Subacute Thyroiditis Masquerading as Fever of Unknown Origin: A Critical Care Perspective

Dr Neeraj Manikath ,claude.ai

Abstract

Background: Subacute thyroiditis (SAT), also known as de Quervain's thyroiditis, represents a frequently overlooked cause of fever of unknown origin (FUO) in critical care settings. This inflammatory thyroid disorder can mimic sepsis and other systemic inflammatory conditions, leading to diagnostic delays and inappropriate antibiotic therapy.

Objective: To provide critical care physicians with a comprehensive understanding of SAT as a cause of FUO, emphasizing diagnostic clues, pathophysiology, and evidence-based management strategies.

Methods: Comprehensive literature review of peer-reviewed articles, case series, and clinical guidelines from 1990-2024.

Conclusions: Early recognition of SAT through clinical vigilance, appropriate biochemical testing, and imaging can prevent unnecessary investigations and treatments while ensuring optimal patient outcomes.

Keywords: Subacute thyroiditis, fever of unknown origin, thyrotoxicosis, critical care, diagnosis

Introduction

Fever of unknown origin continues to challenge clinicians in critical care settings, with infectious causes often suspected first. However, non-infectious inflammatory conditions account for approximately 20-30% of FUO cases¹. Subacute thyroiditis, first described by Fritz de Quervain in 1904, represents a self-limiting inflammatory condition that can present as prolonged fever, mimicking sepsis and leading to extensive workups and inappropriate antibiotic therapy².

The incidence of SAT peaks in the fourth and fifth decades of life, with a female predominance of 3-5:1³. While generally benign, the condition can cause significant morbidity when unrecognized, particularly in critical care environments where the systemic inflammatory response may be attributed to other causes.

Pathophysiology

Viral Trigger and Inflammatory Cascade

Subacute thyroiditis typically follows a viral upper respiratory tract infection by 2-8 weeks. Common preceding viral infections include:

Coxsackievirus
Epstein-Barr virus
Influenza A and B
Adenovirus
Echovirus
Mumps virus⁴

The inflammatory process involves direct viral invasion of thyroid follicular cells, triggering an autoimmune response. This results in:

Follicular disruption leading to thyroid hormone release
Granulomatous inflammation with giant cell infiltration
Cytokine release causing systemic symptoms
Complement activation contributing to the acute phase response

Triphasic Clinical Course

SAT characteristically follows a triphasic pattern:

Thyrotoxic phase (2-6 weeks): Excess hormone release
Hypothyroid phase (2-6 months): Thyroid exhaustion
Recovery phase (6-12 months): Normalization⁵

Clinical Presentation

Cardinal Features

🔍 PEARL: The classic triad consists of:

Neck pain (90% of cases) - often severe, radiating to jaw/ears
Fever (80% of cases) - typically 38-40°C
Thyroid tenderness on palpation

Systemic Manifestations

Patients may present with a constellation of symptoms that can mimic sepsis:

Constitutional symptoms: Fatigue, malaise, weight loss
Cardiovascular: Palpitations, tachycardia, chest pain
Neuropsychiatric: Anxiety, tremor, heat intolerance
Gastrointestinal: Nausea, vomiting, diarrhea
Musculoskeletal: Myalgia, arthralgia

⚠️ OYSTER: Up to 10% of patients may present with painless thyroiditis, making diagnosis particularly challenging⁶.

Diagnostic Approach

Laboratory Investigations

Thyroid Function Tests

TSH: Suppressed (<0.1 mIU/L) in thyrotoxic phase
Free T4/T3: Elevated initially, then low in hypothyroid phase
Thyroglobulin: Markedly elevated (>100 ng/mL)
Anti-TPO/Anti-Tg: Usually negative or low-positive⁷

Inflammatory Markers

ESR: Characteristically very high (>50 mm/hr, often >100 mm/hr)
CRP: Elevated (>50 mg/L)
WBC: Normal or mildly elevated
Procalcitonin: Normal (helps differentiate from bacterial infection)

💡 HACK: An ESR >100 mm/hr in a febrile patient with neck pain should immediately raise suspicion for SAT, even before thyroid function tests are available.

