PUBERTY - TTS...enlargement Penile size Pubic/axillary hair Growth acceleration Voice change Case 1...
Transcript of PUBERTY - TTS...enlargement Penile size Pubic/axillary hair Growth acceleration Voice change Case 1...
PUBERTY
Preetha Krishnamoorthy
Division of Pediatric Endocrinology
Case 1
8-year-old girl referred for breast
development noted by mom
What do you want to know?
Normal or abnormal?
What if this was an 8-year-old boy with
penile enlargement and pubic hair?
Normal or abnormal?
Definitions: Precocious Puberty
Girls: 2º sexual development < 7 y.o. in
Caucasian girls, < 6 y.o. in African-
American girls
Boys: 2º sexual development < 9 y.o.
regardless of ethnicity
2º Sexual Development
Girls
Breast development
Growth acceleration
Enlargement of labia
Vaginal secretions
Change in uterus
Pubic/axillary hair
Boys
Testicular
enlargement
Penile size
Pubic/axillary hair
Growth acceleration
Voice change
Case 1
8 y.o. girl with breast development…
Normal or abnormal?
Case 1
8 y.o. girl with breast development…
Normal or abnormal?
Case 1
8 y.o. girl with breast development…
Normal or abnormal?
8 y.o. boy with penile enlargement and
pubic hair…
Normal or abnormal?
Case 1
8 y.o. girl with breast development…
Normal or abnormal?
8 y.o. boy with penile enlargement and
pubic hair…
Normal or abnormal?
Case 2
2 y.o. girl who has had breast
development
What do you want to know?
Associated features: growth
acceleration, vaginal discharge or
bleeding, pubic/axillary hair
Access to exogenous estrogens?
Case 2
Physical exam
Growth curve
Tanner Stage and breast volume
Vaginal mucosa
Variations in Pubertal
Development
Premature thelarche• unilateral or bilateral
• usually < 3 y.o.
• no other signs of estrogenization (areolar development,
vaginal discharge, growth), normal bone age
• may regress within months or remain
Premature adrenarche• early appearance of pubic or axillary hair without other
signs of virilization or puberty
• usually > 6 y.o., more common in girls
• mildly elevated DHEAS, slightly advanced bone age
Case 3
5 y.o. girl with breast development
What else?
+ growth acceleration
+ vaginal discharge
Normal or abnormal?
Case 3
5 y.o. girl with breast development
What else?
+ growth acceleration
+ vaginal discharge
Normal or abnormal?
Puberty
Hypothalamus
LHRH
Pituitary
LH/FSH
Gonads
Approach to Precocious
Puberty
CENTRAL
– activation of the
hypothalamic
pituitary axis
– tumour, hamartoma,
optic glioma, cyst,
radiation, infection
– idiopathic
PERIPHERAL
– no activation of
hypothalamic-
pituitary axis
– at the level of the
gonads, adrenals,
tumour, exogenous
Central vs. Peripheral
Precocious Puberty
Test to distinguish between the two:
LHRH stimulation test
If LH rises above ~7 IU/L
Prepubertal pituitary is quiescent so LH
levels should remain low despite
exogenous LHRH
Case 3
5 y.o. girl with breast development
LHRH stimulation test
LH max 12 IU/L
central
next step?
MRI
treatment: LHRH agonist
Case 4
4 y.o. boy with pubic hair
What else?
+ axillary hair
+ penile enlargement
+ growth spurt
no testicular enlargement
normal or abnormal?
Case 4
4 y.o. boy with pubic hair
What else?
+ axillary hair
+ penile enlargement
+ growth spurt
no testicular enlargement
normal or abnormal?
Case 4
Central vs. peripheral?
Testicular enlargement usually points to
a central cause
Case 4
Central vs. peripheral?
Testicular enlargement usually points to
a central cause
Case 4
Central vs. peripheral?
