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Factors Influencing Mortality in Acromegaly

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J Clin Endocrinol Metab Holdaway et al. 89 (2): 667. (243K)

Factors Influencing Mortality in Acromegaly

Ian M. Holdaway, Raja C. Rajasoorya and Greg D. Gamble Department of Endocrinology, Auckland Hospital (I.M.H.), and Department of Medicine, Auckland University School of Medicine (G.D.G.), Auckland 1, New Zealand; and Department of Medicine, Alexandra Hospital (R.C.R.), Singapore 159964 Address all correspondence and requests for reprints to: Prof. Ian M. Holdaway, Department of Endocrinology, Auckland Hospital, Auckland 1, New Zealand. E-mail: Dit e-mailadres wordt beveiligd tegen spambots. JavaScript dient ingeschakeld te zijn om het te bekijken. Dit e-mailadres is beschermd tegen spambots. U heeft JavaScript nodig om het te kunnen zien. . Studies of acromegaly have shown a doubling of mortality comparedwith the general population. With the development of new modalitiesof treatment, it has become important to identify prognosticfactors relating to mortality. Between 1964 and 2000, 208 acromegalicpatients were followed for a mean of 13 yr at Auckland Hospital.Treatment was by surgery or radionuclide pituitary implantation,and all except 27 patients received pituitary radiation. Overthe duration of the study, 72 patients died at a mean age of61 ± 12.8 yr. Those dying were significantly older atdiagnosis, had a higher prevalence of hypertension and diabetes,and were more likely to have hypopituitarism. The observed toexpected mortality ratio (O/E ratio) fell from 2.6 (95% confidenceinterval, 1.9–3.6) in those with last follow-up GH greaterthan 5 µg/liter to 2.5 (1.6–3.8), 1.6 (0.9–3),and 1.1 (0.5–2.1) for those with GH less than 5, lessthan 2, and less than 1 µg/liter, respectively (P <0.001). Serum IGF-I, expressed as an SD score, was significantlyassociated with mortality, with O/E mortality ratios of 3.5(95% confidence interval, 2.8–4.2) for those with an SDscore greater than 2, 1.6 (0.6–2.6) for those with anSD score less than 2 (normal or low levels), and 1.0 (0.1–3)for those with an SD score less than zero. When assessed bymultivariate analysis, last serum GH (P < 0.001), age, durationof symptoms before diagnosis (P < 0.03), and hypertension(P < 0.04) were independent predictors of survival. If IGF-Iwas substituted for GH, then survival was independently relatedto last IGF-I SD score (P < 0.02), indicating that GH andIGF-I act equivalently as predictors of mortality. These findingsindicate that reduction of GH to less than 1 µg/literor normalization of serum IGF-I reduces mortality to expectedlevels.This work was supported by a grant from the Ministry of Health,Government of Singapore (to C.R.), and the Grace Ballas TravelingFellowship (to C.R.).Abbreviation: O/E ratio, Observed to expected mortality ratio.