5 February 2013

ABNORMAL PUBERTY AND GROWTH

PROBLEMS
Ryan B. Capitulo, M.D., FPOGS
I.
II.
III.

Objectives
Pubertal Development
Sexual Maturity Rating
a.
Breasts
b.
Pubic Hair
IV.
Precociuos Puberty
a.
Classification of Precocious Puberty
i. Central
ii. Peripheral
iii. Incomplete
b.
Evaluation Of Precocious Puberty
c.
Management of Precocious Puberty
V.
Primary Amenorrhea
a.
Definition
b.
History
i. Patient History
ii. Family History
c.
Physical Examination
d.
Goals of Management
VI.
Quiz
Note: Dr. Capitulo said that he already made the questions for the
exam and all the questions will be based on the lecture.

OBJECTIVES
To review the following:
o Physiology of normal puberty in girls
o Tanner staging of pubertal changes in girls
o Duration of normal puberty in girls
To
discuss
the
definition,
characteristics,
pathophysiology,
types,
evaluation
and
management of precocious puberty.
To
discuss
the
definition,
characteristics,
pathophysiology,
types,
evaluation
and
management of primary amenorrhea.

PUBERTAL DEVELOPMENT
Thelarche beginning of breast development
10/8 +/- 1.10 years

Adrenarche beginning of pubic of axillary

hair growth
11.0 +/- 1.21 years

Max. growth growth spurt (earlier in

girls)
11.8 +/- 0.88 years

Menarche first menstrual

period
12.9 + 1.2 years
What was the first stage? It is breast budding or breast
development. We call that process as thelarche. In
Filipinos, it occurs at around 10 years old 1 year. So
the earliest is around 8-9 years old. Girls will start to
notice a breast bud, thats the first change. And then a
few months later, hair will develop. You will notice
axillary and pubic hair growth. We call that
adrenarche or pubarche. It occurs just a few months
after thelarche. The third is growth spurt - the period of
maximum growth. This occurs early in girls so
around the age of 12, the girls are taller than the boys.
Boys maximum growth occurs 1-2 years later.
Maximum growth occurs 1 year after breast budding.
Then the last change is menarche. It is the passage of
menstrual blood for the first time. It occurs at around

Cams, er, anj

12 years old 1.2 years. REMEMBER the pubertal

changes in girls: breast hair height mens.
So how do we evaluate teenagers? If you encounter
teenage patients, you have to do your Tanner Staging.
Dont forget that you must indicate Tanner Staging in
your physical examination.
Well review Tanner Staging. Its very easy and I ask
this in the exam so MEMORIZE!

SEXUAL MATURITY RATING

BREASTS
B1 prepubertal (no breast devt or pubic hair)
B2 breast budding
B3 enlargement of breasts with glandular tissue
without
separation of breast contour
B4 secondary mound formed by areola
B5 single contour of breast and areola

Stage 1 is always prepubertal no breast, no pubic

hair. B2 is breast budding. You will feel a marble like
structure underneath the areola. Thats the breast bud.
Thats the first change. You see that at around the age
of 10. When its slightly larger than the breast bud, it is
B3. Thats very important to differentiate it from B4
where there is no separation. Theres only one mound
for the breast. Its as if you have a small breast over
your main breast mass. B5 is the normal adult
configuration of the breast. The breast should be
pointing forward.

PUBIC HAIR
PH1 prepubertal, no pubic hair
PH2 labial hair present
PH3 labial hair spreads over mons pubis
PH4 slight lateral spread
PH5 further lateral spread to form inverse triangle
and reach medial thighs

Page 1 of 6

Stage 1, again, it is prepubertal no hair. PH2,

theres hair in the labia only. If it spreads cephalad,
going to the mons pubis area, thats PH3. If it spreads
laterally, going to the inner thigh, thats PH4. If its the
normal inverted triangle adult configuration of the
pubic hair, then thats PH5. REMEMBER these stages!
NORMAL PUBERTY
B2
10.8 + 1.10 years
PH2
11.0 + 1.21 years
Menarche
12.9 + 1.2 years
B2 to peak height velocity
1.0
+ 0.77
years
B2 to PH5
3.1 + 1.04 years
B2 to menarche
2.1 + 1.03 years
B2 to B5
4.5 + 2.04 years

I WONT be asking these. These are the normal age

among Filipinas. We expect these changes to occur.
Whats important here is the B2 to B5 breast
budding to the development of the normal adult
breast. This is the entire duration of puberty. So when
you have your normal configuration of the breast
already, then it means puberty is over. You are now an
adult. It occurs 4.5 2 years. Thats the entire
duration of puberty.

