Precocious puberty

Summary: Key Points

1. Males considered precocious if sexual development before 9 years
2. Females used to be considered precocious if before 8 years
3. Some data suggest that breast development before 7 yrs in Caucasians and before 6 yrs in African-Americans may be more appropriate criteria
4. Consider organic disease in females in the "in-between zone" if clinical findings are suggestive (i.e., rapid height velocity, bone age maturation, rapid change in pubertal status, etc.)
5. HPG axis active in neonatal/infancy period but then quiescent between 2-8 years of age due to inhibitory influences.
6. Adrenarche begins at 6-8 years with increase in adrenal androgens (DHEA & DHEAS)
7. 2 types of precocious puberty
   1. Gonadotropin dependent: Isosexual precocious puberty (2 subtypes)
      1. Complete Precocious Puberty (aka True or Central Precocious Puberty)
      2. Incomplete Precocious Puberty
   2. Gonadotropin independent: Pseudoisosexual Precocious Puberty (or Peripheral Precocious Puberty)
8. Management/treatment:
   1. For workup, consider:
      • bone age, prolactin, head imaging
      • LH/FSH: if increased, do karyotype (get gynecomastia in Klinefelter's); if low, give GnRH test w/ LH level 30-45 min later. If pubertal, do MRI.
      • DHEA, urinary ketosteroids.
      • If excess androgens: DHEAS, 17-OHprogesterone, androstenedione, testosterone/free testosterone, BHCG (note: a small percentage of hepatoblastomas can elaborate HCG and cause precocious puberty)
      • If excess estrogens: estradiol (if normal, check total estrogens)
      • Imaging: US or CT o fpelvis for uterus and ovarian size and abdomen for liver or adrenal tumors
   2. CPP: focus management of underlying disorder if due to specific remediable anatomic abnormality of CNS; may need to inhibit HPG axis with long-acting GnRH agonists
   3. premature thelarche and/or premature adrenarche: follow closely for possible future signs of CPP or functional ovarian hyperandrogenism
   4. pseudoisosexual precocious puberty: treat primary disease

Discussion

Flowsheet for Workup: Females

(also check TFT's)

Flowsheet for Workup: Males

• any sign of secondary sexual maturation before
  • 8 year old in girls (some data to suggest 7 years in caucasians, 6 years in Af-Am)
  • 9 years in boys
• also see Normal Pubertal Development

• Isosexual Precocious Puberty (2 types)
  • Treatment of Complete Precocious Puberty 
  • Treatment of Incomplete precocious puberty
• Pseudoisosexual precocious puberty (aka peripheral precocious puberty)

Psychosocial aspects

Some cases:

• 4y/o female presents with vaginal bleeding; the rest of her exam is normal
• 5y/o female presents with increased growth velocity and breast enlargement
• 5y/o male/female presents with pubic hair
• 6 y/o male presents with bilateral testicular enlargement
• 4y/o male presents with phallus enlargement
• 3y/o female presents with breast enlargement; the rest of her exam is normal

Further discussion

• evaluation of a child must include consideration of the tumors, benign and malignant, that may be the cause.
• Central nervous system tumors, such as intracranial germ cell tumors, may mediate premature pubertal development via hypersecretion of human chorionic gonadotropin (hCG) hormone. These tumors, which typically arise in the pineal gland or suprasellar region, may lead to
  precocious puberty. Hypothalamic hamartomas are the most common
  identifiable central nervous system lesions that cause precocious
  puberty. These benign congenital malformations destroy the normal
  hypothalamic control of the onset of puberty and may secrete
  gonadotropin-releasing hormone (GnRH).
• Headaches, or less commonly, visual changes may be present in a child who has an intracranial tumor, but often a small tumor may be asymptomatic except for causing precocious puberty.
• Given the findings in this vignette, the most appropriate initial study is head computed tomography (CT) or magnetic resonance imaging.
• Obtaining blood tests  for beta-hCG and gonadotropins also would be helpful in the initial evaluation of this child who presents with headaches and precocious puberty because he could have an intracranial germ cell tumor.
• Adrenal or ovarian neoplasms also can cause precocious puberty. Adrenocortical adenomas or carcinomas can secrete hormones, including cortisol, aldosterone, androgens, estrogens, and steroid biosynthesis intermediates. Hyperandrogenism due to abnormal hormone production is characterized  by precocious puberty in boys and virilization in girls, and hyperestrogenism is associated with feminization and hypogonadism in boys and precocious puberty in girls. Ovarian tumors also may cause precocious puberty in girls and are more likely to be of stromal origin, such as granulosa cell tumors, which may secrete estradiol. Malignant ovarian tumors, which most commonly are of germ cell origin in girls, are an uncommon cause of precocious puberty.
  
  For the child described in the vignette, abdominal ultrasonography or CT is less likely to yield the diagnosis because the history suggests an intracranial tumor. Precocious puberty is not associated with neuroblastoma and, therefore, a urine evaluation for vanillylmandelic acid is not indicated. Because testicular tumors in childhood most commonly  are of germ cell origin and not associated with precocious puberty, testicular ultrasonography would not be helpful in this case. A toxicology screen may be valuable in a child who has headaches and difficulty in school, but the presence of precocious puberty should direct the evaluation to rule out a neoplastic process.
  
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