Rheumatic Disorders and Autoimmune Thyroid Disease. A Common Co-occurrence With an Unusual Presentation- A Case Report

Rheumatic Disorders and Autoimmune Thyroid Disease. 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A Common Co-occurrence With an Unusual Presentation- A Case Report Tehreem Manzoor, Aiman Ali, Rida Masood, Syed Muhammad Kashif, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5183368/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Oct, 2025 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Introduction Graves’ disease (GD) and systemic lupus erythematosus (SLE) are two autoimmune disorders well known for their co-existence. Shared genetic susceptibility loci are being increasingly identified, confirming the causal bidirectional association between the two. Case Presentation Our case involves a young woman who presented with chronic symptoms of hyperthyroidism along with anemia, goitre, respiratory distress, and a recent onset of rheumatism. Diagnostic investigations fulfilled the criteria of GD along with SLE and Sjogren’s overlap. Pulmonary arterial hypertension (PAH) was detected via echocardiography, likely indicating the complex interplay between SLE and GD. Significant fetal and embryonic mortality raised the suspicion of anti-phospholipid syndrome, leading to the detection of anti-phospholipid antibodies. The likelihood of adrenal insufficiency and Autoimmune Polyglandular syndrome type 2 was also addressed. The patient was managed with anti-thyroid medications, steroids, and PAH-specific therapy. Our case is unique, as it involves multiple autoimmune disorders of rheumatic and endocrine origin in the same patient. The uniqueness also lies in the temporal sequence of the disorders, with GD being antecedent to SLE, contrary to what the literature suggests. Conclusion Although the patient tragically died, the goal here was to reinforce the idea that autoimmune disorders are complex, revealing themselves in various forms. Scouting for comorbidities and adapting a holistic treatment approach is prudent when dealing with these ailments. The social and financial dilemmas leading to noncompliance with treatment and its detrimental effects are also highlighted. case report goitre Graves’ disease sle Addison’s disease antiphospholipid antibody syndrome (aps) pulmonary hypertension INTRODUCTION Autoimmune thyroid disease (AITD) is a spectrum of disorders ranging from the most common form of Hashimoto’s thyroiditis (HT) to the less common Graves’ disease. Of interest, GD and SLE are two different entities; the former is organ-specific, whereas the latter is a multisystem inflammatory disorder. GD is characterized by agonistic antibodies against the Thyroid stimulating hormone (TSH) receptor on the thyroid gland, causing thyrotoxicosis. SLE involves autoantibody formation against various nuclear antigens and subsequent immune complex deposition, causing organ dysfunction and failure [ 1 ]. The coexistence of AITD and SLE is a well-known phenomenon. A meta-analysis from 1946–2018 revealed an increased prevalence of primary hypothyroidism in SLE patients (15–19% vs. 4.6% in the general population). Although less prevalent, the same study reported that hyperthyroidism was also more common in the lupus group (3–9% vs. 1.5%) [ 2 ]. Researchers are now inclined toward identifying single nuclear polymorphisms (SNPs) in various HLA and non-HLA genes, which serve as common genetic susceptibility loci for both SLE and GD [ 1 ][ 3 ][ 4 ]. This novel discovery can potentially revolutionize our approach toward such complex autoimmune entities. Anti-phospholipid syndrome (APS) is an acquired disorder causing recurrent venous and, notably, arterial thrombosis in young individuals and/or obstetric adversities, with persistent anti-phospholipid antibodies (APLs) [ 5 ]. Secondary APS is its co-existence with other disorders, mostly SLE. Although less acclaim, the association between AITD and APS and/or their antibodies is important, particularly in young women, since both are notoriously known for poor fetal outcomes and recurrent miscarriages (RMs) [ 5 ][ 6 ]. This case report confirms the association between GD and SLE as parent diseases in our patient, along with an interesting linkage with APS and Addison’s disease as probable co-occurrences, which, to our knowledge, is the first reported case involving multiple intricate autoimmune entities in the same patient. CASE PRESENTATION A 35-year-old female, with no comorbidities or family history, presented at our clinic with a one-year history of generalized weakness, postural dizziness, dyspnea (mMRC grade two) and dry cough, which had worsened for the past week. Another chief complaint was the gradual increase in neck swelling for approximately three years, which caused pressure and discomfort. She had experienced palpitations, heat intolerance, diaphoresis, polyphagia, subfertility and proximal muscle weakness, along with substantial weight loss of approximately 10 kg. She also agreed to have polyarthralgia and myalgia with brief morning stiffness, oral ulcers, hair loss, dry mouth and gritty eyes for six months. Menses were heavy since menarche, but she had amenorrhea for three months. The obstetric history was complicated by three miscarriages and five still births, with only one surviving child. She had received several red blood cell transfusions and iron prescriptions in the past, but no formal diagnosis was given. At first glance, our patient was an anxious and fidgety young woman with a staring gaze and a BP of 100/60 with no orthostasis. Vital examination revealed tachycardia at 128 bpm (regular), tachypnea, oxygenation of 94% on room air, and normothermia. The most striking finding was a large, warm and non-tender goiter with a uniform texture and audible bruit. Lymphadenopathy, the Pamberton sign, and increased JVP were absent, as was Thyroid Ophthalmopathy. Physical examination revealed cachexia, clubbing grade two, pallor, dehydration, fine tremors, palmar sweating, receding hairlines, blepharitis, a butterfly rash sparing the nasolabial folds, a fissured beefy tongue, and dental caries. Hyperpigmentation was observed around the palmar creases, knuckles, and oral cavity. She had a hyperdynamic precordium with a loud