Positive Thyroid-stimulating Immunoglobulin Research Articles

8581 Unusual Case of Multifactorial Hyperthyroidism

Abstract Disclosure: D.D. Bagar: None. E. Meyers: None. M. Correia: None. Background: Nivolumab is an immune checkpoint inhibitor that is used to treat specific types of cancer, including melanoma, by increasing the ability of the immune system to detect cancer through activating cytotoxic T-cells. The side effects of immune checkpoint inhibitors are mainly through the overactivation of the immune system that can affect many organs with autoimmune diseases, including endocrine glands, which could be severe and irreversible, like hypothyroidism or immune thyroiditis. The uniqueness of this case is the presence of multifactorial causes of hyperthyroidism; in addition, it is one of the few cases of immune checkpoint inhibitor induced positive TSI thyroiditis.Clinical Case: An 82-year-old male with a known history of atrial fibrillation on amiodarone presented to his dermatologist with a left forearm lesion. A shave biopsy showed melanoma, and he underwent wide local excision with negative sentinel lymph node biopsy. However, he had significant melanoma in situ present within 5 mm of the margin and was deemed not a candidate for further excision. Tumor board recommended close surveillance. He then received two cycles of pembrolizumab for one year, followed by nivolumab. During his treatment course, he had CT scans with iodinated contrast every 8-12 weeks for the clinical trial. At his clinic visit, routine thyroid function tests were significant for hyperthyroidism with a TSH <0.01 and free T4 of 6.07 (0.8-1.8). He was asymptomatic except for unintentional weight loss. He denied using any biotin supplements. His labs also showed positive thyroid stimulating immunoglobulin (TSI) of 1.10 (<=0.54 IU/L). A thyroid US with doppler showed two nodules less than 1.1 cm and no increased vascularity. Amiodarone was discontinued, and prednisone and methimazole were started. His free T4 has since normalized and both prednisone and methimazole are being tapered down. Conclusion: This case is a multifactorial cause of hyperthyroidism. He had been using amiodarone for atrial fibrillation, had multiple imaging studies with iodinated contrast, and was on immune checkpoint inhibitor therapy with a positive TSI. The uniqueness of this case is not only that combined factors can affect thyroid function but also that he developed a positive TSI, which indicates either Graves’ disease or immune-induced thyroiditis by nivolumab, which has been reported only in a few cases. Presentation: 6/3/2024

8581 Unusual Case Of Multifactorial Hyperthyroidism

Abstract Disclosure: D.D. Bagar: None. E. Meyers: None. M. Correia: None. Background: Nivolumab is an immune checkpoint inhibitor that is used to treat specific types of cancer, including melanoma, by increasing the ability of the immune system to detect cancer through activating cytotoxic T-cells. The side effects of immune checkpoint inhibitors are mainly through the overactivation of the immune system that can affect many organs with autoimmune diseases, including endocrine glands, which could be severe and irreversible, like hypothyroidism or immune thyroiditis. The uniqueness of this case is the presence of multifactorial causes of hyperthyroidism; in addition, it is one of the few cases of immune checkpoint inhibitor induced positive TSI thyroiditis.Clinical Case: An 82-year-old male with a known history of atrial fibrillation on amiodarone presented to his dermatologist with a left forearm lesion. A shave biopsy showed melanoma, and he underwent wide local excision with negative sentinel lymph node biopsy. However, he had significant melanoma in situ present within 5 mm of the margin and was deemed not a candidate for further excision. Tumor board recommended close surveillance. He then received two cycles of pembrolizumab for one year, followed by nivolumab. During his treatment course, he had CT scans with iodinated contrast every 8-12 weeks for the clinical trial. At his clinic visit, routine thyroid function tests were significant for hyperthyroidism with a TSH <0.01 and free T4 of 6.07 (0.8-1.8). He was asymptomatic except for unintentional weight loss. He denied using any biotin supplements. His labs also showed positive thyroid stimulating immunoglobulin (TSI) of 1.10 (<=0.54 IU/L). A thyroid US with doppler showed two nodules less than 1.1 cm and no increased vascularity. Amiodarone was discontinued, and prednisone and methimazole were started. His free T4 has since normalized and both prednisone and methimazole are being tapered down. Conclusion: This case is a multifactorial cause of hyperthyroidism. He had been using amiodarone for atrial fibrillation, had multiple imaging studies with iodinated contrast, and was on immune checkpoint inhibitor therapy with a positive TSI. The uniqueness of this case is not only that combined factors can affect thyroid function but also that he developed a positive TSI, which indicates either Graves’ disease or immune-induced thyroiditis by nivolumab, which has been reported only in a few cases. Presentation: 6/3/2024

