Thyroid-stimulating Antibodies Research Articles

Antithyroid drug therapy for Graves’ disease

Background: Graves’ disease is the most common cause of hyperthyroidism which is caused by stimulating autoantibodies against thyroid-stimulating hormone receptor. There is no etiology-specific treatment for Graves’ disease.Current Concepts: Graves’ disease can be treated with antithyroid drugs (ATDs), radioactive iodine, or thyroidectomy. ATDs are the most preferred first-line therapy, because they do not cause either permanent hypothyroidism or exacerbation of orbitopathy, despite low remission rate. ATDs have serious adverse reactions including agranulocytosis and fulminant hepatic necrosis requiring liver transplantation. Methimazole (MMI) is recommended in every patient starting ATD therapy, except during the first trimester of pregnancy and in cases of thyroid storm, because of relatively lower incidence and severity of serious adverse reactions compared with propylthiouracil. Treatment should be continued for 12 to 18 months, then discontinued if the levels of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies are normalized. In cases of relapse of hyperthyroidism, radioactive iodine or thyroidectomy can be recommended for definitive therapy; however, recent studies support longer-term maintenance of low dose MMI as a favorable alternative therapy. All ATDs may induce congenital anomalies when exposed during early pregnancy. Every female patient of reproductive age should be advised to postpone pregnancy until their thyroid function is maintained within normal range and to stop ATDs when pregnancy is confirmed to avoid the risk of congenital anomalies.Discussion and Conclusion: Longer-term low dose MMI therapy can be a good choice for Graves’ hyperthyroidism with relapse. Before pregnancy, hyperthyroidism should be controlled to stop ATDs during pregnancy.

Immunotherapy with a biologically active ICAM-1 mAb and an siRNA targeting TSHR in a BALB/c mouse model of Graves' disease.

The objective was to study targeted therapies using a biologically active monoclonal antibody against intracellular adhesion molecule-1 (ICAM-1 mAb) and an siRNA targeting thyroid-stimulating hormone (TSH) receptor (TSHR) in a BALB/c mouse model of Graves' disease (GD). An improved method for establishing a stable model of GD in BALB/c mice was developed by immunization with pcDNA 3.1/TSHR 289 and electroporation (EP). The mice in which GD was successfully established were divided into a nontreated control group, which was treated with continuous immunization, and treated groups, which were treated with the siRNA and ICAM-1 mAb. Normal mice were included as a blank group. These groups were used to compare the effects of treatment with the ICAM-1 mAb and siRNA. The two novel treatments markedly improved weight loss, serum thyroxine (T4) levels, thyroid-stimulating hormone antibody (TSAb) levels, thyroid-stimulating blocking antibody (TSBAb) levels and thyroid uptake of 99mTcO4 in GD model mice. Compared with the siRNA treatment, treatment with the ICAM-1 mAb produced more obvious benefits. The differences in the posttreatment indexes between the two treatment groups were statistically significant (p < 0.05). These preliminary data suggest that both the biologically active ICAM-1 mAb and the siRNA targeting TSHR were effective. The ICAM-1 mAb exerted a better therapeutic effect than the siRNA targeting TSHR. Both treatments showed potential efficacy as novel treatments for GD and may therefore represent therapeutic options in addition to the existing drugs or interventions.

Comparison of Thyrotropin Receptor Antibodies Levels Before and After Methimazole Therapy for 6 months in Children With Graves Disease

Background : Graves’ disease is the leading cause of hyperthyroidism in children. The increase of hormones thyroxine (T4), free thyroxine (fT4) and triiodothyronine (T3) in Graves' disease is caused by the presence of thyroid stimulating antibodies (TSHR-Ab) or Thyrotopin receptor antibodies (TRAb). Methimazole (MMI) is often use as anti thyroid medication in children. Methimazole therapy may give a good response to patients with new-onset Graves’ disease, high levels of thyroxine, high TRAb), and no or small goiters. Objective : The purpose of this study was to determine the differences in TRAb before and after Methimazole Therapy for 6 months in children with Graves’ disease. Method : Retrospective study on 28 children below 18 year old with Graves’ disease at H. Adam Malik General Hospital Medan with TRAb, fT4, TSH data collection before and after Methimazole therapy for 6 months taken from medical records. Result : Median age 11.85 ± 3.73 with the number of women 85.7% compared to men 14.3%. The median value before Methimazole therapy was TRAb 32,11 IU/L, fT4 3.56 ng/dl and TSH 0.01 mU/l. Median values after 6 months of Methimazolee therapy were TRAb 17.15 IU/L, fT4 1.51 ng/dl and TSH 0.51 mU/l with P values <0.001, P = 0.006, P <0.001 respectively. Conclusion: There was significant differences in TRAb, fT4, and TSH median values before and after 6 months of Methimazole therapy in children with Graves’ disease.