P2 sound on auscultation. She was admitted for severe systemic illness, and serial investigations were carried out. She had severe anemia and thrombocytopenia and a microcytic peripheral film. The corrected retic count was 0.6%. The serum thyroid profile was dramatic, with a very low TSH, high T3 and T4. Other abnormalities included hyponatremia, hypoalbuminemia, and a high ESR. The serum Iron profile suggested iron deficiency. Pregnancy was ruled out by serum β-HCG and sonography. Urinalysis revealed only trace proteinuria ( Table 1 ). Chest imaging was normal, but an echocardiogram revealed an isolated high mean pulmonary artery pressure of 55 mmHg. Thyroid sonography confirmed a uniformly enlarged and hypervascular gland. Immunological testing demonstrated convincing results, including strongly positive antinuclear antibodies along with, positive anti-DsDNA, anti-SS-A/Ro and anti-cardiolipin IgM. Other antibodies, including Smith, Scl-70, U1-RNP, CCP, RA factor, β2GPI and LA, were negative. Serum complement levels were very low. Thyroid receptor antibodies (TRAbs) were also positive. Morning cortisol was substantially low, and anti-TTG (tissue transglutaminase) IgA was negative ( Table 2 ) . Upon constellating the above description with the ACR/EULAR criteria, SLE and Sjogren’s (SS) overlap were diagnosed along with Graves’ disease. APS and Addison’s Disease were among the likely possibilities. Table 1 Baseline laboratory investigations over the course of hospital stay 1 Laboratory Investigations Normal Values Day 1 Day 5 Day 7 Hb 11.9–15.0 (g/dL) 5.5 8.3 9.1 TLC 4–11 (103/uL) 5.6 7.5 8.9 PLT 150–400 (109/L) 74 89 90 PT 10–12 (seconds) 20.4 19.4 APTT 22–41 (seconds) 25.2 30.9 INR < 1.1 1.9 1.8 CRP < 5 (mg/dL) 1.1 5 ESR < 20 (mm/hr) 75 50 BUN 7–20 (mg/dL) 4 12 10 Cr < 1.0 0.3 0.3 0.4 Na 135–146 (mEq/L) 130 135 132 K 3.5-5.0 (mEq/L) 3.4 3.0 3.9 Cl 95–106 (mEq/L) 103 104 97 Ca 8.8–10.6 (mg/dL) 7.9 7.8 Mg 1.4–1.7 (mg/dL) 1.5 1.7 Po4 3.2–6.3 (mg/dL) 3.2 3.1 T Bili 0.2–1.3 (mg/dL) 1.6 1.4 1.2 SGPT 7–55 (U/L) 36 32 31 SGOT 8–45 (U/L) 39 39 40 ALP 44–147 (IU/L) 171 120 T pro 6-8.3 (g/dL) 7.3 7.1 Alb 3.5–5.5 (g/dL) 2.3 2.2 Spot urine PCR < 0.2 0.4 1. Hb, hemoglobin; Hct, hematocrit; TLC, total leukocyte count; PLT, platelets; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; PT, prothrombin time; APTT, activated partial thromboplastin time; INR, international normalized ratio BUN, blood urea nitrogen; Cr, creatinine; Na, sodium; K, potassium; Cl, chloride; Ca, calcium; Mg, magnesium; PO4, phosphorus; T Bili, total bilirubin; SGPT, serum glutamic pyruvic transaminase; SGOT, serum glutamic oxaloacetic transaminase ;ALP, alkaline phosphatase; T pro, total protein; Alb, albumin Table 2 Diagnostic Investigations 2 Laboratory Investigations Normal Range Patient Results TSH 0.5–4.5 (mIU/L) 0.005 T3 1.08–3.14 (nmol/L) 4.65 T4 5.5–11 (5.5–11 mcg/dL) 14 TRAb 0-0.9 (IU/L) 3.9 ANA < 1:80 1:2560 (homogenous pattern) Anti Ds DNA 0–25 (IU/L) 34.9 Anti SSA Ab < 3.2 (IU/mL) 30.8 Anti SSB Ab 0.8 (g/dL) 0.43 C4 levels > 0.129 (g/dL) 0.072 ACLA (IgM) < 20 (U/mL) 57.4 Anti-β2GPI (IgM) < 20 (U/mL) 12 LAA 20–40 (g/L) 35 8am serum cortisol 5.0–23 (mcg/dl) 0.3 2. TSH, thyroid stimulating hormone; T3, total triiodothyronine; T4, total thyroxine; ANA, anti-nuclear antigen; Anti Ds DNA, anti-double stranded deoxyribonucleic acid; Anti SSA Ab, anti–Sjogren's-syndrome-related antigen A autoantibodies; Anti SSB Ab, anti–Sjogren's-syndrome-related antigen B autoantibodies; C3, compliment component 3; C4, compliment component 4; ACLA, Anti cardiolipin autoantibodies; Anti-β2GPI, Anti beta 2 glycoprotein 1 autoantibodies; LAA, lupus anticoagulant antibodies Initial management included blood transfusions, propranolol, omeprazole, and nutritional support. Upon confirmation of the diagnosis, 30 mg of oral Carbimazole and 400 mg of Hydroxychloroquine were started in divided doses. Dyspnea and PAH were curbed with Furosemide and the Endothelin receptor antagonist Bosentan. Given the high inflammatory activity of SLE, intravenous Dexamethasone was started at a dosage of 4 mg eight hourly to supplement hypoadrenalism. Mineralocorticoids were not used. In the absence of pregnancy and thrombosis, anticoagulation was not given. The patient and her family were counseled in detail about the importance of the frequency and timing of the medications to be taken, explaining the severity of her disease(s). With the given treatment, the patient experienced remarkable improvement within one week and was discharged on oral medications, including equivalent doses of Prednisolone. Our further plan included testing for APL after 12 weeks, serum Adrenocorticotropic hormone (ACTH) levels along with adrenal imaging and a CT pulmonary angiogram, which were delayed due to financial limitations. Unfortunately, owing to noncompliance, she returned after two weeks with altered sensorium. Examination revealed hypotension, cold peripheries, tachycardia, and clear chest with respiratory distress. Blood gases revealed metabolic acidosis and hypoxemia. Her blood glucose level was 80 mg/dL. Admission to ICU was made. A whole panel of laboratories, including electrolytes, CBC, D-dimers and cortisol, was sent. The initial CT brain was unremarkable. Oxygen, vasopressors, antibiotics and IV hydrocortisone were initiated. While being prepared for intubation, she experienced intractable seizures and died shortly afterwards. DISCUSSION The coexistence of GD and SLE has been widely reported for more than a decade [ 1 – 4 ][ 7 – 8 ]. Anti-thyroid drugs have also been implicated as an independent cause of lupus [ 1 ]. Various East Asian studies have emerged recently, establishing a bidirectional causal association between the two, concluding that having one disease increases the risk of the other [ 1 ][ 3 ][ 4 ][ 9 ]. This is important, as it eliminates confounding bias, since both SLE and GD predominantly victimize young women. One retrospective cohort of 2796 new SLE patients concluded that patients with lupus with overlap had a greater relative risk of thyreopathy than did those with lupus alone. Additionally, it concluded that SLE patients with thyroid diseases more frequently have renal and CNS involvement [ 7 ]. This is reflected in our patient who had SLE overlapping