The Impact of Interferon Beta-1b Therapy on Thyroid Function and Autoimmunity Among COVID-19 Survivors

BackgroundSome studies have indicated that interferon (IFN) may be valuable in COVID-19. We aimed to evaluate the impact of short-term IFN on incident thyroid dysfunction and autoimmunity among COVID-19 survivors.MethodsWe included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured both on admission and at three months.Results226 patients were included (median age 55.0 years; 49.6% men): 135 were IFN-treated. There tended to be more abnormal TFTs upon reassessment in IFN-treated patients (8.1% vs 2.2%, p=0.080). 179 patients (65.4% IFN-treated) had a complete reassessment of anti-thyroid antibodies. There were significant increases in titres of both anti-thyroid peroxidase antibodies (anti-TPO: baseline 29.21 units [IQR: 14.97 – 67.14] vs reassessment 34.30 units [IQR: 18.82 – 94.65], p<0.001) and anti-thyroglobulin antibodies (anti-Tg: baseline 8.23 units [IQR: 5.40 – 18.44] vs reassessment 9.14 units [IQR: 6.83 – 17.17], p=0.001) in the IFN-treated group but not IFN-naïve group. IFN treatment (standardised beta 0.245, p=0.001) was independently associated with changes in anti-TPO titre. Of the 143 patients negative for anti-TPO at baseline, 8 became anti-TPO positive upon reassessment (seven IFN-treated; one IFN-naïve). Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (phi 0.188, p=0.025).ConclusionIFN for COVID-19 was associated with modest increases in anti-thyroid antibody titres, and a trend of more incident anti-TPO positivity and abnormal TFTs during convalescence. Our findings suggest that clinicians monitor the thyroid function and anti-thyroid antibodies among IFN-treated COVID-19 survivors, and call for further follow-up studies regarding the clinical significance of these changes.

Download Full-text

SAT-576 Possible Involvement of Thyroid Function in PCSK9 Inhibitor Therapy

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.477 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Masayasu Iwabuchi

Keyword(s):

Thyroid Function ◽

Ldl Cholesterol ◽

Inhibitor Therapy ◽

Thyroid Peroxidase ◽

Thyroid Function Tests ◽

Pcsk9 Inhibitors ◽

Free T4 ◽

Hyperthyroid Patient ◽

Pcsk9 Inhibitor ◽

The Impact

Abstract INTRODUCTION Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition is an effective strategy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol lowering ability of statins. PCSK9, a serine protease that binds to the LDL receptor promoting its degradation, is an important regulator of LDL metabolism. In addition, LDL-cholesterol is also controlled by TSH and thyroid hormones via PCSK9. TSH has received increasing attention as being closely associated with increased LDL-cholesterol level and higher atherosclerotic risks. In vitro study, the effects of TSH on hepatic PCSK9 expression in HepG2 cells were reported (1). I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. This case highlights the involvement of thyroid function in PCSK9 Inhibitor therapy. CLINICAL CASE A 65-year-old man had a weight loss of 6 kg (13 lbs.) in 4 months, accompanied with fatigue. He had a past history of myocardial infarction and his LDL was 83 mg/dL by 2.5mg of rosuvastatin and heart rate was controlled by 10mg of carvedilol. Six months ago, he started a PCSK9 Inhibitor therapy with 140mg of evolocumab every 2 weeks for 6 weeks. He had no preceding viral illness and denied anterior neck pain or tenderness. His height was 1.53 m, weight 52.6 kg (115 lbs.), and body mass index (BMI) 22.46 kg/m2. His thyroid was not enlarged and non-tender without clear palpable thyroid nodules or neck lymph nodes. Hyperthyroidism was suspected and confirmed by thyroid function tests: TSH was less than 0.0005 μIU/mL (normal 0.35–4.94), and free T4 1.830 ng/dL (0.70–1.48). Graves’ disease was considered, and thyroid antibody tests performed. Thyroid peroxidase (TPO) antibody titer was less than 9 IU/mL (<9), and TSI 141% (<120%). To confirm the diagnosis of this hyperthyroid patient, Technetium-99m uptake and scan was done which showed uptake of 0.8% (0.5–7%). After careful observation for 2 months with 5mg of carvedilol, he turned asymptomatic and free T4 lowered to 1.480 ng/dL and TSH remained less than 0.0005 μIU/mL. CLINICAL LESSONS I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. There has been no report of hyperthyroidism induced by PCSK9 inhibitors. Immunological influence of anti-PCSK9 therapy on thyroid is unknown. In this case, the decrease of TSH due to hyperthyroidism was considered to reduce hepatic PCSK9 expression, leading to additive effect to PCSK9 inhibitor. PCSK9 inhibitors may modify the effects of hyperlipidemia treatment by causing changes in thyroid function. When using PCSK9 inhibitors, follow-up of thyroid function should be considered. This case highlights the involvement of thyroid function in PCSK9 inhibitor therapy. Reference (1) Gong, Y., Ma, Y., et al. Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression. Metabolism. 2017;76;32–41

