Prof Dr Oya Ercan Early Timing Delayed DELAYED PUBERTY Delayed Puberty Girls gt13 years menarche gt15 Boys gt14 years ID: 259401
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Slide1
PUBERTAL DISORDERS
Prof. Dr. Oya ErcanSlide2
Early
Timing
DelayedSlide3
DELAYED PUBERTYSlide4
Delayed Puberty *
Girls >13 years ( menarche >15 )
Boys >14 years
*
No signSlide5
DELAYED PUBERTY
HYPOGONADISM
Hypogonadotrophic Hypergonadotrophic
Pathologic Non-pathologic
Transient PermanentSlide6
Girls
Hypergonadodotrophic hypogonadism
(Ovarian failure)
Turner syndrome, gonadal dysgenesis/agenesis
Autoimmune ovarian failure
Type 1: Addison’s, hypoparathyroidism, mucocutaneous candidiasis
Type 2: Addison’s, autoimmune thyroid disease, Type 1 DM
Mutations in gonadotrophin and gonadotrophin receptor genesGalactosemiaIrradiationChemotherapyInfectious disease (Malaria, mumps, shigella, varicella)Enzyme deficiencySlide7
Girls
Hypogonadotropic hypogonadism
Constitutional delay
Permanent hypogonadotropic hypogonadism
Congenital
Acquired
Tumors (craniopharyngioma)
Others CNS lesions: Travma, surgery, infections, infiltrative diseases
Temporary hypogonadotropic hypogonadism(secondary causes) Excessive emotional stres Unusual physical activity Inadequate nutritional state Chronic disease Systemic illnessSlide8
BOYS
Hypergonadotrophic Hypogonadism
(Testicular failure)
Klinefelter and Multiple X Syndromes
Anorchia
Bilateral Cryptorchidism with Dysgenetic Testes
Torsion (bilateral)
Travma
Infection ( mumps, coxsackie )
Chemotoxicity
IrradiationInactivating Mutations of LH and its receptorSlide9
BOYS
Hypogonadotrophic Hypogonadism
1- Without a permanent defect
Constitutional delay of growth and development
Systemic illness
Crohn disease
Poorly controlled DM
Systemic therapy for chronic conditions
2- Permanent defect
Isolated gonadotrophin deficiency Multiple Pituitary Hormone Deficiency Congenital. Acquired Tumors, travma, irradiation, surgery, infections, infiltrative disorders
Slide10
Congenital Isolated Hypogonadotrophic Hypogonadism (IHH)
Absent, incomplete or arrested isosexual development
Low gonadotrophins and sex hormones
Absence of systemic disease, syndromic malformations, nutritional deprivation and other functional or anatomic pituitary abnormalitiesSlide11
Inactivating Mutations in Genes Responsible For:
Differentiation and development of GnRH synthesizing neuron
NROB1 or DAX1, CHD7, FGFR 1, FGF8
Migration of neurons that synthesize and secrete GnRHSynthesis, release and action of GnRH
Synthesis, secretion of Gn’s Slide12
Migration of GnRH-synthesizing Nerve Cells
KAL-1 ®
FGFR 1
FGF 8NELFPROK 2PROKR 2 ®Slide13
Loss of function mutations in these genes associated with abnormalities of olfaction (anosmia, hyposmia)
-Kallmann syndrome-Slide14
New Modulators of GnRH Synthesis and Secretion (2009)
Products of TAC3 and TACR3
Prof. Kemal Topaloğlu
-Reproductive function might recover after adolescence in both males and femalesSlide15
These are subjects with CDGD in the families of many patients with IHH
(CDGP=CDGD : Absence of micropenis and crypthorchidism, endogenous initiation of sexual maturation by age 18 yr )
These aberrations of pubertal timing are varying clinical manifestations of a broad phenotypic expression of disordered regulation of GnRH pulse generation. Slide16
Investigation of Delayed Puberty
For practical purposes , the complete absence of signs of puberty after 14 years requires investigation.Slide17
Growth rate
,
rate of epiphyseal maturation
and rate of advance in sexual maturation have all to be considered in order to attempt to separate those children with abnormal endocrine function from those with constitutional delay of growth and puberty. Slide18
Pelvic ultrasound assessment
Unfortunately, there is no equivalent examination in males. Ovarian maturation continues throughout childhood and as the ovarian morphology reflects pulsatile Gn secretion, this examination can be used to distinguish constitutional delay from complete hypogonadotrophic hypogonadism. The examination may also be useful in the diagnosis of Turner’s syndrome and gonadal dysgenesis.Slide19
Serum sex steroid measurements
:
These have little use in the investigation of delayed puberty. In order to be useful, serum testosterone in males in early puberty needs to be measured from samples in the early hours of the morning although in girls in early puberty, measurement of serum estradiol during the daytime is more appropriate than the measurement of testosterone in boys.Slide20
Serum gonadotrophin measurements:
Basal serum Gn is useful in the diagnosis of gonadal failure. After the age of 10 years, both LH and FSH concentrations are markedly elevated in gonadal failure.Slide21
GnRH TestGnRH test has no use in the investigation of delayed puberty. Such a test is inappropriate in that Gn release is tested at the pituitary rather than the hypothalamic level.
