Endocrine Aspects of 11q: Is there a role for GH?
-
Upload
roger961 -
Category
Health & Medicine
-
view
631 -
download
1
Transcript of Endocrine Aspects of 11q: Is there a role for GH?
![Page 1: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/1.jpg)
Endocrine Aspects of 11qIs there a role for GH?
…no issue
Thomas G. Kelly, MD, FAAPPediatric Endocrinology
UC San Diego / Rady Children’s Hospital San Diego
![Page 2: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/2.jpg)
Short Stature Can Be a Stigma
![Page 3: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/3.jpg)
![Page 4: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/4.jpg)
Goals
• Review the process of growth
• Promote an understanding of factors that are critical to this process.
• Discuss examples of growth failure and
discuss how they are treated.
• Discuss 11q syndrome and what is known about growth and growth hormone.
![Page 5: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/5.jpg)
Overview
• Introduction with Basic Growth Vocabulary
• How Do We Grow?
• What can go wrong?
• How do we fix it?
![Page 6: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/6.jpg)
Understanding Your Child’s GrowthWhat you need to know
• Height and Height %- an assessment of stature and its comparison to the general
population
• Growth Velocity- an assessment of the rate of growth
• Mid parental height - a calculation of predicted height based on parental heights
• Bone age- An assessment of the degree of growth plate closure
![Page 7: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/7.jpg)
Assessing Stature
• Current Height
• Growth Velocity
• Predicted Height
![Page 8: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/8.jpg)
OK135S057
Height• Evaluation of height must
be done in the context of normal standards
• Charts compare child’s height with the 3rd-97th% of normal American kids
• Plotting height and weight provides a useful and objective assessment of the adequacy of growth.
• SDS score (Ht-mean HT/SD) describes the location of those whose Ht is >97th +2SD and<3rd % (-2SD).
![Page 9: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/9.jpg)
What creates error in measurement
![Page 10: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/10.jpg)
Good Technique = Good Data
– Method of measurement
– Staff with different techniques
– Standing vs lying– The “birthday
plot”
![Page 11: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/11.jpg)
Incorrect Height Measuring Techniques
• Line of sight not at eye level
• Using floppy arm device
• Child’s back not against board
• Child’s hairpiece not removed
• Child’s socks still on
![Page 12: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/12.jpg)
Scoliosis
![Page 13: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/13.jpg)
Rickets
![Page 14: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/14.jpg)
Height Velocity
• Invaluable in assessing a child with growth abnormalities.
• Kids grow with remarkable fidelity relative to the growth curves from 2yrs to puberty.
• Any crossing of Ht %’s is a concern.
• Velocity should be calculated over at least a 6 month period.
![Page 15: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/15.jpg)
What’s normal ?
![Page 16: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/16.jpg)
Normal Growth Rates During Childhood
National Center for Health Statistics
AgeAge Growth (cm/year)Growth (cm/year)
Birth to 1 yearBirth to 1 year 1717– 26– 26
1 to 2 years1 to 2 years 1010–13–13
2 years to puberty2 years to puberty 55–7–7
PubertyPuberty
GirlsGirls 77–12–12
BoysBoys 88–13–13
![Page 17: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/17.jpg)
Normal Growth Rates During Childhood
Gro
wth
ra
te (
cm/y
)
Age (y)2 193 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
0
13
12
11
10
9
8
7
6
5
4
3
2
1
National Center for Health Statistics.Tanner JM, et al. J Pediatr. 1985.
Girls: solid linesBoys: dashed lines
Girls’ peak growth rate: 11.5 yearsBoys’ peak growth rate: 13.5 years
Boys: dashed lines
Boys’ peak growth rate: 13.5 years
![Page 18: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/18.jpg)
How tall will I be when I grow up?
![Page 19: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/19.jpg)
Height Prediction
• Midparental height– Boys: [(M+F) + 5 inches]/2– Girls: [(M+F) – 5 inches]/2
• Bone Age
![Page 20: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/20.jpg)
Mid-Parental Height-An Assessment of Genetic Potential
• The “mid-parental height” or MPH is a calculation based on parental heights of the expected final height of the child.
• A useful tool in the assessment of whether a child’s current height percentile is appropriate.
• MPH is adjusted ± 5 inches to account for the difference between the male and female heights on the growth curve. .
