puberty Flashcards
definition of:
gonardarche
adrenarche
thelarche
menarche
spermache
pubarche
gonardarche = gonad activation by LH/FSH
adrenarche = release of androgens (DHEA/DHEAS)
thelarche = breast development
menarche = 1st period
spermache = 1st sperm production
pubarche = first pubic hair
age of onset of puberty determined by?
- genetics - boys follow MOTHERS, and vice versa
- BMI - higher BMI, earlier puberty
what governs adrenarche vs thelarche
adrenarche = hair, acne and body odour from ANDROGENS
thelarche from oestradiol (from ovaries)
order of puberty development in boys vs girls
girls: breasts > pubes > growth > period
males: balls >4ml > (penile length) > pubes > growth > sperm
which sex hormone is most important for growth?
oestrogen –> epiphyseal closure and GH (even in boys, oestrogen > T for this)
most reliable marker of androgens
DHEAS
when do GnRH/LH and FSH initially start being produced?
1-2y before clinical puberty
released at night, in pulsatile fashion
growth in males vs females
males: growth spurt 2y after females, ~13-14y, peak rate ~10cm/year
girls: spurt 0.5y before menarche, usually 11-12, 8.5cm/yr
bone development in males vs females
Females = E inhibits apposition + stimulates endocortical formation > narrower medullary cavity
Males = T increases bone size by ↑ apposition and ↑ distance of cortex > thicker cortex
at what age is precocious vs delayed puberty for males vs females?
females: <8y, >12y
males: <9y, >14y
all within 2SD of mean
normal testicular volumes
4-6yrs = 1ml
(>4ml = first sign of puberty)
10-12yrs =5ml
Adults 15-35mls
menstrual cycle summary
follicular phase = D0-13
- FSH stimulates follicles, which produce estradiol
- granulosa’s inhibin -ve FB FSH so it declines afer D5
- estradiol initially inhibits LH, then +ve FB after set point reached
ovulation = D14
luteal phase = D15=18
- corpus luteum > progesterone
- CL degenerates if not fertilised
- lower prog + E > menses
which phase is constant - luteal or follicular?
luteal - ovulation always 2 weeks prior to first day of next cycle
when does ovulation occur in relation to LH/oestradiol peak?
10-12 hours after LH surge, and 24-36 hours after estradiol peak
when do the pubertal progressions happen in males?
- first sign = testicular growth (> 4ml) and thinning of scrotum first sign ( 11-12 years)
- Pubarche = occurs 6 months after testicular enlargement
- Spermache = 2 years post pubarche
- Facial hair = 3 years post pubarche
define true precocious puberty, precocious pseudopuberty, incomplete precocious puberty
true precocious puberty = central, gonadotropin dependent
precocious pseudopuberty = peripheral, gonadotropin independent
incomplete = partial e.g. premature thelarche / adrenarche / menarche
examples of causes of true precocious puberty
- idiopathic - 80%! almost all girls
- hypothalamic hamartoma
- ** brain tumour - glioma, germ cell tumour **
- prolonged, untreated hypothyroid
true precocious puberty vs precocious pseudopuberty
true:
- from maturation of HPG axis
- SEQUENTIAL maturation
- isosexual
- more in girls
psedopuberty:
- from excess sex hormones / steroids / ectopic gonadotropin e.g. tumour
- HPG not activated, so not true puberty
- iso/contrasexual
- NON-SEQUENTIAL maturation
enlargement of penis without testicular enlargement = what hormone problem?
androgen e.g. from tumour
key Ix for central precocious puberty?
elevated basal LH and/or stimulated LH concentration post GnRH
how to treat central precocious puberty? MOA?
GnRH agonist = leuprolide, histrelin, goserelin
Physiolgical GnRH is pulsatile, so continious dose > ‘desensitization’/ -ve FB > inhibit endogenous GnRH
effects of GnRH agonist treatment in central precocious puberty
decreases growth rate > enhanced height
- breasts/balls regress
- public hair slower/regress
- menses cease
how to differentiate girls with CPP from those with premature thelarche
USS - Increased ovarian and uterine volumes with CPP
super rando signs for hypothalamic hamartoma
diabetes insipidus, adipsia, hyperthermia, unnatural crying or laughing (gelastic seizures), obesity, cachexia
most common genetic mutation found in idiopathic CPP
Loss of function mutations in MKRN3
precocious puberty + slow growth =
hypothyroidism!! only cause. also multicystic ovaries
pathogenesis of precocious puberty in hypothyroidism
High levels of TSH interact with FSH receptor, but not the LH receptor
FSH receptor > estradiol secretion by ovaries
LOW LH, FSH
why do we need to monitor pubertal status post treatment for peripheral precocious puberty?
6/12 monitoring as peripheral can trigger central e.g. CAH
pigmented nipples = what?
high oestrogen levels
most common cause of PPP in girls?
large ovarian cyst
summary of causes of PPP
- girls - ovaries (cyst/tumour)
- boys - testes tumour / germ cell in BOYS only/hepblastoma
- both: adrenal (tumour, CAH), McCune-Albright!
McCune-Albright - key features
- alpha subunit of Gs mutation
- classic triad: precocious puberty, cafe au lait macules, polyostotic fibrous dysplasia
- spontaneous activation of ACTH, TSH, FSH, LH
cafe au lait macules in NF vs MAS
MAS: coast of maine, irregular borders, don’t cross midline
NF: coast of cali, regular borers, cross midline
McCune Albright treatment
GnRH independent, so either
- girls: anti-oestrogen / azole
- boys: as above, or anti-androgens e.g. spiro
premature thelarche - key features
<3yo ONLY
normal height/bone age/genitalia
no Ix unless the above aren’t right
observe - 10% have true CPP
premature pubarche - key features
pubic > axillary
SLIGHTLY advanced bone age, still within normal range
no other signs of puberty
if have any other sign, need to exclude virilising disorders e.g. CAH
commonest dx of exclusion for delayed puberty
Constitutional Delay in Growth and Puberty (CDGP) - hallmark is delayed bone age, but height for bone age ok
can give short term steroids to kick start things
how to treat turners from endo perspective
- HRT at 12y: estradiol, then prog
- NO OCP - HTN risk high in Turner - GH
both help with height
