Objective: It is unclear whether mortality still is increased in acromegaly and whether there are gender-related differences. We dynamically assessed outcome during long-term follow-up in our nationwide cohort. Patients and methods: We studied standardized mortality ratios (SMRs) relative to the general population and causes of death in acromegaly (n = 333) compared with age-and gender-matched controls (n = 4995). Results: During 20 (0-33) years follow-up, 113 (34%) patients (n = 333, 52% women) and 1334 (27%) controls (n = 4995) died (P = 0.004). SMR (1.9, 95% CI: 1.53-2.34, P < 0.001) and all-cause mortality (OR 1.6, 95% CI: 1.2-2.2, P < 0.001) were increased in acromegaly. Overall distribution of causes of death (P < 0.001) differed between patients and controls but not cardiovascular (34% vs 33%) or cancer deaths (27% vs 27%). In acromegaly, but not in controls, causes of deaths shifted from 44% cardiovascular and 28% cancer deaths during the first decade, to 23% cardiovascular and 35% cancer deaths during the next two decades. In acromegaly, cancer deaths were mostly attributed to pancreatic adenocarcinoma (n = 5), breast (n = 4), lung (n = 3) and colon (n = 3) carcinoma. In acromegaly, men were younger than women at diagnosis (median 44.5 vs 50 years, P < 0.001) and death (67 vs 76 years, P = 0.0015). Compared with controls, women (36% vs 25%, P < 0.01), but not men (31% vs 28%, P = 0.44), had increased mortality. Conclusions: In acromegaly, men are younger at diagnosis and death than women. Compared with controls, mortality is increased during 20 years of follow-up, especially in women. Causes of deaths shift from predominantly cardiovascular to cancer deaths.

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We demonstrate, for the first time, that AIP protein expression associates with Ga protein intensities in sporadic somatotropinomas, suggesting a joint regulation on somatostatin signaling. Low AIP level associates with higher proliferative activity and predicts high GH concentrations after long-term follow-up. The AIP mutation rate of 6.8% is fairly high, reflecting the genetic composition of the Finnish population.