Endocrine disorders of growth and development Flashcards
When do individual children require further assessment of growth?
If:
- weight/height/BMI is <0.4th centile, unless already fully investigated at an earlier age
- height centile is >3 centile spaced below the mid-parental centile
- drop in height centile of >2 centile spaces
What are the requirements for normal human growth?
- absence of chronic disease
- emotional stability, secure family
- adequate nutrition
- normal hormone growth/ growth factor actions
- healthy growth plates
How should short stature be evaluated? (4 aspects)
- height centile vs. weight centile
- failure to thrive/failure to grow - when it started
- in utero/infancy/childhood/puberty - body proportions
- primary or secondary growth disorder - presenting signs
- Idiopathic Short Stature or specific diagnosis
Why might growth be stunted in:
a. infancy
b. childhood
c. puberty
a. infancy = poor nutrition
b. childhood = GH/thyroid issue
c. puberty = GH/sex hormone/thyroid issue
How is height velocity calculated?
Take serial height (for 6-12 months) and plot over time
compare height velocity to accepted age-related standard
What is the most common causes of short stature?
Delay in bone age + SHOX haploinsufficiency
What is considered to be delayed bone growth?
2 standard deviations below the chronological age
Why might growth failure/short stature be disproportionate?
Skeletal dysplasia examples: - achondroplasia - hypochondroplasia - rickets - Leri-Weill dyschondrosteosis
Why might growth failure/short stature be proportionate?
Psychosocial assessment (psychosocial growth retardation) Karyotype (girls - Turner syndrome) Tests for systemic disorders (chronic renal insufficiency; gastrointestinal disease; nutritional deficiency Tests for endocrine disorders (hyperthyroidism, hypercortisolism)
How is the standard deviation for height calculated?
Plot the sitting height against subiscial length on a graph
Take subiscial length away from sitting height
SDS = measurement - mean / SD (at the relevant age)
What are the different classifications of limb shortening?
Rhizomelic = proximal (e.g. femur) Mesomelic = shortening of middle part Acromelic = shortening of extremities
*can have overlap between these
What is achondroplasia? What gene is mutated? What is this gene responsible for?
Condition that results in dwarfism - lack of long bone elongation
Arises from mutation in the fibroblast growth factor receptor 3 gene
This gene is responsible for the ossification at growth plates
What is hypochondroplasia? What gene is mutated?
This is a milder form of achrondroplasia - features are more subtle and short stature is only noticed later in life
Arises from a mutation in the FGFR3 gene –> receptor is able to retain some of its function and therefore there is still some ossification of long bones
What is Leri-Weill dyschondrosteosis? Which gene is mutated? What are the features of this condition?
This is a pseuodoautosomal dominant genetic condition which results in dwarfism
Mutation occurs in the SHOX gene found in the pseuodoautosomal region of PAR1 in the X and Y chromosomes
Features of this condition are:
- mesomelic limb shortening
- reduced subiscial length
- madelung deformity of the forearm
What is Madelung deformity? What is commonly seen on an x-ray showing Madelung deformity?
Features:
- Bowing of the radius
- dorsal dislocation/displacement of the ulna
- premature epiphyseal fusion
X-ray:
- show a v-shape between the ulna and radius
What does SHOX stand for?
Short stature homeobox
What is haploinsufficiency?
a mechanism of action to explain a pathological phenotype in which a diploid organism has lost one copy of a gene and is left with a single functional copy of that gene
What is the most common karyotype of Turner’s syndrome? What are the common clinical features?
45,X0
Clinical features:
- webbed neck
- shielded chest, widely spaced nipples
- cubitus valgus
- lymphoedema of hands
- shortening of 4th/5th metacarpal
- knock knees
Main features = short stature + gonadal dysgenesis
Give other examples of common syndromic short stature conditions and list some common features of each.
William’s syndrome:
- narrow nose at top
- wide atypical features
- widely spaced teeth
Noonan’s syndrome: (looks similar to turners)
- webbed neck
- shielded chest
- low-set ears
Silver Russel syndrome:
- triangular face shape
- narrow chin
- difficulty feeding in infancy + lose weight
How often are GH pulses secreted?
every 3-4 hours
What is the effect of mutations in IGFBP3 and ALS?
IGF1 binds to IGFBP3 + ALS
if there are mutations then there will be an increase in the amount of bound IGF1
less free IGF1 will result in less growth as IGF1 is unable to bind to IGF1 receptors at target tissues and growth plates
What genes are associated with growth hormone deficiency?
GH1
GHRH
BTK
What is Laron syndrome? What are the key clinical features? How is it treated?
Autosomal recessive disorder that usually arises due to a mutant growth hormone receptor, which causes GH insensitivity and thus dwarfism
Key features:
- normal size at birth
- severe growth restriction in infancy
- distinctive facial features (underdeveloped, flattened)
- blue sclerae
- hypoglycaemia
Treatment:
IGF1
How would you interpret high IGF1, and low, normal, or high results for GH provocation tests?
High IGF1 = IGF1 resistance GH provocation test: low = GH deficiency normal = idiopathic short stature high = consider primary IGF1 deficiency or GH resistance
What treatment options are there to promote height?
GH - will achieve the greatest maximum height when given during puberty
Oxandrolone - will not increase target height, but will increase growth velocity
What conditions are indicated in somatotropin treatment?
GH deficiency SHOX deficiency SGA + subsequent growth failure (4 y/o or later) Chronic kidney disease Prader-Willi syndrome Turner's syndrome
What is a normal age range for the onset of puberty in both males and females?
Females: 8-13 y/o
Males: 9.5-14 y/o
What is precocious puberty?
Early onset puberty
centile 1-3, or >-2SD from the mean
What is part of the 1st-line evaluation in a child with delayed puberty?
Family history of delayed puberty
History of chronic disease, cryptorchidism , anosmia, anorexia, radio or chemotherapy
Groth rate, tanner stage, testis volume
Basal serum LH, FSH, IGF1, prolcatin + testosterone
