Endocrine.scot.nhs.uk

SPEG Dynamic Function Test Handbook – 2012 Edition 4. GROWTH HORMONE STIMULATION TESTS

Indication

Assessment of growth hormone deficiency
These tests are often combined with the LHRH test; the volume of blood collected will need
to be increased accordingly.

The insulin hypoglycaemia test (also known as the insulin tolerance test, ITT) is recognised
as the “gold standard” for assessment of growth hormone deficiency, particularly as it also
tests the hypothalamo-pituitary-adrenal axis. This is a potentially high risk test and should
only be carried out in a specialist centre where the test is being performed on a
regular basis by experienced staff.

Where the ITT is not recommended or not suitable the first line test should be the Arginine
test.

The clonidine test is also an acceptable test for growth hormone.
Other Tests:
The Glucagon test and Exercise test for assessment of growth hormone deficiency are
not recommended, due to problems with late hypoglycaemia and poor reproducibility of
results, respectively. ‘Priming’ before the test If the test is to be done on peri-pubertal children (bone age greater than 10 years, no signs of puberty in girls or testicular volume less than 8mL in boys), discuss with local paediatric endocrinologist the advisability of “priming” with the appropriate sex steroid. SPEG Dynamic Function Test Handbook – 2012 Edition 4.1 INSULIN TOLERANCE TEST

Indications
Any form of stress results in secretion of the hypothalamic hormones, growth hormone
releasing hormone (GHRH) and corticotrophin releasing hormone (CRH). These in turn
stimulate the release of pituitary growth hormone (GH) and adrenocorticotrophic hormone
(ACTH), in the latter case leading to adrenal cortisol secretion. Insulin administration is
used to produce stress in the form of hypoglycaemia, and hypothalamic - pituitary -
adrenal function is assessed by GH and cortisol responses to the hypoglycaemic stimulus.
This test is designed to produce symptomatic hypoglycaemia (palor, sweating). If
symptoms are more severe (impaired or loss of consciousness) the child must be treated
immediately (see below). Continuous observation for the symptoms of severe
hypoglycaemia is essential throughout the test, and for half an hour after its completion.
Contraindications

No child with a history of epilepsy or cardiac arrhythmias should undergo this test
Please use with caution in young children, as symptoms of hypoglycaemia may be difficult
to detect.

