8 BOYS Hypergonadotrophic Hypogonadism (Testicular failure) Klinefelter and Multiple X SyndromesAnorchiaBilateral Cryptorchidism with Dysgenetic TestesTorsion (bilateral)TravmaInfection ( mumps, coxsackie )ChemotoxicityIrradiationInactivating Mutations of LH and its receptor
9 BOYS Hypogonadotrophic Hypogonadism 1- Without a permanent defect Constitutional delay of growth and developmentSystemic illnessCrohn diseasePoorly controlled DMSystemic therapy for chronic conditions2- Permanent defectIsolated gonadotrophin deficiencyMultiple Pituitary Hormone DeficiencyCongenital.AcquiredTumors, travma, irradiation, surgery, infections, infiltrative disorders
10 Congenital Isolated Hypogonadotrophic Hypogonadism (IHH) Absent, incomplete or arrested isosexual developmentLow gonadotrophins and sex hormonesAbsence of systemic disease, syndromic malformations, nutritional deprivation and other functional or anatomic pituitary abnormalities
11 Inactivating Mutations in Genes Responsible For: Differentiation and development of GnRH synthesizing neuronNROB1 or DAX1, CHD7, FGFR 1, FGF8Migration of neurons that synthesize and secrete GnRHSynthesis, release and action of GnRHSynthesis, secretion of Gn’s
13 Loss of function mutations in these genes associated with abnormalities of olfaction (anosmia, hyposmia)-Kallmann syndrome-
14 New Modulators of GnRH Synthesis and Secretion (2009) Products of TAC3 and TACR3Prof. Kemal Topaloğlu-Reproductive function might recover after adolescence in both males and females
15 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.
16 Investigation of Delayed Puberty For practical purposes , the complete absence of signs of puberty after 14 years requires investigation.
17 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.
18 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.
19 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.
20 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.
21 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 secretion
22 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.
23 Serum prolactin:Prolactinomata are a rare cause of delayed puberty. However, this diagnosis will be missed unless serum PRL measurements is undertaken.
24 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.
25 Chromosomes: Turner syndrome GI function: red cell folateanti-gliadin ab coeliacanti-endomysium abinflammatory bowel disease: radiology ,endoscopy
26 CDGP:Stature reduced for chronological age but appropriate for pubertal development and bone maturation.Family history of delayed pubertyMuch more common in boys than girls
27 Idiopathic Hypogonadotrophic Hypogonadism: Normal heightArrested epiphyseal maturation at approximately 13 years(+) anosmia (Kallmann’s syndrome)Colour blindnessCryptorchidism boysmicropenis
28 Sex steroids in boys and girls hCG in boysNot less than 2 years (puberty induction)
30 Classification GnRH-dependent GnRH-independent GnRH-driven Peripheral Central Precocious pseudoTrue puberty
31 Early Puberty Normal Consonance Idiopathic central precocious puberty Central precocious puberty secondary to Hypothalamo-pituitary tumours and infectionsRaised intracranial pressureCranial irradiationGonadotrophin-independent precocious puberty(Testotoxicosis)
32 Loss of consonance (pseudopuberty) Hypothalamo-pituitary endocrinopathyCushing’s DiseaseAdrenal DisordersCushing’s syndromeCongenital adrenal hyperplasiaPrimary tumoursGonadal DisordersMc Cune- Albright syndromePrimary HypothyroidismIsolated Premature Thelarche
33 Etiology FEATURES CENTRAL PRECOCİOUS PUBERTY THELARCHE Age of onset < 8 years< 2 yearsPubic and axillary hairProgressive developmentAbsentMensesAs in normal pubertyUsually absentSkeletal maturationAdvancedAppropriateGrowth velocityAcceleratedNormalGrowth prognosisCompromisedDuration of conditionContinues as adult sexual maturationUsually resolves after a few years, always by 8 years of agePrognosis for fertilityMay be compromisedBreast developmentProgressive developmentMinor (Usually B2 or B3 cycling at approximately 6 week intervals
34 Mc Cune-Albright Syndrome Activating mis-sense mutation in the gene for the α subunit of Gs.Mosaic distribution of cells with mutationPolyostotic fibrous dysplasiaCafé au lait spotsEndocrinopathygonadsadrenal cortexthyroidpituitary glandparathyroid gland“G protein stimulation as if trophic hormones were present.”
35 TestotoxicosisActivating mutation of the LH receptor