Download GROWTH HORMONE DEFICIENCY

Brig Waqar Azim
MBBS, MCPS, Dip Family
Medicine,
FCPS, OJT Endocrinology
Prof & HOD Pathology CMH
Lahore
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Short stature
Small for age.
Reduce bone age.
Pituitary & Hypothalamic disease
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Clinical features include
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alterations in body composition
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reduced lean body mass & bone mineral density
increase in fat mass, particularly abdominal
dry skin with reduced sweating
reduced muscle strength & exercise performance
impaired sense of well-being and other
psychological complaints
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Stunted growth in children
Those with evidence of hypothalamic or
pituitary disease or cranial irradiation
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likelihood of deficiency increases with number of
pituitary hormone deficits
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approaches 100% if 3-4 pituitary hormone deficits
exist
Childhood-onset growth hormone deficiency
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all patients should be re-tested as adults before
continuing treatment with GH
Assessment
suspected GH deficiency after clinical and
radiological assessment
◦ Detailed history and thorough physical
examination
◦ Exact chronological age of the child
◦ Determination of percentile of height and
weight according to the standard height and
weight chart
◦ Parental height and weight
◦ bone age of the patient - x- ray of the non
dominant wrist
Assessment
suspected GH deficiency after clinical and
radiological assessment
◦ Detailed history and thorough physical
examination
◦ Exact chronological age of the child
◦ Determination of percentile of height and
weight according to the standard height and
weight chart
◦ Parental height and weight
◦ bone age of the patient - x- ray of the non
dominant wrist
Stimulation test:
GH stimulation includes
◦ Exercise stimulation test
◦ L-Dopa stimulation test
◦ Clonidine stimulation test
◦Insulin stress test
◦ Arginine stimulation test
◦ Sleep Test
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Dynamic tests of GH secretion
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patients should be on stable & adequate
replacement of other hormonal deficits before
testing
the insulin tolerance test is the diagnostic test of
choice
providing adequate hypoglycaemia is achieved, this
test distinguishes GH deficiency from the reduced
GH secretion with ageing & obesity
Diagnosis of GH related Growth Failure
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For establishing GH deficiency
◦ Two provocative tests (GH levels < 10 mIU/L)
Partial GH deficiency
◦ Borderline response between 10- 20 mIU/L in one or two
provocative tests
Rule Out other Causes of Dwarfism
◦ Chromosomal analysis
◦ X-Ray skull
◦ Thyroid function tests.
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Should be performed in experienced
endocrine units where the test is performed
frequently
Contraindicated in those with ECG evidence
of ischaemic heart disease and in those with
seizure disorders
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in these people, alternative tests should be used
Principle
Hypoglycaemia induced by IV insulin is a potent
stimules
for GH secretion.
Procedure
Basal Growth hormone levels
IV insulin (0.15 U/kg) is given
Hypoglycaemia 2.2 mmol/L should ge obtained.
GH levels are measured at 30, 60, 90 &180 min
Interpertation
> 20mIU/L means adequate stimulation
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EXERCISE STIMULATION TEST
Principle:
Strenuous physical exercise causes GH secretion in normal
subjects
Preparation:
◦ Fasting over night
◦ Early in the morning (0800 hours)
Procedure:
Basal blood specimen for GH
Rigorous exercise on a tread mill for 15-20 minutes
Pulse is monitored during the test
Blood specimen taken 10 minutes after the cessation of exercise
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L- DOPA STIMULATION TEST
Principle
L- Dopa stimulates growth hormone (GH) secretion from the anterior pituitary
gland measurements of which (GH) serve as a test of anterior pituitary function
Preparation
Overnight fast
At 0800 hrs
Procedure
Basal sample for GH
L- Dopa is administered orally preferably with food and milk
Patient > 30 Kg: 500 mg
Patient between 15 - 30 Kg: 250 mg
Patient < 15 Kg: 125 mg
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Sampling
5 ml venous blood is collected at 0 (basal)
60 minutes after L- Dopa administration
Interpretation
GH level > 20 mIU/L Normal response
GH level between 10 - 20 mIU/L -suggestive of
partial GH deficiency
GH levels < 10 mIU/L - GH deficiency
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Arginine Test
Prepration
NPO atleast 8 hrs prior to the test
Procedure
1. Base line serum GH and somatomedin-C levels
2. Inject 0.5 g/kg (maximum 30 g) arginine over
30 min IV
3. Serum GH levels at 30,60,90, 120 mins
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Glucagon stimulation test
Indications
Particularly useful when insulin induced hypoglycaemia is
contraindicated.
Contraindication
Hypothyroidism
Marked adrenal failure
Diabetes millitus
Principle
Glucagon stimulates release of GH and ACTH by
Hypothalamic stimulation and therefore indirectly
stimulates cortisol.
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GHRH -ARGININE STIMULATION TEST
Indication
To confirm persistence of childhood GH deficiency in early
adulthood if ITT is contraindicated, pt is over weight or has DM.
Procedure
Baseline GH and IGF-1 level
Inject GHRH 1meg/kg (maximum dose 100 meg) as bolus.
Infuse 0.5 g/kg arginine as a 10% solution in normal saline over
30 min.
Take sample for GH (but not for IGF-1) at 30,60,90, 120 & 150 min
after start of arginine infusion.
Monitor pule and blood pressure every 15 min
Interpertaion
GH level > 20 mU/L
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Sleep Test
Take advantage of known rise in GH conc. occuring with deep
sleep.
Sample is obtained 60 – 90 mins after on set of sleep.
Patient must be in the hospital or a clinical research centre for
testing.
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Interpertation:
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GH ≥ 15 mU/L ---- normal
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One test in reconfirmation of childhoodonset GHD
One test only in adults with hypothalamic or
pituitary disease and one or more pituitary
hormonal deficits
Two test in adults with isolated GHD
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B.Biochemical Markers of GH Action
Serum IGF-I
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only of value with age-adjusted normal ranges
a normal serum IGF-I does not exclude GHD
a serum IGF-I below the normal range is suggestive
of GHD (in absence of confounding conditions e.g.
malnutrition, liver disease, hypothyroidism)
of greater value in presence of 2 or more hormonal
deficiencies
B. TREATMENT of GROWTH
HORMONE DEFICIENCY in ADULTS
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Patients who should be treated:
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all patients with documented severe growth
hormone deficiency
Goal of therapy:
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to correct abnormalities associated with severe
growth hormone deficiency
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Objective:
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To maximise benefit and minimise side effects
In practice, optimum dose varies greatly
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sensitivity increase with age
men more sensitive than women
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Start with a low dose
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Monitor response carefully
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0.15 - 0.30 mg / day (0.45 - 0.90 U / day)
subcutaneously at bedtime
clinically and biochemically
Increase dose slowly
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no more frequently than at monthly intervals
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Women aged 30 - 50 secrete on average 0.2
mg / day and men 0.1 mg / day
Sensitivity varies considerably between
patients and probably between the sexes
The daily dose rarely exceeds 1 mg (3 U)
Doses used now are lower than previously
and are no longer based on body weight or
surface area
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Good clinical practice requires regular
imaging of any residual pituitary disease
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GH replacement does not impose any need to
intensify this
A baseline MRI or CT scan is to be
recommended before GH replacement is
started
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Growth hormone stimulation tests should
confirm GH deficiency
Those receiving GH replacement should
remain under supervision of an
endocrinologist specialising in pituitary
disorders
Monthly GH monitoring initially but once
stabilised can usually be reduced to one or
two times a year