Immunotherapy-Induced Graves' Disease and Thyroiditis: A State-of-the-Art Review of Immune Checkpoint Inhibitor-Related Thyroid Dysfunction

Dr Neeraj Manikath , claude.ai

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized oncological therapeutics, yet their mechanism of action—unleashing T-cell responses—inevitably precipitates immune-related adverse events (irAEs). Thyroid dysfunction represents one of the most common endocrine irAEs, manifesting along a spectrum from subclinical hypothyroidism to fulminant thyrotoxicosis. This review critically examines ICI-induced thyroid disease, with particular emphasis on distinguishing de novo ICI-triggered Graves' disease from destructive thyroiditis—a clinical differentiation with profound therapeutic implications. We synthesize current evidence on pathophysiology, diagnostic algorithms, management strategies, and provide expert pearls for clinicians navigating this emerging clinical challenge at the intersection of oncology and endocrinology.

Keywords: Immune checkpoint inhibitors, thyroiditis, Graves' disease, immune-related adverse events, thyrotoxicosis, pembrolizumab, nivolumab

Introduction: The Double-Edged Sword of Immunotherapy

The advent of immune checkpoint inhibitors has transformed survival outcomes across multiple malignancies, from metastatic melanoma to non-small cell lung cancer. By blocking inhibitory receptors—primarily CTLA-4, PD-1, and PD-L1—these agents restore T-cell effector functions against tumor antigens. However, this immunological renaissance comes at a price: the same mechanisms that facilitate tumor rejection can precipitate autoimmune phenomena across virtually any organ system.

Thyroid dysfunction emerges as the most prevalent endocrine irAE, occurring in 6-10% of patients receiving PD-1 inhibitors (nivolumab, pembrolizumab), 3-8% with PD-L1 inhibitors (atezolizumab, durvalumab), and up to 15% with combination therapy (ipilimumab plus nivolumab).[1,2] Yet the term "thyroid dysfunction" belies considerable heterogeneity: patients may develop primary hypothyroidism, biphasic thyroiditis with transient thyrotoxicosis, or—less commonly but more dramatically—bona fide autoimmune hyperthyroidism indistinguishable from classical Graves' disease.

For the internist and endocrinologist, the critical challenge lies not merely in recognizing thyroid irAEs but in phenotyping them accurately. The distinction between ICI-induced Graves' disease and ICI-induced destructive thyroiditis dictates entirely different therapeutic pathways: one requires antithyroid drugs, the other supportive care. Misclassification risks both therapeutic misadventure and delayed cancer treatment.

Epidemiology and Risk Factors

Incidence Patterns

Thyroid irAEs demonstrate remarkable variation across ICI classes:

Anti-PD-1 agents: 6-10% overall thyroid dysfunction; thyrotoxicosis in 2.5-5%[3]
Anti-CTLA-4 agents: 3-5% thyroid dysfunction (predominantly hypothyroidism)
Combination therapy: Up to 15-20% thyroid dysfunction; highest rates of biphasic thyroiditis[4]
Anti-PD-L1 agents: 3-8% incidence, similar phenotypes to anti-PD-1

True ICI-induced Graves' disease—defined by positive thyroid-stimulating immunoglobulin (TSI) or TSH receptor antibodies (TRAb)—occurs in approximately 0.3-1% of all ICI recipients, representing roughly 10-15% of those developing thyrotoxicosis.[5,6]

Patient-Specific Risk Factors

Emerging data suggest several predisposing factors:

Pre-existing thyroid autoimmunity: Baseline anti-thyroid peroxidase (TPO) or anti-thyroglobulin (Tg) antibodies increase risk 2-3 fold[7]
Female sex: 1.5-2 times higher incidence, mirroring epidemiology of spontaneous autoimmune thyroid disease
Younger age: Patients <50 years demonstrate higher rates
Concurrent type 1 diabetes or vitiligo: Suggests broader autoimmune diathesis
HLA genotypes: Preliminary data implicate HLA-DR3, though large-scale pharmacogenomic studies are lacking[8]
Pre-existing thyroid nodularity or goiter: May harbor subclinical autoimmunity

Clinical Pearl: Baseline TSH and anti-TPO antibodies before ICI initiation allow risk stratification and facilitate interpretation of subsequent thyroid dysfunction.

