Disease Pathophysiology Research Report

Target Disease

• Disease Name: Graves' Disease
• MONDO ID: MONDO:0005130
• Category: Endocrine Disorder

Plan

Objective 1: Define core mechanisms. Objective 2: Map key molecular players (HGNC), cells (CL), tissues (UBERON), chemicals (CHEBI). Objective 3: Summarize disrupted GO processes and cellular components. Objective 4: Describe disease progression and phenotypes (HP). Objective 5: Incorporate 2023–2024 evidence with URLs/dates, statistics, and expert analyses. Objective 6: Provide ontology-anchored artifact. Objective 7: Synthesize final narrative.

Pathophysiology Description (current understanding)

Graves’ disease (GD) is an organ-specific autoimmune disorder driven predominantly by stimulatory thyrotropin receptor autoantibodies (TRAbs; mainly IgG1) that bind the thyrotropin receptor (TSHR) on thyrocytes, activating G protein–coupled signaling to increase thyroid hormone synthesis and release, and to promote thyrocyte growth (cAMP/PKA; with contributions from PI3K/AKT and MAPK cascades). Loss of tolerance arises from antigen presentation of TSHR peptides by HLA class II on antigen-presenting cells, activation of autoreactive CD4+ T cells, and CD40–CD40L-dependent B-cell help culminating in germinal-center maturation of TRAb-producing B cells; oligoclonal intrathyroidal B cells and possible epitope spreading are characteristic (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5). Epidemiologically, GD prevalence is ~1.2% with female:male ~10:1 and incidence ~20–40 per 100,000/year (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21).

Th subsets are dysregulated: enhanced Th1/Th17 and T follicular helper (Tfh) responses and reduced regulatory T cells (Tregs) support B-cell activation and autoantibody production; IL-17/IL-21 axes are implicated in sustaining autoimmunity and linking to clinical activity (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 21-24).

Genetic susceptibility is polygenic, with robust associations at HLA class II (e.g., HLA-DRB1), immune-regulatory loci CTLA4, PTPN22, CD40, FCRL3, and the thyroid-specific TSHR gene; epigenetic mechanisms and gut microbiome influences (dysbiosis, Th17/Treg imbalance) are recognized modifiers (Dec 2024; Reviews in Endocrine & Metabolic Disorders; https://doi.org/10.1007/s11154-023-09848-8; July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 21-24, lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21).

Thyroid eye disease (TED; Graves’ orbitopathy, GO) is an extrathyroidal manifestation arising when immune responses target antigens on orbital fibroblasts (OFs), notably TSHR and insulin-like growth factor 1 receptor (IGF-1R). Functional crosstalk between TSHR and IGF-1R promotes OF proliferation, hyaluronan (HA) production, adipogenesis (CD90– OFs), and fibrosis (CD90+ OFs), producing proptosis, diplopia, and soft-tissue inflammation; b‑arrestin-1 has been proposed as a scaffold mediating receptor cooperativity (Jan 2023; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2023.1062045; May 2024; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2024.1392956) (cui2023areviewof pages 1-2, shu2024immunecheckpointsnew pages 11-12). TED incidence is estimated ~0.54–0.9/100,000/year in males and 2.67–3.3/100,000/year in females; 25–50% of GD patients develop TED, with ~5–6% severe disease (Jan 2023; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2023.1062045) (cui2023areviewof pages 1-2).

Environmental triggers and modifiers include smoking (strongest TED risk), iodine exposure, infections/stress, postpartum immune shifts, radioiodine, and metabolic/oxidative stress; dyslipidemia has been linked to TED risk and corticosteroid responsiveness (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 21-24, lanzolla2024gravesdiseaselatest pages 18-21).

Immune checkpoint inhibitor (ICI)–related thyroid autoimmunity provides mechanistic insight: PD‑1 blockade (and to a lesser extent CTLA‑4 blockade) precipitates destructive thyroiditis, hypothyroidism, and less often Graves’ disease, highlighting the role of checkpoints in maintaining thyroidal tolerance (May 2024; Frontiers in Oncology; https://doi.org/10.3389/fonc.2024.1381250; Mar 2024; Heliyon; https://doi.org/10.1016/j.heliyon.2024.e27077) (zhao2024theriskof pages 5-8, wang2024thyroiddysfunction(td) pages 7-9).

