Antithyroid Research Articles

Myocardite aiguë secondaire à une maladie de Basedow : à propos d'un cas

The relationships between the thyroid and the heart are close and complex. In rare cases, hyperthyroidism induced by Graves' disease can be complicated by an acute myocarditis, which may be life-threatening. We report the case of a 41-year-old woman with Graves' disease not controlled by antithyroid drugs, hospitalized for odynophagia, palpitations due to atrial fibrillation, diffuse ST elevation on ECG and an increase in cardiac troponin. Coronary angiography was normal, cardiac MRI confirmed acute myocarditis. The evolution was favorable after a phase marked by supraventricular and ventricular rhythm disorders. The diagnostic and therapeutic challenge of this association are discussed, with a review of the literature.

Atrial fibrillation screening to prevent stroke in persons with low-normal thyrotropin

Abstract Background Screening for atrial fibrillation (AF) has been proposed as a method to prevent strokes in high-risk individuals. Recent trials were unable to prove efficacy for stroke prevention but suggested that a more refined approach may be beneficial. Low-normal thyroid-stimulating hormone (TSH) is a marker for AF and stroke risk and may be used to select individuals for AF screening. Purpose To explore TSH as a tool to select individuals for AF screening to prevent stroke. Methods Post hoc analysis of a clinical trial enrolling 6004 participants with stroke risk factors but no known AF randomized 1:3 to implantable loop recorder (ILR) screening for AF and initiation of oral anticoagulation (OAC) upon AF detection versus usual care (control group). The primary outcome was stroke or systemic embolism (SE). Secondary outcomes included the combination of stroke, SE, or cardiovascular (CV) death, all-cause death, AF diagnosis, and OAC initiation. All outcomes were adjudicated. Results Baseline TSH was measured in 6003 participants (99.98%); 1500 randomized to ILR vs 4503 to control. The mean age was 75±4 years, 2836 (47%) were women. The tertiles of TSH were at ≤1.2, 1.2-1.9, and >1.9 mIU/L. Participants in the first tertile had slightly higher levels of the thyroid hormones (T3, T4, and free T4), were slightly younger, had more smoking pack-years, and higher pulse rate compared to other tertiles. The median follow-up duration was 5.4 (4.9-5.8) years, and no participants were lost to follow-up. AF was diagnosed in 476 (31.7%) participants in the ILR group vs 550 (12.2%) in the control group and this difference was similar across tertiles (p-interaction=0.44). Similar patters were observed for OAC initiation. In the first TSH tertile, participants in the ILR group were significantly less likely to experience the primary outcome (hazard ratio 0.52 [0.30–0.90]; p=0.019) or the combination of stroke, SE, or CV death (hazard ratio 0.54 [0.35–0.84]; p=0.006, respectively) compared to control, while there was no effect in participants with higher TSH (p-interaction 0.029 and 0.014, respectively) and there was no effect on all-cause death in any tertile. When TSH was modelled as a continuous variable, the effect of ILR screening gradually increased with decreasing TSH, with the upper bound of the confidence interval reaching HR<1 at TSH<1.2-1.5 mIU/L. Sensitivity analyses excluding participants with baseline TSH outside reference range (0.3-4.0 mIU/L) and/or treated with thyroid hormone replacement or antithyroid agents yielded similar results. Conclusion In persons with stroke risk factors and TSH <1.2-1.5 mIU/L, ILR screening for AF and anticoagulation upon detection led to significantly decreased stroke risk. There was no effect in persons with higher TSH, though the yield of screening was similar across levels. This suggests that low-normal TSH may indicate benefit from AF screening while higher levels may lead to overdiagnosis.TableFigure

Outcomes of Radiofrequency Ablation for Autonomously Functioning Thyroid Adenoma- Mayo Clinic Experience

Abstract Background Autonomously functioning thyroid nodules (AFTNs) constitute 5-7% of thyroid nodules and represent the second most common cause of hyperthyroidism following Graves’ Disease. Currently, radioactive iodine (RAI) and surgery are the standard treatment options, and both incur a risk of post-procedural hypothyroidism and other surgery and radiation- related complications. Methods This work aimed at assessing the efficacy of RFA, as an alternative treatment option, in resolving hyperthyroidism and also assess the nodule volume rate reduction (VRR) and its associated adverse events. Results A total of 22 patients underwent RFA for a solitary AFTN. 72% (n=16) had subclinical hyperthyroidism, 9% (n=2) had overt hyperthyroidism, and 18% (n=4) were biochemically euthyroid on anti-thyroid medication (ATD). Average pre-treatment TSH was 0.41 mIU/L (SD= 0.98) and free T4 1.29 ng/dl (SD= 0.33). Following a single RFA session, hyperthyroidism resolved in 90.9% (n= 20) and average VRR (61.13%) was achieved within 3-6 months following the ablation. Except for one nodule, none of the nodules grew during the follow-up period (16.5 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and two developed mild hypothyroidism requiring levothyroxine therapy. Two patients developed recurrent hyperthyroidism and elected to undergo lobectomy and repeat RFA respectively. No serious adverse effects were noted in this cohort. Conclusions RAI and/or surgery represent the standard of care for toxic adenomas but RFA shows excellent efficacy and safety profile. Therefore, at centers with RFA expertise it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications.

Long-Term Antithyroid Drug Therapy in Smoldering or Fluctuating-Type Graves' Hyperthyroidism with Potassium Iodide.

Graves' hyperthyroidism is characterized by stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibodies (TRAbs). Antithyroid drug (ATD) continuation is recommended as long as the thyroid gland is stimulated. Goiter size, thyroidal 123I uptake, serum thyroglobulin level, and TRAb positivity are reliable markers of thyroid stimulation. Attention must also be paid to the responsiveness of the thyroid gland due to the high prevalence of painless thyroiditis and spontaneous hypothyroidism during treatment. TRAbs disappeared at <5 years entering remission in 36.6% of patients (smooth-type), while re-elevation of TRAb activity occurred in 37.7% (fluctuating-type) and remained positive for >5 years in 21.1% (smoldering-type). Seven percent of patients remained positive for TRAbs for >30 years, requiring life-long ATD treatment. Remission occurred after median 6.8 years (interquartile range, 4.0 to 10.9) of ATD treatment in 55% of patients. However, late relapse may occur after stressful events (dormant type). In apparently intractable Graves' disease (GD) with a large goiter (>40 g), 131I therapy should be considered. For initial and long-term ATD treatment, we must choose effective, safe, and economical drugs such as 100 mg potassium iodide (KI), although KI sensitivity varies in patients with GD. Thionamide, which has notorious side effects, is added only during the KI-resistant period.