with severe GD and later presented with intractable seizures. With respect to temporal associations, the majority of studies report that thyroid disorders are diagnosed months to years later in known SLE patients, mainly because of persistent nonspecific symptoms despite immunosuppression and low disease activity [ 2 ][ 7 ][ 8 ]. In contrast, our patient presented with chronic hyperthyroidism and goiter with acute decompensated thyrotoxicosis. The onset of rheumatism was recent and subtle, submerged in the chronicity and non-specificity of hyperthyroidism. Recurrent miscarriage (RM) and pregnancy loss are some of the highlights of our case. Although a diseased thyroid status and SLE itself are well-known causes of subfertility and recurrent pregnancy loss, the high likelihood of Anti-Phospholipid syndrome (APS) in our patient is worth mentioning. Interestingly, the presence of isolated anti-thyroid antibodies and anti-phospholipid antibodies has been linked to an increased risk of RM and worse pregnancy outcomes, even in the absence of proven disease [ 5 ][ 6 ]. This is of paramount importance, as this association signifies the need for screening women with unexplained RM and poor fetal well-being for the presence of both anti-thyroid antibodies and anti-phospholipid antibodies. On careful analysis, the compelling cause of this patient’s visit alongside thyrotoxicosis was respiratory limitation. The likely cause of this was found to be pulmonary arterial hypertension (PAH), in addition to anemia. The probable confounders of this were SLE and GD since both are recognized causes of pulmonary hypertension (PH) and/or PAH according to the WHO [ 10 ][ 11 ]. APS is also a notable culprit of thromboembolic (CTEPH)[ 12 ] and non-thromboembolic PH [ 13 ][ 14 ]. Recently, a study proposed that the prevalence of PH in GD patients did not differ significantly between the hyperthyroid and euthyroid groups,while 30% of patients sustained PH despite long-term thyrotoxic control, necessitating PAH-specific therapy [ 15 ]. This serves as a potential area of research to establish whether employing cardiorespiratory assessment routinely in evaluating patients with thyrotoxicosis and connective tissue disorder provides any long-term benefit. Finally, shedding light on the gray area, underlying Addison’s disease (AD) in our patient was suggested by a low normal BP despite thyrotoxicosis, hyponatremia, and hyperpigmentation alongside postural dizziness [ 16 ][ 17 ]. Constellation of AITD and AD constitutes a polygenic disorder termed AUTOIMMUNE POLYGLANDULAR SYNDROME TYPE 2 [ 18 ]. Autoimmune polyendocrine syndromes have been reported to accompany rheumatic diseases, altering their natural history and rendering them resistant to rheumatological treatment. Moreover, overlooked endocrinopathies may accentuate the metabolic, musculoskeletal, and cardiovascular disorders encountered in the course of rheumatic disorders [ 19 ]. Although not conclusively diagnosed, identifying the adrenal status of our patient was crucial because the coexistence of AD necessitated the use of steroids, which are not otherwise used in the management of GD. Although highly active SLE also prompted their use in our patient, the indication was momentary. Our report also highlights the dilemma of nonadherence of our community to the treatment advised, stemming from various reasons, notably poverty, illiteracy, relying solely on spiritual treatment and embarrassment. The burden imposed on healthcare in underdeveloped countries such as Pakistan involves not only the disease itself but also the reasons stated above. CONCLUSION We present an interesting and unusual case of Graves’ disease and SLE alongside Sjogren’s syndrome. The simultaneous existence of APS and AD was also highlighted. The clinical domains here, including chronic fatigue, anemia, PH, hypoadrenalism, and obstetric morbidity, can be partly explained by each of these diseases alone. However, it is prudent to realize that the overlap among these disorders is real and challenging, while focusing solely on a single diagnosis is detrimental, leading to treatment failure.Our aim is to therefore remind clinicians of the necessity of vigilant consideration and regular screening of concurrent autoimmune diseases and/or endocrinopathies while treating patients with these diseases. This ensures timely diagnosis and a holistic management approach, thereby reducing all-cause morbidity and mortality and improving the quality of life of patients. Declarations All the abbreviations used in this manuscript are appropriately explained where necessary. Funding Statement: Not Applicable Conflict Of Interest: The author(s) of this work have nothing to disclose. Ethics Approval : Not applicable as no human or animal objects were used, patients’ identity anonymized. Consent to participate : Not Applicable Consent for publication : Given that the patient died before the initiation of report writing, written consent was signed by the patients’ mothers. The translated details were explained in the native language because English was not understood. Patients’ images were not included for social and religious reasons. Availability of data : Not Applicable Code Availability : Not Applicable Authors’ Contribution: Tehreem Manzoor : Concept and design, Acquisition, analysis and interpretation of data, Drafting of the manuscript, Critical review of the manuscript, approved final version Aiman Ali : Concept and design, Drafting of the manuscript, Critical review of the manuscript ,approved final version Rida Masood : Concept and design, Acquisition, analysis and interpretation of data, Critical review of the manuscript ,approved final version Syed Muhammad Kashif : Acquisition, analysis and interpretation of data, Critical review of the manuscript , approved final version Muhammad Tanveer Alam : Acquisition, analysis and interpretation of data, Critical review of the manuscript , approved final version References Lee C, Chen SF, Yang YC, Hsu CY, Shen YC. Association between Graves' disease and risk of incident systemic lupus erythematosus: A nationwide population-based cohort study. 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Int J Endocrinol. 