How to manage subacute thyroiditis

Abstract

Subacute thyroiditis (SAT) is a self-limited inflammatory thyroid disorder classically characterized by anterior neck pain, an enlarged tender thyroid, fever, fatigue, malaise, elevated inflammatory markers and a triphasic course from thyrotoxicosis through hypothyroidism to recovery. It can cause substantial morbidity and remains a frequent diagnostic challenge because it must be distinguished from acute suppurative thyroiditis, Graves’ disease, painless thyroiditis, haemorrhage into a nodule and, rarely, malignant ‘pseudothyroiditis’ (rapidly growing carcinoma). In recent years, the recognized spectrum of triggers has expanded beyond the classical post-viral setting to include SARS-CoV-2 infection or vaccination. This review summarizes current understanding of SAT pathogenesis, including viral and post-viral mechanisms, and HLA-linked susceptibility. We outline the typical and variant clinical phenotypes, emphasising painful classical SAT, painless presentations, pregnancy-associated disease and therapy-related destructive thyroiditis. We then present a practical diagnostic framework based on clinical features, inflammatory markers, thyroid function tests, radionuclide imaging, ultrasound and fine-needle aspiration, when indicated. Management is discussed in a stepwise fashion, including NSAIDs and glucocorticoids for pain and inflammation, β-blockers for symptomatic thyrotoxicosis, selective levothyroxine replacement during the hypothyroid phase, and structured follow-up to detect recurrence and permanent hypothyroidism. Special attention is given to pregnancy and SARS-CoV-2-related SAT cases. Finally, we review long-term outcomes, recurrence risk and future research priorities. The aim is to provide a concise, clinically oriented guide to the contemporary management of SAT and to support rational, evidence-informed decision-making in routine endocrine practice.

Plain Language Summary

Subacute thyroiditis is an inflammatory condition of the thyroid that usually causes neck pain, tenderness and temporary changes in thyroid hormone levels. It often follows a viral illness, but it may also occur during pregnancy or after SARS-CoV-2 infection or vaccination. Because it can resemble other thyroid disorders, diagnosis depends on a careful clinical assessment together with thyroid function tests, inflammatory markers and, in selected cases, ultrasound or radionuclide imaging. Most patients improve with anti-inflammatory treatment, usually starting with non-steroidal anti-inflammatory drugs and moving to glucocorticoids when symptoms are more severe or persistent. During the thyrotoxic phase, treatment is symptomatic, as antithyroid drugs are not helpful. Some patients later develop a temporary hypothyroid phase, and a minority progress to permanent hypothyroidism or experience recurrence. This review provides a practical, clinically oriented approach to the recognition, diagnosis, treatment and follow-up of subacute thyroiditis.

Introduction

Subacute thyroiditis (SAT; also called de Quervain, granulomatous or painful SAT) is a self-limited inflammatory disorder of the thyroid characterized by neck pain, a tender goitre, and a predictable evolution of thyroid function from thyrotoxicosis through hypothyroidism to recovery.1–3 It is the most common cause of thyroid pain and may account for up to 5% of patients seen with clinical thyroid disease in general endocrine practice.4 Although SAT is typically benign and transient, it can cause considerable morbidity due to severe pain, systemic symptoms and transient thyrotoxicosis, and a relevant minority of patients develop permanent hypothyroidism requiring lifelong levothyroxine therapy.5–8

Epidemiological data from population-based cohorts suggest an annual incidence of approximately 10–20 cases per 100,000, with a clear female predominance and peak occurrence in young and middle-aged adults.5,9 More recently, a nationwide Danish register-based study of 1763 hospital-diagnosed cases reported an increase in SAT incidence from 3.3 to 6.2 cases per 100,000 individuals between 1995 and 2016, with no significant regional difference according to previous iodine nutritional status.10 In the past decade, the spectrum of recognized triggers has broadened. SAT has been increasingly reported in association with SARS-CoV-2 infection,11–15 sometimes with atypical or even painless presentations, and cases have also been described after several vaccinations, including influenza, hepatitis B, human papillomavirus and, more recently, SARS-CoV-2 vaccines.16–20 These developments underscore that clinicians will encounter SAT in diverse clinical contexts beyond the classical post-viral scenario.

Despite its usually favourable prognosis, SAT remains difficult to recognize and manage in routine care, as its differential diagnosis is broad and misdiagnosis or delayed recognition may lead to inappropriate treatment. The disorder must be distinguished from acute infectious (suppurative) thyroiditis, which requires urgent antibiotics and often surgical drainage, and from other causes of thyrotoxicosis with low or normal radioiodine uptake, including painless thyroiditis, iodine-induced thyrotoxicosis, and factitious or ectopic hyperthyroidism.2 Because the initial presentation often mimics upper respiratory tract infection, pharyngitis, otitis, dental disease or Graves’ disease, patients are frequently treated inappropriately before the correct diagnosis is established. In a study by Stasiak et al., diagnosis was delayed by more than 2 weeks and up to 6 months in 73% of patients, whilst 46.8% received unnecessary antibiotic therapy before SAT was recognized.21 Similarly, Bostan et al. reported a median diagnostic delay of 23 days (range 6–70 days), with 58.7% of patients receiving antibiotics prior to diagnosis and nearly three-quarters consulting two or more physicians before the diagnosis was made.22 Furthermore, SAT may follow atypical clinical courses, including presentations dominated by unilateral throat pain, fever of unknown origin or focal thyroid lesions, which further increase the risk of misdiagnosis; in one recent series, 43.7% of patients presenting primarily with unilateral pharyngalgia were initially misdiagnosed.23 Consequently, diagnostic errors may lead to unnecessary antibiotic exposure, inappropriate use of antithyroid drugs or radioiodine, delayed drainage of a true thyroid abscess or failure to recognize malignant ‘pseudothyroiditis’ such as rapidly growing thyroid carcinoma.24 Once the diagnosis is established, there is persistent heterogeneity in treatment approaches, particularly concerning when to use non-steroidal anti-inflammatory drugs (NSAIDs) versus glucocorticoids, what steroid dose and tapering schedule to employ, and how to monitor for and manage the hypothyroid phase and potential recurrence (Figure 1).25,26

Figure 1.

Clinical course of subacute thyroiditis.

Subacute thyroiditis typically follows a self-limited course that can be divided into four phases. It usually begins with an acute inflammatory thyrotoxic phase, marked by anterior neck pain, thyroid tenderness and biochemical thyrotoxicosis resulting from the release of preformed thyroid hormones after follicular destruction. This initial phase generally lasts between 2 and 12 weeks. During this period, treatment is usually directed towards symptom control, with non-steroidal anti-inflammatory drugs (NSAIDs) as first-line therapy and glucocorticoids reserved for patients with more severe symptoms or inadequate response to NSAIDs. A transient euthyroid interval may then occur and can persist for several days to weeks. This is often followed by a temporary hypothyroid phase, lasting from a few weeks to several months, during which levothyroxine (LT4) may occasionally be required in symptomatic cases. Recovery is usually complete, with return to normal thyroid function in the great majority of patients, though permanent hypothyroidism has been described in up to 15%. In most patients, the full clinical course does not extend beyond 6 months. Importantly, not all individuals pass through every phase, as only about half develop a transient hypothyroid stage. RAI, radionuclide uptake including technetium-99m; TSH, thyroid-stimulating hormone; T4, thyroxine.

