Normal Pubertal Development
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Childhood
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Minimal gonadotrophin stimulation
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Due to dampening of GNRH stimulation
Signal that “dampens” GNRH stimulation?
 Unknown
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Any interference with this inhibitory signal can
result in early puberty
Congenital CNS disorder
 Acquired CNS disorder
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Normal Pubertal Development
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Adolescent-puberty
 Puberty is a two part event
 Gonadarche and adrenarche
 Triggers for initiation of puberty-still unknown
 Theories include weight, fat, stress
 Adrenal hormonal changes
 DHEA, DHEAS increase
 Occurs 2 years prior to maturation of the HPG axis
 Gonads
 LH predominance-first indication of puberty
Normal Female Development
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Adrenal cortex
Control-->?????
Control
Hormones
 Androstenedione
 DHEAS
 Testosterone
Physical Exam
 Body odor
 Acne
 Pubic Hair
 Axillary Hair
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Gonads->Ovary
GonadsControl
 Hypothalamus
Hypothalamus-GNRH
 Pituitary
Pituitary--FSH/LH
Hormone
 Estradiol
Physical Exam
 Breast development
 Menses
Normal Female Development
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First sign of puberty-breast enlargement
Menarche
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Occurs 2 ½-3 years after breast enlargement
Peak growth velocity at tanner 3-4
Menarche tanner 4, average age 12.8 years
With menses-90% of growth is completed
Mean duration of pubertypuberty-4.2 years
Normal Male Development
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Adrenal Cortex
Control ->????
Hormones
 Androstenedione
 DHEAS
 Testosterone
Physical Exam
 Body odor
 Acne
 Pubic Hair
 Axillary Hair
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Gonads->Testes
GonadsControl
 Hypothalamus
Hypothalamus--GNRH
 Pituitary
Pituitary--FSH/LH
Hormone
 Testosterone
Physical Exam
 Increased testicular size
 >3cc or 2.5 cm length
Normal Male Development
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First sign of puberty
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Testicular enlargement; Greater than 3 cc/2.5 cm
Peak growth velocity tanner stage 4
Axillary hair 1-2 years later than pubic hair
LH-leydig cells-10% of testicular volume
FSH-seminiferous tubules-90% of volume
Gynecomastia-65% of males, tanner 3-4
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Precocious puberty
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Previous definition was evidence of any secondary sexual
characteristics before age 8 in a female and age 9 in a male
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1999-Lawson Wilkins Pediatric Endocrine Society
1999published new recommendations
 Precocious puberty is the appearance of any secondary
sexual characteristics before age 6 in an African
American female, 7 in white female, 9 in a male
 Based on findings of Pediatric Research in Office
Settings (PROS) NetworkNetwork-studied 17000 females
 Not 100% accepted
 Should evaluate if patient’s pubertal progression is rapid,
patient with neurological problems, bone age advanced
> 2 years, predicted adult height < 59 in, family
concerned
Precocious Puberty
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Cause
Brain tumor 10% in females
 Brain tumor 50% time in males
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Definition
Must have adrenal & gonadal changes in female
 Only need gonadal changes in the male
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Remember….no such thing as premature testelarche!!!
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Delayed puberty
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Absence of any secondary sexual characteristics by
age 13 in females and 14 in males; OR if more than 5
years pass between the first signs of puberty and the
onset of menarche in girls or the completion of
genital growth in boys
Variants of Normal Puberty
Premature Thelarche
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Definition
 Isolated breast development
 Females < 6-7 YO (AA vs. Caucasian)
Patient profile
 Chief complaint-breast development, lump
under breast, chest pain
 BA within 2SD of CA, BA=HA
 No other signs of puberty, normal GV
 GNRH-FSH predominant
 Normal estradiol levels-< 10 pg/ml
Variants of Normal Puberty
Premature Thelarche
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Natural history
 40% regress
 50% persist
 10% precocious puberty
 Reason you follow patients for 12-24 months
 Normal pubertal development
 Normal adult height
Differential diagnosis
 Estrogen excess-intrinsic Vs extrinsic
 Rule out early central precocious puberty
Variants of Normal Puberty
Premature Thelarche
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Evaluation and management
 History-estrogen exposure
 Physical exam
 Growth velocity, tanner stage, skin exam
 Lab/X-ray-estradiol, LH/FSH, bone age
 Follow-up-exam every 3-4 months
 Further evaluation if initial screen abnormal
 Head MRI, PUS and GNRH stimulation test
 Only if concerned about precocious puberty
Variants of Normal Puberty
Premature Adrenarche
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Definition
 Presence of adrenarche
 Body odor, pubic hair, axillary hair, acne
 <8YO females or <9YO males
Patient profile
 Chief Complaint: PH, AH, BO,acne
 No virilization
 No breast development or menses in girls
 No testicular enlargement in boys
 Often associated with obesity & CNS insults
Variants of Normal Puberty
Premature Adrenarche
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Natural history
 Normal puberty, fertility and growth
 PCO?