2022;2022(1):8271951. doi: 10.1155/2022/8271951 Liu Y-c, Lin W-y, Tsai M-c, Fu L-s. Systemic lupus erythematosus and thyroid disease– Experience in a single medical center in Taiwan. J Microbiol Immunol Infect. 2019;52(3):480–6. doi: 10.1016/j.jmii.2016.11.008 Muñoz C, Isenberg DA. Review of major endocrine abnormalities in patients with systemic lupus erythematosus. Clin Exp Rheumatol. 2019;37(5):791–6. Wang T, Zhang Y, Chen X, et al. The potential causal association between systemic lupus erythematosus and endocrine and metabolic disorders in the East Asian population: A bidirectional two-sample Mendelian randomization study. Lupus. 2024;33(3):223–31. doi: 10.1177/09612033241227276 Cansu DÜ, Korkmaz C. Pulmonary hypertension in connective tissue diseases: epidemiology, pathogenesis, and treatment. J Clin Rheumatol. 2023;42(10):2601–10. doi: 10.1007/s10067-022-06446-y Song X, Yang K, Chen G, et al. Characteristics and risk factors for pulmonary hypertension in patients with hyperthyroidism. Endocr Pract. 2021;27(9):918–24. doi: 10.1016/j.eprac.2021.02.011 Rosen K, Raanani E, Kogan A, et al. Chronic thromboembolic pulmonary hypertension in patients with antiphospholipid syndrome: Risk factors and management. J Heart Lung Transplant. 2022;41(2):208–16. doi: 10.1016/j.healun.2021.10.016 Puebla-Aldama D, Cueto-Robledo G, Roldan-Valadez E, et al. Review of functional status and hemodynamic parameters in patients diagnosed with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) with and without Antiphospholipid Syndrome (APLS). Curr Probl Cardiol. 2023;48(7):101154. doi: 10.1016/j.cpcardiol.2022.101154 Sarinc Ulasli S, Koksal D, Karcioglu O, et al. Pulmonary manifestations of antiphospholipid syndrome: a retrospective analysis of 67 patients. J Thromb Thrombolysis. 2021;52:640–5. doi: 10.1007/s11239-020-02351-w Araruna LVM, Oliveira DCd, Pereira MC, Moura Neto A, Tambascia MA, Zantut-Wittmann DE. Interplay between thyroid hormone status and pulmonary hypertension in Graves’ disease: relevance of the assessment in thyrotoxic and euthyroid patients Front Endocrinol (Lausanne). 2022;12:780397. doi: 10.3389/fendo.2021.780397 El Hasbani G, Uthman I. An update on the endocrine manifestations of antiphospholipid syndrome. Int J Rheum Dis. 2024;27(7):e15253. doi: 10.1111/1756-185X.15253 Schulz L, Hammer E. Autoimmune polyglandular syndrome type II with comanifestation of Addison’s and Graves’ disease in a 15-year-old boy: case report and literature review. J Pediatr Endocrinol Metab. 2020;33(4):575–8. doi: 10.1515/jpem-2019-0506 Martins SC, Venade G, Teixeira M, et al. Autoimmune polyglandular syndrome type 2. Rev Assoc Med Bras (1992). 2019;65(12):1434-7. doi: 10.1590/1806-9282.65.12.1434 Jankowska K, Dudek P, Stasiek M, Suchta K. Autoimmune polyendocrine syndromes associated with autoimmune rheumatic diseases. Reumatologia. 2023;61(4):225. doi: 10.5114/reum/170266 Additional Declarations No competing interests reported. Supplementary Files CAREchecklistEnglish201311.pdf Cite Share Download PDF Status: Published Journal Publication published 16 Oct, 2025 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted Editorial decision: Revision requested 22 Oct, 2024 Editor assigned by journal 22 Oct, 2024 Submission checks completed at journal 22 Oct, 2024 First submitted to journal 30 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5183368","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":369173875,"identity":"f863828d-ce56-4aad-8b1a-e09f86dacad8","order_by":0,"name":"Tehreem Manzoor","email":"data:image/png;base64,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","orcid":"","institution":"Civil Hospital Karachi","correspondingAuthor":true,"prefix":"","firstName":"Tehreem","middleName":"","lastName":"Manzoor","suffix":""},{"id":369173876,"identity":"f8b696b1-fd1d-49f4-acaa-a8c9d0003457","order_by":1,"name":"Aiman Ali","email":"","orcid":"","institution":"Civil Hospital Karachi","correspondingAuthor":false,"prefix":"","firstName":"Aiman","middleName":"","lastName":"Ali","suffix":""},{"id":369173877,"identity":"bc5ce19e-9257-410b-9307-12e6a859a5dc","order_by":2,"name":"Rida Masood","email":"","orcid":"","institution":"Civil Hospital Karachi","correspondingAuthor":false,"prefix":"","firstName":"Rida","middleName":"","lastName":"Masood","suffix":""},{"id":369173878,"identity":"dd81c396-498e-497c-906e-27ddb2c28b2c","order_by":3,"name":"Syed Muhammad Kashif","email":"","orcid":"","institution":"Civil Hospital Karachi","correspondingAuthor":false,"prefix":"","firstName":"Syed","middleName":"Muhammad","lastName":"Kashif","suffix":""},{"id":369173879,"identity":"1fe504d0-032c-46a1-9669-8acc730974ec","order_by":4,"name":"Muhammad Tanveer Alam","email":"","orcid":"","institution":"Civil Hospital Karachi","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Tanveer","lastName":"Alam","suffix":""}],"badges":[],"createdAt":"2024-09-30 20:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5183368/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5183368/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s42399-025-02112-x","type":"published","date":"2025-10-16T15:57:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":93956724,"identity":"9a08cd23-b0ec-427d-b9e4-d901077f1697","added_by":"auto","created_at":"2025-10-20 16:11:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":569872,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5183368/v1/4c6d0b56-b2f7-40b1-a568-ca6ab40ec533.pdf"},{"id":68177427,"identity":"ad5674d9-464b-48f1-9895-d0fd9fd4eedd","added_by":"auto","created_at":"2024-11-04 11:35:29","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":725596,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish201311.