Graves' Disease Research Articles

SAT490 Graves’ Disease In Remission Aggravated By Himalayan Salt Consumption

Abstract Disclosure: M.K. Shakir: None. K.F. Brown: None. J.S. Hatfield: None. N.O. Vietor: None. T.D. Hoang: None. Introduction: In iodine-replete countries, iodine-induced thyrotoxicosis may occasionally develop after ingestion or therapy with high doses of iodine. Recently, Himalayan salt has become very popular to bridge iodine deficiency, control hypothyroidism, and improve thyroid function. We report a patient with a history of treated Graves’ disease (GD) who developed acute thyrotoxicosis following the use of Himalayan salt. Case report: A 58-year-old woman presented with symptoms of heat intolerance, and unexpected 18-lbs weight loss over 3 months. Physical examination: HR 108 bpm, BP 110/70 mm Hg, normal eye examination, thyroid 45 gms, diffusely enlarged. Examinations of the heart, lungs and abdomen were normal. Lab tests: TSH 0.01 IU/mL, free T4 3.8 ng/dL, T3 308 pg/dL, thyrotropin receptor Ab 4.2 IU/L (<1.0), and thyroid stimulating immunoglobulin 1.89 1U/L (0.06-0.55). The I131 uptake was 60% at 4 hours and the thyroid scan revealed diffuse homogenous uptake confirming GD. She was treated with methimazole (MMI) for 2 years and remission was achieved. MMI was stopped and she remained euthyroid. Twelve months later, she developed hyperthyroid symptoms with a 15-lb weight loss, palpitations, and anxiety. Examination confirmed a 50-gram diffuse goiter and other physical findings consistent with hyperthyroidism. She admitted that she had been taking Himalayan salt (approximately 10 grams daily) in place of regular salt for the past 6 months. Lab tests confirmed recurrent GD: TSH <0.01 IU/mL, FT4 4.1 ng/dL, total T3 278 pg/dL, and I131 uptake was 55% at 24 hours. A 24-hours urine iodine was 898 mcg (normal 100-199) and plasma iodine level was 484 mcg/L (normal 52-109). A diagnosis of iodine-induced recurrence of GD was made, and she was treated with MMI and low iodine diet. After 3 months, she improved significantly and was able to discontinue the MMI by 6 months. A follow- up urine iodine was 189 mcg/L with a plasma iodine level of 78 mcg/L. Subsequently she remained euthyroid for an additional 18 months of follow-up without any treatment. Conclusion: The recommended daily dietary allowance for iodine in adults is 150mcg. Himalayan rock salt may provide a rich source of iodine and consumption of large amounts can lead to iodine excess. However, the available studies do not provide the iodine content in commercially available Himalayan salt preparations. Although the Himalayan salt is advertised to have beneficial effects in patients with thyroid disorders, this food supplement may have deleterious effects in susceptible patients who do not have iodine deficiency, have GD, or are at risk for thyrotoxicosis. Indeed, Himalayan salt use exacerbated GD in our patient, as evidenced by iodine overdose during acute exacerbation and resolution of GD with iodine normalization and low dose MMI. We recommend that patients with thyroid disorders be educated regarding Himalayan salt use. Presentation Date: Saturday, June 17, 2023

FRI565 Spontaneous Conversion Of Long-standing Hypothyroidism To Grave’s Disease: A Case Report

Abstract Disclosure: M. Dominic: None. M. Shakir: None. A. Kakkar: None. O.Z. Syed: None. A. Sood: None. D.A. Alvarez: None. Introduction: Autoimmune thyroid diseases associated with IgG4 include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT involves a combination of antibody-mediated thyroid gland destruction and inhibition of thyroid hormone production through a predominance of TSH receptor-blocking antibodies (TBAb). GD is due to increased thyroid hormone production in response to thyroid-stimulating antibodies (TSAb). Although transition to hypothyroidism in patients with GD is commonly encountered in clinical practice, conversion of primary hypothyroidism to GD is a rare event and is described here. Clinical Case: We describe the case of an 81-year-old female with primary hypothyroidism diagnosed more than 10 years ago. She was briefly treated with desiccated thyroid which was later changed to levothyroxine, and she remained euthyroid for several years on Levothyroxine 88 mcg daily. In 05/2021 her routine blood test showed suppressed TSH of less than 0.01uIU/mL for the first time, and it remained consistently low with elevated free T4 & T3 levels despite gradually reducing levothyroxine dose. Patient also started to have tremors, weight loss and anxiety during this period. She was found to have a hypermetabolic thyroid nodule during a PET-CT for evaluation of newly diagnosed Gastrointestinal Stromal Tumor in 09/2022. Levothyroxine was stopped shortly thereafter, but the hyperthyroid labs persisted, following which TSAb levels were obtained and found positive. She was started on methimazole 10 mg twice daily, which resulted in symptomatic improvement and marked reduction of T3 & T4 levels in one month. Clinical lessons: Over-replacement is the most common cause of hyperthyroid symptoms in patients receiving thyroid hormone replacement. Primary hypothyroidism is usually a permanent condition requiring lifelong therapy. Conversion of this condition to GD is a rare entity and can be missed in clinical practice by being mistaken for levothyroxine over-replacement. Proposed mechanisms for conversion of long-standing hypothyroidism to hyperthyroidism include fluctuating levels of TBAbs and TSAbs, spontaneous development of autoimmunity and rarely, production of TSAbs in patients with established Hashimoto’s thyroiditis. Another proposed theory is initial hypothyroidism due to extensive autoimmune gland damage in patients with GD who later develop hyperthyroidism after tissue recovery. It should be noted that this transition to GD has been reported to occur even 30 years after the diagnosis of hypothyroidism. Thus in patients with well-established hypothyroidism requiring lower thyroid replacement doses than before, and labs showing persistent hyperthyroid picture with no evident cause, a careful evaluation is required to check for conversion to GD in order to start appropriate treatment at the earliest. Presentation: Friday, June 16, 2023

