GHRH-Arginine stimulation test

INDICATION

Used to confirm GH deficiency:

1. In transition, after achievement of final height, to confirm persistence of childhood GH deficiency in late adolescence/early adulthood if insulin tolerance test is contraindicated or patient is overweight or has diabetes mellitus which may limit interpretation of insulin tolerance test or glucagon stimulation test.

2. In adults, if glucagon stimulation test or insulin tolerance test shows GH deficiency (peak GH <5 mcg/L), and 2nd confirmatory test is needed before commencing GH treatment, especially if overweight or ITT contraindicated such as after traumatic brain injury.

PREPARATION

Fasting overnight from midnight (except water)

Arrive by 9 am

At least 1 month off GH treatment if in transition.

7 red top Vacutainers

METHOD

1) Cannulate in both arms, and leave to rest for 45 minutes.

2) Take blood into a plain tube (red top Vacutainer) for baseline GH and IGF-1 measurement (-15 mins), and GH at 0 min.

3) Inject GHRH (Somatorelin, Ferring) 1mcg / kg (maximum dose 100 mcg) as bolus injection.

4) Infuse 0.5 g / kg L-arginine monohydrochloride (maximum dose 30 g) as a 10% solution (30 g / 300 mL) in normal saline over 30 min.

5) Take blood for further GH estimation in red top Vacutainer (but not IGF-1) at + 30, 60, 90, 120 and 150 min after start of arginine infusion.

6) Can eat lunch at +150 min after last blood test.

7) Stay in bed until +240 min.

8) Monitor pulse & BP every 15 min until +150 min, and every 30 min from +150 min to +240 min.

SIDE EFFECTS

Facial flushing is common after GHRH (most patients).

Paraesthesia, nausea, and abnormal taste sensation after GHRH (5–10%).

INTERPRETATION

In adults (>21y), GH deficiency depends on peak GH and BMI:

BMI <25 kg/m2

BMI 25-30 kg/m2

BMI > 30

Peak GH < 11 mcg/L

Peak GH < 8 mcg/L

Peak GH < 4 mcg/L

In transition (adolescence and young adults <21y), peak GH < 19mcg/L confirms GH deficiency if lean. If overweight or obese, cut-offs in transition are unknown and may be higher than in adults. However while using BMI cut-offs given above from adults may pass some patients with GH deficiency as normal, it should correctly identify transition patients who do have GH deficiency.

REFERENCES

Biller BMK et al. J Clin Endocrinol Metab 87: 2067–2079, 2002

Clayton PE et al. Eur J Endocrinol 152:165-70, 2005

Corneli G et al. Eur J Endo 153: 257–264, 2005

Ho KKY et al. Eur J Endo 157 695–700, 2007

Corneli G et al. Eur J Endo 157: 701-708, 2007

Gasco V et al. Eur J Endo 159:S45–S52, 2008