The critical parameters in GH excess.
Effective biochemical control of GH and IGF-I levels in subjects with acromegaly can reduce mortality to that of the general population. Post-treatment mean GH values <2 or 2.5 microg/l are associated with mortality which is not different from the general population. Virtually all evidence from epidemiological studies has related GH and not IGF-I values to long-term mortality; controversy remains regarding relative importance of GH and IGF-I values in determining post-treatment control status. Current approaches to management of acromegaly (surgery, radiotherapy, SRIF analogues) rely on post-treatment monitoring of GH and IGF-I levels. Development of GH receptor antagonist therapy, which inhibits GH activity and normalizes circulating IGF-I, GH levels remaining elevated, requires re-analysis of relationship between GH and IGF-I. Studies have reported that normalization of IGF-I is associated with normalization of SMR, a significant association of IGF-I with survival, that IGF-I is not an independent predictor of mortality, and, in the largest study (419 patients), that there is no increase in mortality in patients with raised serum IGF-I levels. Post-operative subjects with acromegaly, with normal IGF-I levels but persistently abnormal nadir GH levels after glucose, have an increased risk of disease recurrence. Discordant values for GH and IGF-I estimations may be seen in up to 30% of patients following treatment, without knowledge of the impact on morbidity and mortality of this discordance. An optimal level of both GH and IGF-I appears to be required to maintain normal health, emphasizing the need for a clearer understanding of relationship between these two parameters.
Sheppard
M C
MC
School of Medicine, University of Birmingham, Birmingham, UK. m.c.sheppard@bham.ac.uk
D000172:Acromegaly / Q000401:mortality* / Q000503:physiopathology* / Q000628:therapy; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans
D019382:Human Growth Hormone