Subacute Thyroiditis: The Ultimate Guide to de Quervain's, Post-Viral Neck Pain, Fever, and Diagnosis

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We take an in-depth look at subacute thyroiditis, one of the most fascinating yet often misdiagnosed conditions in endocrinology, through a review of the latest literature.

Also known as de Quervain's thyroiditis or subacute granulomatous thyroiditis, this inflammatory thyroid disease can present a confusing clinical picture. 

It often masquerades as a simple pharyngitis or a mysterious fever of unknown origin, leading to diagnostic delays and unnecessary treatments.

This column will explore the multifaceted nature of subacute thyroiditis, using a compelling case of a 36-year-old male whose 18-day fever baffled clinicians before the true culprit was identified. 

We will dissect every aspect of this condition—from its viral origins to its distinct triphasic clinical course and management strategies. 

The Case of the Lingering Fever

Consider a healthy 36-year-old man who presented with an 18-day history of fever and a sensation of neck swelling. 

His journey began with a misdiagnosis of streptococcal pharyngitis, for which he received amoxicillin-clavulanate with no improvement. 

His symptoms persisted: daily fevers peaking at 39.5°C, headaches, fatigue, chills, and night sweats. Critically, his primary complaint was not a sore throat but rather discomfort and swelling in the lower part of his neck.

Physical examination eventually revealed a firm thyroid gland and significant tachycardia (a pulse of 130 beats per minute) even without a fever. 

His laboratory results were starkly abnormal, showing a profoundly suppressed Thyroid-Stimulating Hormone (TSH) level (<0.01 μIU/mL), elevated free thyroxine (T4) and triiodothyronine (T3) levels, and dramatically high inflammatory markers, including an erythrocyte sedimentation rate (ESR) of 81 mm/hr and a C-reactive protein (CRP) level of 138.9 mg/L. 

This classic constellation of findings pointed directly to a diagnosis of subacute thyroiditis with secondary thyrotoxicosis.

Pathophysiology: A Post-Viral Assault

The underlying mechanism of subacute thyroiditis is believed to be a post-viral inflammatory process. 

The condition typically follows an upper respiratory tract infection by several weeks. 

The prevailing theory suggests that a viral infection triggers a robust inflammatory response that cross-reacts with thyroid follicular cells, leading to their destruction. 

This destructive process, characterized by granulomatous inflammation with multinucleated giant cells on histology, causes the release of large quantities of pre-formed T4 and T3 into the circulation, precipitating a state of thyrotoxicosis.

Numerous viruses have been implicated as triggers, including:

  • Coxsackievirus and Mumps Virus: Historically, these were among the most common culprits.

  • Influenza, Adenovirus, and Echovirus: These common respiratory viruses are also well-documented triggers.

  • SARS-CoV-2: Since the recent pandemic, many case reports and series have established a strong association between COVID-19 and the subsequent development of subacute thyroiditis. The thyroid follicular cells express the ACE2 receptor, which the SARS-CoV-2 virus uses for cell entry, providing a direct biological link.

In the presented case, the patient’s wife had a febrile illness consistent with a viral infection just two weeks before his symptoms began, suggesting a likely viral trigger, possibly an asymptomatic SARS-CoV-2 infection.

Epidemiology: Patterns of Inflammation

Subacute thyroiditis is a relatively uncommon cause of thyrotoxicosis, but its distinct demographic and seasonal patterns are noteworthy.

  • Prevalence: It is the cause of approximately 5% of all clinical thyroid disorders.

  • Gender and Age: The condition shows a strong predilection for women, with a female-to-male ratio of about 3-5:1. It most commonly affects individuals between the ages of 30 and 50.

  • Seasonality: A higher incidence is often observed in the summer and fall, mirroring the seasonal peaks of common viral enteroviruses and upper respiratory infections.

Clinical Presentation: The Triphasic Journey

The clinical course of subacute thyroiditis is classically described as triphasic, typically resolving over several months.

  1. Thyrotoxic Phase (2-8 weeks): This initial phase is driven by the unregulated release of stored thyroid hormones from the damaged gland.

    • Symptoms: The onset is often abrupt. Patients typically experience severe anterior neck pain, which may radiate to the jaw, ears, or upper chest. The thyroid gland is exquisitely tender and firm on palpation. Systemic inflammatory symptoms like fever, malaise, myalgias, and fatigue are prominent. Symptoms of thyrotoxicosis, such as palpitations, anxiety, heat intolerance, tremor, and tachycardia, are also common. The case patient's high fever, fatigue, and profound tachycardia perfectly illustrate this phase.

  2. Hypothyroid Phase (Variable duration): As the thyroid's stores of pre-formed hormone are depleted and the gland remains inflamed, a transient period of hypothyroidism often follows. Patients may experience fatigue, cold intolerance, constipation, and mild weight gain. The TSH level, previously suppressed, begins to rise. Our case patient developed this phase approximately six weeks after his initial presentation and required temporary treatment.

