Precocious Puberty

Question 1

What is the definition of precocious puberty?

Answer 1

The onset of secondary sexual characteristics before 8 years of age in girls and 9 years of age in boys.

Question 2

What are the three categories of precocious puberty?

Answer 2

Central, peripheral, and benign precocious variants

Question 3

What is the cause of central precocious puberty?

Answer 3

Central precocious puberty is always caused by early activation of the Hypothalamic-pituitary-gonadal axis.

Question 4

What features are required for the diagnosis of central precocious puberty in girls?

Answer 4

There must be adrenal and gonadal involvement manifested by clinical features of estrogen and androgen secretion.

Question 5

What features are required for the diagnosis of central precocious puberty in boys?

Answer 5

All that is needed in boys is gonadal involvement. There is no such thing as benign premature testelarche.

Question 6

What finding is never benign in males being worked up for precocious puberty?

Answer 6

Testelarche

Question 7

Compare/contrast central precocious puberty in girls vs boys.

Answer 7

CPP is more common in girls and most cases are sporadic and idiopathic, with only a 10% chance of having a brain tumor as the cause. 25-75% of boys with CPP have an underlying structural CNS abnormality.

Question 8

What are the clinical manifestations of central precocious puberty?

Answer 8

Children with CPP follow the typical sequence of sexual maturation in normal puberty. Height, weight, and bone age are advanced for age. Those who do not receive treatment end up being <5th percentile for height due to early epiphyseal closure. Brain development correlates with chronologic age.

Question 9

Which lab result indicates central precocious puberty?

Answer 9

Elevated LH in a prepubertal child is indicative of CPP.

Question 10

What imaging should be performed as part of the workup for central precocious puberty?

Answer 10

Brain MRI

Question 11

How often are CNS lesions discovered as part of the workup for central precocious puberty?

Answer 11

CNS lesions are found in ~10% of girls and 50% of boys. The younger the child, the more likely they are to have a CNS lesion. CNS lesions are rare in girls >6 years of age.

Question 12

What is the treatment for central precocious puberty?

Answer 12

Long acting GnRH analogues are used to interrupt the endogenous pulsatile GnRH from stimulating progression of sexual maturity. In the US, Leuprolide acetate is commonly used as an IM depot preparation. An alternative is Histrelin, which is a long-acting GnRH analogue administered yearly as an implant.

Question 13

What is the most common brain lesion to cause central precocious puberty?

Answer 13

Hypothalamic hamartoma, which consists of ectopic neural tissue containing GnRH-secretory neurons and functions as an accessory GnRH pulse generator.

Question 14

What type of seizure is associated with hypothalamic hamartomas?

Answer 14

Gelastic seizures, frequently manifested by inappropriate laughter.

Question 15

In what situation is surgery warranted for removal of hypothalamic hamartomas?

Answer 15

In patients with intractible seizures.

Question 16

How might intracranial tumors be responsible for peripheral precocious puberty?

Answer 16

Some intracranial tumors hypersecrete human chorionic gonadotropin (hCG), which shares a receptor with LH. Thus, the hypersecretion of hCG results in the activation of the LH receptor and production of testosterone in the gonad.

Question 17

What causes peripheral precocious puberty?

Answer 17

Peripheral precocious puberty (AKA gonadotropin independent precocious puberty) is caused by excess secretion of sex hormones from the gonads, adrenal glands, or germ cell tumors, and from endogenous exposure to sex steroids.

Question 18

What should be on the differential for girls with peripheral/gonadotropin independent precocious puberty?

Answer 18

Ovarian tumors, ovarian cysts that are overproducing hormones, feminizing adrenal tumors, McCune Albright syndrome, and exogenous estrogen ingestion.

Question 19

What should be on the differential for boys with peripheral/gonadotropin independent precocious puberty?

Answer 19

Congenital adrenal hyperplasia, adrenal tumors, Leydig cell tumors, intracranial hCG-secreting tumors, and familial male-limited precocious puberty (testotoxicosis).

Question 20

What is a physical exam clue to a gonadotropin-independent cause for precocious puberty in a boy?

Answer 20

Virilization without increase in testicular size indicates the presence of peripheral precocious puberty because testicular enlargement is stimulated by FSH.

Question 21

What type of precocious puberty is indicated by the presence of virilization without testicular enlargement?

Answer 21

Peripheral precocious puberty, because testicular enlargement is stimulated by FSH.

Question 22

What would you expect to see as part of the genital exam for a male with peripheral precocious puberty due to an hCG-secreting tumor?

Answer 22

The male would have virilization + testicular enlargement. Labs would show elevated hCG with a suppressed LH level because hCG acts on the LH receptors.

Question 23

Which type of tumor is most commonly implicated in peripheral precocious puberty caused by a tumor?

Answer 23

Germ cell tumors are most commonly implicated.

Question 24

What presentation would be expected from an estrogen-secreting tumor causing peripheral precocious puberty?

Answer 24

Breasts become enlarged and tender, uterus becomes enlarged, and the external genitalia become pubescent. The girls are anovulatory but may have menses. Pubic hair is absent.