Pathophysiology: Checkpoint Blockade and Thyroid Autoimmunity

Mechanisms of ICI-Induced Thyroid Dysfunction

The thyroid's vulnerability to ICI-related autoimmunity reflects several converging factors:

1. PD-1/PD-L1 Expression in Thyroid Tissue PD-L1 is constitutively expressed on thyroid follicular cells, particularly in the setting of pre-existing Hashimoto's thyroiditis. Checkpoint blockade removes this tolerogenic brake, permitting autoreactive T-cell infiltration.[9]

2. Epitope Spreading ICI therapy may amplify pre-existing, subclinical thyroid autoimmunity through epitope spreading—the sequential diversification of autoantibody targets following initial tissue damage. Patients with baseline anti-TPO antibodies are particularly susceptible.[10]

3. Molecular Mimicry Intriguing hypotheses suggest tumor antigens may share epitopes with thyroid antigens, such that anti-tumor immune responses "cross-react" with thyroid tissue. This phenomenon has been demonstrated in melanoma patients developing thyroiditis.[11]

4. Cytokine Dysregulation ICI therapy elevates circulating interferon-γ, IL-17, and IL-6—cytokines implicated in thyroid autoimmunity pathogenesis. The thyroid gland becomes collateral damage in the systemic inflammatory milieu.

Destructive Thyroiditis vs. De Novo Graves' Disease

The predominant pattern—destructive (thyrotoxic) thyroiditis—results from direct T-cell–mediated follicular cell destruction, releasing preformed thyroid hormone. Pathologically, this resembles subacute thyroiditis (without the pain) or Hashimoto's thyrotoxicosis.

In contrast, true ICI-induced Graves' disease reflects B-cell activation and production of TSH receptor–stimulating antibodies (TRAb/TSI). Whether ICIs directly trigger de novo TRAb production or unmask latent Graves' disease remains debated. Case series document patients with negative pre-treatment TRAb who develop strongly positive antibodies post-ICI, suggesting genuine induction rather than mere unmasking.[12,13]

Mechanistic Oyster: Why is ICI-induced Graves' rare compared to thyroiditis? The production of TSI requires not just T-cell help but coordinated B-cell activation—a more complex immunological event. Destructive thyroiditis requires only cytotoxic T-cell infiltration, a lower immunological "bar."

Clinical Presentation: Recognizing the Phenotypes

Timeline of Onset

Thyroid irAEs typically emerge within the first 3-6 months of ICI therapy:

Median onset: 6-12 weeks for anti-PD-1; slightly earlier (4-8 weeks) for combination therapy[14]
Range: Reports span from 2 weeks to >12 months after initiation
Pattern: Thyrotoxicosis (destructive or Graves') precedes hypothyroidism temporally

Clinical Hack: Any new-onset palpitations, tremor, or unexplained tachycardia within the first 4 months of ICI warrants immediate TSH assessment—don't wait for scheduled surveillance.

Biphasic Thyroiditis: The Classic Pattern

The archetypal ICI thyroid irAE follows a biphasic course:

Phase 1: Thyrotoxicosis (2-6 weeks duration)

Symptoms: Palpitations, tremor, anxiety, weight loss, heat intolerance
Often mild-to-moderate; rarely precipitates thyroid storm
Biochemistry: Suppressed TSH, elevated free T4/T3
Radioiodine uptake: Low or absent (<5%)

Phase 2: Hypothyroidism (often permanent)

Symptoms: Fatigue, weight gain, cold intolerance, cognitive slowing
Emerges 4-8 weeks after thyrotoxic phase
Biochemistry: Elevated TSH, low free T4
Typically requires long-term levothyroxine replacement

Approximately 40-50% of patients with ICI-induced thyroiditis transition to permanent hypothyroidism requiring levothyroxine.[15]

ICI-Induced Graves' Disease: The Mimetic Presentation

True ICI-triggered Graves' disease presents similarly to spontaneous Graves':

Sustained thyrotoxicosis: Persisting >6-8 weeks without transition to hypothyroidism
Goiter: Diffusely enlarged, firm thyroid gland (present in ~60% of ICI-Graves')
Graves' ophthalmopathy: Rare but reported; periorbital edema, proptosis, diplopia[16]
Dermopathy: Pretibial myxedema extraordinarily rare
Biochemistry: Suppressed TSH, elevated T4/T3, positive TRAb/TSI
Imaging: Elevated radioiodine uptake (if performed; often contraindicated due to iodinated CT contrast from staging scans)

Diagnostic Pearl: The absence of ophthalmopathy does NOT exclude ICI-induced Graves' disease. Only 30-50% of spontaneous Graves' patients have clinically apparent eye disease; ICI-Graves' follows similar patterns.

