Subacute thyroiditis with airway compromise in a 5-year-old boy

Abstract

A 5-year-old boy presented with intermittent fever for 1 month, painful neck swelling associated with dysphagia, hoarseness of voice for 3 weeks and dyspnoea of 1-day duration. On evaluation, he had elevated serum thyroglobulin levels and inflammatory markers. There was a diffuse glandular thyroid enlargement with hypoechoic areas on neck ultrasonography. Fine-needle aspiration cytology was suggestive of subacute thyroiditis (SAT), and MRI of the neck confirmed narrowing of the trachea by the enlarged thyroid. He received steroids to relieve airway compression. Levothyroxine was started. On follow-up, he was symptom-free and euthyroid; steroids and levothyroxine were discontinued. SAT presenting with compression of trachea is rare in children. This highlights the need for identifying the type of thyroiditis to determine treatment modality.

Background

Subacute thyroiditis (SAT), frequently known as granulomatous or de Quervain thyroiditis, is an acute inflammatory condition affecting the thyroid gland, presumably triggered by a viral infection,^{1 2} namely, coxsackievirus, cytomegalovirus, adenovirus, enterovirus, Epstein-Barr virus, mumps, echovirus and influenza virus.^{2 3}

Typically, it is characterised by painful thyroid enlargement with evolution to hyperthyroid, hypothyroid or euthyroid state, along with raised inflammatory markers and thyroglobulin levels. It mimics acute suppurative thyroiditis (AST), which is more prevalent in children. In contrast, SAT is rare in children, and only a few cases have been reported.^2–4 Diagnosis is challenging due to the lack of clear differentiation in clinical features and self-limiting nature of the disease, but nevertheless management differs for SAT and AST. Here, we present SAT in a 5-year-old boy who presented with dyspnoea as a result of airway compromise by the enlarged thyroid.

Case presentation

A 5-year-old boy presented to the emergency department with intermittent fever for 1 month, painful swelling in the neck, difficulty in swallowing, hoarseness of voice for 3 weeks and difficulty in breathing for 1 day.

He had received antibiotics and other supportive measures at a hospital in his hometown and then was referred to our centre due to persistent symptoms. There was no significant family and medical history. He had received his routine immunisations as per the national immunisation schedule.

On examination, he had mild stridor and his respiratory rate was 33 cycles/min, temperature was 100.8°F, heart rate was 118 beats per minute, blood pressure was 100/64 mm Hg (between the 50th and 90th percentile) and oxygen saturation was 99%. He weighed 20.04 kg (between the 75th and 90th centile for age on WHO growth charts). BCG scar was visible on the left upper arm. His development was age-appropriate. He had no clinical features suggestive of hyperthyroid or hypothyroid state.

Local examination showed tender, diffuse midline swelling of the neck, measuring approximately 40 mm×30 mm (figure 1) which moved on deglutition, and there was an absence of cervical lymphadenopathy. Lung auscultation was clear, and other systems were unremarkable. The thyroid swelling being painful and tender made us consider whether it was the more common AST or the rarer SAT that was compressing the airway.

Figure 1.

(A and B) Diffuse midline swelling on the anterior aspect of the neck.

Investigations

He had microcytic, hypochromic anaemia (haemoglobin, 104 g/L; reference range, 110–140 g/L) with leucocytosis (14×10⁹ cells/L; reference range, 5–15×10⁹ cells/L), hypothyroidism (increasing thyroid-stimulating hormone (TSH) levels from 2.52 to 5.05 mIU/L (reference range, 0.4–10 mIU/L), T3 of 1.95 nmol/L (reference range, 1.44–3.7 nmol/L) and decreasing T4 levels from 135 to 128 nmol/L (reference range, 82.38–171.20 nmol/L) over a week’s time), elevated C reactive protein (1113 nmol/L; reference range, 0–57.14 nmol/L) and elevated erythrocyte sedimentation rate (60 mm/hour; reference range, ≤10–20 mm/hour). Serum thyroglobulin levels were elevated (70.1 µg/L; reference range, 1.6–60 µg/L). Blood culture showed no growth.