PRECOCIOUS PUBERTY
Appearance of any signs of secondary sexual
maturation at an early specific age more than 2.5
standard deviations below the mean
Initiation of secondary sexual characteristics before
age 8 or menarche before age 9 (The secondary
sexual characteristics are breast development,
pubic hair growth, maximum growth and
menarche.)
Associated with a wide range of disorders
A very rare disease (1 in 10,000 girls)
Concerns with precocious puberty
o Social stigma of child being physically
different from her peers
o Diminished ultimate height
Shorter than normal adult height due to
o Limited duration of the rapid growth spurt
(The period of maximum growth is limited
when you have precocious puberty. The
shorter the time for the maximum growth,
the shorter your height will be.)
o Accelerated bone maturation
o Premature closure of the distal epiphyseal
growth centers

Cams, er, anj

GnRH is the hormone responsible for the initiation of

pubertal
changes.
GnRH
comes
from
the
hypothalamus. At a certain time in a childs
development, the hypothalamus will start producing
and releasing in a pulsatile manner your GnRH. GnRH
will act on the pituitary gland. It stimulates the release
of gonadotropins (FSH and LH). FSH will stimulate the
follicles in the ovary. It will stimulate the granulosa
cells to secrete estrogen. Then estrogen will initiate
the pubertal changes. It will cause breast enlargement
or development. When estrogen is converted to
androgen in the peripheral tissues, it will cause pubic
hair growth and axillary hair growth. Estrogen is
involved in a lot of things, even in bone growth.
Skeletal growth is initiated by estrogen thats why you
have a period of maximum growth. When estrogen
acts on the uterus, thats the time you will experience
menarche. Thats the normal pubertal changes.
Again, GnRH will act on the pituitary and then the
gonadotropins will act on the ovary. So its a
hypothalamic-pituitary-ovarian axis with feedback
mechanisms.

edited: Sarah

CLASSIFICATION OF PRECOCIOUS PUBERTY

Central Precocious Puberty
Peripheral Precocious Puberty
Incomplete Precocious Puberty

CENTRAL PRECOCIOUS PUBERTY

GnRH-dependent precocious puberty
There is something wrong with the hypothalamus
because it secreted GnRH early. It should secrete it
around the age of 10. In patients with central
precocious puberty, it starts making GnRH at an
early age.
Physiologically normal pubertal development that
is chronologically early
Results
from
hypothalamic
GnRH-stimulated
episodic gonadotrophin secretion
GnRH, LH, FSH, sex steroid levels are similar to
those in normal puberty
Idiopathic in 70% of cases
CNS dysfunction in 30 % of cases
o Congenital defects (septooptic dysplasia)
o Destruction
from
tumors
(craniopharyngioma)
o Destruction from other lesions (arachnoid
cysts)
o Excessive exposure to sex steroids
(McCune Albright)
o Excessive pressure (hydrocephalus)
o Infection or inflammation (brain abscess,
meningitis)
o Injury (head trauma, irradiation)
o GnRH secreting tumors (hypothalamic
hamartomas)
PERIPHERAL PRECOCIOUS PUBERTY
GnRH-independent
precocious
puberty
or
pseudoprecocious puberty
Pubertal development resulting from stimulation
with a hormone other than hypothalamic GnRH
Page 2 of 6

May or may not follow the chronology of normal

pubertal development
Caused by estrogen secreting ovarian tumor in
60% of cases
o Granulosa cell tumor
o Mixed germ cell tumor
o Cystadenomas
o Gonadoblastoma

If that tumor is secreting estrogen only, then you can

have breast development (because its estrogenmediated) but sometimes these patients will not
present with pubarche or adrenarche. But these
patients can have maximum growth and menarche.
Whereas if the tumor is secreting testosterone for
example, you can have a sertoli leydig cell tumor in
the ovary that secretes androgen only. The child will
present with adrenarche only. No breast development
and maximum growth.
I have a patient, she presented with breast
development and menstruation. We worked her up and
we were looking for the cause. All the tests were
normal until the mother discovered that the child was
taking her OCP. The child taught it was candy so she
took it. She was taking 1-2 tablets a day for about a
month. In that span of time, she developed breast
developed budding and she had menarche. She was
just 3 years old! She was taking exogenous estrogen
it is also called peripheral precocious puberty.

