In the past two decades, cancer research has rapidly advanced, spurred by the development of high throughput technology and the maturation of genomic and proteomic research methods. These advances have resulted in treatments that have substantial effects on the outcomes of certain cancers. The continuous development of new antineoplastic agents adds increasing challenges to practicing physicians.
Current cancer treatments include surgery, radiation, cytotoxic chemotherapy, hormonal therapy, bioimmunotherapy, and targeted therapy. Adverse effects of antineoplastic agents on the endocrine system are caused by several different mechanisms and can range from a subtle laboratory abnormality with limited clinical significance to a clinical syndrome with significant morbidity. Antineoplastic agents in general can be cytotoxic to endocrine cells and result in glandular dysfunction. Antineoplastic agents can also interfere with the synthesis or postsynthesis processing of hormones at different levels (ie, transcription, translation, or posttranslation). An agent may inhibit or induce secretion of a hormone by interacting with receptors, perturbating intracellular second messenger metabolism or may affect hormone delivery by changing carrier protein levels in serum or by competing for binding on the carrier protein. Finally, antineoplastic agents can interact with signal transduction pathway to inhibit or enhance hormonal action in the end organs.
In this chapter, we summarize the major and common endocrine complications of cancer therapy and discuss screening and surveillance of these complications in cancer patients and survivors.
Serum glucose is under continuous complex regulation. Many processes can affect glucose levels, including gut absorption, cellular uptake, gluconeogenesis, and glycogenolysis. Multiple hormones also play important roles in overall glucose homeostasis, including insulin, glucagon, growth hormone (GH), cortisol, somatostatin, and incretins.
Glucocorticoids are frequently used with many chemotherapy protocols and can have profound effects on glucose levels by increasing insulin resistance. Glucocorticoids can unmask preexisting prediabetic states by precipitating overt diabetes or make diabetes more difficult to control. The severity may range from asymptomatic hyperglycemia to nonketotic hyperosmolar coma. Most patients taking glucocorticoids with elevated glucose may require insulin therapy to achieve blood glucose control, especially when given high-dose steroids. Long-acting and intermediate-acting insulin formulations are more effective at controlling glucose levels when they are combined with meal time rapid-acting or short-acting insulins than are regimens that use short-acting insulin alone on the basis of sliding scales. Currently, there are no evidence-based specific guidelines for the management of steroid-induced diabetes mellitus in cancer patients. Recent concerns about promotion of malignancy by the mitogenic effect of insulin (1,2) and especially insulin analogues (3) which cross-activate IGF-1 receptors (4) but conflicting clinical study results about glargine and cancer (5,6) have brought attention to the gap in knowledge about the proper diabetic management strategy for cancer patients and survivors to maximize their survival.
Temsirolimus, L-asparaginase, streptozocin, and interferon-alpha (IFNα) are other antineoplastic agents that ...