Immunoglobulin-E and Thyroid-Stimulating Hormone Receptor Antibody in Graves’ disease with Atopy

Background: Graves’ disease is known to have a high recurrence rate with recent evidence linked pollen allergy as one of the factors that might induce relapse in Graves’ disease. Therefore, it was argued that IgE might play a role in inducing relapse of Graves’ Disease. This study aims to investigate the correlation between IgE and Thyroid-Stimulating Hormone ReceptorAntibody (TRAb) in Graves’ disease respondents with a history of atopy.

The association between serum adenosine deaminase levels and Graves’ disease

BackgroundAdenosine deaminase (ADA) is essential for the differentiation and maturation of lymphocytes, while lymphocytes infiltration in thyroid tissue is a vital pathological feature of Graves’ disease (GD). The aim of the present study was to compare the concentration of ADA between healthy controls (HC) and patients with GD, and evaluate the association between ADA and GD.MethodsA total of 112 GD patients and 77 matched HC were enrolled in this study. Each participant was examined for thyroid hormones and autoantibodies, ADA concentration, and thyroid ultrasonography.ResultsSerum ADA levels in GD patients were significantly higher than that in HC subgroup (P < 0.001). In GD patients, serum ADA levels were positively associated with serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb) levels, and total thyroid gland volume (thyroid VolT) and negatively associated with serum thyroid-stimulating hormone receptor (TSH) levels (all P < 0.05). There were no similar correlations in the HC subgroup. Multiple linear regression analysis suggested that serum TSH, FT3, and ADA levels played an important role in serum TRAb levels.ConclusionsOur results demonstrated that serum ADA levels were closely associated with GD.

Therapeutic plasma exchange for Graves' disease in pregnancy.

Graves' disease in pregnancy may be associated with maternal, fetal and neonatal complications, which are proportionate to the severity of hyperthyroidism. Optimal management is detailed preconception counselling, achievement of an euthyroid state prior to conception, and close monitoring of thyroid function and thyroid-stimulating antibodies together with judicious use of anti-thyroid medications during pregnancy. A case of Graves' disease in pregnancy, complicated by pancytopenia, with a deterioration in thyroid function following cessation of thionamide therapy is described here. Therapeutic plasma exchange was subsequently used to achieve rapid control prior to thyroidectomy. Therapeutic plasma exchange is an effective treatment for hyperthyroidism where thionamides are ineffective or contraindicated, as a bridge to definitive management.

Serum thyroid-stimulating hormone receptor antibody levels and thyroid dysfunction after hysterosalpingography: a case-control study

Objective Hysterosalpingography (HSG) performed with an iodine contrast media can cause thyroid dysfunction, including thyrotoxicosis and hypothyroidism. We investigated the association between the serum levels of thyroid-stimulating hormone receptor antibody (TRAb), an indicator of Graves’ disease, and abnormal thyroid function after performing HSG. Methods The screening of TRAb was conducted in 362 patients who first visited the Tawara IVF Clinic between April and September 2018. The association between TRAb levels and the effects of HSG examinations on thyroid function were evaluated. Results Of the 362 patients, 2 (0.55%) had high levels (>2.0 IU/L) of TRAb, whereas 18 (5.0%) had intermediate TRAb levels, ranging from 0.3 to 1.9 IU/L. Of the 98 women (including 7 of the 18 women with TRAb level 0.3–1.9 IU/L, and 91 of the 342 women with TRAb level <0.3 IU/L) who had undergone HSG, two women developed overt thyrotoxicosis after HSG, and the frequency was significantly higher (p = .0044) in the group with intermediate levels of TRAb (28.6%, 2 of 7) than that in the group with low TRAb levels (<0.3 IU/L; 0.0%, 0 of 91). Conclusions These findings indicate that increased serum levels of TRAb are significantly associated with the development of thyrotoxicosis after HSG.