Download Full-text

An autoimmune cause of confusion in a patient with a background of hypothyroidism

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-19-0014 ◽

2019 ◽

Vol 2019 ◽

Author(s):

Jonathan Brown ◽

Luqman Sardar

Keyword(s):

Thyroid Function ◽

Thyroid Stimulating Hormone ◽

Healthy Population ◽

List Type ◽

Thyroid Function Tests ◽

Thyroid Antibodies ◽

Fluid Analysis ◽

Normal Thyroid Function ◽

Function Tests ◽

Antibody Titres

Summary A 68-year-old previously independent woman presented multiple times to hospital over the course of 3 months with a history of intermittent weakness, vacant episodes, word finding difficulty and reduced cognition. She was initially diagnosed with a TIA, and later with a traumatic subarachnoid haemorrhage following a fall; however, despite resolution of the haemorrhage, symptoms were ongoing and continued to worsen. Confusion screen blood tests showed no cause for the ongoing symptoms. More specialised investigations, such as brain imaging, cerebrospinal fluid analysis, electroencephalogram and serology also gave no clear diagnosis. The patient had a background of hypothyroidism, with plasma thyroid function tests throughout showing normal free thyroxine and a mildly raised thyroid-stimulating hormone (TSH). However plasma anti-thyroid peroxidise (TPO) antibody titres were very high. After discussion with specialists, it was felt she may have a rare and poorly understood condition known as Hashimoto’s encephalopathy (HE). After a trial with steroids, her symptoms dramatically improved and she was able to live independently again, something which would have been impossible at presentation. Learning points: In cases of subacute onset confusion where most other diagnoses have already been excluded, testing for anti-thyroid antibodies can identify patients potentially suffering from HE. In these patients, and under the guidance of specialists, a trial of steroids can dramatically improve patient’s symptoms. The majority of patients are euthyroid at the time of presentation, and so normal thyroid function tests should not prevent anti-thyroid antibodies being tested for. Due to high titres of anti-thyroid antibodies being found in a small percentage of the healthy population, HE should be treated as a diagnosis of exclusion, particularly as treatment with steroids may potentially worsen the outcome in other causes of confusion, such as infection.

Download Full-text

Erratic movement disorders disclosing Graves’ disease and paralleling thyroid function but not autoantibody levels

Journal of International Medical Research ◽

10.1177/0300060518816873 ◽

2019 ◽

Vol 47 (3) ◽

pp. 1378-1386 ◽

Cited By ~ 1

Author(s):

Sébastien Delhasse ◽

Ines Debove ◽

Gabriella Arnold-Kunz ◽

Joseph-André Ghika ◽

Joelle Nsimire Chabwine

Keyword(s):

