Immune checkpoint inhibitors have become mainstays of therapy for a broad range of cancers and can lead to a variety of endocrinopathies, including hypophysitis, thyroiditis, primary hypothyroidism, Graves disease, primary adrenal insufficiency, lipodystrophy, and autoimmune diabetes.
A broad range of antineoplastic agents, including agents that target the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway and tyrosine kinase inhibitors (TKIs), alter glucose homeostasis and can lead to hyperglycemia, which may require monitoring and treatment.
Hormone-suppressive therapies, radiation treatments, chemotherapeutics, and corticosteroids can all lead to increased bone fragility, which may be ameliorated by antiresorptive agents such as bisphosphonates or denosumab.
Patients who receive cranial or craniospinal radiation therapy are at risk for hypothalamic and pituitary dysfunction, and those who receive radiation to the head and neck or other sites close to the thyroid are at risk for hypothyroidism and thyroiditis.
Cytotoxic chemotherapy and radiation therapy are common causes of hypogonadism and infertility in both male and female cancer survivors and should be discussed with patients before initiation of therapy.
Childhood cancer survivors, especially those who received abdominal radiation or total-body irradiation, are at increased risk of diabetes mellitus and metabolic syndrome as long-term sequelae of cancer treatment and need continued follow-up and screening for these conditions in survivorship care.
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.
Current cancer treatments include surgery, radiation, cytotoxic chemotherapy, hormonal therapy, targeted therapy, and immunotherapy. 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 potentially lethal clinical syndromes. Antineoplastic agents are cytotoxic to endocrine cells and result in glandular dysfunction and 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, perturbing intracellular second messenger metabolism, interfering with hormone delivery by changing carrier protein levels in serum, competing for binding on the carrier protein, or interacting with signal transduction pathways, which can alter hormonal action in the end organs.
Immune checkpoint inhibitors have become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies, anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti–programmed cell death protein 1 (PD-1) and anti–PD-1 ligand molecules (PD-L1 and L2), reactivate the immune system against tumor cells and trigger a myriad of autoimmune side effects, including several important endocrine side effects.
This chapter summarizes the endocrine complications of cancer therapy and discusses screening and surveillance of these complications in patients with cancer and survivors.