8578 Papillary Thyroid Carcinoma in Autonomous Nodule with Low Risk Characteristics in Adolescent

Abstract Disclosure: A. Aponte Velez: None. M.M. Mangual Garcia: None. Thyroid nodules in children are uncommon but are known to carry a greater risk of malignancy than adult thyroid nodules. Additionally, differentiated thyroid cancer (DTC) in children is more commonly found with extrathyroidal extension and metastases which makes the approach and treatment similar but with important differences. The incidence of DTC in children is increasing, making a personalized evaluation of thyroid nodules in pediatric patients even more valuable. Guidelines recommend evaluation of nodules based on sonographic characteristics rather than size of nodule. However, not having worrisome sonographic characteristics may not be as reassuring as in adult patients. A 13 year old female patient presented with a palpable non tender right sided solid thyroid mass. She had no family history of thyroid cancer or history of irradiation. Thyroid function tests were remarkable for TSH:0.017 and positive thyroid stimulating immunoglobulin. Thyroid Ultrasound findings described heterogenous parenchyma with multiple discrete lesions on right thyroid lobe with a dominant solid isoechoic nodule at upper lobe measuring 2.1 x 3.5 x 1.9cm and a smaller nodule in lower lobe. Thyroid scan demonstrated a large functional hot nodule occupying most of right thyroid lobe with suppression of rest of thyroid parenchyma. Ultrasound guided FNA was performed of this lesion and results were negative for malignancy. Patient underwent total thyroidectomy with pathology report revealing right thyroid nodule encapsulated classical variant of papillary thyroid carcinoma. No lymph node metastases were identified. Non neoplastic thyroid parenchyma revealed chronic lymphocytic thyroiditis. Patient underwent radioiodine therapy with Whole Body Scan post radioiodine therapy demonstrating focal increased radionuclide localization at in region of neck consistent with functional thyroid tissue. There was no evidence of metastatic disease. In children, risk of malignancy is underestimated in ultrasonography and cytology. In this patient, papillary thyroid carcinoma was identified despite being stratified as having low risk of malignancy based on ultrasonography characteristics, hyperfunctioning nodule in scintigraphy study along with negative FNA results. Hyperfunctional nodules are usually reassuring for low risk of malignancy but rarely DTC can be found as in our patient. Guidelines agree that FNA is not recommended in functional nodules as surgical resection is the main therapy in children. However, surgery may be deferred if subclinical hyperthyroidism and low risk sonographic characteristics are present such as in our patient. If surgery had been deferred, based on low risk of malignancy, the risk of progression of disease would have been higher. Prognosis of DTC in children is good but the recurrence rate along with morbidity at such a young age may improve with more studies of DTC in children. Presentation: 6/2/2024

9188 Hashitoxicosis To Graves': A Case Of Fluctuating Thyroid Autoimmunity Induced By The Covid Vaccine

Abstract Disclosure: K. Lamar: None. N. Meda: None. J. Straughan: None. D. John: None. S.K. Suryanarayanan: None. Introduction: Thyroid antibodies are essential for identifying autoimmune thyroid disease. In Graves' disease thyroid stimulating immunoglobulin (TSI) is crucial to diagnosing, guiding treatment, and determining prognosis for ophthalmopathy; thyroid peroxidase (TPO) antibody is likewise crucial in the diagnosis of Hashimoto’s Thyroiditis. Conversion between these two diseases is extremely rare. Case: The patient is a 60-year-old female with a medical history of hypertension, asthma, T2NxM0 low grade gastrointestinal stromal tumor (GIST), and hyperaldosteronism who was referred to the endocrine clinic for “thyroid disorders'' with symptoms including weight gain and palpitations. Her labs showed thyroid stimulating hormone (TSH) <0.01mIU/L, free Triiodothyronine (fT3) 6.5ng/mL, free Thyroxine (fT4) 1.6ng/dL, TPO antibodies 46IU/mL, negative TSI antibodies 102%, and a negative Thyroglobulin antibody (Tg Ab) <1IU/mL. A slightly enlarged thyroid was noted on ultrasound. Radioactive iodine uptake (RAI) was normal with 15% uptake at 6 hours and 25% at 24 hours. These findings led to the diagnosis of Hashimoto thyrotoxicosis. She started methimazole 10mg and atenolol 50mg. One year later, she received the Pfizer mRNA COVID-19 vaccine and had her GIST tumor resected. She then began switching between hyper-, hypo-, and euthyroid states with multiple titrations of her Methimazole dose. Repeat testing demonstrated a positive TPO 41 IU/mL, negative Tg Ab <1, positive TSI 294%, and positive RAI with 47% uptake at 6 hours and 61% at 24 hours, consistent with Graves’ disease. It was found that even minor titration by 2.5mg in her Methimazole led to profound changes in her thyroid laboratory values and symptoms. She underwent total thyroidectomy and was started on levothyroxine with significant improvement. Discussion: This patient initially presented with antibodies as well as low uptake on the radio-iodine scan indicating her state of hyperthyroidism was due to Hashitoxicosis, but then later these tests were repeated and were more indicative of Grave’s disease. This was possibly due to immune challenges in the patient, assay inter-variability of thyroid autoantibodies, or an effect of the patient receiving the COVID vaccine. The phenomenon of TSI antibodies converting from negative to positive has not been well documented previously. The goal of this case was to report an interesting conversion of Grave’s disease identifying antibodies and the importance of evaluating underlying immune challenges which could play a role in altering clinical disease. Presentation: 6/1/2024