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5183368/v1/daaf562b324347205e2a0cb9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eRheumatic Disorders and Autoimmune Thyroid Disease. A Common Co-occurrence With an Unusual Presentation- A Case Report\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAutoimmune thyroid disease (AITD) is a spectrum of disorders ranging from the most common form of Hashimoto\u0026rsquo;s thyroiditis (HT) to the less common Graves\u0026rsquo; disease. Of interest, GD and SLE are two different entities; the former is organ-specific, whereas the latter is a multisystem inflammatory disorder. GD is characterized by agonistic antibodies against the Thyroid stimulating hormone (TSH) receptor on the thyroid gland, causing thyrotoxicosis. SLE involves autoantibody formation against various nuclear antigens and subsequent immune complex deposition, causing organ dysfunction and failure [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The coexistence of AITD and SLE is a well-known phenomenon. A meta-analysis from 1946\u0026ndash;2018 revealed an increased prevalence of primary hypothyroidism in SLE patients (15\u0026ndash;19% vs. 4.6% in the general population). Although less prevalent, the same study reported that hyperthyroidism was also more common in the lupus group (3\u0026ndash;9% vs. 1.5%) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Researchers are now inclined toward identifying single nuclear polymorphisms (SNPs) in various HLA and non-HLA genes, which serve as common genetic susceptibility loci for both SLE and GD [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This novel discovery can potentially revolutionize our approach toward such complex autoimmune entities. Anti-phospholipid syndrome (APS) is an acquired disorder causing recurrent venous and, notably, arterial thrombosis in young individuals and/or obstetric adversities, with persistent anti-phospholipid antibodies (APLs) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Secondary APS is its co-existence with other disorders, mostly SLE. Although less acclaim, the association between AITD and APS and/or their antibodies is important, particularly in young women, since both are notoriously known for poor fetal outcomes and recurrent miscarriages (RMs) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e][\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This case report confirms the association between GD and SLE as parent diseases in our patient, along with an interesting linkage with APS and Addison\u0026rsquo;s disease as probable co-occurrences, which, to our knowledge, is the first reported case involving multiple intricate autoimmune entities in the same patient.\u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003eA 35-year-old female, with no comorbidities or family history, presented at our clinic with a one-year history of generalized weakness, postural dizziness, dyspnea (mMRC grade two) and dry cough, which had worsened for the past week. Another chief complaint was the gradual increase in neck swelling for approximately three years, which caused pressure and discomfort. She had experienced palpitations, heat intolerance, diaphoresis, polyphagia, subfertility and proximal muscle weakness, along with substantial weight loss of approximately 10 kg. She also agreed to have polyarthralgia and myalgia with brief morning stiffness, oral ulcers, hair loss, dry mouth and gritty eyes for six months. Menses were heavy since menarche, but she had amenorrhea for three months. The obstetric history was complicated by three miscarriages and five still births, with only one surviving child. She had received several red blood cell transfusions and iron prescriptions in the past, but no formal diagnosis was given.\u003c/p\u003e \u003cp\u003eAt first glance, our patient was an anxious and fidgety young woman with a staring gaze and a BP of 100/60 with no orthostasis. Vital examination revealed tachycardia at 128 bpm (regular), tachypnea, oxygenation of 94% on room air, and normothermia. The most striking finding was a large, warm and non-tender goiter with a uniform texture and audible bruit. Lymphadenopathy, the Pamberton sign, and increased JVP were absent, as was Thyroid Ophthalmopathy. Physical examination revealed cachexia, clubbing grade two, pallor, dehydration, fine tremors, palmar sweating, receding hairlines, blepharitis, a butterfly rash sparing the nasolabial folds, a fissured beefy tongue, and dental caries. Hyperpigmentation was observed around the palmar creases, knuckles, and oral cavity. She had a hyperdynamic precordium with a loud P2 sound on auscultation.\u003c/p\u003e \u003cp\u003eShe was admitted for severe systemic illness, and serial investigations were carried out. She had severe anemia and thrombocytopenia and a microcytic peripheral film. The corrected retic count was 0.6%. The serum thyroid profile was dramatic, with a very low TSH, high T3 and T4. Other abnormalities included hyponatremia, hypoalbuminemia, and a high ESR. The serum Iron profile suggested iron deficiency. Pregnancy was ruled out by serum β-HCG and sonography. Urinalysis revealed only trace proteinuria \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e Chest imaging was normal, but an echocardiogram revealed an isolated high mean pulmonary artery pressure of 55 mmHg. Thyroid sonography confirmed a uniformly enlarged and hypervascular gland. Immunological testing demonstrated convincing results, including strongly positive antinuclear antibodies along with, positive anti-DsDNA, anti-SS-A/Ro and anti-cardiolipin IgM. Other antibodies, including Smith, Scl-70, U1-RNP, CCP, RA factor, β2GPI and LA, were negative. Serum complement levels were very low. Thyroid receptor antibodies (TRAbs) were also positive. Morning cortisol was substantially low, and anti-TTG (tissue transglutaminase) IgA was negative \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Upon constellating the above description with the ACR/EULAR criteria, SLE and Sjogren\u0026rsquo;s (SS) overlap were diagnosed along with Graves\u0026rsquo; disease. APS and Addison\u0026rsquo;s Disease were among the likely possibilities.