Graves' disease (GD) is a classical autoimmune disorder caused by interactions between genetic susceptibility and immune dysregulation. However, the transcriptomic mechanisms underlying disease relapse and remission, particularly those involving alternative splicing (AS), remain poorly understood.

Thyroid eye disease (TED) is the most common extra-thyroidal complication of Graves' disease, but its molecular pathogenesis is not fully understood. This study explored the mechanism associated with methyltransferase like 3 (METTL3), NOP2/Sun RNA methyltransferase 4 (NSUN4), and solute carrier family 2 member 3 (SLC2A3) in an in vitro TED model. Human normal orbital fibroblasts were stimulated with platelet-derived growth factor BB (PDGF-BB) to establish in vitro TED model. Differentially expressed genes were screened using online databases. Western blotting was performed for protein detection, and qPCR was used for mRNA quantification. CCK-8 assay and EdU assay were conducted to examine metabolic viability and proliferation, respectively. Hyaluronan (HA) production and glycolysis metabolism were assessed via commercial kits. Methylated RNA immunoprecipitation (MeRIP), RIP, dual-luciferase reporter assay, and RNA-protein pull-down assay were utilized for interaction analysis. Bioinformatics screening obtained 1139 differential genes and 45 glycolytic genes, yielding 2 overlapping genes that were considered as glycolysis-related genes in TED. SLC2A3 was highly expressed in TED and PDGF-BB-stimulated orbital fibroblasts, and silencing SLC2A3 suppressed PDGF-BB-induced cell proliferation, HA production and glycolysis. NSUN4 mediated the m5C methylation modification to increase SLC2A3 expression in an YBX1-dependent manner. NSUN4 inhibition restrained PDGF-BB-induced effects via downregulating SLC2A3. METTL3 mediated m6A methylation modification to reduce NSUN4 expression, with YTHDF2 as a reader protein. The influences of PDGF-BB on human orbital fibroblasts were significantly alleviated by METTL3 overexpression to down-regulate NSUN4. NSUN4 downregulation caused by METTL3-induced m6A modification of NSUN4 mRNA regulated m5C modification of SLC2A3 mRNA, thereby ameliorating PDGF-BB-induced proliferation, HA generation and glycolysis of human orbital fibroblasts in TED. The evidence uncovered the specific molecular mechanism underlying TED pathogenesis.

Graves' orbitopathy (GO) is a representative extrathyroidal manifestation of autoimmune thyroid disease. Despite extensive research, the precise pathogenic mechanisms remain incompletely understood. Moreover, the lack of an ideal animal model has limited in vivo investigation, with most studies relying on in vitro systems using orbital fibroblasts. In this review, we discuss currently available mouse models of GO and recent advances in experimental modeling strategies, aiming to provide an integrated framework for future research.

Sphenoid wing dysplasia is a recognized diagnostic feature of neurofibromatosis type 1, yet it rarely occurs in isolation. We present the case of a girl who had pulsatile exophthalmos since birth and was diagnosed with sphenoid wing dysplasia at 1 year and 2 months of age, with no clinical or familial evidence of neurofibromatosis type 1 identified during long-term follow-up. Progressive herniation of the temporal lobe into the left orbit prompted surgical intervention at age 12. Using a 3-dimensional printed skull base model, a patient-specific, hand-bent titanium mesh was preoperatively fabricated and implanted via a frontotemporal approach to reconstruct the superior orbital wall and restore separation between the cranial and orbital compartments. Postoperatively, the pulsatile exophthalmos resolved completely, and a transient abduction deficit recovered within 6 months. Follow-up imaging confirmed stable mesh positioning and durable compartment separation, with satisfactory cosmetic results maintained at 2 years. This case expands the clinical spectrum of sphenoid wing dysplasia by illustrating a neurofibromatosis type 1-negative phenotype and supports 3-dimensional model-assisted, patient-specific titanium mesh reconstruction as an effective strategy for correcting spheno-orbital defects and eliminating pulsatile exophthalmos. Accumulation of similar cases is needed to refine surgical indications, optimize timing, and assess the long-term durability of implant materials.

IntroductionOrbital involvement is a serious complication of ethmoiditis in children, often occurring because the ethmoid sinuses are very close to the orbit. Our work aimed to report the clinical presentation, treatment modalities and the outcome of orbital complications of acute ethmoiditis to identify common indicators for surgery.MethodsRetrospective observational study to review cases that were hospitalized in pediatrics and otorhinolaryngology departments of the Farhat Hached Hospital in Sousse, Tunisia, during the period from January 2013 to December 2023.ResultsWe collected 79 cases. The mean age was 4,55±3,64 years old. Five of our patients had anemia, six had allergic rhinitis, and one had asthma. Two other patients had undergone recent dental care. Palpebral edema and fever were the most frequently reported symptoms. A palpebral abscess was present in five cases, while nineteen cases exhibited exophthalmos. Seven children had limited occulomotricity, and one child had ophthalmoplegia.In addition, reduced visual acuity was reported in 3 cases. Referring to Chandler's stratification, we report 37 cases of preseptal cellulitis, 10 cases of orbital cellulitis and, 31 cases of subperiosteal abscess. Eleven patients required surgical treatment consisting of orbitotomy. Age equal to or above 5 years old was more associated with surgical treatment (p<0.001). The outcome was generally favorable.ConclusionOrbital complications of acute ethmoiditis are a low-prevalence high risk disease. Most patients are successfully treated without long-term complications. Younger children (<5 years) are less likely to undergo surgery.

Hyperthyroidism is characterized by elevated circulating thyroid hormone levels with suppressed levels of thyroid-stimulating hormone (TSH). Common manifestations include weight loss, tremor, palpitations, and heat intolerance, while psychosis is a rare neuropsychiatric manifestation. We report the case of a 47-year-old woman who presented with a three-month history of worsening irritability, destructive behavior, irrelevant speech, and multiple delusions, including grandiose, persecutory, and erotomanic types. She also exhibited excessive spending behavior, increased energy, and a reduced need for sleep. Further history revealed symptoms suggestive of untreated hyperthyroidism for three years before presentation. Physical examination showed exophthalmos, goiter, tachycardia, and mild hypertension. Thyroid function tests confirmed thyrotoxicosis, and she was diagnosed with organic psychosis secondary to Graves' disease. Despite treatment with antithyroid medication and beta-blockers, thyrotoxicosis and psychotic symptoms initially persisted. Adjunctive treatment with lithium, combined with psychotropic medication, resulted in marked biochemical and clinical improvement. This report highlights psychosis as a rare manifestation of untreated hyperthyroidism and emphasizes the importance of early recognition and multidisciplinary management involving both endocrinology and psychiatry.