![Page 21: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/21.jpg)
Examples of Mid-Parental Height
• Dad = 66”; • Mom = 61”• MPH for a girl = Dad’s ht -5 or 66-5= 61”+Mom’s ht = 61Divided by 2(61+61)/2 = 61”MPH for a boy =
Dad’s Ht + Mom’s Ht +52
66” 61” 61”
![Page 22: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/22.jpg)
A bone age demonstrates growth potential
Phalanges(Finger Bones)
Epiphysis(Growth Plate)
Metacarpal(Hand Bones)
Carpal(Wrist Bones)
Epiphysis(Growth Plate)
![Page 23: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/23.jpg)
Male, 8 years Male, 14 years
![Page 24: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/24.jpg)
![Page 25: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/25.jpg)
BA
MPH
![Page 26: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/26.jpg)
Factors Affecting Growth
GrowthEnvironmental Influences
EconomicFactors
Genes
NutritionBiological Factors
![Page 27: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/27.jpg)
GenesAlthough length and
weight at birth depend on the intrauterine environment the final height achieved by a child is largely dependent on their genetic endowment.
Height is highly heritable!
![Page 28: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/28.jpg)
Although this achievable height is limited by genetic factors …
up to this limit height potential depends on environmental factors
![Page 29: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/29.jpg)
Environment• Normal interaction between
infants and children and their environment is necessary for normal growth and development.
• Syndrome of growth failure and weight loss is long recognized in infants separated from their mothers or socially isolated, subject to cruelty, neglect, or institutional upbringing.
![Page 30: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/30.jpg)
Economics
• Socioeconomic Deprivation -Poverty leads to Stunting from:– Poor nutrition – Increased susceptibility
to infections – Limited access to
health care– Recurrent and/or
chronic infections
![Page 31: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/31.jpg)
Nutrition
• Adequate Nutrition is essential for good linear growth.
• Growth Failure may be the direct result of inadequate protein or other essential nutrients.
• Alternatively, biologic influences such as disturbances of bowel endocrine, or metabolic function may play a role
![Page 32: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/32.jpg)
Examples of Feeding Problemsthat can lead to impaired Nutrition
• Problems with gastroesophageal reflux (GER) can contribute to problems with feeding. Many children with neurodevelopmental problems have GER
• Tactile sensitivity or sensory defensiveness, common among children with cerebral palsy, autism, and spina bifida may cause a child to avoid putting things in his/her mouth.
• Children with feeding problems as a result of behavioral or emotional issues. Or, the result of complex perinatal medical interventions that center around feeding or around the mouth, making subsequent oral experiences, including feeding, unpleasant.
![Page 33: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/33.jpg)
Low Birth Weight• Intrauterine Growth Retardation (IUGR) is a fetus with an
estimated weight < 10th % for gestational age.• Small for gestational age (SGA) is an infant with a
birthweight <10th%. • Depending on the timing, duration and severity of the insult,
and success of postnatal intervention, the growth potential of IUGR/SGA children may be permanently adversely affected.
• IUGR leading to SGA is an approved indication for Growth Hormone if growth deficit is not overcome in the first 3 yrs of life.
Nutritional/Biologic Factors and Growth
![Page 34: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/34.jpg)
Generalizations About Growth
• Despite all the factors mentioned– Genes– Environment– Nutrition– Economics
• Children normally grow at a remarkably predictable rate.
• The sequence of growth is usually uncomplicated and orderly, but variations exist and individual growth patterns may be confused with problems of hormonal regulation
![Page 35: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/35.jpg)
Normal Growth Patterns associated with Short Stature
Two Common Conditions
• Genetic Short Stature
• Late Bloomer (Constitutional Delay)
![Page 36: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/36.jpg)
Familial Short Stature
• Diagnosis– Growth chart pattern– Family history (with
accurate family heights)
– Normal bone age– Normal growth
velocity
![Page 37: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/37.jpg)
Constitutional Delay
• Late Bloomers• Generally refers to a
delay in growth as well as pubertal development
• More common in boys
• Possibly related to nutrition
![Page 38: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/38.jpg)
The Late Bloomer(AKA Constitutional Delay)
• Not associated with growth failure
• Adolescents channeled to a curve that may be short for the population and/or family
• Family history of late puberty with catch-up growth at puberty
![Page 39: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/39.jpg)
Pubertal Delay
• Growth Velocity: prepubertal
• BA<CA
• May intervene to initiate puberty
![Page 40: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/40.jpg)
What Can Go Wrong?
GrowthEnvironmental stressors
EconomicStressors
Genetic/Chromosomal Abnormalities
MalnutritionAnd Disease
![Page 41: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/41.jpg)
Genetic and Chromosomal Abnormalities
• A genetic disorder is any disorder caused by faults in inherited genetic material within a persons cells.
• In these conditions there is the potential for altered growth because the affected metabolic pathways disturb energy production and/or the building of body tissue.Examples: Genetic abnormalities of bone, cartilage
![Page 42: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/42.jpg)
Genetic and Chromosomal Abnormalities
• A Chromosomal Abnormality is any change in the normal structure or number of chromosomes.
• It can be associated with growth patterns that differ from those of children without chromosomal abnormalities.