Differential diagnosis
 Congenital adrenal hyperplasia
 Tumor
Tumor--adrenal, Gonadal
 Cushings
Variants of Normal Puberty
Premature Adrenarche
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Evaluation and management
 History and physical exam
 Androgen exposure, family history
 Vital signs, tanner stage, growth velocity
 Lab/x-ray
 DHEAS, androstenedione, testosterone, 17OHP
 Bone age-Normal
 Follow-up q 4 months
 Further evaluation if initial screen abnormal
 ACTH stimulation test
 Adrenal/pelvic imaging
 24 hour 17-Keto steroids
Variants of Normal Puberty
Premature Menarche
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Definition
 Isolated menses in a female
 Normal growth, bone age and gonadotrophins
Patient profile
 Presents 9 monthsmonths-9 years; Cycling may persist
 Normal growth velocity and tanner 1
Natural history
 Normal onset of central puberty
 Normal adult height
Variants of Normal Puberty
Premature Menarche
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Differential diagnosis
 Must rule out
 Trauma, sexual abuse, GI and GU bleeding
 Foreign body, vulvovaginitis, tumor
 Study of 50 females
 1/2 with local lesions
 1/2 of which were rhabdomyosarcoma
 Another report-25% with foreign body
 If presentation of precocious puberty
 Must rule out McCune Albright syndrome
Variants of Normal Puberty
Premature Menarche
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Patient evaluation
History-estrogen exposure
History PE
PE--general exam, tanner stage, skin, pelvic
 Labs
Labs--estradiol, FSH/LH
 Xray
Xray--bone age
 Follow
Follow--up
up--every 4 months
 Additional evaluation
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PUS, head/pituitary MRI
Variants of Normal Puberty
Premature Testelarche
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No such diagnosis!!!
Enlarged testes (> 3 cc or 2.5 cm)
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Less than 9 YO is ABNORMAL!!!!!!
This is an endocrine emergency!!!!
50% of patients have a brain tumor!
Approach to pubertal disorders
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Is there a problem?
Where is the problem?
What is the differential diagnosis?
How do you evaluate?
Case #1
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6 YO female with early pubic hair development. No
body odor, acne or axillary hair. Denies breast
development or menses
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Labs-all normal
Labs fT4, TSH, BHCG, 11DOC, Estradiol, FSH/LH,
 Free and total testosterone, SHBG
 17OHP
Case #1
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Is there a problem?
Where is the problem?
What is the differential diagnosis?
How do you evaluate?
Do you agree with the evaluation?
 Additions? Subtractions?
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Case #2
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17 MO WF presented for first endocrinology
evaluation for early breast development. Breast
tissue first noted at 1 year—
year—FSH 8.8, LH 0.1,
estradiol < 30 pg/ml. Over the year, her breast
development has increased. On exam, T3 breast
, T1 GU, normal growth velocity
Case # 2
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Do you agree with the initial evaluation? Any
concerns?
Is there a problem?
Where is the problem?
What is the differential diagnosis?
How do you evaluate?
Case # 3
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7 6/12 YO BF
 Evaluated at age 5 for early puberty.
 She was T2 breast and GU at that time.
 Nl TFTs, nl 17OHP, testosterone, DHEAS
 LH 1.0 FSH 3.4, nl head MRI, nl PUS
Lost to followfollow-up
 Seen by me 2 1/2 years later
On examexam-4’9”, T4 breast and GU
Case # 3
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Is there a problem?
Where is the problem?
What is the differential diagnosis?
How do you evaluate?
Thoughts/comments on evaluation?
Case # 4
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16 YO male presents for routine PE
PMH--healthy
PMH
PE--Tanner 3 PH, 3 cc testes
PE
Case # 4
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Is there a problem?
Where is the problem?
What is the differential diagnosis?
How do you evaluate?
Case # 5
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7 YO male with early puberty
History of early PH and growth spurt
Denied any body odor or acne
Exam Tanner 2 PH and 5 cc testes with
increased growth velocity
PMH--Healthy
PMH
Case # 5
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Is there a problem?
Where is the problem?
What is the differential diagnosis?
How do you evaluate?
Case # 6
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8 YO malemale-AH and BO at 18 months
Presence of pubic hair for 1 year
Evaluated in pastpast-no records
PMH--RAD tx intal and proventil
PMH
PE--T3 PH, + axillary hair, 3 cc testes, increased
PE
growth velocity
Case # 6
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Is there a problem?
Where is the problem?
What is the differential diagnosis?
How do you evaluate?
Case # 7
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13 11/12 YO male with height at 3% and
decreasing growth velocity
PMH--healthy
PMH
PE--Height and weight <3% with decreasing
PE
velocity
Tanner 1 PH and 3 cc testes
Case # 7
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Is there a problem?
Where is the problem?
What is the differential diagnosis?
How do you evaluate?