Ultrasonogram of the neck showed a large collection measuring 6.3×2.7×4.0 cm with internal echoes and few internal septations in the bilateral paratracheal region encasing the thyroid gland (figure 2). Fine-needle aspiration cytology (FNAC) done to rule out an infective aetiology showed predominantly macrofollicular pattern with neutrophils, histiocytes and few lymphoid cells. Colloid was absent with amorphous necrotic material and a few cysts, as well as haemosiderin-laden macrophages. Occasional multinuclear giant cells were seen with many epithelioid cells with small, round and dark nuclei, features suggestive of granulomatous thyroiditis (figure 3A–D).

Figure 2.

Ultrasonogram showing a large collection with internal echoes and few internal septations in the bilateral paratracheal region encasing the thyroid.

Figure 3.

Fine-needle aspiration cytology of subacute granulomatous thyroiditis. (A) Thyroid follicular epithelial cells in a macrofollicular pattern (Papanicolaou stain; 400×); inset: follicular cells in a microfollicular pattern (Papanicolaou stain; 400×). (B, C) Scattered granulomas composed of epithelioid histiocytes (Papanicolaou stain; 400×). (D) Variably sized multinucleated giant cells (May-Grunwald Giemsa stain; 400×; inset: Papanicolaou stain; 400×).

MRI of the neck was performed because of airway compromise, and it showed gross enlargement of both lobes of the thyroid, with the right lobe measuring 56×28×20 mm and the left lobe measuring 65×34×32 mm. Severe narrowing of the tracheal lumen was seen, with trachea at narrow segment measuring 7×3 mm (anteroposterior×transverse) with no retrosternal extension (figure 4A–E).

Figure 4.

MRI of the neck. (A) T2-FATSAT coronal image and (B) T2 sagittal image showing enlarged thyroid gland with fluid collection; (C) T1 axial image, (D) T2 axial image and (E) FATSAT axial image showing enlarged thyroid with compression of the trachea with deviation to the right.

Differential diagnosis

In the presence of thyroid pain and symptoms as in this case, AST, SAT and tuberculous thyroiditis are to be considered.

SAT is usually not described in children and is a self-limiting illness, and its presentation mimics AST. Typically, on ultrasonography (USG), there are localised hypoechoic areas of low vascularisation isolated mostly to the left side upper pole in AST versus the diffuse involvement of the thyroid gland with hypoechogenic areas with characteristic glandular oedema in SAT.⁵ In our case, USG had diffuse involvement of the thyroid gland, along with collection of fluid, internal echoes and septations, thereby having overlapping features of both AST and SAT. The absence of cervical lymphadenopathy was more in favour of SAT. Also, the diffuse enlargement of the gland as in SAT is usually capable of compressing the airways when compared with the localised involvement of the thyroid in AST. All these features made us think that SAT is more likely to be the diagnosis in this case. FNAC was conclusive of granulomatous thyroiditis. The child required an MRI of the neck because of airway compromise, and it showed a diffuse involvement of the thyroid gland with tracheal compression.

Tuberculous thyroiditis is extremely rare with focal (least common), diffuse and miliary (most common) involvement. Clinical presentation could vary from indolent and asymptomatic form to acute form with abscess and fistula formation.⁶ USG shows a localised abscess and fistula formation with adjacent tuberculous lymphadenopathy.⁵ No such findings were present in our case.

Other forms of thyroiditis such as Hashimoto’s thyroiditis and Riedel’s thyroiditis are usually painless and are extremely rare in children, hence was not considered in the list of differential diagnosis.

Treatment

Steroids (hydrocortisone injection) were given to relieve from compression effects of the oedematous thyroid gland. He was supported with intravenous fluids, oxygen and analgesics.

Once he was symptomatically better, he was continued on oral steroids (deflazacort) at 0.5 mg/kg/day. Levothyroxine was initiated as the serum TSH levels were high, although he did not have overt features of hypothyroidism.

Outcome and follow-up

Within 48 hours of initiating steroids, his stridor/swallowing improved, voice had normalised, he was afebrile and had no thyroid pain. Swelling minimally persisted on day 3 of steroids. Oral steroid, deflazacort at 0.5 mg/kg/day, was continued, and at 2 weeks of follow-up, he was asymptomatic with no thyroid swelling. Steroids were tapered and stopped after a month. At follow-up, he was found to be euthyroid (serial thyroid profiles as in table 1), and he is doing well with regular follow-up for the last 2 years.

Table 1.

