RECURRENT PAINFUL HASHIMOTO THYROIDITIS SUCCESSFULLY TREATED BY THYROIDECTOMY

Abstract

Objective:

Painful Hashimoto thyroiditis (HT) is a rare HT variant characterized by neck pain. The clinical differentiation between painful HT and subacute thyroiditis is challenging, as the diagnosis cannot be confirmed without histopathological evidence. Here we present a patient who had anterior neck pain who was diagnosed with HT.

Methods:

We present the patient's clinical examinations and laboratory findings (white blood cell count, thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibody, and erythrocyte sedimentation rate). Ultrasound images of the thyroid gland and pathology images representative of marked HT with positive IgG4 immunohistochemical stain after thyroidectomy are also presented.

Results:

A 42-year-old female with a 3-year history of HT developed recurrent anterior neck pain with bilateral radiation to the ears as well as a tender, enlarging thyroid goiter. She had no signs of fever or a preceding infection of the upper respiratory tract. Her pain was only temporarily alleviated by oral corticosteroids. According to the serial ultrasound records, both thyroid lobes decreased in size after 2 pain episodes. She eventually underwent total thyroidectomy and remained pain-free for 1.5 years, up to the last office follow-up visit. Histopathology confirmed the diagnosis of HT.

Conclusion:

In patients with HT, recurrent thyroid pain despite steroid treatment is the clinical hallmark of diagnosis of painful HT. The reference standard of diagnosis is pathology. Thyroidectomy may be considered after recurrent painful episodes.

INTRODUCTION

Painful Hashimoto thyroiditis (HT) is a rare variant of HT which features thyroid pain and pathologic features revealing lymphocytic thyroiditis. It was first described by Doniach et al (1) in 1960, followed by a case series reported by Zimmerman et al (2) in 1986. Since 2000, only 20 cases have been reported (3).

The most common form of painful thyroiditis is subacute thyroiditis (SAT), also known as de Quervain thyroiditis. SAT is usually preceded by upper respiratory tract viral infection and responds well to steroid treatment. Patients with painful HT are usually misdiagnosed with SAT given the similar clinical features such as fever, elevated erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentration (4). However, steroid treatment only gives a temporary pain relief. Most patients develop recurrent neck pain that eventually requires thyroidectomy to permanently relieve pain (5). The definitive method to differentiate between the 2 diseases is through pathologic examination.

We report here the case of a patient affected with HT for 3 years, who subsequently developed recurrent attacks of thyroid pain requiring steroid treatment. The patient has been pain-free after a total thyroidectomy.

CASE REPORT

A 42-year-old female with a 3-year history of HT and diffuse goiter who was being treated with levothyroxine presented in May of 2014 after her first attack of anterior neck pain. She had bilateral radiation to the ears and a tender, enlarged thyroid goiter. In the previous week, the patient had experienced neck pain with occasional radiation to the ears and gradual enlargement of the goiter.

No fever or history of recent upper respiratory tract infection was present. The patient was hypothyroid, with a serum thyroid-stimulating hormone level of 6.01 mIU/mL (normal range is 0.47 to 4.68 mIU/mL) and a free thyroxine of 1.0 ng/dL (normal range is 0.82 to 1.77 ng/dL). Furthermore, the levels of thyroid peroxidase antibody were significantly elevated (>600 IU/mL). A neck computed tomography scan, which was done in the emergency department, showed symmetric heterogeneous goiter without tracheal compression or substernal extension. The symptoms resolved completely after the administration of 10 mg of prednisone daily for 5 days along with 600 mg of ibuprofen 3 times a day. However, her thyroid function fluctuated and required periodic levothyroxine titration.

The patient remained pain-free until 20 months later, when she developed a second attack of neck pain. Before going to the emergency department, the patient took 800 mg of ibuprofen 3 times a day for a couple of days, with minimal response. The patient visited the emergency department after having a swollen and painful neck, with the pain radiating to her ears. She was also experiencing fluctuations in the size of the thyroid gland.

There was no sign of a recent upper respiratory tract infection or fever. Laboratory tests showed a mild leukocytosis (white blood cell count of 12,000 cells/μL, reference range is 4,500 to 11,000 cells/μL) without neutrophilia. The patient was hypothyroid, with a serum thyroid-stimulating hormone level of 6.48 mIU/mL and a free thyroxine of 1.47 ng/dL, despite being on levothyroxine. Ultrasound revealed a slightly decreased thyroid size with internal vascularity. No thyroid nodule was found. Treatment with acetaminophen and codeine failed to relieve the patient from pain. She was then administered 40 mg of prednisone daily, with a taper. The prednisone treatment helped in relieving her neck pain and reduced the goiter size. The leukocytosis status resolved after the treatment.

