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Delayed pubertyDelayed pubertyMehdi salek MD

Delayed pubertyDelayed puberty

Initial physical changes of puberty are not present by age

13 years in girls 14 years in boys

Delayed pubertyDelayed puberty

lack of appropriate progression of puberty lack of appropriate progression of puberty more than more than 4.5-54.5-5 years years

A boy who has’nt completed secondary A boy who has’nt completed secondary

sexual development within 4.5 yearssexual development within 4.5 years A girl who does’nt menstruate within 5 A girl who does’nt menstruate within 5

yearsyears

Classification of Delayed PubertyClassification of Delayed Puberty

Gonadotropin deficiencyGonadotropin deficiency CNS tumorsCNS tumors Functional HHFunctional HH InfiltrativeInfiltrative Trauma Trauma Isolated GonadotropinIsolated Gonadotropin Genetic formsGenetic forms CDPCDP Hypergonadotropic HypogonadismHypergonadotropic Hypogonadism

Classification of Delayed PubertyClassification of Delayed Puberty

Non-pathologic pathologic

Classification of Delayed PubertyClassification of Delayed Puberty

Transient Permanent

Evaluation

Evaluation

History Infertility Anosmia → HH Cryptorchidism → HH Small penis in neonate → HH low Gn in neonatal period → HH

Evaluation

Family pattern attainment of menarche Family history of delay pubertal Constitutional delay often have a positive

family Birth trauma Familial marriage

Evaluation

Chemotherapy Glucocorticoid therapy Surgery History of intense exercise Exposures to irradiation

Growth chart

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 ExaminationPhysical Examination

Neurologic examination Gynecomastia midline facial malformations Size of glandular breast tissue ,areolarsize Testing of sense of smell Galactorrhea Turner stigma Retractile testes

Physical ExaminatinPhysical Examinatin

Height especially HT velocity at least 6 -12 months

upper to lower segment ratio

↑↑U/L → CDG ↓↓U/L → Hypogonadism

Physical ExaminatinPhysical Examinatin

Signs of puberty Testicular location ,size, and consistency

Prepubertal: Normal size testis <2.0 cc or longer<1.5 cmEarly puberty: Normal size testis >3.0 cc or longer >2.5 cmpubertal-aged A testis ≤1.0cm particularly if unusually firm or soft

suggestive of a hypogonadal state.

Skeletal age Gonadotropin status

initial Approach

initial Approach

BA = 11-13 years

Gonadotropin measurement

High Primary gonadal failure

Girl Turner

Boy 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

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 MIH,INSL3,PSA

Laboratory assessment

Karyotype Bone age Brain imaging for HH or

hyperprolactinemia pelvic ultrasound urinary pH,SG urea nitrogen, creatinine

Treatment

Management

Girls low dose estrogen therapy started at 13

years or bone age >11 years

Continue 3- to 4-month in CDP

Management

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

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

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

Management

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

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

No dysmorphic features CVS, Resp, Abd Exam normal Normal development Ht= 135cm Wt= 30kg U/l = near one Testicular volume =2.5ml

Case physical

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

Normal BUN /ESR Normal T4 &TSH Low IGF1& IGFBP3 for age Normal IGF1& IGFBP3 for BA Decreased FSH& LH

Hormonal and biochemical studies

Testosterone= 0/15ng / ml Celiac test= ok Cortisol levels = ok LHRH shows not yet in puberty Normal prolactin

Case treatment

Oxandrolon for 6 month Zinc 12.5 mg/day12.5 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

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

DiscussionDiscussion

Constitutional Delay Puberty

Multifactorial Fathers has similar pattern often in boys Normal size at birth

. .

.

- .

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

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Constitutional Delay Puberty

No history of systemic illness. Normal nutrition. Normal P/E. Normal hormones

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Constitutional Delay Puberty

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

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

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