7081 A Spotlight on Marine Lenhart Syndrome

Abstract Disclosure: R. Alshantti: None. A.M. San Hernandez: None. J. Wu: None. C.P. Barsano: None. M.F. Siddiqui: None. Introduction: Marine-Lenhart Syndrome is a rare condition with a prevalence of 0.8-4.1% of cases with Graves’ disease. It is defined by the coexistence of Graves’ disease and autonomously functioning thyroid nodule(s). It is an under-recognized cause of hyperthyroidism. A limited number of cases have been reported in the literature. We report an interesting case of Marine-Lenhart Syndrome characterized by the presence of elevated thyroid stimulating immunoglobulins (TSI) and an autonomous right thyroid nodule. Case Description: A 37-year-old man with a history of hyperthyroidism from Graves’ disease and a right thyroid nodule was referred to endocrinology clinic. He was diagnosed with hyperthyroidism in 2015 at an outside facility. He had elevated thyroid stimulating immunoglobulins (TSI) and a 2.9 cm right thyroid nodule which was biopsied and had benign cytopathology. Hyperthyroidism was treated with methimazole (MMI) but without subsequent remission of Graves’ disease. He ran out of MMI and re-presented with symptomatic hyperthyroidism with fatigue, tremors, and hyperdefecation. There was no ocular involvement or thyroid compressive symptoms. Biochemical work up was consistent with uncontrolled hyperthyroidism (suppressed TSH 0.01 uIU/mL [Ref range: 0.45-5.33], and elevated FT4 2.58 ng/dl [Ref range: 0.70-2.20], elevated free T3 8.7 pg/ml [Ref range: 2.5-3.9], and mildly elevated TSI 0.72 IU/L [Ref range: 0.54 or less]. MMI was therefore reinitiated. Thyroid Uptake scan demonstrated an increased focal 24-hour Iodine-131 uptake of 57% in the right lobe with suppression of the left lobe. Thyroid ultrasound support the finding of large right thyroid nodule (2.3 x 2.4 x 3.9 cm) with diffuse heterogeneous thyroid. The presence of TSI, lack of control of hyperthyroidism for more than 2 years of treatment, and presence of a functioning thyroid nodule raise the suspicion of Marine-Lenhart Syndrome. Indeed, the findings of an autonomously functioning right thyroid nodule with concomitant Graves’ disease establish the diagnosis of Marine-Lenhart Syndrome. The option of RAI ablation vs total thyroidectomy was discussed with the patient. The patient opted for thyroidectomy. Conclusion: Based on studies, approximately 35% of patients with Graves’ disease have thyroid nodule(s) and only 2.7% are functioning adenomas. The combination of positive TSI or TrAb and functioning thyroid nodules has been termed Marine-Lenhart syndrome. The syndrome was named after David Marine and Carl Lenhart who initially described it in 1911. Unlike Graves’ disease, patients with Marine-Lenhart Syndrome have a lower remission rate with thioamides, require definitive treatment with RAI ablation at a high dose or total thyroidectomy, and may easily be misdiagnosed by many endocrinologists. Presentation: 6/2/2024

FRI557 Don’t Forget The Incidental Thyroid Nodule In Graves’ Disease. A Case of Marine-Lenhart Syndrome

Abstract Disclosure: K.N. Andino-Lebrón: None. A. Martinó-Morales: None. J.M. Colón-Castellano: None. Marine-Lenhart syndrome (MLS) was initially described by Charkes in 1972 as he observed patients with Graves’ disease (GD) and incidental functioning thyroid nodules. He named the disease Marine-Lenhart syndrome based on a paper published by Marine and Lenhart in 1911. MLS is a variant of GD now described as the coexistence of GD and autonomous functional thyroid nodules (AFTN); thus, patients present with thyrotoxicosis due to GD and AFTN. MLS is very rare, and prevalence is estimated to be around 0.8%-2.7%. Here, we present a case of MLS in a 79-year-old female. A 79-year-old Hispanic woman with history of breast metaplasia s/p chemoprevention with tamoxifen for 5 years, atrial premature contractions on metoprolol, among other medical conditions was referred to Endocrinology clinics by her primary care physician (PCP) because of abnormal thyroid function tests and ultrasound. She reported feeling anxious with associated palpitations, she denied weight loss. Physical examination was remarkable for regular rate and rhythm, no goiter, no palpable nodules, no proptosis, and deep tendon reflexes +1. Laboratory testing revealed a suppressed TSH of 0.224 uIU/mL, normal free T4 at 1.17 ng/dL, normal total T3 at 142.5 ng/dL, and positive thyroid stimulating immunoglobulins at 345%. Thyroid ultrasound showed a normal size gland with multiple complex nodules. In the right lobe there was a mixed cystic and solid nodule, measuring 1.48x1.21x1.71cm, wider than tall, with internal vascularity and punctate calcifications. In the left lobe there was an isoechoic and solid nodule measuring 0.7x0.5x0.7cm, wider than tall, without calcifications. Thyroid uptake scan with SPECT-CT demonstrated a focus of increased tracer uptake on the upper pole of the right thyroid lobe that corresponds to the one found on CT scan and a diminished and nonuniform uptake of the tracer in the reminders of the thyroid gland. The 24-hour radioactive iodine uptake was 17.5%. Diagnosis of MLS was made, and the patient was started on methimazole 5mg daily, which she has been tolerating well. Follow up laboratories show a biochemically euthyroid state. Marine-Lenhart syndrome is a rare entity of Graves’ disease which is currently defined as GD and accompanying functioning nodule(s). To establish the diagnosis, it is important the evaluation with scintigraphy and autoimmune testing. Multiple treatment options are available and patients with GD should be evaluated for the presence of thyroid nodules and their functional status to achieve optimal therapy. Patients with GD have a chance of remission when treated with antithyroid drugs. Due to the pathophysiology of AFTN, patients with MLS (concurrent GD and AFTN) have lower remission rates with antithyroid drugs and may require definitive management therapy with radioactive iodine or surgery. Presentation: Friday, June 16, 2023

A-052 The Importance of Thyroid-stimulating Immunoglobulin (TSI) in the Diagnosis and Follow-up of Marine-Lenhart Syndrome