Question 25

What is McCune-Albright syndrome?

Answer 25

MAS is an endocrine disorder characterized by precocious puberty, patchy pigmentation (café-au-lait macules with irregular “coast of Maine” borders), and fibrous dysplasia of the skeletal system.

Question 26

What disorder is characterized by precocious puberty, patchy pigmentation (café-au-lait macules with irregular “coast of Maine” borders), and fibrous dysplasia of the skeletal system.

Answer 26

McCune-Albright syndrome

Question 27

What is the classic presentation for McCune-Albright syndrome?

Answer 27

Isolated vaginal bleeding is the classic endocrine presentation for MAS in girls. LH and FSH are low and there is no response to GnRH.

Question 28

How do the Café-au-lait macules present in McCune-Albright syndrome differ from those present in Neurofibromatosis type 1?

Answer 28

Café-au-lait macules associated with MAS have an irregular “coast of Maine” border, in contrast to the smoother “coast of California” border found in NF1.

Question 29

What is premature thelarche?

Answer 29

Premature thelarche is usually a variant of normal and a diagnosis of exclusion. It is defined as isolated breast development that occurs in the first two years of life. Breast development can be unilateral and can fluctuate.

Question 30

What workup should be performed prior to the diagnosis of premature thelarche?

Answer 30

You must rule out excessive exposure to exogenous estrogen. Consider obtaining an estradiol level, an FSH level, an LH level, and a bone age. If the diagnosis is premature thelarche, labs should be normal for age.

Question 31

Does premature thelarche in a 6 month old require treatment?

Answer 31

No. It is a diagnosis of exclusion, but once diagnosed is known to be benign.

Question 32

What is the typical course for patients diagnosed with premature thelarche?

Answer 32

The diagnosis must be made before 2 years of age. Breast tissue usually persists for 3-5 years but can regress during this time.

Question 33

What is premature adrenarche?

Answer 33

Premature adrenarche is a benign condition caused by the early production of adrenal androgens.

Question 34

What are the typical physical exam findings for patients with premature adrenarche?

Answer 34

Affected children get any combination of pubic or axillary hair, body odor, or acne before 8 years of age in girls and 9 years of age in boys. There is no gonadal involvement, so there is no breast development in girls or testicular enlargement in boys.

Question 35

Which disorders have an increased prevalence in females diagnosed with premature adrenarche?

Answer 35

PCOS and hyperandrogenism are more commonly diagnosed in adult women who were found to have premature adrenarche as children.

Question 36

What must be ruled out before the diagnosis of premature adrenarche can be made?

Answer 36

Other causes of androgen excess, either endogenous or exogenous, must be ruled out prior to making a diagnosis of premature adrenarche.

Question 37

What workup should be performed prior to making the diagnosis of benign(idiopathic) premature adrenarche?

Answer 37

Testosterone level, DHEAS level, androstenedione level, 17-OHP level, and bone age.

Question 38

What are some endogenous causes of premature adrenarche?

Answer 38

Tumors or late-onset CAH

Question 39

What follow-up testing should be performed if the initial workup for premature adrenarche is abnormal?

Answer 39

Order an ACTH stim test with measurement of the 17-OHP level to rule out CAH due to 21-hydroxylase deficiency. Adrenal CT should be used to rule out an adrenal tumor.

Question 40

What common and uncommon causes of isolated vaginal bleeding must be ruled out prior to making a diagnosis of premature menarche?

Answer 40

Common: foreign body, vulvovaginitis, and sexual abuse. Uncommon: urethral prolapse and sarcoma botryoides.

Question 41

What must be ruled out if a boy <9 years of age presents with enlarged testes?

Answer 41

If a boy < 9 years of age has enlarged testes, there is a 25-75% chance that he has a brain tumor and a brain MRI should be ordered promptly.

Question 42

What causes pubertal gynecomastia?

Answer 42

Pubertal gynecomastia is a benign and self-limited increase in breast tissue speculated to result from a temporary alteration in the testosterone:estrogen ratio in prepubertal boys.

Question 43

In what stages of puberty my pubertal gynecomastia be diagnosed?

Answer 43

It can occur in Tanner stages 2-4, is usually bilateral, and generally resolves after 2 years.

Question 44

What findings would prevent one from making a diagnosis of benign pubertal gynecomastia?

Answer 44

Patients with breasts at Tanner stage 3 or greater (macrogynecomastia), presentation at Tanner stages 1 or 5 of puberty, age <10 or >16, or abnormal pubertal progression

Question 45

What is the recommended workup for patients presenting with pubertal gynecomastia?

Answer 45

Estradiol, estrone, testosterone, and LH to rule out an LH-secreting tumor. DHEAS to rule out an adrenal tumor, and hCG to rule out a germ cell tumor. For galactorrhea, consider ordering a prolactin level. Consider a karyotype, as patients with Klinefelter are at risk for gynecomastia, which may be the presenting symptom. Secondary screening is indicated if any of the initial workup is abnormal.