pubertal disorders
DESCRIPTION
Pubertal disorders. Dr Olcay Evliyaoğlu Pediatric Endocrinology Department. Puberty. Sexual differentiation begins on 4-5th week of gestational age. ADOLE SENCE. Foliküler faz. Phy s ical, sexual, physcological development. Transition to adulthood from childhood Not an adult nor child - PowerPoint PPT PresentationTRANSCRIPT
Pubertal disorders
Dr Olcay Evliyaoğlu
Pediatric Endocrinology Department
Puberty
Sexual differentiation begins on 4-5th week of gestational age.
ADOLESENCE Physical, sexual, physcological
development. Transition to adulthood from childhood
Not an adult nor child Time of transition Establishment of individualism.
Foliküler faz
PUBERTY
Secondary sex characteristics are developed
Includes Physical growth Sexual development Psychological development
Growth spurt, disturbution of muscle and fat
bone maturation and fusion of epiphysical centers
Adult height At the end of this period
spermatogenesis in boys, ovulation in girls occur
hypothalamus LHRH neurons
LHRH
PituitaryGonadotroph cells
FSH , LH
GONADs
Testes Ovaries
Testosteron Estradiol
HPG axis
STRESS
MATURATİON NUTRİTİON+ +CENTRAL NERVOUS SYSTEMCENTRAL NERVOUS SYSTEM
++ - - +
+ +
- - -
- -
- -
+ +
--
-- --
GLUTAMAT GABA ENDROFIN
HYPOTHALAMUSHYPOTHALAMUS
GnRHGnRH
PİTUİTARYPİTUİTARY
PRLPRL
LHLH FSHFSH
TEKA TEKA OVARYOVARYGRANULOZA GRANULOZA
ANDROGENANDROGEN ESTROGEN INHIBINESTROGEN INHIBIN
-
LEPTIN
What makes HHG axis work
Genetic and environmental conditions effect timing of puberty
Environmental factors: Socioeconomic factors Nutrition General health Geographical place lived
Hypothalamus GnRH pulse frequency and amplitude increase
LH pulse frequency and amplitude increaseAt early stages at nights With progression of puberty pulses occur during day
Pituitary
Gonadotropins
FSH, LH Glucoprotein Alpha ve beta subunits ( alpha subunits are
same, differences are on beta subunits)
FSH sertoli cells (testis) Granulosa cells (over) Stimulate LH rec production on Leyding cells
gamotogenesis
LH Leydıng cells ( testis) Teca cells ( over) Gonadal steroids
LH
Granulosa cellsFSH
estrogen
androstenedionTeca cells
LH Leydig cells
testosteron
Adrenarche
Increase in the secretion of adrenal androgens
Appearance of pubic hair (pubarche) Axillary hair
CRH
ACTH
Adrenal androgens
Hypothalamus
Pituitary
Adrenal cortex
Adrenarche
Nutrition and puberty
Menarche is earlier in obese girls
Malnutrition , chronic diseases, and excessive physical activity delay puberty and menarche
Timing of puberty is related to bone age rather than chronological age
BA< CY ------------- delay in puberty BA = CA ------------- puberty on expected age BA>CA -------------- early puberty (puberty
precocous)
girls the first sign of puberty is telarche, generally observed on 10 - 11 ages, menarche is observed 2-3 years after telarche.
In girls growth spurt occurs 2 years earlier than boys. Growth spurt in girls is at the time of telarche,
In boys growth spurt occur at the time when testes volumes are 10 ml.
Telarche Pubarche Menarche
Tanner stage 42-3years after telarche
Menarche
Pituitary hormones
Ovarian hormones
ovary
Endometrium
İstihdam Seçim
dominant istihdam
Follicular /proliferative phase Luteal /secretuary phase
folliculeovulation
corpus luteumcorpus albicans
In boys initial finding of puberty is enlargement of testes. This is followed by scrotum pigementation and thinning of scrotal skin. Penis enlarges. Pubic hair develops. Growth spurt occurs at 14-16 years and usually continues until 18 years.