Perinatal exposure to environmental chemicals that disrupt thyroid function can perturb testis development

Thyroid hormones (THs) are essential for normal growth and development. Their role in skeletal and brain development is well established, with congenital hypothyroidism causing stunted growth and severe intellectual disability. THs are also important for the development of other tissues and organs, including the testis. Developmental hypothyroidism can manifest as smaller testes in early postnatal life that later develop into macroorchidism in adulthood due to increased proliferation of Sertoli cells. Effects of hypothyroidism on the testes can be modelled in rodents by exposing developing animals to TH-suppressing pharmaceuticals such as propylthiouracil (PTU) and methimazole (MMI). These drugs act by inhibiting the thyroperoxidase (TPO) enzyme in the thyroid gland, inhibiting the synthesis of THs. It is possible that environmental chemicals that inhibit TPO activity can also cause TH-mediated effects on the developing testis, but the extent to which this occurs is not known. Herein, we characterized the effects of perinatal exposure to the herbicide amitrole together with the antithyroid drug MMI. Pregnant Sprague-Dawley rats were exposed by oral gavage to two doses of amitrole (25 or 50 mg/kg body weight/day) or MMI (8 or 16 mg/kg body weight/day) from gestational day 7 until birth. After birth, pup exposure was continued by dosing lactating dams from day of delivery until pup day 16. Both chemicals caused a significant reduction in TH levels on day 16. This perinatal hypothyroidism disrupted both germ and Sertoli cell development, resulting in smaller testes and reduced seminiferous tubule diameter in 16-day old pups. Notably, fetal male blood progesterone levels were increased after exposure to both amitrole and MMI, whereas the amitrole-exposed animals also displayed increased estradiol levels. Our study raises concerns that exposure to environmental chemicals that happen to disrupt TH production may disrupt TH-dependent testis development, with adverse consequences to human reproductive health.

New onset of Graves' disease after controlled ovarian stimulation: A case report and brief literature review.

De novo onset of Graves' disease (GD) after controlled ovarian stimulation (OS) is exceptional. Only one case of progression to GD after OS in a patient with pre-existing subclinical hyperthyroidism has been reported. We describe the case of a patient with neither previous thyroid disorders nor autoimmunity who developed GD after OS for primary infertility. A 40-year-old woman with primary infertility underwent four cycles of OS. Her thyroid function performed before the last cycle was unremarkable (thyroid stimulating hormone [TSH] 1.9 mU/L, fT4 1.3 ng/dL, fT3 2.4 pg/mL), and thyroid autoimmunity was negative (anti-thyroperoxidase antibodies and anti-thyroglobuline antibodies). Six weeks after the last cycle she developed overt thyrotoxicosis (TSH < 0.005 mU/L, fT4 4.79 ng/dL, fT3 15.6 pg/mL) with anti-thyrotropin receptor antibodies (TRAb) positivity (9.2 IU/L). She was diagnosed with GD and anti-thyroid therapy was instituted. After 1 year of treatment, thyroid function was still suboptimal (TSH 0.2 mU/L, fT4 1.04 ng/dL, fT3 2.2 pg/mL), and TRAb titer still elevated (8.75 IU/L). Despite her desire to achieve pregnancy, a further cycle of OS was postponed until complete remission of thyroid dysfunction and withdrawal of anti-thyroid therapy. Although TSH assay after OS is not recommended in euthyroid women without autoimmunity, in the presence of hyperthyroid symptoms throughout OS it is advisable to evaluate thyroid function and TRAb. It is advisable to carefully evaluate the course of GD before proceeding with further courses of OS that could lead to its exacerbation or recurrence. In cases where a strong desire for pregnancy persists, thyroidectomy may be proposed.

Long-term retreatment outcomes after definitive management of Graves’ disease with radioactive iodine versus surgery

BackgroundCommon treatments for Graves’ disease include antithyroid drugs (ATD), radioactive iodine (RAI), and surgery. RAI avoids surgical morbidity, but rate and durability of remission varies across studies. This study directly compared the long-term results of Graves’ disease treated by surgery versus RAI and hypothesized that RAI would be associated with lower rates of long-term biochemical remission and higher likelihood of retreatment. MethodsThis retrospective cohort study included individuals diagnosed with Graves’ disease who were treated surgically, with RAI, or both at a tertiary referral center. Definitive retreatment was defined as additional RAI or surgery after index treatment, and retreatment was defined as requiring ATD or a second definitive treatment after index treatment. Remission was defined by normalization of thyroid stimulating hormone without retreatment at 6 months. ResultsIndex definitive therapy was total thyroidectomy for 72 patients and RAI for 104 patients. The median follow-up time was 3.6 years. The rate of remission at 6 months in the RAI group (68.8%) was lower than that in the surgery group (98.6%) (odds ratio: 0.03, P < .001). Patients who underwent index RAI experienced a significantly higher cumulative incidence of any retreatment at all time points than those who underwent index surgery (P < .001). Among RAI patients who achieved euthyroidism within 6 months, 19% developed subsequent relapse requiring ATD therapy or retreatment. ConclusionThe need for retreatment after index therapy for Graves’ disease is significantly lower after thyroidectomy than after RAI.

