|Ahead of print publication
Primary hypothyroidism on follow-up in a cohort of Indian patients with subacute thyroiditis
Pramila Kalra1, KM Prasanna Kumar2
1 Professor and Consultant, Department of Endocrinology, M S Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
2 Ex HOD and Professor Department of Endocrinology, M S Ramaiah Medical College and CEO CDEC Bengaluru, Karnataka, India
|Date of Submission||06-Dec-2020|
|Date of Acceptance||10-Dec-2020|
|Date of Web Publication||19-Apr-2021|
Ramaiah Medical College, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Objectives: Subacute thyroiditis (SAT) is a temporary dysfunction of the thyroid gland and is commonly due to its viral infection. Permanent hypothyroidism after recovery from SAT has been reported in various studies.
Methodology: This was a prospective study conducted in two tertiary care centers in South India to follow-up these cases for the development of permanent primary hypothyroidism at 1-year follow-up after recovery from SAT.
Results: The total number of cases followed up was 146, including 103 females (70.5%) and 43 males (29.5%). Females' mean age was 33.03 ± 11.7 years, and males' mean age was 40.17 ± 11.84 years. Seven patients reported the second attack of thyroiditis. The mean thyroid-stimulating hormone (TSH) recorded at baseline was 0.042 ± 0.056 µIU/ml. Permanent hypothyroidism was seen in 19.86% of the cases at a 1-year follow-up and was found to be higher in patients with lower TSH at baseline. The females and males were affected at a younger age as compared to other studies. The incidence of permanent hypothyroidism was found to be higher as compared to some but lesser compared to a few others. The iodine supplementation could also be one of the postulates for this higher incidence of hypothyroidism. The severity of thyrotoxicosis was a significant determinant of the future development of hypothyroidism.
Conclusions: The patients with SAT need to be followed up for the development of permanent hypothyroidism. The prevalence of hypothyroidism at 1 year was 19.86% after an attack of thyroiditis.
Keywords: Primary hypothyroidism, subacute thyroiditis, thyrotoxicosis
|How to cite this URL:|
Kalra P, Prasanna Kumar K M. Primary hypothyroidism on follow-up in a cohort of Indian patients with subacute thyroiditis. Thyroid Res Pract [Epub ahead of print] [cited 2021 Jun 22]. Available from: https://www.thetrp.net/preprintarticle.asp?id=314050
Thyroiditis is defined as inflammation of the thyroid gland. The types include acute suppurative thyroiditis, which is due to bacterial infection; subacute thyroiditis (SAT), which results from a viral infection of the gland; and chronic thyroiditis, which is usually autoimmune. Secondary thyroiditis may be due to amiodarone administration to treat cardiac arrhythmias or the administration of interferon-alpha to treat viral diseases. Sometimes, there can be no evident inflammation of the gland when the illness is manifested primarily by thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous [Riedel's] thyroiditis).,,,
| Introduction|| |
SAT is commonly called De Quervain's thyroiditis or nonsuppurative thyroiditis. However, other eponyms include granulomatous, pseudotuberculosis, pseudogiant cell, giant cell thyroiditis, migratory or creeping thyroiditis, or struma granulomatosa. It is also called painful SAT, but sometimes, it may be painless also., Various viruses have been implicated in the etiology, and virus-like particles have been seen in the follicular cells of the thyroid in these patients.
The common etiologies include viruses such as mumps virus, hepatitis B and C viruses, cytomegalovirus, enterovirus, and coxsackie viruses A and B.,,,
The other SAT variety is called painless autoimmune SAT, which occurs spontaneously or following delivery when it is called postpartum thyroiditis. The pathophysiology is similar to Hashimoto's thyroiditis and is seen in 3.9%–10% of pregnancies. The autoimmune origin is confirmed by the fact that these patients are mostly HLA-Bw35 positive, and they also frequently have thyroid peroxidase or thyroglobulin (TG)-antibody positivity. The association of subacute thyroiditis with other alleles like HLA-B*18:01 and DRB1*01 has also been shown apart from HLA-Bw35.
The diagnosis is mostly clinical. The disease mostly has four phases. The destructive inflammation results temporarily in the thyrotoxic phase, followed by euthyroidism. After transient hypothyroidism, the disease becomes inactive, and the thyroid function is normalized, but some patients become permanently hypothyroid on recovery.,
The toxic phase's laboratory evaluation will be normal or high total T4, normal or high total T3, and suppressed thyroid-stimulating hormone (TSH).
The TC99 pertechnetate or iodine scan helps confirm the diagnosis, showing a reduced uptake in the thyroid gland. The scan typically shows a markedly reduced uptake in the gland.
