SUN-LB48 Increased Mortality in Acromegaly Is Mainly Due to Vascular and Respiratory Disease and Is Normalized by Control of Growth Hormone Hypersecretion

Abstract

Introduction: Epidemiological studies in acromegaly have shown increased mortality rates from vascular, respiratory and malignant diseases. We aimed to use a large national cohort of subjects with acromegaly to determine mortality rates due to the above disease categories and to determine whether suppressing post treatment growth hormone (GH) levels to < 1 ng/ml improved survival compared with GH levels of 1-2.5 ng/ml.Methods: We identified 1845 cases from the UK Acromegaly database diagnosed 1970-2016 (31,768 person-yrs.), determined population mortality rates (for the period in question, age and sex of the study population) based on historic data, and death certification data for the study population from NHS digital. We were then able to determine standardized mortality rates (SMR) for the above conditions and determine whether they were associated with with age at diagnosis, duration of disease, post treatment (last recorded random or mean of profile) and mean GH levels (day weighted average of all GH measurements). Data presented as SMR, 95% CI and P value.Results: Overall standardised mortality rate (SMR) was increased, Observed 556 vs. Expected 412.74, 1.35 (1.24 -1.46, P <0.001), with increased deaths from cardiovascular 1.38 (1.16-1.63, P<0.0001), cerebrovascular 1.49 (1.10-1.97, P <0.006) and respiratory disease 1.55 (1.22-1.93, P< 0.001), but not malignancy 0.94 (0.78-1.11, P=0.786).We found no increase in mortality from breast 0.62 (0.25-1.27, P=0.936), lung 0.87(0.58-1.26, P=0.789) or colon cancer 1.26(0.63-2.25, P= 0.265).There was no relationship between age at diagnosis and SMR, however, there was a declining relationship between duration of acromegaly and all-cause SMR <5 yrs. 6.02 (4.59-7.75) 5-10 yrs. 2.42 (1.9-3.03) >10yrs.1.13 (1.03-1.25) P <0.001.Lowering post-treatment GH levels lead to a significant reduction in all-cause SMR <2.5 ng/ml 1.15 (1.03-1.28) 2.5- 9.9 ng/ml 1.73 (1.47-2.02) ≥10 ng/ml 2.27 (1.72-2.95) P<0.001 and SMR in all disease categories. A similar relationship between mean GH levels and SMR was found for all disease categories and all-cause SMR < 2.5 ng/ml 1.00 (0.89-1.18) 2.5- 9.9 ng/ml 1.50 (1.33-1.69) ≥ 10 ng/ml 2.28 (1.85-2.79) P<0.001.Lowering post-treatment GH levels to less than 1 ng/ml appeared to have an additional beneficial effect for all-cause SMR, <1ng/ml 1.03 (0.89-1.18) 1-2.5 ng/ml 1.38 (1.16-1.62) P<0.001. A similar relationship was shown in cardiovascular, respiratory and malignant disease, but not cerebrovascular disease.Conclusion: Acromegaly is associated with an increased mortality from vascular, respiratory, but not malignant disease. The highest risk is within the first 5 years following diagnosis and the risk is abrogated by lowering GH levels to <1.0 ng/ml.On behalf of UK Acromegaly Register Study Group 2020