Increased soluble interleukin 2 receptor levels in autoimmune thyroid disease

Abstract. We measured soluble interleukin 2 receptor, a part of the Tac protein (p55), in peripheral blood to study the immunological condition of the T cell in autoimmune thyroid disease. In 26 patients with untreated Graves' disease and 7 hyperthyroid patients with Hashimoto's thyroiditis, the mean levels of soluble IL-2 receptor were both significantly higher than in normal controls (1497±649 (mean ± sd), 641±137 vs 221±63 103 U/l, p<0.001). There was good correlation between soluble IL-2 receptor levels and blood thyroxine levels (r=0.684, p<0.001) in patients with untreated Graves' disease, but no correlation of soluble IL-2 receptor with TSH-inhibitory immunoglobulins, TS-ab, thyroidal autoantibodies to thyroglobulin and thyroidal microsomal antigen was found. We thought that the level of soluble IL-2 receptor is not dependent only on immunological conditions, but also on thyroid hormone status. When T3 was administered to subjects in remission from Graves' disease and in normal controls, the soluble IL-2 receptor levels significantly increased. Moreover, the mean level of soluble IL-2 receptor in patients with toxic multinodular goitre was also significantly higher than in normal controls (411±148 vs 221±63 103U/l, p<0.05). We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone.

Download Full-text

Familial dysalbuminemic hyperthyroxinemia confounding management of coexistent autoimmune thyroid disease

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-19-0161 ◽

2020 ◽

Vol 2020 ◽

Author(s):

Serena Khoo ◽

Greta Lyons ◽

Andrew Solomon ◽

Susan Oddy ◽

David Halsall ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Graves Disease ◽

Thyroid Function Tests ◽

Thyroid Status ◽

Free T4 ◽

Autoimmune Thyroid ◽

Analytical Interference ◽

Tsh Levels

Summary Familial dysalbuminemic hyperthyroxinemia (FDH) is a cause of discordant thyroid function tests (TFTs), due to interference in free T4 assays, caused by the mutant albumin. The coexistence of thyroid disease and FDH can further complicate diagnosis and potentially result in inappropriate management. We describe a case of both Hashimoto’s thyroiditis and Graves’ disease occurring on a background of FDH. A 42-year-old lady with longstanding autoimmune hypothyroidism was treated with thyroxine but in varying dosage, because TFTs, showing high Free T4 (FT4) and normal TSH levels, were discordant. Discontinuation of thyroxine led to marked TSH rise but with normal FT4 levels. She then developed Graves’ disease and thyroid ophthalmopathy, with markedly elevated FT4 (62.7 pmol/L), suppressed TSH (<0.03 mU/L) and positive anti-TSH receptor antibody levels. However, propylthiouracil treatment even in low dosage (100 mg daily) resulted in profound hypothyroidism (TSH: 138 mU/L; FT4: 4.8 pmol/L), prompting its discontinuation and recommencement of thyroxine. The presence of discordant thyroid hormone measurements from two different methods suggested analytical interference. Elevated circulating total T4 (TT4), (227 nmol/L; NR: 69–141) but normal thyroxine binding globulin (TBG) (19.2 µg/mL; NR: 14.0–31.0) levels, together with increased binding of patient’s serum to radiolabelled T4, suggested FDH, and ALB sequencing confirmed a causal albumin variant (R218H). This case highlights difficulty ascertaining true thyroid status in patients with autoimmune thyroid disease and coexisting FDH. Early recognition of FDH as a cause for discordant TFTs may improve patient management. Learning points: The typical biochemical features of familial dysalbuminemic hyperthyroxinemia (FDH) are (genuinely) raised total and (spuriously) raised free T4 concentrations due to enhanced binding of the mutant albumin to thyroid hormones, with normal TBG and TSH concentrations. Given the high prevalence of autoimmune thyroid disease, it is not surprising that assay interference from coexisting FDH may lead to discordant thyroid function tests confounding diagnosis and resulting in inappropriate therapy. Discrepant thyroid hormone measurements using two different immunoassay methods should alert to the possibility of laboratory analytical interference. The diagnosis of FDH is suspected if there is a similar abnormal familial pattern of TFTs and increased binding of radiolabelled 125I-T4 to the patient’s serum, and can be confirmed by ALB gene sequencing. When autoimmune thyroid disease coexists with FDH, TSH levels are the most reliable biochemical marker of thyroid status. Measurement of FT4 using equilibrium dialysis or ultrafiltration are more reliable but less readily available.

