puberty

Question 1

Hypothalamic pituitary gonadal axis variations by age

Answer 1

Active in fetal development, functions in infancy and after infancy enters quiescent state (juvenile pause). FSH > LH in prepuberty. LH > FSH in puberty

Question 2

gonadarche

Answer 2

Hypothalamic GnRH secretion stimulates gonadotropes to secrete FSH and LH causing gonadal maturation and production of sex steroids

Question 3

adrenarch

Answer 3

maturation of the adrenal gland and production of the adrenal androgens, primarily DHEA-S and androstenedione. Causes pubic hair, axillary hair, body odor and acne in both boys and girls

Question 4

Normal age of pubertal onset

Answer 4

Boys: 9-14 years. Girls: 8-13yrs (caucasian), but on avg 1 year earler for African American and Hispanic girls. Menarche usually occurs 1.5-2 years after pubertal onset

Question 5

First physical signs of puberty

Answer 5

testicular enlargement >3 ml (or >2.2 cm) in boys (mediated by FSH and LH) and breast bud development in girls (mediated by estrogen)

Question 6

timing of puberty in boys

Answer 6

Testes (11.8 yrs) > pubic hair (12 yrs) > penile enlargement (13 yrs) and peak height velocity (14 yrs)

Question 7

What determines bone age advancement

Answer 7

estrogen in both boys and girls (testosteron is converted to estrogen by aromatase enzyme in boys). Onset of puberty correlates with bone age. Girls start puberty at bone age of 10.5-11yrs. Boys start puberty at bone age of 11.5-12 yrs

Question 8

Define delayed puberty

Answer 8

Boys with delayed puberty have no testicular enlargement by age 14 years or no completion of genital growth after 5 yrs. Girls with delayed puberty have no breast development by age 13 years or no menses 4 years after pubertal onset or by age 16 years

Question 9

Causes of delayed puberty

Answer 9

1. hypothalamic-pituitary axis dysfunction: hypogonadotropic hypogonadism. 2. Gonadal dysfunction: hypergonadotropic hypogonadism (decreased negative feedback of sex steroids on brain causes elevated gonadotropins)

Question 10

Most common cause of delayed puberty associated with low gonadotropins

Answer 10

Constitutional delay of growth and puberty. Children grow at normal prepubertal rate but are at shorter height percentile than expected. Bone age is delayed and onset of puberty is delayed, but puberty follows normal pattern of progression. Growth continues after peers stop gorwing and genetic height pontential is usually acheived. Family history of late bloomers

Question 11

Types of hypogonadotropic hypogonadism

Answer 11

Reversible: FSH/LH levels suppressed during chronic illness, malnutrition, stress, anorexia, hyperprolactinemia and hypothyroid. Permanent: idiopathic, Kallmann syndrome (GnRH deficiency with anosmia aka lack of smell), congenital hypopituitarism, CNS defects, Prader-Willi, pituitary tumor, CNS infection, infiltrative dz, autoimmune hypophysitis

Question 12

Causes of primary gonadal failure

Answer 12

Cogenital: Klinefelters (47, XXY), Turners (45, XO), gonadal dysgenesis, vanishing testes syndrome, and Noonan syndrome. Acquired: chemo, irradiation, galactosemia,testicular torsion, mumps orchitis and cryptorchidism

Question 13

Klinefelters phenotype

Answer 13

microphallus, small testes, learning disabilities, eunochoid, delayed puberty, gynecomastia, infertility

Question 14

Workup for delayed puberty

Answer 14

sense of smell, Bone age, gonadotropins, CBC, ESR, BMP, Thyroid, prolactin, testosterone/estradiol. Karyotype if hypergonadotropic

Question 15

Treatment of delayed puberty

Answer 15

Testosterone replacement therapy in boys. Low dose estrogen followed by cyclic therapy of estrogen and progestin in girls

Question 16

Define precocious puberty

Answer 16

boys: pubertal development before 9 years. Girls: development before 8 years (caucasian) or 7 years (african american and hispanic)

Question 17

complete vs incomplete precocious puberty

Answer 17

Complete: early onset and progression of pubertal development with linear growth acceleration and bone age advancement. Early closure of growth plates possible. Incomplete: early onset but not progressive. This includes benign premature thelarche and benign premature adrenarche

Question 18

Central vs peripheral precocious puberty

Answer 18

Central: Premature activation of hypothalamic-pituitary-gonadal axis. 5% of girls have CNS abnormality. 50% of boys have CNS abnormality. Peripheral: Puberty occurs independent of GnRH and gonadotropin stimulation.

Question 19

Causes of central precocious puberty

Answer 19

CNS causes: hypothalamic hamartoma, suprasellar tumor, hydrocephalus, previous CNS infection, major head trauma, cranial irradiation

Question 20

Causes of peripheral precocious puberty in boys

Answer 20

due to excess androgen production caused by congenital adrenal hyperplasia, adrenal tumor, Leydig cell tumor, hCG tumor, testotoxicosis (mutation of LH receptor causing it to be constitutively activated) or exogenous androgens

Question 21

Causes of peripheral precocious puberty in girls

Answer 21

excess estrogens producd by ovarian cyst, ovarian granulosa cell tumor or exogenous estrogens. Also lavender products. Girls may present only with signs of androgen effects such as pubic hair, axillary hair, oily skin and/or acne

Question 22

Causes of peripheral precocious puberty in both sexes

Answer 22

hypothyroidism (TSH is like FSH, breast development or testicular enlargement with delayed bone age and poor linear growth), McCune-Albright syndrome (triad of precocious puberty, café au lait spots and polyostotic fibrous dysplasia caused by activated mutation in G protein).

Question 23

Precocious puberty Physical exam - testes

Answer 23

Bilaterally testicular enlargement may be due to central precocious puberty, activation of the LH receptor by a hCG producing tumor, testotoxicosis, or McCune-Albright Syndrome. Unilateral testicular enlargement is usually associated with a testicular tumor. prepubertal sized testes seen in adrenal disorder and exogenous androgen exposure

Question 24

Precocious puberty labs

Answer 24

Central: LH and FSH may or may not be in pubertal range. GnRH stimulation test shows pubertal LH response to GnRH. Peripheral: LH and FSH levels are suppressed. GnRH stimulation test shows prepubertal LH response

Question 25

precocious puberty additional tests

Answer 25

pelvic ultrasound, adrenal/testicular ultrasound, estradiol, androgens

Question 26

Treatment of central precocious puberty

Answer 26

GnRH analogues- leuprolide acetate or histrelin down regulate pituitary GnRH receptors and decrease gonadotropin secretion

Question 27

Treatment of peripheral precocious puberty

Answer 27

Surgery if tumor. Glucocorticoids for congenital adrenal hyperplasia. Watchful waiting for ovarian cysts. Aromatase inhibitor for girls with McCune-Albright syndrome. Boys with this syndrome are treated with ketoconazole or androgen blocker + aromatase inhibitor

Question 28

Incomplete precocious puberty

Answer 28

Premature thelarche (onset of breast development, can occur under 2 years due to ovarian hormone production during infancy. Often regresses by 2 yrs.) and adrenarche (pubic hair/ axillary hair with normal height and bone age)- variants of normal development and do not require intervention.

Question 29

Premature adrenarche differential

Answer 29

adrenal/ovarian tumors, late onset congenital adrenal hyperplasia