Assessment of GH status in adults with GH deficiency using serum growth hormone, serum insulin-like growth factor-I and urinary growth hormone excretion.

Abstract

The benefits of treating adults with GH deficiency are now well recognized although the criteria for deciding which patients to treat are still not clear. At present the 'gold standard' is the insulin stress test (IST) which is unpleasant and potentially dangerous, particularly in patients with hypopituitarism. The aim of this study was to determine whether alternative methods of assessing GH status are reliable in predicting GH deficiency. Forty-four patients with unequivocal GH deficiency (peak IST < 2 mU/l) and 17 with partial deficiency (peak IST 2-10 mU/l) were studied. Each patient was assessed clinically with respect to the number of other pituitary axes affected and biochemically with an estimate of urinary GH excretion (uGH) and serum IGF-I. These markers were then related to GH status as defined by insulin stress testing. Insulin stress tests were performed using 0.1 units/kg i.v. and accepted with a blood glucose < 2 mmol/l. Serum GH and IGF-I were measured by radioimmunoassay whilst uGH was estimated by an immunoradiometric assay using commercially available reagents. uGH was estimated from the mean of two overnight urine collections which consisted of all urine passed from last voiding through to the first morning sample. The presence of unequivocal GH deficiency (peak IST < 2 mU/l) was predictable if 2 or more other pituitary axes were affected (90%). uGH declined significantly with the level of peak IST response (P < 0.001) and almost so with the number of other deficient hypothalamic-pituitary axes affected (P = 0.057). Thus, uGH accurately reflected GH status and showed good separation from normal controls in patients less than 40 years (specificity 79%) and between 40 and 60 years (specificity 67%). Above this age the method is less specific (36%). Patients excreted significantly less GH than controls in all three age groups (P < 0.01). Subnormal levels of IGF-I were strongly predictive of unequivocal GH deficiency (91% with subnormal IGF-I have a peak IST GH < 2 mU/l) although a normal value does not reliably exclude the diagnosis. A diagnosis of adult GH deficiency can be reliably made without the need for an insulin stress test by using a combination of low urinary GH excretion, subnormal IGF-I levels and clinical assessment with regard to the number of other pituitary axes affected.