• It is assumed that these differing growth patterns represent altered growth potential related to the underlying chromosomal abnormality.– Turner’s Syndrome missing an X chromosome or
parts of an X. – Down’s Syndrome has an extra chromosome.
![Page 43: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/43.jpg)
What Can We Do?
![Page 44: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/44.jpg)
Evaluate For:
• Conditions that alter growthKnown or suspected Chromosomal disorders.History of IUGR/SGAGenetic Syndrome
• Conditions that have the potential to alter growth.
Metabolic Disorders RenalEndocrine Disorders CardiacGastrointestinal InfectiousHematologic PsychosocialImmune Pulmonary
![Page 45: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/45.jpg)
Endocrine Causes of Short Stature
• Low Thyroid Function• Decreased appetite• Constipation• Lethargy• Dry skin and hair• GROWTH FAILURE
• Growth Hormone Deficiency• GROWTH FAILURE • Decreased lean body mass, increased fat mass• Decreased bone mineral content
![Page 46: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/46.jpg)
Endocrine Causes of Short Stature
![Page 47: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/47.jpg)
Growth Hormone Deficiency
• Prevalence is 1/4000-1/80000• Diagnosis is suspected by poor growth, history
of brain irradiation or trauma• Since growth hormone secretion is pulsatile so
random growth hormone measures are useless.
• IGF-1 and IGFBP-3 are surrogate markers of GH sufficiency
• Note that IGF-1 is significantly affected by nutritional status.
![Page 48: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/48.jpg)
![Page 49: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/49.jpg)
GH Testing
• GH deficiency is confirmed using stimulatory tests– Arginine, clonidine, L Dopa
and insulin– Some agents (arginine and
clonidine) may act as GHRH agonists in the pituitary
• Stimulatory tests are not perfect:– May miss partially deficient
patients
![Page 50: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/50.jpg)
Etiologies of Pediatric GHD
Early NCGS Pediatric Registry
(1986-1994)
Later NCGS Pediatric Registry
(1995-2002)
N % N %
Idiopathic GHD 10,106 72.8 9190 81.7
Organic GHD 3767 27.2 2059 18.3
Other/unknown 996 26.4* 955 46.4*
CNS irradiation 884 23.5* 317 15.4*
Other CNS tumor 799 21.2* 308 15.0*
Craniopharyngioma 600 15.9* 214 10.4*
Septo-optic dysplasia 413 11.0* 248 12.0*
Trauma 75 2.0* 17 0.8*
Levy RA, et al. J Pediatr Endocrinol Metab. 2003.* Percentage of organic GHD cases
![Page 51: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/51.jpg)
Pediatric Indications For Growth Hormone
• The FDA has approved GH for the following pediatric conditions associated with short stature:– GH deficiency (defined as on the basis of the
provocative tests)– Turner Syndrome– Chronic renal insufficiency– SGA or IUGR infants that fail to demonstrate catch-up
growth– Prader-Willi Syndrome– Idiopathic short stature (<2.5 SD below the mean and
not expected to meet a normal adult height)
![Page 52: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/52.jpg)
![Page 53: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/53.jpg)
![Page 54: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/54.jpg)
![Page 55: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/55.jpg)
Cancer and GH Therapy
• No definitive link between GH therapy and an increased incidence of leukemia.
• Currently GH therapy is not recommended in patients with an active malignant condition.
![Page 56: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/56.jpg)
Endocrine Abnormalitiesin 11q- Syndrome
9 children with Jacobsen (11q-) were studied in San Diego with the following findings:
• 8/9 had short stature (ht<5th%)Six with >-2SDOne had IUGRFour had low IGF-1 levels
• 4/9 males had cryptorchidism (failure of testes to descend).
![Page 57: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/57.jpg)
Endocrine Abnormalitiesin 11q- Syndrome
Case Reports suggest an association of 11q deletions or translocations with short stature.
6 publications with 5 single case reports plus the small series from San Diego of 8 affected patients
One publication of central GH and TH deficiencies.
Studies suggest that genetic information encoded in 11q is important for normal growth.
Insufficient data is available to suggest a mechanism for growth failure in these children.
![Page 58: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/58.jpg)
Take-away Messages
• Growth Velocity correlates with good health
• Abnormal growth velocity merits evaluation
• A good history and exam are often diagnostic
• Laboratory and Imaging studies may be helpful
• Timing is everything
![Page 59: Endocrine Aspects of 11q: Is there a role for GH?](https://reader035.fdocuments.in/reader035/viewer/2022062702/554b2d89b4c905ce088b4cd9/html5/thumbnails/59.jpg)
Resources For Patients & Families
MAGIC Foundation: www.magicfoundation.org
Human Growth Foundation:
www.hgfound.org