Thyroid-Stimulating Hormone Receptor Antibodies in Refractory Graves’ Disease Change Differently According to the Type of Definitive Therapy Administered

Clinical ThyroidologyVol. 33, No. 8 HyperthyroidismThyroid-Stimulating Hormone Receptor Antibodies in Refractory Graves’ Disease Change Differently According to the Type of Definitive Therapy AdministeredUlla Feldt-RasmussenUlla Feldt-RasmussenDepartment of Medical Endocrinology and Metabolism, Rigshospitalet (Copenhagen University Hospital) and Department of Clinical Medicine, Faculty of Health and Medical Science, Copenhagen University, Copenhagen, DenmarkSearch for more papers by this authorPublished Online:6 Aug 2021https://doi.org/10.1089/ct.2021;33.350-353AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 33Issue 8Aug 2021 InformationCopyright 2021 American Thyroid Association, Inc.To cite this article:Ulla Feldt-Rasmussen.Thyroid-Stimulating Hormone Receptor Antibodies in Refractory Graves’ Disease Change Differently According to the Type of Definitive Therapy Administered.Clinical Thyroidology.Aug 2021.350-353.http://doi.org/10.1089/ct.2021;33.350-353Published in Volume: 33 Issue 8: August 6, 2021PDF download

Overtreatment of Transient Maternal Hyperthyroidism Resulting in Fetal Goiter.

Overtreatment of Transient Maternal Hyperthyroidism Resulting in Fetal Goiter.

Clinical efficacy of thyroid-stimulating immunoglobulin detection for diagnosing Graves’ disease and predictors of responsiveness to methimazole

BackgroundAs thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients and compared it to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored. MethodsThis study involved 324 subjects, comprising patients with untreated GD (GD-UT), Graves’ ophthalmopathy (GO) patients, GD patients who had been treated for > 12 months (GD-T), autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). The Immulite™ TSI and Elecsys Anti-TSHR assay were performed on all samples. According to their responsiveness to methimazole, the GD-UT patients were divided into rapid and slow responder groups, and their clinical characteristics were compared. ResultsA receiver operating characteristic (ROC) curve analysis of GD-UT patients showed that the optimal TSI cut-off value was 0.57 IU/L. Logistic regression revealed that age and initial FT4 and TSI levels in the middle-dose methimazole group were related to a rapid response, while the initial FT4 level, but not TSI, in the high-dose group was also associated with a rapid response. ConclusionsThe clinical diagnostic performance of the Immulite™ TSI assay for diagnosing GD was comparable to that of the Elecsys Anti-TSHR assay. The initial FT4 and TSI levels can be used as predictors of the responsiveness to methimazole in patients with newly diagnosed GD.

Imaging Algorithm-Based Real-Time Shear Wave Elastography Combined with Thyroglobulin Antibodies in Diagnosis of Thyroid Cancer

To analyze the effect of real-time shear wave elastography (SWE) optimized by mathematical algorithms combined with thyroglobulin antibodies (TGAb) on the clinical diagnosis of differentiated thyroid carcinoma (DTC), a hybrid displacement estimation algorithm based on weighted phase separation and two-dimensional cross correlation was proposed. 102 patients with DTC were divided into a test group (TGAb-positive) and a control group (TGAb-negative). Real-time SWE based on hybrid displacement estimation algorithm was performed. Receiver operating characteristic (ROC) curve was adopted to analyze the characteristics of real-time SWE and its combination with TGAb to detect the sensitivity, specificity, and area under the curve (AUC) of the malignant degree of thyroid cancer. The results showed that the preoperative thyroid-stimulating hormone (TSH), thyroglobulin autoantibodies (TGAb), and thyroid peroxidase antibody (TPOAb) of TGAb-positive patients were higher than those of the TGAb-negative group ( P &lt; 0.05 ). The preoperative tumors of TGAb-positive patients were multifocal, and the tumor size was larger than that of the TGAb-negative patients ( P &lt; 0.05 ). The maximum Young’s modulus Emax of TGAb-positive patients was greater than that of TGAb-negative group ( P &lt; 0.05 ). In addition, there was a very significant positive correlation between the patient’s TGAb level and Emax of Young’s modulus ( P &lt; 0.001 ). The sensitivity, specificity, and AUC of the joint detection of real-time SWE Emax and TGAb for the malignant degree of thyroid cancer were significantly greater than those of the single real-time SWE and TGAb, and the difference was substantial ( P &lt; 0.05 ). In short, joint detection of real-time SWE based on hybrid displacement estimation algorithm combined with TGAb had high sensitivity, specificity, and AUC for the diagnosis of DTC, which was suitable for clinical application.