Key Concepts and Definitions

• TRAbs: Functionally classified into stimulating (TSAb), blocking (TBAb), and neutral antibodies to TSHR; TSAb dominate in GD and drive thyrotoxicosis via cAMP/PKA, with PI3K/AKT and MAPK co-activation (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 1-5).
• TSHR–IGF‑1R crosstalk: Cooperative signaling on OFs explains HA accumulation and adipogenesis in TED; therapeutic targeting of IGF‑1R (teprotumumab) validates this axis (Jan 2023; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2023.1062045) (cui2023areviewof pages 1-2).
• Germinal-center autoimmunity: CD40–CD40L interactions between T cells and B cells are pivotal for TRAb maturation (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 18-21).

Key Molecular Players (HGNC), Cells (CL), Tissues (UBERON), Chemicals (CHEBI)

Table: Compact ontology-anchored table listing key genes, processes, compartments, cell types, anatomical sites and chemical entities implicated in Graves' disease and thyroid eye disease, with short mechanistic roles and primary supporting sources (2023–2024 reviews).

Biological Processes (GO) and Cellular Components

• Disrupted GO processes include cAMP-mediated signaling (GO:0019933), MAPK cascade (GO:0000165), PI3K signaling (GO:0014065), B-cell activation (GO:0042113), germinal center formation, adipocyte differentiation (GO:0045444), extracellular matrix organization (GO:0030198), and hyaluronan biosynthesis (GO:0030213) (July 2024; Nature Reviews Endocrinology; Jan 2023; Frontiers in Immunology) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21, cui2023areviewof pages 1-2).
• Key cellular locales: Plasma membrane (TSHR/IGF‑1R), cytosol (cAMP/PKA, PI3K/AKT, MAPK), extracellular space (TRAbs; shed TSHR A‑subunit) (July 2024; Nature Reviews Endocrinology) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21).

Disease Progression (sequence of events)

1) Genetic/epigenetic predisposition plus environmental triggers (e.g., smoking, iodine) initiate antigen presentation of TSHR peptides via HLA‑DR to autoreactive CD4+ T cells. 2) Tfh help and CD40–CD40L costimulation drive B-cell activation and germinal-center maturation to produce high-affinity TRAbs. 3) TSAb stimulate TSHR on thyrocytes activating cAMP/PKA and growth pathways (PI3K/AKT, MAPK), causing thyrotoxicosis and goiter. 4) In a subset, autoreactivity extends to orbital fibroblasts expressing TSHR and IGF‑1R; receptor crosstalk plus cytokine milieu (e.g., IL‑6, Th17 signals) promotes HA deposition, adipogenesis (CD90– OFs), and fibrosis (CD90+ OFs), driving TED. 5) Chronicity features epitope spreading and fluctuating TRAb titers; external modifiers (radioiodine, dyslipidemia) influence TED risk and activity (July 2024; Nature Reviews Endocrinology; Jan 2023; Frontiers in Immunology) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21, cui2023areviewof pages 1-2, lanzolla2024gravesdiseaselatest pages 21-24).

Phenotypic Manifestations (HP terms; selected)

• Hyperthyroidism/thyrotoxicosis (HP:0000820), weight loss (HP:0001824), tachycardia/atrial fibrillation (HP:0005110), goiter (HP:0004373), ophthalmopathy with proptosis (HP:0000520) and diplopia (HP:0000651), pretibial myxedema (HP:0010971), acropachy (HP:0006265). AF occurs in ~10% overall and is more prominent in older adults; pretibial myxedema 0.5–4.3%; acropachy ~1% (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 18-21).

