Advances in cancer therapy in the past few years have include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed death 1 (PD1), are two coinhibitory receptors that are expressed on activated T cells to which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory side effects, termed as immune-related adverse events (IRAEs), which resemble autoimmune disease. In this Review, we describe the current data regarding immune-related endocrinopathies, including hypophysitis, thyroid dysfunction and the development of diabetes mellitus. We discuss the clinical management of these endocrinopathies within the context of our current understanding of the mechanisms of IRAEs.

Clinical trials in the past decade have established the antitumor effects of immune checkpoint inhibition as a revolutionary treatment for cancer. Namely, blocking antibodies to cytotoxic T-lymphocyte antigen 4 and programmed death 1 or its ligand have reached routine clinical use. Manipulation of the immune system is not without side effects, and autoimmune toxicities often known as immune-related adverse events (IRAEs) are observed. Endocrine IRAEs, such as hypophysitis, thyroid dysfunction, and insulin-dependent diabetes mellitus, can present with unique profiles that are not seen with the use of traditional chemotherapeutics. In this Review, we discuss the current hypotheses regarding the mechanism of these endocrinopathies and their clinical presentations. Further, we suggest guidelines and algorithms for patient management and future clinical trials to optimize the detection and treatment of immune checkpoint–related endocrinopathies.

Anabolic skeletal agents have recently broadened our therapeutic options for osteoporosis. By directly stimulating bone formation, they reduce fracture incidence by improving bone qualities in addition to increasing bone mass. Teriparatide [recombinant human parathyroid hormone(1-34)], the only anabolic agent currently approved in the United States for osteoporosis, has emerged as a major therapeutic approach to selected patients with osteoporosis. Teriparatide is approved for both postmenopausal women and men with osteoporosis who are at high risk for fracture. With the use of this anabolic agent, bone density and bone turnover increase, microarchitecture improves, and bone size is beneficially altered. The incidence of vertebral and nonvertebral fractures is reduced with teriparatide use. Combination therapy with parathyroid hormone and an antiresorptive does not appear to offer definitive advantages over the use of PTH or an antiresorptive alone, although recent ideas about combining these agents may offer new insights. In order to maintain increases in bone density acquired during PTH therapy, it is important to follow its use with an antiresorptive agent.

Background. Patients with pituitary metastasis (PM) have a relatively poor prognosis. We describe the presentation, management, and outcomes of patients with PM. Subjects, Materials, and Methods. We performed a retrospective review of patients diagnosed with PM at a single institution from 1996 to 2015. Eighty-five patients diagnosed with metastasis to the pituitary or sella turcica by pathology or based on a combination of neuroimaging and clinical findings were included. Univariate and multivariable Cox regressions evaluated associations between clinical factors and overall survival. Results. The most frequent sites of primary malignancies resulting in PM were lung (26%) and breast (26%). Median age at diagnosis was 60 years (range, 18-95). The most common complaints at diagnosis included visual deficits (62%), headache (47%), and cranial nerve palsy (31%). Seventy percent of patients had pituitary insufficiency-adrenal insufficiency (59%), hypothyroidism (59%), or diabetes insipidus (28%). Management of PM included radiation therapy (76%), chemotherapy (68%), surgical resection (21%), or combination therapy (71%). Fifty percent and 52% of patients who received surgical treatment and irradiation, respectively, reported symptomatic improvement. Median overall survival (OS) was 16.5 months (95% confidence interval: 10.7-25.4). On multivariable analysis, a primary cancer site other than lung or breast (p = .020), age <60 years (p = .030), and surgical resection (p = .016) were associated with longer OS. Conclusion. Patients <60 years of age, those with primary tumor sites other than lung or breast, and those who undergo surgical resection of the pituitary lesion may have prolonged survival. Surgical resection and radiation treatment resulted in symptomatic improvement in~50% of patients. The Oncologist 2020;25:e789-e797Implications for Practice: This study is the largest original series of patients with metastatic disease to the sella. In patients with pituitary metastasis, younger age, primary site other than lung or breast, and metastatic resection may prolong survival. Resection and radiation led to symptomatic improvement in $50% of patients. Seventy percent of patients had hypopituitarism. These hormonal deficiencies can be life threatening and can result in substantial morbidity if left untreated. Patients should be treated using a multimodality approach-including a potential role for surgery, radiation, chemotherapy, and hormone replacement-with the goal of improving survival and quality of life.