7860 Predictors of Remission in Patients with Graves' Disease Treated with Antithyroid Drugs at the University of Santo Tomas Hospital - A Retrospective Cohort Study

Abstract Disclosure: F.E. Sorsona: None. E.C. Cunanan: None. This is a local study with the objective to determine the predictors of remission in Graves’ disease patients who completed 12 to 18 months of antithyroid drug therapy in University of Santo Tomas Hospital (Manila, Philippines) from 2017 to 2022. The study employed a retrospective cohort design. Patients included were all Graves’ disease patients seen at University of Santo Tomas Hospital who were treated with antithyroid drug methimazole. Data were collected via a retrospective review of medical charts. From the 203 Graves’ disease patients, a total of 59 patients met the inclusion criteria and were included in the study. Following completion of antithyroid drug therapy, patients were divided into remission and non-remission groups. Predictive factors analyzed were age, gender, smoking history, presence of orbitopathy and goiter, duration of ATD therapy, and thyroid function tests (TSH, free T3 and free T4) at time of initiation and completion of ATD. Forty-nine patients (83%) were females, and ten patients (17%) were males. The median age at the time of ATD initiation was 35 years old. The median duration of ATD therapy was 24.2 months. Following completion of ATD, 34 patients had remission with incidence of 57.63% (95% CI: 44.07-70.39%). Age, gender, smoking history, presence of goiter and orbitopathy, duration of ATD therapy, thyroid function tests at initiation, and FT3, FT4 and FT3/FT4 ratio at time of completion showed no significant differences between the two groups. After univariate and multivariate analyses, only one factor was significantly associated with 1-year remission which was the TSH at the time of ATD completion, with a median of 1.54 mIU/L, range: 0.001-7.94 mIU/L. Median TSH was significantly higher among patients who had remission than those with non-remission. Compared to patients with normal TSH at the time of ATD completion, the odds of remission was 14 times lower among patients with low TSH, and 7 times lower among patients with high TSH. A normal TSH at the time of ATD completion was associated with 1-year remission from Graves’ disease. Presentation: 6/2/2024

7589 A Survey On the Current Status of Universal Screening Thyroid Indicators During Pregnancy in Real World Study

Abstract Disclosure: N. Zhou: None. W. Sun: None. H. Meng: None. Y. Huang: None. J. Zhao: None. Y. Gao: None. H. Yang: None. Y. Zhang: None. A Survey on the current status of universal screening thyroid indicators during pregnancy in real world study Background: Thyroid dysfunction and thyroid auto-immunity (TAI) are common in women of childbearing age, which have been proven to increase the risk of maternal and fetal adverse pregnancy outcomes. China has adhered to the strategy of universal screening for early pregnancy thyroid indicators since 2012, and is currently the only country that recommends universal screening. This study aimed to investigate the implementation situation of universal screening for thyroid indicators during pregnancy in real world study. Methods: We retrospectively collected medical record information from 18,932 women who underwent regular prenatal examinations at Peking University First Hospital from January 2014 to December 2016 until the end of pregnancy, grouping based on whether thyroid indicators were screened during pregnancy, and comparing the general characteristics and pregnancy outcomes. Furthermore, the treatment compliance status of women who took levothyroxine and antithyroid drugs (ATD) before pregnancy was also analyzed. Results: The screening rate for thyroid indicators in pregnancy was 88.7% in our hospital, 93.3% of pregnant women underwent screening in early pregnancy, with a median gestational age of 7.0 (6.6, 10.1) weeks. Non-screening ones were more inclined to be aged&amp;gt;40 years or &amp;lt;25 years, with a BMI ≥24 kg/m2, pluriparity (≥2), and without thyroid disease history prior to conception (P &amp;lt; 0.05). After correcting covariates, the risks of early miscarriage (8-12 weeks) (OR=21.96, 95% CI: 19.2, 25.1) and late miscarriage (12-28 weeks) (OR=3.0, 95% CI: 2.5, 3.6) were significantly higher in non-screening group than in the screening group, but there was no significant difference in the risk of preterm labor between the two groups (P=0.985). The achievement rate (0.23≤TSH&amp;lt;2.5uIU/mL, FT4 within normal range, 53.7%-64.2%) of early pregnancy thyroid function among levothyroxine intervention participants increased from 2014 to 2016. Compared with those in the thyroid function controlled group, the patients in the uncontrolled group had earlier screening gestational weeks (6.7 vs. 8.0 weeks), higher TPOAb positivity (58.6% vs. 44%), and a greater incidence of other autoimmune disorders (14.2% vs. 9.8%) (P&amp;lt;0.05). The achievement rate of early pregnancy thyroid function among ATD intervention participants ranged from 63.6 to 71.2%. Conclusions: The screening rate for thyroid indicators in pregnancy is nearly 90% in comprehensive hospitals. The lack of screening may be related to miscarriage to some extent. The current treatment compliance status pre-pregnancy neither for levothyroxine nor ATDs was not satisfactory. Presentation: 6/2/2024

8124 Prevalence and Characteristics of Patients with Hypothyroidism in the Danish Blood Donor Study

Abstract Disclosure: N.L. Frisk: None. J.R. Shorter: None. O.B. Pedersen: None. L.T. Dalgaard: None. Introduction: While impaired thyroid function leading to subclinical hypothyroidism and overt hypothyroidism is common in Denmark, the knowledge about the paths by which patients’ progress to impaired thyroid function is limited. Undiagnosed hypothyroidism as well as subclinical hypothyroidism constitute serious risk factors for development of cardio metabolic disease. The Danish Blood Donor Study (DBDS) is a large longitudinal cohort and biobank containing information and samples dating more than 10 years back. Blood donors donate blood every 3-6 months and each time provide a sample for research. Research question: The aim of the study was to obtain up-to-date information about prevalence and characteristics of patients with hypothyroidism in a Danish longitudinal cohort of blood donors. Methodology: The study employed a cross-sectional design. Hypothyroidism was defined based on at least two prescriptions of levothyroxine (LT4) and used for calculations of prevalence. Case numbers were compared to all controls that were currently not being prescribed LT4 nor anti-thyroid drugs (carbimazole, propylthiouracil, thiamazole). We compared cases of hypothyroidism to two different control (ctrl) groups: 1) All the participants of the DBDS having TSH levels in the normal range, and 2) Normothyroid participants matched to hypothyroid cases based on age and sex. Incidence was determined based on DBDS participants developing hypothyroidism after being enrolled into the DBDS during a 10-year follow-up. Men and women were compared separately among cases and controls. Students’ t-test was used to compare cases and controls, and corrected using Bonferroni. Major results: There were 3397 cases of hypothyroidism and 153791 ctrl subjects in the DBDS, giving a prevalence of 2.2%. 85% of cases were female, while among ctrl 50% were female. Average age of cases was 52±13 years (mean±SD) for women and 58±13 for men, while ctrls were 45±13 and 48±14 years, respectively (both P&amp;lt;0.001). BMI among cases were: 25.8±4.7 for women and 26.8±3.9 kg/m2, while cases were 25.1±4.4 and 26.0±3.6, respectively (both P&amp;lt;0.001). TSH levels were, for female cases: 4.6±4.0 iu/mL and 5.7±4.9 for men, while ctrls were 1.8±1.1 and 1.7±1.1, respectively (both P&amp;lt;0.001). Free (F) T4 levels were, for female cases: 14.4±6.4pmol/L and male: 14.0±4.6, while ctrls were: 14.8±4.5 and 15.0±3.9 respectively (P&amp;lt;0.003 for females, P&amp;lt;0.0001 for males), while FT3 levels were for cases: 4.3±1.7 and 4.3±1.4 pmol/L and 4.5±2.0 and 4.7±1.5 for ctrls (both P&amp;lt;0.0001). Conclusion: Hypothyroidism is less prevalent among blood donors than reported in the general Danish population, which is accordance with ‘the healthy donor’ bias. Hypothyroid donors were on average older and with higher BMI than normothyroid controls. Donors with hypothyroidism were generally well regulated, but despite that FT4 and FT3 levels were lower than ctrls. Presentation: 6/1/2024

