Endocrine disorders of development and growth Flashcards
when do individuals need further assessment of growth
Where weight or height or BMI is below the 0.4th centile, unless already fully investigated at an earlier age.
If the height centile is more than 3 centile spaces below the mid-parental centile.
A drop in height centile position of more than 2 centile spaces, as long as measurement error has been excluded.
why is monitoring heigh and weight important
Monitoring height and weight is useful to identify disorders affecting growth
what are the requirements for normal human growth
- Absence of chronic disease
- Emotional stability, secure family environment.
- Adequate nutrition
- Normal hormone/growth factor actions
- Healthy growth plates.
what 4 aspects to you use to evaluate short stature
- heigh centile versus weight centile
- when it started
- body proportions
- presenting signs
describe the 4 aspects that you use to evaluate short stature
- Height centile vs weight centile.
• Failure to thrive vs failure to grow.
2. When started. • In utero • In infancy • In childhood • In puberty
- Body proportions.
• Primary or secondary growth disorder - Presenting signs.
• Idiopathic
what are the phases of growth in the ICP model and what causes the growth
Infancy: rapid growth (nutritionally determined, up to two years).
Childhood: relatively steady (primarily regulated by GH and T4).
Puberty: acceleration and then cessation (GH, sex steroids, T4).
How do you calculate height velocity
- Serial height
- Plotted over time
what is a primary growth disorder
Primary growth disorders include clinically-defined syndromes such as Turner’s and Cornelia de Lange, children who are small for gestational age (SGA) with failure to catch up, and skeletal dysplasias.
what is a secondary growth disorder
A secondary growth disorder is a condition where there is an identifiable cause. Examples include: Disease e.g. disorder of the pituitary gland. Hormonal issues e.g. growth hormone deficiency.
What an cause disproportionate growth
Skeletal dysplasia
- achondroplasia
- hydrochondroplasia
- leri-welli dyschonrosteosis
rickets - caused by Vitamin D deficiency
List three types of skeletal dysplasia
- achondroplasia
- hydrochondroplasia
- leri-welli dyschonrosteosis
how do you know the body portions are disproportions
- calculate Standard deviation difference
Subiscial length SDS
LESS
Sitting height SDS
Followed by skeletal survey: Skull Spine Pelvis Upper limb Lower limb
what is the equation for the standard deviation score
SD = measurement - mean / SD at relevant age
What are the three classification of limb shortening
- rhizomelic
- mesmeric
- acromelic
what mutation causes achondroplasia
FGFR3 Mutations
= autosomal dominant
what does achondroplasia do
- Inhibits ossification at growth plates
- Lack of long bone elongation
what is the mutation in hypochondroplasia
Also caused by mutations in FGFR3 other than the 1138 position.
describe characteristics of hypochondroplasia
Affects structure and function of receptor
Features milder than achondroplasia:
- Short stature noticed later
describe the genetics of leri-weill dyschondrosteosis
- it is an autosomal dominant skeletal dysplasia
describe the characteristics of leri-weille dyschondrosteosis
Mesomelic (mid parts) limb shortening
Reduced subischial length
Madelung deformity of the forearm
- Bowing of the radius
- Dorsal dislocation of the ulna
- Premature epiphyseal fusion
what does madeulung deformity consist of
- Bowing of the radius
- Dorsal dislocation of the ulna
- Premature epiphyseal fusion
who has madeulung deformities
Present in
50-74% of LWD
3-7% of Turners
1-3% of Idiopathic Short Stature
what is the most important cause of short stature in humans
SHOX Haploinsufficiency/Phenotypes
• Most important monogenic cause of short stature in humans.
o Found in 1:1000.