Testicular enlargement usually points to
a central cause
Peripheral
– gonads (testes)
– adrenals
– tumours
– exogenous
Case 4
Exceptions to the rule that testicular
enlargement usually points to a central
cause:
– testicular tumour (unilateral, large,
asymmetric)
– testotoxicosis
– hCG or LH-secreting tumour
Case 4
No testicular enlargement: likely
peripheral
Measure adrenal androgens,
testosterone
If adrenal androgens high, consider
CAH, adrenal tumour
If testosterone high, consider
testosterone producing tumour
21-OH deficiency
Salt-wasting (75%) - present in first few
weeks of life
Boys normally virilized, present in crises
Girls have ambiguous genitalia
Non salt-wasting forms
21-OH deficiency
Precocious puberty in boys and girls
PCOS-like picture in older girls with
menstrual irregularity, acne, hirsutism
Fertility problems
Cryptic CAH
Prenatal Rx of CAH
Who?
– Previous child affected
– Parents known to be carriers
Goals
– Prevention of genital ambiguity in a girl
– Lessen surgical intervention required
Prenatal Rx of CAH
Start Rx as soon as pregnancy is
diagnosed
Mom is given dexamethasone 20 μg/kg
Dx of fetus is made by CVS at 9-11
weeks or amniocentesis
Rx is stopped if it is a boy or an
unaffected girl
Prenatal Rx of CAH - PROS
Prenatal diagnosis
– prevent crisis in a boy who may have
otherwise been undiagnosed
– anticipatory guidance for parents
May lessen degree of surgery needed
Potential avoidance of surgery
? Effect of high androgen levels on
female brain
Prenatal Rx of CAH - CONS
Unnecessary Rx of 7/8
Risks of CVS/amniocentesis
Effects of high-dose steroids on mom
Long-term effects of fetal treatment
unknown
RECAP: Precocious Puberty
Normal or abnormal?
If precocious, is it one of the benign
variants of normal?
If not, is it central or peripheral?
LHRH stimulation test may be the only
way to tell
If central, MRI needed!
Case 5
13 y.o. girl who has not shown any
signs of puberty?
Normal or abnormal?
What if this was a 13 y.o. boy?
Normal or abnormal?
Definitions: Delayed Puberty
Girls: absence of any signs of pubertal
development by age 13
Boys: absence of any signs of pubertal
development by age 14
Case 5
13 y.o. girl who has not shown any
signs of puberty?
Normal or abnormal?
Case 5
13 y.o. girl who has not shown any
signs of puberty?
Normal or abnormal?
Case 5
13 y.o. girl who has not shown any
signs of puberty?
Normal or abnormal?
What if this was a 13 y.o. boy?
Normal or abnormal?
Case 5
13 y.o. girl who has not shown any
signs of puberty?
Normal or abnormal?
What if this was a 13 y.o. boy?
Normal or abnormal?
Case 5
13 y.o. girl with no signs of puberty
What do you want to know?
Previously healthy
Shorter than peers
No meds
Review of systems normal
Mother had menarche at age 17
Constitutional Delay of
Puberty
History of being shorter than age-
matched peers, normal growth velocity
delayed bone age
family history
Key: good follow-up!
Turner Syndrome
45 XO karyotype
Mosaicism
Presentation
– prenatal dx (karyotype, U/S)
– lymphedema
– short stature
– delayed puberty/amenorrhea
Turner Syndrome
Cardiovascular
Renal
Growth
Eyes
Ears
Muscolskeletal
Autoimmune
GI
Puberty
Fertility
Gonadoblastoma
Neuropsychological
Turner Syndrome
JCEM 2001 Recommendations for Adult
Care of Turner Syndrome
Transition after completion of puberty
Multidisciplinary team
Gyne with expertise in fertility
Turner Syndrome
Annual
– history
– P/E
• BP
• cardiac
• thyroid
• breast
• PAP
Turner Syndrome
Regular otologic exam
Sensorineural HL, >35 y.o. rapid
progression
If a dip q3-5 y, otherwise q10y
Turner Syndrome
Obesity
Lifestyle recommendations
Aim for a BMI <25
Osteoporosis BMD q3-5y, if stable, can
space it out
Turner Syndrome
Labs q2y
– Hgb
– BUN, creat
– ac gluc, lipids
– liver enzymes
– TSH, free T4
If known GU abN, screen for UTI prn
Turner Syndrome
Cardiac
– if N in childhood, echo q5y
– if echo poor quality do CT or MRI
– take chest pain seriously!