7245 A case of refractory methimazole-induced agranulocytosis treated with high-dose G-CSF

Abstract Disclosure: S. Shah: None. D. Mathur: None. G. Bao: None. S. Shah: None. D.M. Antoniucci: None. Case Presentation: Despite their efficacy in treating hyperthyroidism, antithyroid drugs (ATDs) carry a rare risk of life-threatening agranulocytosis (ANC &amp;lt;500/μL), with incidence varying from 0.1 to 0.4%. Patients with agranulocytosis may benefit from granulocyte-colony stimulating factor (G-CSF) to shorten recovery and reduce hospitalization costs. We present the case of a 37-year-old woman with Graves disease, who developed methimazole (MMZ)-induced agranulocytosis and was treated with high-dose G-CSF. At diagnosis, MMZ 10 mg BID was started and later reduced to 5 mg BID. After 2 months, she presented to the ED with a dental infection, an arm abscess after a cat scratch, and fevers. Blood-work showed WBC of 1500/μL, ANC of 0/μL, and rare granulocytes on manual differential. Flow cytometry did not show clonal lymphoid or blast populations. MMZ was stopped and antibiotics were started. Her hyperthyroidism was managed with propranolol and iodine solution in anticipation of definitive thyroidectomy. On day 4 of admission, tbo-filgrastim 450 mcg daily injections were started for persistent neutropenia. Despite 3 doses of G-CSF, ANC remained at 0/μL, prompting a bone marrow biopsy that showed no dysplastic or aplastic phenotype. After 9 doses of G-CSF up to 600 mcg daily, ANC fully recovered on day 14. She underwent thyroidectomy, and 2 months later her ANC and thyroid hormone levels were within normal. Discussion: This report illustrates a case of severe, refractory ATD-induced agranulocytosis and highlights the utility of G-CSF in treating high risk patients. Classically, ATD-induced agranulocytosis occurs in those aged &amp;gt;65 years, follows high dose therapy, and occurs within 60 days of treatment initiation. G-CSF is often used in clinical practice, although its efficacy is not well established. A recent meta-analysis demonstrated that G-CSF can hasten recovery by 3 days. Other studies report no difference or prolonged agranulocytosis up to 14 days despite G-CSF, especially in patients with ANC &amp;lt;100/μL. Whether this is a lack of true benefit or inadequate dosing is unclear. This case reviews the use of high dose G-CSF in a patient with profound neutropenia. Prompt ANC recovery was crucial given neutropenic fevers and need for thyroidectomy. Even with escalating doses of G-CSF, her ANC required 14 days to recover - twice the typical length of recovery. Whether G-CSF impacted the time course of her recovery is difficult to discern. Identifying the mechanisms underlying ATD induced agranulocytosis may explain delayed responses to G-CSF. Notably, the 2016 ATA guidelines do not incorporate G-CSF into ATD-induced agranulocytosis management. This conservative approach reflects a paucity of evidence supporting G-CSF use. Further research must investigate underlying mechanisms and clarify indications for G-CSF use to improve outcomes and reduce costs of care. Presentation: 6/1/2024

7684 Resistance to Thyroid Hormone Beta Mistaken as Primary Hypothyroidism: Variable Phenotypes and Diagnostic Dilemmas

Abstract Disclosure: H.F. Belal: None. A.N. Mukhtar: None. J.M. Chehade: None. Background: The differential diagnosis of hyperthyroxinemia and nonsupressed TSH includes assay interference, resistance to thyroid hormone beta (RTHb) and TSHoma. Correlation of laboratory findings with clinical presentation is crucial to avoid misdiagnosis. Clinical Case: A 50 year old female presented with palpitations, tremors, headaches, diarrhea, heat intolerance, chronic attention difficulty, pre-syncope and fatigue over several years. She had regular menses with no birth control use. There was no amiodarone, lithium or biotin use. Exam: vitals stable, no thyromegaly, no hand tremors, no exophthalmos. At 26 years old she was started on Levothyroxine (LEVO) 50 mcg for elevated TSH; FT4 was not measured. Over the past 10 years her labs demonstrated elevated FT4, elevated FT3, elevated FT4 by direct dialysis, normal TBG and inappropriately normal/elevated TSH while on LEVO 75 - 175 mcg. On LEVO 75 mcg: elevated TSH 5.94 uIU/mL (0.27-4.2), elevated FT4 2.2 ng/dL (0.8-1.7), elevated FT3 6.0 pg/mL (2.0-4.4), elevated FT4 direct dialysis 2.9 ng/dL (0.8-1.7), normal pituitary panel (including alpha subunit), low alpha subunit/TSH molar ratio (0.71). During an ED visit for chest pain, EKG revealed poor R wave progression, non-specific T wave abnormality. She was also found to have hepatic steatosis. RTHb was diagnosed and her LEVO was gradually tapered. Conclusion: TSH receptor beta is expressed in hypothalamus, pituitary, cochlea, retina, liver and kidney. TSH receptor alpha is expressed in skeletal muscle, heart, brain and bone. RTHb occurs at a frequency of 1 in 19,000 to 40,000 leading to resistance to thyroid hormone action at the HPA axis and liver. This produces higher FT4 and FT3 that act on normal TSH alpha receptors. Clinical phenotypes vary from euthyroid to hyperthyroid. Mistreating RTHb as hypothyroidism can worsen the thyrotoxic state. Testing for RTHb genetic mutation is available, yet 15% of RTHb patients do not have an identifiable pathogenic variant[1]. Treatment of RTHb ranges from observation, beta blockade, antithyroid drugs or TRIAC, a thyroid hormone analog which act at the HPA axis to inhibit TSH secretion.[1] Life threatening cases may require total thyroidectomy or radioiodine ablation; often avoided due to difficulty managing thyroid hormone replacement afterwards. Cases of goiter and ADHD in RTHb have been successfully treated with supraphysiologic every-other-day liothyronine.2 Management should be patient tailored and symptom specific.

