Thyroid Disease Research Articles

7637 Characteristics of Thyroid Nodules Among Adolescents and Adults in Medina, Saudi Arabia

Abstract Disclosure: R. Alradadi: None. M. Sindi: None. O. Alrehaili: None. S. Alanazi: None. S. Alahmadi: None. F. Mansuri: None. A. Zain: None. Background: Thyroid Nodules are common clinical finding, with a prevalence of about 20% in young adults and around 70% in the elderly population. A significant increase in the incidence rate of Thyroid Cancer in our population has been noted, over the past 30 years. The aim of the study is to define the characteristics of Thyroid Nodules in adolescents and adults in our region compared to what published worldwide. Method: A retrospective chart review, conducted at our Health Institution. The study included adolescents and adult who had Thyroid Nodules and was seen in the outpatient endocrine clinic in the period between 2018 and 2022, using non-probability consecutive sampling. Patient medical records provided demographic, medical, and laboratory data, and the analysis employed SPSS for statistical assessment​​. Data collection conducted from October through December of 2023 Result: Out of the total sample of 552 patients, there were 84.8% females. More than half of the patients (55.9%) were between 36-55 years of age. 57.4% of patients were overweight or obese. 56.4% presented with goiter. FT3, FT4 and TSH levels were normal among 88.4%, 78% and 83.3% respectively. Anti TPO antibodies were reported in 14.2% as compared to thyroglobulin antibodies in 2.2%.Follicular neoplasm/suspected neoplasm was detected among 8.15% of the sample. Papillary thyroid carcinoma [27/41] was the most frequent finding with positive FNA. Multiple nodules were more prevalent 38.8% as compared to solitary nodules in 34.1%. The right sided nodules were mostly solid 49.2% while hypervascularity was noted in 9.1% and51.4% were of more than 1.5cm. In contrast, left lobe nodule 37% were found to be solid and 6.2% showed hypervascularity and size was more than 1.5cm in 45% of the left nodules Conclusion: The vast majority of adults and adolescents with thyroid nodule were female as expected based on what reported from previous studies. Preexisting Thyroid Diseases present in only small number of patients 15.4 %. Anti-TPO antibody was more predominant than Thyroglobulin Antibody. Follicular neoplasm/suspected neoplasm was detected among 8.15% of the sample. Papillary thyroid carcinoma was the most frequent finding among the positive FNA results. Presentation: 6/3/2024

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 < 0.01, FT4 5.57 ng/dL (0.89-1.76), and TT3 201 ng/dL (60-181). TPO Ab 51 (< 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 >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

8373 High suspicion for thyroid cancer in patient with thyroid Hemiagenesis

Abstract Disclosure: L. Aoun: None. S. Almardini: None. M. Anise: None. F. Haddadin: None. F. Saliba: None. J. Zaidan: None. Background: Thyroid Hemiagenesis (THA) is a rare condition characterized by congenital absence of one lobe of the thyroid gland. Notably, THA is more prevalent in females and the left lobe is more likely to be absent with or without the isthmus. Most patients are euthyroid, and diagnosis is usually incidental, so the true prevalence of THA is uncertain as there are certainly undiagnosed cases. Studies have shown a link between THA, thyroid cancer, and hyperparathyroidism. We present a case of THA and high suspicion for thyroid cancer. Case Presentation: 54-year-old female with history of Rheumatoid arthritis who presented for evaluation of incidental thyroid nodules, occasional palpitations, tremors, and mild change in her voice. She denied abnormal weight loss or diarrhea. No history of radiation to the neck and no family history of thyroid disease or thyroid cancer. The thyroid exam showed an enlarged left palpable nodule. Labs significant for TSH 1.6 mIU/L (normal: 0.4-4 mIU/L), FT4 0.8 ng/dl (normal 0.7-1.9 ng/dL) and T3 77ng/dL (normal: 60-180 ng/dL). Thyroid U/S showed left hemiagenesis and right sided nodules biggest is 1.1 cm solid, hypoechoic with coarse calcifications, FNA was recommended and showed follicular lesion of undetermined significance, molecular testing was done and Thyroseq came back intermediate to high risk RAS and EIF1AX positive reflecting a 70 % probability of cancer. Based on these results, surgery was recommended, and the patient underwent right thyroidectomy. Surgery was uncomplicated and despite reported higher risk of hyperparathyroidism patient’s calcium and PTH were normal, and no parathyroid adenomas were identified intraoperatively. The pathology from the thyroidectomy showed follicular adenoma of 1 cm and no malignancy. She was started on Synthroid 100mcg daily post op. Discussion: This case demonstrates a case of a benign thyroid nodule and preserved parathyroid levels in the setting of thyroid hemiagenesis. Usually in THA, the contralateral lobe is at an increased risk for pathology of compensatory hypertrophy or hyperplasia. According to available studies, cancer association with THA was more common in left hemiagenesis and parathyroid adenomas more common ipsilateral to hemiagenesis . Despite Our patient’s FNA revealed atypical findings, molecular testing revealed RAS and EIF1AX positive, marking intermediate to high cancer risk. However, the thyroidectomy pathology report unveiled no evidence of malignancy, contraindicating the anticipated high cancer risk in those with left THA. This case highlights the rarity of THA and different possible presentations and cancer risks. Presentation: 6/2/2024

