Case Presentation:
This is a 76 year old male with PMH of hypertension who developed severe dyspnea with exertion while at the grocery store. He was taken by EMS to a local ER where he reported fatigue, orthopnea and dyspnea with exertion over the prior 3 weeks. Cardiac markers and echocardiogram were normal. Chest x-ray showed prominence in the left hilum and CT scan revealed two anterior mediastinal masses. He was transferred to our facility for further evaluation. On initial exam was noted to have diplopia with upward gaze, intermittent facial asymmetry, lower extremity fatigability as well as respiratory muscle weakness. Pulmonary and neurology were consulted given concern for myasthenia gravis (MG). Appropriate lab evaluation for MG was sent as well as work up for germ cell tumor and lymphoma. He was started on IVIG and Pyridostigmine and any medications known to exacerbate MG were discontinued. His lab evaluation did confirm MG (positive AChR antibody). His work up for lymphoma and germ cell were negative. No biopsy was obtained as the masses were felt certain to be thymoma. CT surgery was consulted and once the course of treatment for MG was completed he was readmitted for resection of the thymoma. Pathology confirmed thymoma, WHO type A/B. Margins were negative but close so post-operative radiation was recommended and completed. The patient continues on Pyridostigmine with his MG symptoms well controlled.
Discussion:
MG is an autoimmune disorder caused by interference with acetylcholine receptors of voluntary muscle at the neuromuscular junction. Patients present with weakness and fatigability of skeletal muscle. Most patients with seropositive MG (AChR antibody positive) have abnormalities of thymic tissue with hyperplasia present in 60-70% and thymoma in 10 to 12%. In patients presenting with anterior mediastinal differential should include: lymphoma, thymoma and germ cell tumors. MG is the most common paraneoplastic syndrome associated with thymoma, though it is unclear as to why some patients with thymoma develop MG and others do not. Thymoma subtype does play a role and MG is strongly associated with mixed type thymomas, as in our patient, but not with cortical type thymomas. The MG will often resolve following thymectomy. Pyridostigmine, an acetylcholinesterase inhibitor, acts by inhibiting destruction of acetylcholine by acetylcholinesterase thus allowing impulse transmission across the neuromuscular junction. When rapid treatment is needed plasmapheresis is often used to remove the AChR antibodies from circulation. As in our patient IVIG used for its immunomodulating effect can also be used for rapid treatment.
Conclusions:
This case highlights a presentation in which quick and thoughtful diagnostic approach was able to yield a diagnosis in a timely manner. It serves to remind hospitalists seeing a patient with the common complaint of dyspnea on exertion, that rapid and stepwise evaluation may reveal unexpected disease and allow for life saving therapy to be initiated.