Abstract Introduction Marine-Lenhart syndrome is a rare cause of hyperthyroidism, occurring in 0.8%–2.7% of patients with Graves’ disease (GD). In this syndrome, GD, which is an autoimmune disease, coexists with one or more hyperfunctioning nodules—Toxic nodular goiter (TNG), or toxic multinodular goiter (TMNG)—which are usually thyroid adenomas. Both induce clinical hyperthyroidism, with suppressed thyroid-stimulating hormone (TSH) and elevated thyroid hormones (TH). Radioactive iodine uptake and thyroid scintigraphy are indicated when there is a nodule on ultrasonography (US) with suppressed TSH, for the differential diagnosis between GD and toxic nodules. However, in this syndrome, scintigraphy does not always define the diagnosis, as the aspects observed do not show the usual pattern. In these cases, it is necessary that a reliable autoimmune thyroid disease marker be performed in order to prove the concomitant autoimmunity. Objectives The aim of this study was to demonstrate the usefulness of thyroid-stimulating immunoglobulin (TSI) for diagnosing hyperthyroidism due to Marine-Lenhart syndrome. Methods The authors prospectively followed 19 patients with suspected Marine-Lenhart syndrome between 2018 and 2020. TSH and TH were measured by Electrochemiluminescence, Roche Diagnostics, and TSI was measured by Chemiluminescence, Siemens Diagnostics. Results All patients had TSH ≤ 0.01 mIU/L, free thyroxine (FT4) was 3.1 ± 0.9 ng/dL, and triiodothyronine (TT3) 312 ± 42.1 ng/dL. All of them had increased radioactive iodine uptake, but the scintigraphy showed nodules sometimes with increased, normo, or low uptake in relation to the adjacent tissue, a finding that is explained by the fact that, both, the nodule and the rest of the thyroid tissue, uptake the radioidine in excess and the pattern varies according to the activity of the DG and nodules in the period in which the test was performed. TSI was 3.98 ± 0.9 IU/L (Negative if <0.55). All patients had positive TSI, confirming concomitant GD with TNG/TMNG. During treatment monitoring, in 14 cases the hyperfunctioning nodules were treated by local sclerosis procedure, with percutaneous injection of ethanol. Despite complete nodular sclerosis, with normal TH but still suppressed TSH, the TSI still remained elevated. This demonstrated that, despite the successful treatment of the nodule, the underlying GD was still active, requiring complementary treatment with antithyroid drugs until TSI was negative, after 18 ± 4 months of treatment. Conclusion In atypical cases of hyperthyroidism, the TSI measurement is decisive for the diagnosis, as in the rare Marine-Lenhart syndrome. This contributes in a relevant way to the definition of the treatment, which can be different between the two causes that occur concomitantly. Likewise, during treatment follow-up, the TSI was essential in defining the need to maintain clinical treatment, even if the nodule had been already adequately treated.

ODP518 Three Cases of Autoimmune Thyrotoxicosis after the BNT162b2 mRNA Covid-19 Vaccine

Abstract Background Various vaccines have been produced around the world in the battle against coronavirus disease 2019 (COVID-19) in the past year. Clinical trials and approvals of these vaccines were expedited at an unprecedented speed, with some of them approved under emergency use. Since March 2021, government coordinated vaccination program using two types of vaccines against COVID-19 were being undertaken in Hong Kong. BNT162b2 mRNA COVID-19 vaccine under the name of BioNTech was one. While it is a promising measure to control COVID-19, the new mRNA vaccine technology does cast some doubts, particularly its safety. In addition to the commonly reported injection site reactions and systemic upsets, less reported reactions after this new vaccine requires more clarifications. Here, we report 3 cases of autoimmune thyrotoxicosis all happened soon after the vaccination. Clinical Cases: Case1 A 40-year-old man with family history of thyroid cancer (mother had thyroid cancer with operation done) developed palpitations 17 days after receiving the first dose of BioNtech vaccine. Investigations confirms Graves’ thyrotoxicosis as evidenced by elevated fT4 and suppressed sTSH with positive thyroid stimulating immunoglobulin (TSI) and a diffuse vascular goiter on ultrasound (USG) thyroid. He was started on a course of anti-thyroid drug and had been advised to defer the second dose of vaccine until clinically stable. Case2 A 44-year old lady without personal/family history of thyroid disease developed progress neck swelling and palpitation with tremor 3 days after receiving the first dose of BioNtech vaccine. Investigations confirmed Graves’ thyrotoxicosis with elevated fT4 and suppressed sTSH with positive TSI, anti-TPO, and anti-ATG. USG thyroid showed diffuse vascular goiter. She was treated with a course of anti-thyroid drug and had been advised to defer the second dose of vaccine until stabilization of thyroid function. Case3 A 56-year-old man with positive family history of thyrotoxicosis (elder brother with history of thyrotoxicosis treated with radioactive iodine) developed progressive weight loss, increased appetite, insomnia, palpitation, and tremor around 7 days after the first dose of BioNtech vaccine. Patient only presented to an Endocrinologist for further workup 63 days after the first dose (42 days after second dose of BioNtech). Biochemically he had high fT4, suppressed sTSH, with positive anti-ATG, anti-TPO and TSI. USG thyroid revealed a small diffuse goiter. He was treated with a course of anti-thyroid drug with regular follow-up and monitoring. Conclusion This is the first case-series in Hong Kong demonstrating the possible triggering of Graves’ thyrotoxicosis after BioNTech vaccination. TSI and USG thyroid are invaluable tools to confirm the autoimmunity nature of the disease. Further studies are needed to clarify the prevalence, mechanisms, preventions, and treatments of this vaccine complication. Presentation: No date and time listed

