Prospective, longitudinal study of cancer predictors and rates in a New York City cohort of 598 patients with acromegaly

Pamela U Freda; Jeffrey N Bruce; Zhezhen Jin; Jane Kostadinov; Alexander G Khandji; Serge Cremers; Kalmon D Post

doi:10.1210/clinem/dgae469

Prospective, longitudinal study of cancer predictors and rates in a New York City cohort of 598 patients with acromegaly

J Clin Endocrinol Metab. 2024 Jul 10:dgae469. doi: 10.1210/clinem/dgae469. Online ahead of print.

Authors

Pamela U Freda¹, Jeffrey N Bruce², Zhezhen Jin³, Jane Kostadinov^{2

4}, Alexander G Khandji⁵, Serge Cremers⁶, Kalmon D Post⁴

Affiliations

¹ Departments of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, 10032.
² Department of Neurosurgery, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, 10032.
³ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032.
⁴ Department of Neurosurgery, Mt. Sinai School of Medicine, New York, NY, 10029.
⁵ Department of Radiology, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, 10032.
⁶ Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, 10032.

PMID: 38986012
DOI: 10.1210/clinem/dgae469

Abstract

Purpose: Long-term GH/IGF-1 excess could increase risk of cancer in acromegaly, but individual levels of these hormones do not relate to this risk. Therefore, we newly investigated longitudinally-measured IGF-1 levels as a potential predictor of cancer in a large NYC acromegaly cohort.

Methods: We conducted a prospective, longitudinal study of 598 acromegaly (309 men, 289 women) and 292 clinically nonfunctioning pituitary adenoma (CNFPA)(140 women, 152 men) patients from the same underlying population. GH and IGF-1 levels were measured longitudinally and outcomes were observed during long-term follow-up. Cumulative exposure to IGF-1 excess was tested as a predictor of cancer. We compared cancer prevalence in acromegaly and CNFPA cohorts and incidence in each to that expected from SEER data.

Results: Cancer prevalence by last follow up was 22.6% in acromegaly and 12.7% in CNFPAs (OR = 1.99 (95% CI, 1.34, 2.97)(P=0.0005). Overall SIR for cancer was 1.78 (1.51, 1.81) in the acromegaly and 1.26 (0.89, 1.70) in the CNFPA cohorts. Cumulative exposure to IGF-1 excess, OR=1.278 (1.060, 1.541)(P = 0.01), years from acromegaly diagnosis to cancer or last follow up, OR= 1.03 (1.004, 1.057)(P=0.024), and age at follow up, OR =1.064 (1.047, 1.082)(P<0.001), were predictors of cancer.

Conclusions: Cancer risk is increased in acromegaly, but not in CNFPA patients. Cumulative exposure to IGF-1 excess is a predictor of cancer in acromegaly. Our data suggest that cancer risk in acromegaly relates to the degree and duration of IGF-1 excess and that full appreciation of this risk requires long-term follow up.

Keywords: Acromegaly; IGF-1; cancer; pituitary tumor.

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