The gold standard for making the diagnosis of GH excess relies on the inability to suppress serum GH to an appropriate level following an oral glucose load. While the OGTT has been the diagnostic test of choice for many years, numeric guidelines for the expected degree of suppression in a normal individual have steadily decreased. This trend is the direct result of newer assays with an improved threshold of sensitivity for detection (71). A normal response to a standardized glucose bolus (1.75 gm/kg up to 75 grams) utilizing the newer IRMA/ICMA assays is considered to be a GH level below 1 ng/ml (72). However, given the observation that biochemical recurrence of GH excess may be detected in patients with a GH nadir less than 1 ng/dl, and that healthy subjects nearly always suppress to below 0.14 ng/ml, some investigators have suggested that this cut-off is too liberal (73). Typically, the nadir in serum GH is expected to occur within the first 2 hours of the test. Along with a lack of suppression following oral glucose, individuals with GH hypersecretion characteristically exhibit a paradoxical response to other forms of hypothatlamic-pituitary stimulation testing. Occasionally, 24 hour integrated GH assessment may be helpful in cases in which an equivocal response to OGTT is seen (74). Depending on the individual circumstance, measurement of peripheral GHRH may also be indicated to investigate the possibility of ectopic GHRH secretion. Once biochemical evidence of GH excess has been demonstrated, MRI scanning of the H-P region is obviously the next step. Figure 5 illustrates the typical appearance of a GH-secreting pituitary macroadenoma in an adolescent with gigantism.
A potential pitfall in the evaluation of gigantism in adolescents is the fact that significant elevations of IGF-1 may be present during normal puberty (75). The effect of sex steroids on IGF-1 must also be taken into account when a diagnosis of gigantism is being considered in a child with concurrent precocious puberty, as may be the case in NF-1 or MAS. Adding to the possible diagnostic ambiguity is the fact that a significant percentage of normal tall adolescents fail to suppress serum GH in response to oral glucose testing (76). Therefore, both screening and definitive testing for GH excess should be performed in the context of clinical suspicion, and IGF-1 levels interpreted according to age and pubertal stage-adjusted normal ranges.