Recent Developments and Latest Research (2023–2024 focus)

• Authoritative synthesis: Lanzolla et al. delineate modern GD immunobiology, genetics, microbiome influences, and the mechanistic basis for targeted therapies (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 21-24, lanzolla2024gravesdiseaselatest pages 18-21).
• TED mechanism and targeting: Reviews highlight TSHR–IGF‑1R crosstalk and OF subset biology, supporting IGF‑1R inhibition (teprotumumab) and exploration of IL‑6R blockade and other immunomodulators (Jan 2023; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2023.1062045; May 2024; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2024.1392956) (cui2023areviewof pages 1-2, shu2024immunecheckpointsnew pages 11-12).
• Microbiome: Integrative evidence implicates dysbiosis and Th17/Treg imbalance in GD/TED; interventional microbiome strategies are under study (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 21-24).
• Immune checkpoint inhibitor–related thyroid dysfunction: Recent meta-analysis (48 RCTs through Nov 2023) shows PD‑1 inhibitors increase risk of hypothyroidism (RR≈4.76–9.69 by agent), hyperthyroidism (RR≈9.22–9.69), thyroiditis (RR≈5.95) and other endocrinopathies; tumor-specific risks vary (May 2024; Frontiers in Oncology; https://doi.org/10.3389/fonc.2024.1381250). Real-world 2019–2023 retrospective data show 22.3% thyroid irAEs after PD‑1/PD‑L1 therapy, 75.1% hypothyroidism; baseline TPOAb/TgAb positivity increases risk (BMC Endocrine Disorders; 2025 online; data through 2023; https://doi.org/10.1186/s12902-025-01986-1). A 2024 review in advanced lung cancer summarizes improved outcomes in patients who develop TD (Mar 2024; Heliyon; https://doi.org/10.1016/j.heliyon.2024.e27077) (zhao2024theriskof pages 5-8, gong2025riskfactorsand pages 1-2, wang2024thyroiddysfunction(td) pages 7-9).

Current Applications and Real-World Implementations

• TRAb assays (3rd generation binding and cell-based bioassays) are central to diagnosis, differential diagnosis, prognostication (risk of relapse), pregnancy management, and neonatal risk assessment; for example, maternal TRAb ≥5–5.9 IU/L in mid–late pregnancy predicts fetal/neonatal thyroid dysfunction (Dec 2024; BMC Endocrine Disorders; https://doi.org/10.1186/s12902-024-01809-9) (kalra2024bestpracticesin pages 7-9).
• Targeted therapies informed by mechanism: IGF‑1R inhibition (teprotumumab) is an FDA-approved therapy for moderate–severe active TED, reducing proptosis and inflammatory activity, consistent with TSHR–IGF‑1R crosstalk in OFs (Jan 2023; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2023.1062045) (cui2023areviewof pages 1-2). Additional mechanistically aligned agents under evaluation include anti‑CD40 (iscalimab), B‑cell depletion (rituximab), IL‑6R blockade (tocilizumab), antigen-specific TSHR peptide immunotherapy (ATX‑GD‑59), TSHR‑blocking monoclonals (K1‑70), and small-molecule TSHR antagonists (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 18-21).

Expert Opinions and Authoritative Analyses

• Nature Reviews Endocrinology (2024) provides consensus-level synthesis across genetics, immunopathogenesis, environmental risks, and targeted therapy rationale, and emphasizes the transition from symptomatic control toward mechanism-based interventions (July 2024; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21).
• Frontiers in Immunology (2023, 2024) reviews detail TSHR/IGF‑1R biology, fibroblast subsets, cytokine circuits, and immune checkpoints in TED pathogenesis, supporting current and emerging targeted strategies (Jan 2023; https://doi.org/10.3389/fimmu.2023.1062045; May 2024; https://doi.org/10.3389/fimmu.2024.1392956) (cui2023areviewof pages 1-2, shu2024immunecheckpointsnew pages 11-12).