FRI558 Hidden Cause Of Decreased Fertility Rate During Grave’s Disease

Abstract Disclosure: T. Kutchukhidze: None. T. Khurodze: None. Introduction: Thyroid autoimmune disorders interfere with the physiology of reproduction, cause premature ovarian aging, and mimic the early stage of menopause. Recently, no specific research was made to measure Grave’s disease and infertility rates in young patients. Case Report: Due to an inability to conceive for two years, a 24-year-old Caucasian female was referred to the clinic with typical symptoms and complaints of Grave's disease. She has a family history of Grave’s disease and Diabetes mellitus. Ultrasound confirmed the presence of a highly vascularized non-homogeneous hyperplastic thyroid gland. A thyroid scan with Tc99m revealed generalized increased uptake. Laboratory investigations showed a decrease in TSH-<0.005mIU/ml (n.0.4mIU/ml - 4.0mIU/ml), elevated FT4-31.8 pmol/l (n.8.0pmol/l-22.0pmol/l), FT3- 9.69pmol/l (n3.4 pmol/l-6.76pmol/l) and positive Anti-TG -190.05 AU/ml (n>150), Anti-TPO -75.7 IU/ml (n>75) Anti-TSHR-27.3 IU/l (n>1,5). Prolactin and gonadal hormones were within normal limits AMH - 1.8 ng/ml(n1.52ng/ml-9.95ng/ml), FSH- 6mIU/ml(n3.9mIU/ml-12.4mIU/ml). The patient was started on Methimazole and Beta-blocker. While decreasing the Methimazole dosage for further discontinuation, disease recurrence developed, and a total thyroidectomy was performed. Postoperatively, the patient was maintained on Levothyroxine. After 6 months of follow-up due to irregular Levothyroxine intake, the patient reached a hypothyroid status, during which, the patient had 2 consecutive spontaneous pregnancies, from which, one ended with spontaneous miscarriage in the early weeks of pregnancy and another, ectopic pregnancy treated with right salpingectomy. HSG confirmed weak left fallopian tube patency. After several months of keeping TSH below 2.5 mIU/ml, IVF treatment was scheduled. The results of the infertility workup showed a decrease in ovarian reserve AMH - 0.163ng/ml (n1.52ng/ml-9.95ng/ml), FSH-16.23 mIU/ml(n3.9mIU/ml-12.4mIU/ml), due to it, modified natural cycle IVF was performed. She received 2 oocytes and 2 embryos. One high-grade blastocyst was transferred in a fresh cycle that ended with pregnancy and delivery. The child was born without a genetic disorder but with natal teeth. Conclusion: This is a rare case of infertility with diminished ovarian reserve due to Grave’s disease. A pregnancy was reached by proper correction of thyroid hormonal parameters and modified natural cycle IVF. It indicates a possible need for close monitoring of the functional ovarian reserve in patients planning pregnancy even in the young age group. Presentation: Friday, June 16, 2023

FRI494 Ischemic Stroke After Radioactive Iodine Therapy In Graves Disease

Abstract Disclosure: T. Rave: None. J. Giunta: None. Hyperthyroidism is defined as excess thyroid hormone, most commonly due to Graves Disease. Thiomides are first line therapy, however more definitive options are radioactive iodine (RAI) or thyroidectomy. RAI enters thyroid follicular cells and destroys the thyroid tissue with beta ray emissions. Patients with Graves disease, toxic multinodular goiter, and thyroid cancer can benefit from RAI, but it is contraindicated in pregnancy, breast feeding, and severely uncontrolled thyrotoxicosis. Early side effects are pancytopenia, thyrotoxicosis, and later complications are bone marrow suppression and cancer. There are several reports of cerebral vascular accidents (CVA) after RAI therapy, however, there is limited research demonstrating whether CVA is a direct consequence of RAI or secondary to thyrotoxicosis. This case describes a possible RAI-induced CVA. A 60-year-old female with a past medical history of type 2 Diabetes Mellitus, hypertension, obesity, and Graves disease presented with altered mental status and gait instability for 1 day. She received RAI therapy 1 day prior to symptom onset for uncontrolled Graves disease. She was previously on Methimazole and PTU, however, both were discontinued due to an intolerable rash. As a result, she was maintained on a beta blocker prior to RAI. On presentation, she was afebrile, normotensive with a heart rate of 79. She was oriented only to person and place and had an unbalanced gait. Her Burch-Wartofsky score was 30, which was concerning for thyrotoxicosis. Her TSH was undetectable and EKG showed normal sinus rhythm. She was placed on atenolol, PTU and hydrocortisone. Her CT head was negative for acute disease, however, her MRI brain diagnosed an acute ischemic stroke. During admission, she had episodes of atrial fibrillation with rapid ventricular response. This patient presented with thyrotoxicosis after RAI therapy complicated by a CVA. It is important to note that on presentation she was reliably taking a beta blocker outpatient and her EKG was normal sinus rhythm making atrial fibrillation a less likely culprit of her CVA. Research has found that hyperthyroidism alone can lead to a prothrombotic state, however, additional literature reports that both hyperthyroid and euthyroid patients have an increased risk of CVA following RAI. Whether a CVA is secondary to thyrotoxicosis or a direct effect of RAI, this potentially life-threatening complication should be discussed with patients prior to treatment. Presentation: Friday, June 16, 2023

FRI553 ICI-induced Thyroid Ophthalmopathy With De Novo Graves’ Disease

Abstract Disclosure: S.I. Moctezuma: None. J. Perlman: None. J.S. Mammen: None. Background: Immune checkpoint inhibitors frequently target the thyroid gland. However, immune checkpoint inhibitor (ICI)-induced Graves’ disease (GD) is rare. To our knowledge, there are no reported cases of thyroid eye disease after immune checkpoint inhibitor therapy in patients with newly positive anti-thyroid antibodies. Clinical Case: An 81-year-old man developed thyroiditis within three weeks of a single dose of ipilimumab/nivolumab for the treatment of metastatic cholangiocarcinoma. ICI therapy was discontinued for cardiotoxicity. He presented one year later with onset of periorbital edema, pain with downgaze, redness, irritation and progressive proptosis with diplopia. He did not have a prior history of thyroid disease. Thyroid function tests before the start of ICI therapy revealed euthyroidism [TSH 2.982 uIU/mL (0.55 - 4.78)]. Symptoms of palpitations, weight loss, and hyper-defecation that characterized his initial presentation with thyroiditis were absent at the time of onset of eye disease. At presentation of thyrotoxicosis his TSH was <0.01 uIU/mL, free T4 3.6 ng/dL (0.89 - 1.76) total T3 190 ng/dL (60-180) Thyroid-peroxidase autoantibodies (TPOAb) and thyroid-stimulating immunoglobulin (TSI) were negative. When his visual symptoms appeared, TPOAb remained negative while a repeat TSI antibody was positive [0.64 IU/L (0.00 - 0.55)]. Thyroid ultrasound at the time of thyroiditis revealed a heterogeneous gland without discrete nodules and a normal vascular flow. Most cases of ICI-induced GD have been reported at the start of therapy, particularly in the first 6 weeks, although thyrotoxicosis has been described to occur as late as 224 days after starting PD-1 inhibitor. GD is more frequently reported with combination anti-CTLA-4 and anti-PD-1 therapy. Patients with thyroid ICI-induced adverse events experience either isolated hypothyroidism or thyroiditis spontaneously evolving towards hypothyroidism. However, ICI-induced GD is more likely to have a relapsing-remitting disease. In 2021, Peiffert et al. described the antibody profile for 243 patients with ICI-induced thyrotoxicosis. In this case series, 5 patients developed thyrotoxicosis with positive thyrotropin-receptor antibodies (TRAb). Only 2 patients had a typical clinical presentation of GD. TSI antibodies were not reported. Furthermore, none of the patients with positive TRAb had Graves’ ophthalmopathy. Conclusion: Our case demonstrates the acquisition of auto-antibodies capable of mediating Graves’ disease, and raises the possibility that thyroid eye disease-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy. These symptoms developed as late as one year after initiation of therapy. As with sporadic cases, this can occur in the absence of clinically significant hyperthyroidism. Presentation: Friday, June 16, 2023