5128 Role of Plasmapharesis- A Tale of Two Thyroid Storms

Abstract Disclosure: Z. Zhang: None. S. Joseph: None. A.M. Kodali: None. D. Eagerton: None. Background: Thyroid storm is an acute life threatening endocrinological emergency. The standard treatment for a thyroid storm is antithyroid medication, iodine, beta blockers and corticosteroids. However, when patients are refractory to standard treatment, plasmapheresis may be an effective and safe intervention. Case 1: A 49-year-old male with typical symptoms of hyperthyroidism, presented with a Ventricular tachycardia arrest. After the return of spontaneous circulation, he was febrile, and developed new onset atrial fibrillation (AF) and Amiodarone drip was started. Physical exam showed a thin gentleman with an enlarged thyroid. ECHO showed LVEF 50% with moderate to severe dilatation of left atrium and mild mitral and tricuspid valve regurgitation. CT abdomen/pelvis and CTA chest did not show any pathology. Labs showed TSH of 0.02 (reference range: 0.465-4.68); Free T 4 &amp;gt;6.99 (reference range: 0.78- 2.19). He was started on Propylthiouracil (PTU), Hydrocortisone, Potassium Iodide, and Cholestyramine. His blood pressure was too low to tolerate a beta blocker. He developed increased liver enzymes thought to be due to shocked liver. PTU was switched to Methimazole due to less risk of hepatotoxicity. A Thyroid Stimulating immunoglobulin was 13.40 (reference range 0.00-0.55), confirming Graves’ disease. He developed multiorgan failure and plasmapheresis was initiated. His Free T4 level prior to his first apheresis was still &amp;gt;6.99 but improved to 6.20 after two days. After the second session, free T4 level drastically improved to 2.65. He sustained a level of 2.09 until his hospital discharge. Case 2: A 59-year-old male with untreated hyperthyroidism and AF, who presented with shortness of breath. He was tachycardic, febrile and developed AF with rapid ventricular response. A TSH and free T4 level showed &amp;lt;0.02 (reference range: 0.465-4.68); and &amp;gt;6.99 (reference range: 0.78- 2.19), respectively. Physical exam shows a cachectic man with an enlarged thyroid. ECHO showed reduced ejection fraction of 35% with biventricular failure. He was initially started on PTU, Potassium Iodide, hydrocortisone and esmolol drip and eventually Cholestyramine. Patient developed multisystem organ failure and PTU was switched to methimazole due to continued deterioration of his liver enzymes. Plasmapheresis started with a total of 3 sessions. His free T4 improved from 4.32 to 3.59 by the second session. Round three was performed when his Free T4 increased back to 4.56. Unfortunately, he had a sudden decline in mentation and CT head showed an acute/subacute left anterior parietal stroke and after family discussion, was palliatively extubated and expired. Discussion: This case series shows two cases of thyroid storm treated with plasmapheresis and had two stark contrasts. Further studies should be done to elucidate the usefulness of plasmapheresis for thyroid storm when refractory to standard of treatment. Presentation: 6/2/2024

7375 Severe Hypoglycemia In Graves’ Hyperthyroidism: A Rare Consequence Of Methimazole Induced Insulin Autoimmune Syndrome

Abstract Disclosure: J. Ratnasingam: None. N. Ismail: None. Y. Ng: None. T. Sarvanandan: None. N. Hee: None. Q. Lim: None. L. Lim: None. S. Paramasivam: None. P. Sthaneshwar: None. S. Vethakkan: None. Background: Islet autoimmune syndrome (IAS) is a rare disease characterized by elevated insulin autoantibodies (IAA), triggered by genetic, environmental or drug (sulfhydryl containing) factors. We describe a case of Graves’ hyperthyroidism who developed IAS with methimazole. Clinical Case: A 28-year-old Malaysian-Chinese woman presented with tremors and palpitations. She weighed 56 kg, had no palpable goiter or thyroid eye signs. The diagnosis of Graves’ disease was confirmed with ft4 66.5 (11.5-22.7)pmol/L and TSH &amp;lt;0.01 (0.55-4.78)mIU/L with elevated thyroid stimulating immunoglobulin of 5.4 (&amp;lt; 0.55)IU/L. She was treated with methimazole 20mg BID and Propranolol 20mg TID. After 5 weeks of methimazole, she experienced recurrent episodes of sweating and presented with a generalized tonic-clonic seizure with capillary blood glucose of 27mg/dL. Seizures aborted after resuscitation with dextrose. There was no history of fever, exposure to insulin or other drugs, weight gain, family history of diabetes or alcohol use. CT brain and other parameters were normal and she had no other apparent cause of seizures. During the hypoglycemic episode; with the plasma glucose of 32 mg/dL, she had disproportionately high insulin: 9309 (3-25)mIU/L relative to C-peptide: 18.6 (0.9-7.1)ng/mL, with appropriate cortisol levels of 958 nmol/L. Sulphonylurea screen and pancreatic imaging was negative. Low insulin recovery was documented following PEG precipitation suggesting the presence of anti-insulin antibody. Elevated serum IAA levels at &amp;gt;20 (&amp;lt;2.4)U/mL with positive HLA-DRB1*04:06, confirmed the diagnosis of IAS. Multiple small, low carbohydrate and frequent meals were prescribed to prevent hypoglycemia and methimazole was discontinued as she had mild hyperthyroidism at this point (ft4 20.6 pmol/L, TSH &amp;lt;0.01mIU/L). Three days after discontinuation of methimazole, hypoglycemia completely resolved without need for dextrose infusion or corticosteroids. She received immediate 131-iodine therapy and developed hypothyroidism within two months, requiring levothyroxine replacement. She had not reported any hypoglycemia since and repeated IAA titre significantly diminished to 3.2 U/mL two months after discontinuation of methimazole. Conclusion: Methimazole-induced IAS is a rare cause of insulin mediated hypoglycemia, caused by cleaving of the disulphide bonds of insulin by the drug, leading to a cascade of autoimmune response in susceptible individuals. This is the first reported Malaysian case of methimazole- induced IAS. To date, this condition have almost always been reported in East- Asians in whom the DRB1*0406 genotype is relatively common. Unprovoked hypoglycaemia in a patient on anti-thyroid medications should prompt clinicians to consider methimazole-induced IAS. Presentation: 6/1/2024