Relevant Statistics and Data (recent)

• Epidemiology: GD prevalence ~1.2%; incidence 20–40/100,000/year; female:male ~10:1 (July 2024; Nature Reviews Endocrinology; https://doi.org/10.1038/s41574-024-01016-5) (lanzolla2024gravesdiseaselatest pages 1-5).
• TED burden: 25–50% of GD with TED; severe in ~5–6% (Jan 2023; Frontiers in Immunology; https://doi.org/10.3389/fimmu.2023.1062045) (cui2023areviewof pages 1-2).
• ICI-related thyroid dysfunction: PD‑1 therapy increases relative risk of hypothyroidism (RR≈5–10), hyperthyroidism (RR≈9), thyroiditis (RR≈~4–6) vs controls; real-world incidence ~22% any thyroid irAE (2019–2023) with 75% hypothyroidism dominance (May 2024; Frontiers in Oncology; https://doi.org/10.3389/fonc.2024.1381250; Jul 2025 online/BMC Endocrine Disorders data through 2023; https://doi.org/10.1186/s12902-025-01986-1) (zhao2024theriskof pages 5-8, gong2025riskfactorsand pages 1-2).
• TRAb clinical performance/use: Maternal TRAb >5–5.9 IU/L predicts neonatal thyroid dysfunction, with reported sensitivity 100% and specificity up to 82% for significant fetal/neonatal thyroid effects; TRAb ≥10.67 IU/L predicts severe TAO with 66.7% sensitivity and 84.9% specificity; TRAb declines of ~90% over 3 years correlate with pediatric remission on antithyroid drugs (Dec 2024; BMC Endocrine Disorders; https://doi.org/10.1186/s12902-024-01809-9) (kalra2024bestpracticesin pages 7-9).

Evidence Items (selected with PMIDs/DOIs/URLs)

• Lanzolla G, Marinò M, Menconi F. Graves disease: latest understanding of pathogenesis and treatment options. Nature Reviews Endocrinology. 2024-07. https://doi.org/10.1038/s41574-024-01016-5 (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21).
• Shu X et al. Immune checkpoints: new insights into the pathogenesis of thyroid eye disease. Frontiers in Immunology. 2024-05. https://doi.org/10.3389/fimmu.2024.1392956 (shu2024immunecheckpointsnew pages 11-12).
• Cui X et al. TSHR- and IGF‑1R-related pathogenesis and treatment of Graves’ orbitopathy. Frontiers in Immunology. 2023-01. https://doi.org/10.3389/fimmu.2023.1062045 (cui2023areviewof pages 1-2).
• Zhao P et al. Endocrine irAEs with PD‑1 inhibitors: systematic review/meta-analysis. Frontiers in Oncology. 2024-05. https://doi.org/10.3389/fonc.2024.1381250 (zhao2024theriskof pages 5-8).
• Wang Y et al. Thyroid dysfunction induced by PD‑1/PD‑L1 inhibitors in lung cancer. Heliyon. 2024-03. https://doi.org/10.1016/j.heliyon.2024.e27077 (wang2024thyroiddysfunction(td) pages 7-9).
• Kalra S et al. Best practices: TRAb in diagnosis, prognosis, pregnancy. BMC Endocrine Disorders. 2024-12. https://doi.org/10.1186/s12902-024-01809-9 (kalra2024bestpracticesin pages 7-9).

Structured Annotations for Knowledge Base

• Genes/Proteins (HGNC): TSHR, IGF1R, CTLA4, PTPN22, CD40, FCRL3, HLA‑DRB1, FOXP3, IL6, IL17A, IL21, PDCD1 (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 21-24, lanzolla2024gravesdiseaselatest pages 18-21, cui2023areviewof pages 1-2, shu2024immunecheckpointsnew pages 11-12).
• Biological Processes (GO): cAMP-mediated signaling (GO:0019933), MAPK cascade (GO:0000165), PI3K signaling (GO:0014065), B-cell activation (GO:0042113), germinal center formation, adipocyte differentiation (GO:0045444), extracellular matrix organization (GO:0030198), hyaluronan biosynthetic process (GO:0030213) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21, cui2023areviewof pages 1-2).
• Cellular Components (GO): plasma membrane (GO:0005886), extracellular space (GO:0005615), cytosol (GO:0005829) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21, cui2023areviewof pages 1-2).
• Cell Types (CL): thyrocyte (CL:0000066), B cell (CL:0000236), Tfh (CL:0000913), Th17 (CL:0000894), Treg (CL:0000815), orbital fibroblast (CL:0000057), fibrocyte CD34+ (CL:0002324) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21, cui2023areviewof pages 1-2).
• Anatomical (UBERON): thyroid (UBERON:0002046), orbit (UBERON:0001651), extraocular muscle (UBERON:0001134) (cui2023areviewof pages 1-2, lanzolla2024gravesdiseaselatest pages 18-21).
• Chemical entities (CHEBI): cAMP (CHEBI:17489), hyaluronan (CHEBI:18064), iodine (CHEBI:24858), selenium (CHEBI:27568), thyroxine/T4 (CHEBI:18332), triiodothyronine/T3 (CHEBI:28775) (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 18-21, cui2023areviewof pages 1-2).