Thyroid Function ◽

Movement Disorders ◽

Thyroid Dysfunction ◽

Neurological Symptoms ◽

Graves Disease ◽

Thyroid Antibodies ◽

Autoimmune Pathology ◽

The Impact ◽

Complex Movement

Graves’ disease (GD) is an autoimmune pathology characterized by hyperthyroidism and the presence of specific anti-thyroid antibodies. Neurological symptoms such as seizures, cognitive impairment, and tremor can be observed during the course of GD, but more complex movement disorders such as chorea and myoclonus are less frequent. The mechanisms underlying movement disorders in GD are not fully understood. While some authors relate movement disorders to thyroid dysfunction, others claim an autoimmune origin. We herein report a case involving a 60-year-old woman who presented with erratic, intricate movement disorders for which a medical workup revealed GD. During the 2-year follow-up period, her neurological symptoms evolved in parallel with her thyroid function, but not with her autoimmune anti-thyroid antibody level. Her neurological symptoms completely disappeared when she became euthyroid. We herein discuss the complicated clinicobiological relationship between thyroid function and movement disorders. This relationship involves several factors, including the impact of radioactive treatment. The present case emphasizes the importance of including thyroid function screening in the workup of unexplained movement disorders.

Download Full-text

Insights From Prospective Follow-up of Thyroid Function and Autoimmunity Among Covid-19 Survivors

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1715 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A840-A841

Author(s):

David T W Lui ◽

Chi Ho Lee ◽

Wing Sun Chow ◽

Alan C H Lee ◽

Anthony Raymond Tam ◽

...

Keyword(s):

Thyroid Function ◽

Thyroid Dysfunction ◽

Thyroid Autoimmunity ◽

Clinical Severity ◽

Thyroid Peroxidase ◽

Thyroid Function Tests ◽

Free Triiodothyronine ◽

Thyroid Antibody ◽

Antibody Titers

Abstract Objective: Occurrence of Graves’ disease and Hashimoto’s thyroiditis after coronavirus disease 2019 (COVID-19) raised the concern about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggering thyroid autoimmunity. Uncertainties remain regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. We carried out a prospective study to characterize the evolution of thyroid function and autoimmunity among COVID-19 survivors. Method: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for confirmed COVID-19 from 21 July to 21 September 2020 were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and anti-thyroid antibodies were measured on admission and at 3 months. Positive anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) was defined by >100 units. Results: Among 200 COVID-19 survivors, 122 had reassessment thyroid function tests (TFTs) (median age: 57.5 years; 49.2% men). Baseline characteristics of patients who did and did not have reassessment were comparable. Among the 20 patients with baseline abnormal TFTs on admission, mostly low fT3, 15 recovered. Of the 102 patients with normal TFTs on admission, two (2.0%) had new onset abnormal TFTs, which may represent TFTs in different phases of thyroiditis (one had mildly elevated TSH 5.8 mIU/L, with normal fT4 [16 pmol/L] and fT3 [4.3 pmol/L], the other had mildly raised fT4 25 pmol/L with normal TSH [1.1 mIU/L] and fT3 [4.7 pmol/L]). Among 104 patients with anti-thyroid antibody titers reassessed, we observed increases in anti-TPO (baseline: 28.3 units [IQR 14.0-67.4] vs reassessment: 35.0 units [IQR: 18.8-99.0]; p<0.001) and anti-Tg titers (baseline: 6.6 units [IQR 4.9-15.6] vs reassessment: 8.7 units [IQR: 6.6-15.4]; p<0.001), but no change in anti-TSHR titer (baseline: 1.0 IU/L [IQR: 0.8-1.2] vs reassessment: 1.0 IU/L [IQR: 0.8-1.3]; p=0.486). Of the 82 patients with negative anti-TPO at baseline, 16 had significant interval increase in anti-TPO titer by >12 units (2×6 [precision of the anti-TPO assay in normal range being 6 units per SD]), of these, four became anti-TPO positive. Factors associated a significant increase in anti-TPO titer included worse baseline clinical severity (p=0.018), elevated C-reactive protein during hospitalization (p=0.033), and higher baseline anti-TPO titer (p=0.005). Conclusion: Majority of thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis could occur during convalescence, though uncommon. Importantly, we provided the novel observation of an increase in anti-thyroid antibody titers post-COVID-19, suggesting the potential of SARS-CoV-2 in triggering thyroid autoimmunity, which warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Download Full-text

