Longer exposure to excess IGF-I levels may raise cancer risk for adults with acromegaly
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Key takeaways:
- Cancer rates for adults with acromegaly are higher than those observed in the U.S. cancer registry.
- Cumulative exposure to excess IGF-I levels was associated with higher odds for cancer.
Having high insulin-like growth factor I levels over a longer duration increased risk for cancer among adults with acromegaly, but not for those with nonfunction pituitary adenoma, according to study data.
“Our data newly suggest that cumulative exposure to IGF-I excess may better appreciate the impact of disease activity on cancer risk than isolated values,” Pamela U. Freda, MD, associate professor of medicine at NewYork-Presbyterian Hospital, College of Physicians and Surgeons, Columbia University, and colleagues wrote in a study published in The Journal of Clinical Endocrinology & Metabolism. “To adjust for the potential effect of longer follow-up among cancer patients, we confirmed greater IGF-I exposure among cancer patients who were matched to [patients without cancer history] for age, length of follow up and other important factors.”
Researchers conducted a prospective study of 598 adults diagnosed with acromegaly who underwent transsphenoidal surgery or had prior surgery. Visits took place before surgery and then 1 month, 3 months and annually after surgery. Medical history, family history, smoking status, acromegaly medication status, physical examination information and fasting blood samples were collected at each visit. Data were also collected from 292 adults with a clinically nonfunctioning pituitary adenoma enrolled in a prospective observational study. Visits among the group occurred at 6 months, 12 months and annually for adults who were only observed, and at 1 month, 3 months, 6 months, 12 months and annually for those who underwent surgery. Cumulative exposure to IGF-I excess was calculated by averaging each person value for IGF-I percent of the upper limit of normal range and then multiplying them by the years elapsed between them. The values were then added to the time from acromegaly diagnosis to the time of cancer diagnosis or final follow-up to determine cumulative exposure to excess IGF-I, which was expressed as arbitrary units.
The acromegaly group included 135 adults with 156 cancer diagnoses, whereas the nonfunctioning pituitary adenoma group had 37 adults with 39 cancer diagnoses. Adults with acromegaly were 99% more likely to be diagnosed with cancer than those with a nonfunctioning pituitary adenoma (OR = 1.99; 95% CI, 1.34-2.97; P = .0005).
Adults with acromegaly had a higher total number of cancer cases than the expected cancer rate in the U.S. cancer registry (standardized incidence ratio = 1.78; 95% CI, 1.51-1.81). Cancer rates for adults with a nonfunctioning pituitary adenoma were similar to those observed in the U.S. cancer registry.
Adults diagnosed with cancer after acromegaly diagnosis were older (mean age, 62 years vs. 54 years; P = .0001) and had a longer follow-up since acromegaly diagnosis (mean follow-up, 13.5 years vs. 11.1 years; P = .02) than those not diagnosed with cancer. Excess exposure to IGF-I was higher in those who developed cancer after acromegaly diagnosis than adults without cancer (1,448 arbitrary units vs. 1,092 arbitrary units; P = .008).
In post hoc analysis, adults diagnosed with cancer after acromegaly diagnosis were matched by sex, age at acromegaly diagnosis, years since acromegaly diagnosis and age at cancer diagnosis or last follow-up, to three to five adults who were not diagnosed with cancer. The results were similar to the main analysis, with adults diagnosed with cancer after acromegaly diagnosis having higher exposure to excess IGF-I than those without cancer.
Excess IGF-I exposure was lower among adults diagnosed with acromegaly at age younger than 60 years than those diagnosed with acromegaly at age 60 years and older (906 arbitrary units vs. 1,230 arbitrary units; P = .01). IGF-I excess was higher for those diagnosed with cancer than adults without cancer in both age groups.
The researchers said providers should consider cancer risk for adults with acromegaly and conduct recommended screening evaluations.
“Population-specific underlying genetic and other influences on cancer risk may also contribute to the heterogeneity in reported cancer rates,” the researchers wrote. “Region-specific studies may be needed to fully appreciate the cancer risk in an acromegaly population.”
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