9189 Medullary Thyroid Cancer Due To A Novel Ret Oncogene Mutation In A Patient On Glp-1 Receptor Agonist

Abstract Disclosure: K. Lamar: None. D. John: None. O. Faour: None. N. Meda: None. M. Kinaan: None. Introduction: Mutations in the RET oncogene have been associated with increased risk of endocrine neoplasia and Medullary Thyroid Cancer (MTC). We report the case of a patient who has a (c.3281G>A) RET mutation, previously reported as a variant of uncertain significance. Case: A 51-year-old lady presented to our endocrine clinic for routine management of hypothyroidism, type 2 diabetes mellitus, and obesity. She had been on liraglutide, metformin, glipizide, and basal insulin for several years with good diabetes management. She had also been on levothyroxine for more than 10 years. On physical examination, a right thyroid lobe nodule was palpated. We performed a neck ultrasound which revealed a solid, isoechoic nodule measuring (1.23 x 1.42 x 2.00 cm) with no calcifications. Fine needle aspiration was consistent with MTC. She denied family history of thyroid cancer. She was advised to stop liraglutide immediately given risk of MTC with GLP-1 receptor agonist use. Preoperative calcitonin and CEA were markedly high at 935 pg/mL and 60.3 ng/mL, respectively. Fortunately, Gallium Ga-68 dotatate PET CT showed no signs of metastatic disease. The patient underwent a total thyroidectomy with bilateral central and lateral neck dissection. No cervical metastases were noted on lymph node dissection. Genetic tumor testing demonstrated a mutation in the RET oncogene (c.3281G>A), which was previously reported as a variant with unknown significance. Screening for hyperparathyroidism and pheochromocytoma was normal. Postoperative calcitonin and CEA were <2.0 pg/mL and 3.2 ng/mL respectively. The patient continues MTC surveillance under the care of a multidisciplinary team. Discussion: Our case is the first case in literature that identifies the RET oncogene (c.3281G>A) mutation as a pathogenic variant associated with MTC. It also emphasizes the need for close monitoring for thyroid nodules in patients on GLP-1 receptor agonists and pre-existing thyroid disease, through a comprehensive physical examination and neck ultrasound if needed. Presentation: 6/2/2024

