Childhood Growth Flashcards
Why is it important to measure children?
- measurements of growth provide a sensitive indication of health in childhood
- growth rates are well defined in healthy children with adequate nutrition and an emotionally supportive environment
- changes in growth rates can provide an early and sensitive pointer to health problems in children
How are body proportions of newborns and adolescents different?
Newborns = larger head, smaller mandible, short neck, chest rounded, abdomen prominent, limbs short Adolescents = more growth of limbs relative to trunk
How can body proportions me measured?
- arm span should equal height in adolescence
- arm span is shorter than height in children
- sitting height indicates torso, also limb development
What are the different names for short stature?
- proportional short stature
- short trunk dysplasia
- short limb dysplasia
- rhizomelic = short proximal limbs
- mesomelic = short distal limbs
- acromelic = affecting terminal part of limb
- asymmetry
Describe growth charts
- Standard UK growth charts based on height measurements of several thousand children over 10 years
- separate charts for boys and girls
- based on white UK children only
- normal range 3rd-97th centile
What are the three components of childhood growth?
- infancy component
- childhood component
- puberty component
What is the infancy component?
- rapid, but rapidly decelerating growth in first 2-3 years
- determined by nutrition
- long term growth failure, if underfed in infancy
What is the childhood component?
- switch from nutritional to hormonal dependence
- growth and thyroid hormones most important
- heigh velocity slows 2-3 years before puberty
What is the puberty component?
- growth spurt, increased height velocity due to sex hormones (oestrogen and testosterone)
- ends age 14-15 girls, age 16-17 boys
How does growth end?
- growth ends with fusion of epiphyses due to influence of oestrogen in girls and boys
- boys convert testosterone to oestrogen in fatty tissues (aromatase enzyme)
What is the first sign of puberty in girls and boys?
girls - breast development
boys
boys - testicular enlargement
What defines precocious puberty in boys and girls?
boys = >9 girls = >8
What are the important determinants of growth?
- parental phenotype and genotype
- quality and duration of pregnancy
- nutrition
- specific system and organ integrity
- psycho-social environment
- growth promoting hormones and factors
How are parents heights used in determining if child height is normal?
Boys = fathers ht + (mothers height +12.5cm) /2
Girls = mothers height + (fathers height -12.5cm)/2
95% CI = mid-parental ht +/- 8.5cm
What is growth of the growth plate called?
chondrogenesis
How is the growth plate involved in growth disorders?
- all growth disorders originate from, or affect the growth plate
- building material needed every day - direct effect of nutrition and calcium/phosphate supply on growth rate and bone architecture
What are the layers of the growth plate?
resting
proliferative
hypertrophic
osteogenic
What are main regulators of growth?
- nutrition
- inflammatory cytokines, TNFalpha, IL-1beta, IL-6
- extracellular fluid, oxygen deficiency, acidosis, toxins
What are the 3 classifications of growth retardation?
- primary growth plate abnormalities
- secondary growth disorders
- idiopathic short stature
Give examples of primary growth abnormalities and the characteristics of them
A: Osteochondrodysplasia = skeletal dysplasia
- genetic abnormalities of cartilage and bone growth
- abnormal shape and size of the skeleton, and disproportion of the long bones, spine and head
- >350 disorders
B: Chromosomal abnormalities
What is the major chromosomal reason of short stature in girls?
Turners syndrome
- at birth oedema of the dorsal of the hands/feet and loose skin folds at nape of the neck
- webbing of neck, low posterior hairline, small manidble, prominent ears, epicanthal folds, high arched palate, broad chest, wide nipple distance, cubitus valgus, hyperconvex fingernails
- hypergonadotrophic hypogonadism, streak gonads
- cardiovascular/renal malformations
- recurrent otitis media
- short stature
What do girls with short stature due to turners need to be treated with?
exogenous growth hormone
What are the four categories of secondary growth disorders?
A: malnutrition
B: chronic disease
C: intrauterine growth retardation
D: endocrine disorders e.g. GH and IGF-1 deficiency, hypothyroidism, cushing syndrome, pseudohypoparathyroidism, rickets
What chronic diseases cause short stature?
- Gastrointestinal: coeliac disease, IBD
- Cardiovascular: congenital heart disease
- Renal disease
- Haematologic: chronic severe anaemia
- Pulmonary: cystic fibrosis, bronchopulmonary dysplasia
- Chronic inflammation and infection
- Hypothyroidism: athyrosis/agenesis, dyshormogeneis, autoimmune, post-surgery
Describe the regulation growth hormone secretion
Hypothalamus –> somatostatin, GHRH
Anterior pituitary –> GH
Liver –> IGF-1
Bone
What are the causes of IGF-1 deficiency?
hypothalamic dysfunction
pituitary GH deficiency
How is the hypothalamus involved?