Imaging Studies

Thyroid Ultrasound

Hypoechoic areas corresponding to inflammation
Decreased vascularity on Doppler
Heterogeneous echogenicity
Pseudonodular appearance⁸

Radioiodine Uptake Scan

Suppressed uptake (<5% at 24 hours) - pathognomonic
Patchy uptake pattern in some cases
Essential for differential diagnosis⁹

🔍 PEARL: The combination of thyrotoxicosis with suppressed radioiodine uptake is virtually diagnostic of SAT.

Differential Diagnosis

Infectious Causes

Acute suppurative thyroiditis: Usually unilateral, abscess formation
Pneumonia with thyroid involvement: Rare but reported
Sepsis: Procalcitonin elevation, positive cultures

Non-infectious Causes

Graves' disease: High radioiodine uptake, positive TRAb
Toxic multinodular goiter: Patchy increased uptake
Amiodarone-induced thyrotoxicosis: Drug history, different uptake pattern
Postpartum thyroiditis: Timing, painless presentation¹⁰

Management Strategies

Acute Phase Management

Symptomatic Relief

First-line therapy:

NSAIDs: Ibuprofen 400-600 mg TID or naproxen 500 mg BID
Aspirin: 650 mg QID (anti-inflammatory dose)
Duration: 2-4 weeks, then gradual taper

💡 HACK: Start with maximum anti-inflammatory doses of NSAIDs rather than analgesic doses - the response is often dramatic within 24-48 hours.

Corticosteroids

Indications:

Severe symptoms unresponsive to NSAIDs
Contraindications to NSAIDs
Significant systemic illness

Regimen:

Prednisolone: 40-60 mg daily × 2 weeks
Taper: Reduce by 10 mg weekly
Duration: 6-8 weeks total¹¹

⚠️ OYSTER: Premature discontinuation of steroids can lead to symptom recurrence in up to 20% of patients.

Thyrotoxicosis Management

Beta-blockers for symptom control:

Propranolol: 40-80 mg BID
Metoprolol: 50-100 mg BID
Atenolol: 50-100 mg daily

Important: Antithyroid drugs (methimazole, propylthiouracil) are contraindicated as they don't affect hormone release from destroyed follicles¹².

Monitoring and Follow-up

Acute Phase (First 2 months)

Weekly: Thyroid function tests
Bi-weekly: ESR, CRP monitoring
Clinical assessment: Symptom resolution

Recovery Phase (2-12 months)

Monthly: Thyroid function tests
Quarterly: Clinical evaluation
Annual: Long-term thyroid function assessment

🔍 PEARL: Approximately 10-15% of patients develop permanent hypothyroidism requiring lifelong levothyroxine therapy¹³.

Critical Care Considerations

ICU Presentation Scenarios

Mimicking Sepsis

SAT patients may present with:

High fever (>39°C)
Tachycardia (>120 bpm)
Altered mental status (thyrotoxic delirium)
Elevated inflammatory markers

💡 HACK: In any ICU patient with unexplained fever and tachycardia, palpate the thyroid gland - tenderness may be the only clue.

Thyrotoxic Crisis

Rare but life-threatening complication:

Hyperthermia (>40°C)
Severe tachycardia/atrial fibrillation
Heart failure
Altered consciousness
Gastrointestinal dysfunction¹⁴

Management:

Immediate beta-blockade: Propranolol 1-2 mg IV q2-4h
Corticosteroids: Hydrocortisone 300 mg IV q8h
Supportive care: Fluid resuscitation, cooling measures
Avoid antithyroid drugs

Antibiotic Stewardship

⚠️ OYSTER: Inappropriate antibiotic therapy is common in undiagnosed SAT, contributing to:

Antibiotic resistance
Adverse drug reactions
Healthcare costs
Delayed appropriate treatment

Best practice: Obtain thyroid function tests and ESR before initiating empirical antibiotics in patients with FUO and neck symptoms.

