192b - Puberty Flashcards
GPR54 knockout mice have which clinical finding?
A. Central precocious puberty.
B. Delayed puberty in females.
C. Gonadotropin independent precocious puberty.
D. Hypogonadotropic hypogonadism
D. Hypogonadotropic hypogonadism
GPR54 is necessary to initiate puberty (activated by kisspeptin)
No kisspeptin also results in hypogonadotropic hypogonadism
What defines precocious and delayed puberty in:
- People with ovaries:
- People with testes:
Ages refer to *onset* of puberty
-
People with ovaries: Thelarche
- Precocious: < 8 years old (or 7, in African American populations)
- Delayed: > 13 years, or >4 years between onset of thelarche and menses
-
People with testes: Testicular growth
- Precocious: < 9 years
- Delayed: > 15 years, or >4 yeasrs between onset of testicular growth and full testicular maturation
A 16 year old girl had thelarche at age 11 years, but has not had menses yet.
Is this delayed puberty?
Yes
- Onset of thelarche at a normal age, but >4 years since onset of thelarche without menses
As children approach adolescence, GnRH secretion increases.
When are secretions highest?
Are they continuous or pulsatile?
Highest during sleep
Pulsatile
Continuosu GnRH secretion, even if high, will suppress LH/FSH
What is the peripheral “permissive hormone” that allows puberty to happen?
Leptin
- Signals to the hypothalamus that there is adequate fat/energy for puberty
- Allows the NKB -> kisspeptin -> GPR54 pathway to initiate puberty
- Promotes gonadotropin synthesis
What is the first sign of central puberty in:
- People with ovaries:
- People with testes:
- People with ovaries: thelarche (breast development)
- People with testes: testicular enlargement
List 3 congenital causes of hypoergonadotropic hypogonadism
- Klinefelter syndrome (XXY)
- Turner syndrome (XO)
- Gonadal dysgenesis
In all 3 cases, GnRH, LH, FSH will be high - but there is not gonadal response; low sex steroids feed back centrally -> continued increased LH/FSH
In puberty, pubic hair, axillary hair, acne, and body odor ususally result from increased levels of what hormone?
What is the source of this hormone in people with ovaries vs. people with testes?
Testosterone
- People with ovaries: adrenal testosterone
- People with testes: gonadal testosterone
A 7 year old girl presents with concern for early puberty. She has had some acne + body odor and pubic hair for the last 6 months. No growth spurt.
PE: Tanner 1 breast tissue, Tanner 3 pubic hair, axillary hair present
Is this precocious puberty?
What would you expect labs to show? (general)
Not precocious puberty
Signs point to increased testosterone, but not increased estradiol
=> suspect premature adrenarche
- LH/FSH: low
- Estradiol: low
- DHEA-S: high
DHEA-S is a marker of adrenal testosterone production
What is the role of NKB (aka TAC3) in puberty?
NKB regulates kisspeptin release - important for the onset of puberty
(and kisspeptin activates GPR54 -> puberty)
Mutation in NKB -> hypogonadotrypic hypogonadism, then reversal in adultood (not important for reproduction
What is the effect of a mutation in the ANOS1 gene?
Kallman syndrome: hypogonadotripic hypogonadism + anosmia
- ANOS1 (aka KAL1) tells GnRH neurons to migrate with the olfactory placode
- Mutation -> Failure to migrate -> Kallman syndrome
During which periods of childhood ar LH, FSH, and sex steroids elevated?
- Fetal life (subclinical neonatal mini-puberty)
- Infancy (mini-puberty of infancy)
- Puberty
An 8 year old Caucasian girl presents with breast development, left greater than right, over the past year. Her mother had menarche at 15 years and her father remembers pubertal timing being normal. Examination reveals left breast is Tanner Stage 2 and right is Tanner stage 3.
What would be your evaluation and next step?
This is premature thelarche
Asymmetric growth is common, but breast development beofre age 8 (7 in African-American girls) is considered premature
Evaluate for precocious puberty (measure LH/FSH, sex steroids)
I’m not really sure if you would treat precocious puberty? But evaluating for the cause may reveal other endocrine abnormalities, which may require intervention?
What is the role of kisspeptin in puberty?
kisspeptin activates GPR54, causing initiation of puberty
Note: kisspeptin is regulated by NKB (aka TAC3)
- Missing either kisspeptin or GPR54 -> hypogonadotropic hypogonadism*
- Missing NKB -> hypogonadotropic hypogonadism THEN reversal in adulthood (important for puberty, not reproduction)*
What is pubarchy?
Pesence of pubic hair
This is not delayed puberty
Would count as “constitiuttional delay of puberty”
Reassure and observe
(normal range = 9-15 years old for people with testes)
