Evaluation of Worrisome Growth Flashcards Preview

DEMS: Unit III > Evaluation of Worrisome Growth > Flashcards

Flashcards in Evaluation of Worrisome Growth Deck (28):
1

Worrisome growth: definition

Can be worrisome along two variables:

  • Height
    • Short stature: height below -2 SD for age and gender OR height more than 2 SD below the midparental target height
    • Dwarfism: height below -3 SD for age
    • Midget: dwarf with normal body proportions
  • Growth velocity
    • Abnormally slow linear growth velocity or dropping across two major centile lines on growth chart

2

Causes of short stature

  • Normal
    • Constitutional short stature
    • Familial short stature
  • Pathological
    • Nutritional
    • Endocrine
    • Chromosome defects
    • Skeletal dysplasias
    • IUGR/SGA
    • Metabolic
    • Chronic diseases
    • Psychosocial deprivation
    • Drugs

3

Nutritional causes of short stature

  • Zinc, iron deficiency
  • Anorexia
  • IBD, celiac disease, CF

4

Endocrine causes of short stature

  • Hypothyroid
  • Growth hormone deficiency
  • Cushing's disease
  • Rickets

5

Causes of short stature: chromosome defects

  • Turner syndrome
  • Down syndrome
  • Prader-Willi syndrome

6

Drugs causing short stature

  • Glucocorticoids
  • Stimulants

7

Constitutional growth delay

  • Growth deceleration during first 2 years of life
  • Normal growth paralleling lower percentile curve throughout prepubertal years
  • Delayed skeletal maturation and fusion of growth plates
  • Catch-up growth achieved by late puberty
  • End up along lower end of normal height range for family
  • Polygenic trait - positive family in 60-80%
    • Genetic defects unclear
  • Reassurance of normal growth pattern

8

Constitutional growth delay: treatment

  • Boys:
    • Testosterone if bone age >/= 11.5 years to avoid compromising final height
  • Girls:
    • Estrogen (not as common)

9

Familial short stature

  • Children with normal growth velocity & height within normal limits for parents' heights
  • Initially have decrease in growth rate between 6-18 months of age
  • Some families may have tubular bone alterations
    • Brachydactyly syndromes, SHOX haploinsufficiencies

10

Failure to thrive

  • Infants or young children with:
    • Deceleration of weight gain to a point < 3%
    • Fall in weight across two or more major percentiles
  • Non-organic causes most common 
    • Poor nutrition
    • Psychosocial factors
  • May look like constitutional growth delay

11

Nutritional growth retardation

  • Linear growth stunting from poor weight gain in children > 2 years of age
  • May be 2/2 systemic illnesses
    • Celiac disease, IBD
  • May be 2/2 stimulant medications
  • Sometimes hard to distinguish from constitutional growth delay, constitutional thinness

12

Hormonal causes of worrisome growth

  • Generally, weight is spared 
  • Hypothyroidism
  • Growth hormone/IGF-1 abnormalities
  • Cushing's syndrome
  • Rickets 

13

Hypothyroidism

  • Can result in profound growth failure
  • Many clinical features seen in hypothyroid adults are lacking in children
  • Primary hypothyroidism:
    • Increased TSH, low T4
  • Central hypothyroidism
    • Normal TSH, low T4

14

Growth hormone

  • AP hormone
  • Main function to promote linear growth
  • Also affects body composition
    • Increases lean body mass, decreases fat

15

Growth hormone deficiency 

  • Absent/inadequate production of growth hormone
  • Continuum - range of GH levels seen
  • May be associated with deficiencies in other pituitary hormones
  • Abnormal growth velocity with exclusion of other causes

16

Congenital GH deficiency

  • Hypothalamic-pituitary malformations:
    • Holoprosencephaly/schizencephaly
    • Isolated Cleft lip or palate
    • Septo-Optic-Dysplasia – 50% have hypopituitarism
    • Optic nerve hypoplasia
    • Empty sella syndrome

17

Acquired GH deficiency

  • Trauma
  • CNS infection
  • Hypophysitis
  • CNS tumors
    • Craniopharyngioma
    • Germinoma
  • Cranial irradiation