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline laboratory investigations over the course of hospital stay\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory Investigations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal Values\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDay 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDay 5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDay 7\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.9\u0026ndash;15.0 (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.3\u003c/p\u003e \u003c/td\u003e \u003ctd 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\u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGPT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u0026ndash;55 (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGOT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u0026ndash;45 (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44\u0026ndash;147 (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e171\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT pro\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6-8.3 (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5\u0026ndash;5.5 (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpot urine PCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003cspan\u003e1. Hb, hemoglobin; Hct, hematocrit; TLC, total leukocyte count; PLT, platelets; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; PT, prothrombin time; APTT, activated partial thromboplastin time; INR, international normalized ratio BUN, blood urea nitrogen; Cr, creatinine; Na, sodium; K, potassium; Cl, chloride; Ca, calcium; Mg, magnesium; PO4, phosphorus; T Bili, total bilirubin; SGPT, serum glutamic pyruvic transaminase; SGOT, serum glutamic oxaloacetic transaminase ;ALP, alkaline phosphatase; T pro, total protein; Alb, albumin\u003c/span\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDiagnostic Investigations\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory Investigations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal Range\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient Results\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5\u0026ndash;4.5 (mIU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.08\u0026ndash;3.14 (nmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5\u0026ndash;11 (5.5\u0026ndash;11 mcg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTRAb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-0.9 (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eANA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1:80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1:2560 (homogenous pattern)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti Ds DNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;25 (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti SSA Ab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;3.2 (IU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti SSB Ab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;7 (IU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC3 levels\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.8 (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC4 levels\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.129 (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACLA (IgM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;20 (U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-β2GPI (IgM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;20 (U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u0026ndash;40 (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8am serum cortisol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.0\u0026ndash;23 (mcg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003cp\u003e\u003cspan\u003e2. TSH, thyroid stimulating hormone; T3, total triiodothyronine; T4, total thyroxine; ANA, anti-nuclear antigen; Anti Ds DNA, anti-double stranded deoxyribonucleic acid; Anti SSA Ab, anti\u0026ndash;Sjogren's-syndrome-related antigen A autoantibodies; Anti SSB Ab, anti\u0026ndash;Sjogren's-syndrome-related antigen B autoantibodies; C3, compliment component 3; C4, compliment component 4; ACLA, Anti cardiolipin autoantibodies; Anti-β2GPI, Anti beta 2 glycoprotein 1 autoantibodies; LAA, lupus anticoagulant antibodies\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eInitial management included blood transfusions, propranolol, omeprazole, and nutritional support. Upon confirmation of the diagnosis, 30 mg of oral Carbimazole and 400 mg of Hydroxychloroquine were started in divided doses. Dyspnea and PAH were curbed with Furosemide and the Endothelin receptor antagonist Bosentan. Given the high inflammatory activity of SLE, intravenous Dexamethasone was started at a dosage of 4 mg eight hourly to supplement hypoadrenalism. Mineralocorticoids were not used. In the absence of pregnancy and thrombosis, anticoagulation was not given. The patient and her family were counseled in detail about the importance of the frequency and timing of the medications to be taken, explaining the severity of her disease(s).\u003c/p\u003e \u003cp\u003eWith the given treatment, the patient experienced remarkable improvement within one week and was discharged on oral medications, including equivalent doses of Prednisolone. Our further plan included testing for APL after 12 weeks, serum Adrenocorticotropic hormone (ACTH) levels along with adrenal imaging and a CT pulmonary angiogram, which were delayed due to financial limitations. Unfortunately, owing to noncompliance, she returned after two weeks with altered sensorium. Examination revealed hypotension, cold peripheries, tachycardia, and clear chest with respiratory distress. Blood gases revealed metabolic acidosis and hypoxemia. Her blood glucose level was 80 mg/dL. Admission to ICU was made. A whole panel of laboratories, including electrolytes, CBC, D-dimers and cortisol, was sent. The initial CT brain was unremarkable. Oxygen, vasopressors, antibiotics and IV hydrocortisone were initiated. While being prepared for intubation, she experienced intractable seizures and died shortly afterwards.