Spontaneous Remission of Encephalopathy Associated with Autoimmune Thyroid Disease in a Patient with Graves’ Disease: A Rare Occurrence in a Rare Clinical Picture

Autoimmune thyroid disease (AITD) is the most common organ specific autoimmune disorder usually resulting in dysfunction (hyperfunction, hypofunction or both) of the thyroid gland. The syndromes comprising autoimmune thyroid disease are many intimately related illnesses: Graves? disease with goitre, hyperthyroidism and, in many patients, associated ophthalmopathy, Hashimoto?s thyroiditis with goitre and euthyroidism or hypothyroidism but also thyroid dysfunction occurring independently of pregnancy and in 5-6% of postpartum women and thyroiditides induced by different drugs and other environmental influences. The immunological mechanisms involved in these diseases are closely related, while the phenotypes probably differ because of the specific type of immunological response that occurs. The syndromes are connected together by their similar thyroid pathology, similar immune mechanisms, co-occurrence in family groups, and transition from one clinical picture to another within the same individual over time. In some patients, other organ specific and nonorgan specific autoimmune syndromes are associated with autoimmune thyroid disease, including pernicious anemia, vitiligo, myasthenia gravis, primary adrenal autoimmune disease, celiac disease, rheumatoid arthritis or lupus. Thyroid peroxydase, TPO, the primary enzyme involved in thyroid hormonogenesis, was initially identified in 1959 as the ?thyroid microsomal antigenn. It is uncertain whether TPO autoantibodies or TPO-specific T cells are the primary cause of thyroid inflammation, which can lead, in some individuals, to thyroid failure and hypothyroidism. TPOAbs are the hallmark of AITB and are present in almost all patients with Hashimoto?s thyroiditis, in two-thirds of patients with postpartum thyroiditis and also in 75% of patients with Graves? hyperthyroidism. The antibodies are mainly produced by lymphocytic infiltrate in the thyroid gland and only to a small extent by regional lymph nodes or the bone marrow. Unlike antibodies against thyroglobulin (Tg), TPO antibodies are capable of inducing antibody-dependent cell-mediated cytotoxicity. Antibodies to TSH?R mimic the function of TSH, and cause disease by binding to the TSH?R and stimulating (or inhibiting) thyroid cells. The TSHR, a member of the G protein?coupled receptor family with seven membrane- spanning segments. Patients with autoimmune thyroid disease may have both stimulating and blocking antibodies in their sera, the clinical picture being the result of the relative potency of each species; blocking antibodies seem more common in Graves? patients with ophthalmopathy compared to those without this complication. The major T cell epitopes are heterogeneous and T cell reactivity against certain TSH-R epitopes has been present in high proportion in normal subjects. More diversified response to TSH-R, with heterogeneity of epitope recognition by TSAb, is predictive of likely remission after antithyroid drug treatment for Graves? disease.

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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.

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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.

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Autoimmune Thyroid Disease and Psoriasis Vulgaris after COVID-19 in a Male Teenager

Case Reports in Pediatrics ◽

10.1155/2021/7584729 ◽

2021 ◽

Vol 2021 ◽

pp. 1-3

Author(s):

Nadia K. Qureshi ◽

Sanjay K. Bansal

Keyword(s):

Family History ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Psoriasis Vulgaris ◽

Thyroid Diseases ◽

Graves Disease ◽

Healthy Male ◽

Autoimmune Thyroid

COVID-19 is implicated in triggering autoimmune, dermatologic, and thyroid diseases. We present a first known case of development of Graves’ disease and psoriasis vulgaris in a previously healthy male teenager without any family history, diagnosed after COVID-19 infection. Evaluation of “long COVID syndrome” should include thorough history and thyroid evaluation.