9398 Early Identification of Impending Thyroid Storm Leading to Improved Thyrotoxic Induce Cardiomyopathy

Abstract Disclosure: D.H. Sacoto: None. D. Patel: None. A. De Rosairo: None. K. Madani: None. B. Singh: None. A. Bonilla Campos: None. R. Belokovskaya: None. F. Alberto A.: None. Introduction: Heart failure can be the leading presentation in 6% of thyroid storm cases and is the leading cause of death, particularly in elderly patients. However, its importance lies in symptom control and heart function reversibility once the euthyroid state is achieved. We present a caseof thyroid storm-induced atrial fibrillation (Afib) leading to severe systolic dysfunction. Case: A 61-year-old female with a history of Graves’ disease (GD) presented to the ED with two months of palpitations and one week of shortness of breath. There were bibasilar lung crackles, irregular heart rhythm, pedal edema, and thyromegaly at the examination. EKG was consistent with Afib with rapid ventricular response (123-135 beats per minute); She was tachypneic (respiratory rate: 40 per minute) and hypoxemic (87% O2 saturation), which required bilevel positive airway pressure. Otherwise, hemodynamically stable (BP: 127/106 mmHg). Laboratories showed negative troponin T (&amp;lt;0.010 ng/mL, n &amp;lt;0.01 ng/mL). However, elevation of Pro-B-type natriuretic peptide (6000 pg/mL, n &amp;lt;125 pg/mL), an x-ray displaying bibasilar pleural effusions and an echocardiogram demonstrating a severely reduced ejection fraction (EF) (21%, n 50-70%), myocardial perfusion scan was normal. Thyroid evaluation showed a suppressed TSH (&amp;lt;0.01 uIU/mL, n 0.27-4.20 uIU/mL) with elevated free T4 (5.8 ng/dL, n 0.9-1.8 ng/dL), free T3 (202 ng/dL, n 2.0-4.4 ng/dL), and TSI (8.25 IU/L, n 0-0.55 IU/L). A thyroid ultrasound revealed increased vascular flow on the left thyroid lobe. A Burh-Schakowsky score of 45 points was consistent with impending thyroid storm. She was started on methimazole, cholestyramine, and propranolol. Three months follow-up, she was asymptomatic, TSH normalized (4.12 uIU/mL), and mild improvement of cardiac EF 25%. Discussion: A thyroid storm in the setting of GD often presents after precipitating factors such as surgery, infection, or, as in our case, anti-thyroid medication non-compliance. Increased thyroid hormone levels upregulate cardiac β receptors, enhancing sensitivity to sympathetic innervation. These can shorten the refractory period of cardiomyocytes, leading to tachyarrhythmias, with Afib occurring in 20% of patients. Chronic tachycardia finally impairs left ventricle function, with heart failure as an outcome. A high index of suspicion and the ability of early diagnosis of impending thyroid storm is critical since the first laboratory confirmation is often delayed, and second, either anti-thyroid medication, radioactive iodine ablation or thyroidectomy, in addition to non-selective beta-blockers, can reverse cardiac dysfunction and lead to clinical improvement as early as 12 -Twenty-four hours of medical treatment. In our case, the early diagnosis and treatment of thyroid storm, in addition to the rate control prevented a deadly outcome and contributed to the improvement of heart failure. Presentation: 6/1/2024

12214 Metastatic Functional Thyroid Carcinoma As An Unusual Cause Of Hyperthyroidism

Abstract Disclosure: S. Jimenez Salazar: None. N. Aristizabal Henao: None. C. Aguilar Londoño: None. N. Buitrago Gómez: None. S. Saldarriaga Betancur: None. D.L. Beltran: None. J.L. Torres: None. Background: Differentiated thyroid carcinoma (DTC) represents the most prevalent endocrine neoplasm. Less than 10% present distant metastases, with the lung (50%), and skeleton (25%) being the most frequently affected sites. The location of bone metastases predominates in the spine and pelvis; usually as osteolytic lesions, being more frequent in follicular thyroid cancer (FTC) (7-28%) than in patients with papillary thyroid cancer (PTC) (1.4-7%). In rare cases this metastasis can be functional and trigger a thyrotoxicosis syndrome with or without recombinant human TSH injections prior to therapy with 131-I. Clinical case: 59-year-old woman with a history of bone metastatic follicular thyroid cancer (FTC) presented with 1 month of palpitations, 4 kg weight loss, non-dysenteric diarrhea and progressive dyspnea. Her FTC had been diagnosed 8 years prior her consultation. In that time iodine refractoriness was considered due to the progression of bone lesions, and Sorafenib 800 mg per day was initiated, which was not tolerated due to severe dermatological manifestations, and the patient decided not to continue with TKI therapy. Since then, she has been treated with zoledronic acid and local radiotherapy as part of palliative care. On physical examination, she was tachycardic (150 bpm), and hypertensive (BP 160/100 mmHg). A suppressed TSH (&amp;lt;0.01 uUI/mL, n: 0.4-4 uUI/mL) with elevation of thyroid hormones (free T4 3.99 ng/dL, n: 0.8-2 ng/dL and total T3 480 ng/dL, n: 45-140 ng/dL) was documented, associated with a patient who had required a dose adjustment of levothyroxine from 700 mcg to 350 mcg weekly 2 months prior to admission. Additionally, she had a significantly elevated thyroglobulin (&amp;gt;5000 ng/mL, n: 0.1-64.1 ng/mL) with undetectable antithyroglobulin antibodies (1.09 UI/mL, n: 0-4.11 UI/mL). Considering the history of total thyroidectomy and the high tumor burden, secondary thyrotoxicosis due to functioning bone metastases of DTC was considered. Levothyroxine was discontinued, and propranolol was initiated for the control of adrenergic symptoms, along with methimazole, cholestyramine, and systemic steroids to control thyroid hormone production. 3 days after therapy adjustment dyspnea, palpitations, and thyroid function tests improved significantly (free T4 1.43 ng/dL, n: 0.8-2 ng/dL and total T3 178 ng/dL, n: 45-140 ng/dL). A new administration of therapy with 131-I 200 mCi was indicated. Antithyroid therapy and beta-blockers were continued with sustained biochemical control. Conclusion: Functional bone metastases of FTC can lead to high morbidity and mortality. Treatment consists of surgical cytoreduction of any large accessible metastatic lesion, therapy with 131-I, and high-dose antithyroid drugs to control hyperthyroidism. It is important to avoid the use of recombinant human TSH due to the risk of secondary thyrotoxicosis following its administration. Presentation: 6/2/2024

