Increased serum tumor necrosis factor α levels in patients with lenalidomide-induced hypothyroidism

Abstract

As the use of lenalidomide expands, the poorly understood phenomenon of lenalidomide-induced thyroid abnormalities will increase. In this study we compared rates of therapy-induced hypothyroidism in 329 patients with DLBCL treated with conventional chemotherapy (DLBCL-c) or conventional chemotherapy plus lenalidomide (DLBCL-len). We measured serum levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-6 (IL-6), interleukin-12 (IL-12), and interleukin-15 (IL-15) before and after treatment. We found a significantly higher rate of therapy-induced hypothyroidism in the DLBCL-len group (25.8% vs 1.3%), and we found a statistically significant increase in serum TNF-α in patients with lenalidomide-induced hypothyroidism.

The presence of gastroesophageal reflux disease increases the risk of developing postoperative shoulder stiffness after arthroscopic rotator cuff repair

“…This inflammatory-fibrotic cascade is triggered by over-expression of transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and other cytokines 36,37 , and leads first to a fibroblastic hyperplasia of the synovium, then to a phenotypic shift of fibroblasts to myofibroblasts and an imbalance in matrix metalloproteinases (MMPs) homeostasis; this eventually leads to the alterations of the connective tissue in the glenohumeral capsule typical of the final stage of the disease 36 . In some clinical conditions associated to increased risk of both primary and postoperative SS 4 , TGF-β and TNF-α are hyperexpressed: diabetes mellitus is associated with increased TGF-β1 and TNF-α serum concentrations 8,28,47 and subclinical hypothyroidism with high serum levels of TGF-β1, markers of endothelial dysfunction 1 and, in experimental models, with high TNF-α serum concentrations 25 . Furthermore, gene polymorphisms of TGF-β1, interleukin 6 and MMPs have been associated to increased susceptibility to SS and other fibrotic diseases 38,39 .…”

Risk Factors for Shoulder Stiffness: Current Concepts

“…14 15 Furthermore, in some clinical conditions with increased risk for development of SS, as hypothyroidism and diabetes, TGF-β and TNF-α are hyperexpressed: 16 diabetes was related to increased TGF-β1 and TNF-α serum concentrations 17 18 and subclinical hypothyroidism was also associated with higher serum levels of TGF-β1 and markers of endothelial dysfunction 19 and, in experimental models, with high TNF-α serum concentrations. 20 Surprisingly, even depressive disorders, often detected as coexistent personality traits in patients with clinical pictures of SS, are related to high levels of serum TGF-β and TNF-α. 21 22 23 These evidences seem to suggest the possibility of an underlying aspecific pro-inflammatory condition, characterized by increased expression of TNF-α and TGF-β, which may represent itself a predisposing risk factor for the development of SS.…”

Anticancer Drug-induced Thyroid Dysfunction

“…64 In another series, lenalidomide caused hypothyroidism in 25.8% of cases after a median duration of 5.2 months in patients with diffuse large B-cell lymphoma. 65 Two case reports of pomalidomide-induced hypothyroidism have been described in the literature. 66,67 Slean and Silkiss reported a case of lenalidomide-induced eyelid retraction in a 76-year-old woman who was euthyroid but had elevated thyroid antibodies.…”

“…63 Elevated anti-thyroid peroxidase antibodies and increased TNF-α levels have been demonstrated in these patients, further corroborating the possibility of immune-mediated pathogenesis. 65,69 Additionally, lenalidomide might cause increased T-cell proliferation and activation by stimulating tyrosine phosphorylation of T-cell costimulatory molecules (e.g., CD28).…”