Endocrine side effects of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have increasingly been the mainstay of treatment for numerous malignancies. However, due to their association with autoimmunity, ICIs have resulted in a variety of side effects that involve multiple organs including the endocrine system. In this review article, we describe our current understanding of the autoimmune endocrinopathies as a result of the use of ICIs. We will review the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of the most commonly encountered endocrinopathies, including thyroiditis, hypophysitis, Type 1 diabetes, adrenalitis, and central diabetes insipidus.

Adipsic diabetes insipidus.

Adipsic diabetes insipidus (ADI) is a rare but devastating disorder of water balance with significant associated morbidity and mortality. Most patients develop the disease as a result of hypothalamic destruction from a variety of underlying etiologies. Damage to osmolar-responsive neuroreceptors, primarily within the supraoptic and paraventricular nuclei, results in impaired production and release of arginine vasopressin (AVP). Important regulating circuits of thirst sense and drive are regionally colocalized with AVP centers and therefore are also injured. Patients with central diabetes insipidus with impaired thirst response, defined as ADI, suffer from wide swings of plasma osmolality resulting in repeated hospitalization, numerous associated comorbidities, and significant mortality. Treatment recommendations are based largely on expert advice from case series owing to the rarity of disease prevalence. Acute disease management focuses on fixed dosing of antidiuretic hormone analogues and calculated prescriptions of obligate daily water intake. Long-term care requires patient/family education, frequent reassessment of clinical and biochemical parameters, as well as screening and treatment of comorbidities.

Sleep interventions and glucose metabolism: systematic review and meta-analysis.

OBJECTIVE: Sleep disturbances (insufficient or poor sleep quality) have been linked to abnormal glucose metabolism. This systematic review and meta-analysis aimed to explore the effects of behavioral and pharmacological sleep interventions on glucose metabolism. METHODS: Medline and Embase were used for systematic search. Studies reporting behavioral or pharmacological interventions in population with sleep disturbances, with measured outcomes of glucose metabolism and sleep parameters were selected. RESULTS: Twenty two studies were eligible for review (eight were conducted in people with type 2 diabetes). Studies were grouped into three types of intervention: sleep extension (n = 6), sleep education or cognitive behavioral therapy for insomnia (CBT-I, n = 6) and pharmacological interventions (n = 10). CBT-I and sleep education resulted in significantly improved self-reported sleep quality (Pittsburgh Sleep Quality Index, mean difference, MD, -1.31, 95% confidence interval (CI) -1.83, -0.80), non-significant reduction in hemoglobin A1c level (MD -0.35%, 95% CI -0.84, 0.13), and non-significant reduction in fasting glucose levels (MD -4.76 mg/dL, 95% CI -14.19, 4.67). Other studies were not eligible for meta-analysis due to heterogeneity of interventions or outcomes. Sleep extension was able to increase sleep duration by varying degrees in short sleepers, and five of six studies demonstrated relationships between the intervention and measures of insulin resistance. A majority of pharmacological intervention studies showed improved sleep but the effects on glucose metabolism were mixed. CONCLUSIONS: Available sleep interventions were effective in improving sleep but the effects on glucose metabolism were inconclusive. Larger randomized studies with consistent outcome measurements are needed to demonstrate this potential causal relationship.