The treatment is mostly symptomatic with anti-inflammatory and beta-blockers, but some patients require steroids if the pain is severe or if the symptoms are not responding to treatment.
Although rarely required, thyroidectomy may be indicated in cases of recurrent thyroiditis or in those cases which are not responding to steroids, and the pain is severe and debilitating.,,,
Permanent hypothyroidism after recovery from SAT has been reported in various studies.,,,,
Aims and objectives
The present study was done to find the incidence of permanent primary hypothyroidism in patients presenting with SAT after 1 year of follow-up.
This prospective study was done in two tertiary care centers in South India to evaluate and follow-up on these cases to develop permanent primary hypothyroidism at 1 year after recovery from SAT. The diagnosis of SAT was confirmed in all cases with a biochemical profile of thyroid function tests TSH, total T4, and total T3 (done by Roche ECLIA) confirming thyrotoxicosis and technetium (Tc) 99 pertechnetate thyroid scan showing a reduced or absent uptake. The demographic data of the patients were also collected. The levels of TSH, T4, and T3 were collected at baseline and 1-year follow-up. At 1 year, the patients who continued to have hypothyroidism were labeled as permanent hypothyroidism, further classified as subclinical or overt as per the ATA guidelines. The patients who were classified as postpartum thyroiditis were excluded from the study.
| Methodology|| |
The study was approved by the institutional ethics review board. Descriptive statistics of of TSH, total T3, total T4 were analyzed and presented in terms of mean and standard deviation and median and interquartile range. Independent t-test was used to compare the mean TSH, T3, T4 and BMI between the two groups. Chi square test was used for categorical variables. All the statistical analyses were performed using Statistical Package for Social Sciences version 18.0 (SPSS, Inc).
The total number of cases was 146, including 103 females (70.5%) and 43 males (29.5%). Females' mean age was 33.03 ± 11.7 years, and males' mean age was 40.17 ± 11.84 years. The total number of cases recruited was 154, but 8 cases were lost to follow-up. The final analysis was done with 146 patients.
| Results|| |
Seven patients reported a second attack of thyroiditis. The maximum number of cases was recorded in February, followed by July, December, January, September, October, April, May, March, August, June, and November (11.7%, 11.0%, 9.7%, 9.7%, 9.1%, 9.1%, 7.8%, 7.8%, 7.1%, 6.5%, 5.8%, and 4.5%, respectively) [Figure 1]. The mean TSH recorded at baseline was 0.042 ± 0.056 µIU/ml, T4 was 169.63 ± 73.75 nmol/L, and T3 was 3.19 ± 2.53 nmol/L. Permanent hypothyroidism was seen in 29 (19.86%) cases at 1-year follow-up and low baseline TSH was the determinant factor for the development of permanent hypothyroidism [Table 1]. The median TSH at follow-up was 2.1 µIU/ml (1.23–3.32) (interquartile range [IQR]) in patients who became euthyroid at the end of the study and 8.2 µIU/ml (6.88–15.02) (IQR) in patients who had permanent hypothyroidism at 1-year follow-up. The steroids were used in 12 patients (8.22%) and were tapered over 4–6 weeks.
|Table 1: Comparison between patients who became euthyroid versus who became hypothyroid|
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This is the first study of it's kind as per our knowledge from India, which followed up patients with SAT for 1 year for the development of hypothyroidism.
| Discussion|| |
As seen in most studies, the peak incidence of thyroiditis has been in the fourth or fifth decade of life for both sexes. This age is again higher than what was seen in our study. Our population got thyroiditis at a much earlier age, i.e., in the third decade for females and the fourth decade for males. The similar findings were seen in our previous study where thyroiditis was seen at a much lower age.
Martino et al. followed eighty consecutive patients with typical SAT. Sex distribution showed a higher incidence in females (3.2/1 for females to males), with a mean age of 44 years. In the majority of patients (66%), the onset of the disease was between June and September (46% in July and August). This is somewhat similar to our study, where we have seen maximum cases in February, followed by July. This could be attributed to the seasonal variation in our city.
In the study published by Alfadda et al. women were more affected than men with similar gender ratios, as reported in the literature. Our study also has reciprocated the same data, and it was even more skewed in our study (2.39:1).
In Olmsted County, Minnesota, USA, over 37 years, SAT recurred in 4% of the patients 6 to 21 years after the initial episode. Permanent hypothyroidism was seen in 15% of the patients at follow-up at 28 years, whereas in our study, it was seen in 19.86% of patients at follow-up until 1 year. We have not collected these patients' data after 1 year to see for recovery from hypothyroidism, if any. Although hypothyroidism, which persists for 1 year after SAT, is mostly permanent, some cases may recover later also. Irregular scarring between islands of residual functioning parenchyma of the thyroid may be seen histopathologically.
