Snapshot A 5-year-old boy is referred to the pediatric endocrinology clinic by his pediatrician due to concerns about pubic hair growth. The parents report that he began showing signs of pubic hair growth over the past 3 months, and his height has accelerated markedly in the past half year. At the current visit, his height is at the 99th percentile for height and 98th percentile for weight. Physical examination shows that he has developed pubic hair and has a testicular length of 2.8 cm. A radiograph of his left hand and wrist is obtained and reveals that his bone age is 10 years. Introduction Overview precocious puberty is the appearance of pubertal development in children at a younger age than is considered normal (around 8 years for girls and 9 years for boys) Epidemiology Incidence 1 in 5,000-10,000 children Demographics 10:1 female-to-male ratio ETIOLOGY Pathophysiology onset of puberty is caused by the pulsatile release of GnRH by the hypothalamus ↑ in LH & FSH levels, which stimulate production of sex steroids androgens and estrogens cause the physical changes of puberty in boys and girls, as well as a growth spurt and enlargement of the gonads if child has advanced bone age central precocious puberty high FSH and LH may be caused by CNS tumors peripheral precocious puberty low FSH and LH abnormal secretion of sex hormones from ovaries, testes, or adrenal glands if child has normal bone age isolated premature thelarche isolated premature adrenarche may occur secondary to obesity Presentation History girls breast enlargement may be unilateral enlargement initially appearance of pubic and axillary hair menarche may occur 2-3 years after onset of breast enlargement early pubertal growth spurt boys testicular enlargement, followed by growth of the penis and scrotum pubertal growth spurt occurs later in boys than in girls Physical exam girls breast budding light pink vaginal mucosa color is a deeper red in pre-pubertal girls mild acne boys testicular enlargement (testicular length > 2.5 cm) mild acne facial hair Imaging Radiography of the hand and wrist determine bone age if bone age is within 1 year of child's age, puberty likely has not started if bone age is > 2 years of child's age, puberty has either been present for a year or longer Head MRI may identify an underlying tumor or hamartoma causing central precocious puberty Studies Sex steroid levels DHEA and DHEA-S levels ↑ in boys and girls with premature pubertal onset testosterone levels in boys < 30 ng/dL pre-pubertal 30-100 ng/dL early pubertal 100-300 ng/dL mid-to-late pubertal > 300 ng/dL adult estradiol levels in girls > 20 pg/mL pubertal levels may fluctuate from week to week, so not a consistently reliable indicator LH and FSH levels after GnRH stimulation measure LH and FSH levels after stimulation with GnRH or a GnRH analog ↑ in LH > 8 IU/L is diagnostic of central precocious puberty ↑ in FSH levels > ↑ in LH levels pre-pubertal Differential Premature pubarche key distinguishing factor early appearance of pubic and/or axillary hair but no other signs of puberty and no changes in sex hormones Treatment Medical GnRH analog (i.e., leuprolide) +/- growth hormone follow-up every 4-6 months to assess slowing/arrest of the progression of puberty ↓ acceleration of growth suppression of FSH and LH levels after GnRH challenge ↓ advancement of bone age Surgical resection of CNS tumor if present indications central precocious puberty caused by a CNS tumor Prognosis Majority of girls who experience precocious puberty at ages 6-8 years will achieve an average adult height without treatment extent of improvement in adult height compared with predicted height at start of treatment is correlated with the age of onset of precocious puberty