This narrative review addresses the practical management of SAT in contemporary clinical practice. Relevant literature was identified through searches of PubMed/MEDLINE, Scopus, and Google Scholar using tailored combinations of keywords and related terms. Studies were selected based on relevance, scientific quality, and their contribution to understanding the disease’s clinical features, diagnosis, treatment and pathophysiology. Priority was given to systematic reviews, meta-analyses, clinical guidelines, consensus statements and high-quality original studies. Additional references were identified through manual review of bibliographies. As a narrative review, no formal systematic review methodology was applied. Drawing on recent evidence, large observational cohorts, and newer data on COVID-19-related and drug-induced cases, we summarize current understanding of pathogenesis, outline the typical and variant clinical presentations, and emphasize a structured diagnostic approach that reliably distinguishes SAT from its main mimics. We then provide an evidence-informed, stepwise framework for treatment, covering pain control, management of thyrotoxicosis and hypothyroidism, follow-up strategies and special situations such as pregnancy and SARS-CoV-2 infection. The aim is to offer clinicians a concise, clinically oriented guide that supports timely diagnosis, rational use of NSAIDs and glucocorticoids, avoidance of unnecessary or harmful interventions, and optimal long-term thyroid outcomes for patients with SAT.

Pathogenesis and triggers

SAT is widely regarded as a post-viral inflammatory disorder that develops in genetically predisposed individuals rather than a classic primary autoimmune disease.2,27 The central pathologic event is a destructive inflammation of thyroid follicles, leading to leakage of preformed hormone into the circulation and subsequent, usually complete, structural and functional recovery of the gland.

Viral and post-viral mechanisms

Several lines of evidence support a viral or post-viral trigger. Many patients report an upper respiratory tract infection 2–8 weeks before the onset of thyroid pain, and early epidemiological studies described clustering in summer and early autumn, coinciding with peaks of common respiratory viruses.28,29 Associations have been described with Coxsackievirus, mumps, measles, adenovirus, influenza (including H1N1), Epstein–Barr virus, and other agents, and some patients demonstrate rising viral antibody titres during the illness.30 Nonetheless, direct virological proof is inconsistent: viral inclusion bodies are not seen in thyroid tissue, and viral cultures or nucleic acid detection are often negative, suggesting that, in many cases, the relevant trigger is a transient infection or a post-infectious immune response rather than an ongoing viral replication within the gland.31 In addition, contemporary data do not support a causal association with these viruses.29

During the COVID-19 pandemic, SARS-CoV-2 has emerged as an additional trigger for SAT.11–15 Case series document SAT occurring shortly after or even concurrently with COVID-19, with classical painful presentations as well as painless or oligosymptomatic forms.12 SAT has also been reported following vaccination against influenza, hepatitis B, human papillomavirus and more recently SARS-CoV-2, reinforcing the concept that immune activation, rather than specific viral cytopathicity, is central to disease initiation.16–20

Genetic susceptibility and immune response

Genetic susceptibility appears to play a major role in determining who develops SAT after common viral exposures. A strong association with HLA-B*35 was recognized decades ago, with this allele present in approximately two-thirds of affected patients in some cohorts.32–34 More recent work has expanded this risk profile to include HLA-B*18:01, DRB1*01 and C04:01, and combinations such as co-occurrence of HLA-B*35 and HLA-B*18:01 have been linked to a higher risk of recurrence.35 A unifying model proposes that viral or virus-induced host antigens bind to these HLA molecules on macrophages, forming antigen–HLA complexes that activate cytotoxic T lymphocytes; these, in turn, recognize structurally similar epitopes on thyroid follicular cells, leading to targeted follicular injury through molecular mimicry.2

Unlike chronic autoimmune thyroid diseases, such as Hashimoto thyroiditis, the immune reaction in SAT is not self-sustaining. Histology in the acute phase shows a mixed inflammatory infiltrate with neutrophils, lymphocytes, histiocytes and multinucleated giant cells, disruption and collapse of follicles, and necrosis of follicular cells. In later stages, mild fibrosis may appear but gland architecture eventually returns to normal.36,37 As inflammation subsides, follicles regenerate, thyroid hormone synthesis resumes, and most patients regain normal thyroid function, consistent with a time-limited immune insult.36

Thyroid autoantibodies (thyroid peroxidase antibodies, thyroglobulin antibodies and, less commonly, thyroid-stimulating hormone (TSH) receptor antibodies (TRAb)) are usually absent or present at low titres at presentation, and any rise during the hypothyroid phase is thought to reflect secondary immune responses to released thyroid antigens rather than a primary autoimmune driver.31,38–41 This immunological profile supports the classification of SAT as an inflammatory, virus-triggered, HLA-linked, but non-self-perpetuating thyroiditis distinct from classical autoimmune thyroid disease.

Collectively, these observations indicate that SAT represents a final common pathway of thyroid injury resulting from diverse triggers in individuals with specific HLA backgrounds. The shared outcome is a self-limited, cell-mediated destructive process that produces the characteristic clinical sequence of painful thyrotoxicosis followed by hypothyroidism and, in most patients, eventual recovery.

Clinical course and phenotypes

SAT follows a characteristic but variable clinical course that reflects a self-limited, destructive inflammatory process of the thyroid. It typically evolves through an initial painful thyrotoxic phase, a transient hypothyroid phase, and eventual recovery, although not all patients experience each phase to the same degree (Figure 1).2 Recognising this pattern, as well as important variant presentations, is central to timely diagnosis, appropriate treatment and realistic counselling about prognosis.

Typical painful SAT

In the classic form, the illness begins with a viral-like prodrome characterized by low-grade fever, myalgias, malaise and symptoms of an upper respiratory tract infection that precede thyroid pain by several days to weeks.5,42,43 Patients then develop anterior neck pain localized to the thyroid region, often starting unilaterally and radiating to the jaw, ears or upper chest, which is exacerbated by swallowing, coughing, or turning the head and may be severe enough to limit examination.5 On palpation, the thyroid is typically slightly to moderately enlarged, firm and considerably tender, sometimes with asymmetry between the lobes; as the disease evolves, the pain and tenderness may ‘migrate’ from one lobe to the other, a phenomenon often termed creeping thyroiditis.42

Systemic symptoms, such as fatigue, fever, anorexia and generalized myalgias, are common and may dominate the early clinical picture. Approximately half of patients manifest clinical features of thyrotoxicosis, such as palpitations, heat intolerance, tremor and weight loss, during the initial phase but, in many cases, these symptoms are mild compared with the neck pain and systemic inflammation.42 The thyrotoxic phase generally lasts 2–8 weeks, during which thyroid function tests typically show suppressed TSH with mildly to moderately elevated free thyroxine (T4) and triiodothyronine (T3); notably, T3 is not disproportionately elevated relative to T4, which helps distinguish SAT from Graves’ disease in some patients.44

The typical clinical constellation that should raise suspicion for SAT is summarized in Figure 2, Step 1.