In a study done in Saudi Arabia, the follow-up of SAT showed that 14.3% of patients developed permanent hypothyroidism. This is also lower than what we have seen in our study. The reasons for higher rates of hypothyroidism in our study could be a higher prevalence of iodine deficiency in our country previously, and now, more iodine supplementation might have led to aggravation or inducement of autoimmunity.
It has been postulated that excess iodine may lead to apoptosis of thyroid follicular cells and endothelial cells, leading to TG accumulation in connective tissue.,, Iodine supplementation also affects other aspects of thyroid health. In genetically susceptible mice, high iodine uptake has been reported to initiate and exacerbate infiltration of the thyroid by lymphocytes and may worsen the uptake defect of iodine, thus decreasing the thyroid hormone synthesis.
The other causes could be the unregulated use of pesticides and exposure to endocrine disruptors. The use of unclean drinking water and exposure to industrial pollutants like resorcinol and phthalic acid has also been suggested as causes.
In another study where the patients were followed up for 30 years, more than 26.8% of SAT patients developed permanent hypothyroidism within 3 years of treatment. The patient groups developing hypothyroidism did not differ in age, body mass index, pretreatment TSH levels, or initial dosage of prednisolone treatment. However, high cumulative doses of prednisolone were associated with a higher prevalence of hypothyroidism, though in another study, the use of steroids was found to prevent the development of permanent hypothyroidism. Furthermore, women were more likely to develop hypothyroidism. The swift establishment of the diagnosis and rapid tapering of steroids was associated with a higher proportion of euthyroidism in patients., In our study, the factors associated with the development of hypothyroidism were the lower TSH levels at baseline. The people younger in age became hypothyroid numerically more, but it was not significant.
In the study done by Qari and Maimani et al. 23 adult patients with SAT (Fifteen females and eight males with a female to male ratio of 1.9:1) and a mean age of 35.8 ± 9.2 years were studied. This area is located along the Red Sea shore and as such, represents a different environment and lifestyle. They had no case of permanent hypothyroidism in their study at 2-year follow-up. Our study shows a similar mean age compared to their study though they did not have hypothyroidism at follow-up, unlike our study. The number of patients in our study was much higher, though, as compared to their study.
A prospective population-based study done in Denmark focusing on patients with overt hyperthyroidism in two cities with slightly different iodine deficiency status has confirmed the previously reported low incidence of SAT. Permanent hypothyroidism after an attack of SAT has been reported to 15% in different studies.,
In the study published by Zhao et al., 61 patients with SAT were followed up for 2 years. It was seen that the incidence of hypothyroidism was much higher at 1 and 2 years as compared to our study, i.e., 45.8 and 32.8%, respectively.
Permanent hypothyroidism can be sequelae of SAT. In about 85% of patients, there is a recovery of normal thyroid function after recovery from SAT. The thyroid may show scarring postrecovery with islands of healthy functioning thyroid tissue. The rate of permanent hypothyroidism has been reported to range from 5.9% to 15% in some studies,, while others show 26%–45.8% after recovery.
Recurrence of thyroiditis is rare and mostly occurs after 12 months of thyroiditis. The recurrences in up to 2% of cases have been reported after the first episode, and the clinical manifestations are mostly milder in the second episode. In our study, recurrent thyroiditis was seen in about 4.5% of the patients according to the retrospective data analysis, which is slightly higher than the other studies' recurrence. Although on follow-up, none of the patients developed a repeat attack of thyroiditis at 1 year. In previous studies, SAT recurred in 4% of the patients 6–21 years after the initial episode.
Our study's strengths are that the follow-up is for 1 year and a large number of patients. This is the first data from India on the follow-up of a cohort of SAT for 1 year. It adds more knowledge to the follow-up guidelines for these patients. These patients need to be followed up to develop primary hypothyroidism routinely as the incidence of hypothyroidism after recovery is very high in our population. The limitations are that we do not have to follow-up data after 1 year, and thyroid antibody status is not known for many patients.
Permanent hypothyroidism after recovery from SAT was seen in about 19.86% of the patients. Patients with SAT need to be followed up after recovery for the development of permanent hypothyroidism. Transient hypothyroidism is common, but approximately 20% of patients can continue to be permanently hypothyroid, as seen in our study. This is one of the largest cohort studies from Asia of thyroiditis patients who were followed up for 1 year for the development of hypothyroidism.
| Conclusions|| |
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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