Exogenous sex steroids or gonadotrophin

Chronic primary hypothyroidism
Feminizing adrenal tumors

INCOMPLETE PRECOCIOUS PUBERTY

Incomplete meaning she has only one pubertal
change.

Premature Thelarche
o Isolated unilateral
or bilateral breast
development
o Not accompanied by other signs of pubertal
development
o Usually occurs at age 1 to 4 years
o Benign self-limiting condition that does not
require treatment
The patient will just come to you with breast
enlargement. No axillary or pubic hair growth. No
increased in height. No menarche. This usually occurs
at the age of 1-4. It is benign self-limiting condition
that does not require any treatment, so you only have
to reassure the mother. Thats if you are sure that its
just premature thelarche. So when you encounter this
patient, you should follow her up for a couple of
months to see that she wont develop the other
changes.

Premature Pubarche or Adrenarche

o Early isolated development of pubic or
axillary hair without other signs of secondary
sexual maturation
o Self-limited but must be followed up carefully

The patient will come to you with pubic hair growth

and axillary hair growth but no breast development, no
increase in height and no menarche. It also self limited
Cams, er, anj

but we have to still have to follow up and eventually

reassure the parents that it will go away by itself.
Recap: Central precocious puberty is GnRH mediated,
so the patient will go through all the changes of
puberty. In peripheral precocious puberty it is no
caused by GnRH, it is caused by an individual hormone
responsible for puberty, so if the patient has a tumor
secreting estrogen, you will only expect changes due
to estrogen, if she has a tumor secreting androgen,
you will only expect changes due to androgen etc. So if
the patient has Incomplete precocious puberty then
she can only have premature thelarche or pubarche.
EVALUATION OF PRECOCIOUS PUBERTY
Meticulous history and PE
o Height
o Tanner stage
o Neurologic exam
When the patient comes to you, it is highly emphasize
that you do a very meticulous PE. Get the patients
height and compare it with her age group and then do
a tanner staging and neurologic exam because 30% of
the time, the patient would have neurologic problem if
she have central precocious puberty.

Serum estradiol, FSH, LH, androgens and thyroid

function tests
Thyroid function test is requested because sometimes,
patient with thyroid problems also presents with
central precocious puberty problem.

Bone age (hand-wrist films) repeated every 6

months
Bone aging is very important. This is done by
radiologist using hand-wrist films. They compare the
hand-wrist film of the patient with that of the film of
the same age group, and they will be able to say the
exact bone age of the patient. So if a patient comes to
you, she is age 4 but her hand-wrist film will show that
she is 7 years old then that patient has central
precocious puberty.

Imaging studies like ultrasound, skull x-ray, cranial

CT scan and MRI
Done to check for masses or tumors. Cranial CT and
MRI to rule out any CNS dysfunction that is usually
present 30% of the time.

MANAGEMENT OF PRECOCIOUS PUBERTY

Depends on the cause, extent and progression of
precocious signs
For PPP: remove the source of the hormone
o Ovarian tumor/adrenal tumor causing the
precocious puberty surgericaly removal
o Taking exogenous estrogen- stop taking it
o Incomplete precocious puberty- observe
since it is self limiting
For CPP: treat the patient if with
o PROGRESSIVE thelarche and pubarche and
menarche
o Bone age >2 years for age
Risk for having short stature
Goals of treatment of CPP:
o Reduce GnRH secretion by the hypothalamus
and peripheral actions of sex steroids.
We want to reduce and stop it! Because we know that
the menarche stage should happened around the age

edited: Sarah

Page 3 of 6

of 10! Not 3 years old! So we have to keep treating the

patient until she reach the proper age.
o Decrease growth rate to normal
o Slow
skeletal
maturation
to
allow
development of maximal adult height

GnRH analogues drug of choice

You might wonder why we are treating CPP with a
GnRH analogue instead of an antagonist. The reason
for this is because this analogue saturates the
receptors in the pituitary gland until the GnRH
produced by the hypothalamus will not be able to act
on the pituitary gland.
o Most effective in 4 to 6 year olds
o Decreases gonadotrophin and sex steroids to
prepubertal levels
o Causes regression of precocious signs
o Continue treatment until progress of puberty is
age- appropriate and consistent with emotional
maturity, current height and height potential
so if you have a patient with CPP at the age of4
years old, then you should treat the patient for
6 years until she reaches the proper age.
According to Sir, he had a patient who had a CPP but
refused treatment because the treatment is really
expensive and requires monthly injections of about
16K. Also, for the mother of the patient, the
consequence of having a short statue is not much of a
consequence.