Thyroid profiles at follow-up

Repeat thyroid profiles at follow-up	Serum T3 levels	Serum T4 levels	Serum TSH levels
2 weeks	1.81	108.12	3.93
3 months	2.53	105.55	2.99
6 months	2.86	107.10	3.83
12 months	2.96	113.27	3.96
18 months	3.10	110.12	3.99
24 months	3.30	111.69	3.95

*Reference ranges for a 5-year-old—serum T3: 1.44–3.7 nmol/L; serum T4: 82.38–171.20 nmol/L; serum TSH: 0.4–10 mIU/mL.

TSH, thyroid-stimulating hormone.

Discussion

The term ‘thyroiditis’ includes a broad spectrum of disorders characterised by inflammation of the thyroid gland. It is broadly classified into AST, subacute (de Quervain) thyroiditis and chronic thyroiditis. Differentiation is vital because aetiology, clinical features, clinical course and management are specific to the type of thyroiditis.

Both AST and SAT usually present as painful swelling of the neck. On the contrary, chronic thyroiditis like Hashimoto’s usually presents as a painless swelling of the thyroid gland. Most of the SAT cases are triggered by a viral upper respiratory infection, following which the thyroid follicles have inflammatory destruction.⁷ On the contrary, AST is more common following bacterial infections.³ SAT is seen usually in adults and in female gender, with peak incidences being in the fourth and fifth decades of life and rare in the first 10 years of life.⁸ Its incidence in the paediatric age group is not known due to its rarity.³

The usual postnatal development of the thyroid gland is characterised by numerous colloid filled-follicles by the end of the second week. The follicles increase in size, and by 35 days postnatal, the thyroid shows mature adult features.⁹ The production rate of T4 is in the order of 5–6 µg/kg/day, decreasing slowly to 2–3 µg/kg/day at ages 3–9 years. In contrast, the T4 production rate in adults is 1.5 µg/kg/day. Hence, comparing with age-appropriate normative values is mandatory. The gland weighs approximately 1 g at birth and increases about 1 g per year until 15 years (adult size of 15–20 g).¹⁰ Thus, by 5 years of age, the thyroid gland is developed to have mature follicles as in adults; however, the production rate of hormones varies by age, and the size of the thyroid gland is nearly half of the adult thyroid gland

In the natural clinical course of SAT, there is a flu-like prodrome about 1–3 weeks before the onset of thyroiditis. The antigen provided by viral infection binds to the HLA-Bw35 molecule or macrophages, forming an HLA-Bw35 antigen complex.¹¹ This complex further activates the cytotoxic T lymphocytes and in turn damages the thyroid follicular cells due to molecular memory. The thyroid follicular epithelium gets destroyed and loses its integrity and thereby releases the preformed thyroid hormone into circulation, triggering the pathophysiological mechanisms for SAT.

SAT evolves through four phases during its clinical course. The acute phase (3–6 weeks) is associated with features of hyperthyroidism, with radioiodine uptake being low. Low-grade fever, dysphagia, history of upper respiratory infection and excruciating neck pain are other associated presenting complaints. This is followed by a transient asymptomatic euthyroid phase (1–3 weeks). The third phase (weeks to months) is the hypothyroid phase and corresponds to the phase when there is colloid depletion and the thyroid is incapable of producing thyroid hormone. Once the thyroid follicular epithelium regenerates, the recovery phase sets in with the euthyroid status.

Ogawa et al in his study had reported seven cases since 1969.³ Following this, Engkakul et al² and Bilbao et al⁴ reported SAT in 2010 and 2018, respectively. Few atypical presentations of SAT being unilaterally involved in 20%–33% of cases^{12 13} and being localised to the left lobe of the thyroid gland mimicking AST^{3 14} have been described. Literature search showed very few cases of SAT to be reported in children. Our case also had airway compromise due to compression of trachea by the enlarged thyroid, which is sparsely reported in the literature.

In our case, the child presented with no symptoms suggestive of the hypermetabolic state as well as symptoms of hypothyroidism, although the serum TSH levels were high for age. There was a clear history of prodromal symptoms such as fever, followed by neck swelling associated with dysphagia and tenderness. USG usually includes enlarged thyroid gland with hypoechoic areas in most of the cases.¹⁵ However, in our case, USG showed overlapping features of SAT and AST. FNAC would provide assistance to identify the form of thyroiditis as in our case, but is rarely indicated. Similarly, MRI is not usually indicated in SAT. The unique feature in our case was the tracheal compression caused by the enlarged thyroid gland, causing upper airway compromise and thus warranting an MRI study.