PUBERTAL PROBLEMS Precocious puberty Delayed puberty Pubertal gynecomastia Gynecological problems Pyschological problems Sexual identity problems Eating disorders: Anoreksia
nervoza, Bulimia Nervoza Enuresis Nocturna Orthopedical problems
PRECOCİOUS PUBERTY
Breast development before 8 years in girls and testes development more than 4 ml or any other pubertal sign before 9 years in boys are considered precocious .
Central Precocious Puberty (CPP): Activation of hypothalamus-pituitary-gondal (HHG) axis.
Peripheric Precocious Puberty (PPP) : Signs of puberty with out activation of HHC axis. Izosexual perifpheric PP: Secondary sexual characteristics are appropriate for the sex of the child.heterosexual peripheric PP: Secondary sexual characteristics are inappropriate for the sex of the child.
Etiology : Central PP
Idiopathic: sporadik, familial CNN disorders: Tumors (Optic glioma, hypothalamic gliom,
astrositoma, epandimoma, kraniopharengioma), sarkoidosis, suprasellar cysts
Nörofibromatosis, Tuberosclerosis
Peripheric PP Gonadotropin secreting tumors: Hepatomas, hepatoblastoma,
teratoma, choriocarsinoma, germinoma Any disorder resulting in gonadal steroid secretion
Excess androgen: Congenital Adrenal Hyperplasia, testes tumorsExcess estrogen: Ovarian cysts or tumors
Mc Cune Albright Syndrome Activation mutation in LH receptors
Severe hypothyroidism
Clinical Height Midparental height and target height Height velocity Pubertal stage Bone age
Central PP: diagnostic criteria
Central PP: diagnostic criteria Pelvic USG findings supporting CPP
Uterus long diameter 34-50mm Pear shaped uterus (F/C>2:1) Endometrial echo specifity (100%) but sensivity
(42%-87%) Ovarian volume <2-3 ml (v:a x b x c x 0,5233) Follikul number>6 size>8mm
Central PP: diagnostic criteria Laboratory :
1) Pubertal levels of LH amplitude and pulsity2) Gn-RH stimulation test: Pubertal LH responsepeak > 5 IU /L 3) Gn-RH stim LH/FSH>1
Criteria suggesting progressive precocious puberty Progression of breast staging in less than 3-6 months Growth velocity > 6cm /year Bone age advanced more than 1,5-2 years PAH below target height and decline in PAH during
follow up. Uterine volume>2 ml, long diameter >35 m, endometrial
echo Ovarian volume >2-3 ml Peak LH>5 mIU/L at GnRH test Basal LH >0,3
Puberte prekoks
McCune Albright Syndrome
Cafe au lait patches on skin Polyostotic fibrous dysplasia Endocrine disorders:
Peripheric PPCushing syndrome, hyperthyroidism
Mc cune albrigt - 4.5 years old -polyostotik fibrous dysplasia
Treatment
Goals: Synchronosing puberty with peers (ameliorating
pshchological stress) Decreasing the rate of bone maturation so as to
acheive a normal final height
Treatment(SPP)
GnRH analogs.