THU670 Serum TSI Concentration In Patients With Graves’ Disease Undergoing Maintenance-dose Of Antithyroid Drug (ATD) And Its Relationship With Disease Relapse After ATD Withdrawal

Abstract Disclosure: P.V. Nguyen: None. K.T. Nguyen: None. Background: Graves' disease (GD) is an autoimmune disorder in which thyroid-stimulating immunoglobulin (TSI) plays a key role in its pathogenesis. TSI assays have been recently optimized in their accuracy, and the procedure has also been simplified, which can potentially replace TRAb measured by conventional TSH-binding inhibitory immunoglobulins (TBII) assays in routine clinical practice. Objectives: Our objective was to study the serum TSI concentration in patients with Graves’ disease undergoing maintenance-dose ATD. We also aimed to assess the predictive value of TSI immunoassay, as well as the clinical signs and thyroid function tests in predicting Graves’ disease relapse following ATD discontinuation. Finally, follow-up would be continued to check for relapse or long term euthyroid status. Methods: Retrospective follow-up study of 352 patients with hyperthyroidism due to GD, treated at the endocrine outpatient clinic of Medic Medical Center, Ho Chi Minh City from January 2000 to April 2021. TSI was measured several times during the course of treatment when planning to stop the medication (at the discretion of the attending physician). ATD withdrawal would be considered when the patients achieved clinical euthyroidism with normal FT4 tests for at least 3 months with minimal dose of ATD. The decision to withdraw ATD was also based on TSI concentration, as well as the goiter’s characteristics and parenchymal vascularity observed via thyroid Doppler ultrasound. Results: The median TSI concentration of patients with GD undergoing maintenance-dose ATD was 1.45 IU/L (normal range <0.10 IU/L), and their thyroid function measured at the same time tended to be euthyroid in our study. TSI cut-off level at ATD withdrawal to predict the recurrence of GD was 1.31 IU/L which corresponded with the sensitivity, specificity, positive and negative predictive values of 63.64%, 78,79%, 50% and 86.67%, respectively. Multiple logistic regression analysis showed that the following factors were associated with an increased risk of relapse after the end of medical treatment: Graves' ophthalmopathy (GO), OR 3.69 (95% CI: 1.06-12.87; p=0.04), treatment duration less than 18 months, OR 7.77 (95% CI: 1.92-31.42; p<0.01), TSI level before ATD withdrawal ≥1.31 IU/L, OR 9.92 (95% CI: 2.77-35.42; p<0.01). Conclusion: At the time of ATD withdrawal, while normal FT4 levels were observed, high TSI levels were indicative of an ongoing immune process. These findings suggest that TSI measurements, in addition to clinical and ultrasound evaluations, may aid in the prediction of GD relapse after ATD discontinuation. In addition, GO, treatment duration of less than 18 months and TSI level before ATD withdrawal ≥1.31 IU/L were associated with an increased risk of relapse of GD after ATD discontinuation. Our study contributes to the expanding literature supporting the clinical utility of TSI assay in the management of GD. Presentation: Thursday, June 15, 2023

FRI542 Long-term Metabolic Outcomes In Graves’ Disease: Is There A Difference Between Oral Anti-thyroid Medications And Radioactive Iodine Treatment?

Abstract Disclosure: E. Shemesh: None. T. Kolitz: None. A. Nathan: None. K.M. Tordjman: None. Y. Greenman: None. E. Izkhakov: None. Introduction: The treatment of hyperthyroidism in patients with Graves’ disease (GD) is associated with various metabolic comorbidities, including weight gain and an increased risk of cardiovascular and cerebrovascular diseases. Few studies have assessed the potential differences in metabolic outcomes between radioactive iodine (RAI) and oral anti-thyroid drug (ATD) therapies. Aim: We sought to investigate the long-term (>10 years) metabolic effects of RAI versus ATD therapy in GD. We also compared the occurrence rates following long-term use to those with short-term (<5 years) use in order to explore a potential "legacy effect". Hypothesis: RAI and oral ATD treatment will differ in their associated risk of metabolic sequelae, including the occurrence of hypertension, dyslipidemia, obesity, and diabetes. Methods: Patients attending the Institute of Endocrinology at the Tel Aviv Sourasky Medical Center filled in a questionnaire on post-RAI or post-ATD treatment for GD. Results: In total, 143 participants had been followed-up for 5 years, and 87 of them (age range 31-88 years, 65 females [74.7%]) had completed >10 years of follow-up (mean follow-up period 14±1 years). During the initial 5-year follow-up period, RAI treatment was associated with a significantly increased rate of obesity and dyslipidemia in the short-term, but no comparable differences persisted into the >10-year follow-up period. However, mean fasting glucose concentrations were higher among RAI recipients compared to ATD recipients (106 and 91 mg/dL, respectively, p=0.037) even after 10 years, and the mean triglyceride concentration was also higher in the former (127 and 88 mg/dL, respectively, p=0.02). There were no significant group differences in the rates of diabetes mellitus or dyslipidemia in the >10-year follow-up period. Conclusions: RAI therapy is associated with long-term higher glucose and triglyceride levels compered to ATD therapy in patients with GD. Clinical metabolic diagnosis are comparable. The significant group differences in the occurrence of metabolic morbidities that had been observed after the first 5 years of follow-up persisted to a greater or lesser extent into the extended >10-year follow-up period, as evidenced by fasting glucose and triglycerides concentrations Presentation: Friday, June 16, 2023

