Puberty and its abberrations

Question 1

What neurons acts as central processors for relaying signals from the periphery to GnRH neurons?

Answer 1

Kisspeptin neurons

Question 2

What is pubarche?

Answer 2

presence of pubic hair

Question 3

What is adrenarche?

Answer 3

presence of androgen dependent changes including pubic hair, apocrine body odor, acne, body hair

Question 4

What is gonadarche?

Answer 4

earliest changes of gonads due to gonadotropin stimulation

Question 5

What is thelarche?

Answer 5

presence of estrogen dependent breast tissue

Question 6

What is menarche?

Answer 6

onset of menses

Question 7

What is gynecomastia?

Answer 7

enlargement of male breast tissue resultant of imbalance of hormones

Question 8

How is puberty defined in females?

Answer 8

presence of pubarche with thelarche

Question 9

How is puberty defined in males?

Answer 9

presence of pubarche with gonadarche

Question 10

What age defines precocious puberty in boys?

Answer 10

Before 9 years of age

Question 11

What age is normal pubertal onset for boys and girls?

Answer 11

1) girls: 8-13

2) boys: 9-14

Question 12

What hormones signify gonadarche?

Answer 12

1) in boys - testosterone

2) in girls - estrogen

Question 13

What hormones signify adrenarche?

Answer 13

adrenal androgens (testosterone, DHEAS, androstenedione)

Question 14

What hormone influences growth plate fusion?

Answer 14

estrogen in both sexes

Question 15

What non-invasive test can be used to further define pubertal advancement?

Answer 15

bone age

Question 16

What are the risks for precocious puberty?

Answer 16

1) early maternal menarche
2) low birth weight
3) excessive weight gain or obesity in infancy
4) after international adoption
5) after intercranial radiation

Question 17

Is isolated FSH elevation idicative of precocious puberty?

Answer 17

No - FSH spikes with GnRH occur even in prepuberty states

Question 18

What findings will you have gonadotropin-dependent puberty? (true puberty)

Answer 18

1) secondary sexual characteristics
2) bone age advancement
3) accelerated linear growth
4) gonadal maturation
5) gonadotropins (LH/FSH) - pubertal baseline and stimulated
6) sex steroids - pubertal

Question 19

What findings will you have in gonadotropin independent puberty? (pseudoprecocity)

Answer 19

1) secondary sexual characteristics
2) bone age advancement
3) accelerated linear growth
4) None/minimal gonadal maturation
5) prepubertal gonadotropins (LH/FSH)
6) sex steroids - pubertal

Question 20

What are some symptoms of McCune Albright Syndrome?

Answer 20

precocious puberty, cafe au lait pigmentation (coast of maine), polyostotic fibrous dysplasia

Question 21

What mutation is found in McCune Albright syndrome?

Answer 21

activating mutation of the GNAS1 gene which encodes the alpha subunit of the G protein

Question 22

What is testitoxicosis?

Answer 22

familial or sporadic male-limited sexual precocity

Question 23

What mutation is found in testitoxicosis?

Answer 23

constitutive activation of mutant LH receptors (autosomal dominant or sporadic)

Question 24

What are the signs/symptoms of testitoxicosis?

Answer 24

precocious puberty early in childhood (often by 2-3 years of age) , high testosterone, suppressed gonadotropins (testicular volume is less than expected for degree of sexual development)

Question 25

What mutation is found in Albright's hereditary osteodystrophy?

Answer 25

GNAS activating mutation that encodes for a Galpha subunit

Question 26

How does temperature affect the mutation in albright's?

Answer 26

1) at lower temperature (in gonads) gain of function - gonadotropin independent precocious puberty 2) at normal body temperature - loss of function (pseudohypoparathyroidism)

Question 27

What is hCG?

Answer 27

human chorionic gonadotropin - an LH receptor agonist (high levels stimulate LH receptor thereby promoting androgen production)

Question 28

What does hCG mediated sexual precocity rarely occur in girls?

Answer 28

both LH and FSH are needed for ovarian stimulation

Question 29

What is the only form of sexual precocity with growth arrest?

Answer 29

Van Wyk-Grumbach Syndrome

Question 30

What is Van Wyk-Grumbach syndrome?

Answer 30

sexual precocity in association with hypothroidism (often associated with galactorrhea, multiple ovarian cysts, little/no pubarche)

Question 31

What can testosterone exposure cause?

Answer 31

isolated pubarche

Question 32

What can estrogen exposure cause?

Answer 32

1) isolated thelarche in boys and girls | 2) menstrual bleeding in girls

Question 33

What defines delayed puberty?

Answer 33

lack of secondary sexual findings in boys by age 14 and age 12 or 13 in girls (lack of menarche by age 15-16 in girls)

Question 34

What describes constitutional delay of growth and puberty?

Answer 34

1) short stature AND delayed puberty 2) see fall in growth % over first two years of life followed by normal pre-pubertal growth velocity and then delayed puberty

Question 35

What is the differential for someone with normal growth, slight bone age delay and poor weight?

Answer 35

1) eating disorder 2) nutritional problem 3) competitive athlete

Question 36

What is the differential for someone with normal growth, slight bone age delay and normal weight?

Answer 36

1) if LH/FSH is high - hypergonadotropic hypogonadism 2) prepubertal LH/FSH levels - if prolactin is normal (hypogonadotropic hypogonadism), if prolactin is elevated (prolactinoma or CNS mass)

Question 37

What is the DD for decreased growth velocity, fairly normal bone age and elevated weight?

Answer 37

1) if prepubertal LH/FSH with normal thyroid function - cushing's 2) prepubertal LH/FSH with elevated TSH - hypothyroidism

Question 38

What is the DD for decreased growth velocity, fairly normal bone age and normal weight?

Answer 38

1) elevated LH/FSH and normal IGF-1 - Turners 2) prepubertal LH/FSH, low IGF-1 a) normal T4 and prolactin = isolated GH deficiency b) low T4, variable prolactin = consider hypopituitarism

Question 39

What is Kallman syndrome?

Answer 39

X-linked recessive form of hypogonadotropin hypogonadism associated with anosmia due to failed migration of GnRH neurons from the olfactory placode into the forebrain

Question 40

What mutations are found in Kallman syndrome?

Answer 40

mutations in the KAL gene of Xp22.3

Question 41

What is klinefelter syndrome?

Answer 41

the most common cause of male hypogonadism and infertility

Question 42

What is the clinical course of klinefelters?

Answer 42

1) enter puberty normally but testosterone levels fall in late adolescence and early adulthood 2) some academic delays 3) long extremities 4) gynecomastia

Question 43

When should you consider Turner Syndrome in your DD?

Answer 43

with short stature and ovarian dysfunction

Question 44

What is the clinical course of Turners?

Answer 44

1) normal statural growth for 1st 2-3 years followed by deceleration and typically normal bone age 2) 1/3 enter puberty normally