Thyroid nodule malignancy is associated with increased non-invasive hepatic fibrosis scores in metabolic subjects

Front Oncol. 2023 Oct 26:13:1233083. doi: 10.3389/fonc.2023.1233083. eCollection 2023.

Abstract

Introduction: Thyroid cancer incidence is increasing, and adiposity-related conditions are gaining space in its pathogenesis. In this study, we aimed to detect any anthropometric, biohumoral, and clinical features that might be associated with thyroid nodule malignancy, potentially representing novel non-invasive markers of thyroid cancer.

Materials and methods: The study was conducted in a group of 142 consecutive outpatients (47 men and 95 women) who underwent fine-needle aspiration biopsy/cytology (FNAB/C) due to suspicion of malignancy from January 2018 to September 2022. We compared lipid and glycemic blood profiles as well as non-invasive liver fibrosis indexes such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) between patients with benign and malignant newly diagnosed nodules. Then, we performed receiver operating characteristic (ROC) analysis to assess their best cutoff values for discrimination of malignant nodules and chi-squared test to evaluate the association of specific dysmetabolic conditions with malignancy. To understand whether and to what degree dysmetabolic conditions increased the risk of thyroid nodule malignancy, we also calculated the odds ratio (OR) of the main biomarkers.

Results: After FNAB/C, 121 (85%) patients were diagnosed with benign thyroid nodules, while 21 (15%) individuals were diagnosed with thyroid cancer. Comparing patients with benign and malignant nodules, we found that individuals with thyroid cancer exhibited increased body mass index (BMI) (p = 0.048) and fasting plasma glucose (p = 0.046). Intriguingly, considering non-invasive scores for liver fibrosis, subjects with thyroid cancer presented increased AAR (p < 0.001) and APRI (p = 0.007), and these scores were associated with malignancy (p < 0.005) with OR = 7.1 and OR = 5, respectively. Moreover, we showed that only in the cancer group, low levels of vitamin D correlated with stigmata of impaired metabolism.

Discussion: In our study, AAR and APRI scores were associated with thyroid nodule malignancy and could be used to predict it and to speed up the diagnostic process. From a pathogenic point of view, we speculated that metabolic-associated fatty liver disease (MAFLD) along with hyperglycemia and vitamin D deficiency may represent putative drivers of thyroid carcinogenesis.

Keywords: BMI; liver fibrosis; malignant thyroid nodule; obesity; thyroid cancer.

Grants and funding

AM is funded by Italian Association for Cancer Research—AIRC IG 2019 Id 23239; EU-JPI HDL-INTIMIC—MIUR FATMAL; MIUR-PON “R&I” 2014–2020 “BIOMIS” cod. ARS01_01220; POR Puglia FESR—FSE 2014–2020, “INNOMA” cod. 4TCJLV4. AM and PS are funded by the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3—Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union—NextGeneration EU; Project code PE00000003, Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001, Project title “ON Foods— Research and innovation network on food and nutrition Sustainability, Safety and Security—Working ON Foods”. LC is funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3—Call for tender No. 341 of March 15, 2022, of Italian Ministry of University and Research funded by the European Union—NextGeneration EU; Award Number: Project code PE0000015, Concession Decree No. 1243 of August 2, 2022, adopted by the Italian Ministry of University and Research, CUP H33C22000680006, Project title “Ageing well in an ageing society—A novel public-private alliance to generate socioeconomic, biomedical and technological solutions for an inclusive Italian ageing society—AGE-IT.