The patient underwent left thyroidectomy in August of 2016, 27 months after the first pain episode. Preoperative thyroid sonogram showed an enlarged, hypoechoic, and heterogeneous thyroid gland in both lobes (Fig. 1). Both thyroid lobes had decreased in size according to the serial ultrasound records (Table 1). Because she had a large and extremely firm goiter that took an extended time to remove, the surgeon was only able to perform a left hemithyroidectomy.

Fig. 1.

Ultrasound of the thyroid gland showing both the left (A) and right (B) lobes. Bilateral lobes showed heterogeneous echogenicity. There was no evidence of discrete nodules.

Table 1.

Thyroid Size by Ultrasound Examination

	Right lobe	Left lobe
Before first attack	5.5 × 2.8 × 3.2 cm	6.5 × 2.8 × 3.6 cm
During second attack	5.4 × 3.3 cm	5.0 × 3.5 cm
After second attack	5.0 × 2.5 × 3.2 cm	5.9 × 2.4 × 2.6 cm

Four months after the surgery, the patient developed right thyroid swelling and pain radiating to the ears for 1 month. Similar to the previous pain episodes, we observed no sign of fever or recent upper respiratory tract infection. ESR was elevated at 53 mm/hour (reference range is 0 to 32 mm/hour). Symptoms resolved after a treatment with 30 mg of prednisone daily and 800 mg of ibuprofen 3 times a day. The patient underwent a completion right thyroidectomy 3 months after the May 2017 attack. The pathology examination of both removed thyroid lobes showed marked HT with positive IgG4 immunohistochemical stain (Fig. 2). The patient has been actively followed in our clinic, and she has remained pain-free for 1.5 years after surgery so far.

Fig. 2.

Histopathology of the thyroid gland under hematoxylin and eosin stain (A and B) and IgG4 immunohistochemical stain (C and D). Low-power view of the Hashimoto thyroiditis with its recognizable germinal centers and low-to-moderate levels of fibrosis (A). High-power view of a group of germinal centers with entrapped thyroid follicles and marked lymphocytic and plasmacytic infiltrate (B). Panels C and D show the same area stained with IgG4 immunohistochemistry, revealing many interspersed IgG4-positive plasma cells (up to 50 per high-power field).

DISCUSSION

Painful HT is also known as acute exacerbation of HT or painful variant of HT. Due to its atypical presentation, this variant has not been well studied. Its pathophysiology remains unknown because while it was hypothesized capsular stretching caused the pain (2), this cannot explain pain in patients whose thyroid gland decreased in size during the disease's course

Most reported cases of painful HT occur in females with a known history of HT or seronegative goiters (4–9), and rarely with preexisting Graves disease (4,9–11). Most patients do not have signs of a recent upper respiratory tract infection or leukocytosis. However, about 40% of all the reported cases present signs of fever, elevated ESR, or CRP. The thyroid function at the initial painful event can vary; hypothyroid, euthyroid, and hyperthyroid states have been reported (2,7,12). The presence of thyroid auto-antibodies, including anti-thyroid peroxidase and anti-thyroglobulin, are diagnostic markers of the disease. Even patients with a history of seronegative goiters are positive for thyroid autoantibodies at the time of diagnosis.

Sonography is an important imaging technique used to differentiate between SAT and the painful variant of HT. Most cases of the latter reveal a diffuse heterogeneous hypoechoic change of the thyroid. If there is any hypoechoic nodule within the thyroid, Doppler sonography always shows an increased flow in the lesion (4,8,10). After the treatment, neck pain persists, regardless of the blood flow status, which could be decreased (4) or unchanged (8).

Treating patients with painful HT is challenging, as there is no consensus on how to manage this rare disorder. The majority of patients in the previous studies received corticosteroids (2,4–8,10,13–16). However, less than 30% of patients experienced sustained pain relief. The patients usually reported temporary improvement from pain but experience pain again after dose reduction. The dose of corticosteroids does not correlate with pain reduction and may even lead to iatrogenic Cushing syndrome (10). Other medical treatments include levothyroxine, aspirin, and nonsteroidal antiinflammatory drugs. Both Zimmerman et al (2) and Kon et al (7) administered levothyroxine to nonhypothyroid patients. Most of the patients achieved permanent pain relief in Zimmerman's group, while none became pain-free in Kon's group. No patients receiving nonsteroidal antiinflammatory drugs reported sustained pain relief.

Surgical intervention, including total thyroidectomy, subtotal thyroidectomy, or near-total thyroidectomy, remains the last resort when all medical treatments fail (2,4–6,10,11,15,16). Every patient that underwent total thyroidectomy has been pain-free during the follow-up period. However, 1 patient who underwent subtotal thyroidectomy and 1 that underwent near-total thyroidectomy developed recurrent pain, despite a treatment with radioactive iodine ablation after surgery (7). Our patient also experienced pain after the initial hemithyroidectomy. Therefore, total thyroidectomy is probably the best treatment for permanent thyroid pain relief in the cases where analgesic drugs are not effective anymore.

