Thyroid cancer (TC) remains the most common cancer in endocrinology. Differentiated thyroid cancer (DTC), the most common type of TC, generally has a favorable outlook with conventional treatment, which typically includes surgery along with radioiodine (RAI) therapy and thyroid-stimulating hormone (TSH) suppression through thyroid hormone therapy. However, a small subset of patients (less than 5%) develop resistance to RAI. This resistance occurs due to the loss of Na/I symporter (NIS) activity, which is crucial for iodine absorption in thyroid cells. The decline in NIS activity appears to be due to gene modifications, reconfigurations with irregular stimulation of signaling pathways such as MAPK and PI3K/Akt pathways. These molecular changes lead to a diminished ability of DTC cells to concentrate iodine, which makes RAI therapy ineffective. As a consequence, patients with radioiodine-refractory DTC require alternative treatments. Therapy with tyrosine kinase inhibitors (TKIs) has emerged as the primary treatment option to inhibit proliferation and growth of RAIR-DTC, targeting the pathways responsible for tumor progression. In this article, we analyze molecular processes responsible for RAI resistance and explore both conventional and emerging therapeutic strategies for managing RAIR-DTC, aiming to improve patient outcomes.

Non-functioning adrenal incidentalomas (NFAIs) have been placed in relationship with a higher risk of glucose profile anomalies, while the full-blown typical picture of Cushing’s syndrome (CS) and associated secondary (glucocorticoid-induced) diabetes mellitus is not explicitly confirmed in this instance. Our objective was to highlight the most recent data concerning the glucose profile, particularly, type 2 diabetes mellitus (T2DM) in NFAIs with/without mild autonomous cortisol secretion (MACS). This was a comprehensive review of the literature; the search was conducted according to various combinations of key terms. We included English-published, original studies across a 5-year window of publication time (from January 2020 until 1 April 2024) on PubMed. We excluded case reports, reviews, studies on T1DM or secondary diabetes, and experimental data. We identified 37 studies of various designs (14 retrospective studies as well 13 cross-sectional, 4 cohorts, 3 prospective, and 2 case–control studies) that analysed 17,391 individuals, with a female-to-male ratio of 1.47 (aged between 14 and 96 years). T2DM prevalence in MACS (affecting 10 to 30% of NFAIs) ranged from 12% to 44%. The highest T2DM prevalence in NFAI was 45.2% in one study. MACS versus (non-MACS) NFAIs (n = 16) showed an increased risk of T2DM and even of prediabetes or higher fasting plasma glucose or HbA1c (no unanimous results). T2DM prevalence was analysed in NFAI (N = 1243, female-to-male ratio of 1.11, mean age of 60.42) versus (non-tumour) controls (N = 1548, female-to-male ratio of 0.91, average age of 60.22) amid four studies, and two of them were confirmatory with respect to a higher rate in NFAIs. Four studies included a sub-group of CS compared to NFAI/MACS, and two of them did not confirm an increased rate of glucose profile anomalies in CS versus NFAIs/ACS. The longest period of follow-up with concern to the glycaemic profile was 10.5 years, and one cohort showed a significant increase in the T2DM rate at 17.9% compared to the baseline value of 0.03%. Additionally, inconsistent data from six studies enrolling 1039 individuals that underwent adrenalectomy (N = 674) and conservative management (N = 365) pinpointed the impact of the surgery in NFAIs. The regulation of the glucose metabolism after adrenalectomy versus baseline versus conservative management (n = 3) was improved. To our knowledge, this comprehensive review included one of the largest recent analyses in the field of glucose profile amid the confirmation of MACS/NFAI. In light of the rising incidence of NFAI/AIs due to easier access to imagery scans and endocrine evaluation across the spectrum of modern medicine, it is critical to assess if these patients have an increased frequency of cardio-metabolic disorders that worsen their overall comorbidity and mortality profile, including via the confirmation of T2DM.

Background: Irisin, a recently discovered muscle-originating hormone, has been found to act as a biomarker of several ailments, while no guideline clearly indicates its testing so far in any particular population category or pathological condition. Objective: We analyzed blood (circulating) irisin in relation to the potential correlations with the evaluation of glucose and bone profile. Methods: This was a prospective, pilot, exploratory study (between December 2024 and August 2025). The enrolled patients were menopausal women aged ≥50. Exclusion criteria: Endocrine tumors, thyroid dysfunction, malignancies, or chronic kidney disease. Baseline (fasting) testing was followed by 75 g oral glucose tolerance test (OGTT). Enzyme-linked immunosorbent assay (ELISA)-based irisin assay (MyBioSource) was performed. The subjects underwent central Dual-Energy X-Ray Absorptiometry (DXA), which provided lumbar, femoral neck and total hip bone mineral density (BMD)/T-score (GE Lunar Prodigy), and lumbar DXA-based trabecular bone score (TBS iNsight). Results: We enrolled 89 females [mean age of 62.84 ± 9.33 years, average years since menopause (YSM) of 15.94 ± 9.23]. Irisin (102.69 ± 98.14 ng/mL) did not correlate with age, YSM, but with body mass index (r = 0.36, p < 0.001). Bone formation marker osteocalcin (r = −0.25, p = 0.018) was negatively associated with irisin, amidst multiple other mineral metabolism assays (including PTH and 25-hydroxyvitamin D). Irisin positively correlated with insulin (r = 0.385, p = 0.0008), HbA1c (r = 0.243, p = 0.022), and HOMA-IR (r = 0.313, p = 0.007). Additional endocrine assays pointed a statistically significant association between irisin and TSH, respectively, ACTH (r = 0.267, p = 0.01, and r = 0.309, p = 0.041, respectively). No correlation irisin-BMD/T-score/TBS was confirmed. Conclusions: Irisin correlates with markers of glucose status (insulin, HOMA-IR, and HbA1c), as well as body mass index and, to a lesser extent, bone metabolism markers. Interestingly, TSH and ACTH correlations open a new (hypothesis-generating) perspective in the endocrine frame of approaching this exerkine. To the best of our knowledge, no distinct study has so far addressed the TBS–irisin relationship or pinpointed the glucose effects on TBS, particularly in menopausal women.