- GHRH cell bodies in arcuate nucleus, project to portal capillaries
- regulated by food, sleep, steroids
- negative feedback: SST, GH, IGF-1
- neurotransmitters: adrenergic, cholinergic, opioids
- other hypothalamic hormones: TRH, CRH
What are the characteristics of congenital hypothalamic hypopituitarism?
- doll like face
- short stature
Where is GH produced?
Describe its secretion
- synthesised in somatotroph cells, these account for 40-50% of the anterior pituitary
- most abundant hormone
- pulsatile secretion, max at night
What actions just GH have?
Growth Hormone Binding Protein GHPH
Stimulates IGF-1 from the liver
Direct effect on growth plate and cortical bone
Decrease glucose use, increase lipolysis, increase muscle mass
What stimulates GH secretion?
exercise stress hypoglycaemia fasting high protein meals perinatal development puberty
What suppresses GH secretion?
hypothyroidism hyperglycaemia high carbohydrate meals glucocorticoid excess aging
What are the three classifications of IGF-1 deficiency?
A: GH deficiency (secondary IGFD)
- GH deficiency - hypothalamic dysfunction
- GH deficiency - pituitary GH deficiency
B: primary IGFD
- primary GH insufficiency (GH receptor, Laron syndrome)
- secondary GH insensitivity (signalling cascade, Stat-5)
- primary defects of IGF-1 synthesis
- primary defects of IGF-1 transport/clearance (ALS)
C: IGF-1 resistance
- defects of IGF-1 receptor
- post receptor defects
Describe GH and IGF-1 signalling
GH liver factors nucleus IGF-1 transcription binding proteins in blood chondrocytes growth via transcription
Describe IGF-1 and its effects
- small protein secreted in response to stimulation by GH
- stimulates multiple processes of growth and metabolism
- also regulated by nutritional status
- mild glucose-lowering effects - IGF and insulin receptor structurally similar
What 3 compounds does GH regulate and where are these produced?
- IGF-1 - hepatocytes
- ALS - hepatocytes
- IGFBP-3 - Kuppfer cells
What are the characteristics of a boy with IGF-1 deficiency?
- extreme short stature
- mid facial hypoplasia, lots of subcutaneous fat, small genitalia
What are the 3 types of idiopathic short stature (ISS)?
- familial short stature
- constitutional delay of growth and puberty with normal height prediction
- ISS with/without delated bone age (tempo of puberty) or with/without familial component
What are the sequence variants in growth plate genes and height?
gain of function –> tall stature
normal sequence –> normal stature
mild polymorphisms –> low-normal stature
less severe –> isolates short stature
severe loss of function mutations –> skeletal dysplasias
How is bone age used to assess delays in growth and puberty?
- left hand X-ray
- delayed bone age in GH deficiency
- adnaved bone age in precocious puberty
What is the most common form of short stature in children?
Constitutional delay in growth and puberty
Usually boys
“transient short stature”
“late bloomers”
What is psychosocial short stature?
- usually seen over age of 3 years
- emotional rejection key factor, physical/sexual abuse may be associated
- hyperphagia (hyperphagic short stature)
- 50% show reversible GH deficiency
- poor response to GH treatment
- reverses when child nurtured outside the stressful environment
Give examples of the following:
- Overgrowth with impaired final height
- Overgrowth with normal final height
- Overgrowth with increased final height
- Overgrowth with impaired final height
- precocious puberty
- congenital adrenal hyperplasia
- McCune Albright syndrome
- Hyperthyroidism - Overgrowth with normal final height
- Beckwith-Weidemann syndrome
- Sotos syndrome - Overgrowth with increased final height
- androgen or oestrogen deficiency
- oestrogen resistance
- pituitary gigantism (GH XS)
- Klinefelter syndrome (XXY)
- Marfan syndrome
- Homocystinuria
What are the essential steps i assessment of growth disorders?
- measure the height of the child
- measure height of parents and determine mid-paretnal centile
- compare child’s height gentile with mid-parental centile
- re-measure child’s height after a period of time has elapsed
- calculare present growth velocity
- if normal –> pathology unlikely
- abnormally slow or rapid –> investigate further irrespective of height of patient