Special Populations

Pregnancy and Postpartum

Diagnosis: More challenging due to physiological changes
Treatment: Avoid NSAIDs in third trimester
Monitoring: Increased risk of postpartum thyroiditis overlap¹⁵

Elderly Patients

Presentation: Often atypical with predominant cardiovascular symptoms
Complications: Higher risk of atrial fibrillation and heart failure
Treatment: Lower initial doses of beta-blockers

Immunocompromised Patients

Differential: Broader, including opportunistic infections
Treatment: Careful steroid use, consider infectious workup
Monitoring: Enhanced surveillance for complications

Prognosis and Long-term Outcomes

Acute Phase Recovery

Symptoms: Resolve within 2-6 weeks with appropriate treatment
Biochemical: Normalization within 2-4 months
Recurrence: <2% of patients experience relapse¹⁶

Long-term Sequelae

Permanent hypothyroidism: 10-15% of patients
Thyroid nodules: May develop in 5-10% of cases
Psychological impact: Anxiety about recurrence

🔍 PEARL: Patients with higher initial thyroglobulin levels (>300 ng/mL) have increased risk of permanent hypothyroidism.

Future Directions and Research

Biomarkers

Thyroglobulin: Potential prognostic marker
Cytokine profiles: IL-6, TNF-α as severity indicators
Genetic markers: HLA associations under investigation¹⁷

Therapeutic Advances

Targeted anti-inflammatory therapy: Tocilizumab case reports
Novel imaging techniques: Elastography for diagnosis
Personalized treatment: Based on genetic profiles

Clinical Decision-Making Algorithm

Fever + Neck Pain + Thyroid Tenderness
                    ↓
        Obtain: TSH, Free T4, ESR, CRP
                    ↓
    Low TSH + High T4 + ESR >50 mm/hr
                    ↓
        Radioiodine Uptake Scan
                    ↓
            Suppressed Uptake
                    ↓
        Diagnosis: Subacute Thyroiditis
                    ↓
    Treatment: NSAIDs + Beta-blockers
                    ↓
        If Severe: Add Corticosteroids

Key Teaching Points for Critical Care

🔍 PEARLS:

High ESR (>100 mm/hr) + thyroid tenderness = SAT until proven otherwise
Suppressed radioiodine uptake differentiates SAT from Graves' disease
Antithyroid drugs are contraindicated in SAT
Beta-blockers control symptoms; NSAIDs treat inflammation
Procalcitonin remains normal, helping exclude bacterial infection

⚠️ OYSTERS:

10% of SAT cases are painless
Premature steroid discontinuation causes relapse
Thyrotoxic crisis can occur but is extremely rare
Permanent hypothyroidism develops in 10-15% of patients
Clinical improvement precedes biochemical normalization

💡 HACKS:

ESR >100 mm/hr in FUO → Check thyroid function immediately
Dramatic response to NSAIDs within 24-48 hours confirms diagnosis
Thyroid palpation should be routine in all FUO evaluations
Avoid antibiotics if SAT suspected - obtain thyroid tests first
Follow thyroglobulin levels to predict permanent hypothyroidism risk

Conclusion

Subacute thyroiditis represents a frequently underdiagnosed cause of fever of unknown origin in critical care settings. The condition's ability to mimic sepsis, combined with its characteristic clinical and biochemical features, requires heightened clinical awareness among critical care physicians. Early recognition through systematic evaluation of neck symptoms, appropriate laboratory testing, and judicious use of imaging can prevent unnecessary interventions while ensuring optimal patient outcomes.

The key to successful management lies in understanding the pathophysiology, recognizing the clinical patterns, and implementing evidence-based treatment strategies. As our understanding of SAT continues to evolve, future research may provide additional insights into personalized treatment approaches and improved prognostic markers.

For critical care physicians, SAT should remain high on the differential diagnosis list for any patient presenting with fever of unknown origin, particularly when accompanied by neck symptoms or an elevated ESR. The dramatic response to appropriate anti-inflammatory therapy serves as both a diagnostic and therapeutic triumph in the challenging landscape of critical care medicine.

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Saturday, June 28, 2025