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Learn about the classification, evaluation, and treatment options for delayed puberty in children. Includes information on physical examination, laboratory assessments, and appropriate hormone replacement therapy.
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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 • Non-pathologic • pathologic
Classification of Delayed Puberty • Transient • Permanent
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 Examination • 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 • 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.
initialApproach • Skeletal age • Gonadotropin status
initialApproach BA = 11-13 years Gonadotropin measurement HighPrimary gonadal failure Girl Turner Boy Klinefelter
initialApproach Mild Elevated→ GnRH Test Exaggerated response Primary gonadal failure
initialApproach Low or lower limit of normal level • Constitutional Delay • Chronic disease • permanent Gonadotropin
initialApproach • 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
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