Progressive Cachexia: Tuberculosis, Cancer, or Thyrotoxicosis? Disease-Directed Therapy and Atypical Courses of Autoimmune and Malignant Thyroid Diseases in a High Specialization Era: Case-Control Study with a Critical Literature Review

<b>Background.</b> Critical and progressive cachexia may be observed in numerous medical disciplines, but in patients with various diseases, several pathways overlap (endocrine, inflammatory and kidney diseases, heart failure, cancer). <b>Methods.</b> Unlike numerous cohort studies that examine thyroid cancer and risk factors, a different method was used to avoid bias and analyze the sequence of events, i.e., the pathway. A case-control analysis is presented on patients with initial immune-mediated thyroiditis complicated by cachexia, presenting pulmonary pathology coexisting with opportunistic infection, and ultimately diagnosed with cancer (TC-thyroid cancer, misdiagnosed as lung cancer). <b>Results.</b> Contrary to other patients with lung cancer, the presented patients were not active smokers and exclusively women who developed cachexia with existing autoimmune processes in the first phase. Furthermore, the coexistence of short overall survival without cancer progression in the most seriously ill patients, as well as correlation with sex (contrary to history of smoking) and predisposition to mycobacterial disease, are very suggestive. Although we describe three different autoimmune conditions (de Quervain's, Graves', and atrophic thyroiditis), disturbances in calcium and metabolic homeostasis, under the influence of hormonal and inflammatory changes, are crucial factors of cachexia and prognosis. <b>Conclusions.</b> The unique sequence sheds light on immune-mediated thyroid disease as a subclinical paraneoplastic process modified by various therapeutic regimens. However, it is also associated with cachexia, systemic consequences, and atypical sequelae, which require a holistic approach. The differential diagnosis of severe cachexia, adenocarcinoma with pulmonary localization, and tuberculosis reactivation requires an analysis of immunological and genetic backgrounds. Contrary to highly specialized teams (e.g., lung cancer units), immunotherapy and general medicine in aging populations require a multidisciplinary, holistic, and inquiring approach. The lack of differentiation, confusing biases, and discrepancies in the literature are the main obstacles to statistical research, limiting findings to correlations of common factors only. Time-lapse case studies such as this one may be among the first to build evidence of a pathway and an association between inflammatory and endocrine imbalances in cancer cachexia.