PUBERTAL DISORDERS - PowerPoint Presentation

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