5125 Severe Gestational Thyrotoxicosis Leading to Unwarranted Treatment

Abstract Disclosure: C. Bell: None. L.A. Barbour: None. Introduction: Gestational transient thyrotoxicosis (GTT) is the most common cause of thyrotoxicosis in pregnancy yet is often confused with Graves’. Although usually mild, we present a severe case leading to the unsupported use of anti-thyroid drugs (ATDs), which could have resulted in fetal hypothyroidism if continued. Case: A 30-year-old female G1P0 at 10 wks with a single gestation presented with 4 wks of vomiting, palpitations, and weight loss. She had no history of thyroid disease. She was diaphoretic and ill-appearing and had a non-tender, smooth normal-sized thyroid, a stare without exophthalmos, and a fine tremor. TSH was &amp;lt; 0.01, FT4 5.57 ng/dL (0.89-1.76), and TT3 201 ng/dL (60-181). TPO Ab 51 (&amp;lt; 60). TRAb, TSI Ab, and TgAb were negative. β-hCG level was 334,106 mIU/mL. She was diagnosed with GTT and briefly hospitalized for dehydration but was re-hospitalized 2 wks later with worsening symptoms and 25 lb weight loss. Unexpectedly, her FT4 and TT3 rose to 6.24 ng/dL and 339, respectively. A thyroid ultrasound showed mildly increased vascularity. PTU was started for seronegative Graves’ at 50 mg tid with metoprolol. After 3 days, her FT4 improved to 3.59 ng/dL and TT3 was 176. Further consultation recommended stopping PTU. She was sent home with metoprolol. Her symptoms and FT4 levels improved. FT4 was normal and hCG levels dropped to 54,821 by 18 wks. Discussion: GTT is caused by a transient elevation in T4 due to direct hCG stimulation of the TSH receptor. It is more common with multiple or molar gestations and hyperemesis gravidarum, also mediated by hCG. It typically results in mild thyrotoxicosis, highlighting the uniqueness of this case. Only a couple of case reports exist where GTT presented as severe thyrotoxicosis or thyroid storm and persisted this long. It is critical to distinguish GTT from Graves’ given their different outcomes and treatment. GTT is commonly misdiagnosed as Graves’ as both result in thyrotoxic labs and symptoms and can present in 1st trimester. GTT typically presents at 8-10 wks and lasts until 14-16 wks when hCG levels fall, but Graves’ may also improve by 2nd trimester due to the immune suppression of pregnancy. It is also possible for both to co-exist. hCG levels &amp;gt;100,000 are associated with GTT but due to the variable sialylation of hCG, which changes its affinity to the TSH receptor and half-life, they are unreliable diagnostically. Key clues supporting GTT include no goiter, exophthalmos, or symptoms pre-pregnancy, negative TRAb and TSI, and, notably, a lower T3/T4 ratio compared to Graves’, as seen in this case. To conclude, GTT is often mistaken for Graves’ but inappropriate use of ATDs can result in fetal hypothyroidism and does not improve outcomes. Although the severity of our case is unusual, accurate distinction from Graves’ by endocrinologists is crucial to ensure optimal maternal-fetal outcomes. Presentation: 6/1/2024

8806 A Case of Autoimmune Thyroid Switching

Abstract Disclosure: J. Case: None. R.V. Chemitiganti: None. D. Suravajjala: None. Autoimmune thyroid disease comprises both hyper- and hypothyroid states including Graves' disease and Hashimoto's thyroiditis, respectively. The predominant antibody activity, demonstrable by thyrotropin receptor antibody, predicts the clinical presentation and treatment; thyrotropin receptor antibodies may act as a stimulatory or inhibitory stimulus upon the thyroid gland recognized as thyroid stimulating antibody(TSAb) and thyroid blocking antibody(TBAb). Rarely patients may transition from a hyperthyroid to a hypothyroid state and vice versa if the predominant antibody activity shifts which may occur due to a variety of mechanisms and characteristics related to each individual patient and treatment course. A 29 year old female presented to establish care for autoimmune thyroiditis. She was diagnosed with Graves' disease at age 19 when pregnant and treated with propylthiouracil; she switched to methimazole for the next six years when her thyroid function normalized and therapy discontinued. Two years later she became concerned with weight gain and her thyroid function was reevaluated demonstrating hypothyroidism and she was treated with levothyroxine 25mcg daily until presentation. Further labwork revealed undetectable TSI, and TPO antibody elevated at 177 u/mL. She became clinically and biochemically euthyroid on levothyroxine 50mcg daily. Switching between hyper- and hypothyroid states is a rare occurrence among patients with may attributable factors. Both antithyroid drugs including methimazole as well as replacement therapy with levothyroxine may alter the antibody milieu and so the predominant ratio and activity among TSAb and TBAb thereby leading to a shift in clinical presentation and thyroid state. Pregnancy may lead to hemodilution contributing to lessening of autoimmune activity which may return following delivery leading typically to a shift from TSAb to TBAb. Uncontrolled hyper- and hypothyroidism may affect dendritic activity leading to altered presentation and increased immune reactivity. The unlikely occurrence of switching from a hyperthyroid to a hypothyroid state based upon autoimmunity as in this patient was likely affected these factors. Recognition of this potential transition and associated factors would lead to beneficial monitoring and possibly development of assays more attuned to this phenomenon with better capability in maintaining a euthyroid state and potentially predicting a transition. Presentation: 6/3/2024