Special Populations and Contexts

• Neonatal Graves’ disease: Transplacental maternal TRAb drives fetal/neonatal thyrotoxicosis; maternal TRAb ≥5–5.9 IU/L in mid–late pregnancy is a high-risk threshold guiding fetal surveillance and neonatal planning (Dec 2024; BMC Endocrine Disorders; https://doi.org/10.1186/s12902-024-01809-9) (kalra2024bestpracticesin pages 7-9).
• ICI-induced thyroid autoimmunity: Quantitatively elevated risks with PD‑1 inhibitors, particularly hypothyroidism and hyperthyroidism; risk is higher with pre-existing thyroid autoantibodies and varies by agent and tumor type (May 2024; Frontiers in Oncology; https://doi.org/10.3389/fonc.2024.1381250; Mar 2024; Heliyon; https://doi.org/10.1016/j.heliyon.2024.e27077) (zhao2024theriskof pages 5-8, wang2024thyroiddysfunction(td) pages 7-9).

Conclusion

GD pathophysiology reflects a canonical model of loss of tolerance to TSHR with Th1/Th17/Tfh–B-cell collaboration, yielding TSAb-mediated hyperthyroidism through cAMP/PKA and growth signaling. Genetic susceptibility (HLA, CTLA4, PTPN22, CD40, FCRL3, TSHR), environmental modifiers (e.g., smoking, iodine), and gut dysbiosis shape disease risk and expression. TED emerges from TSHR–IGF‑1R-driven OF activation, HA accumulation, adipogenesis, and fibrosis. Translationally, TRAb assays underpin precision diagnosis, risk stratification in pregnancy, and prognostication, while IGF‑1R inhibition (teprotumumab) and emerging CD40/TSHR-targeted therapies exemplify mechanism-based interventions. The expanded experience with ICI-related thyroiditis/hypothyroidism illuminates checkpoint roles in thyroidal tolerance and provides quantitative risk benchmarks for modern oncology care (lanzolla2024gravesdiseaselatest pages 1-5, lanzolla2024gravesdiseaselatest pages 21-24, lanzolla2024gravesdiseaselatest pages 18-21, cui2023areviewof pages 1-2, shu2024immunecheckpointsnew pages 11-12, kalra2024bestpracticesin pages 7-9, zhao2024theriskof pages 5-8, wang2024thyroiddysfunction(td) pages 7-9).

References

1. (lanzolla2024gravesdiseaselatest pages 1-5): Giulia Lanzolla, Michele Marinò, and Francesca Menconi. Graves disease: latest understanding of pathogenesis and treatment options. Nature reviews. Endocrinology, 20:647-660, Jul 2024. URL: https://doi.org/10.1038/s41574-024-01016-5, doi:10.1038/s41574-024-01016-5. This article has 72 citations.

2. (lanzolla2024gravesdiseaselatest pages 18-21): Giulia Lanzolla, Michele Marinò, and Francesca Menconi. Graves disease: latest understanding of pathogenesis and treatment options. Nature reviews. Endocrinology, 20:647-660, Jul 2024. URL: https://doi.org/10.1038/s41574-024-01016-5, doi:10.1038/s41574-024-01016-5. This article has 72 citations.