SAT553 A Case of Metastatic Functional Papillary Thyroid Cancer in the Setting of Graves’ Disease

Abstract Disclosure: N. Manuel: None. S.J. Sternlieb: None. J. Dendy: None. Q.Z. Iqbal: None. A Case of Metastatic Functional Papillary Thyroid Cancer In the Setting of Graves’ DiseaseManuel, N., Sternlieb, S., Grissett, B., Iqbal, Q., Dendy, J. Background: Grave’s disease (GD) and papillary thyroid cancer (PTC) can be concomitant diseases. We report a rare case of metastatic PTC with concomitant GD leading to symptomatic hyperthyroidism despite total thyroidectomy. Clinical Case: A 58-year-old woman with longstanding history of thyroid nodules and left dominant nodule with benign biopsy on multiple occasions presented to her PCP with dyspnea, weight loss and globus sensation. CT of the chest was obtained revealing tracheal deviation from neck mass, mediastinal lymphadenopathy and multiple pulmonary nodules. Biopsy of lung nodule showed follicular features consistent with tumor cells of thyroid origin. She had a total thyroidectomy with central neck dissection with a final diagnosis of left sided 5 cm infiltrative follicular variant papillary thyroid carcinoma. Thyroid hormone replacement was initiated and on follow up 4 weeks later she was noted to be tachycardic at weight-based dose. At that time TSH was <0.010 uIU/mL (0.400 - 4.00), free T4 was 1.96 ng/dL (0.71 – 1.51) and Thyroglobulin was found to be 31516 ng/dL (Athyrotic <0.1). Prior to planned RAI she developed symptoms of dyspnea on exertion and edema and was sent to the ER for abnormal D. Dimer. Workup for PE was negative including CTA of the chest. A follow up visit showed further symptoms of hyperthyroidism with worsening fatigue, dyspnea, palpitations and new onset tremor. Levothyroxine dose was decreased further but 2 weeks later she returned to the ER with worsened thyroid function tests, and she was admitted for symptomatic hyperthyroidism. Levothyroxine was held and she was placed on PTU and propranolol. Given the overt symptomatic hyperthyroidism there were concerns for either Jod-Basedow phenomenon from iodine load with recent imaging or for hyperfunctioning PTC metastasis as the cause. Thyrotropin receptor antibody level was checked to further clarify and was elevated at 22 IU/L (0.00 – 1.75) consistent with GD. An I-131 diagnostic whole-body scan demonstrated small foci of right thyroid bed remnant and iodine-avid metastases involving mediastinal nodal disease as well as pulmonary and osseous metastases. She then underwent RAI therapy with 104.5 mCi I-131 without Thyrogen stimulation. Follow up whole body scan showed persistence of iodine-avid metastasis without any new foci of uptake compared to pretreatment scans. Conclusion: Although the coexistence of them is rare, GD should be put into the differential of rapidly progressive metastatic PTC especially if patient markedly hyperthyroid on lower doses of thyroid hormone. While functional thyroid carcinoma is rare, with less than 100 cases in literature, thorough investigation should be completed in order to not miss this concomitant disease process. Presentation Date: Saturday, June 17, 2023

THU240 A Study Of 21 Cases Of Graves Disease In Childhood Presenting At Our Hospital For The First Time

Abstract Disclosure: T. Kashima: None. N. Ujita: None. H. Konno: None. A. Fujioka: None. H. Miyagi: None. M. Igarashi: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. M. Noordin: None. Although Graves disease is most common among women in their 20s and childhood-onset cases account for less than 5% of all cases of Graves disease, they account for the majority of hyperthyroidism in children. We report here a retrospective review of data on pediatric patients with Graves' disease who visited our hospital for the first time at the time of their initial examination. Methods We analyzed 21 pediatric patients with Graves disease who visited our hospital between November 2004 and January 2022. The electronic medical records of 21 patients were retrospectively reviewed for sex, age, height SD score, weight SD score, underlying disease, blood test results, and treatment initiation. Results There were 17 girls and 4 boys. The median age was 11 years and 5 months. Symptoms such as fever, feverishness, palpitations, weight loss, hyperactivity, and irritability were observed in 5 of the patients. Four patients had symptoms related to academic performance, such as low grades and poor concentration. Median physical findings were height SD score 0.62 (N=21), weight SD score 0.06 (N=21), and body mass index -4.4%. Two patients had bronchial asthma and atopic dermatitis, and one had myasthenia gravis and trisomy21 as underlying diseases. One patient was considered to have attention deficit hyperactivity disorder and was receiving antipsychotic medication. The median blood test values at the first visit were ALP 857 U/L (N=19), total cholesterol level 122 mg/dL (N=19), fT3 14.31 pg/mL (N=21), fT4 4.60 ng/dL (N=21), thyroid stimulating antibody 668 % (N=7), TSH receptor antibody 16.6 IU/L (N=20 TSH was less than sensitive in all cases. Nineteen patients received thiamazole. Fourteen patients received propranolol. Five patients received inorganic iodine. Five patients received inorganic iodine, starting at a median of 0.926 mg/kg/day of body weight. Discussion As with adults, females were more common. The symptoms were similar to those of attention deficit hyperactivity disorder, and thus warranted attention. Symptoms related to poor academic performance were also considered important. Anti-thyroglobulin antibodies and anti-TPO antibodies were also detected, suggesting that we should be careful about the possibility of the disease progressing to Hashimoto's disease. Presentation: Thursday, June 15, 2023