Download Full-text

Cold reactive lymphocytotoxic activity in autoimmune thyroid disease

Acta Endocrinologica ◽

10.1530/acta.0.1090492 ◽

1985 ◽

Vol 109 (4) ◽

pp. 492-498 ◽

Cited By ~ 1

Author(s):

Marilyn Ryan ◽

Vitaya Sridama ◽

Leslie J. DeGroot

Keyword(s):

Monoclonal Antibodies ◽

T Cell ◽

B Cells ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

T Cell Subsets ◽

Graves Disease ◽

Positive Correlation ◽

Autoimmune Thyroid ◽

Normal Controls

Abstract. An increased incidence of cold-reactive lymphocytotoxic activity (LCTA) has been demonstrated in the sera of patients with autoimmune thyroid disease. Twenty-six of 79 (33%) patients with Graves' disease and 9 of 21(43%) patients with Hashimoto's thyroiditis had cold-reactive LCTA detected by microcytotoxicity assay compared to 6 of 42 (14%) normal controls. There was no correlation between LCTA and age, sex, MCHA titre or TGHA titre. A positive correlation with FTI and LCTA in Hashimoto's patients was demonstrated, but no such correlation was demonstrable in Graves' patients. The lymphocytotoxic activity was directed preferentially against B cells. There was no preferential lysis of T-cell subsets as defined by monoclonal antibodies, and the lymphocytotoxins were equally reactive with normal lymphocytes and toxic Graves' lymphocytes. The significance of cold-reactive lymphocytotoxic activity in the pathogenesis of autoimmune thyroid disease remains to be determined.

Download Full-text

Autoimmune thyroid disease in the presence of resistance to thyroid hormone or TSH-secreting pituitary tumour: a diagnostic challenge

Endocrine Abstracts ◽

10.1530/endoabs.34.p423 ◽

2014 ◽

Author(s):

Carla Moran ◽

Olympia Koulouri ◽

Fleur Talbot ◽

Catherine Mitchell ◽

Nadia Schoenmakers ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Pituitary Tumour ◽

Diagnostic Challenge ◽

Resistance To Thyroid Hormone ◽

Autoimmune Thyroid

Download Full-text

Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa453 ◽

2020 ◽

Vol 105 (9) ◽

pp. e3392-e3399 ◽

Cited By ~ 1

Author(s):

Alina Sovetkina ◽

Rans Nadir ◽

Antonio Scalfari ◽

Francesca Tona ◽

Kevin Murphy ◽

...

Keyword(s):

Multiple Sclerosis ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Graves Disease ◽

Autoimmune Thyroid ◽

Tertiary Referral Center ◽

T2 Lesions ◽

Relapsing Remitting ◽

Edss Score ◽

Multiple Sclerosis Patients

Abstract Context Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. Objective The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. Design, Setting, and Patients A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. Main Outcome Measures Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. Results Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: –0.25 [–1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. Conclusion Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

Download Full-text

A Case of Thyrotoxicosis due to Simultaneous Occurrence of Subacute Thyroiditis and Graves’ Disease

Case Reports in Endocrinology ◽

10.1155/2018/3210317 ◽

2018 ◽

Vol 2018 ◽

pp. 1-3

Author(s):

Kazunori Kageyama ◽

Noriko Kinoshita ◽

Makoto Daimon

Keyword(s):

Thyroid Hormones ◽

Thyroid Disease ◽

Rare Case ◽

Autoimmune Thyroid Disease ◽

Subacute Thyroiditis ◽

Simultaneous Occurrence ◽

Graves Disease ◽

Inflammatory Disorder ◽

Autoimmune Thyroid ◽

Prompt Diagnosis

Subacute thyroiditis is an inflammatory disorder of the thyroid. Graves’ disease is an autoimmune thyroid disease in which thyroid hormones are overproduced. Here we present a rare case of thyrotoxicosis due to the simultaneous occurrence of both diseases. Prompt diagnosis and therapy are required to prevent complications in patients with thyrotoxicosis.

Download Full-text