Most children evaluated for short stature are normal stature variants The slow growth patterns of these children reflect familial short stature andor constitutional delay of growth and puberty ID: 411270
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Slide1
Growth DisordersSlide2
Most children evaluated for short stature are
normal stature variants
.
The slow growth patterns of these children reflect familial short stature and/or constitutional delay of growth and pubertySlide3Slide4Slide5Slide6Slide7
Familial short stature
Tend to be small at birth
They grow approximately parallel to the normal curve but below the 3rd percentile from infancy
Pubertal development and the acceleration of growth occur normally and they ultimately achieve a short adult height(Father <163 cm,Mother <150 cm)Slide8
They have no clinical or laboratory evidence of endocrine or systemic disease
Their annual growth rates are within normal limits
The bone age is appropriate for his or her chronological ageSlide9Slide10
The diagnosis of familial short stature has been perpetuated in families in which impaired growth was eventually proved to be consequence of a defined genetic disorder.Slide11
Constitutional delay in growth and puberty(CDGP)
They mature at a slower than normal rate
Height and bone age are usually delayed by 2-4 years
Onset of pubertal maturation is understandably delayed appropriate to the child’s bone age
Often there is a history of delay in growth and pubertal development of either parent or another relative
Final adult stature, which may not be reached until the age of 20 or more years, is appropriate for parental target height rangeSlide12
They are usually of normal size at birth
They grow normally for several months or years but then deviate from the “normal” growth centiles, particularly in the pre/peri-pubertal years
They grow at a normal rate for their bone age
There is a later than average adolescent “growth spurt”
Treatment: controversial
Synthetic steroids designed to have an increased anabolic-androgenic ratio:oxandrolone(oral)(hepatotoxic-hepatic tumors!)
No suitable equivalent for the girlSlide13Slide14
A child’s current centile must be evaluated in terms of:
Genetic background
Gestational or past medical history
Environment
Physical findings
Growth pattern since birth
Current growth rate(height velocity)Slide15
Causes of short stature
1- Familial or congenital conditions
Skeletal dysplasias
Chromosomal abnormalities
Forms of intrauterine growth retardation which may result in show or abnormal growth throughout later life
2- Chronic systemic disorders:
(Due to) insufficient intake of energy and/or protein-nutritional insufficiency, malabsorption syndromes and chronic inflammatory bowel disease)
Insufficient oxygenation of tissues
Electrolyte imbalance(chronic renal failure)Slide16
3-Endocrine abnormalities
CNS or hypothalamic abnormalities which affect regulation of the anterior pituitary
Anterior pituitary disorders, either developmental or acquired which can affect synthesis or secretion of growth hormone or the trophic hormones(TSH,LH,FSH,ACTH)
Primary dysfunction of the target organs e.g. Thyroid,adrenal or gonadal diseaseSlide17
Peripheral target tissue abnormalities
- a diminished or absent hormone receptor or tissue enzyme defect
Laron type “dwarfism” – failure of IGF1 generation in response to GH (A GH receptor defect)
- Disorders related to the interaction of the IGF’s or other related peripheral growth factors with chondrocytes and mucopolysaccharides in epiphyseal growth cartilage
Pygmies:genetic defect in IGF-1 responsiveness associated with diminished IGF-1 bindingSlide18Slide19Slide20
Normal human growth hormone secretion
In the first days of life, very high levels of GH occur. After 2 weeks of age, lower mean levels are found.
In pubertal children, the basal plasma GH concentration is not significantly different from that reported for adults but more peaks of GH may occur during the day with greater amplitude of GH peaks during the night
The most consistent period of GH secretion for both children and adults occurs within one hour or so after the onset of sleep.The initial surge of GH secretion often correlates with the onset of stage 3 or 4 (slow wave) sleepSlide21
Control of human growth hormone secretion
Positive releasing factor GHRH-Ghrelin
Inhibitory factor:GHRIH
Naturally occurring events that trigger GH secretion in man are exercise, physical and emotional stresses and high protein intakeSlide22
Normal regulation of GH
The neurone system regulating GHRH and GHRH release receives a variety of normal impulses.Impulses arising in the hippocampus are stimulatory whereas those arising in the amygdaloid nuclei can be either stimulatory or inhibitory. The inhibitory inputs are presumed to activate GHRIH release via the anterior somatostinergic pathways,the stimulatory pathway is by way of the ventromedial(VM) nucleus of the hypotalamus Slide23
The GH regulatory neurone system also recieves impulses from each of the ascending monoaminergic neuronal systems :
dopaminergic, noradrenergic and serotonergic
- L-Dopa(converted to dopamine) in the brain leads to a release of GH
- Sleep induced GH release is predominantly mediated by serotonergic fibres.