6770 Graves’ disease induced by COVID-19 infection in a 49 year old male

Abstract Disclosure: N. Al-hosainat: None. A. Al Najada: None. T. Salar: None. S. Iqbal: None. K. Abdel Gadir: None. Introduction: Graves’ disease is an autoimmune disease causing hyperthyroidism, characterized by elevated thyrotropin-receptor antibodies. COVID-19 infection has been increasingly reported as a trigger of thyroid illness including Graves’ disease. We present a unique case of 49-year-old patient who was diagnosed with Graves’ disease after COVID-19 infection. Case description: A 49-year-old male patient with history of prediabetes presented with complaints of tremor, fatigue, generalized itching, and unintentional weight loss (30 Ibs in 6 months). He had COVID-19 infection 3 months prior. The remainder of review of systems was negative. No family history of thyroid disease. On exam, the patient had sinus tachycardia with otherwise normal vital signs. Diffuse thyromegaly was noted along with an intermittent fine tremor of the extremities. Blood work was notable for low TSH &amp;lt;0.01 uIU/mL, elevated free T4 (3.4 ng/dL), free T3 (17.6ng/dL), and TSH receptor antibody (12 IU/L). Thyroid ultrasound showed mild goiter with 2 nodules, one of which was TIRADS 4 and 1.5cm. This nodule was biopsied and found to be benign. Radioactive iodine uptake scan revealed homogeneous diffuse increased thyroid uptake. The diagnosis of Graves’ disease was made, and the patient was started on propranolol and methimazole with significant improvement of his symptoms and his laboratory tests normalizing. Discussion: Graves' disease is an autoimmune disease, characterized by hyperthyroidism, goiter, occasional orbitopathy and dermopathy. Caused by antibodies against thyroid-stimulating hormone receptors which stimulate thyroid hormone secretion and thyroid growth. Treatment is aimed to decrease thyroid hormone synthesis by either a Thionamide, radioiodine ablation, or surgery. Remission rates with antithyroid drugs average under 40 percent after one to two years of treatment and could exceed 80 percent after 5 to 10 years of treatment. COVID-19 is a multi-system disease, caused by SARS-CoV-2 virus, transmitted by large droplets and small particle aerosols, was declared a pandemic in 2020 and affected millions of people worldwide. There is emerging data showing the association of COVID-19 with various thyroid diseases including thyroiditis and relapse of known Graves' disease after the infection. We present a case of newly diagnosed Graves’ disease after COVID-19 infection in a patient with no personal or family history of such disease which raises the concern of autoimmune pathway activation induced by the infection. The onset of Graves’ disease after COVID-19 infection does not depend on the presence of pre-existing thyroid pathology and in this case responded well to antithyroid medication. Conclusion: COVID-19 can lead to the development of a range of medical illnesses. In patients who develop symptoms of thyrotoxicosis, Graves’ disease should be suspected, investigated, and treated appropriately Presentation: 6/3/2024

7876 Complex Complications of Thionamide Therapy in One Patient: Methimazole-Induced Agranulocytosis and PTU-Induced ANCA-Vasculitis

Abstract Disclosure: E. Zweibach: None. A. Chang: None. Introduction: Thionamides, including methimazole and propylthiouracil (PTU), are essential for treating Graves' disease but can cause serious side effects such as agranulocytosis and ANCA-vasculitis. Although agranulocytosis itself is quite uncommon, the incidence of ANCA vasculitis is even more infrequent, making combination of conditions particularly exceptional. We present a unique case of a Graves' disease patient who suffered both complications: agranulocytosis due to methimazole and ANCA vasculitis from PTU, with successful resolution of both the clinical signs and laboratory findings following drug discontinuation. Case: 61-year-old female with a history of Graves' disease previously managed with methimazole but discontinued due to agranulocytosis, presented with lower extremity swelling, atrial fibrillation with RVR, and high output cardiac failure. Laboratory tests showed hyperthyroidism (TSH 0.008, Free T4 3.07), leading to a diagnosis of thyroid storm. Patient was started on PTU inpatient and discharged with this medication to home. Eight months later, the patient developed alarming signs including gross hematuria, oral ulcers, widespread muscle pain, found to have AKI with Cr of 2.79 and hospitalized for further eval. While hospitalized, the patient was found to have a range of complications including leukopenia with normal granulocyte count, anemia, AKI, proteinuria, and microscopic hematuria. Rheumatological evaluation showed +ANA and a high ANCA titer &amp;gt;1:1280, along with elevated levels of MPO and PR-3, and reduced complement levels. These symptoms and laboratory findings led to a diagnosis of ANCA vasculitis induced by PTU, resulting in the cessation of this medication. Following the discontinuation of PTU there was a notable improvement with normalization of serum Cr and resolution of proteinuria within 1.5 months. Concurrently, MPO and PR-3 levels began to decrease, and her hematological abnormalities resolved. During this period, her Free T4 levels gradually increased, leading to the administration of radioactive iodine for the treatment of her Graves' disease. Discussion: This case underscores the complexities in treating a patient with Graves' disease highlighting the unpredictable and severe side effects of antithyroid drugs like agranulocytosis and ANCA vasculitis. We report the first documented case of sequential thionamide-induced complications: agranulocytosis with methimazole, followed by ANCA vasculitis with propylthiouracil. Although both can arise from immune responses to these medications, they are distinct in their pathophysiology and are not associated with one another. The unpredictable nature of these side effects complicates prevention. Educating patients to promptly report any unusual symptoms and immediate medical intervention with drug discontinuation are key to managing these adverse reactions effectively. Presentation: 6/1/2024