Subclinical Hypothyroidism: The Silent Majority?

Many patients develop isolated TSH elevation (subclinical hypothyroidism) without a preceding thyrotoxic phase:

Incidence: 5-8% of ICI recipients[17]
May represent "burnt-out" thyroiditis (unrecognized thyrotoxic phase) or primary autoimmune hypothyroidism
Management threshold: Generally treat if TSH >10 mIU/L or symptomatic

Diagnostic Evaluation: The Critical Differentiation

The sine qua non of clinical management is distinguishing destructive thyroiditis from Graves' disease. This determination hinges on four pillars: clinical course, antibody testing, imaging, and occasionally functional studies.

Step 1: Biochemical Confirmation

Initial Testing (all patients with suspected thyroid irAE):

TSH, free T4, free T3
Anti-TPO antibodies, anti-thyroglobulin antibodies
TRAb or TSI (critical for phenotyping)

Interpretation Framework:

Finding	Thyroiditis	Graves' Disease
TSH	Suppressed	Suppressed
Free T4/T3	Elevated (transient)	Elevated (sustained)
TRAb/TSI	Negative	Positive
Anti-TPO	Often positive	May be positive
Duration	2-6 weeks → hypothyroid	Persistent (>8 weeks)

Oyster for Fellows: Why measure both TRAb AND TSI? TRAb (by receptor binding assay) detects both stimulating and blocking antibodies; TSI (by bioassay) specifically measures thyroid-stimulating activity. In ICI-induced disease, TRAb typically suffices (sensitivity ~95%), but rare patients demonstrate TSI positivity with negative TRAb.[18]

Step 2: Imaging When Diagnosis Unclear

Thyroid Ultrasound with Doppler

Thyroiditis: Heterogeneous echotexture, hypoechogenicity, minimal vascularity
Graves' disease: Diffusely hypoechoic gland, markedly increased vascularity ("thyroid inferno")
Utility: Non-invasive, readily available, distinguishes two entities in 80-85% of cases[19]

Radioactive Iodine Uptake and Scan (RAIU)

Thyroiditis: Low uptake (<5% at 24 hours)
Graves' disease: Elevated uptake (>25-35% at 24 hours), diffuse uptake pattern
Limitations:
- Contraindicated if recent iodinated contrast (CT staging scans)
- Many centers avoid due to radiation exposure in cancer patients
- Increasingly supplanted by Doppler ultrasound

Clinical Hack: In patients with recent iodinated contrast (common in oncology), defer RAIU and rely on TRAb/TSI + Doppler ultrasound for phenotyping. If absolutely necessary, delay RAIU for 6-8 weeks post-contrast.

Step 3: Clinical Course Observation

When antibodies are negative but thyrotoxicosis persists:

Recheck TRAb/TSI in 2 weeks: Antibodies may "evolve" after symptom onset
Monitor duration: Thyroiditis rarely persists >6-8 weeks; sustained thyrotoxicosis favors Graves'
Assess response to beta-blockade: Thyroiditis symptoms resolve with supportive care; Graves' requires definitive therapy

Diagnostic Algorithm Summary

Thyrotoxicosis on ICI
↓
Measure: TSH, fT4, fT3, TRAb/TSI, anti-TPO
↓
TRAb/TSI Positive → Graves' Disease → Antithyroid drugs
↓
TRAb/TSI Negative → Thyroid Doppler ultrasound
↓
High vascularity → Consider Graves' (repeat TRAb in 2 weeks)
Low vascularity → Thyroiditis → Beta-blockade + supportive care
↓
If still uncertain → Observe course (thyroiditis self-limited <6 weeks)

Management: Tailored Therapeutic Strategies

Destructive Thyroiditis: Supportive Management

Acute Thyrotoxic Phase:

1. Beta-Adrenergic Blockade

Agent of choice: Propranolol 10-40 mg TID or metoprolol 25-50 mg BID
Rationale: Ameliorates adrenergic symptoms; propranolol also inhibits T4→T3 conversion
Duration: Continue until biochemical euthyroidism (typically 4-6 weeks)
Caution: Assess for contraindications (asthma, severe bradycardia)

