Immunotherapy can treat cancer and prevent future cancer relapse by enhancing the body's immune system. With novel immunotherapeutic agents like checkpoint inhibitors come unique immune-related adverse events. Hypophysitis, one of the lesser known immune-related complications, may be observed in patients receiving checkpoint inhibitors. Although the acute symptoms of immune-related hypophysitis may be managed with attentive monitoring and high-dose corticosteroids, lifelong hormone substitution therapy may be warranted. Oncology nurses are responsible for educating themselves and their patients on the complications of immunotherapy.
AT A GLANCE
- Early identification and treatment of hypophysitis is important in the management of patients receiving immunotherapy.
- Oncology nurses should educate themselves and their patients on the signs of hypophysitis.
- A thorough baseline history and physical examination are required of every patient receiving immunotherapy.
A 63-year-old female, R.B., presents for an evaluation prior to her fifth cycle of ipilimumab (Yervoy®) immunotherapy (IT) for advanced stage melanoma. She was first evaluated in the office by an advanced practice nurse (APN) to whom she reports recent changes in her level of activity. She is no longer able to stand for long periods of time: “I am so tired. I don’t have the energy to take a shower without sitting in a bath chair.” R.B. states that, during the past week, she has been having episodes of dizziness and headaches. The APN assesses the patient, reviews the case with the nurse, and orders a workup consisting of a complete blood count, comprehensive metabolic panel, thyroid function tests, and magnetic resonance imaging (MRI) of the brain.
The results of the blood work show elevated thyroid-stimulating hormone and decreased thyroxine. The MRI of the brain reveals an enlarged pituitary gland, and immune-related hypophysitis is diagnosed by the APN. R.B. is started on systemic steroid treatment and a thyroid hormone replacement drug. As part of her evaluation, R.B. meets with the APN, who discusses the course of treatment, possible side effects, and expectations. The APN explains to R.G. that her IT treatment will be withheld because of the diagnosis of immune-related hypophysitis. Depending on how R.B. responds, she may be treated chronically with oral steroids. The APN emphasizes the importance of R.B. reporting any changes in her activity or performance status, because they may be relevant in the management of IT-related adverse events.
One of the less common IT-related adverse events is hypophysitis, an inflammation of the pituitary gland (Vinken, Bruyn, & Klawans, 2014). In patients who are not on IT, hypophysitis is a rare and not fully understood condition (Torino, Barnabei, de Vecchis, Salvatori, & Corsello, 2012). The incidence of hypopituitarism is 4.2 cases per 100,000 each year, with hypophysitis being among the rarest cause (Torino et al., 2012). The pituitary gland regulates and secretes hormones that affect different parts of the body, and is responsible for the production of growth hormones, regulation of the endocrine system, and storage of hormones produced by the hypothalamus (Porter, Kaplan, & Beers, 2006).
When the pituitary gland becomes inflamed, as in hypophysitis, normal body functions may be altered. Ongoing research continues to investigate how the pituitary gland is injured. Although hypophysitis is not one of the more common adverse events of patients on IT, healthcare providers must familiarize themselves with it. Reports have shown that hypophysitis in patients treated with IT occurs in 0.6% of patients receiving pembrolizumab (Keytruda®) (Merck Sharp & Dohme Co., 2016), 0.6% of patients receiving nivolumab (Opdivo®) alone (Bristol-Myers Squibb Company, 2017), and 9% of patients receiving nivolumab and ipilimumab (Bristol-Myers Squibb Company, 2017). To date, no data support a higher prevalence of hypophysitis in certain genders, races, or past medical histories.
The advancement of cancer treatments through the use of new immunotherapeuticagents is changing the care management of patients with cancer. In the past five years, three different immunotherapeutic drugs known as monoclonal antibodies have been approved for the treatment of metastatic melanoma and non-small cell lung cancer. These and other agents are being investigated in a number of different malignancies as well. As new agents are explored, a combination of more than one checkpoint inhibitor (CI) is being studied in clinical trials. Therapy that groups a CI with a targeted therapeutic agent is also hypothesized to be more effective than monotherapy. Although a two-drug combination may be better than one, the side effects of two drugs are showing to be more toxic. With the approval and use of these immunotherapeutic agents, new immune-related adverse events (irAEs) are also present.
