Molecular mechanisms of resistance to tyrosine kinase inhibitors in patients with iodine-refractory differentiated thyroid carcinoma

2025-07-14T11:20:29-05:00

Background: Iodine-refractory differentiated thyroid carcinoma (IRDTC) is associated with increased recurrence, metastatic disease, and mortality. Sorafenib and lenvatinib are approved in IDC for the treatment of locally unresectable disease and/or progressive metastatic disease, considering their positive impact on progression-free survival (PFS) and disease control. However, some patients develop resistance from the outset or after initiating these treatments.

Objective: To identify the molecular resistance mechanisms described to these tyrosine kinase inhibitors (TKIs) in IDC.

Methodology: A literature search was conducted, including articles in English or Spanish, all study types, and studies from the past 15 years. The PICO search strategy was: thyroid cancer OR thyroid carcinoma OR thyroid neoplasms AND sorafenib OR lenvatinib AND resistance OR non-response OR therapeutic failure. It does not present ethical implications.

Results: Three studies reported resistance to sorafenib and one to lenvatinib in IDC.

Conclusions: The identified resistance mechanisms were decreased miR-124/506, increased TSP-1 and TFG? induced by tumor pericytes, and KRAS and TERT mutations.

Polyserositis and endocrine disorders in a patient with anorexia nervosa: A case report

2025-07-01T12:01:51-05:00

Introduction: Anorexia nervosa is a psychiatric disorder that entails serious somatic sequelae, including endocrine and cardiovascular involvement. One of its rarest and most severe manifestations is polyserositis, which demands prompt clinical management.

Objective: To describe a case of anorexia nervosa complicated by polyserositis and profound endocrine dysfunction, emphasizing the diagnostic process, multidisciplinary management, and clinical evolution.

Case presentation: A 17-year-old female adolescent presented with a 10-month history of progressive weight loss, amenorrhea, cold intolerance, and autonomic symptoms. She was admitted after a syncopal episode with signs of shock—hypotension, bradycardia, and cachexia. Transthoracic echocardiography revealed a moderate-to-severe pericardial effusion with hemodynamic compromise, necessitating pericardiectomy and drainage. An exudative pleural effusion was also documented. Rheumatologic and oncologic work-ups were negative. Endocrine assessment showed hypogonadotropic hypogonadism, suppressed insulin-like growth factor-1 (IGF-1), elevated growth hormone levels, and dysregulation of the thyrotropic axis, all in the context of severe malnutrition. A progressive nutritional rehabilitation program was instituted, achieving a weekly weight gain of 600 g, which led to normalization of the hormonal profile and complete clinical resolution.

Discussion: Polyserositis in anorexia nervosa is a rare yet potentially life-threatening presentation. Its pathophysiology involves prolonged malnutrition, neuroendocrine dysfunction, and cardiovascular alterations. Diagnostic evaluation must rule out infectious, neoplastic, and autoimmune etiologies and should be conducted within a multidisciplinary framework.

Conclusion: This case underscores the need to consider anorexia nervosa as an underlying cause of polyserositis in severely malnourished adolescents. Monitored nutritional rehabilitation and a coordinated multidisciplinary approach were pivotal to achieving clinical and hormonal recovery.

Revista Colombiana de Endocrinología, Diabetes & Metabolismo

Molecular mechanisms of resistance to tyrosine kinase inhibitors in patients with iodine-refractory differentiated thyroid carcinoma

Polyserositis and endocrine disorders in a patient with anorexia nervosa: A case report