Background: In patients with acromegaly, mortality depends most on achievement of control of GH/IGF1 levels. However, some of the complications of acromegaly still develop, despite successful control of disease. The aim of the study is to correlate mortality and morbidity with cumulative GH exposure in these patients compared to last GH/IGF1 level.
Methods: We studied retrospectively 336 patients with acromegaly consecutively evaluated at least twice during January 2001June 2017. Cumulative GH exposure was calculated as a weighted arithmetic mean of GH during time. IGF1 levels were expressed as IGF1/age and sex upper limit of normal (ULN) ratio. A multivariable Cox regression was used to calculate hazard ratios (HR) for all-cause mortality/morbidity risk factors.
Results: There were 226F/110M patients with acromegaly, mean age 48.14±12.12 years. During follow up (9.43±4.67 years), 53 patients died, mean age at death was 66.06±10.88 years. Comorbidities were high blood pressure (HBP) (53.9%), cardiovascular diseases (14.4%), diabetes mellitus (27.4%), neoplasia (43.8%), colon polyps (6.8%), meningioma (1.5%). 49.1% of patients were cured after surgery/irradiation or controlled with medication. Patients who died were older at first visit (57.19±9.93 vs 46.45±11.75, P<0.001), had longer duration of GH hypersecretion exposure (15.43±10.80 vs 9.13±8.09 years, P=0.01), had at last evaluation higher blood pressure (131.86±18.62 vs 125.02±18.78 mmHg, P=0.003), higher levels of GH (11.20±28.25 vs 4.36±12.56 ng/ml, P=0.02), and nonsignificantly higher IGF1 levels (1.60±1.74 vs 1.28±0.93 xULN), and cumulative GH (13.63±26.23 vs 9.64±14.71 ng/ml) compared with patients who survived. Cumulative GH correlated with last GH levels (r=0.4, P<0.001). There was no correlation of last GH, IGF1 or cumulative GH with HBP, neoplasia, diabetes mellitus. Multivariate analysis revealed last GH level as an independent risk factor for mortality (HR=1.010, 95% CI 1.0031.018, P=0.008). When cumulative GH replaced last GH, HR=1.021 (95%CI 1.0101.032), P<0.001. Also, last IGF1 ratio proved as an independent factor correlated to mortality: HR=1.352 (95%CI 1.1081.672), P=0.003. A cutoff level of last GH >1 ng/ml predicted mortality: AUC=0.659, P<0.001, while for cumulative GH, a cutoff level of 5 ng/ml was found, AUC=0.579, P=0.06.
Conclusion: This study confirms the importance of last GH levels and IGF1 ratio as mortality risk factors in patients with acromegaly. Last GH level is a stronger predictor for mortality than cumulative GH exposure. Continuous surveillance and treatment of comorbidities should be done, apart for controlling GH levels, in order to enhance survival.
18 - 21 May 2019
European Society of Endocrinology