Age and Assay Related Changes of Laboratory Thyroid Function Tests in the Reference Female Population

Journal of Medical Biochemistry ◽

10.2478/jomb-2018-0020 ◽

2019 ◽

Vol 38 (1) ◽

pp. 22-32 ◽

Cited By ~ 2

Author(s):

Najdana Gligorovic Barhanovic ◽

Tanja Antunovic ◽

Sreten Kavaric ◽

Aleksandar Djogo ◽

Vesna Kalimanovska Spasojevic

Keyword(s):

Thyroid Function ◽

Correlation Coefficients ◽

Thyroid Peroxidase ◽

Thyroid Function Tests ◽

Cross Sectional ◽

Female Population ◽

Reference Limit ◽

Function Tests ◽

Age Related ◽

The Impact

Summary Background: Laboratory thyroid function tests play a central role in the diagnosis of thyroid disorders. The aim of our cross-sectional study was to determine reference values for thyroid tests in a rigorously selected group of Montenegrin females, investigate the impact of possible age-related changes and the influence of the interassay bias between three frequently used immunoassays. Methods: Female subjects were randomly selected, aged between 20 and 69 and 946 of them met the selection criteria. TSH, fT3, fT4, thyroid peroxidase and thyroglobulin antibodies were measured. Eighty samples were further analyzed on two other immunochemistry platforms. Results: Median TSH progressively increased with age, there was no difference in fT3, while fT4 was significantly higher in the two oldest groups compared to the others. When using the age-related 97.5 percentile of TSH the percentage of reclassification was highest in the 20–29 years of age group (5.2%, p<0.05). In the oldest band, 7.7% had TSH values above cohort-specific and below the age-related upper reference limit. Bland-Altman bias plots revealed the highest interassay absolute mean difference between compared TSH assays of 24.5% and for fT4 assays of 13.8%. Conclusions: The correlation coefficients between fT3 assays from different manufacturers were low. Serum TSH and fT4 concentrations increased with age and the implementation of age-specific TSH reference intervals would be of interest. The bias between the three commercial immunoassays indicated that the standardization of thyroid function tests is a task of great importance.

Download Full-text

Association between Thyroid Function and Body Mass Index: A 10-Year Follow-Up

Annals of Nutrition and Metabolism ◽

10.1159/000477497 ◽

2017 ◽

Vol 70 (4) ◽

pp. 338-345 ◽

Cited By ~ 12

Author(s):

Hengameh Abdi ◽

Elham Kazemian ◽

Safoora Gharibzadeh ◽

Atieh Amouzegar ◽

Ladan Mehran ◽

...

Keyword(s):