FRI572 Teprotumumab In Unexplored Presentation Of Thyroid Eye Disease

Abstract Disclosure: M.T. Torres Torres: None. A.N. Gonzalez Bossolo: None. M.M. Mangual Garcia: None. Thyroid eye disease (TED) is an autoimmune disease of the orbital soft tissue associated with facial disfigurement, diminished quality of life, and potentially vision-threatening consequences that can occur in 40% of patients with Graves’ disease (GD). All the therapies for this condition were off-label with questionable long-term effects until 2020 when the Federal Drug Administration approved teprotumumab, a human monoclonal antibody against insulin-like growth factor-1 receptor, for the treatment of TED. Randomized placebo-controlled trials have demonstrated that teprotumumab reduces proptosis, diplopia, and Clinical Activity Score (CAS) in patients with active TED of less than 1.3 years of duration who were treatment-naïve or previously treated with < 1g of methylprednisolone equivalent therapy. Data on the efficacy of teprotumumab on cases of longer TED duration or previously treated with eye surgery or > 1g of methylprednisolone equivalent therapy for TED is limited as these patients were excluded from the trials. A 76-year-old nonsmoker male with long-standing hyperthyroidism due to GD, glaucoma, and type 1 diabetes mellitus was referred by ophthalmologist due to TED. He received radioactive iodine (RAI) for treatment of GD after failure to Methimazole therapy. After RAI, he reported progressively worsening bilateral eye edema, redness, pain, vision loss, and diplopia requiring hospitalization for an emergent orbital decompressive surgery and intravenous steroid therapy due to sight-threatening Grave’s orbitopathy. He was discharged home with oral prednisone taper down until it was discontinued 6 months later with mild improvement of symptoms. Physical exam was remarkable for bilateral strabismus, orbital chemosis, conjunctival injection and redness, eyelid swelling, limited eye motion, severely impaired visual acuity and color vision, no proptosis, and a CAS of 5 suggesting active TED. Laboratories showed biochemical euthyroidism and controlled glycemia. Teprotumumab was started 2 years and 8 months after symptom onset with marked improvement of inflammatory signs and symptoms, eye motion, visual acuity, diplopia, intraocular pressure, and CAS score decrease to 1 point suggesting inactive disease within 4 weeks of therapy without adverse side effects. This case describes the positive effects of teprotumumab in a patient with characteristics not previously studied such as active TED of longer duration than in clinical trials, previous treatment with orbital surgery or > 1g of methylprednisolone equivalent therapy, and increased IOP. Rather than drawing conclusions, our goal is to create awareness and promote further research of teprotumumab and novel agents in patients with TED with previously uncharacterized presentations as it may have important implications for their management including significant improvement in their quality of life. Presentation: Friday, June 16, 2023

THU665 Unilateral Graves’ Disease In A Bilobar Thyroid Gland: Unusual Cause Of Hyperthyroidism

Abstract Disclosure: K.H. Alaybaa: None. O. Alhuzaim: None. Introduction: Graves' disease (GD) is an autoimmune condition that affects both thyroid gland lobes. GD patients with unilateral thyroid scan uptake are rare. These patients present with classic Graves' symptoms, occasionally with Graves' ophthalmopathy characteristics and increased thyroid hormones, and scintigraphic assessment reveals radiotracer uptake in only one lobe of the thyroid gland. Patient Findings: In this case, a 48-year-old female presented with symptoms and signs indicative of thyrotoxicosis. Lab results revealed that thyroid-stimulating hormone (TSH) was undetectable, while free thyroxine (T4) and free triiodothyronine (T3) were in the high-normal range. Positive results were observed for both thyroid-stimulating immunoglobulin and TSH receptor antibodies. Ultrasonography of the thyroid gland revealed an enlarged left lobe with heterogeneous echotexture and a hyperemic gland without any focal lesions, distinct nodules, or cysts. The NM TC-99M thyroid scintigraphy revealed enlarged and increased radioisotopes uptake in the left thyroid lobe and decreased uptake in the right thyroid lobe, with no hot or cold nodules. The calculated thyroid uptake is 4.5 percent (normal range: 0.5% to 3.5 percent). The most likely diagnosis was unilateral GD. The patient was administered carbimazole and within eight weeks had improved clinically and biochemically. Summary: This patient has thyrotoxicosis symptoms and positive autoantibodies. Tc99m uptake was increased in the left thyroid lobe and decreased in the right thyroid lobe. The left thyroid lobe was hypervascular and enlarged on ultrasonography, indicating the presence of unilateral GD. Unilateral GD is a rare disease with a poorly understood pathophysiology. Presentation: Thursday, June 15, 2023

FRI571 Maternal Graves’ Disease With Foetal Thyrotoxicosis And Goitre

Abstract Disclosure: D. Fennell: None. J. Walsh: None. M. Hatunic: None. Background: Graves’ disease (GD) is an uncommon condition affecting 0.2% of pregnancies. Foetal and neonatal thyrotoxicosis occurs in between 1-5% of pregnant patients with a history of GD, typically beyond 20 weeks gestation. Given its potential for serious morbidity and mortality, prompt recognition and treatment of the condition is essential. Clinical case: A 34-year-old female was referred at 21+2 weeks’ gestation from another hospital due to concerning cardiac findings noted on routine prenatal ultrasound (US). Her medical history was significant for GD (TRAb positive) with moderate ophthalmopathy and total thyroidectomy ten months prior, on L-thyroxine 150 mcg daily. Foetal tachycardia 170-180bpm was noted, with US showing with right ventricular hypertrophy, small pericardial effusion and a 1.9 x 2.7 x 2.8cm neck mass, suspicious for foetal goitre. Maternal laboratory studies showed TSH 2.38mIU/L (0.27-4.2), FT4 16.0pmol/L (12-22), TPO antibody negative <3.0IU/ml and TRAb markedly elevated >30IU/L (0-1.8). A diagnosis of foetal thyrotoxicosis secondary to placental passage of maternal TRAb was made. She was commenced on carbimazole 20mg twice daily at 21+6 weeks’ gestation as treatment, with the goal of normalising foetal heart rate. Careful, weekly follow-up with US scanning noted gradual improvement in the foetus’ condition, with resolution of pericardial effusion and foetal heart rate normalisation. Maternal TFTs were monitored weekly and she remained euthyroid on increased dose L-thyroxine (200 mcg daily). Multidisciplinary team consensus was to proceed with elective Caesarean section at 34 weeks’ gestation, to avoid risk of airway obstruction from foetal goitre. A healthy male infant was born with spontaneous breathing and normal heart rate at delivery. Apgar scores were 9 and 9 at 1 and 5 minutes. Maternal carbimazole was immediately discontinued post-delivery and L-thyroxine reduced to 150 mcg daily. She had an uncomplicated recovery post-Caesarean section. The infant was closely monitored in the neonatal ICU. On day five of life, he became unwell, developing a supraventricular tachycardia. Thyrotoxicosis was confirmed on laboratory studies (FT4 >100pmol/L). Carbimazole, propranolol and Lugol’s iodine were all used as treatment. Thyroid hormone levels normalised within days, with gradual clinical improvement. He was discharged home well four weeks after birth, remaining on propranolol 0.3mg four times daily and carbimazole 0.5mg twice daily, with close paediatric outpatient follow-up planned. Conclusion: Foetal thyrotoxicosis is a rare condition, but can cause serious morbidity, as demonstrated here. First trimester maternal thyroid antibody testing is recommended for all patients with a history of GD, to identify those at risk. Management of the condition is complex, requiring multidisciplinary specialist input for favourable outcome. Presentation: Friday, June 16, 2023