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Co-existent ocular myasthenia gravis and Graves’ disease in a 5 year old

RRNMF Neuromuscular Journal ◽

10.17161/rrnmf.v2i4.15203 ◽

2021 ◽

Vol 2 (4) ◽

Author(s):

Olivia Watson ◽

Michelle Jack ◽

Helen Young

Keyword(s):

Myasthenia Gravis ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Clinical Presentation ◽

Graves Disease ◽

Autoimmune Thyroid ◽

Ocular Myasthenia ◽

Ocular Myasthenia Gravis ◽

The Relationship ◽

Symptom Recurrence

Myasthenia gravis and Graves’ disease are known to co-exist in adults, yet there have only been a small number of paediatric cases reported. We report a 5 year old female who was diagnosed with ocular myasthenia gravis after presenting with unilateral ptosis and subsequently found also to have Graves’ disease. She was treated successfully with pyridostigmine, corticosteroids and carbimazole without symptom recurrence or progression to generalised myasthenia gravis. The aetiology of the coexistence is not fully understood, nor is the relationship between the two disorders’ presentation and treatment. We discuss the variation in clinical presentation of myasthenia gravis between populations and when associated with autoimmune thyroid disease, potential HLA-related genetic susceptibility and the varying approaches to treatment of the co-existent disorders.

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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.

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TSH RECEPTOR ANTIBODIES: RELEVANCE & UTILITY

Endocrine Practice ◽

10.4158/ep-2019-0363 ◽

2020 ◽

Vol 26 (1) ◽

pp. 97-106 ◽

Cited By ~ 7

Author(s):

George J. Kahaly ◽

Tanja Diana ◽

Paul D. Olivo

Keyword(s):

Differential Diagnosis ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Hashimoto Thyroiditis ◽

Rapid Diagnosis ◽

Tsh Receptor ◽

Graves Disease ◽

Thyrotropin Receptor ◽

Blocking Antibody ◽

Autoimmune Thyroid

Objective: Antibodies (Abs) to the thyrotropin (TSH) receptor (TSH-R) play an important role in the pathogenesis of autoimmune thyroid disease (AITD). We define the complex terminology that has arisen to describe TSH-R-Abs, review the mechanisms of action of the various types of TSH-R-Abs, and discuss significant advances that have been made in the development of clinically useful TSH-RAb assays. Methods: Literature review and discussion. Results: TSH-R-Abs may mimic or block the action of TSH or be functionally neutral. Stimulating TSH-R-Abs are specific biomarkers for Graves disease (GD) and responsible for many of its clinical manifestations. TSH-R-Abs may also be found in patients with Hashimoto thyroiditis in whom they may contribute to the hypothyroidism of the disease. Measurement of TSH-R-Abs in general, and functional Abs in particular, is recommended for the rapid diagnosis of GD, differential diagnosis and management of patients with AITD, especially during pregnancy, and in AITD patients with extrathyroidal manifestations such as orbitopathy. Measurement of TSH-R-Abs can be done with either immunoassays that detect specific binding of Abs to the TSH-R or cell-based bioassays that also provide information on their functional activity and potency. Application of molecular cloning techniques has led to significant advances in methodology that have enabled the development of clinically useful bioassays. When ordering TSH-R-Ab, clinicians should be aware of the different tests available and how to interpret results based on which assay is performed. The availability of an international standard and continued improvement in bioassays will help promote their routine performance by clinical laboratories and provide the most clinically useful TSH-R-Ab results. Conclusion: Measurement of TSH-R-Abs in general, and functional (especially stimulating) Abs in particular, is recommended for the rapid diagnosis, differential diagnosis, and management of patients with Graves hyperthyroidism, related thyroid eye disease, during pregnancy, as well as in Hashimoto thyroiditis patients with extra-thyroidal manifestations and/or thyroid-binding inhibiting immunoglobulin positivity. Abbreviations: Ab = antibody; AITD = autoimmune thyroid disease; ATD = antithyroid drug; cAMP = cyclic adenosine 3′,5′-monophosphate; ELISA = enzyme-linked immunosorbent assay; GD = Graves disease; GO = Graves orbitopathy; HT = Hashimoto thyroiditis; MAb = monoclonal antibody; TBAb = thyrotropin receptor blocking antibody; TBII = thyroid-binding inhibiting immunoglobulin; TSAb = thyrotropin receptor–stimulating antibody; TSB-Ab or TRBAb = thyrotropin receptor–stimulating blocking antibody; TSH = thyrotropin; TSH-R = thyrotropin receptor

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Echographic diagnosis of pretibial myxedema in patients with autoimmune thyroid disease

Acta Endocrinologica ◽

10.1530/eje.0.1310113 ◽

1994 ◽

Vol 131 (2) ◽

pp. 113-119 ◽

Cited By ~ 23

Author(s):

Mario Salvi ◽

Flavia De Chiara ◽

Eliana Gardini ◽

Roberta Minelli ◽

Lina Bianconi ◽

...

