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)?