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe coexistence of GD and SLE has been widely reported for more than a decade [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Anti-thyroid drugs have also been implicated as an independent cause of lupus [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Various East Asian studies have emerged recently, establishing a bidirectional causal association between the two, concluding that having one disease increases the risk of the other [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This is important, as it eliminates confounding bias, since both SLE and GD predominantly victimize young women. One retrospective cohort of 2796 new SLE patients concluded that patients with lupus with overlap had a greater relative risk of thyreopathy than did those with lupus alone. Additionally, it concluded that SLE patients with thyroid diseases more frequently have renal and CNS involvement [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This is reflected in our patient who had SLE overlapping with severe GD and later presented with intractable seizures. With respect to temporal associations, the majority of studies report that thyroid disorders are diagnosed months to years later in known SLE patients, mainly because of persistent nonspecific symptoms despite immunosuppression and low disease activity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e][\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In contrast, our patient presented with chronic hyperthyroidism and goiter with acute decompensated thyrotoxicosis. The onset of rheumatism was recent and subtle, submerged in the chronicity and non-specificity of hyperthyroidism.\u003c/p\u003e \u003cp\u003eRecurrent miscarriage (RM) and pregnancy loss are some of the highlights of our case. Although a diseased thyroid status and SLE itself are well-known causes of subfertility and recurrent pregnancy loss, the high likelihood of Anti-Phospholipid syndrome (APS) in our patient is worth mentioning. Interestingly, the presence of isolated anti-thyroid antibodies and anti-phospholipid antibodies has been linked to an increased risk of RM and worse pregnancy outcomes, even in the absence of proven disease [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e][\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This is of paramount importance, as this association signifies the need for screening women with unexplained RM and poor fetal well-being for the presence of both anti-thyroid antibodies and anti-phospholipid antibodies.\u003c/p\u003e \u003cp\u003eOn careful analysis, the compelling cause of this patient\u0026rsquo;s visit alongside thyrotoxicosis was respiratory limitation. The likely cause of this was found to be pulmonary arterial hypertension (PAH), in addition to anemia. The probable confounders of this were SLE and GD since both are recognized causes of pulmonary hypertension (PH) and/or PAH according to the WHO [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. APS is also a notable culprit of thromboembolic (CTEPH)[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] and non-thromboembolic PH [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Recently, a study proposed that the prevalence of PH in GD patients did not differ significantly between the hyperthyroid and euthyroid groups,while 30% of patients sustained PH despite long-term thyrotoxic control, necessitating PAH-specific therapy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This serves as a potential area of research to establish whether employing cardiorespiratory assessment routinely in evaluating patients with thyrotoxicosis and connective tissue disorder provides any long-term benefit.\u003c/p\u003e \u003cp\u003eFinally, shedding light on the gray area, underlying Addison\u0026rsquo;s disease (AD) in our patient was suggested by a low normal BP despite thyrotoxicosis, hyponatremia, and hyperpigmentation alongside postural dizziness [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e][\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Constellation of AITD and AD constitutes a polygenic disorder termed AUTOIMMUNE POLYGLANDULAR SYNDROME TYPE 2 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Autoimmune polyendocrine syndromes have been reported to accompany rheumatic diseases, altering their natural history and rendering them resistant to rheumatological treatment. Moreover, overlooked endocrinopathies may accentuate the metabolic, musculoskeletal, and cardiovascular disorders encountered in the course of rheumatic disorders [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Although not conclusively diagnosed, identifying the adrenal status of our patient was crucial because the coexistence of AD necessitated the use of steroids, which are not otherwise used in the management of GD. Although highly active SLE also prompted their use in our patient, the indication was momentary.\u003c/p\u003e \u003cp\u003eOur report also highlights the dilemma of nonadherence of our community to the treatment advised, stemming from various reasons, notably poverty, illiteracy, relying solely on spiritual treatment and embarrassment. The burden imposed on healthcare in underdeveloped countries such as Pakistan involves not only the disease itself but also the reasons stated above.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eWe present an interesting and unusual case of Graves\u0026rsquo; disease and SLE alongside Sjogren\u0026rsquo;s syndrome. The simultaneous existence of APS and AD was also highlighted. The clinical domains here, including chronic fatigue, anemia, PH, hypoadrenalism, and obstetric morbidity, can be partly explained by each of these diseases alone. However, it is prudent to realize that the overlap among these disorders is real and challenging, while focusing solely on a single diagnosis is detrimental, leading to treatment failure.Our aim is to therefore remind clinicians of the necessity of vigilant consideration and regular screening of concurrent autoimmune diseases and/or endocrinopathies while treating patients with these diseases. This ensures timely diagnosis and a holistic management approach, thereby reducing all-cause morbidity and mortality and improving the quality of life of patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAll the abbreviations used in this manuscript are appropriately explained where necessary.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e\u003cu\u003eFunding Statement:\u003c/u\u003e\u003c/strong\u003e Not Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eConflict Of Interest:\u003c/u\u003e\u003c/strong\u003e The author(s) of this work have nothing to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eEthics Approval\u003c/u\u003e\u003c/strong\u003e: Not applicable as no human or animal objects were used, patients\u0026rsquo; identity anonymized.