- Hypoglycemia induced GH release is mediated by noradrenergic pathways.Slide24
GH provocation tests
Exercise
Sleep
Arginine infusion
Glucagon
Clonidine (alfa adrenergic receptor stimulant)
ITT
L-Dopa
Priming(sex hormones)??Slide25
Physiologic effects of human growth hormone
Anabolic-promotes protein synthesis in muscle cells
Catabolic effect- on fat and carbonhydrate metabolism (short term hypoglycemic effect) inducing lipolysis in adipoctytes
Long term effect of high GH levels:plasma glucose concentration increases(increased glucose production and reduced glucose utilization)Slide26
Evalution of height measurements
1- Growth charts
2- Parental heights- target height
3- Height SDS
4- Height velocity
5- Predicted ht
SDS:
X-x*
SD
x*:mean height for age and genderSlide27
Etiology and pathogenesis of growth failure
Chromosomal assessment
Turner Sydrome
FSS
IUGR “Catch up”
CDGP
Skeletal dysplasia osteochondrodysplasias(achondroplasia, hypochondroplasia)Slide28
Chronic systemic disorders- asthma
Nutritional insufficiency
Chronic gastrointestinal diseases
Coeliac disease
Crohn’s disease
Ulcerative colitis
Chronic renal disease
Cardiac disease
DMSlide29
Endocrine abnormalities
Primary hypothyrodism
Gonadal dysgenesis
GHD
Glucocorticoid excess
Growth failure to pyschosocial deprivationSlide30
Etiology of GHD
Congenital
Acquired
İsolated
MPHDSlide31Slide32Slide33
Incidence 1/4000-10000 live births
(50-60%) idiopathic
Hereditary (aut.recessive or dominant)Slide34
Developmental defects
Pituitary aplasia-hypoplasia
Midline abnormalities
- Severe holoprosencephaly septooptic dysplasia (SOD):Hypoplasia of the optic nerves dysgenesis or agenesis of the infundibulum and septum pellucidum +/- pituitary hormone deficiency
-Cleft lip palate
-Single upper central incisor syndromeSlide35
Fizik Muayene-1:
TY
: 11 yaş 11 ay iken
Boy
: 131 cm
Boy SDS
: - 3.4
VA
: 28 kg
BMI
: 16,32 kg/m²
KY
: 11-12 YAŞSlide36
Radyoloji:Slide37Slide38
BH gene defects
All patients with classical GH gene deletions have complete GHD(IGHD IA, IB,2,3(+hypogammaglobulinemic))Slide39
GH gene regulation:
Pit1 (pituitary transcription factor):stimulatory effect on GH gene transcription
Pit 1 mutations
- Severe deficiencies in GH PRI
- Often develop secondary hypothyrodism
Prop 1 (Prophet of pit 1) mutations combined pituitary hormone deficiency(secondary hypogonadism)Slide40Slide41
Davis 2010Slide42
Clinical features of GHD
Growth failure
Normal birth weight and birth length
Skeletal proportions normal for age
Somewhat overweight for height(increased subcutaneous fat)
Head circumference normal
Disparity between the size of face and the calvarium: “doll like” “cherubic” facies most pronounced in panhypopituitarism (crowding of the facial features to the centre of the face suggesting maxillary hypoplasia)- frontal bossing, saddle nose
Skeletal maturity delayed
High pitched voice
Males: penis,scrotum small, hypoplastic testis
HypoglycemiaSlide43Slide44Slide45Slide46
Radiological assessment: Skull x rays,CT, MRI
IGF 1 measurement, physiological tests of GH secretionSlide47
O.ESlide48
G.ÖSlide49
B.YSlide50
M.Ş