Careful monitoring for pregnancy, do
echo preconception for aortic root
dimensions
Turner Syndrome
E2 replacement
– Estrace 0.5 mg q2d x 3 mos, qd x 3-6 mos,
increase to 1 mg qd x3-6 mos, then to 2
mg qd
– Switch to OCP once she has a bleed
– Most need at least 2 mg 17β estradiol
Androgen concentration is decreased,
may consider replacement
Turner Syndrome
Fertility
– cardiac, renal, thyroid and glucose
tolerance pre-pregnancy
Functional ovaries
– think of conception early because of POF
– oocyte cryopreservation (under
investigation)
– risk of miscarriage
Turner Syndrome
Non functional ovaries
– oocyte or embryo donation may be
considered
– uterus will need special prep with E2 to be
7 mm thick
Vaginal delivery is an acceptable option,
C/S more common because of narrow
pelvis
Turner Syndrome
Psych
– Female gender ID is unambiguous
– Dating and sex - delayed and less
frequent, same as a woman who is short
and has primary amenorrhea
Turner Syndrome
More problems in school and with peers
Cognitive
– no decreased IQ, except with small ring X
chromosome
– selective impairment of visual-spatial and
nonverbal programming
Turner Syndrome
Turner Syndrome Society
Career planning
Independent living
Sex education
Case 6
17 y.o. girl who moved here from St.
Vincent
Had some breast development at age
12, did not progress
No vaginal discharge, no menarche
Short (height < 3rd percentile)
What else do you want to know?
Normal or abnormal?
Case 6
17 y.o. girl who moved here from St.
Vincent
Had some breast development at age
12, did not progress
No vaginal discharge, no menarche
Short (height < 3rd percentile)
What else do you want to know?
Normal or abnormal?
Approach to Delayed Puberty
Central = HPA axis problem
– hypogonadotropic
hypogonadism
– low LH and FSH
– illness, tumour,
prolactinoma,
anorexia, radiation,
Kallman’s, T4,
syndromes (PWS)
– other hormone
deficiencies
Peripheral = gonadal failure
– hypergonadodtropic
hypogonadism
– high LH and FSH
– gonadal dysgenesis
– mumps
– chemo, radiation to
gonads
– boys: XXY, anorchia,
cryptorchidism
– girls: XO, POF
Case 6
No underlying illness
No excess exercise, no anorexia
No sx or sx of hypothyroidism
No galactorrhea
Normal sense of smell
Headaches
Normal exam
Case 6
Work-up: LH, FSH, E2, prolactin, TSH,
T4, am cortisol + LHRH stim test
Bone age X-ray
Image head - skull films, CT or MRI
Delayed bone age
Skull film: enlarged sella turcica,
calcifications
Dx: craniopharyngioma
Case 7
16 y.o. boy with no signs of puberty
PMHx normal
Mild developmental delay, behavioural
problems in school
Review of systems otherwise
unremarkable
Physical exam reveals small, firm testes
Case 7
Likely central or peripheral?
Case 7
Likely central or peripheral?
Case 7
Likely central or peripheral?
Work-up: LH, FSH, testosterone,
prolactin, thyroid function
LH = 65 IU/L, FSH > 100
Confirms gonadal failure (peripheral)
Karyotype: 47, XXY
RECAP: Delayed Puberty
Normal or abnormal?
Could it just be constitutional delay?
Is it central (HYPOgonadotropic
hypogonadism)?
Is it peripheral (HYPERgonadotropic
hypogonadism)?