2. Corticosteroids (Selective Use)

Indications:
- Severe thyrotoxicosis (fT4 >5 ng/dL, resting HR >120 bpm)
- Refractory symptoms despite beta-blockade
- Concurrent grade 3-4 non-thyroidal irAEs requiring steroids
Regimen: Prednisone 0.5 mg/kg/day (30-40 mg daily) for 5-7 days, then taper
Evidence: Small case series suggest symptom acceleration; no RCT data[20]
Caveat: May blunt anti-tumor efficacy of ICIs—oncology input essential

3. Monitoring Schedule

TSH, fT4 every 2 weeks during thyrotoxic phase
Anticipate transition to hypothyroidism at 4-8 weeks
Initiate levothyroxine when TSH >10 mIU/L or symptomatic

What NOT to Do:

❌ Antithyroid drugs (methimazole, propylthiouracil): Ineffective in destructive thyroiditis (no new hormone synthesis occurring)
❌ Routine corticosteroids: Reserve for severe cases; indiscriminate use risks infection and anti-tumor compromise
❌ ICI discontinuation: Thyroiditis alone (without concurrent severe irAEs) does NOT require ICI cessation

Clinical Pearl: Explain to patients that the thyrotoxic phase is self-limited—analogous to "inflammation releasing preformed hormone"—and will resolve spontaneously. This counseling reduces anxiety and sets realistic expectations.

ICI-Induced Graves' Disease: Definitive Thyroid Management

Acute Management:

1. Antithyroid Drugs (Primary Therapy)

Agent: Methimazole preferred (longer half-life, once-daily dosing, lower hepatotoxicity)
- Dosing: 10-20 mg daily (mild-moderate); 30-40 mg daily (severe)
Alternative: Propylthiouracil (PTU) 50-100 mg TID
- Indications: First trimester pregnancy, methimazole intolerance, thyroid storm
- Concern: Higher hepatotoxicity risk (FDA black box warning)
Monitoring: CBC, liver enzymes at baseline and 2-4 weeks (detect agranulocytosis, hepatitis)
Counseling: Warn about agranulocytosis symptoms (fever, pharyngitis) → immediate discontinuation

2. Beta-Blockade (Symptomatic Control)

Same regimen as thyroiditis (propranolol or metoprolol)
Continue until biochemical euthyroidism achieved (typically 6-12 weeks)

3. Monitoring and Titration

TSH, fT4 every 4-6 weeks
Target fT4 in upper-normal range initially (avoid over-suppression → worsening thyrotoxicosis)
Once euthyroid, reduce methimazole gradually (5 mg decrements every 4-6 weeks)

Definitive Therapy Considerations:

The management trajectory for ICI-induced Graves' differs from spontaneous Graves' due to competing oncologic priorities:

Radioactive Iodine Ablation (RAI):

Advantages: Definitive cure; avoids prolonged antithyroid drugs
Disadvantages:
- Requires ICI cessation for 4-6 weeks (radiation safety + potential RAI uptake interference)
- Risk of worsening Graves' ophthalmopathy (if present)
- Contraindicated with recent iodinated contrast
Role: Consider if sustained remission unlikely and cancer prognosis favorable

Thyroidectomy:

Indications:
- Large goiter causing compressive symptoms
- Failure/intolerance of antithyroid drugs
- Concurrent thyroid nodule requiring surgery
- Patient preference for rapid definitive therapy
Advantages: Immediate cure; enables prompt ICI resumption
Risk: Surgical morbidity (hypoparathyroidism, recurrent laryngeal nerve injury) in potentially immunocompromised hosts

"Block-Replace" vs. Titration Strategy:

Most favor titration (adjust methimazole dose to maintain euthyroidism) over block-replace (high-dose methimazole + levothyroxine) given simpler monitoring and lower drug burden

Therapeutic Hack: For patients with favorable cancer prognosis (expected survival >2 years) and poor Graves' control on antithyroid drugs, early thyroidectomy offers the advantage of "one-and-done" management—eliminating ongoing thyroid medication adjustments that complicate oncologic care.

The Critical Question: When to Hold or Discontinue ICIs?