Prognostic factors of restrictive myopathy in thyroid eye disease

To investigate the prognostic factors of extraocular muscle restriction in patients with thyroid eye disease (TED), 65 patients with TED and restrictive myopathy were evaluated. Demographics, clinical activity score (CAS), smoking status, thyroid disease status, thyroid hormone status, thyroid autoantibody status, orbital computed tomography (CT) scan at initial presentation, and treatment regimens were assessed. The movements of the most severely affected extraocular muscles were categorized into five grades. The patients were divided into the improved and the not-improved group based on the improvement in the limitation of the extraocular muscle excursion (LOM) throughout the follow-up, and the groups were compared using clinical factors. The mean LOM significantly improved from 2.3 ± 1.1 to 1.7 ± 1.2 after 1 year of follow-up. The excursion of the most restricted muscle improved in 32 patients but not in 33 patients during the follow-up. The initial concentration of the thyroid-stimulating antibody (TSAb) was significantly lower in the improved (229.3 ± 114.1) than in the not-improved group (345.0 ± 178.6) (P = 0.02) Age, sex, smoking status, CAS, thyroid status, and muscle thickness on the CT scan did not significantly differ in the groups. This study showed that the initial concentration of TSAb is a factor affecting the recovery of restrictive myopathy.

Relationship between autoimmune thyroid disease and nephropathy: A clinicopathological study.

The association of nephropathy with autoimmune thyroid disease (AITD) has been reported previously. However, there is limited information on the relationship between thyroid autoantibodies and nephropathy. A retrospective study was conducted using the medical records of 246 patients with nephropathy, 82 of whom had concurrent AITD. General characteristics, thyroid function, autoantibodies, and the pathological types of nephropathy were analyzed. Immunohistochemistry was used to detect the thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) in the kidneys. We found nephropathy patients with AITD exhibited higher serum levels of TPO-Ab, TG-Ab, thyroid-stimulating hormone receptor antibody (TR-Ab), and immunoglobulin G (IgG) (P < .05). Compared with the nephropathy without AITD group, the nephropathy with AITD group exhibited higher proportions of membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS), and relatively lower proportions of mesangial proliferative glomerulonephritis (MsPGN) and minimal change nephropathy (MCN) (P = .005). TPO-Ab and TG-Ab levels in the kidney were more prevalent in nephropathy patients with AITD than those without AITD (P = .015 and P = .026, respectively). Subgroup analysis demonstrated that serum levels of thyroid stimulating hormone (TSH), TG-Ab, TPO-Ab, immunoglobulin M (IgM), and IgG in the MN group were significantly higher, whereas the levels of free thyroxine (FT4) and estimated glomerular filtration rate (eGFR) were lower, as compared with MN with Hashimoto thyroiditis (HT) group (P < .05). TPO-Ab and TG-Ab expression levels in the kidneys were more prevalent in the MN group than in the MN with HT group (P = .034). The expression levels of FT4, TG-Ab, TPO-Ab, and thyroid-stimulating hormone receptor antibody (TSHR-Ab) in the serum were significantly higher in the MN group than in the MN with Graves disease (GD) group (P < .05). The expression of TPO-Ab in the kidneys was more prevalent in the MN group than in the MN with GD group (P = .011). In sum, the expressions of TPO-Ab and TG-Ab were more prevalent in the kidneys of patients with nephropathy and AITD. Our findings indicate that TPO-Ab and TG-Ab may play a role in the development of AITD-related nephropathy.

Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves’ disease (GD). Although fibroblast stimulated by thyroid‐stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM.Results obtained on PTM patients indicate increased thyroid‐stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin‐associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.

Abstract #996726: Clinical Efficacy of Thyroid-stimulating Immunoglobulin Detection for Diagnosing Graves’ Disease and Predictors of Responsiveness to Methimazole

As thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. Only a few studies have assessed the efficacy of TSI detection for diagnosing GD in a Chinese population. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (ImmuliteTM TSI assay) in GD patients and compared it to a thyroid-stimulating hormone receptor antibody (TRAb) immunoassay (ELiATM TRAb assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored.

Painful Hashimoto Thyroiditis in a 7-Year-Old Girl: Differential Diagnosis and Medical Treatment

Painful Hashimoto thyroiditis (HT) is a rare pediatric condition. Because of the rarity of painful HT, it can be misdiagnosed as other thyroid diseases, and there is limited evidence regarding its clinical course and treatment. A 7-year-old girl presented to the emergency room with neck pain. A physical examination revealed diffusely enlarged thyroid gland with firm consistency and without tenderness. Her serum free thyroxine level was decreased and levels of thyroid-stimulating hormone, thyroglobulin antibody, and thyroid-stimulating antibody were elevated. The ultrasonography revealed a diffusely enlarged thyroid gland with homogeneously hypoechoic parenchyma and lobulated contours. She was diagnosed with painful HT based on the clinical presentations, laboratory tests, and ultrasonography findings, and was treated with a steroid, levothyroxine, and nonsteroidal anti-inflammatory drugs, after which her clinical symptoms improved dramatically. We should consider the possibility of painful HT in children with neck pain; HT could be treated with medical treatment.

Abstract #1004269: Subacute Thyroiditis in Patients Infected with SARS-COV-2

Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid gland that causes destructive thyrotoxicosis and is attributed to a viral or post-viral response. The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters human cells through the angiotensin-converting enzyme 2 (ACE2) receptor. Thyroid follicular cells express the ACE2 receptor, thus making thyroid tissue a possible target of direct infection by the SARS-CoV-2 virus. The aim was to describe cases of SAT associated with SARS-CoV-2 infection to alert physicians that SAT may be a manifestation of SARS-CoV-2 infection. We describe clinical, biochemical, and imaging features of 11 patients with SAT related to SARS-CoV-2 infection. All patients were female (age, 30-45 years). Neck pain radiated to the jaw, fatigue, tremors, and palpitations were the main presenting symptoms and were associated with fever and asthenia. Physical examination revealed mild tremors of the extremities, a diffuse and painful goitre, and enlarged and tender cervical and submandibular lymph nodes. At biochemical evaluation, inflammatory markers were high. Thyroid function tests were suggestive of destructive thyroiditis. TSH was suppressed, free thyroxine (FT4) and free triiodothyronine (FT3) levels were elevated, and serum thyroglobulin was markedly increased (175 ng/ml; referral range 2.68-33.2). Anti-thyroid peroxidase, anti-thyroglobulin, and thyroid-stimulating hormone receptor antibodies were negative. At neck ultrasound the thyroid was enlarged, with diffuse and bilateral hypoechoic areas and absent vascularization at colour Doppler. Thyroid scintigraphy showed markedly reduced 99mTc-perthecnetate uptake in the gland. Reverse transcription-polymerase chain reaction for SARS-CoV-2 using nasopharyngeal and oropharyngeal swabs were positive. Chest X-rays and computed tomography scanning of the chest were normal. Symptoms were alleviated a few days after commencement of treatment (aspirin in 3 patients, prednisone in 2 patients, paracetamol in 3 and ibuprofen in 3) together with propranolol for tachycardia and tremors. Ten weeks after the onset of SAT, all patients were asymptomatic and inflammatory markers had returned to normal range. Eight patients were euthyroid, whereas 3 were with subclinical hypothyroidism. Conclusion: Clinicians should be aware of thyroid manifestations potentially associated with COVID-19.