Figure 2.

Practical diagnostic and therapeutic algorithm for subacute thyroiditis.

This figure summarizes a stepwise clinical approach to subacute thyroiditis, beginning with recognition of the typical painful inflammatory presentation, followed by confirmation of the biochemical-inflammatory pattern, exclusion of important mimics and selective use of imaging. It then outlines symptom-based treatment of pain and thyrotoxicosis, monitoring for the hypothyroid phase, follow-up until recovery, recognition of recurrence, and adaptation of management in special situations such as pregnancy and SARS-CoV-2-related disease. CBC, complete blood count; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FNA, fine-needle aspiration; NSAID, non-steroidal anti-inflammatory drug; SAT, subacute thyroiditis; TSH, thyroid-stimulating hormone.

Phases of thyroid function

The evolution of thyroid function in SAT is classically described as triphasic, although individual courses vary. In the initial destructive phase, damage to thyroid follicles and proteolysis of stored thyroglobulin lead to unregulated release of preformed T4 and T3 into the circulation, causing transient thyrotoxicosis that persists until intrathyroidal hormone stores are depleted. As the inflammatory process subsides and hormone stores fall, there is often a brief euthyroid interval during which thyroid hormone levels and TSH normalize.2

A subsequent hypothyroid phase is common, reflecting both the temporary loss of functioning follicular tissue and continued suppression of thyroid-stimulating hormone by previously elevated thyroid hormone levels.5 This hypothyroid phase typically emerges several weeks after symptom onset, lasts for weeks to a few months, and is characterized biochemically by elevated TSH with low or low-normal free T4; clinically, many patients are asymptomatic or report only non-specific fatigue and cold intolerance.5 Not all patients progress through an overt hypothyroid phase — approximately half in some series develop clear biochemical hypothyroidism — yet, in most cases, thyroid function ultimately returns to normal as follicles regenerate and hormone synthesis resumes.45

Overall, the entire clinical course of SAT rarely exceeds 4–6 months from the onset of pain to full recovery.5 Long-term outcome is favourable in the majority of patients: most regain normal thyroid function, but approximately 5–15% develop permanent hypothyroidism requiring ongoing levothyroxine therapy,5–8 particularly those with more extensive thyroid destruction or coexisting autoimmune thyroid disease.43

Variant presentations

Although the classic phenotype is that of a painful, inflammatory thyrotoxic illness, several variant presentations are increasingly recognized. Painless SAT, in which neck pain and tenderness are minimal or absent despite a similar pattern of transient thyrotoxicosis, low radioiodine uptake, and subsequent hypothyroidism, has been reported, particularly in association with SARS-CoV-2 infection and some drug-induced cases.43,46 These forms may be difficult to distinguish clinically from painless (silent) thyroiditis and require careful integration of history, inflammatory markers and imaging findings.

SAT during pregnancy and in the postpartum period represents another important variant. In pregnant women, fever and overt thyrotoxicosis appear less prominent, and the clinical picture may overlap with hyperemesis gravidarum, gestational thyrotoxicosis or postpartum thyroiditis, complicating diagnosis and influencing the choice of investigations and treatment.47–49 In these settings, a high index of suspicion and reliance on clinical features, inflammatory markers and ultrasound, avoiding radioiodine imaging, are essential.

Recurrence and long-term course

Whilst SAT is usually a one-time, self-limited event, recurrence is well documented and clinically relevant. Cohort studies suggest recurrence rates ranging from very low to approximately 10–20%, with recurrent episodes occurring either shortly after tapering anti-inflammatory therapy or many years after the initial illness.5,50–52 Recurrence often involves the contralateral lobe and may present with similar or slightly milder symptoms; it responds to the same management principles but may require a more cautious and prolonged taper of glucocorticoids.50,51 Recent genetic data implicate certain HLA constellations, particularly co-occurrence of HLA-B*35 and HLA-B*18:01, as potential risk factors for recurrence, suggesting that host factors contribute not only to initial susceptibility but also to disease relapse.52

Diagnostic workup

SAT is fundamentally a clinical diagnosis supported by characteristic laboratory and imaging findings. The key task of the workup is to confirm a destructive, inflammatory thyrotoxicosis and to distinguish it from acute infectious thyroiditis, Graves’ disease, and other causes of hyperthyroidism with low radioiodine uptake. The main differential diagnoses of SAT and their distinguishing clinical, biochemical and imaging features are summarized in Table 1.

Table 1.

Differential diagnosis of subacute thyroiditis.

Disorder	Pain/tenderness	Fever/systemic inflammation	ESR/CRP	Thyroid function	TRAb/thyroid antibodies	Radionuclide uptake	Ultrasound/Doppler	FNA/key clue
Subacute thyroiditis	Prominent, often severe	Common	Markedly elevated	Early thyrotoxicosis, later hypothyroidism, then recovery	TRAb negative; TPOAb/TgAb absent or low	Low or absent	Ill-defined hypoechoic areas; low/normal vascularity	Usually not needed
Acute suppurative thyroiditis	Severe, usually unilateral	High fever common	Elevated	Often normal; occasionally thyrotoxic	Not diagnostic	Variable	Focal collection/abscess, surrounding inflammation	Purulent aspirate; culture positive
Graves’ disease	Usually absent	Usually absent	Normal or mildly raised	Thyrotoxicosis	TRAb positive	High diffuse uptake	Diffuse enlargement, marked hypervascularity (‘thyroid inferno’)	Not needed
Toxic nodular goitre/toxic adenoma	Absent	Absent	Normal	Thyrotoxicosis	TRAb negative	Focal or patchy increased uptake	Nodules with increased vascularity	Not needed; imaging usually diagnostic
Painless/silent thyroiditis	Absent	Mild or absent	Normal or mildly elevated	Destructive thyrotoxicosis followed by hypothyroidism	TPOAb often positive	Low uptake	Mild hypoechogenicity; no marked hypervascularity	Usually not needed
Postpartum thyroiditis	Absent	Absent	Usually normal	Destructive thyrotoxicosis followed by hypothyroidism	TPOAb often positive	Low uptake	Similar to painless thyroiditis	Not needed; context of postpartum period
Haemorrhage into cyst/nodule	Sudden focal pain	Usually absent	Usually normal	Usually normal	Not helpful	Normal or focal cold defect	Haemorrhagic cyst or complex nodule	Aspirate yields blood
Painful Hashimoto thyroiditis	Possible	Mild	Variable	Usually hypothyroid or euthyroid	TPOAb/TgAb often positive	Variable	Chronic autoimmune pattern	Not needed; antibody profile supports diagnosis
Thyroid malignancy with pain	Possible	Usually absent	Variable	Usually euthyroid	Not diagnostic	Variable	Suspicious focal lesion, invasive features	FNA/core biopsy required

CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FNA, fine-needle aspiration; TgAb, thyroglobulin antibodies; TPOAb, thyroid peroxidase antibodies; TRAb, thyroid-stimulating hormone receptor antibodies.