General Principle: Thyroid irAEs alone rarely necessitate ICI discontinuation. Thyroid dysfunction is manageable and rarely life-threatening, whereas ICI cessation may compromise cancer outcomes.

CTCAE Grading for Thyroid irAEs:[21]

Grade 1 (asymptomatic): Continue ICI, initiate appropriate thyroid management
Grade 2 (symptomatic): Continue ICI, optimize medical therapy
Grade 3 (severe symptoms): Consider temporary ICI hold (1-2 weeks) if refractory; resume once controlled
Grade 4 (life-threatening, e.g., thyroid storm): Hold ICI; manage crisis; resume ICI only after multidisciplinary discussion

Thyroid Storm: Extraordinarily rare with ICI therapy (<10 case reports), but catastrophic. If suspected:

Emergency admission, ICU-level care
High-dose PTU (200 mg q4h) or methimazole (20 mg q4h), propranolol (60-80 mg q4h), hydrocortisone (100 mg q8h), cholestyramine (4 g q6h)
Hold ICI until resolved

Multidisciplinary Coordination: Every decision regarding ICI continuation/cessation should involve oncology. The risk-benefit calculus depends on cancer type, stage, alternative therapies, and thyroid irAE severity.

Practice Pearl: Document your rationale for continuing or holding ICIs explicitly in the medical record. This protects clinical decision-making and facilitates communication across subspecialties.

Special Populations and Scenarios

ICI-Induced Thyroid Disease in Pregnancy

While rare (most ICI recipients are not pregnant), case reports exist:

PTU preferred in first trimester (methimazole associated with aplasia cutis, choanal atresia)
Methimazole acceptable in second/third trimester
Levothyroxine dosing: Increase by 25-30% once pregnancy confirmed
Coordinate with maternal-fetal medicine: Fetal thyroid function monitoring may be needed

Concurrent Multiple Endocrine irAEs

Polyglandular autoimmune syndromes may emerge:

Hypothyroidism + type 1 diabetes + adrenal insufficiency
Recognize "polyendocrinopathy syndrome" pattern: unexplained hypoglycemia, electrolyte disturbances, refractory fatigue
Screen: Morning cortisol, ACTH stimulation test, hemoglobin A1c, GAD65 antibodies

Recurrence with ICI Re-Challenge

Limited data suggest:

Thyroid dysfunction recurs in 50-70% upon ICI resumption[22]
Typically reproduces original phenotype (thyroiditis → thyroiditis; Graves' → Graves')
Prophylactic levothyroxine does NOT prevent recurrence
Strategy: Heightened surveillance (TSH every 3-4 weeks) if ICI restarted

Prognostic Considerations: Thyroid irAEs and Cancer Outcomes

The irAE-Response Paradox

Intriguing observational data suggest patients developing irAEs demonstrate superior oncologic outcomes:

Meta-analyses show irAE development associated with improved progression-free survival (HR 0.48) and overall survival (HR 0.54)[23]
Thyroid irAEs specifically correlate with enhanced tumor responses in melanoma, NSCLC, RCC

Mechanistic Hypotheses:

irAEs as biomarker of robust immune activation
Shared antigens between thyroid and tumor (molecular mimicry)
Confounding by indication (patients surviving longer have more time to develop irAEs)

Clinical Implication: Thyroid dysfunction should be viewed as a potential favorable prognostic indicator—reassure patients and oncologists that management strategies exist.

Emerging Therapies and Future Directions

Novel Checkpoint Inhibitors

Next-generation agents targeting LAG-3, TIGIT, TIM-3 demonstrate distinct irAE profiles:

Relatlimab (anti-LAG-3): Lower thyroid irAE rates (~3%)
Combination regimens: May exhibit additive or synergistic irAE risks

Predictive Biomarkers

Research aims to identify pre-treatment predictors:

Baseline thyroid antibodies: Most robust predictor currently available
HLA genotyping: HLA-DR15, HLA-B*46:01 implicated in Asian cohorts[24]
Circulating cytokines: IL-17, CXCL10 under investigation

Prophylactic Strategies

Could high-risk patients benefit from prophylaxis?