Hyperthyroidism: A Rare Cause of Cerebral Venous Thrombosis

Background: Cerebral venous thrombosis (CVT) accounts for <1% of strokes. In most cases, there is a predisposition to hypercoagulability; however, in about 30% of cases there is no identifiable etiology. Risk factors include pregnancy, puerperium, oral contraceptives, and coagulopathies and rarely hyperthyroidism. To the best of our knowledge there is no reported cases of CVT in uncontrolled hyperthyroidism with no underlying hypercoagulable disorder. We present a case where a woman developed CVT in the setting of uncontrolled hyperthyroidism. Clinical Case: A 24 year-old Caucasian woman was diagnosed with hyperthyroidism during 1st trimester of pregnancy based labs and was treated with propylthiouracil (PTU) 150 mg bid. At 34 weeks of pregnancy her FT4 normalized and PTU was discontinued. Three and half months post-partum she presented with left frontal headache, photophobia, phonophobia and transient visual loss on the right. Physical exam revealed right homonymous hemianopia without meningismus and an enlarged thyroid. Vitals showed BP 108/57 mm of Hg, HR 162 beats/min, RR of 23/min. CT head without contrast showed 8 mm focal hyperdensity along the left tentorium projecting at the left occipital lobe. She developed seizures after admission. MRI brain with and without contrast showed diffusely small left transverse and sigmoid sinus with a focal area of dural sinus thrombosis. MRI venogram of head confirmed CVT. She was started on levetiracetam and low dose heparin drip. Further workup showed: TSH <0.005 UIU/ml with FT4>8 ng/dl, TSH receptor antibodies 11.10 (normal range 0.00 - 1.75 IU/L), thyroid peroxidase antibody >1300 (normal range <=59 u/ml), and thyroid stimulating antibodies 6.85 (0.00 - 0.55 IU/L) suggestive of Graves disease. She was initiated on PTU 200 mg Q8hrs, propranolol 80 mg Q8hrs and lugol’s iodine 5 drops Q8hrs. Hypercoagulable workup except for protein C and S returned unremarkable. Over the next several days, thyroid levels improved significantly. She was discharged home on warfarin and methimazole. Conclusion: The exact pathophysiology of CVT in hyperthyroidism remains unclear. Some proposed mechanisms include increased activity of pro coagulative plasma constituents including Von Willebrands Factor, Factor IX, X, antithrombin, and fibrinogen as well as an increased aPTT and a decrease in thrombolytic factors like t-PA. These changes result in an increased risk of thrombosis. This case demonstrates the potential development of CVT as a result of untreated overt hyperthyroidism. It highlights the importance of treatment and close follow up of Graves’ disease to prevent severe complications. Further studies need to be done to understand the process of coagulation in hyperthyroidism and this could allow clinicians to better identify hyperthyroid patients at risk for clotting.

Postpartum Thyroid Abnormalities and Systemic Lupus Erythematosus: Is There a Link?

Abstract Introduction: Postpartum Thyroiditis (PPT) is an autoimmune disorder characterized by destruction of the thyroid gland within the first year after delivery. Systemic Lupus Erythematosus (SLE), another autoimmune disease, has been associated with a spectrum of thyroid disorders. While the prevalence of thyroid diseases in patients with SLE is increased, the association between SLE and PPT is not well known. The infrequency of encountering SLE and PPT makes abnormal thyroid tests in the postpartum period a diagnostic challenge. Clinical Case: A 27-year-old G1P1001 who was five months postpartum and not breast feeding was referred to Endocrinology clinic for evaluation of abnormal thyroid function tests. Past medical history was significant for SLE with renal and pericardial involvement. SLE was well controlled, treated with hydroxychloroquine. Family history was significant for hypothyroidism in her mother. She was asymptomatic and appeared clinically euthyroid. Vitals were stable and physical exam was negative for goiter, nodule or orbitopathy. Lab results at two months postpartum showed an elevated TSH of 3.87 UIU/mL (Normal 0.40-3.8 UIU/mL) and at four months postpartum TSH was low at 0.012 UIU/mL. Repeat labs at five months postpartum continued to show a low TSH at 0.007 UIU/mL with mildly elevated Free T4 at 1.7 ng/dL (Normal 0.6-1.6 ng/dL) and elevated Free T3 of 6.0 pg/mL (Normal 2.1-3.8 pg/mL). Anti-thyroid peroxidase antibodies (TPO), thyroid stimulating antibodies (TSI) and TSH receptor antibodies (TRAb) were negative. Thyroid Ultrasound with Doppler was within normal limits. Radioactive Iodine Uptake and Scan, obtained at 6 months postpartum, showed high normal uptake (17% and 32% at 4 hours and 24 hours respectively), suggestive of recovery phase of PPT. The most recent TSH was elevated at 8.5 UIU/mL and Free T4 was low at 0.7 ng/dL. Disease course was consistent with PPT. Conclusion: The Th1 (T-helper) lymphocyte immune predominance in autoimmune thyroid disease and SLE is the immune-pathogenetic base of the association between both diseases. Postpartum thyroiditis is a variant of chronic autoimmune thyroiditis. Serum anti-TPO antibodies vary during pregnancy and tend to increase early and may decline later. Immunologic tolerance increases during pregnancy, fades in the postpartum period and makes interpretation of thyroid function tests and disease process challenging. Pregnant and postpartum patients who have SLE have increased prevalence of thyroid disease. Causes are multifactorial with a higher prevalence of hypothyroidism and thyroid autoantibodies. Hyperthyroidism is much less likely. One comparable study found 6 of 43 (14%) women with SLE developed PPT and only one of these patients had positive thyroid antibodies. These reports and our patient illustrate the variability of thyroid function tests in patients with SLE.