Lucrin
3.75mg IM /month 7,5mg IM /month
22,5mg /3 months
11,25mg months
When to stop treatment
Much depends on the primary goal of treatment , patient – parent preference
Average age of treatment discontinuation CA:10,6 -11,6 years BA:12,1 – 13,9 years
Max adult height CA:11-11,5 ve BA: 12-12,5 years
Treatment (PPP)
Boys Antiandrogens ( andr rec inhibition) İnhibitors of 17,20 liyase ve testosteron
synthesis Aromatase inhibition (arimidex)
Girls Aromatase inhibitors E2 rec inhibition
İNCOMPLETE PP
Only one pubertal sign. Premature telarche Premature adrenarche Premature menarche
Premature Telarche
End organ increased sensivity There can be difference in 2 breasts, one
can start development 6 months earlier than the other
Premature telarche PP
------------------------------------------------------------------Growth velocity not increased increased
Bone age not advanced advanced
Vagen mucosa not obvious obvious
E2 effect
Uterus size Prepubertal Pubertal
GnRH response Prepubertal Pubertal
Adrenarche no can be
Premature Adrenarche PPPenis size Prepubertal Pubertal
Growth velocity not rapid rapid
Bone age not advanced advanced
Testes size Prepubertal Pubertal
Serum Testesteron Prepubertal Pubertal
DHEA-SO4 Prepubertal Pubertal or 17-OH progesterone Prepubertal high in CAH
11-Deoksikortisol Prepubertal high in 11-OH lase deficiency
Bazal LH/FSH Prepubertal Pubertal
Puberty tarda-PT (Pubertal delay)
Not if any sign of puberty has been observed in 13 years old girls and 14 years old boys
Males
If Sexual development has not been developed
until13.7 years. Transition from stage II to III is more than 2.2 years Transition from stage III to IV is more than1.6 years Transition from stage IV to V is more than 1.9 years Sexual development has not reached stage V until
17.1 years Bone age>12 years and pubertal development has
not begun
Females
If Breast development not started until 13.4 years Transition from stage II to III is more than 1 year Transition from stage III to IV is more than 2.2
years Transition from stage IV to V is more than 1.8
years Not menarche at the 5th year of telarche Bone age >11 and pubertal development has not
begun
Etiology of PT
Konstitutional growth and pubertal delay Hypogonadotropic hypogonadism
CNS disorders: Tumors, congenita disorders, radiation Isolated gonadotropin deficiency: Multiple pituitary hormone deficiency Prader-Willi syndrome Laurence-Moon, Bardet Biedle syndrome Chronic diseases Sudden weight loss, anoreksia nervoza Hypothyroidism İncrease in physical activity
Etiology of PT
Hypergonadotropic hypogonadism
A. Males Kleinfelter syndrome Primary testicular insufficiency Anorchia or kriptorchidismB. Females Primary ovarian insufficiency Noonan syndrome, Ulrich syndrome) XX veya XY gonadal dysgenesis Turner Syndrome
Constitutional growth and pubertal delay Pubertal development is delayed concordant
with growth CA>BA=HA Growth velocity is normal Height sds is between -2sd and -3sd With the onset of puberty and pubertal growth
spurt final height becomes appriate to target height
Treatment (constitutional growth and pubertal delay)
1. Phsychologic treatment
2. Gonadal steroids: 13 years old girls and 14 years old boys who have not developed any pubertal sign can be treated
Girls : For 3 months Conjugated E2 (0.3 mg/day) or ethynyllestradiol (5-10 g /day)
Boys : For 3 months testesteron enanthate (50-100 mg/ month) IM
Development of pubertal signs and an increase in growth velocity is what expected from this treatment.
Hypogonadism / treatment Males
By gradually increasing testosterone dose adult dose of 300mg/month is acheived.
In the case of hypogonadotropik hypogonadism to increase endogenous testosterone production and testes size HCG treatment can be initiated
Females 5 g/ day10 - 20 g/ day etynyllestradiol 0.3 - 0.625 mg/day conjugated estrogen . With the appearence of physical effects of E2
Medroksiprogesterone acetate on days 12. - 21. of cycle can be added
Gynecomastia Observed in 30 - 35 % of males Generally bilateral In P3 and P4 stages; 14 - 14.5 years Glandular tissue diameter is generally less than
4 cm, resembles stage II in girls Glandular tissue > 5cc and resembles stage III
and IV in girls Pubertal Macrogynecomastia , do not regress spontaneously
Etiology for pathologic gynecomastia : Endocrinopathies Tumors Chronic diseases Drugs : Hormones, antidepresants, anti Tbc
drugs, etc
Pathophysiology:
a) Disturbance of E2 and testosterone balance
b) Increment of conversion of testosterone to estradiol
Increase in E2 sensivity of breast tissue
Generally regresses in one year If persists more than 2 years, leads to
physcological problems and is a macrogynecomastia surgery is a treatment option