• Wide range: idiopathic short stature and LWD.
what can cause propionate growth failure
- psychosocial assessment = psychical growth retardation
- Syndrome features karyotypes = such as turners syndrome, Noonan, Williams
- tests for systemic disorders = such as chronic renal insufficiency, gastrointestinal disease, nutritional deficiency
test for endocrine disorder s= hypothyroidism and hypercortisolism
what is missing in the turners syndrome
• Missing whole/part of X syndrome.
what do people with Turner syndrome benefit from
- benefit from growth hormone but early diagnosis is key
why do all short stature girls need karyotype analysis
- to scan for Turner syndrome so they can be given growth hormone
what are the phenotypes of turner syndrome
- short stature due to SHOX haplo-insufficiency
- webbed neck
- shield chest, widely spaced nipples
- cubitus valgus
- lymphedema of the hands
- shortening of 4th/5th metacarpal
- knocked knees
- gonadal dysgensis
how should you manage someone with syndromic short stature
Be familiar with genetic syndromes that cause short stature
Diagnosis is based on clinical findings and dysmorpic features
Refer to geneticist if necessay
Genetic testis may help especially in atypical cases
How do you test for endocrine disorder s
Complete blood count ESR sodium, potassium, chloride, bicarbonate calcium, phosphate, alkaline phosphatase Blood urea nitrogen, creatinine insulin-like growth factor-1 insulin-like growth factor binding protein-3 (<3 years only), immunoglobulin A (IgA), tissue transglutaminase TSH, FT4 karyotype (female only)
what specific tests can you use for endocrine disorders in terms of the IGF system
IGF-1
GH stimulation test
MRI scan
- These look for GH insensitivity/resistance
- GH deficiency
- if we do these tests and find nothing then idiopathic short stature is defined as the condition
what is growth hormone stimulated by and inhibited by
GNRH is stimulatory
Somatomstatin is inhibit r
-
what causes the pulses of growth hormone
somatostatin
when are growth hormone pulses secreted
every 3-4 hours
what is the main regulatory of growth in childhood
growth hormone
What is the function of growth hormone
• Main regulator of growth in childhood.
o Systemic effects in through the liver.
o Direct effect on growth plates.
what can cause growth hormone deficiency
Can be isolated or part of panhypopituitarism.
Acquired causes include – Trauma, Irradiation, Tumours
Associated genes: GH1 , GHRHR , BTK .
what is an example of Growth hormone insensitivity
Larons syndrome
What are the key features of Larons syndrome
Normal size at birth Severe growth restriction in infancy Distinctive facial features Blue sclerae Hypoglycaemia (Insulin sensitivity
How do you manage idiopathic short stature
• Administration of GH
• Oxandrolone - anabolic steroid used for a long time and extradites growth but doesn’t increase adult height
o Very little change in most cases.
who does NICE recommend be given somatostatin as treatment
Have growth hormone deficiency.
Have Turner syndrome.
Have Prader-Willi syndrome.
Have chronic kidney disease.
Are born small for gestational age with subsequent growth failure at 4 years of age or later.
Have short stature homeobox-containing gene (SHOX) deficiency
when does puberty happen in girls
In girls between 8-13 years
when does puberty happen in boys
In boys between 9.5-14 years
in girls what is the first marker of puberty
- breast budding
what is precocious puberty
before age 8/9.5.
what is delayed puberty
after age of 13/14
first sign of puberty in boys is
testes volume increasing
how do you investigate delayed puberty
Family history of delayed puberty ! - usually autosomal dominant
History of chronic disease, cryptorchidism, anosmia, anorexia, radio- or chemotherapy
Growth rate, Tanner stage, testis volume
Tests: Biochemistry, Bone Age x-ray,
Basal serum LH, FSH, IGF-I, (prolactin) and testosterone (in boys)
what can breast development be activated without
In girls Tanner stage B2 is usually the first physical marker of puberty, but may be present without central activation of the HPG-axis
what does testicular volume increase indicate
Testicular volume of > 3 cc (≥ 2.5 cm in length) indicates central puberty.
- Most healthy boys with a testicular volume >3 cc or greater will have a further increase in testicular volume when re-examined 6 months later.
what happen if there is high FSH after 13 years in girls or 14 years in boys
means you have primary hypogonadism
- then you should test karyotype for example for turner syndrome
- serum inhibit B in boys should be tested
what happens if you have low or normal serum LH and FSH for early tanner stages
- have normal growth rate for bone age
- then check GnRH deficiency or CDGP
- Then you would test GnRH, hCG stimulation test, serum inhibinB, olfactory function test, genetic testing
slow growth rate for bone age
- function hypogonadotropic hypogonadism
- low BMI - GI disorder underfeeding
- Normal BMI - hypothyreosis, hyper-PRL GHD
- High BMI - iatrogenic (Corticoids)
- then examine further for chronic disease and consider GH provocation tests