Management of the condition is usually supportive. There are no definitive treatment guidelines set up because of the few numbers of cases in the paediatric age group. Anti-inflammatory agents such as salicylates and non-steroidal anti-inflammatory drugs have been used in mild-to-moderate cases to relieve pain. In severe cases, corticosteroids are used at appropriate dosages.¹⁶ There is no recommendation so far for steroid dosing in children; previous case reports have used 1–2 mg/kg/day of prednisolone.^{2 4} Since our case had hypothyroidism, levothyroxine was supplemented. At follow-up, steroids were gradually tapered and stopped along with levothyroxine. Late-onset permanent hypothyroidism (between 2 and 24 years) and Graves’ disease have been reported to occur after an episode of SAT.¹⁷ Recurrence rates of 1.4%–4% for SAT have been reported, with recurrences usually being milder and occurring 6–23 years after the first episode of SAT.^{8 17 18} Thus, long-term follow-up is essential for SAT with treatment strategies based on the hormone production levels. This boy has been followed up for 24 months and is euthyroid and doing well.

Thus, to conclude, among the paediatric age group, there are limited cases of paediatric SAT presenting with airway compression due to an enlarged thyroid gland. Although the clinical attributes of SAT in children and adults are almost the same, differentiating it from AST may be difficult in paediatrics as the occurrence of SAT is far less. High index of suspicion would aid in the right diagnosis with appropriate management.

Patient’s perspective.

It started as fever, we thought it is like any other common fever. Over the next week, my son had pain in the front part of the neck. We thought it was a sore throat. He also had some change in the voice.

Panic struck us when there was swelling appearing on the front part of the neck. The first thought that comes to the mind of common people usually is the doubt of cancer.

By then, we had met our family paediatrician. Blood tests were conducted. Ultrasound of the neck was done, and we were told there was swelling of his thyroid gland with some fluid collections. As advised by our family doctor, fine-needle aspiration cytology (FNAC) was done. I felt so relieved that it was not cancer and it was thyroiditis confirmed by FNAC. The doctor told us it is a rare condition.

He was given medicines, and we were reassured that things would settle down. For the next 2 weeks, he continued to have on and off fever with thyroid swelling.

At the end of weeks, one day my son told me that he had difficulty breathing. We rushed to our doctor; MRI of the neck was done and it showed some compression of the windpipe, so we were referred to a paediatric surgeon of a tertiary centre in a nearby city. The fear of a possible surgery for my son was lingering in the back of my mind.

At the centre, after a preliminary examination, my son was shifted to the paediatric intensive care unit. The team of doctors after analysing and reviewing the reports reassured me that my child would be fine with steroid injections to relieve the compression on the windpipe. I felt so relieved that my son did not require a surgical procedure. He was looked after well. Within 48 hours, my son had no difficulty in breathing with voice quality normalising. The size of the swelling was decreasing … it was magical … I could see the joy on my son’s face … we were discharged on oral steroids. At our follow-up after 2 weeks, my child was symptom-free and my son could attend school and play like before. His thyroid profiles were monitored serially and hormone supplementation stopped.

We are thankful to the doctors’ team and nurses at the tertiary centre. They were fantastic and awesome.

Looking back, the suffering that my son had gone through in that 1 month is painful at times. But in the end, all is well and back to normal. We at home try to forget it and will be ever grateful to doctors who supported my son and us when he had difficulty in breathing …

Learning points.

• Subacute thyroiditis is rare in children; a high index of clinical suspicion is required.

• Painful thyroid swelling, elevated erythrocyte sedimentation rate, increased thyroglobulin levels, diffuse glandular involvement of thyroid on sonography and decreased radioactive iodine uptake are sufficient for arriving at a diagnosis.

• In its natural course, there is transient elevation of serum T3 and T4 levels during the acute phase of thyroiditis, followed by transient asymptomatic euthyroid levels and later on low levels of thyroid hormones, leading to hypothyroidism requiring hormone replacement therapy

• Fine-needle aspiration cytology and MRI of the neck are not usually indicated; however, in select cases they would help in differentiating the thyroiditis type and whether it is associated with complications (compression of airways).

• It is a self-limiting disease usually, with requirement for supportive treatment. At times of associated complications such as airway compression, steroid therapy is life-saving.