ODP533 Graves’ Ophthalmopathy in the Setting of Primary Hypothyroidism

Abstract Background Graves’ ophthalmopathy (GO) is commonly associated with hyperthyroidism secondary to Graves’ disease (GD). Although rare, there have been case reports of it occurring in patients who are hypothyroid with underlying Hashimoto's thyroiditis (HT), as well as in euthyroid patients. It is thought that the mechanism behind developing GO in these patients is due to the presence of stimulating thyrotropin receptor antibodies (TRAB). Below we describe a case of GO developing in a patient who has hypothyroidism secondary to HT. Clinical Case A 53 years-old female non-smoker, known to have primary hypothyroidism (Hashimoto's thyroiditis) diagnosed at the age of 39 years, on levothyroxine 75 mcg/day. Presented to our endocrine clinic complaining of diplopia and periorbital swelling for the past 5 months. The diplopia occurs on left gaze while both eyes are open, it resolves with closure of either eye. No history of ocular surgeries, injections, or trauma. No previous hyperthyroid state or radioactive iodine therapy. On physical examination there was no goiter, bruit, palpable lymphadenopathy, tremor, or pretibial myxedema. Ophthalmic examination showed left sided upper and lower eyelid swelling, limited abduction with diplopia and mild punctate keratopathy. Laboratory investigation revealed TSH 3.6 mIU/L (0.250 - 5), T4 14.6 pmol/L (11.5 - 22.7), positive thyroid peroxidase antibody 173.9 units (> 100 units positive) and positive thyroid stimulating immunoglobulin 500IU/ml (Normal < 140). On ultrasound the thyroid gland was small and heterogeneous. MRI orbits demonstrated bilateral ocular proptosis with intraocular muscles enlargement particularly the medial, inferior, superior rectus as well as the levator palpebrae superioris muscles. Our impression was active moderate-severe isolated GO with aBackground of HT, clinically and biochemically euthyroid on levothyroxine. The patient was referred to an ophthalmologist and was started on a course of high dose oral prednisone tapered over 3 months. She reported a 50% improvement in her symptoms after the first month of therapy. Patient was then started and maintained on selenium 100 mcg oral twice daily with lubricating eyedrops. During her last clinic visit she had stable thyroid eye disease and there was no need for further medical or surgical intervention. Conclusion GO can occur in patients with HT due to the development of stimulating TRAB targeting thyrotropin receptors expressed on orbital fibroblasts. The incidence varies between studies from 2-7.5%. Awareness of this clinical presentation is important, as early detection and treatment can prevent visual complications. To date there are no clear guidelines on how to treat GO with underlying HT. Treating our patient with high dose steroids extrapolated from treating GO secondary to GD showed significant improvement in her symptoms. Presentation: No date and time listed

ODP447 A Case of Hidden Grave's After Total Thyroidectomy

Abstract Introduction A Sub-sternal goiter is a condition where there is an abnormal enlargement of thyroid gland that extends into the chest. The most commonly accepted definition is when >50% of the volume of a goiter extends into the thoracic inlet. We present an interesting case of a Sub-sternal goiter emerging as a cause of Grave's disease, years after Total Thyroidectomy. Clinical Case The Patient is a 75 year old female with PMH of endometrial cancer, who initially underwent total thyroidectomy due to Thyromegaly causing dysphagia, and was started on Levothyroxine therapy after surgery. Three years later, a sub-sternal mass, was incidentally found via CT chest, which measured 3.7cm in largest diameter. Nuclear Medicine uptake and scan confirmed thyroid origin of this mass with an increased uptake but no percentage uptake was provided. Patient's Thyroid functions tests remained within normal range on levothyroxine. But over the next 2 years,the patient needed declining doses of LT4, then became euthyroid, off of levothyroxine and eventually became hyperthyroid, with positive Thyroid stimulating immunoglobulin. She also developed symptoms of tremors and tachycardia, and developed Atrial fibrillation as well. Noophthalmopathyor dermopathy was found on exam. Repeat CT chest showed the sub-sternal goiter had increased to a partially calcified mass of 5.6 cm. NM uptake scan showed 38.6%, at 24 hour, generalized uptake of this mass. Radioactive Iodine Ablation was performed with 30.1mCi and she subsequently became hypothyroid again until 1 year ago when she had episodes of A-fib again, and was found with TSH of 0. 09(0.45-5.33mIU/L) and FT40.9 (0.6- 1.2 ng/dl) and free T3 of 6.4 (pg/dl), off of levothyroxine. NM uptake and scan was repeated which indicated recurrence of Grave's disease from the same source. The Patient chose to initiate Methimazole therapy while contemplating surgical resection. Clinical Lesson: This is a unique case of Sub-sternal goiter, presenting as grave's disease, years after total thyroidectomy. This case emphasizes on the importance of identifying and treating sub-sternal goiter, as it can cause severe Grave's disease and thyrotoxicosis. Especially in this case, since Grave's caused by this sub-sternal goiter was recurrent after Radioactive iodine ablation. Presentation: No date and time listed

Graves disease in infancy: a patient presentation and literature review.

SummaryWe describe a case of an infant who presented with clinical features of hyperthyroidism. The child was found to be tachycardic, hypertensive and diaphoretic, she was noted to have poor weight gain and difficulty in sleeping. The child was admitted to the pediatric intensive care unit for care. She was found to have biochemical evidence of hyperthyroidism with positive thyroid stimulating immunoglobulin. She responded well to methimazole and propranolol and had a remarkable recovery. She is the youngest patient to be diagnosed with Graves disease in the English literature, at 12 months of life.Learning pointsHyperthyroidism must always be considered even at very young age, for patient presenting with poor weight gain and hyperdynamic state.Autoimmune diseases are becoming more common in infancy.Craniosynostosis and increased height for age are well-documented consequences of untreated hyperthyroidism in developing children.

