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.

Riedel thyroiditis (RT) is a rare immune-mediated inflammatory disease that destroys the thyroid parenchyma, replacing it with storiform fibrosis extending to the extrathyroidal tissue. Secondary fibrotic lesions can be associated as parts of the systemic IgG4-related disease. We present the case of a 52-year-old female patient who presented initially with subacute thyroiditis when corticosteroid treatment was initiated. After a year, compressive respiratory symptoms and dysphagia appear, and fine-needle aspiration cytology is performed to rule out malignancy, but without results. Thyroidectomy is performed, and histopathology shows scleroatrophic thyroiditis, with chronic inflammatory infiltrate containing eosinophils extending in the neighboring tissue, rare atrophic follicles, and obliterative vasculitis. Immunohistochemistry proves abundant plasma cells with IgG4 secretion; the macrophage is mainly the M2 subtype. RT is diagnosed, and a CT (computed tomography) scan is performed to detect peritracheal fibrosis and subtle pulmonary modifications. A literature review was performed that situates our findings in the context of the current literature. The last part discusses the immuno-inflammatory mechanisms behind IgG4-related diseases.

Introduction: Most differentiated thyroid cancers (DTC) have a good response to treatment. However, about 5% of DTC exhibit resistance to radioiodine (RAI), thus having a poor prognosis. Resistance to RAI occurs as a result of losing thyroid differentiation. Immunohistochemical analysis of thyroid cancers shows a substantial ability to predict cancer recurrence and its resistance to RAI. Case reports: The first case is a of a 66-year-old female, known with total thyroidectomy and bilateral laterocervical lymphodissection for papillary thyroid carcinoma. At the last assessment, whole body scintigraphy showed lung metastasis and an iodine fixing area in the right paratracheal region for which 140 mCi RAI was administered. Tissue section from the lateral and lower tracheal tumor block was subjected to immunostaining (TTF1, PAX8, Thyroglobulin, CK19 were positive in tumor cells, Ki67 15%) which confirmed the local secondary determination of poorly differentiated carcinoma originating in papillary carcinoma with clear and tall cells with weak affinity for capturing RAI. The second case is of a 77-year-old female, known with poorly DTC with trabecular pattern and outstanding areas of sclerohyalising type, with areas of capsular angioinvasion. Immunohistochemical markers (TTF1, PAX8 and Thyroglobulin positivity over 80%, Ki67 3%) indicated the possibility of response to radiotherapy, but with high risk of distant metastases. The third case is of a 45-year-old female, known with total thyroidectomy for poorly DTC and pulmonary and supradiaphragmatic lymph node metastases. Increased value of thyroglobulin (5141 ng/ml, N:3.5-77), the cumulative dose of 240 mCi RAI, the lack of iodine capturing images on anterior cervical region and whole body scintigraphy, as well as positive immunohistochemical markers (TTf1, PAX8, Thyroglobulin, CK19, Ki67 25%) for poorly DTC may suggest a decrease in the chances of response to future radiotherapy. Conclusion: The case series highlights the predictive capabilities of the immunohistochemical analysis concerning the dedifferentiation of thyroid cancers and their resistance to RAI.

Skin aging is a multidimensional biological process driven by intrinsic chronological changes, exposomal stress, endocrine–metabolic shifts, extracellular matrix remodeling, inflammaging, oxidative injury, barrier impairment, and microbiome dysbiosis. This review integrates current evidence on the endocrine–microbiome–skin axis and evaluates microbiome-directed bioactive strategies for preserving cutaneous homeostasis during aging. Particular attention is given to probiotics, prebiotics, postbiotics, synbiotics, phytoestrogens, polyphenols, bioactive peptides, antioxidants, mitochondrial protectors, adaptogens, and metabolic modulators. Their mechanisms are discussed in relation to collagen homeostasis, mitochondrial function, lipid barrier integrity, immune regulation, microbial metabolite signaling, and systemic endocrine–metabolic status. The review also examines advanced delivery platforms, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocarriers, nanoemulsions, encapsulated microbiome-active systems, and stimuli-responsive carriers, emphasizing their potential to improve compound stability, skin retention, controlled release, and target-site precision. Translational limitations are critically addressed, including strain and formulation specificity, insufficient long-term safety data, incomplete nanocarrier toxicology, regulatory ambiguity, and the need for personalization according to hormonal, metabolic, and microbiome profiles. Overall, microbiome-directed bioactive compounds combined with precision delivery systems represent a promising, but still evolving, strategy for delaying skin aging and restoring cutaneous homeostasis.