Myxedema

BackgroundNivolumab is an anti-programmed cell death (anti-PD-1) monoclonal antibody that is approved by Food and Drug Administration for treatment of metastatic non-small cell lung cancer, metastatic melanoma, relapsed Hodgkin lymphoma and advanced renal cell cancer. We report a rare case of myxedema crisis induced by nivolumab in a patient with metastatic squamous cell carcinoma of lung.Case presentationFifty three-year old woman with metastatic squamous cell carcinoma currently on treatment with nivolumab presented with diffuse facial and tongue swelling, slurred speech, depressed mentation, fatigue and weakness. Initial evaluation revealed severe hypothyroidism with thyroid stimulating hormone of 237 micro Unit/mL (Normal Reference range: 0.27-4.20 micro unit/mL) and undetectable free T4. Patient was diagnosed with nivolumab induced myxedema crisis. She was treated successfully with levothyroxine with complete resolution of her symptoms. Nivolumab was safely restarted once the symptoms of myxedema resolved.ConclusionNivolumab can cause immune-mediated endocrinopathies including thyroiditis, hypophysitis, adrenal insufficiency and type 1 diabetes mellitus. High index of suspicion and periodic measurement of thyroid function tests are recommended in patients receiving nivolumab therapy. Our case also suggests that once the myxedema crisis is treated and symptoms are resolved, nivolumab can be safely re-challenged.

BackgroundMyxedema coma, which occurs due to hypothyroidism, is a rare and life-threatening condition. Some patients have hemodynamic dysfunction, which consequently leads to cardiac arrest. The rarity of this condition makes it difficult to determine the cause of cardiac arrest. It is important to diagnose myxedema coma based on clinical findings, including physical examination and laboratory parameters. We present a case of undiagnosed and untreated hypothyroidism that initially caused myxedema coma and then led to cardiac arrest.Case presentationA 56-year-old woman who had no medical history was transferred to our hospital for the management of return of spontaneous circulation due to sudden cardiac arrest. Findings of laboratory tests revealed that she had hypothyroidism. On physical examination, she was found to have a puffy face, thin eyebrows, and severe systemic non-pitting edema. Therefore, the patient was clinically diagnosed with myxedema coma, which was the cause of cardiac arrest. She was treated with thyroid hormone and hydrocortisone, resulting in improvement in her general condition, except for the neurological dysfunction.ConclusionsThis case suggests that myxedema coma is caused by undiagnosed and untreated hypothyroidism, leading to sudden cardiac arrest. Our findings are useful in the differential diagnosis of hypothyroidism based on characteristic physical examination findings. Clinicians should be aware of the differential diagnosis of myxedema coma based on findings from physical examination and laboratory testing of thyroid function, and the treatment should be started immediately.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves' disease (GD). Although fibroblast stimulated by thyroid-stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM. Results obtained on PTM patients indicate increased thyroid-stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin-associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.

ContextThe clinical relevance of thyroid hormone-mediated inotropic effects in humans remains uncertain.ObjectiveWe evaluated ventricular function in patients with severe hypothyroidism and myxedema coma using transthoracic echocardiography and speckle-tracking echocardiography.MethodsMulticenter, retrospective cross-sectional study of adults admitted to intensive care units with severe hypothyroidism who underwent transthoracic echocardiography during hospitalization. Left ventricular (LV) systolic and diastolic function and myocardial deformation, assessed by global longitudinal strain (GLS), were analyzed.ResultsOne hundred and twelve patients were included (mean age 53.9 ± 13.7 years; 64.3% female). Myxedema coma was present in 33 patients (29.5%), and 13 (11.6%) had severe hypothyroidism with altered mental status without hypothermia or bradycardia. Median admission thyroid-stimulating hormone was 113.9 (41.9-500.0) mIU/L. The mean LV ejection fraction (LVEF) was 53.9 ± 13.7%, LV GLS -13.5 ± 4.2% (reference -24% to -16%), and right ventricular (RV) GLS -17.9 ± 6% (reference -35% to -17%). Reduced LVEF occurred in 37.5% of patients, abnormal LV diastolic function in 66.7%, and impaired LV and RV GLS in 68.2% and 34.0%, respectively. In multivariable models, β-blocker treatment was associated with lower LVEF and worse biventricular GLS; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment with lower LVEF; and calcium channel blocker exposure was associated with improved RV GLS. In-hospital mortality was 4.5% and occurred in patients with preserved LVEF.ConclusionSevere hypothyroidism is associated with frequent systolic and diastolic ventricular dysfunction and prevalent impairment of myocardial deformation. Associations between cardiovascular medication exposure and echocardiographic abnormalities likely reflect confounding by indication and underlying clinical phenotype rather than reflecting causal drug effects. Despite substantial myocardial abnormalities, short-term mortality was low.