Diagnostic criteria

Although no universally accepted diagnostic criteria exist, the diagnosis of SAT is generally based on a compatible clinical presentation together with characteristic biochemical and imaging findings. A practical diagnostic framework includes (1) anterior neck pain and thyroid tenderness, often following a recent viral illness; (2) biochemical thyrotoxicosis with suppressed TSH and elevated free T4 and/or free T3; (3) elevated inflammatory markers: erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP); and (4) supportive imaging findings such as low or absent radionuclide uptake and/or characteristic hypoechoic lesions with reduced vascularity on ultrasound. The diagnosis is further supported by exclusion of alternative causes of painful thyroid disease and by a rapid clinical response to glucocorticoid therapy.

Initial clinical and laboratory evaluation

As outlined above, once SAT is clinically suspected, the diagnosis is usually confirmed by a combination of thyroid function tests, inflammatory markers and selective imaging. During the early phase, thyroid function tests typically show suppressed TSH with mildly to moderately elevated free T4 and T3, usually without disproportionate T3 excess, whilst ESR and/or CRP are commonly markedly elevated. Complete blood count findings are supportive but non-specific. The leukocyte count is normal or slightly elevated in most cases.53 When present, leucocytosis is generally mild and reflects the inflammatory process, often with neutrophil predominance and an increased neutrophil-to-lymphocyte ratio.54 In contrast, Graves’ disease is usually associated with normal inflammatory markers and generally lacks the neutrophilic leucocytosis characteristic of SAT, although mild relative lymphocytosis or neutropenia may occasionally occur.55,56 Marked neutrophilic leucocytosis should prompt consideration of acute suppurative thyroiditis rather than SAT.57 Mild anaemia may also be observed.58 Other haematological indices, including increased platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammatory response index, and lower mean platelet volume-related indices, have been reported in patients with SAT and may help distinguish SAT from Graves’ disease in diagnostically challenging cases.54,59 However, these parameters are non-specific and should be interpreted only as supportive inflammatory markers rather than standalone diagnostic criteria (Figure 2, Step 2).

Radionuclide imaging

Radioiodine uptake or technetium-99m thyroid scintigraphy can be highly useful for confirming the diagnosis of SAT. In patients with SAT, either radioactive iodine uptake is low (often <1–3%) or technetium-99m thyroid scintigraphy demonstrates absent tracer uptake, with no visualisation of the thyroid gland during the thyrotoxic phase (Figure 3). These findings reflect destruction of thyroid tissue and suppression of TSH rather than increased hormone synthesis.2 This pattern contrasts with the high uptake seen in Graves’ disease and toxic nodular goitre. Technetium-99m thyroid imaging is preferred in daily practice because it offers similar diagnostic information with lower radiation exposure and wider availability. In the absence of recent iodine exposure, a radioactive iodine uptake above ~5% at 24 hours makes the diagnosis of SAT unlikely and should prompt reconsideration of other causes of thyrotoxicosis.2 However, radionuclide imaging is not required in every patient and should be reserved for cases in which the diagnosis remains uncertain, particularly when differentiation from Graves’ disease, iodine-induced thyrotoxicosis, factitious thyrotoxicosis or ectopic thyroid hormone production cannot be achieved by clinical assessment, laboratory findings, and ultrasound. In contrast, when the clinical picture is typical, with anterior neck pain, elevated inflammatory markers, characteristic ultrasonographic findings and biochemical thyrotoxicosis, the diagnosis can usually be established without scintigraphy.60,61 Radioisotope imaging should be avoided during pregnancy or breastfeeding (Figure 2, Step 4).48,49

Figure 3.

Imaging findings in subacute thyroiditis.

Thyroid scintigraphy shows faint bilateral radioisotope uptake, supporting destructive thyrotoxicosis. B-mode ultrasonography shows preserved echostructure without nodules, with right and left thyroid lobe volumes of 4.4 mL and 3.8 mL, respectively. Colour Doppler ultrasonography shows no increased vascularity or thyroid artery velocities. Image adapted and modified with permission from ref.9

Ultrasound and Doppler ultrasonography

Thyroid ultrasonography should be performed as part of the initial evaluation of suspected SAT because it provides characteristic diagnostic findings, facilitates differentiation from Graves’ disease, acute suppurative thyroiditis and thyroid malignancy, establishes a baseline for follow-up, and offers the advantages of wide availability, low cost and absence of ionising radiation.61–64 In SAT, ultrasound typically reveals diffuse or multifocal hypoechoic areas with blurred margins, sometimes corresponding to the most tender regions of the gland (Figure 3).65,66 Colour Doppler ultrasonography shows low or normal vascularity in the affected areas, contrasting with the marked hypervascularity seen in Graves’ disease.61

Ultrasound is particularly helpful in excluding acute suppurative thyroiditis, in which focal hypoechoic collections, perithyroidal fluid, and effacement of planes between the thyroid and surrounding tissues may indicate abscess formation or spread of infection.57,67 In such cases, ultrasound-guided fine-needle aspiration allows both cytological confirmation and microbiological culture.68,69 Because SAT may occasionally mimic thyroid malignancy and inflammatory hypoechoic regions can obscure coexisting thyroid tumours, repeat ultrasonography after clinical resolution is advisable to document resolution of inflammatory abnormalities and to identify persistent nodules or suspicious lesions that may require fine-needle aspiration (FNA), especially in patients with persistent focal hypoechoic lesions, asymmetric gland involvement, atypical imaging findings or incomplete radiological resolution.70–72 In pregnancy, ultrasound, together with thyroid function tests and inflammatory markers, is central to the diagnostic workup, given the constraints on radionuclide imaging.48,49

Fine-needle aspiration

Whilst FNA is not routinely required in straightforward cases of SAT, it becomes important when the diagnosis is uncertain. Indications include unilateral painful thyroid enlargement with suspicious ultrasonographic features, failure to respond to appropriate anti-inflammatory therapy, suspicion of a thyroid abscess or the presence of a concurrent hypoechoic, irregularly shaped thyroid nodule suggestive of malignancy that may be obscured by, or mistaken for, SAT.69 In the latter situation, biopsy can often be deferred until resolution of the acute inflammatory process unless urgent tissue diagnosis is clinically indicated.70 Tissue sampling should also be considered when aggressive malignancies, such as rapidly growing thyroid carcinoma or lymphoma presenting as ‘malignant pseudothyroiditis’, are suspected. However, these entities may not always be definitively diagnosed by cytology alone and may require core needle biopsy or surgical tissue sampling for confirmation.2,73 Cytology in SAT typically shows inflammatory cells with multinucleated giant cells, disrupted follicular cells and colloid, whereas acute infectious thyroiditis yields abundant neutrophils and, often, identifiable pathogens on stains and culture.69,73,74

Differential diagnosis

The main conditions to distinguish from SAT are acute infectious (suppurative) thyroiditis, haemorrhage into a thyroid nodule, Graves’ disease and toxic nodular goitre, painless/postpartum thyroiditis and nonthyroidal causes of anterior neck pain.

