Oncological complications of excess GH in acromegaly

Around fifteen percent of the deaths reported in acromegaly are attributable to malignancy (SM Melmed, J Clin Endocrinol Metab 2001;86:2929-2934; A Mestrón, SM Webb, In: Endocrine Society, San Francisco, June 2002 (abstract)), uncontrolled disease is associated with a growth advantage for concurrent neoplasms, which are more likely to be aggressive; however, there is no clear evidence of de novo cancer initiation in acromegaly and no proven causal relationship of acromegaly with malignant disease. Overall and cancer mortality in acromegaly have been shown to correlate with the degree of GH control; if post therapy GH is controlled, both the overall and cancer mortality do not appear to differ from that of the normal population (SM Orme et al., J Clin Endocrinol Metab 1998;83:2730-2734; JD Nabarro, Clin Endocrinol 1987;26:481-512). However, no long-term prospective evaluation of cancer prevalence or its relation to biochemical or clinical disease activity is available. IGF-1 appears to exert a permissive effect on tumorigenesis; there is no clear evidence that tumor initiation is triggered by IGF-1 in acromegaly; nevertheless, since IGF-1 may be higher in neoplasms, aggressive treatment aimed at controlling the disease activity will theoretically be advantageous for acromegalic patients with cancer. The prevalence of colon polyps and colon cancer appear to be incresed in acromegaly as is mortality for colon cancer (Orme et al., 1998), so regular colonoscopy screening and polypectomy would seem advisable, especially in older patients with active acromegaly. Surveillance for prostate cancer in elderly males with high IGF-1, especially if also receiving testosterone replacement therapy, is recommendable, by measurement of serum PSA, rectal examination and/or prostatic ultrasound. In women, mammography should be offered, especially after the age of 50 years, as in the normal population. Neither prostate nor breast cancer have been consistently shown to have an increased prevalence in acromegaly, but larger prospective epidemiological studies are required to study this further.