Thyrotoxicosis: A Primary Cause of Arrhythmias and Acute Heart Failure

Thyrotoxicosis results from excessive thyroid hormone and may occur in Graves’ disease, multinodular goiter, and thyroiditis. The association of hyperthyroidism with the worsening of pre-existing heart disease is very well recognized. Additionally, hyperthyroidism can also cause primary cardiac disease including arrhythmias and congestive heart failure. We present a 65-year-old female with a past medical history of intermittent palpitations who came to the emergency department with shortness of breath and bilateral lower extremity swelling. Physical exam revealed an anxious woman with bilateral proptosis, jugular venous distention, bibasilar crackles, and bilateral lower extremity edema. Laboratory data was significant for a brain natriuretic peptide level of 1,930. Chest x-ray revealed vascular congestion. Transthoracic echocardiogram showed an ejection fraction of 63% and diastolic dysfunction. She was admitted and received diuretics for acute heart failure. She developed atrial fibrillation with a rapid ventricular response, managed with a diltiazem infusion and anticoagulation. This event prompted thyroid evaluation which showed a thyroid-stimulating hormone (TSH) of 0.01mU/L, elevated free T4 at 3.37ng/dl, free T3 at 5.8pg/ml, positive Thyroid-stimulating immunoglobulins (TSI) 473%, and thyroid peroxidase (TPO) antibodies 158U/ml. Her symptoms improved after treatment with methimazole. The heart is susceptible to hyperthyroidism due to multiple thyroid hormone receptors on cardiac myocytes causing high sympathetic stimulation from an increased number of myocardial beta-cell receptors. Atrial fibrillation occurs in 10 to 20% of patients with hyperthyroidism and is prevalent among the elderly population. People 60 years and above with a low serum thyrotropin concentration are at a threefold higher risk of developing atrial fibrillation in the subsequent decade. Complications such as cerebrovascular accidents occur in about 14% of cases. About 6% of thyrotoxic individuals develop heart failure secondary to a tachycardia mediated mechanism, leading to an increased level of cytosolic calcium during diastole. This causes reduced ventricular contractility and diastolic dysfunction, often associated with tricuspid regurgitation. Graves’ disease is an autoimmune process characterized by hyperthyroidism due to circulating autoantibodies. TSI binds to and activates thyrotropin receptors, causing the increased synthesis of thyroid hormones. If left untreated, Graves’ disease can lead to severe thyrotoxicosis. Clinicians should be aware of this disease association and ensure thorough clinical investigation, prompt diagnosis, and treatment of thyrotoxicosis to avert these life-threatening events.

Graves’ Thyrotoxicosis and Fulminant Myopericarditis: A Clinical Dilemma!

Abstract Myocarditis is a rare presentation of Graves’ disease, fulminant myocarditis is even rarer. We report a woman with Graves’ disease with fulminant myopericarditis as the presenting clinical feature. A 23-year-old healthy woman presented with acute onset pleuritic chest pain, palpitations, diaphoresis, heat intolerance, and dyspnea. There was no history of fever, upper respiratory tract infection, diarrhea, or weight loss. Physical exam revealed sinus tachycardia and palpable non-tender thyroid. Blood work was pertinent for TSH <0.01uIU/ml(0.3-4.5), free T4 2.8ng/dl(0.6-1.5), free T3 > 32.6pg/ml (2.4-4.2) and positive TSI (thyroid-stimulating immunoglobulin) 12.4 IU/L (<0.54). She had a diffusely enlarged vascular thyroid on ultrasound, all findings consistent with hyperthyroidism due to Graves’ disease. Electrocardiogram showed sinus tachycardia with diffuse PR depression and ST-segment elevation, troponin was 0.85 which increased to 17.5 within 12 hours, an echocardiogram showed normal ejection fraction (EF) with mild pulmonary hypertension but no pericardial effusion. She improved symptomatically with beta-blockers, methimazole, and colchicine but unfortunately had a witnessed ventricular fibrillation cardiac arrest in the next 12 hours with return to spontaneous circulation achieved after 90 minutes of bystander cardiopulmonary resuscitation. Coronary angiogram revealed normal coronaries with post-cardiac arrest EF of 5%. She subsequently developed acute respiratory distress syndrome secondary to massive pulmonary hemorrhage requiring extracorporeal mechanical support for worsening cardiogenic shock, succumbing to her illness a few hours later. Graves’ disease affects 0.5% of the population and causes hyperthyroidism in 50-80% of cases. Thyrotoxicosis may be associated with supraventricular arrhythmias and cardiomyopathy due to long-standing untreated hyperdynamic heart failure, but myopericarditis is an unusual presentation of Graves’ thyrotoxicosis with fulminant myopericarditis being even rarer. Fulminant myocarditis can present with ventricular tachyarrhythmias and can rapidly deteriorate into shock which may be difficult to distinguish from other causes of cardiogenic shock such as acute coronary syndromes or stress-induced cardiomyopathy. Myopericarditis associated with Graves’ is thought to be due to autoimmunity against functional TSH receptors identified in human cardiomyocytes. Fulminant myocarditis is a common cause of sudden cardiac death in young healthy adults, which is also the same population that gets Graves’ disease. It is critical to recognize the unusual presenting features of Graves’ disease such as fulminant myopericarditis, as timely aggressive intervention can reduce the risk of sudden cardiac death.