Acute infectious thyroiditis typically presents in children or adolescents with high fever, severe unilateral neck pain, prominent leucocytosis and erythema or fluctuance over the thyroid and is often associated with anatomic risk factors such as a pyriform sinus fistula or immunosuppression.75 Rarely, it could follow medical interventions such as FNA of a thyroid nodule76 or percutaneous ethanol ablation of a benign thyroid nodule.77 Thyroid function is usually normal, although transient thyrotoxicosis can occur, and ESR/CRP are elevated; ultrasound and CT often reveal focal abscesses, and FNA demonstrates purulent material and allows pathogen identification.57 By comparison, SAT typically follows a characteristic course of destructive thyrotoxicosis with low radioactive iodine uptake, often involves bilateral or migratory thyroid pain, and usually responds rapidly to glucocorticoid therapy.

Spontaneous haemorrhage into a pre-existing thyroid cyst or nodule is a rare condition. It typically presents with sudden unilateral pain and swelling, often without fever or systemic inflammatory signs, and thyroid function is typically normal.78 Mild fever and transient thyrotoxicosis may occasionally occur. In an Italian study conducted from 2009 to 2018 at the emergency department, 59 cases were identified amongst 631,129 adults, corresponding to a frequency of approximately 0.009%.79 Radionuclide uptake shows a cold defect corresponding to the haemorrhagic nodule, and ultrasound reveals fluid levels or echogenic clot; FNA yields blood rather than inflammatory exudate.2

Graves’ disease and toxic nodular goitre usually cause painless thyrotoxicosis with a diffuse or nodular goitre, high radioiodine uptake and, in Graves’ disease, TRAb and a hypervascular ‘thyroid inferno’ on Doppler ultrasonography.80 Silent (painless) thyroiditis and postpartum thyroiditis also cause destructive thyrotoxicosis with low radionuclide uptake and may therefore resemble SAT biochemically. However, unlike SAT, they are characterized by the absence of thyroid pain and tenderness, usually occur without systemic inflammatory symptoms, are associated with normal or only minimally elevated inflammatory markers, and frequently occur in individuals with positive thyroid autoantibodies.81

Non-thyroidal causes of anterior neck pain include cervical lymphadenitis, retropharyngeal or parapharyngeal abscess, infected thyroglossal duct or branchial cleft cyst, cellulitis of the anterior neck and temporally associated conditions, such as giant cell arteritis, which presents with jaw and temporal pain.2 In these conditions, palpation often localizes tenderness away from the thyroid, ultrasound or CT shows extra-thyroidal pathology and thyroid function tests are normal.

In practice, a structured diagnostic approach, combining history, physical examination, thyroid function tests, ESR/CRP and selective use of radionuclide imaging, ultrasound and FNA when indicated, allows reliable diagnosis of SAT and timely exclusion of conditions that require very different management, such as acute suppurative thyroiditis or Graves’ disease (Figure 2, Step 3).

Principles of management

Management of SAT is guided by the self-limiting nature of the disease and the goals of relieving pain, controlling thyrotoxic and hypothyroid symptoms, and avoiding unnecessary or harmful interventions such as antithyroid drugs, radioiodine or antibiotics when not indicated.2,25 Treatment intensity should be individualized according to symptom burden, comorbidities and the phase of thyroid dysfunction, with close follow-up to detect hypothyroidism and recurrence. The main treatment strategies for SAT, including anti-inflammatory therapy and management of the thyrotoxic and hypothyroid phases, are summarized in Table 2.

Table 2.

Treatment of subacute thyroiditis.

Treatment	Main indication	Example regimen	Expected effect	Important cautions/comments
Observation alone	Very mild symptoms, improving spontaneously	No specific treatment	Spontaneous improvement	Requires close follow-up
Acetaminophen/paracetamol	Mild pain, especially in pregnancy	Standard analgesic dosing	Symptomatic pain relief	Limited anti-inflammatory effect
NSAIDs	Mild to moderate pain/inflammation	Ibuprofen 1200–3200 mg/day; naproxen 500–1000 mg/day; aspirin 2.0–2.6 g/day	Improvement within 48–72 hours	Avoid/use cautiously in renal disease, gastrointestinal risk, anticoagulation, late pregnancy
Glucocorticoids	Severe pain, major systemic symptoms, NSAID failure	Prednisone/prednisolone 15–40 mg/day, then gradual taper over 4–6 weeks	Often dramatic relief within 24–48 hours	Lack of response should prompt reconsideration of diagnosis; avoid abrupt taper
β-Blocker	Symptomatic thyrotoxicosis (palpitations, tremor, anxiety)	Propranolol 40–120 mg/day or atenolol 25–50 mg/day	Rapid symptom control	Usually temporary; caution in asthma, bradycardia, pregnancy
Levothyroxine	Symptomatic hypothyroidism or TSH ≥10 mU/L	Individualized; e.g. 50–100 μg/day in healthy adults	Corrects hypothyroid symptoms/biochemistry	Often temporary; reassess after withdrawal
Antithyroid drugs	Not indicated	—	No benefit	Hormone excess is due to release not increased synthesis
Radioiodine therapy	No role	—	No benefit	Uptake is low; disease is self-limited
Antibiotics	Not indicated unless infectious thyroiditis suspected	—	No role in SAT	Use only if suppurative thyroiditis is suspected/confirmed

NSAID, non-steroidal anti-inflammatory drug; SAT, subacute thyroiditis; TSH, thyroid-stimulating hormone.

Pain and inflammation

Pain and thyroid tenderness, often accompanied by systemic symptoms, are the principal determinants of treatment in SAT. Most symptomatic patients benefit from anti-inflammatory therapy, with NSAIDs recommended as first-line treatment and glucocorticoids reserved for patients with more severe symptoms or an inadequate response to NSAIDs.25,82,83 For mild to moderate pain, high-dose aspirin or NSAIDs, such as naproxen or ibuprofen, are usually effective. Common regimens include aspirin 2.0–2.6 g/day in divided doses, naproxen 500–1000 mg/day in two divided doses or ibuprofen 1200–3200 mg/day in three or four divided doses. Doses should be adjusted according to renal function, gastrointestinal risk and other comorbidities.2 Symptomatic improvement should be evident within 2–3 days; if there is no clear benefit, NSAIDs should be discontinued and glucocorticoid therapy initiated.2,84,85

Glucocorticoids are indicated for patients with severe neck pain and systemic symptoms, those who fail an adequate NSAID trial, and those in whom rapid symptom control is important, such as individuals with significant dysphagia or impaired daily function.58 Typical regimens include prednisone or prednisolone 30–40 mg daily. The duration of therapy is not standardized and is determined by the clinical response; it most commonly lasts for 1–2 weeks, followed by tapering by 5–10 mg every 5–7 days over 4–6 weeks, though lower starting doses (15–20 mg/day) may suffice in milder disease.86–88 Pain relief is often rapid, frequently within 24–48 hours; lack of a brisk response should prompt reconsideration of the diagnosis, particularly the possibility of acute infectious thyroiditis.2 Recurrence of pain during tapering is not uncommon and may require temporarily increasing the dose before resuming a slower taper; longer tapering schedules, rather than higher starting doses, appear more important in reducing relapse risk (Figure 2, Step 5).50,85,89,90

Although SAT is traditionally regarded as a self-limited disorder, evidence regarding whether anti-inflammatory treatment modifies the risk of permanent hypothyroidism remains inconsistent. Earlier observational studies suggested that treatment choice had no influence on the risk of permanent thyroid dysfunction,5,91,92 whereas more recent cohort data have suggested a lower risk amongst patients treated with glucocorticoids compared with NSAIDs alone85,88. The recently published study by Soyer et al. reported a higher rate of permanent hypothyroidism amongst untreated patients than amongst those treated with NSAIDs or corticosteroids.59 However, this finding should be interpreted cautiously because of the retrospective, non-randomized design, potential confounding by indication, inclusion of painless SAT, limited adjustment for established predictors of permanent hypothyroidism and the exploratory nature of the treatment analysis. Moreover, permanent hypothyroidism was assessed after 12 months without standardized reassessment following levothyroxine withdrawal, raising the possibility of outcome misclassification.