Pubertal History

PHYSICAL EXAMINATION
Anthropometric Measurements
BMI
Dysmorphic Features congenital anomalies
Rudimentary or Absent Uterus
Pubic Hair Pattern
Striae, buffalo hump, central obesity, etc.
Tanner Staging
Thyroid Examination
Vaginal Septum or Imperforate Hymen
Signs of Virilization
EVALUATION
History and P.E. completed

Secondary Sexual Characteristics Present?

NO
Measure FSH and LH

PRIMARY AMENORRHEA
`DEFINITION
(+) secondary sexual characteristics and
(-) menarche by age 16.5 years (16 years and 6
months)
OR
(-) secondary sexual characteristics and
(-) menarche by age 14

Low
FSH & LH

Delay puberty or primary amenorrhea. The patient has

secondary sexual characteristics BUT no Menarche at
the age of 16.5 years then we diagnose her as having
primary amenorrhea or if the patient has NO
secondary sexual characteristics and menarch at the
age of 14.

Cams, er, anj

High
FSH & LH

Ultrasound of Uterus

Uterus (-)
or
abnormal

Uterus (+)
or
normal

NO SECONDARY SEXUAL CHARACTERISRICS

Measure FSH and LH

HISTORY
PATIENT HISTORY
Menstrual History
Illness, Drug Use
CNS Chemotherapy or Radiation (Brain
radiation will cause ischemia of pituitary
gland)
Pelvic Radiation
Psychosocial Stressors
Sexual Activity (Consider pregnancy)
Breast Changes
Anosmia
Abdominal Pain
Vasomotor Symptoms
FAMILY HISTORY
Genetic Defects
Pubic Hair Pattern
Infertility
Menarche and Menstrual History of Mother and
Sisters

YES

Low
FSH & LH

Hypogonadotropic
Hypogonadism
Hypothalamic
Failure
Pituitary Failure

High
FSH & LH

Hypergonadotropic
Hypogonadism
KARYOTYPE
POF
(46,XX)

Turners
Syndrome (45,XO)

If the patient comes to you with NO secondary sexual

characteristics, we measure for FSH and LH, if it is low,
we call it hypogonadotropic hypogonadism
meaning the pituitary gland or the hypothalamus is
NOT functioning. And because of this, there is no
stimulation of the ovaries, hence no production of
edited: Sarah

Page 4 of 6

estrogen, and therefore absence of secondary sexual

characteristics.
If the FSH and LH are high (hypergonadotropic),
meaning the pituitary gland and the hypothalamus are
fine or are working perfectly. The reason however for
their absence of secondary sexual characteristics
(hypogonadism) is because the ovaries are not
functioning. If we have a patient with this condition,
we request for karyotyping, if the results showed that
the patient have normal karyotype, then we conclude
that the patient have POF or premature ovarian
failure, meaning that the ovaries just died at such a
young age. The other reason however, for having
hypergonadotropic hypgonadism could be that the
patient have turners syndrome, and patients with
turners syndrome have NO gonads
The other concept that we have to remember in the
hypergonadotropic hypogonadism, is the concept of
feedback mechanism. Normally, the ovaries should
produce inhibin in the event that the there is already
enough FSH and LH, but since there are no ovaries or
gonads in POF and Turners syndrome, then there
would be no production of estrogen and no production
of inhibin, hence the hyperogonadotropism.
WITH SECONDARY SEXUAL CHARACTERISTICS