Our case also further supports the hypothesis that the pain originates from thyroid, rather than from other tissues in the neck. Patients with painful HT usually have extreme fibrotic changes in the thyroid gland that make surgical removal difficult. An experienced surgeon is crucial to perform successful surgery and to prevent the complications of hypoparathyroidism or recurrent laryngeal nerve damage. All the previously reported cases showed lymphocytic infiltration with varying degrees of fibrosis and destruction of follicle structure upon pathologic examinations of the thyroid tissue obtained either from fine-needle aspiration or surgery. These pathological findings are consistent with HT.

However, cases of IgG4-positive thyroiditis have also been reported, which shares the same features of HT but is characterized by a higher grade of fibrosis and stains positive for IgG4 (17). Our case showed evidence of IgG4-positive plasma cells, up to 50 cells per high-power field, but with only low-to-moderate levels of fibrosis. The severity of fibrosis observed made Riedel thyroiditis less likely. Without available serum IgG and IgG4 levels, the diagnosis of IgG4-positive thyroiditis could not be confirmed.

In the diagnosis of patients presenting with a painful thyroid, the most common differentials include SAT, suppurative thyroiditis, trauma events, and nodular hemorrhage (18). The distinction between painful HT and SAT is especially difficult at the initial presentation, given that the symptoms originate from the acute inflammation of the thyroid (Table 2). Fever, elevation of ESR and CRP were previously considered to be representative of SAT. However, about 50% of the reported cases of painful HT also present with fever, elevated ESR, and CRP.

Table 2.

Comparison Between Painful Hashimoto Thyroiditis and Subacute Thyroiditis

	Painful Hashimoto thyroiditis	Subacute thyroiditis
Fever	Variable	Usual
ESR/CRP	Normal or elevated	Elevated
Prior thyroid disease	Usual	Rare
Prior viral infection	Rare	Usual
Antithyroid antibodies	Present	Usually absent
Corticosteroid response	Poor	Good
Thyroid function at onset	Variable	Usually thyrotoxicosis
Thyroid function during recovery	Variable, euthyroid, or hypothyroid	Usually euthyroid
Sonography features	Diffuse heterogeneous hypoechoic pattern, and increased vascular flow to hypoechoic lesions if present	Diffusely hypoechoic with decreased blood flow to ill-defined hypoechoic thyroid lesions
Pathology	Lymphocytic infiltration, Hürthle cells, and variable fibrosis	Noncaseating granulomas, neutrophils, and giant cells

Abbreviations: CRP = C-reactive protein; ESR = erythrocyte sedimentation rate.

The lack of defined characteristics distinguishing SAT and painful HT contributes to the diagnostic difficulty in clinical practice. Patients with SAT rarely have a preexisting clinical thyroid disease, and usually develop the condition after an upper respiratory tract infection. Most of the patients with painful HT have either a history of HT, Graves disease, or seronegative goiters. Antithyroid antibodies are always high in patients with painful HT, while are usually absent in patients with SAT. In a cohort of 73 patients with painful thyroiditis, a large proportion of patients had elevated levels of antithyroid antibodies, but only 2 patients were diagnosed with painful HT on the basis of the final pathology examination (8). SAT is usually characterized by a transient thyrotoxicosis, with 5% of patients becoming hypothyroid afterward. Painful HT is characterized by various changes in thyroid function initially and during the recovery period (6,9). SAT responds to corticosteroid treatment rapidly without recurrence of pain, while most cases of painful HT are refractory to this treatment.

Thyroid sonography provides different features to distinguish SAT from painful HT. In patients with SAT, the thyroid gland appears diffusely hypoechoic with decreased blood flow and may show ill-defined hypoechoic thyroid lesions (19). On the other hand, in painful HT the gland reveals a diffuse heterogeneous hypoechoic pattern, and an increased vascular flow to hypoechoic lesions, if present (4,8,10,16). Only pathology examination can give a definitive diagnosis. By microscopic examination, SAT shows the presence of noncaseating granulomas, neutrophils, and giant cells, whereas painful HT shows the classic HT signs of lymphocytic infiltration, Hürthle cells, and variable fibrosis.

CONCLUSION

For patients with painful HT refractory to medical therapy, surgical intervention should be considered as a treatment option as it usually yields permanent pain control.

Abbreviations

CRP

C-reactive protein

ESR

erythrocyte sedimentation rate

HT

Hashimoto thyroiditis

SAT

subacute thyroiditis