Keyword(s):

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Subcutaneous Tissue ◽

Normal Subjects ◽

Graves Disease ◽

Skin Thickness ◽

Autoimmune Thyroid ◽

Tissue Sections ◽

Pretibial Myxedema ◽

Ultrasound Scanner

Salvi M, De Chiara F, Gardini E, Minelli R, Bianconi L, Alinovi A, Ricci R, Neri F, Tosi C, Roti E. Echographic diagnosis of pretibial myxedema in patients with autoimmune thyroid disease. Eur J Endocrinol 1994;131:113–19. ISSN 0804–4643 In the present study we have evaluated the use of pretibial ultrasound for the diagnosis of pretibial myxedema (PTM). We studied 76 patients, 58 with Graves' disease, 13 with Hashimoto's thyroiditis and five with idiopathic hypothyroidism. Thirty-two normal subjects were also studied as controls. Sixty-four patients had associated ophthalmopathy. The ultrasound scanner was equipped with 10-and 13-MHz probes. Punch biopsies were carried out in 11 patients and tissue sections examined on a light microscope. On clinical examination 21 patients (28%) had suspected PTM. By ultrasound, we measured the thickness of dermis and subcutaneous tissue (Dl) and that including only deeper dermis (D2) in normal subjects to define the echographic parameters of normal pretibial skin. We then found increased skin thickness in 25 patients (33%), with mean Dl and D2 values significantly higher than those measured in controls (p < 0.00001). The echographic study was positive in 20 patients with ophthalmopathy (31%). Ultrasound showed increased skin thickness in 16 of 21 patients (76%) with clinically suspected PTM. Histopathological findings confirmed the presence of PTM in all the patients who underwent pretibial skin biopsy. We believe that the measurement of pretibial skin thickness by ultrasound may be useful for revealing the presence of PTM. Mario Salvi, Cattedra di Endocrinologia, Università di Parma, Via Gramsci 14-43100 Parma, Italy

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Hashimoto’s Thyroiditis and Graves’ Disease in One Patient: The Extremes of Thyroid Dysfunction Associated with Interferon Treatment

Case Reports in Endocrinology ◽

10.1155/2016/6029415 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

R. H. Bishay ◽

R. C. Y. Chen

Keyword(s):

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Pegylated Interferon ◽

Thyroid Stimulating Hormone ◽

Tracer Uptake ◽

Graves Disease ◽

Interferon Treatment ◽

Autoimmune Thyroid ◽

Technetium Scan ◽

Chronic Hcv

Autoimmune thyroid disease associated with interferon therapy can manifest as destructive thyroiditis, Graves’ Hyperthyroidism, and autoimmune (often subclinical) hypothyroidism, the latter persisting in many patients. There are scare reports of a single patient developing extremes of autoimmune thyroid disease activated by the immunomodulatory effects of interferon. A 60-year-old man received 48 weeks of pegylated interferon and ribavirin therapy for chronic HCV. Six months into treatment, he reported fatigue, weight gain, and slowed cognition. Serum thyroid stimulating hormone (TSH) was 58.8 mIU/L [0.27–4.2], fT4 11.1 pmol/L [12–25], and fT3 4.2 pmol/L [2.5–6.0] with elevated anti-TPO (983 IU/mL [<35]) and anti-TG (733 U/mL [<80]) antibodies. He commenced thyroxine with initial clinical and biochemical resolution but developed symptoms of hyperthyroidism with weight loss and tremor 14 months later. Serum TSH was <0.02 mIU/L, fT4 54.3 pmol/L, and fT3 20.2 pmol/L, with an elevated TSH receptor (TRAb, 4.0 U/L [<1.0]), anti-TPO (1,163 IU/mL) and anti-TG (114 U/mL) antibodies. Technetium scan confirmed Graves’ Disease with bilateral diffuse increased tracer uptake (5.9% [0.5–3.5%]). The patient commenced carbimazole therapy for 6 months. Treatment was ceased following spontaneous clinical and biochemical remission (TSH 3.84 mIU/L, fT4 17pmol/L, fT3 4.5 pmol/L, and TRAb <1 U/L). This raises the need to monitor thyroid function closely in patients both during and following completion of interferon treatment.

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