THU364 A Rare Case Of Concurrent Diabetic Ketoacidosis And Grave’s Thyrotoxicosis

Abstract Disclosure: A.D. Teixeira: None. E. Ukponmwan: None. P. Kachhadia: None. S. Aldasouqi: None. A. Abu Limon: None. Introduction: Type 1 Diabetes Mellitus (T1DM) is marked by deranged glycemic control due to the autoimmune destruction of insulin producing β cells in the pancreas. It affects 1.5 million adults in the United States. Approximately one-third of these patients may develop autoimmune polyglandular syndrome (APS). Autoimmune Thyroid Disease (AITD) is the most commonly associated autoimmune disease, with Hashimoto’s Thyroiditis more commonly observed than Graves Disease (GD). Patients with AITD and T1DM meet criteria for APS type 3A. Here, we present a case of a patient hospitalized for T1DM with diabetic ketoacidosis (DKA) who was also found to have concurrent GD. Case Presentation: Our patient was a 50 year old male who presented to the hospital with complaints of nausea and vomiting for a two day duration. He had symptoms of unintentional weight loss, polyuria and polydipsia for about two months prior to presentation. He was found to have blood sugar level of 438 mg/dL, with pH of 7.05 (7.35-7.45), anion gap of 30, bicarbonate level of 7.0 mmol/L (20-30 mmol/L), Beta-hydroxybutyrate level of 82mg/dL (n<4.10 mg/dL). Hemoglobin A1C was 15.1% . EKG revealed atrial fibrillation with RVR, and therefore thyroid function tests (TFTs) were ordered and showed a thyroid stimulating hormone (TSH) level of 0.01uIU/mL (0.35-4 uIU/mL), free thyroxine (FT4) of 1.29 ng/dL (0.61-1.37 ng/dL) and free triiodothyronine (FT3) levels of 4.4 pg/mL (2.8-4.4 pg/mL). Endocrinology evaluation of the patient’s Thyroid US showed some mild vascularity. Cardiac evaluation of patient’s atrial fibrillation did not reveal any other causes of arrythmia. Further labs showed TSI of 2.6 (n<1.3 TSI index) with normal TRAb and TPO levels. T1DM antibody testing revealed GAD-65 antibody (Ab) level of 51.3 nmol/L (n <0.02 nmol/L), Zinc Transporter 8 Ab level of >500 U/mL (n<15 U/mL). He was started on methimazole with good tolerance and was discharged upon resolution of his DKA with multiple daily injections of insulin. Discussion: AITD is the most prevalent autoimmune disease associated with T1DM, with GD being a less common association compared to Hashimoto’s thyroiditis. Many patients diagnosed with T1DM may develop other autoimmune conditions. On rare occasions these diseases can present concurrently, as it did with our patient. Recognition and awareness of APS types helps physicians recognize and screen for other autoimmune conditions that have previously been seen together. Literature search shows very few cases with both diseases presenting at the same time on hospitalization. However, with the recent COVID-19 pandemic, 5 cases were reported of simultaneous disease following vaccination. Our patient had no known exposure to COVID-19 virus or vaccine when he developed symptoms. Presentation: Thursday, June 15, 2023

OR26-03 Treatment With Linsitinib, An IGF-1 Receptor Inhibitor, Prevents Disease Development And Progression In An Experimental Model Of Thyroid Eye Disease

Abstract Disclosure: A. Gulbins: Grant Recipient; Self; Sling therapeutics, Inc. M. Horstmann: Grant Recipient; Self; Sling therapeutics, Inc. A. Daser: None. U. Flögel: None. M. Oeverhaus: Grant Recipient; Self; Sling therapeutics, Inc. B.E. Nikolaos: None. J.P. Banga: None. G. Krause: None. G.D. Hammer: Research Investigator; Self; Sling therapeutics, Inc. A.G. Spencer: Research Investigator; Self; Sling therapeutics, Inc. R. Zeidan: Research Investigator; Self; Sling therapeutics, Inc. A. Eckstein: Grant Recipient; Self; Sling therapeutics, Inc. S. Philipp: Grant Recipient; Self; Sling therapeutics, Inc. G. Görtz: Grant Recipient; Self; Sling therapeutics, Inc. Study objective: We investigated the effect of linsitinib, a small molecule inhibitor of the Insulin like growth factor 1 receptor (IGF-1R), on Graves’ disease and thyroid eye disease. Graves‘ disease (GD), also known as “Basedow's disease“, is the most common cause for hyperthyroidism, typically presenting in patients between 40-60 years. GD is an autoimmune condition of the thyroid which is caused by autoantibodies against the thyroid stimulating hormone receptor (TSHR). Thyroid eye disease (TED) is the most common extra thyroidal manifestation of GD and occurs in about 50% of the clinical cases. Methods: To induce Graves’ Disease in mice we immunized mice 3-times with a plasmid encoding for the A-subunit of the TSHR. During each active (early) and chronic (late) states of the autoimmune disease, linsitinib was administered orally for four weeks. Endocrine orbitopathy and inflammation were determined by histology and MRI. Results: As seen in the histology, linsitinib prevented autoimmune hyperthyroidism, morphological changes, formation of brown adipose tissue in the orbita and orbital T-cell and macrophage infiltration into the orbit in the active state as well as the chronic phase. To evaluate the effect of linsitinib during the course of therapy, living mice were examined via MRI. A distinctive migration of immune cells in the orbit with consecutive inflammation can be seen in the TSHR-immunized group, which is completely blocked by treatment with linsitinib. In addition, the orbital inflammation was partnered with the onset of muscle edema and formation of brown adipose tissue in TSHR-immunized mice, effects that were abrogated upon application of linsitinib. Conclusion: In summary, we demonstrate the development of GD and TED in a mouse model upon immunization against the TSHR. The IGF-1R antagonist linsitinib blocks the development of the local pathologies of GD and TED in an early and late phase of the autoimmune disorder and also prevents development of the autoimmune response. We show that treatment of immunized mice with linsitinib after disease onset significantly limited the severity of the disease, indicating the clinical significance of the findings and providing a path to therapeutic intervention of Graves’ Disease. Our data support the use of linsitinib as a novel first line treatment of thyroid eye disease. Presentation: Saturday, June 17, 2023