3. (lanzolla2024gravesdiseaselatest pages 21-24): Giulia Lanzolla, Michele Marinò, and Francesca Menconi. Graves disease: latest understanding of pathogenesis and treatment options. Nature reviews. Endocrinology, 20:647-660, Jul 2024. URL: https://doi.org/10.1038/s41574-024-01016-5, doi:10.1038/s41574-024-01016-5. This article has 72 citations.

4. (cui2023areviewof pages 1-2): Xuejiao Cui, Futao Wang, and Cong Liu. A review of tshr- and igf-1r-related pathogenesis and treatment of graves’ orbitopathy. Frontiers in Immunology, Jan 2023. URL: https://doi.org/10.3389/fimmu.2023.1062045, doi:10.3389/fimmu.2023.1062045. This article has 50 citations and is from a peer-reviewed journal.

5. (shu2024immunecheckpointsnew pages 11-12): Xingyi Shu, Yuchao Shao, Yuqing Chen, Chengcheng Zeng, Xiao Huang, and Ruili Wei. Immune checkpoints: new insights into the pathogenesis of thyroid eye disease. Frontiers in Immunology, May 2024. URL: https://doi.org/10.3389/fimmu.2024.1392956, doi:10.3389/fimmu.2024.1392956. This article has 16 citations and is from a peer-reviewed journal.

6. (zhao2024theriskof pages 5-8): Pengfei Zhao, Ting Zhao, Lihong Yu, Wenming Ma, Wenyu Liu, and Chenning Zhang. The risk of endocrine immune-related adverse events induced by pd-1 inhibitors in cancer patients: a systematic review and meta-analysis. Frontiers in Oncology, May 2024. URL: https://doi.org/10.3389/fonc.2024.1381250, doi:10.3389/fonc.2024.1381250. This article has 9 citations and is from a poor quality or predatory journal.

7. (wang2024thyroiddysfunction(td) pages 7-9): Yanling Wang, Xiaoxuan Yang, Jia Ma, Shenglan Chen, Ping Gong, and Ping Dai. Thyroid dysfunction (td) induced by pd-1/pd-l1 inhibitors in advanced lung cancer. Heliyon, 10:e27077, Mar 2024. URL: https://doi.org/10.1016/j.heliyon.2024.e27077, doi:10.1016/j.heliyon.2024.e27077. This article has 4 citations and is from a peer-reviewed journal.

8. (viola2025graves’diseaseis pages 11-13): Nicola Viola, Alessandro Colleo, Mauro Casula, Chiara Mura, Francesco Boi, and Giulia Lanzolla. Graves’ disease: is it time for targeted therapy? a narrative review. Medicina, 61:500, Mar 2025. URL: https://doi.org/10.3390/medicina61030500, doi:10.3390/medicina61030500. This article has 5 citations and is from a poor quality or predatory journal.

9. (gong2025riskfactorsand pages 1-2): Wenwen Gong, Erhan Zheng, Minchao Liu, Yaliang Han, Zhaohui Lyu, and Qinghua Guo. Risk factors and outcomes of thyroid immune-related adverse events following pd-1/pd-l1 inhibitors treatment in a large tertiary chinese center. BMC Endocrine Disorders, Jul 2025. URL: https://doi.org/10.1186/s12902-025-01986-1, doi:10.1186/s12902-025-01986-1. This article has 0 citations and is from a peer-reviewed journal.

10. (kalra2024bestpracticesin pages 7-9): Sanjay Kalra, Shahjada Selim, Dina Shrestha, Noel Somasundaram, Syed Abbas Raza, Manash P. Baruah, Saptarshi Bhattacharya, Sharvil Gadve, Ganapathi Bantwal, and Rakesh Sahay. Best practices in the laboratory diagnosis, prognostication, prediction, and monitoring of graves’ disease: role of trabs. BMC Endocrine Disorders, Dec 2024. URL: https://doi.org/10.1186/s12902-024-01809-9, doi:10.1186/s12902-024-01809-9. This article has 2 citations and is from a peer-reviewed journal.