Overall, current evidence remains insufficient to conclude that anti-inflammatory therapy independently prevents permanent hypothyroidism. Disease severity, thyroid autoimmunity and markers of structural thyroid damage appear to be more consistent predictors of long-term dysfunction.5,85,88,93 Therefore, whilst routine non-treatment cannot be recommended in patients with typical symptomatic SAT, there is currently insufficient high-quality evidence to support NSAID therapy solely to prevent permanent hypothyroidism in otherwise minimally symptomatic patients. Careful clinical and thyroid function follow-up remains essential regardless of the initial treatment strategy.

Management of thyrotoxicosis

The thyrotoxic phase of SAT results from the release of preformed hormones rather than increased synthesis, so treatment focuses on symptomatic control rather than antithyroid drugs or radioiodine. Many patients have only mild thyrotoxic symptoms, and some require no specific therapy beyond pain management and reassurance; in others, adrenergic symptoms, such as palpitations, tremor, anxiety and heat intolerance, justify short-term use of β-adrenergic blockers.58

β-Blockers, such as propranolol or atenolol, are effective in alleviating sympathetic overactivity. Propranolol may be given at 40–120 mg/day in divided doses (or long-acting formulations such as 80 mg once daily), whilst atenolol is typically used at 25–50 mg once daily, titrated according to heart rate, blood pressure and symptom control.2 Therapy is usually needed only for several weeks until the thyrotoxic phase resolves, and can then be tapered and discontinued. In patients with reactive airway disease or other relative contraindications to non-selective β-blockade, a cardioselective β1-selective agent may be considered, with appropriate clinical caution. In contrast, β-blockers should generally be avoided in patients with significant bradycardia or atrioventricular conduction disease. When β-blockers are contraindicated or not tolerated, symptomatic management should include reassurance, adequate rest, avoiding exertion and reduction of stimulants such as caffeine. In selected patients with persistent symptomatic tachycardia and no contraindications, short-term use of a non-dihydropyridine calcium-channel blocker, such as diltiazem or verapamil, may be considered (Figure 2, Step 6).

Management of hypothyroid phase

The hypothyroid phase of SAT is typically transient but may be clinically significant in some patients.6 Many individuals are asymptomatic or have only mild, non-specific symptoms such as fatigue or cold intolerance and a proportion will normalize thyroid function without treatment over subsequent weeks to months.5,91,93 Treatment decisions should therefore balance symptom severity, TSH elevation, patient characteristics and the desire to avoid unnecessary long-term levothyroxine therapy.

In general, levothyroxine replacement is recommended for patients with symptomatic hypothyroidism or those with a TSH ≥10 mU/L, even if symptoms are modest.94 In younger, otherwise healthy adults, an initial dose of 50–100 μg/day is reasonable, with lower starting doses in older individuals or those with cardiovascular disease. In pregnancy or in women planning conception, lower thresholds for treatment should be applied to maintain TSH within pregnancy-specific target ranges, given the potential impact of maternal hypothyroidism on foetal development.

Because hypothyroidism after SAT is often temporary, levothyroxine therapy should not be assumed to be lifelong at the outset. A common approach is to treat for approximately 6–8 weeks, then discontinue levothyroxine and reassess thyroid function 4–6 weeks later to determine whether endogenous function has recovered.84,95 If TSH remains elevated with low or low-normal free T4, permanent hypothyroidism is likely and long-term replacement should be instituted; if TSH is normal, no further treatment is needed aside from periodic monitoring. Patients treated with higher doses of glucocorticoids, those with coexisting autoimmune thyroid disease, or those with more extensive parenchymal damage may be at greater risk of permanent hypothyroidism and merit closer follow-up (Figure 2, Step 7).5–8 Recent nationwide registry data further emphasize the importance of structured follow-up after SAT: In a Danish cohort of 1763 hospital-diagnosed patients, 26.0% initiated levothyroxine within 4 years, and nearly half of treated patients continued therapy beyond 36 months, highlighting the need to reassess whether hypothyroidism is permanent before continuing long-term replacement.10

Follow-up and monitoring

Systematic follow-up is crucial to ensure resolution of inflammation, appropriate tapering of anti-inflammatory therapy, and detection of hypothyroidism and identification of recurrence. During the active phase, thyroid function tests (TSH and free T4, with T3 as needed) should be checked every 4–8 weeks to track progression from thyrotoxicosis through hypothyroidism towards recovery.91,96 More frequent testing may be warranted in patients with significant symptoms, pregnancy or those requiring dose adjustments of levothyroxine.

Inflammatory markers, such as ESR and C-reactive protein, are helpful at diagnosis and can be reassessed when clinical relapse is suspected, but routine serial measurement is not necessary once pain and systemic symptoms have resolved.89 Clinical follow-up should focus on resolution of neck pain and tenderness, control of thyrotoxic or hypothyroid symptoms and monitoring for adverse effects of NSAIDs or glucocorticoids, with attention to blood pressure, glycaemic control, gastrointestinal symptoms and infection risk.

After apparent recovery, at least one additional thyroid function assessment several months later is advisable to confirm euthyroidism and exclude delayed hypothyroidism.97 Patients should be educated about the possibility of recurrence, which, although uncommon, can occur months to years after the initial episode, and instructed to seek evaluation if they develop recurrent anterior neck pain or symptoms suggestive of thyrotoxicosis.43 In those with established permanent hypothyroidism, long-term follow-up is similar to that for other causes of primary hypothyroidism, with annual or semi-annual TSH monitoring and dose adjustments as needed.

By combining judicious use of NSAIDs and glucocorticoids, targeted symptomatic treatment of thyrotoxicosis, conservative and time-limited levothyroxine replacement in the hypothyroid phase, and structured follow-up, clinicians can manage SAT effectively whilst minimising overtreatment and ensuring early detection of the minority of patients who develop permanent thyroid dysfunction (Figure 2, Step 8).

Special situations

SAT usually follows a benign, predictable course; however, certain clinical contexts, such as pregnancy and recent SARS-CoV-2 infection or vaccination, require specific diagnostic and therapeutic strategies (Figure 2, Step 10). Special clinical situations that require diagnostic or therapeutic adaptation in SAT are summarized in Table 3.

Table 3.

Special situations in SAT.