THU669 Time To Achieve Euthyroidism In Graves Disease Using Methimazole In An Urban Population

Abstract Disclosure: S.S. Habbsa: None. E. Yunasan: None. A. Krishnan: None. K.M. Munir: None. Context: Previous studies of treatment response in Graves disease have shown that that the mean time to reach euthyroidism with methimazole (MMI) was several weeks to months. In 1987 Okamura et al. concluded that the average period was 6-7 weeks with MMI 30mg daily. Nakamura et al. showed similar data in 2007 (5.8 +/- 4 weeks). These studies were performed in Japanese hospitals over 15 years ago. Limited data exists regarding treatment response times with different doses in a diverse urban population, which may vary with regards to typical dietary patterns, thyroid hormone metabolism and thionamide pharmacokinetics. Objective: The objective of this retrospective chart review was to determine the mean time to achieve euthyroidism with MMI in patients with newly diagnosed Graves disease in Baltimore City. Methods: Patients with Graves hyperthyroidism newly diagnosed in the last 5 years were identified from outpatient endocrine and primary care clinics within the University of Maryland Medical Center healthcare system. Time to achieve euthyroidism (from the start of thionamide therapy to date of euthyroid labs, defined as normal free T4 level) was assessed. Results: 128 patients with recently diagnosed Graves hyperthyroidism were identified (126 patients treated with MMI only and 2 with PTU only). 78% of subjects were female and the mean age at diagnosis was 47 years. The average daily dose of MMI ranged from 2.5mg to 60mg. On average, Free T4 decreased by 0.47 ng/dL per week. The mean time to achieve euthyroidism was 10.1 weeks (8.6, 11.6) overall, similar in males and females. On sub analysis, time to achieve euthyroidism was lower in younger males (age < 40 years) [6.6 weeks (3.9, 9.3)] and older females (age > 40 years) [8.3 (6.9, 9.7)]. Conclusion: The above data may inform expectations for treatment response for newly diagnosed Graves disease, specifically in an urban population on a Westernized diet. Patient forums have shown increasing interest in therapeutic alternatives to thionamides, including specialized diets. This data may help to determine whether other proposed therapies for initial treatment of Graves hyperthyroidism are more or less efficacious. Presentation: Thursday, June 15, 2023

FRI549 The See-Saw Theory - Hypothyroidism Due To Hashimoto's Thyroiditis Followed By Hyperthyroidism Due To Graves' Disease

Abstract Disclosure: P. Sharma: None. Introduction: Hashimoto's thyroiditis is an autoimmune disorder characterized by chronic inflammation of the thyroid gland that leads to hypothyroidism due to formation of autoantibodies against thyroid antigens such as thyroid peroxidase (TPO Ab). Graves' disease is caused by stimulating TSH-receptor antibodies (TRAb) that cause hypertrophy of the thyroid gland leading to hyperthyroidism. While the transformation of Graves' disease to Hashimoto's thyroiditis has been reported, flipping from Hashimoto's thyroiditis to Graves' disease is uncommon. Case Report: A 62 year old female with 20 year history of hypothyroidism secondary to Hashimoto's thyroiditis presented to establish care. She had run out of levothyroxine refills one year prior during COVID-19 pandemic restrictions. She had tachycardia, diarrhea, fatigue, tremors, hair loss, dysphagia, and weight gain. Thyroid panel testing showed hyperthyroidism with an undetectable TSH (normal range 0.45-4.5uIU/ml) and elevated free T4 (2.84, normal 0.82-1.77ng/ml). Patient denied recent infections, iodine intake or iodine contrast exposure. Repeat labs confirmed hyperthyroidism with undetectable TSH with elevated free T4 (3.17ng/ml). Antibody testing comfirmed hyperthyroidism secondary to Graves disease (TRAb 20.7, normal <1.75IU/L). Patient has been on methimazole with fluctuating response and is reviewing definitive therapy options. Discussion: We demonstrate the rare phenomenon of thyroid function transformation from long-standing inhibition to stimulation after 20 years. Hashimoto's thyroiditis is characterized by chronic inflammation due to autoantibodies against TPO, thyroglobulin and the TSH receptor with gradual gland destruction and hypothyroidism. Stimulating autoantibodies to the TSH receptor (thyroid stimulating immunoglobulin (TSIg), TRAb) in Graves' disease lead to hyperthyroidism from gland hypertrophy. The flip from underactivity to overactivity can be explained by recovery of the gland from Hashimoto's thyroiditis injury which gradually leads to an overt response to TSIg, causing a hyperfunctioning gland. An imbalance between the inhibitory and stimulating antibodies can also lead to this transformation. Age, pregnancy and immunomodulating drugs such as alemtuzumab are also thought to play a role. The recovery theory is unlikely in our patient with a 20 year history of Hashimoto's thyroiditis. We believe that she had a high inhibitory antibody titre initially and now has higher titre of stimulating antibodies later, leading to Graves' disease. Luckily, she ran out of levothyroxine otherwise the additive effect of levothyroxine and intrinsic gland activity could have led to worse symptoms. This case highlights that autoimmune hypothyroidism and hyperthyroidism are conditions in the same spectrum, rather than two distinct entities as previously thought. Presentation: Friday, June 16, 2023

FRI531 IgG4 Related Mass -forming Thyroid Disease: Two Case Reports

Abstract Disclosure: R.S. Braham: None. C. Droumaguet: None. M. Vitellius: None. J. Tran-van-nhieu: None. E. Béquignon: None. P. Desgranges: None. N. Limal: None. M. Mahevas: None. B. Godeau: None. IgG4 thyroiditis is an invasive fibrotic process involving the thyroid in a systemic disease. It is a rare inflammatory autoimmune disease with insidious presentation and nonspecific symptoms.We describe two unusual cases of mass forming IgG4 thyroiditis that were diagnosed recently in our department. The first case is about a 42-year-old woman who has a history of Hashimoto thyroiditis with hypothyroidism presenting with a rapid goiter growth, neck pain, dysphagia and hoarseness. A lymphoma was suspected. Ultrasonography shows heterogeneous hypoechoic lesions that may infiltrate the perithyroid muscles. Fine-needle aspiration (FNA) was suspicious of IgG4 infiltrative disease which was confirmed by microbiopsy. Only the thyroid was hypermetabolic on fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) Scan. No improvement under corticosteroid treatment and Rituximab. Surgery was planified to relieve pressure symptoms. The thyroid surgery was very difficult because of the extensive fibrosis and only a biopsy was performed, confirming the diagnosis and excluding malignancy. The second case is about a 68-year-old woman with a history of hypertension and Graves disease presented with a neck right mass that was suspected to be a paraganglioma, hypermetabolic on FDG PET scan with no other localisation. This mass was surrounding the right primitive carotid artery, associated with thrombi of the internal jugular vein. FNA and microbiopsy found a fibrotic non specific tissue. Thyroidectomy and surgical biopsy of the neck mass were performed with histopathology confirming IgG4 disease on the thyroid gland with fibrosis. There were no hypocalcemia in the two cases and no other localisation. IgG4 related mass-forming thyroiditis is an extremely rare disease. It is now a recognizable pattern of IgG4 thyroiditis, and has as differential diagnosis Hashimoto’s thyroiditis, Graves disease and thyroidal carcinoma.We will discuss through these cases the different clinical presentation of this rare disease, the diagnostic tools, the treatment and the long term follow up. Presentation: Friday, June 16, 2023