18

GH deficiency: clinical features

  • Abnormal growth velocity with exclusion of other causes
  • Decreased muscle build
  • Increased subcutaneous fat, especially around trunk
  • Face immature for age
  • Prominent forehead, depressed midface
  • Other midline facial defects
  • In males: small phallus
  • May have history of prolonged jaundice and/or hypoglycemia in newborn period

19

GH deficiency: evaluation

  • Bone age
  • IGF-1 (IGFBP-3 in infant) 
    • Low in underweight children regardless of GH status
  • Stimulation testing (never draw random GH level)
    • Clonidine, arginine, glucagon, L-dopa

20

Syndromic short stature

  • Skeletal dysplasias and other genetic syndromes
  • Turner syndrome
    • Haploinsufficiency of SHOX genes
  • Prader-Willi syndrome
    • GH deficient
  • Noonan syndrome
    • Abnormal GH post-receptor signaling

21

Turner Syndrome

  • Most common sex chromosome abnormality of females
    • Affects ~3% of female concepti
  • Caused by complete or partial absence of 1 of X chromosomes
  • Occurs in approximately 1/2000 live-born females
  • Virtually all affected exhibit short stature
  • Final height if untreated: about 20cm less than target height 
  • Haploinsufficiency of SHOX genes responsible for skeletal and growth abnormalities
  • Generally not GH deficient but GH therapy improves growth and final adult height - start treatment early

22

Turner Syndrome: clinical features

  • May be subtle - diagnosis and treatment often delayed
  • Skeletal abnormalities:
    • Short stature
    • Increased carrying angle
    • Short neck
    • Micro- or retrognathia (abnormal jawline)
  • Lymphatic obstruction:
    • Low hairline
    • Webbed neck
    • Lymphedema
  • Cardiac abnormalities - bicuspid aortic valve, coarctation of aorta
  • Renal - horseshoe kidney
  • Ovarian insufficiency
  • Hypothyroid/celiac disease
  • Otitis media
  • Hearing loss
  • Non-verbal learning disability

23

Evaluation of worrisome growth

  • Growth charts (obviously)
  • Bone age (L hand and wrist)
  • Screening labs:
    • BMP
    • CBC
    • UA
    • Karyotype in girls
    • TSH, T4
    • IGF-1
  • Nutritional growth retardation:
    • ESR
    • TTG
    • IgA

24

rhGH

  • Recombinant human GH
  • Identical to pGH by physiochemical techniques
  • Allowed pediatric endocrinologists to reinstitute GH therapy in deficient patients
  • Pathogen-free
  • Unlimited supply
  • BUT criteria used to diagnose GH deficiency became less stringent
    • "Cure goes in search of diseases" 
    • Use of GH in GH-deficient adults and in many non-GH-deficient conditions in adults & children

25

FDA-approved uses of rhGH

  • GH deficiency
  • Chronic renal insufficiency
  • Adult GH deficiency
  • Turner syndrome
  • Prader-Willi syndrome
  • Small for gestational age
  • Idiopathic short stature
  • SHOX deficiency
  • Noonan syndrome

26

Next uses for rhGH in the pipeline

  • Cystic fibrosis
  • Inflammatory bowel disease
  • Juvenile rheumatoid arthritis
  • Glucocorticoid induced growth retardation

27

Ethical issues of GH use

  • How good is GH testing?
    • Deficient response seen without endocrine disease
    • Variability in assays
    • Intra-individual variability from day to day
    • Definition of normal response is arbitrary
  • Who to treat?
    • Just because there is FDA approved indication?
    • What if family wants to pay?
    • Developmentally delayed children?
    • Who makes these decisions?
  • How long to treat?
    • Until final height is reached (growth plate closure)
    • Until reach genetic potential (MPH)
    • Until normal height - but how to define this? 
    • Until a height that is no longer a disability
  • Who pays?
    • Mean cost $20,000/year
    • $35,000 per inch of height

28

Side effects of GH replacement therapy

  • Slipped capital femoral epiphysis
  • Pseudotumor cerebri
  • Long term risks? 
  • Benefits besides height - are taller people any happier or more successful?