Mortality and Cancer Incidence in Acromegaly: A Retrospective Cohort Study¹

Abstract

Patients with acromegaly have a reduced life expectancy, with the accepted causes for premature death being vascular and respiratory disease. Increased mortality from malignant disease has also been reported. We, therefore, performed a multicenter retrospective cohort study of 1362 patients with acromegaly and investigated the relationships of mortality and cancer incidence with GH levels, duration of disease, and age at diagnosis. The overall cancer incidence rate [standardized incidence ratio, 0.76; 95% confidence interval (CI), 0.60-0.95] was lower than that in the general population of the United Kingdom, and there was no significant increase in site-specific cancer incidence rates. The overall cancer mortality rate was not increased, but the colon cancer mortality rate (standardized mortality ratio, 2.47; 95% CI, 1.31-4.22) was higher than expected. Mortality rates due to colon cancer, all malignant disease, cardiovascular disease and overall mortality were increased with higher posttreatment GH levels (P for trends, <0.02, <0.05, <0.02, and <0.0001). The overall mortality rate in patients with acromegaly with posttreatment GH levels less than 2.5 ng/mL (5 mU/L) was comparable to that in the general population of the United Kingdom (standardized mortality ratio, 1.10; 95% CI, 0.89-1.35). We conclude that high posttreatment GH levels are associated with an increased overall mortality rate and increased mortality rates due to colon cancer, cardiovascular disease, and all malignant disease. Posttreatment GH levels less than 2.5 ng/mL (5 mU/L) result in an overall mortality rate similar to that in the general population.

Could different treatment approaches in acromegaly influence life expectancy? A comparative study between Bulgaria and Campania (Italy)

“…In accordance with our results of the Bulgarian cohort, increased vascular mortality has been reported in several studies (20,21,22,23,24). On the other hand, a tendency toward increased life expectancy has been observed in recent studies (22,23,24,25,26,27,28,29,30,31,32,33,34).…”

“…Bates et al (38) were the first to demonstrate that an increased mortality was reduced to normal when GH levels reached !2.5 mg/l. Their observations were supported by numerous further studies (22,26,27,28,29,30,32,38,39) with a pooled SMR of 1.1 (0.9-1.4; PZ0.50) (7). Some research groups reported even lower GH targets: 2 mg/l by Ayuk et al and a further improvement in mortality when GH was reduced to !1 mg/l (23,26).…”

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

“…The pooled odds ratio (OR) are increased for both benign tumors (2.48 for adenomas and 3.557 for hyperplastic polyps) and colon cancer (2.04-4.351) (Renehan et al 2003, Rokkas et al 2008. The SMR for colon cancer is also higher in active ACM (2.47) compared to the general population (Orme et al 1998). …”

“…Less stringent endpoints might be better related to normal agematched IGF1 concentrations (Costa et al 2002) and also have meaningful effects in terms of disease-related morbidity and mortality. Mean basal GH levels below 2.5 mg/l and normal IGF1 levels restore the SMR to that of healthy controls (Bates et al 1993, Orme et al 1998, Holdaway et al 2003. Therefore, in clinical practice, aiming for 'safe' values, such as those recommended by the current guidelines, is more realistic.…”

Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study

“…In particular, epidemiological studies have shown an association between high levels of serum IGF1 and risk of developing certain malignancies, namely breast, prostate, and colorectal cancers (8,9,10). Furthermore, patients with acromegaly, a condition caused by endogenous excess of GH and consequent increased levels of IGF1, have increased risk for development of, or mortality due to, colorectal cancer (11,12,13).…”