A Case of Thyrotoxic Periodic Paralysis

Introduction: Thyrotoxic periodic paralysis (TPP) is an uncommon disorder characterized by simultaneous thyrotoxicosis, hypokalemia, and paralysis. It is a rare complication of hyperthyroidism with a prevalence of 1 in 100,000. It has a higher prevalence in young Asian males, with much fewer cases reported in Hispanic patients. The majority of cases are seen in hyperthyroidism due to Grave’s disease, however other causes of thyrotoxicosis have been associated with TPP. Hypokalemia occurs when thyroid hormone stimulates the sodium-potassium-ATP pump by binding to the thyroid response elements upstream of the genes for this pump, increasing its activity and thereby causing a transcellular shift of potassium into the intracellular fluid. Attacks usually begin with proximal muscle weakness of the lower extremities and may progress to tetraplegia, with the degree of muscle weakness corresponding to serum potassium levels. Interestingly, no correlations with serum T3 or T4 levels have been found.Clinical Case: A 38-year-old Hispanic man with a history of GERD presented to the emergency department with an inability to move his extremities. Initial labs were significant for profound hypokalemia to 2.0 mEq/L (3.5-5) and hyperthyroidism, with TSH<0.05 uU/mL (0.3-4.2) and free T4 2.4 ng/dL (0.6-1.5). Additional workup revealed a positive thyroid stimulating immunoglobulin and a positive thyrotropin binding inhibitor, and thyroid ultrasound demonstrated a hyperemic thyroid with numerous subcentimeter hypoechoic nodules, all of which was suggestive of Grave’s disease. His symptoms resolved with potassium repletion, suggesting thyrotoxic periodic paralysis secondary to hyperthyroidism. Upon further evaluation, the patient endorsed several months of hyperthyroid symptoms such as tremors, heat intolerance, and weight loss. He also endorsed alcohol use, a high carbohydrate diet, and recent life stressors, a combination of which likely precipitated his thyrotoxic periodic paralysis. He was discharged on methimazole 10 mg daily and propranolol 40 mg BID, with a decrease in his free T4 and improvement in his symptoms. He has been educated to avoid alcohol consumption and high-carbohydrate meals to avoid precipitating another episode of periodic paralysis, and once his hyperthyroidism is under better control he plans to undergo radioactive iodine ablation (RAI) for definitive management.Conclusions: Thyrotoxic periodic paralysis is a rare but dangerous complication of hyperthyroidism, and should be considered in the differential diagnosis when young individuals present with otherwise unexplained hypokalemia and paralysis. Acute management is potassium repletion, long term management involves treatment of thyrotoxicosis and avoiding precipitating factors, and definitive therapy is RAI or thyroidectomy.

The prognostic value of thyroid-stimulating immunoglobulin in the management of Graves' disease.

Background:The bioassay of thyroid-stimulating immunoglobulin was reported to have a similar performance to the commonly used thyroid-stimulating hormone binding inhibition assay, also known as thyroid receptor antibody assay. The normal reference range of thyroid receptor antibody levels indicates the withdrawal of anti-thyroid drugs in the recent clinical guidelines.Methods:A prospective, longitudinal observational study was conducted to evaluate the prognostic value of thyroid-stimulating immunoglobulin in patients with Graves’ disease.Results:A total of 77 patients with Graves’ disease treated with anti-thyroid drugs were in a continuous follow-up until 1 year after anti-thyroid drugs discontinuation. Commercial kits of thyroid-stimulating immunoglobulin and M22-thyroid-stimulating hormone binding inhibition assay were used and compared. Thyroid-stimulating immunoglobulin was all negative in healthy controls, Hashimoto thyroiditis, and subacute thyroiditis. Thyroid-stimulating immunoglobulin value was highest in untreated patients with Graves’ disease (p < 0.001). Under anti-thyroid drugs treatment, thyroid-stimulating immunoglobulin value decreased gradually. A total of 21 patients had positive thyroid-stimulating immunoglobulin at the end of treatment. According to clinical fate of patients with Graves’ disease after withdrawal of anti-thyroid drugs, thyroid-stimulating immunoglobulin value and positivity in patients with relapse were significantly higher than that reported in patients with remission (p = 0.001, p < 0.001). After adjustment for age, gender, initial thyroid receptor antibody, initial thyroid-stimulating immunoglobulin, and thyroid receptor antibody at the end of treatment, the odds ratio of positive thyroid-stimulating immunoglobulin for the risk of relapse was 33.271 (95% confidence interval: 4.741–233.458, p < 0.001) and odds ratio of quantitative thyroid-stimulating immunoglobulin was 1.009 (95% confidence interval: 1.002–1.015, p < 0.001).Conclusion:Thyroid-stimulating immunoglobulin is a good predictor of relapse in patients with Graves’ disease treated with anti-thyroid drugs. It might be safer to discontinue anti-thyroid drugs when thyroid-stimulating immunoglobulin and thyroid receptor antibody were both negative.

SAT-588 Unique Presentation of Postpartum Thyroiditis with Features of Graves' Disease

Introduction - Postpartum thyroiditis (PPT) is a rare medical condition occurring after pregnancy. Postpartum thyroiditis is a syndrome of transient or permanent thyroid dysfunction occurring in the first year after delivery. It can present as clinical thyrotoxicosis, followed by hypothyroidism and subsequent recovery of thyroid function or it may present as an isolated thyrotoxicosis or hypothyroidism. An estimated 20-40% of women develop permanent hypothyroidism; usually during the 3 to 10 year interval following an episode of PPT. PPT is the most common thyroid disease in the postpartum period with an incidence between 5-9%. The condition is most common in patients with positive thyroid antibodies (TPO), type 1 diabetes or prior history of PPT. We present a unique case of postpartum thyroiditis with postpartum hyperthyroidism, with markers of Graves’ disease, in a patient with a maternal history of Graves’ disease. Case description - An 18 year old female, without prior medical history, presented with thyrotoxicosis following delivery of her first child. Initially, she responded to therapy with propranolol; however, when her thyroid function became increasingly symptomatic, therapy was augmented with methimazole. Methimazole was selected because of the corresponding clinical features of Graves’ disease coupled with a positive thyroid stimulating immunoglobulin (TSI = 431) and family history of Graves’ disease. Thyroid scan and uptake showed homogenous thyroid without discrete nodule with normal thyroid uptake. Unfortunately, methimazole precipitated urticaria and pruritus, without any liver abnormalities, necessitating its’ discontinuance. Propranolol monotherapy subsequently provided effective symptomatic relief. The patient’s thyroid levels eventually peaked following delivery (fT4 -4.32) before trending downward (fT4 = 1.79), paralleling the resolution of her symptomatic biochemical thyrotoxicosis and resolution of her goiter. Conclusion - Literature review revealed lack of similar case report. Our patient benefitted from symptomatic therapy with propranolol. Women with preexisting thyroid disorders are at high risk for developing postpartum thyroiditis and should be closely monitored for one year post-partum. We hypothesize that our patient most likely had preexisting Grave’s disease that was exacerbated after her delivery. Reference - Pearce EN. Thyroid disorders during pregnancy and postpartum. Best Pract Res Clin Obstet Gynaecol. 2015;29(5); 700-706.