The Grave Hematologic and Hepatic Effects of Hyperthyroidism

Background: Hyperthyroidism can present with a myriad of symptoms including some rare, but morbid systemic manifestations. Here we present the case of a patient who presented with thyrotoxicosis, pancytopenia and cholestatic liver disease. Clinical Case: A 37 year-old Hispanic female with no significant past medical history presented with weight loss, fatigue, jaundice and irregular menstrual cycles ongoing for 10 months. Upon presentation, vitals were notable for mild tachycardia. She had significant jaundice and a visibly enlarged thyroid gland, while no thyroid eye disease was noted. The patient was found to have a hemoglobin level of 6.5 g/dL (12.0 - 16.0 g/dL), white blood cell level of 2.3 K/uL (4.5 - 11.0 K/uL) and platelet count of 82 K/uL (150 - 400 K/uL). Alkaline phosphatase was elevated to 214 U/L (34.0 - 104.0 U/L) and total bilirubin was 8.7 mg/dl (0.2 - 1.2 mg/dL) with direct bilirubin of 5.4 mg/dL (0.0 - 0.2 mg/dL). Thyroid panel revealed an undetectable TSH and a free T4 of 5.58 ng/dL (0.61 - 1.18 ng/dL). Hematological work-up was negative for malignancy but did note severe iron deficiency. Hepatitis B and C virus, parvovirus B19 serology, magnetic resonance cholangiopancreatography, and autoimmune disease work-up all returned normal. Thyroid uptake scan showed diffuse uptake without nodular disease and a 24-hour uptake of 57% (normal 7-32%). Thyroid stimulating antibodies were positive at 115 IU/L (0.00-0.55 IU/L). Since all other work up was negative, it was concluded that her pancytopenia and cholestatic pattern of liver injury were likely due to hyperthyroidism with plan to do a bone marrow biopsy if she does not have improvement in blood cell counts. Patient was treated with radioactive iodine (RAI) ablation. A week after treatment she had further elevation in total bilirubin, whereas her blood counts had improved. It was decided to initiate methimazole with close monitoring of her liver function tests. Two months after treatment, her thyroid function improved and she was eventually transitioned to levothyroxine for post-ablative hypothyroidism. Bilirubin improved to normal range and her pancytopenia resolved without additional intervention. She had complete resolution of jaundice and started having regular menses 2 months after her RAI treatment. Conclusion: The etiology of pancytopenia has been thought to be multifactorial with consumption of nutrients (including iron, manifesting as iron deficiency anemia), stimulation of erythropoiesis and sequestration of blood cells due to splenomegaly. Thyroid associated hepatic dysfunction has been proposed to be secondary to relative hypoxia in the perivenular regions and the direct toxic effect of thyroid hormone on hepatic tissue. In patients with concurrent hepatic disease and thyrotoxicosis, it is reasonable to consider treatment with thionamides with close monitoring, if other etiologies for hepatic disease are ruled out.