A 56-year-old man who had been suffering from diarrhea since the age of 50 was diagnosed with Crohn’s disease. He had no previous history of a thyroid disease or the use of other medications known to induce thyroid dysfunction. He had no history of neck pain, irradiation, or recent fever and no family history of thyroid disease. At the age of 56 years, he was treated with the TNF inhibitor infliximab (5 mg/kg) on April 26, 2012, and May 9, 2012, to improve diarrhea. He noticed neck swelling with right neck tenderness and fever 4 days after the second injection of infliximab and thus was referred to our department on May 23, 2012.
Q What is the relation of Infliximab with thyroid dysfunction ?
Infliximab can lead to destructive thyroiditis.
Physical examination revealed that he was undernourished, with a height of 1.67 m and a weight of 52.0 kg. His body temperature was 36.5 °C because had been taking acetaminophen since May 13, 2012. His blood pressure was 154/80 mmHg, and his pulse was 71 bpm. He did not have lid retraction, hyperhidrosis, or tremor of the fingers. An elastic, firm goiter was palpable, primarily in the right lobe of the thyroid, which was tender.
The laboratory data revealed hypochromic anemia, hypoalbuminemia, and hypolipidemia (Table 1).
Q What is your interpretation from the thyroid function test ?
- TSH is low and Free T4 is high. Suggests Thyrotoxicosis
- TSAb is negative and so is anti TPO antibody. Also the patient is a male. Grave’s seems to be less likely.
Q What is the importance of Eosinophils and Monocytes in differentiating Subacute thyroiditis from Grave’s disease ?
- Eosinophils are increases in Grave’s disease and Monocytes are increased in subacute thyroiditis
- Ratio of E/M < 0.2 goes in favour of subacute thyroiditis over Grave’s disease (Ref)
Q What is the importance of Total T3/T4 ratio ?
Total T3/ T4 ratio >20 suggests Grave’s disease and ratio <15 suggests Subacute thyroiditis
Q From this report, what would your next step be ?
I would advise a Tc99 Pertechnatate thyroid Scan.
His renal function was normal, with the exception of a slightly elevated urinary protein level. His serum C-reactive protein (CRP) was elevated, whereas his white blood cell count was within normal range. His serum free triiodothyronine (fT3) and serum free thyroxine (fT4) were both elevated, and his serum thyroid stimulating hormone (TSH) was low. His serum thyroglobulin (Tg) was elevated, and anti-Tg and anti-thyroid peroxidase antibodies were absent.
Thyroid-stimulating antibodies were not elevated. Ultrasonography of his thyroid gland revealed an enlarged goiter (estimated thyroid volume: 46.8 ml), particularly in the right lobe, with irregular hypoechoic region in the right lobe and posterior attenuation of echogenicity (Fig. 1).
Q What is the normal volume of the thyroid gland ?
Q What would you consider doing for the Thyroid nodule detected ?
I would still consider doing a Tc99 thyroid scan and if the nodule is a cold nodule- then consider doing a FNAC of the nodule.
The thyroid uptake value on technetium-99m scintigraphy was near the lower limit of the normal range (Fig. 2).
Q What is the your diagnosis after the thyroid scintigraphy ?
We are probably dealing with Subacute thyroiditis. I would still consider doing a FNAC of the nodule, though we don’t have a cold nodule since the nodule has irregular margins . I would also ask the radiologists considering the vascularity of the lesion.
Thus, his condition at that time was diagnosed as thyrotoxicosis resulting from subacute thyroiditis but not from Graves’ disease.
Q How would you treat this case ?
- I would consider giving NSAIDs for a 2-3 days
- If the symptoms don’t resolve then I would consider giving Prednisolone 40 mg once a day
- If the patient does not improve in 1-2 days after giving glucocorticoids, I would reassess the diagnosis
- If there is relief in pain, I would taper the dose by 5-10 mg every week
- If the pain recurs, I would increase the dose to the last dose and taper more slowly
- Typically steroids would be required for 4-8 weeks
As the administration of acetaminophen for another 2 weeks did not ameliorate his symptoms and thyroid dysfunction, oral prednisolone (20 mg/day) was initiated on June 6, 2012. Instantly, his fever and thyroid pain were improved. Treatment with prednisolone was stopped on November 8, 2012 because his thyroid function had normalized and his symptoms were gone. His goiter was reduced in size after the treatment with prednisolone, but it remained swollen.
He suffered from diarrhea after the withdrawal of prednisolone; therefore, another TNF inhibitor, adalimumab, was administered starting on December 13, 2012. After three injections, his abdominal symptoms were ameliorated, but his thyroid pain and fever returned on January 10, 2013. The laboratory data on January 16 revealed elevated serum CRP (9.88 mg/dl) without thyroid dysfunction.
Q How commonly does the subacute thyroiditis recur ?
Recurrence is not that common. Studies have shown recurrence of 1-4% over a long follow up period.
Serum Tg had increased from 200.7 ng/ml (December 5, 2012) to 753.2 ng/ml (January 16, 2013). Adalimumab was discontinued, and oral prednisolone (10 mg daily) was restarted. His symptoms vanished immediately after retreatment with prednisolone, but the elastic, firm goiter in the right lobe remained. A fine-needle biopsy of the thyroid gland was performed on November 7, 2013, and it revealed amyloid deposition in his thyroid gland. Amyloid deposition was histologically confirmed in biopsied tissues from his stomach and duodenum. As his serum TSH level increased, levothyroxine has been prescribed since July 2013, which has yielded a euthyroid state
Q How common is permanent hypothyroidism after Subacute thyroiditis ?
10% of patients with Subacute thyroiditis develop permanent hypothyroidism. Bilateral hypoechoic areas on ultrasound is an important marker of permanent hypothyroidism.
LEARNING OUTCOMES FROM THIS CASE
- Infliximab can lead to destructive thyroiditis and Subacute thyroiditis like picture
- Recurrence of Subacute thyroiditis is rare, though it can occur.
- Risk of permanent hypothyroidism after subacute thyroditis is around 10%