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eConsent to participate\u003c/u\u003e\u003c/strong\u003e: Not Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eConsent for publication\u003c/u\u003e\u003c/strong\u003e:\u0026nbsp;Given that\u0026nbsp;the patient died before the initiation of report writing, written consent was signed by\u0026nbsp;the\u0026nbsp;patients\u0026rsquo;\u0026nbsp;mothers. The translated\u0026nbsp;details were explained in\u0026nbsp;the\u0026nbsp;native language because\u0026nbsp;English was not understood. Patients\u0026rsquo; images were not included\u0026nbsp;for\u0026nbsp;social and religious reasons.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAvailability of data\u003c/u\u003e\u003c/strong\u003e: Not Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eCode Availability\u003c/u\u003e\u003c/strong\u003e: Not Applicable\u003cstrong\u003e\u003cu\u003e\u003cbr\u003e\u003c/u\u003e\u003cbr\u003e\u003cu\u003eAuthors\u0026rsquo; Contribution:\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTehreem Manzoor\u003c/strong\u003e: Concept and design, Acquisition, analysis and interpretation of data, Drafting of the manuscript, Critical review of the manuscript, approved final version\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAiman Ali\u003c/strong\u003e: Concept and design, Drafting of the manuscript, Critical review of the manuscript ,approved final version\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRida Masood\u003c/strong\u003e: Concept and design, Acquisition, analysis and interpretation of data, Critical review of the manuscript ,approved final version\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSyed Muhammad Kashif\u003c/strong\u003e : Acquisition, analysis and interpretation of data, Critical review of the manuscript , approved final version\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMuhammad Tanveer Alam\u003c/strong\u003e: Acquisition, analysis and interpretation of data, Critical review of the manuscript , approved final version\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee C, Chen SF, Yang YC, Hsu CY, Shen YC. 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J Pediatr Endocrinol Metab. 2020;33(4):575\u0026ndash;8. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1515/jpem-2019-0506\u003c/span\u003e\u003cspan address=\"10.1515/jpem-2019-0506\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartins SC, Venade G, Teixeira M, et al. Autoimmune polyglandular syndrome type 2. Rev Assoc Med Bras (1992). 2019;65(12):1434-7. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1590/1806-9282.65.12.1434\u003c/span\u003e\u003cspan address=\"10.1590/1806-9282.65.12.1434\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJankowska K, Dudek P, Stasiek M, Suchta K. Autoimmune polyendocrine syndromes associated with autoimmune rheumatic diseases. Reumatologia. 2023;61(4):225.\u003c/span\u003e \u003cspan\u003edoi: 10.5114/reum/170266\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"case report, goitre, Graves’ disease, sle, Addison’s disease, antiphospholipid antibody syndrome (aps), pulmonary hypertension","lastPublishedDoi":"10.21203/rs.3.rs-5183368/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5183368/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eGraves\u0026rsquo; disease (GD) and systemic lupus erythematosus (SLE) are two autoimmune disorders well known for their co-existence. Shared genetic susceptibility loci are being increasingly identified, confirming the causal bidirectional association between the two.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003eOur case involves a young woman who presented with chronic symptoms of hyperthyroidism along with anemia, goitre, respiratory distress, and a recent onset of rheumatism. Diagnostic investigations fulfilled the criteria of GD along with SLE and Sjogren\u0026rsquo;s overlap. Pulmonary arterial hypertension (PAH) was detected via echocardiography, likely indicating the complex interplay between SLE and GD. Significant fetal and embryonic mortality raised the suspicion of anti-phospholipid syndrome, leading to the detection of anti-phospholipid antibodies. The likelihood of adrenal insufficiency and Autoimmune Polyglandular syndrome type 2 was also addressed. The patient was managed with anti-thyroid medications, steroids, and PAH-specific therapy. Our case is unique, as it involves multiple autoimmune disorders of rheumatic and endocrine origin in the same patient. The uniqueness also lies in the temporal sequence of the disorders, with GD being antecedent to SLE, contrary to what the literature suggests.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eAlthough the patient tragically died, the goal here was to reinforce the idea that autoimmune disorders are complex, revealing themselves in various forms. Scouting for comorbidities and adapting a holistic treatment approach is prudent when dealing with these ailments. The social and financial dilemmas leading to noncompliance with treatment and its detrimental effects are also highlighted.\u003c/p\u003e","manuscriptTitle":"Rheumatic Disorders and Autoimmune Thyroid Disease. A Common Co-occurrence With an Unusual Presentation- A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-04 11:35:24","doi":"10.21203/rs.3.rs-5183368/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-22T16:11:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-22T06:05:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-22T04:57:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2024-09-30T20:49:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ce18c29e-024f-46c3-acc6-c7b825c34236","owner":[],"postedDate":"November 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-20T16:09:05+00:00","versionOfRecord":{"articleIdentity":"rs-5183368","link":"https://doi.org/10.1007/s42399-025-02112-x","journal":{"identity":"sn-comprehensive-clinical-medicine","isVorOnly":false,"title":"SN Comprehensive Clinical Medicine"},"publishedOn":"2025-10-16 15:57:58","publishedOnDateReadable":"October 16th, 2025"},"versionCreatedAt":"2024-11-04 11:35:24","video":"","vorDoi":"10.1007/s42399-025-02112-x","vorDoiUrl":"https://doi.org/10.1007/s42399-025-02112-x","workflowStages":[]},"version":"v1","identity":"rs-5183368","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5183368","identity":"rs-5183368","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}