Body Mass Index ◽

Regression Analysis ◽

Body Mass ◽

Thyroid Function ◽

Normal Weight ◽

Thyroid Peroxidase ◽

Thyroid Function Tests ◽

Serum Concentrations ◽

Binary Outcome

Background/Aims: We aimed to evaluate the association between change in thyroid function tests within the euthyroid range and body mass index (BMI) in persons with normal weight at baseline. Methods: This study investigated 1,100 normal-weight euthyroid persons in a population-based cohort study, Tehran Thyroid Study. BMI was calculated and serum concentrations of thyrotropin (TSH) and free T4 (FT4) were assayed at baseline and after 10 years of follow-up. We evaluated the relationship between thyroid and obesity based on 2 definitions for outcome: (1) a binary outcome as BMI <25 or ≥25 kg/m2, and (2) a multinomial outcome as normal BMI, overweight, and obese. Results: A total of 569 women and 531 men, aged 36.3 ± 13.5 years, were included. Modified Poisson regression analysis for binary outcome, after adjustment for age, sex, smoking, and anti-thyroid peroxidase antibody status, revealed a negative association between delta serum FT4 and follow-up BMI (relative risk 0.55 [95% CI 0.37-0.80]) without any significant association between change in serum TSH and follow-up BMI. However, in multinomial logistic regression analysis, we found no relationship between delta serum FT4 or TSH and follow-up BMI categories, for either overweight or obese vs. normal-weight participants. Conclusions: In normal-weight euthyroid individuals, changes in serum concentrations of FT4, but not TSH, may contribute to change in body weight.

Download Full-text

Plasma mineral (selenium, zinc or copper) concentrations in the general pregnant population, adjusted for supplement intake, in relation to thyroid function

British Journal Of Nutrition ◽

10.1017/s000711452000255x ◽

2020 ◽

Vol 125 (1) ◽

pp. 71-78

Author(s):

Victor Pop ◽

Johannes Krabbe ◽

Wolfgang Maret ◽

Margaret Rayman

Keyword(s):

Thyroid Function ◽

Reference Range ◽

First Trimester ◽

Future Research ◽

Thyroid Peroxidase ◽

Reference Ranges ◽

Lower Plasma ◽

The Mean ◽

The Impact ◽

Supplement Intake

AbstractThe present study reports on first-trimester reference ranges of plasma mineral Se/Zn/Cu concentration in relation to free thyroxine (FT4), thyrotropin (TSH) and thyroid peroxidase antibodies (TPO-Ab), assessed at 12 weeks’ gestation in 2041 pregnant women, including 544 women not taking supplements containing Se/Zn/Cu. The reference range (2·5th–97·5th percentiles) in these 544 women was 0·72–1·25 µmol/l for Se, 17·15–35·98 µmol/l for Cu and 9·57–16·41 µmol/l for Zn. These women had significantly lower mean plasma Se concentration (0·94 (sd 0·12) µmol/l) than those (n 1479) taking Se/Zn/Cu supplements (1·03 (sd 0·14) µmol/l; P < 0·001), while the mean Cu (26·25 µmol/l) and Zn (12·55 µmol/l) concentrations were almost identical in these sub-groups. Women with hypothyroxinaemia (FT4 below reference range with normal TSH) had significantly lower plasma Zn concentrations than euthyroid women. After adjusting for covariates including supplement intake, plasma Se (negatively), Zn and Cu (positively) concentrations were significantly related to logFT4; Se and Cu (but not Zn) were positively and significantly related to logTSH. Women taking additional Se/Zn/Cu supplements were 1·46 (95 % CI 1·09, 2·04) times less likely to have elevated titres of TPO-Ab at 12 weeks of gestation. We conclude that first-trimester Se reference ranges are influenced by Se-supplement intake, while Cu and Zn ranges are not. Plasma mineral Se/Zn/Cu concentrations are associated with thyroid FT4 and TSH concentrations. Se/Zn/Cu supplement intake affects TPO-Ab status. Future research should focus on the impact of trace mineral status during gestation on thyroid function.

Download Full-text

Case Report: De Quervain’s Thyroiditis as a Long-Term Sequelae Complication to SARS-CoV-2 Infection

Case Reports in Acute Medicine ◽

10.1159/000517705 ◽

2021 ◽

pp. 64-70

Author(s):

Mark Kong ◽

Sarah La Porte

Keyword(s):

