Endocrine Causes of Short Stature ✅ Flashcards
What are the endocrine causes of growth failure?
- GH deficiency
- Hypothyroidism
- Cushing’s syndrome
What is growth hormone deficiency characterised by?
- Growth failure
- Delayed skeletal maturation and puberty
- Increased body fat
- Micropenis
- Hypoglycaemia in infancy
When does GH deficiency cause hypoglycaemia in infancy?
When severe
What features may be present when GH deficiency is caused by hypopituitarism?
- Signs of TSH, ACTH, and gonadotrophin deficiencies
- Midline craniofacial skeletal abnormalities
- Optic atrophy and visual impairment
- Signs of raised ICP
- Bitemporal hemianopia
What does optic atrophy and visual impairment alongside GH deficiency suggest?
Septo-opticd dysplasia
What does bitemporal hemianopia alongside GH deficiency suggest?
Pituitary tumour compressing optic chiasm
What does a family history of other similarly affected individuals in GH deficiency suggest?
A mutation in GHRH or GH-1 gene, or genes that encode transcription factors involved in pituitary development
When is investigation for possible GH deficiency indicated?
Once baseline investigations for non-GH-related causes of short stature have been performed and found to be normal
What are the options for measuring GH levels?
- Random blood sample measuring
- Monitoring blood samples every 20 minutes to produce a 24 hour GH secretory profile
- Stimulatory tests
Why is using random blood samples to measure GH levels generally unhelpful?
GH is secreted in a pulsatile fashion, so levels are low throughout most of a 24 hour period
What are the options for measuring GH levels?
- Random blood sample measuring
- Monitoring blood samples every 20 minutes to produce a 24 hour GH secretory profile
- Stimulatory tests
What are the options for measuring GH levels?
- Random blood sample measuring
- Monitoring blood samples every 20 minutes to produce a 24 hour GH secretory profile
- Stimulatory tests
What is the limitation of measuring blood samples every 20 minutes to produce a 24 hour GH secretory profile?
It is challenging to organise and interpret
What is the most clinically useful way to diagnose GH deficiency?
Stimulatory tests of GH secretion
What is the gold standard GH stimulation test?
Insulin-induced hypoglycaemia
What effect does insulin-induced hypoglycaemia have on GH?
It promotes a counter-regularity GH secretory response
Other than GH levels, what does insulin-induced hypoglycaemia allow the measurement of?
ADTH-induced cortisol response
What is the limitation of insulin-induced hypoglycaemia to test for GH?
It is potentially dangerous, and should only be performed in children over 5 years old in units experienced in its use
What are the alternative options for stimulatory tests of GH secretion?
- Glucagon
- Clonidine
- Arginine
- GNRH
What does glucagon stimulate?
Secretion of GH and cortisol
What does clonidine stimulate?
Secretion of GH alone
What does arginine stimulate?
Secretion of GH alone
What does GNRH stimulate?
The pituitary directly
What is the limitation of a GNRH stimulation test?
It is poor at distinguishing hypothalamic forms of GH deficiency from a normal short child
What is the implication of the limitations of a GNRH stimulation test?
It is rarely used in childhood testing
What is a high peak GH response defined as in stimulatory testing?
Over 8.5ng/dL
What does a high peak GH response mean in stimulatory testing?
Excludes a diagnosis of GH deficiency
What is defined as intermediate GH response in stimulatory testing?
5-8.3ng/dL
What does an intermediate GH response to stimulatory testing suggest?
Suggests GH insufficiency if growth pattern is consistent with this diagnosis
What is defined as low GH response in stimulatory testing?
<5ng/dL
What does a low GH response to stimulatory testing suggest?
Severe forms of GH deficiency
What is required to make a diagnosis of GH deficiency?
2 abnormal responses to GH testing, or 1 abnormal response with radiological evidence of intracranial abnormalities consistent with the diagnosis
Why are 2 abnormal responses to GH testing required to make a diagnosis of deficiency in the UK?
Due to limited sensitivity and specificity of tests to diagnose GH deficiency
What investigation should be done if a diagnosis of GH deficiency is made?
An MRI scan
Why should an MRI be done if a diagnosis of GH deficiency is made?
To exclude an underlying tumour
What tests should be considered when a diagnosis of GH deficiency is made?
Testing for wider pituitary dysfunction
What should be obtained prior to treating GH deficiency?
Accurate growth data, preferably over a 1 year period
Why is accurate growth data required prior to starting GH deficiency treatment?
To allow the benefits of GH treatment to be assessed
How is synthetic GH produced?
Using recombinant DNA technology
How is GH therapy administered?
Daily SC injection
How should the growth response to GH therapy be evaluated?
Measurements every 4-6 months
What is the level of response to GH therapy related to?
- Severity of deficiency
- Pre-treatment height velocity
- Age
- Difference in child’s height from parent’s height
- Birth weight
- Current weight
- Dose of GH
What can be done by taking into account factors that affect the effectiveness of GH therapy?
Predict the response to GH and ‘personalise’ the dose of GH
What is the advantage of personalising the dose of GH?
Ensure maximal and cost-effective response
When does the maximal growth response to GH therapy occur?
In the first year
What happens to the effectiveness of GH after the first year?
Tachyphylaxis
What does tachyphylaxis mean?
The appearance of progressive decrease in response to a given dose after repetitive administration of a pharmacologically or physiologically active substance
What causes tachyphylaxis of GH therapy after the first year?
Down-regulation of the GH receptor
What is indicative of a successful response to GH therapy?
An increase in height-velocity of at least 2cm/year
What should be done if there is a less than 2cm/year increase in growth velocity with GH therapy?
- Consider adherence
- Consider if wrong diagnosis
- Consider discontinuation of therapy
What should be done with GH therapy once growth is complete after puberty?
GH testing should be repeated
Why should GH testing be repeated once growth is complete at the end of puberty?
Mild forms of GH deficiency do not require ongoing therapy into adult life
Why do milder forms of GH deficiency not require ongoing therapy into adult life?
During adult life lower levels of GH are required
What is GH required for in adult life?
- Maintenance of normal body composition
- Bone health
- Avoidance of cardiovascular risk factors
What monitoring is required during GH therapy?
Ongoing monitoring for wider defects in pituitary function
When is GH therapy ineffective?
In the very rare circumstance of GH resistance
What is used to treat GH resistance?
Recombinant IGF-1
Does congenital or acquired hypothyroidism cause growth failure?
Both
Why does hypothyroidism cause growth failure?
- Suppresses GH secretion
- Growth and anabolic effects of GH and IGF-1 are downregualted
Why are the growth and anabolic effects of GH and IGF-1 downregulated in hypothyroidism?
Due to the absence of thyroid hormone action through its receptor sites
How can the growth failure caused by hypothyroidism be reversed?
Thyroxine treatmnt
How does Cushing’s syndrome cause growth failure?
Excess cortisol levels directly suppress GH secretion and action, and delay onset of puberty
