Chiefs’ Inquiry Corner-5/9/22

May 9, 2022

Chief residents of the NYU Langone Internal Medicine Residency give quick-and-easy, evidence-based answers to interesting questions posed by house staff, both in their clinics and on the wards.

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 Calculating the anion gap is an essential part of evaluating a patient with hyperglycemia and evidence of acidosis on a blood gas. Hyperglycemia increases the tonicity of extracellular fluid, which is then results in intracellular fluid moving into the extracellular space. This fluid shift results in a dilution or lowering of the serum sodium measured on a basic metabolic panel. When evaluating a patient with hyperglycemia and apparent hyponatremia, the sodium should be corrected to take this fluid shift into account. However, this correction should not be used when calculating the anion gap. This is because the chloride and bicarbonate measurements are proportionally diluted with the sodium. Adjusting only the sodium to account for this fluid shift would artificially raise the anion gap.

References: Approach to Patients With High Anion Gap Metabolic Acidosis: Core Curriculum 2021
 Nonbacterial thrombotic endocarditis (NBTE), also known as marantic endocarditis, is an entity associated with malignancy and other hypercoagulable states like systemic lupus erythematosus or antiphospholipid syndrome. NBTE results in the formation of sterile thrombi made of fibrin and immune complexes most commonly on the aortic and mitral valves. Importantly, the thrombi are not well-adhered to the valves and are prone to embolization. The imaging finding of multiple infarctions of different sizes should raise suspicion for NBTE. The diagnosis is definitively made by pathology, usually done at time of autopsy or after valve replacement surgery. However, the diagnosis should be suspected in patients with advanced malignancy who are found to have multiple or recurrent strokes, a vegetation on TTE or TEE, and no infectious symptoms or positive blood cultures. Treatment focuses on addressing the underlying disease and decreasing the risk of systemic embolization with therapeutic anticoagulation with heparin or enoxaparin.

References: Nonbacterial Thrombotic Endocarditis: Pathogenesis, Diagnosis, and Management
 Up to 30% of people with cancer will develop hypercalcemia during the course of their disease. While it can be seen with virtually any type of cancer, hypercalcemia is most frequently associated with non-small-cell lung cancer, breast cancer, multiple myeloma, squamous cell cancers of the head and neck, urothelial malignancies, and ovarian cancers. Increased osteoclastic bone resorption is the underlying pathophysiologic mechanism responsible for nearly all cases of malignancy-associated hypercalcemia. For example, in humoral hypercalcemia of malignancy (typically associated with squamous tumors of the lung, head, and neck, urothelial malignancies, and breast cancers, although it can be seen with almost any other type of tumor), the tumor secretes PTHrP and binds to the PTH-PTHrP type 1 receptor in the bones and kidneys, leading to increased osteoclastic bone resorption and renal tubular reabsorption of calcium, respectively. In most such cases, there are few, if any metastatic lesions to the bone. In local osteolytic hypercalcemia (seen most often in breast cancer or multiple myeloma), extensive bone metastases are present, and the tumor cells in bone produce cytokines that locally increase osteoclastic bone resorption and inhibit osteoblastic bone formation. Less frequently, other mechanisms include production by tumors of hormones involved in bone remodeling, including ectopic PTH or mediators that upregulate 1,25-dihydroxyvitamin D.  Regardless of the exact cancer or mechanism underlying the hypercalcemia, its presence portends a poor prognosis: studies have demonstrated that median survival after onset of hypercalcemia is just 25 to 52 days. Treatment includes hydration, bone resorption inhibitors (typically intravenous bisphosphonates), and treatment of the underlying cancer. Improved survival appears to be more likely among people with hematologic or breast cancers, as well as in those who had normalization of calcium levels with treatment and also received concomitant chemotherapy.

References: Cancer-Associated Hypercalcemia