Selenium supplementation: No evidence of benefit
Prophylactic levothyroxine: Does not prevent thyroiditis onset
Close surveillance: Current best strategy—TSH every 6 weeks for first 6 months

Clinical Pearls and Oysters: Synthesizing Expert Wisdom

Pearls for Practice

TRAb/TSI is your North Star: Positive = Graves', negative = thyroiditis in >90% of cases. Don't manage empirically—measure antibodies.
Thyroiditis is self-limited; Graves' is not: Duration of thyrotoxicosis is the single best clinical discriminator if antibodies are equivocal.
Never stop ICIs for thyroid irAEs alone: Coordinate with oncology, but isolated thyroid dysfunction is manageable without ICI cessation.
Anticipate the hypothyroid transition: Counsel patients with thyroiditis that levothyroxine will likely be needed within 4-8 weeks—this prevents the "surprise" of lifelong medication.
Beta-blockers are your friend: They address symptoms rapidly while you phenotype the disorder. Start immediately, sort out details later.
Steroids are rarely necessary: Reserve for severe thyrotoxicosis or concurrent grade 3-4 non-thyroidal irAEs. Routine use risks infection and may blunt anti-tumor response.
Methimazole over PTU: Unless first-trimester pregnancy, methimazole's safety profile and once-daily dosing make it preferable for ICI-induced Graves'.
Document your reasoning: The medicolegal landscape of irAE management is evolving. Explicitly document why you continued or held ICIs.
Think polyglandular: Isolated "fatigue" may be adrenal insufficiency, not hypothyroidism. Maintain broad differential in patients on ICIs.
irAEs may be prognostically favorable: Frame thyroid dysfunction positively—it suggests robust immune engagement that may translate to better cancer outcomes.

Oysters: Counterintuitive Insights

Oyster #1: Why is ICI-Graves' rare? True Graves' requires coordinated B-cell activation and TRAb/TSI production—a higher immunological threshold than simple T-cell–mediated destruction (thyroiditis). This explains the 10:1 ratio of thyroiditis to Graves'.

Oyster #2: Negative TRAb doesn't exclude Graves' entirely In 5-10% of cases, TRAb may be negative early; TSI bioassays detect additional cases. If clinical suspicion high (sustained thyrotoxicosis, thyroid inferno on Doppler), recheck antibodies in 2 weeks or proceed to RAIU.

Oyster #3: Corticosteroids don't "treat" thyroiditis—they modulate inflammation Steroids accelerate symptom resolution but don't alter disease course or hypothyroidism risk. Their benefit is symptomatic, not disease-modifying.

Oyster #4: The absence of ophthalmopathy is reassuring but not diagnostic Only 30-50% of spontaneous Graves' patients have clinically evident eye disease at diagnosis. ICI-Graves' mirrors this—lack of eye findings does NOT rule out Graves'.

Oyster #5: Cancer prognosis should guide definitive thyroid therapy For patients with limited life expectancy (<1 year), avoid thyroidectomy or RAI—medical management suffices. Reserve definitive therapy for those expected to survive long enough to benefit.

Conclusion: An Integrative Approach to ICI-Induced Thyroid Disease

Immune checkpoint inhibitors have irrevocably changed oncologic practice, yet their success obligates endocrinologists and internists to master the management of iatrogenic autoimmunity. ICI-induced thyroid disease exemplifies the complexity of modern immuno-oncology: a spectrum of disorders demanding precise phenotyping, individualized therapy, and multidisciplinary collaboration.

The core principle is straightforward—distinguish destructive thyroiditis from de novo Graves' disease using TRAb/TSI and clinical course. Yet the nuances are manifold: when to use steroids, whether to pursue definitive ablative therapy, how to balance thyroid management against oncologic imperatives, and how to counsel patients facing lifelong hormone replacement.

As checkpoint inhibitors proliferate—with novel targets, combination regimens, and expansion into adjuvant settings—the incidence of thyroid irAEs will only rise. Internists and endocrinologists must remain vigilant, protocol-driven yet flexible, and above all, communicative with oncology colleagues. The patient caught between cancer and autoimmunity deserves nothing less than seamless, expert, compassionate care that optimizes both their malignancy outcomes and their endocrine health.

The state-of-the-art in 2026 is clear: measure antibodies, phenotype accurately, treat appropriately, and never discontinue life-saving immunotherapy for a manageable thyroid disorder. Master these principles, and you will navigate this emerging frontier with confidence and competence.

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Author Contributions: This state-of-the-art review synthesizes current evidence and expert opinion for the practicing internist navigating ICI-induced thyroid disease.

Conflicts of Interest: None declared.

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