Preparation
•
The patient should be fasted overnight (4 hours for infants); drinks of water are allowed. Before beginning the test, have available glucose drink: 4 heaped teaspoons (equivalent to approximately 40g) dextrose powder dissolved in approximately half a glass of squash. Alternatively standard glucose drink e.g. Lucozade 50mls. Ensure that glucose, and hydrocortisone are also available for intravenous injection, if necessary (see emergency treatment of severe hypoglycaemia, below). Observe the child continuously during the test for symptoms of severe hypoglycaemia, and check the glucose concentration in each blood sample collected using the ward blood glucose meter or more frequently if the child is developing hypoglycaemic If symptoms of severe hypoglycaemia do develop they must be treated immediately. See below. Before beginning the test, weigh the patient and insert a cannula at least 30 minutes before taking the baseline samples. The patient should be resting throughout the test. Start the test between 0800h and 0900h. SPEG Dynamic Function Test Handbook – 2012 Edition Emergency treatment of severe hypoglycaemia during the ITT
If the child does not tolerate oral glucose, or shows signs of severe hypoglycaemia
(reduced conscious level) give iv treatment by giving intravenous glucose 200 mg per kg body weight (10% dextrose, 2mL per kg) over 3 minutes. If the response is poor, give 100 mg hydrocortisone by intravenous injection. Continue with a glucose infusion iv at 10 mg per kg per minute (6 millilitres per kilogram per hour of 10% dextrose). Check blood glucose using the ward meter after 5 min and adjust the glucose infusion to maintain a blood glucose of 5-8 mmol/L and no higher. If there is no improvement in conscious level after normal blood glucose is restored, an alternative explanation should be sought. It is not necessary to discontinue the test and, if possible, continue blood sampling.
IMPORTANT
50% dextrose should NEVER be used in the resuscitation of a child with severe
hypoglycaemia following an endocrine test.
SPEG Dynamic Function Test Handbook – 2012 Edition
Procedure
-30 min TAKE Blood for glucose, cortisol and GH determinations. (+ ward meter TAKE baseline blood sample for glucose, cortisol and GH. (+ ward meter glucose) If blood glucose, measured using the ward meter, is less than 3.5 mmol/L in either of the two baseline samples, do NOT give insulin but continue to take blood samples (see below) and record whether child has symptoms (pale, sweating). If blood glucose, measured using the ward meter, is between 3.5 and 4.5 mmol/L in either of the two baseline samples, give half the dose of insulin (see below) and continue the test. GIVE IV soluble insulin (Actrapid) diluted with normal saline to give a solution containing 1 unit per ml. Dose = 0.1 units per kg body weight (Reduced to 0.05 units per kg in patients who might be unduly sensitive to insulin. These include patients with suspected hypofunction, those with severe malnutrition (e.g. due to anorexia nervosa) or those with baseline blood glucose between 3.5 and 4.5 mmol/L) When adequate hypoglycaemia has been established (< 2.2 mmol/L laboratory blood glucose or a 50% reduction in the baseline level), or if the child shows signs of hypoglycaemia (e.g. is sweaty and drowsy), a glucose drink should be given - see preparation notes above. If this is not tolerated, or if there are more severe symptoms of hypoglycaemia
(impaired or loss of consciousness), intravenous glucose may be required
– see above.
NOTE ward meters frequently overestimate blood glucose levels.
6 15 min TAKE blood samples for glucose, cortisol and GH (+ ward meter glucose) 7 30 min TAKE blood samples for glucose, cortisol and GH (+ ward meter glucose) 8 60 min TAKE blood samples for glucose, cortisol and GH (+ ward meter glucose) 9 90 min TAKE blood samples for glucose, cortisol and GH (+ ward meter glucose)
After the test
Give a sweet drink and a meal after the test and ensure that the meal has been eaten.
Keep the child under observation for at least 1 hour after the meal has been consumed.
Keep the cannula in position until lunch has been assimilated. Ensure that a blood glucose measured on the ward meter reads greater than 4 mmol/L before discharge. If there is any doubt about the child's wellbeing, keep him/her in overnight for observation. SPEG Dynamic Function Test Handbook – 2012 Edition Interpretation
If Growth Hormone >5ug/l at any point this indicates there is a normal response, which
rules out growth hormone deficiency. If Growth Hormone <5ug/l in the presence of adequate hypoglycaemia (<2.2mmol/l or 50% drop in plasma glucose < 5ug/L indicates a growth hormone deficiency. Hypoglycaemia of this magnitude should also cause an increase in the plasma cortisol. Please check with local labs for cut offs. SPEG Dynamic Function Test Handbook – 2012 Edition 4.2 ARGININE STIMULATION TEST FOR GROWTH HORMONE

Indications
Short stature and/or consistent abnormally low growth velocity.
Growth hormone deficiency

Preparation
Patient to have water only for 8 hours prior to the test.
Arginine may cause nausea and some irritation at the infusion site.

Procedure

INSERT a reliable cannula, TAKE blood for growth hormone – baseline test. INFUSE arginine monohydrochloride IV over half an hour in a dose of 0.5g/kg up to a maximum of 30g (discuss with local pharmacist) TAKE samples for growth hormone and glucose
Samples
In children with suspected hypopituitarism prolonged fasting may induce hypoglycaemia.
Blood glucose should be checked by ward meter with each sample in these patients
whenever a sample is taken.
Note
This test can be combined with synacthen test to assess HPA axis in addition to growth
hormone deficiency
Interpretation
If the plasma GH concentration reaches 6 ug/L or more, further investigations are not
indicated. If the response is below this level, then an insulin hypoglycaemia test may be
SPEG Dynamic Function Test Handbook – 2012 Edition 4.3 CLONIDINE TEST FOR GROWTH HORMONE

Indication
This test is used in the investigation of suspected Growth Hormone (GH) deficiency in
childhood (not in adults). Clonidine is administered orally to provoke GH release.
Preparation
Fast the patient overnight (4h for infants), and measure height and weight.
Calculate surface area from appropriate tables.
Start the test by 0900h whenever possible.

Procedure
INSERT reliable canula TAKE blood sample for GH GIVE Clonidine (150 micrograms per m2 body surface area) by mouth with a small, sugar-free drink. Round up the calculated dose to the nearest 25 micrograms. (after completion)
After the test
Side effects of Clonidine (hypotension and drowsiness) may persist for several hours after
the test. Keep the patient lying down for at least an hour after the test, and check pulse
and blood pressure half-hourly and also before allowing him/her to get up. Careful
observation of the patient is necessary until late afternoon.
Interpretation
If the plasma GH concentration reaches 6 ug/L or more, further investigations are not
indicated. If the response is below this level, then an insulin hypoglycaemia test may be

Source: http://www.endocrine.scot.nhs.uk/Protocols/DFT%20-%20Growth%20Hormone%20Stimulation%20Test.pdf