‫به نام خدا‬
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Delayed puberty
Mehdi salek MD
Delayed puberty
Initial physical changes of puberty are not
present by age
 13 years in girls
 14 years in boys
Delayed puberty
lack of appropriate progression of puberty
more than 4.5-5 years


A boy who has’nt completed secondary
sexual development within 4.5 years
A girl who does’nt menstruate within 5
years
Classification of Delayed Puberty
Gonadotropin deficiency
 CNS tumors
 Functional HH
 Infiltrative
 Trauma
 Isolated Gonadotropin
 Genetic forms
 CDP
Hypergonadotropic Hypogonadism
Classification of Delayed Puberty
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Non-pathologic
pathologic
Classification of Delayed Puberty
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Transient
Permanent
Evaluation
Evaluation
History
 Infertility
 Anosmia →
HH
 Cryptorchidism →
HH
 Small penis in neonate →
HH
 low Gn in neonatal period →
HH
Evaluation
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Family pattern attainment of menarche
Family history of delay pubertal
Constitutional delay often have a positive
family
Birth trauma
Familial marriage
Evaluation
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Chemotherapy
Glucocorticoid therapy
Surgery
History of intense exercise
Exposures to irradiation
Growth chart
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Growth pattern
Late onset growth failure
CNS mass lesion
Organic disease
Occasionally MRI IS necessary
Growth chart

Normal growth velocity for BA →
CDGP
Normal growth pattern without growth spurt
 With anosmia
Kallmann syndrom
 Without anosmia
↓isolated gonadotropin
Physical Examination
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Neurologic examination
Gynecomastia
midline facial malformations
Size of glandular breast tissue ,areolarsize
Testing of sense of smell
Galactorrhea
Turner stigma
Retractile testes
Physical Examinatin

Height especially HT velocity at least 6 12 months
upper to lower segment ratio

↑↑U/L →
CDG

↓↓U/L →
Hypogonadism

Physical Examinatin
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Signs of puberty
Testicular location ,size, and consistency
Prepubertal:
 Normal size testis <2.0 cc or longer<1.5 cm
Early puberty:
 Normal size testis >3.0 cc or longer >2.5 cm
pubertal-aged
 A testis ≤1.0cm particularly if unusually firm or soft
suggestive of a hypogonadal state.
initial Approach


Skeletal age
Gonadotropin status
initial Approach
BA
= 11-13 years
Gonadotropin measurement
High

Primary gonadal failure
Girl
Boy
Turner
Klinefelter
initial Approach
Mild Elevated→
GnRH Test
Exaggerated response
Primary gonadal failure
initial Approach
Low or lower limit of normal level

Constitutional Delay

Chronic disease

permanent Gonadotropin
initial Approach

Low gonadotropin levels and pubertal
delay may result from a physiologic delay
or a permanent defect
General Approach
Diagnosis of HH versus CDP is more
difficult because of
Overlap in physical and laboratory
finding
General Approach
Hypogona Hypogo
 FSH and LH are low
 They haven't a pulsatile LH with↑ bone
age
General Approach
Overlap between HH and an immature
hypothalamus if
BA<10–11 years for girls
BA<12–13 for boys
General Approach
In older adolescent
 Minimal response to GnRH Test suggests
Gonadotropin Deficiency
 Pubertal rise in the child with delayed
puberty suggests CDP
General Approach
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Patients with HH have normal height in
early or mid adolescent
Patients with CDP have a normal growth
rate for BA but are short for CA.
Laboratory assessment

CBC
Electrolytes
LFT
ESR
Prolactin
Cortisol
IGF-1
TSH, Free T4
Sex steroids ,DHEAS
FSH, LH
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MIH,INSL3,PSA
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Laboratory assessment
Karyotype
 Bone age
 Brain imaging for HH or
hyperprolactinemia
 pelvic ultrasound
 urinary pH,SG
 urea nitrogen, creatinine
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Treatment
Management
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Girls
low dose estrogen therapy started at 13
years or bone age >11 years

Continue 3- to 4-month in CDP
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Management
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0.3mg of conjugated estrogens every
other day
5ug of ethinyl estradiol daily
0.025 mg transdermal estrogen twice
weekly
Management
If permanent HH
Estrogen can be increased every 6 to 12
months in order to reach full replacement
doses after two to three years of therapy
Management
During 2-3 years
 Daily doses of 0.6 - 1.25mg of conjugated
estrogen or 10 -20ug ethinylestradiol are
accepted as full replacement doses
Cyclical progesterone 5 to 10mg of
daily for 12 days can be added every month
to induce monthly menstrual bleeding