IT has become an important treatment of certain types of cancer, and CIs have revolutionized treatment. The immune system helps protect the body from infection and other diseases, including cancer. T lymphocytes are cells of the immune system that identify and assist in the body’s destruction of foreign cells. CIs work by preventing tumor cells from attaching to T cells so the immune system can identify them as foreign and attack them. In addition, CIs can work on different tumor types.
Historically, barriers have prevented further exploration of immunotherapies. The high costs of these medications, frequent observation of irAEs, distinctive evaluation criteria responses, patient selection standards, and the unfamiliarity of usage are some concerns of researchers and clinicians. Immune CIs are currently approved as monotherapy and being studied in clinical trials in combination with other IT agents and targeted therapies. The results have been promising, particularly in malignancies that previously have not been susceptible to immune-based treatment.
Symptoms of Immune-Related Hypophysitis
Symptoms of an inflamed pituitary gland tend to be very nonspecific, making them difficult to identify. This can be particularly challenging in patients with cancer who already present with a variety of baseline symptoms from their disease and/or previous treatments. Some general side effects of hypophysitis include headache, change in appetite, altered vision, impaired blood glucose, cessation of menstruation, decreased libido, loss of body hair, and hot flashes. In one study, the median time to onset of hypophysitis symptoms was nine weeks after the first dose of IT (Villadolid & Amin, 2015). Once considered a differential diagnosis in patient treatment plans, hypophysitis is now easily diagnosed and treated through imaging studies and oral steroids. If not recognized early, however, hypophysitis can be life-threatening.
Treatment for irAEs varies depending on the symptom and severity of the side effect, and nurses are responsible for evaluating and treating patients and their symptoms. Published algorithms serve as guides for treatment but are not absolute. When a patient on IT presents with new nonspecific symptoms, clinicians must act quickly, hold therapy, and rule out other causes. Differential diagnoses and focused workups should be ordered as a priority.
The use of immunosuppressant agents (e.g., prednisone [Deltasone®]) is common in the treatment of IT adverse events. Therefore, an infectious evaluation must be included in the workup. The diagnosis of hypophysitis in a patient receiving IT is rarely reversible. Patients may need to take long-term immunosuppressive drugs and other agents, depending on the endocrinopathies discovered. Research shows that the immunosuppressive treatments for irAEs do not seem to reduce CIs’ effectiveness in overall anticancer activity.
Implications for Nursing
From a nursing perspective, the use of immunotherapeutic agents offers hope for patients with cancer. Challenges for healthcare professionals include educating patients and clinicans about these new agents and associated irAEs. Obtaining a patient’s thorough history is imperative, particularly regarding a past history of autoimmune system issues (e.g., ulcerative colitis, lupus). Close monitoring throughout treatment is important, and nurses must not discount minimal changes in a patient’s baseline performance status, because hypophysitissymptoms are nonspecific. A therapeutic relationship must be established among the patient, nurse, and provider. The topic of communication should be highlighted when developing a treatment plan with a patient and caregivers. Patients should feel comfortable reaching out to the oncology team with any questions or concerns related to treatment, and patients and caregivers must understand the importance of reporting any new or changing symptoms.
Education of oncology nurses is critical in the recognition and management of hypophysitis. They should also be aware that the side effects of IT differ from those of conventional chemotherapy and biotherapy. The American Society of Clinical Oncology has published articles and developed educational plans that oncology nurses are encouraged to use to familiarizethemselves with IT (Carra et al., 2012; Postow et al., 2015).
As the care of patients with cancer continues to evolve, so do treatments. Immunotherapeutic agents are transitioning to the forefront of cancer care, and nurses should educate themselves and their patients on their side effects. Many times, irAEs are subtle and difficult to differentiate from a patient’s baseline conditions. Obtaining a thorough history and physical examiniation prior to starting IT is vital. Early recognition and management of symptoms are critical. The main treatments of irAEs are immunosuppressive medications, such as steroids. Algorithms currently in place are to be used as treatment guides, but healthcare professionals must evaluate patients individually and customize their treatment based on their signs and symptoms.
About the Author(s)
Adrienne Vazquez, MSN, ACNP-BC, AOCNP®, is an acute care nurse practitioner at the University of Miami Sylvester Comprehensive Cancer Center in Florida. The author takes full responsibility for this content and did not receive honoraria or disclose any relevant financial relationships. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Oncology Nursing Society. Vazquez can be reached at firstname.lastname@example.org, with copy to editor at CJONEditor@ons.org.