precocious puberty in girls: an evidence-based diagnosis tree to predict central nervous system abnormalities. Pediatrics, 109(1), 61-67. 
  3. Diamantopolous, S. and Bao, Y. (2007). Gynecomastia and premature thelarche: a guide for practioners. Pediatrics in Review, 28(9), 57-68. 
  4. Kaplowitz, P. (2008). Link between body fat and the timing of puberty. Pediatrics, 121(3), S208-217. 
  5. Muir, A. (2008). Precocious pubertyPediatrics in Review, 27(10), 373-381.
  6. Pathomvanich, A., et. al. (2000). Early puberty: a cautionary tale. Pediatrics, 105(1), 115-116.

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