Management
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Boys
The initial dosage should be low to avoid
priapism and rapid pubertal development
Dose should be adjusted based on
intellectual maturation, and psychological
needs
Response, age, social
Treatment
If skeletal age is immature

Risk of accelerating BA, short adult
height
If it is started at pubertal bone age 12-13

No detrimental effect on adult height

leads to somatic and genital growth
Treatment
In boys of age 14
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Testosterone Dose
50 to 100mg IM every four weeks
Three to six months
Oxandrolone 2.5mg/day
Management
After a few months Treatment should be
stopped for
Differentiation temporary from permanent
Then
Testosterone level to determine for
endogenous androgen production.
Management
Testosterone <50 ng/dl
 Give another course
After a few months Treatment should be
stopped for
Differentiation temporary from permanent
 Given 1-2 course
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Management
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If testosterone remain low→ Gona
Continue treatment with androgen
Dosages gradually increase to full
replacement after three to four years
100 mg/wk, 200 mg/ two wk or 300mg
three week intervals
Management

The skin gel preparation
50, 75, or 100 mg
Absorption over a 24-hours
Recommended sites are the shoulders,
upper arms and abdomen

Management

Testosterone >50 ng/dl
→CDP
Treatment should be stop
 To assess progression of puberty
Hypothalamic-pituitary-testicular
function can be assumed if
 Testosterone > 275 ng/dl
 Testicular examination is normal

Management
Bone age
 12 to 13 years in girls
 13 or 14 years in boys
 patients with CDP usually continue
pubertal development
 patients with gonadotropin deficiency do
not progress and may regress.
Management
when fertility is desired
 Biosynthetic LH and FSH administration is
utilized
 Episodic administration of LHRH
 Portable pumps to administer LHRH in
episodic fashion over prolonged periods
Case History
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15yr old boy
Shortest in his class
No problem at school
Always a small boy
No chronic disease
Father didn’t grow till he entered college
Case physical
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No dysmorphic features
CVS, Resp, Abd Exam normal
Normal development
Ht= 135cm
Wt= 30kg
U/l = near one
Testicular volume =2.5ml
Case physical
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Testicular length = 1.5cm
Penis = 4cm
Normal Testicular consistency
No gynecomastia
Arm span – height span= 2cm
GV =5cm/yr
PH=1
Hormonal and biochemical studies
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Normal BUN /ESR
Normal T4 &TSH
Low IGF1& IGFBP3 for age
Normal IGF1& IGFBP3 for BA
Decreased FSH& LH
Hormonal and biochemical studies
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Testosterone= 0/15ng / ml
Celiac test= ok
Cortisol levels = ok
LHRH shows not yet in puberty
Normal prolactin
Case treatment
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Oxandrolon for 6 month
Zinc 12.5 mg/day
Iron 12mg/day for 3 mo
Vitamin A = 6000IU/week for 3 mo
But Testicular volume &Testicular length
Didn’t change
Case imaging

BA=12yr
Diagnosis?
Any treatment ?
Case treatment
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Testosteron 1mg/kg for 4 month
Letrozol 2.5mg
Case treatment
Six month after stopping of Testosteron
 Testosteron level was 0/8ng/ml
 Testicular volume =5ml
 Testicular length = 3cm
Discussion
Constitutional Delay Puberty
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Multifactorial
Fathers has similar pattern
often in boys
Normal size at birth
.
.
.
.
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Constitutional Delay Puberty
By three years of age
 Decrease height ,BA, growth velocity
By usual age of puberty
 immaturity become more noticeable as the
approaches with somatic and sexual pubertal
At older age than typical
 Puberty occurring spontaneously
Constitutional Delay Puberty
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61
No history of systemic illness.
Normal nutrition.
Normal P/E.
Normal hormones
Constitutional Delay Puberty
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62
Delayed puberty.
Delayed bone age.
a short adolescent with bone age delay
greater than three years is more likely to
have a pathologic problem .
Constitutional Delay Puberty
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Growth velocity and height are usually
appropriate for bone age
Delay in the reactivation of the GnRH
pulse generator
Adrenarche and gonadarche occur later
Constitutional Delay Puberty
Outcome is benign
 Normal physical development, sexual and
reproductive function

Constitutional Delay Puberty

Not one test yet distinguishes between
CDP and HH, so watchful waiting is
usually in order
Constitutional Delay Puberty
Hypogonadotropin hypogonadism
 Adrenarche at a normal age
 Higher DHEAS than CDG

Failure of a rise in Gonadotropin or sex
steroid by age 18
Treatment
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Assurance to family
GH treatment
Treatment for BA>12y
Don’t Treatment for BA<10y or CA<12
Oxandrolon
Transdermal patch and gel preparations of
testosterone