Clinical context	Diagnostic adaptation	Treatment adaptation	Follow-up considerations
Pregnancy	Avoid radionuclide imaging; rely on clinical features, ESR/CRP, ultrasound, TRAb if needed	Prefer acetaminophen first; cautious NSAID use only when appropriate; low-dose steroids if necessary; lower threshold for levothyroxine	Closer thyroid function test monitoring; obstetric co-ordination
Lactation	Avoid radionuclide imaging unless breastfeeding interruption is specifically planned and justified	Choose lactation-compatible analgesics/β-blockers/steroids	Counsel regarding medication compatibility
SARS-CoV-2 infection-associated SAT	Symptoms may overlap with infection; imaging often selective	Standard SAT treatment, but consider concurrent systemic steroid use	Monitor for atypical/painless course
Vaccine-associated SAT	Temporal association important; otherwise, same workup	Same as classical SAT	Individualize future vaccination decisions
Refractory or recurrent SAT	Reassess diagnosis and exclude alternative causes of thyroid pain or thyrotoxicosis; evaluate treatment adherence and relapse during steroid taper	Consider prolonged/slower steroid taper; colchicine as a steroid-sparing option; selected cases may benefit from intrathyroidal corticosteroid injection or ultrasound-guided lidocaine; thyroidectomy rarely required	Closer clinical and thyroid function test monitoring; individualized management, preferably in experienced centres

CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; SAT, subacute thyroiditis; TRAb, thyroid-stimulating hormone receptor antibodies.

Pregnancy and lactation

SAT during pregnancy appears to be uncommon and may present with attenuated systemic symptoms and less pronounced thyrotoxicosis, which increases the risk of misdiagnosis as gestational thyrotoxicosis, hyperemesis gravidarum or other causes of pregnancy-related thyroid dysfunction.48 Distinguishing SAT from gestational thyrotoxicosis is particularly important because the latter is far more common and is typically associated with elevated hCG levels, hyperemesis gravidarum, absence of neck pain or thyroid tenderness and lack of systemic inflammatory findings.49 In contrast, classical features of SAT, including anterior neck pain, thyroid tenderness, elevated ESR and/or CRP above that expected for gestational age and a characteristic triphasic evolution of thyroid function, remain key diagnostic clues.49 In this setting, diagnosis relies on careful clinical evaluation, thyroid function tests, inflammatory markers and ultrasound (often showing hypoechoic, poorly marginated areas with low or normal vascularity), whilst other causes, such as Graves’ disease, are excluded by history, Doppler hypervascularity and TRAb testing when needed.47

Management in pregnancy focuses on symptom relief whilst minimising risks to the mother and fetus. For pain control during pregnancy, acetaminophen is the preferred first-line therapy.47 Given the potential foetal risks associated with NSAID exposure and their limited role in routine obstetric practice, NSAIDs are generally not recommended.49 In patients with severe symptoms that are inadequately controlled with acetaminophen, glucocorticoids may be considered and should be administered at the lowest effective dose for the shortest possible duration, ideally in consultation with obstetric colleagues.49 β-Blockers can be used cautiously for bothersome thyrotoxic symptoms but should be prescribed at the lowest effective dose and for the shortest possible time to reduce the risk of fetal growth restriction or neonatal hypoglycaemia.98 During the hypothyroid phase, treatment thresholds are lower than in non-pregnant patients: levothyroxine is generally recommended when TSH exceeds pregnancy-specific upper limits, even if symptoms are mild, to safeguard foetal neurodevelopment, especially during the first trimester.47,49 In the postpartum period, breastfeeding does not substantially alter the management of SAT, although medications such as β-blockers and glucocorticoids should be selected and dosed with consideration of their compatibility with lactation.

SAT after SARS-CoV-2 infection or vaccination

SARS-CoV-2 infection has emerged as a notable trigger for SAT, with cases reported during acute COVID-19 and in the post-infectious period.11–15 Presentations range from classic painful SAT with fever and neck tenderness to atypical or painless forms in which thyrotoxicosis and systemic symptoms predominate, sometimes overlapping with non-thyroidal manifestations of COVID-19.11–15 Similar SAT-like syndromes have been described after SARS-CoV-2 vaccination, usually within weeks of immunisation, supporting a role for immune activation rather than direct viral cytotoxicity in triggering thyroid inflammation.16,99

Diagnosis of SAT in the context of COVID-19 relies on the same core criteria — neck pain or discomfort, thyroid tenderness, elevated ESR/CRP, low radioisotope uptake when performed and a typical evolution of thyroid function — but clinical interpretation can be complicated by overlapping symptoms such as myalgias, fever and fatigue. Ultrasound and Doppler findings are similar to those of classical SAT, and radionuclide imaging should be deferred or omitted in acutely ill patients with COVID-19 unless absolutely necessary.

Treatment principles remain unchanged: NSAIDs or glucocorticoids for pain and inflammation, β-blockers for symptomatic thyrotoxicosis and temporary levothyroxine during the hypothyroid phase when indicated. However, glucocorticoid decisions must factor in the severity of COVID-19 infection and concurrent steroid therapy, as existing systemic steroids for COVID-19 may already be modulating SAT symptoms in some patients, whereas in others, additional or prolonged tapering targeted to thyroid pain is required.11,13 For SAT after vaccination, management is the same as for classic SAT, and current evidence does not support withholding further vaccination solely on the basis of a prior SAT episode, though decisions should be individualized.16

Altogether, these special situations illustrate that, whilst the fundamental pathophysiology and management principles of SAT remain constant, clinical contexts, such as pregnancy and concurrent viral infection, should shape diagnostic choices, treatment thresholds and the involvement of other specialties in patient care.

Difficult cases: refractory disease and recurrences

Most patients with SAT respond promptly to NSAIDs or glucocorticoids and experience complete resolution. However, a minority develop refractory disease, characterized by persistent pain and inflammation despite adequate anti-inflammatory therapy or experience relapse during glucocorticoid tapering or after treatment discontinuation. When symptoms persist despite appropriate NSAID therapy, glucocorticoids remain the standard next step. In patients who fail to respond adequately to corticosteroids or who experience repeated relapses, several alternative approaches have been described. Colchicine has emerged as a potential steroid-sparing option, with case reports and small series suggesting benefit in reducing inflammation and preventing recurrent episodes.100–102 Local therapies, including intrathyroidal corticosteroid injection and ultrasound-guided lidocaine injection, have also been reported to provide rapid pain relief in selected patients with localized, treatment-resistant disease.25,103,104 Although evidence remains limited, these interventions may be considered in specialized centres when conventional therapy fails.

Thyroidectomy is rarely required but remains a definitive option for exceptional cases with severe, persistent symptoms, multiple recurrences, intolerance to medical therapy or substantial impairment of quality of life.105,106 Because evidence for these alternative treatments is largely derived from observational studies and case reports, management should be individualized and preferably undertaken in consultation with clinicians experienced in complex thyroid inflammatory disorders.

