Evaluation of Worrisome Growth Flashcards
1
Q
Worrisome growth: definition
A
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
Q
Causes of short stature
A
- Normal
- Constitutional short stature
- Familial short stature
- Pathological
- Nutritional
- Endocrine
- Chromosome defects
- Skeletal dysplasias
- IUGR/SGA
- Metabolic
- Chronic diseases
- Psychosocial deprivation
- Drugs
3
Q
Nutritional causes of short stature
A
- Zinc, iron deficiency
- Anorexia
- IBD, celiac disease, CF
4
Q
Endocrine causes of short stature
A
- Hypothyroid
- Growth hormone deficiency
- Cushing’s disease
- Rickets
5
Q
Causes of short stature: chromosome defects
A
- Turner syndrome
- Down syndrome
- Prader-Willi syndrome
6
Q
Drugs causing short stature
A
- Glucocorticoids
- Stimulants
7
Q
Constitutional growth delay
A
- 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
Q
Constitutional growth delay: treatment
A
- Boys:
- Testosterone if bone age >/= 11.5 years to avoid compromising final height
- Girls:
- Estrogen (not as common)
9
Q
Familial short stature
A
- 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
Q
Failure to thrive
A
- 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
Q
Nutritional growth retardation
A
- 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
Q
Hormonal causes of worrisome growth
A
- Generally, weight is spared
- Hypothyroidism
- Growth hormone/IGF-1 abnormalities
- Cushing’s syndrome
- Rickets
13
Q
Hypothyroidism
A
- 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
Q
Growth hormone
A
- AP hormone
- Main function to promote linear growth
- Also affects body composition
- Increases lean body mass, decreases fat
15
Q
Growth hormone deficiency
A
- 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
Q
Congenital GH deficiency
A
- Hypothalamic-pituitary malformations:
- Holoprosencephaly/schizencephaly
- Isolated Cleft lip or palate
- Septo-Optic-Dysplasia – 50% have hypopituitarism
- Optic nerve hypoplasia
- Empty sella syndrome
17
Q
Acquired GH deficiency
A
- Trauma
- CNS infection
- Hypophysitis
- CNS tumors
- Craniopharyngioma
- Germinoma
- Cranial irradiation
18
Q
GH deficiency: clinical features
A
- 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
Q
GH deficiency: evaluation
A
- 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
Q
Syndromic short stature
A
- 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
Q
Turner Syndrome
A
- 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
Q
Turner Syndrome: clinical features
A
- 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
Q
Evaluation of worrisome growth
A
- 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
Q
rhGH
A
- 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?