  3. Recovery Phase: In over 85-90% of cases, the inflammation subsides, the thyroid follicular cells regenerate, and normal thyroid function is restored. The entire process usually resolves within 6 to 12 months.

Imaging Features: Visualizing the Inflammation

While subacute thyroiditis is primarily a clinical diagnosis, imaging plays a crucial role in confirming the condition and ruling out other pathologies.

  • Neck Ultrasound: This is the imaging modality of choice. It typically reveals ill-defined, hypoechoic regions within the thyroid gland, often with blurred margins. A key feature is markedly reduced or absent vascularity on color Doppler imaging, reflecting the lack of true hormone production. In the case study, bedside ultrasonography confirmed decreased vascularity.

  • Computed Tomography (CT) of the Neck: A CT scan is not typically used for diagnosis but may be performed when the clinical picture is unclear. In our case patient, a CT scan was done to investigate the persistent fever. It showed a heterogeneous appearance of the thyroid gland, which, while non-specific, was consistent with an inflammatory process.

Figure. Axial (Image A) and Coronal (Image B) CT Images of the Neck. These images, obtained after the administration of intravenous contrast, show a heterogeneous appearance of the thyroid gland. The red arrow points to a possible nodule within the right lobe, highlighting the inflammatory changes seen in the presented case of subacute thyroiditis.

  • Radioactive Iodine Uptake (RAIU): A 24-hour RAIU scan is a classic and highly definitive test. In subacute thyroiditis, the uptake of radioactive iodine is characteristically very low (typically <5%). This is because the inflamed follicular cells are unable to trap iodine and the pituitary production of TSH is suppressed by the high levels of circulating thyroid hormone. This finding starkly contrasts with Graves' disease, where the RAIU is diffusely high.

Diagnosis and Differential Diagnosis

The diagnosis of subacute thyroiditis is established through a combination of clinical findings and laboratory tests.

Key Diagnostic Pillars:

  1. Clinical Features: A history of a preceding viral illness followed by acute, painful neck swelling and fever.

  2. Physical Exam: A firm, tender, and often asymmetrically enlarged thyroid gland.

  3. Laboratory Tests:

    • Markedly elevated ESR and CRP: Often the ESR is >50 mm/hr.

    • Suppressed TSH with elevated free T4 and T3: This confirms the thyrotoxic state.

    • Negative Thyroid Autoantibodies: The absence of TSH receptor antibodies (TRAb) and typically negative or low-titer Thyroid Peroxidase (TPO) antibodies helps differentiate it from autoimmune causes like Graves' disease or Hashimoto's thyroiditis.

Differential Diagnosis: It is crucial to differentiate subacute thyroiditis from other conditions presenting with neck pain or thyrotoxicosis:

  • Graves' Disease: The most common cause of hyperthyroidism. Differentiated by the presence of TSH receptor antibodies, high RAIU, and clinical signs like ophthalmopathy.

  • Acute Suppurative Thyroiditis: A rare bacterial infection of the thyroid. Patients are typically more systemically unwell, with high fevers, leukocytosis, and a fluctuant, erythematous neck mass.

  • Infectious Pharyngitis: As seen in the case study, this is a common misdiagnosis. The key is localizing the pain and tenderness to the thyroid gland itself, not the pharynx.

  • Hemorrhage into a Thyroid Cyst: Can cause sudden neck pain but is usually not associated with fever or systemic inflammation.

Treatment and Prognosis

Management of subacute thyroiditis is primarily focused on symptom control, as the disease is self-limiting.

  • Pain and Inflammation:

    • Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): High-dose NSAIDs (e.g., ibuprofen, naproxen) are the first-line treatment for mild to moderate pain.

    • Glucocorticoids: For patients with severe pain or those who do not respond to NSAIDs, a course of prednisone (e.g., 20-40 mg daily) is highly effective, often providing dramatic relief within 24-48 hours. The dose is then tapered over 4-6 weeks as symptoms subside.

  • Thyrotoxic Symptoms:

    • Beta-blockers (e.g., propranolol, atenolol) are used to manage adrenergic symptoms like palpitations, tremor, and anxiety.

  • Hormone Management:

    • Anti-thyroid drugs (e.g., methimazole) have NO role in treatment, as the thyrotoxicosis is due to hormone leakage, not overproduction.

    • During the transient hypothyroid phase, levothyroxine replacement may be necessary if the patient is symptomatic, as was done in the presented case.

The prognosis for subacute thyroiditis is excellent. Over 90% of patients experience a complete recovery of thyroid function. Permanent hypothyroidism is rare (<10%), and recurrence occurs in less than 5% of cases.