If however the karyotype of the patient with no uterus,

showed that the patient is really a male (46 XY), the
patient therefore as androgen insensitivity syndrome.
AIS (androgen insensitivity syndrome)- also
known as testicular feminization syndrome; no
receptor for androgens; therefore even if they have
capability of producing androgen, there body will not
be able to read the androgens, hence the body will
not be capable of producing male characteristics. Also,
remember that all embryos are destined to become
females unless there is androgen. They are
phenotypically female.
If there is a uterus, we inspect for outflow
obstruction, the patient might have imperforate
hypemen or septum.
The hymen usually perforates just before the female
child is born. Sometimes, it doesnt perforate.
Abdominal pain every month since the patient is really
menstruating is just that the the blood is accumulated
inside, until there would be uterine enlargement.
Tx- hymenectomy. Remove a portion of the
hymen and then all the menstrual blood that
accumulated will go out.
Or the patient have transverse vaginal septum

Ultrasound of Uterus

Transverse vaginal septum- during development,

the vaginal canal should canalize. Just remove the
septum for the menstrual blood to come out.
Note: Jamie Lee Curtis actress with AIS

Uterus (-)
or
abnormal

Uterus (+)
or
normal
OUTFLOW
OBSTRUCTION?

KARYOTYPE
Mullerian
Agenesis
(46,XX)

AIS
(46,XY)

NO
Others

YES
Imperforate
Hymen or
septum

Now, in patients with primary amenorrhea BUT with

secondary sexual characteristics, we request for
ultrasound thinking that there might be NO uterus.
If on ultrasound and on PE, the patient has NO uterus,
we request again for karyotype. If the karyotype,
showed that the patient is really a female (46, XX) then
the patient must have Mullerian Agenesis.
Mullerian agenesis- mullerian ducts, which are the
precursor for fallopian tubes and uterus, disintegrated
during intrauterine development. She has no uterus,
fallopian tubes, and upper 2/3 vagina. She however,
still has ovaries (reason for having secondary sexual
characteristics) because in embryology, the origin of
ovaries is not from the mullerian ducts. This is also
known as MRKH (Mayer-Rokitansky-Kuster-Hauser
syndrome).

Cams, er, anj

GOALS OF MANAGEMENT
Progression of normal pubertal development
Preservation of fertility if possible
Prevention of complications of hypoestrogenic
state

Estrogen is involved in bone and lipid metabolism.

Upon menopause, the bones will start to soften leading
to osteoporosis. Since estrogen is involved in lipid
metabolism, they may have dyslipidemia

NO SECONDARY SEXUAL CHARACTERISTICS

Progression of normal pubertal development HRT
(pills contain estrogen and some progesterone);
she may menstruate.
Preservation of fertility HMG or pulsatile GnRH
(to stimulate FSH and LH secretion)
Prevention of complications of hypoestrogenic
state HRT, calcium, vitamin D
Remove gonads if with Y chromosome-AIS

(HRT = Hormone Replacement Therapy)

(HMG= Human Menopausal Gonadotropin)
Sidenote: women with our age should already start
taking calcium, except for women on the heavy side,
since women on the heavy side actually developed
stronger bones. In fact, women who are thin their
entire life, are most at risk for having osteoporosis.

edited: Sarah

ANDROGEN INSENSITIVITY SYNDROME

Page 5 of 6

Progression of normal pubertal development

remove gonads after full breast development and
epiphyseal closure or after puberty, then give
them HRT
Preservation of fertility- indefinitely, they cant get
pregnant, they have no mullerian ducts in the first
place
Prevention of complications of hypoestrogenic
state estrogen replacement therapy
MULLERIAN AGENESIS
Progression of normal pubertal development
Prevention of complications of hypoestrogenic
state
Surgical reconstruction of absent vagina

Note: these patients will never get pregnant. However,

since they have no vaginal canal, we can surgically
reconstruct so that they can have a vaginal canal so
that when they get married they can make talik

OUTFLOW TRACT OBSTRUCTION

Hymenectomy
Resection of Vaginal Septum
End
QUIZ
1) Proper order of Pubertal Development?
2) Tanner stage: Enlargement of breasts with
glandular tissue without separation of breast
contour?
3) Tanner stage: Pubic hair over mons pubis?
4) Precocious puberty is initiation of secondary
sexual characteristic before age 8 and
menarche before age ___?
5) Most common ovarian neoplasm is ____?

Answers:
1) Thelarche Adrenarche Max Growth Menarche
2) B3
3) PH3
4) 9
5) Granulosa cell tumor

Cams, er, anj

edited: Sarah

Page 6 of 6