FRI554 Pretibial Myxedema Associated With Hashimoto Thyroiditis Treated With Teprotumumab

Abstract Disclosure: E.M. Niedzialkowska: None. B. Ajaz: None. A. Pokharel: None. Introduction: Pretibial myxedema (PTM) is a localized thyroid-associated dermopathy characterized by local thickening of the skin of the lower extremities. It mostly develops after the onset of thyroid eye disease (TED). Majority of the cases are associated with Graves disease (GD) but infrequently it can occur in Hashimoto thyroiditis (HT) in the presence of thyroid stimulating immunoglobulins (TSIs). Orbital fibroblasts and the pretibial dermis share antigenic sites that underlie autoimmune thyroid disease. IGF-1 has been reported to potentiate the effects of TSH and TSI on TSHR signaling and fibroblast proliferation. Teprotumumab, a novel monoclonal antibody that blocks IGF-1R receptors, is registered for TED treatment. It is plausible it also improves outcomes in PTM through the same mechanism. Clinical case: 52 year old female reported to our Endocrinology clinic with proptosis and myxedema. The patient was diagnosed with hypothyroidism at the age of 21 and was on substitutional dose of levothyroxine, 125 mcg daily. She developed TED 7 years prior with bilateral exophthalmos with medial rectus muscle infiltration. She underwent 5 decompression surgeries and steroid courses due to concern for optic nerve compression. 4 years prior to the visit she developed bilateral, erythematous pitting edema of the lower extremities with involvement of the pretibial areas, ankles and toes and underwent excess left toe callus excision. Despite multiple courses of intralesional steroid injections and topical ammonium lactate use the patient reported persistent edema, pruritus, and restriction of motion. Laboratory results were significant for TSH of 1.73 uIU/mL (n 0.40 - 4.50 uIU/mL), TRAB >40 IU/L (0.00 - 1.75 IU/L), TSI 4.95 (n <0.10 IU/L), TPO antibody <=35 IU/mL, free ft3 2.5 pg/ml (1.7 - 3.7 pg/mL), free ft4 1.0 (0.7 - 1.5 ng/dL). The patient underwent thyroidectomy with pathology results consistent with Hashimoto thyroiditis (thyroiditis with thyroid follicles, Hurthle cell change, marked lymphoid and fibroadipose tissue). Following the procedure she experienced PTM and TED flare up. Subsequent orbital decompression and orbital steroid injections provided minimal improvement. The patient was started on Teprotumumab (8 infusions every 3 weeks) with marked improvement of orbitopathy (CAS reduction from 6/10 to 1/10) and significant reduction of lower extremity edema and rash. Conclusion: We present the case of Hashimoto thyroiditis associated with TED with PTM successfully treated with Teprotumumab. In TED, TSI binds to IGF-1R creating a complex that promotes orbital inflammation. Teprotumumab is believed to degrade antibody-receptor complex and downregulate fibroblast activation and glycosaminoglycans deposition. We postulate the same process may occur in dermal fibroblasts in the light of PTM improvement after teprotumumab treatment. Presentation: Friday, June 16, 2023

Thyroid Autoimmunity and SARS-CoV-2 Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological culprit of COronaVIrus Disease 19 (COVID-19), can enter the cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which has been found in several tissues including in endocrine organs, such as the ovaries, testes, pancreas, and thyroid. Several thyroid disorders have been associated with SARS-CoV-2 infection [subacute thyroiditis (SAT), thyrotoxicosis, and non-thyroidal illness syndrome (NTIS)] and, in part, they are believed to be secondary to the local virus replication within the gland cells. However, as documented for other viruses, SARS-CoV-2 seems to interfere with several aspects of the immune system, inducing the synthesis of autoantibodies and triggering latent or new onset autoimmune disease (AID), including autoimmune thyroid disease (AITD), such as Hashimoto Thyroiditis (HT) and Graves' disease (GD). Several mechanisms have been hypothesized to explain this induction of autoimmunity by SARS-CoV-2 infection: the immune system hyper-stimulation, the molecular mimicry between the self-antigens of the host and the virus, neutrophils extracellular traps, and finally, the virus induced transcriptional changes in the immune genes; nonetheless, more evidence is needed especially from large, long-term cohort studies involving COVID-19 patients, to establish or reject this pathogenetic relationship.

THU228 Thyrotoxic Periodic Paralysis In Three Adolescent Males

Abstract Disclosure: E. Ra: None. J. Austin: None. Thyrotoxic periodic paralysis (TPP) is a rare but potentially fatal complication of hyperthyroidism associated with Graves disease. Paralysis is due to hypokalemia caused by overactivation of the sodium potassium adenosine triphosphatase (Na+/K+ ATPase). TPP is usually seen in males between 20 - 40 years of age who are of Asian descent. We report 3 Hispanic American adolescent males, as young as 13 years old, who presented with TPP without an existing diagnosis of Graves disease. All three presented with leg weakness and were found to be hypokalemic and ultimately diagnosed with hyperthyroidism. Each patient was supplemented with potassium, either intravenously or orally, with their symptoms resolving within 24 hours. Although TPP is most prevalent in Asian adult males, theorized to be due to an underlying genetic preposition related to a variant of the KCNJ18 gene, there are increasing reports of non - Asian adolescents presenting in TPP. Therefore, pediatric care providers should consider TPP in their differential if a patient presents with weakness and hypokalemia, even without a pre-existing diagnose of hyperthyroidism. Presentation: Thursday, June 15, 2023