Long-term outcomes and prognosis

SAT is generally associated with an excellent long-term prognosis, but a minority of patients develop permanent thyroid dysfunction or recurrent disease, and these risks should be discussed during follow-up. In most series, the entire clinical course, from onset of neck pain through thyrotoxicosis, hypothyroidism and recovery, rarely exceeds 4–6 months, and most patients ultimately regain normal thyroid function without lasting sequelae (Figure 2, Step 9).5

Permanent hypothyroidism

The most important long-term complication is permanent hypothyroidism. Most patients experience full recovery of thyroid function after the transient hypothyroid phase, but observational cohorts suggest that approximately 5–15% develop sustained elevation of TSH compatible with chronic primary hypothyroidism requiring ongoing levothyroxine therapy.5–8

Factors associated with this outcome may include more extensive parenchymal destruction, higher TSH levels during the hypothyroid phase, positive thyroid autoantibodies indicating coexisting autoimmune thyroid disease, and possibly more severe inflammatory episodes.6–8

Recurrence

Recurrence of SAT, whilst not the norm, is well documented and clinically relevant. Reported recurrence rates vary between studies, from very low to approximately 10–20%, reflecting differences in follow-up duration and diagnostic thresholds.5,50–52 Recurrent episodes can occur shortly after tapering anti-inflammatory therapy or many years after the initial illness, and they often present with similar symptoms, sometimes involving the contralateral lobe. Recent genetic data suggest that specific HLA constellations, particularly co-occurrence of HLA-B*35 and HLA-B*18:01, may confer a higher risk of recurrence, implying that host immunogenetic factors influence not only susceptibility but also the likelihood of relapse. Nonetheless, recurrent episodes are typically managed successfully with the same therapeutic principles as the initial event, although a more gradual glucocorticoid taper may be prudent.24,90,104 Patients with severe initial disease requiring prolonged or higher-dose glucocorticoid therapy have also been reported to experience more frequent recurrences; however, it remains unclear whether this association reflects the effects of treatment itself or the underlying severity of the inflammatory process.87,89 Risk factors associated with recurrence and permanent hypothyroidism are summarized in Table 4.

Table 4.

Risk factors for recurrence and permanent hypothyroidism.

Factor/marker	Association	Evidence summary (brief)	Practical implication
HLA-B*35	Increased risk of SAT and possible recurrence	Observational cohorts	Flag for closer follow-up
HLA-B*18:01 and combinations (e.g. B*35+B*18:01)	Increased recurrence risk	Recent genetic association studies	Consider slower steroid taper and longer monitoring
Positive thyroid autoantibodies (TPOAb/TgAb)	Increased likelihood of permanent hypothyroidism	Follow-up studies	Lower threshold for long-term LT4
Extent of hypoechogenicity on ultrasound	More extensive tissue damage linked to hypothyroidism	Ultrasound–outcome correlations	Anticipate higher risk of permanent dysfunction
Severe initial episode requiring high-dose or prolonged steroids	Possible increased risk of recurrence or hypothyroidism; association may reflect underlying disease severity rather than steroid exposure itself	Retrospective series	Plan longer follow-up and cautious taper
Pre-existing autoimmune thyroid disease (e.g. Hashimoto thyroiditis), irrespective of antibody status	Increased risk of permanent hypothyroidism	Cohort data	Early transition to chronic hypothyroidism management

HLA, human leukocyte antigen; LT4, levothyroxine; SAT, subacute thyroiditis; TgAb, thyroglobulin antibodies; TPOAb, thyroid peroxidase antibodies.

Impact on quality of life and broader thyroid autoimmunity

During the acute phase, pain, systemic inflammatory symptoms and transient thyrotoxicosis can substantially impair quality of life and functional capacity, but these effects are usually confined to the first weeks of illness and improve rapidly with appropriate treatment. Long-term quality of life is generally good, provided that permanent hypothyroidism is recognized and adequately treated. Some patients develop or reveal concomitant autoimmune thyroid disease, and there are reports linking SAT with later autoimmune thyroiditis or Graves’ disease, but these associations appear uncommon and causal relationships remain uncertain.105–108

Overall prognosis

Overall, patients can be reassured that SAT is a self-limited condition with a high likelihood of complete recovery, whilst also being informed that a minority will require long-term levothyroxine replacement and that recurrence, though infrequent, is possible. Clear communication of these expectations and appropriate long-term monitoring help ensure timely detection and management of residual thyroid dysfunction and reinforce the generally favourable prognosis of this disorder.

Practical algorithm

A practical approach to SAT begins with recognising the clinical pattern of a painful, inflammatory, destructive thyroiditis and then proceeding through a structured sequence of confirmation, exclusion of important mimics, symptom-directed treatment, and biochemical follow-up (Figure 2). The key management principle is that SAT is usually self-limited, so the aim is not to suppress thyroid hormone synthesis but to control pain and systemic symptoms, manage the transient phases of thyroid dysfunction, and avoid unnecessary interventions such as antibiotics, antithyroid drugs or radioiodine in the wrong setting.

Future directions

SAT is well described clinically; however, important unmet needs remain regarding prevention and the selection and optimisation of treatment.

Novel biomarkers could be helpful; for example, cytokine profiles, HLA-based risk markers and transcriptomic signatures could be helpful for improving diagnostic accuracy, predicting recurrence, and identifying patients who may benefit from tailored anti-inflammatory treatment. Current practice is based largely on observational data and small trials comparing different glucocorticoid doses and tapering schedules, with some evidence that shorter steroid courses combined with NSAIDs can control symptoms whilst limiting adverse effects. Larger, well-designed randomized studies are needed to determine the minimum effective glucocorticoid dose and taper length, quantify the impact on recurrence risk, and assess whether certain subgroups, such as patients with specific HLA backgrounds or severe systemic manifestations, benefit from distinct regimens. Similarly, evidence-based thresholds for initiating levothyroxine in the hypothyroid phase, particularly in non-pregnant patients with modest TSH elevation and minimal symptoms, could reduce unnecessary long-term treatment whilst maintaining safety.

Finally, advances in imaging (such as standardized use of Doppler and elastography) and biomarker discovery (including cytokine profiles and transcriptomics) may ultimately improve diagnosis, prognosis and therapeutic decision-making in SAT, moving care towards more individualized, mechanism-based management.

Conclusions

SAT is a self-limited, destructive inflammatory disorder that requires a structured and evidence-based approach to ensure accurate diagnosis and appropriate management. Recognition of its characteristic clinical presentation, that is, painful thyroid enlargement, systemic inflammation and transient thyrotoxicosis, is fundamental for early suspicion. The diagnosis is confirmed by biochemical findings and by selective imaging demonstrating low or absent radionuclide uptake, whilst important mimics, such as acute suppurative thyroiditis, spontaneous haemorrhage into a pre-existing thyroid nodule and Graves’ disease, must be excluded. Treatment is primarily supportive and guided by symptom severity, with NSAIDs or glucocorticoids for pain and inflammation, β-blockers for symptomatic thyrotoxicosis, and selective, time-limited levothyroxine therapy during the hypothyroid phase. As thyrotoxicosis results from the release of preformed hormones rather than increased synthesis, antithyroid drugs and radioiodine are not indicated. Regular biochemical follow-up is essential to monitor the characteristic triphasic course, detect recurrence and identify the minority of patients who develop permanent hypothyroidism. Special clinical settings, including pregnancy and SARS-CoV-2-associated disease, require individualized diagnostic and therapeutic considerations. Overall, a systematic and patient-centred approach facilitates optimal outcomes whilst minimising unnecessary interventions.