Quiz

Question 1: A 36-year-old male presents with a 2-week history of fever, fatigue, and anterior neck pain that radiates to his jaw. On examination, his heart rate is 120 bpm, and his thyroid gland is firm and exquisitely tender to palpation. Which of the following is the most likely diagnosis? 

A) Graves' disease 

B) Acute suppurative thyroiditis 

C) Subacute thyroiditis 

D) Anaplastic thyroid cancer

Question 2: For the patient in Question 1, which set of laboratory findings would be most expected? 

A) High TSH, Low Free T4, Normal ESR 

B) Low TSH, High Free T4, Markedly elevated ESR 

C) Normal TSH, Normal Free T4, Elevated ESR 

D) Low TSH, High Free T4, Positive TSH-receptor antibodies

Question 3: What is the most definitive test to differentiate subacute thyroiditis from Graves' disease? 

A) Thyroid ultrasound 

B) Fine-needle aspiration biopsy 

C) Measurement of TPO antibodies 

D) 24-hour radioactive iodine uptake (RAIU) scan

Question 4: What is the most appropriate initial management for controlling the patient's palpitations and anxiety? 

A) Methimazole 

B) Propranolol 

C) Levothyroxine 

D) Prednisone

Question 5: The pathophysiology of the thyrotoxic phase in subacute thyroiditis is best described as: 

A) Autoimmune stimulation of the TSH receptor. 

B) Increased synthesis and production of new thyroid hormone. 

C) Destructive release of pre-formed thyroid hormone from inflamed follicles. 

D) Malignant infiltration of the thyroid gland.

Answer & Explanation

1. Answer: C) Subacute thyroiditis. Explanation: The combination of a post-viral prodrome, high fever, severe neck pain with a tender goiter, and symptoms of thyrotoxicosis (tachycardia) is classic for subacute thyroiditis.

2. Answer: B) Low TSH, High Free T4, Markedly elevated ESR. Explanation: The thyrotoxic phase of subacute thyroiditis is characterized by pituitary suppression (low TSH) due to hormone leakage (high Free T4) and profound systemic inflammation (markedly elevated ESR and CRP).

3. Answer: D) 24-hour radioactive iodine uptake (RAIU) scan. Explanation: An RAIU scan will show near-absent uptake in subacute thyroiditis due to follicular cell damage, whereas it will be diffusely elevated in Graves' disease. The presence of TSH-receptor antibodies is also diagnostic for Graves' disease.

4. Answer: B) Propranolol. Explanation: Beta-blockers like propranolol are the mainstay for controlling the adrenergic symptoms of thyrotoxicosis, regardless of the cause. Methimazole is not indicated as there is no new hormone synthesis.

5. Answer: C) Destructive release of pre-formed thyroid hormone from inflamed follicles. Explanation: The core pathophysiological event is the destruction of thyroid follicles and the subsequent leakage of stored T4 and T3, not an increase in hormone production.

References

[1] N. A. S. Al-Shoumer and S. H. Al-Zuhair, "Clinical perspective of subacute thyroiditis," Indian J. Endocrinol. Metab., vol. 26, no. 5, p. 386, 2022. 

[2] J. R. Stasiak and C. A. M. H. de Carvalho, "Subacute thyroiditis (de Quervain’s): a review of the literature," Rev. Assoc. Med. Bras., vol. 68, no. 10, pp. 1435–1439, Oct. 2022. 

[3] I. Muller, M. Cannavaro, G. Dazzi, L. Covelli, V. Mantovani, P. G. Sberveglieri, and M. C. Zatelli, "SARS-CoV-2-related subacute thyroiditis: a case series and review of the literature," J. Endocrinol. Invest., vol. 44, no. 5, pp. 1121–1126, May 2021. 

[4] L. C. S. C. dos Santos, L. G. de J. de Souza, C. R. D. da Silva, A. P. C. de Saboia, and F. J. de P. Martins, "Subacute thyroiditis (De Quervain’s) after COVID-19: a literature review," J. Clin. Med. Res., vol. 14, no. 1, p. 38, 2022. 

[5] S. Benbassat, J. Olchovsky, and D. Tsvetov, "Subacute thyroiditis: an updated review," Endocrine, vol. 68, no. 3, pp. 492–499, Jun. 2020. 

[6] D. S. Ross, H. B. Burch, D. S. Cooper, M. C. Greenlee, P. Laurberg, A. L. Maia, S. J. Rivkees, M. Samuels, J. A. Sosa, M. N. Stan, and M. A. Walter, "2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis," Thyroid, vol. 26, no. 10, pp. 1343–1421, Oct. 2016. 

[7] E. A. Meyerowitz et al., "Case 15-2024: A 36-Year-Old Man with Fevers," N. Engl. J. Med., vol. 390, no. 20, pp. 1913–1923, May 2024. [DOI: 10.1056/NEJMcpc2312724]

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