Positive Thyrotropin Receptor Antibodies in Patients with Transient Thyrotoxicosis

Thyrotropin (TSH) receptor antibody (TRAb) testing is considered accurate for the diagnosis of Graves disease (GD) and has been identified rarely in thyrotoxic patients without GD. We describe 4 patients with transient thyrotoxicosis and positive TRAb to highlight this clinical possibility. Patient demographics, symptoms, laboratory findings, and time to resolution of thyrotoxicosis are summarized. TRAb testing was performed by either a third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) competitive-binding assay or a thyroid-stimulating immunoglobulin (TSI) bioassay from either Mayo Clinic Laboratory or Quest Diagnostics. Four patients with transient thyrotoxicosis and positive TRAb testing were identified. Of these, three were female, and the median age was 44 years (range, 25 to 49 years). Median symptom duration at evaluation was 6.5 weeks (range, 3 to 12 weeks). No patient had any clinical manifestations unique to GD or exposure to biotin, thyroid hormone, supplements, iodine, or relevant medications. The TSH was <0.1 mIU/L in all patients. Three patients had a positive TSI, which was elevated less than twice the upper limit of the reference range in all cases, and 1 patient had a strongly positive TBII. None of the patients were treated with thionamides or radioactive iodine. Spontaneous resolution occurred in all patients at a median of 5.5 weeks (range, 2 to 14.4 weeks). These cases demonstrate that TSI or TBII may be present in thyrotoxic patients with transient thyrotoxicosis. For clinically stable patients presenting without pathognomonic evidence of GD, mildly elevated TRAb results may require cautious interpretation, and alterative diagnostic testing or close monitoring should be considered. cAMP = cyclic adenosine monophosphate; FT4 = free thyroxine; GD = Graves disease; TBII = thyrotropin-binding inhibitory immunoglobulin (also known as TBI); TRAb = thyrotropin receptor antibody; TSH = thyrotropin; TSHR = thyrotropin receptor; TSI = thyroid-stimulating immunoglobulin; TT3 = total triiodothyronine; TT4 = total thyroxine.

A Novel Mutation Causing Complete Thyroid Binding Globulin Deficiency (Tbg-Cd Mia) In A Male With Coexisting Graves Disease

An asymptomatic male was found on screening to have a low serum TSH and total T4. The diagnosis of Graves' disease was made with positive thyroid stimulating immunoglobulin (TSI) and elevated free T4 in the presence of complete TBG deficiency (TBG-CD). Genetic testing of the patient and family members revealed a novel frameshift mutation in the TBG (SERPINA7) gene resulting in a complete deficiency of the protein. The laboratory testing included total T4, free T4 by analog method and direct dialysis and TBG measurements. Sequencing of genomic DNA was performed from peripheral blood. A 35-year-old East Indian male was referred to endocrinology because of abnormal thyroid function tests (TFTs): TSH 0.01 mIU/L (0.4-3.6), total T4 3.0 µg/dl (5.5-10.5) done as part of a "routine office visit". Upon further testing, the serum free T4 2.0 ng/dl (0.8-1.8) and TSI 355% (<140% baseline) were elevated and the diagnosis of Graves' disease was made. TBG deficiency was suspected because the total T4 concentration was inconsistent with hyperthyroidism and further testing confirmed TBG was undetectable. Sequencing of the TBG gene revealed a novel hemizygous frameshift mutation: p.Ala64ProfsTer106, TBG-CD Mia (numbering excludes 20 a.a. signal peptide) associated with the complete deficiency of TBG in a patient with Graves' disease. Patients with Graves' disease harboring a TBG mutation have conflicting TFTs. If a clinically hyperthyroid patient presents with normal or low total T4, serum TBG should be measured to identify an abnormality and prevent unnecessary testing.

Graves' disease in children: long‐term outcomes of medical therapy

Management options are limited for the treatment of Graves' disease, and there is controversy regarding optimal treatment. We describe the demographic and biochemical characteristics of children with Graves' disease and the outcomes of its management. This is a retrospective study reviewing medical records from 2001 to 2011 at a tertiary-care paediatric hospital. Diagnostic criteria included elevated free T4 and total T3, suppressed TSH, and either positive thyroid-stimulating immunoglobulin or thyroid receptor antibodies or clinical signs suggestive of Graves' disease, for example exophthalmos. Patients were treated with antithyroid drugs (ATD), radioactive iodine, or thyroidectomy. The main outcome measures were remission after medical therapy for at least 6 months and subsequent relapse. A total of 291 children met diagnostic criteria. A total of 62 were male (21%); 117 (40%) were Hispanic, 90 (31%) Caucasian, and 59 (20%) African American. Mean age (±standard deviation) at diagnosis was 12·3 ± 3·8 (range 3-18·5) years. At diagnosis, 268 patients were started on an antithyroid drug and 23 underwent thyroid ablation or thyroidectomy. Fifty-seven (21%) children achieved remission and 16 (28%) of these patients relapsed, almost all within 16 months. Gender and ethnicity did not affect rates of remission or relapse. Of 251 patients treated with methimazole, 53 (21%) had an adverse reaction, including rash, arthralgias, elevated transaminases, or neutropenia. Most children with Graves' disease treated with ATD do not experience remission, but most remissions do not end in relapse. Adverse reactions to methimazole are common but generally mild.

Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. (99m)Tc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.