Case Report ◽

Thyroid Function ◽

Elevated Serum ◽

Subacute Thyroiditis ◽

Thyroid Function Tests ◽

Thyroid Function Testing ◽

Neck Lump ◽

Function Testing

A 44-year-old man presented with an enlarged painful lower anterior neck lump with elevated serum concentrations of free thyroxine (T4) and tri-iodothyronine (T3), alongside the presence of antithyroid peroxidase antibodies. Prior to presentation, the patient was demonstrating recovery from a SARS-CoV-2 infection that required sedation, intubation, and invasive ventilation in the intensive care unit (ICU) for 11 days. Ultrasound examination of the thyroid demonstrated features of De Quervain’s (subacute) thyroiditis. This corresponded to the clinical picture, and continuous thyroid function tests were arranged. Emerging evidence throughout the SARS-CoV-2 pandemic describes the long-term sequelae of the infection, including developing atypical effects on the thyroid gland. This case report emphasises the association of painful subacute thyroiditis with post-viral infection and its manifestation during recovery from severe SARS-CoV-2, suggesting that follow-up thyroid function testing should be considered in patients discharged from the ICU who develop neck discomfort.

Download Full-text

THYROID FUNCTION TESTS: A REVIEW

10.36106/ijsr/2502260 ◽

2021 ◽

pp. 73-76

Author(s):

Vasudev Sankhla ◽

Aman Deep

Keyword(s):

Thyroid Function ◽

Thyroid Dysfunction ◽

Radioactive Iodine ◽

Thyroid Stimulating Hormone ◽

Thyroid Function Tests ◽

Function Tests ◽

Tsh Secretion ◽

Line Test ◽

Radioactive Iodine Uptake

Thyroid function tests are one of the most common endocrine panels in general practice because a good understanding of when to order them, indications for treatment are important for the optimal treatment of thyroid dysfunction. Thyroid-stimulating hormone (TSH) should be the rst test to be performed on any patient with suspected thyroid dysfunction and in follow-up of individuals on treatment. It is useful as a rst-line test because even small changes in thyroid function are sufcient to cause a signicant increase in TSH secretion. Thyroxine levels may be assessed in a patient with hyperthyroidism, to determine the severity of hyperthyroxinemia. Antithyroid peroxidase measurements should be considered while evaluating patients with subclinical hypothyroidism and can facilitate the identication of autoimmune thyroiditis during the evaluation of nodular thyroid disease. The measurement of TSH receptor antibody must be considered when conrmation of Graves’ disease is needed and radioactive iodine uptake cannot be done.

Download Full-text

Sea water desalination and removal of iodine: effect on thyroid function

Journal of Water and Health ◽

10.2166/wh.2018.372 ◽

2018 ◽

Vol 16 (3) ◽

pp. 472-475

Author(s):

Gideon Koren ◽

Yona Amitai ◽

Meital Shlezinger ◽

Rachel Katz ◽

Varda Shalev

Keyword(s):

Thyroid Function ◽

Sea Water ◽

Population Based ◽

Thyroid Stimulating Hormone ◽

Water Desalination ◽

Thyroid Function Tests ◽

School Aged Children ◽

Before And After ◽

Using Data ◽

The Impact

Abstract In Israel, about 55% of drinking water is derived from desalination (DSW) which removes all iodine. A recent study from Israel demonstrated high rates of iodine deficiency among school-aged children and pregnant women. There are concerns that low iodine may lead to impaired thyroid function. However, to date, the impact of consuming DSW on body iodine status has not been studied. The objective was to assess whether the increased use of DSW is associated with increased rates of hypothyroidism. Using data from a large health fund in Israel, we compared proportions of patients with higher than normal thyroid stimulating hormone (TSH), and lower than normal T3 and T4 levels before and after a massive desalination project became operational in August 2013 in areas with high vs. low use of DSW. Over 400,000 cases were compared in 2010–2013 vs. 2014–2016. Overall, there was no increase in the proportion of individuals with higher than normal TSH levels, or lower than normal T3 and T4 levels. In conclusion, in this population-based study, following the introduction of DSW, there was no evidence of increased incidence of low thyroid function tests, and the trends were similar in both areas highly consuming, or not consuming, DSW.

Download Full-text