Spontaneous Gn secretionSlide22
hCG Test:
Serum testosterone concentrations before and after hCG offers a method of distinguishing between constitutional delay of growth and puberty and complete hypogonadotrophic hypogonadism in the majority of cases.Slide23
Serum prolactin
:
Prolactinomata are a rare cause of delayed puberty. However, this diagnosis will be missed unless serum PRL measurements is undertaken.Slide24
Neuroradiology:
Tms of the hypothalamo-pituitary region may present as an evolving endocrinopathy of which the loss of Gn and GH are early in the sequence of the development of panhypopituitarism.Slide25
Chromosomes:
Turner syndrome
GI function: red cell folate
anti-gliadin ab coeliac
anti-endomysium ab
inflammatory bowel disease: radiology ,endoscopySlide26
CDGP:
Stature reduced for chronological age but appropriate for pubertal development and bone maturation.
Family history of delayed puberty
Much more common in boys than girlsSlide27
Idiopathic Hypogonadotrophic Hypogonadism:
Normal height
Arrested epiphyseal maturation at approximately 13 years
(+) anosmia (Kallmann’s syndrome)Colour blindness
Cryptorchidism boys
micropenisSlide28
Sex steroids in boys and girls
hCG in boys
Not less than 2 years (puberty induction)Slide29
EARLY PUBERTYSlide30
Classification
GnRH-dependent GnRH-independent
GnRH-driven Peripheral
Central Precocious pseudo
True pubertySlide31
Early Puberty
Normal Consonance
Idiopathic central precocious puberty
Central precocious puberty secondary to
Hypothalamo-pituitary tumours and infections
Raised intracranial pressure
Cranial irradiation
Gonadotrophin-independent precocious puberty(Testotoxicosis
)Slide32
Loss of consonance (pseudopuberty)
Hypothalamo-pituitary endocrinopathy
Cushing’s Disease
Adrenal Disorders
Cushing’s syndrome
Congenital adrenal hyperplasia
Primary tumours
Gonadal Disorders
Primary tumours
Mc Cune- Albright syndromePrimary HypothyroidismIsolated Premature ThelarcheSlide33
Etiology
FEATURES
CENTRAL
PRECOCİOUS PUBERTY
THELARCHE
Age
of
onset
< 8
years
< 2 yearsPubic and axillary hairProgressive
developmentAbsent
MensesAs in normal puberty
Usually absent
Skeletal
maturationAdvanced
Appropriate
Growth
velocity
Accelerated
Normal
Growth
prognosis
Compromised
Normal
Duration
of
condition
Continues
as
adult
sexual
maturation
Usually
resolves
after
a
few
years
,
always
by
8
years
of
age
Prognosis
for
fertility
Normal
May be
compromised
Breast
development
Progressive
development
Minor
(
Usually
B2
or
B3
cycling
at
approximately
6
week
intervalsSlide34
Mc Cune-Albright Syndrome
Activating mis-sense mutation in the gene for the
α
subunit of Gs.
Mosaic distribution of cells with mutation
Polyostotic fibrous dysplasia
Café au lait spots
Endocrinopathy
gonads
adrenal cortex
thyroid pituitary gland parathyroid gland“G protein stimulation as if trophic hormones were present.”Slide35
Testotoxicosis
Activating mutation of the LH receptor