6651 A Traceable Clinical Free Thyroxine Assay Based on Equilibrium Dialysis ID-LC/MS/MS

Abstract Disclosure: D. Spector: None. L. Zhang: None. A. Ribera: None. A. Doty: None. C. Tse: None. O. Sugahara: None. N. Vazquez: None. U. Danilenko: None. H.W. Vesper: None. Accurate diagnosis and effective treatment of thyroid diseases rely on reliable thyroid function tests. Serum free thyroxine (FT4) immunoassays (IAs) are most commonly used for FT4 measurements in clinical practice. However, FT4 IAs have not been standardized with large variations between different assay platforms. A reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established for CDC standardization program to support the standardization of clinical assays for patient care. In the current study, we aim to develop a routine clinical FT4 assay based on ED-LC/MS/MS that is traceable to the RMP. ED-LC/MS/MS analysis was performed using a commercially available micro-ED plate. FT4 in dialysate was extracted with a 96-well C18 SPE plate. FT4 in the samples was quantitated by using LC/MS/MS in positive ion mode. The assay was calibrated with the certified primary reference material. By using RMP as a reference, we compared the analysis of 40 single donor sera between the ED-LC/MS/MS assay and FT4 IA on Roche e401platform. ED-LC/MS/MS assay could resolve T4, T3, reverse triiodothyronine (rT3), and other interferences in the samples with C18 chromatography in 4 min. The linear range of the routine FT4 assay was from 0.5-100 pg/mL covering clinically relevant FT4 concentrations including hypo-, hyperthyroid patient samples. The intra and inter-run CV% of the assay in 20 days was 3.72 and 5.25%, respectively. The effect of minor changes to the method conditions was studied. It was determined that serum/buffer ratios from 1:1 to 1:2 in the ED inserts, speeds of shaker for ED, and ED incubation time, did not influence the FT4 measurement. However, elevated ED temperature at 38°C could result in a more than 10% increase in FT4 values. A microplate format for the procedures of ED and SPE is amiable to the application of an automation system which significantly improves the throughput of the procedure. Method comparison showed good agreement between ED-LC/MS/MS assay and RMP in Deming regression analysis with a slope close to 1, while there was significant bias of IA from RMP. ED-LC/MS/MS assay was also applied for pregnancy serum samples with minimal difference on the FT4 measurement from RMP. We have developed a routine clinical FT4 assay that is traceable to RMP. The accuracy, precision, and sensitivity of the assay are suitable for high-throughput FT4 measurements in clinical laboratories and large epidemiologic studies. We demonstrate that the developed method can provide accurate FT4 measurements in patients including pregnant women. Presentation: 6/3/2024

6581 Case of Conversion from Hashimoto’s Thyroiditis to Graves’ Disease: An Unusual Sequence

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: The two most common autoimmune thyroid diseases are Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT is a destructive thyroiditis, via autoantibodies most commonly against the thyroid peroxidase enzyme (anti-TPO), while GD results in hyperthyroidism, due to TSH-receptor stimulating antibodies (TSAb) and Thyroid Stimulating Immunoglobulin (TSI). Case Report: A 23-year-old male presented to the clinic with complaints of weight gain, dry skin and excessive hair loss. His physical examination was non-contributory and laboratory evaluation revealed a TSH of 130 uIU/ml (ref: 0.45-4.5), free T4 (fT4) 0.4 ng/dl (ref: 0.82-1.77), and positive anti-TPO antibodies, for which he was started on levothyroxine (LT4) supplementation for newly diagnosed HT. Over the first five months on treatment, his TSH and T4 progressively improved to 31.8 uIU/ml and 1.48 ng/dl, respectively. Six months later, his TSH rapidly decreased to 0.01 uIU/ml, with an fT4 elevation to 2.45 ng/dl, alongside developing hyperthyroid symptoms like weight loss, insomnia and palpitations. Due to persistently positive anti-TPO antibody titers, his hyperthyroidism was considered iatrogenic, and LT4 dose was gradually reduced, but eventually required to be discontinued. A thyroid ultrasound depicted generalized increase in vascularity, consistent with active thyroiditis. He continued to have a significantly suppressed TSH <0.005 uIU/ml and elevated fT4, off all medications, and was also found to have multiple positive antibody titers [TSI of 1.02 IU/L (ref: < 0.55), thyroglobulin antibody of 351 IU/ml (< 0.9) and anti-TPO Ab >600 IU/ml (ref< 34)]. He was then diagnosed with new GD, and thyroid suppression therapy with 10mg/day of methimazole was initiated, to which he rapidly responded, with a TSH of 0.059 uIU/ml and reduced fT4 of 1.37 ng/dl. His diagnosis of GD was confirmed via an I-123 thyroid uptake scan which revealed a homogenous increased tracer uptake of 57% at 24 hours (ref 15-35%), following which he received definitive therapy for GD, with radio-active iodine (RAI) ablation with 20.6 mCi of I-131. Discussion: As HT and GD have a common autoimmunity-based pathophysiology, conversions between the two clinical states have been described, though HT to GD, as seen in our patient is much less common than the reverse conversion. Some described mechanisms include an antibody switch from thyrotropin receptor blocking to stimulating action, HT-induced thyrotroph destruction resulting in GD antibody formation, and treatment with LT4. Simultaneously elevated levels of both TSI and anti-TPO can occur, and therefore treatment and diagnosis should be based on thyroid function tests and clinical presentation. Patients with autoimmune thyroid disease require close monitoring, due to the potential risk of conversion from one clinical end of the spectrum to the other, and early recognition is important. Presentation: 6/1/2024

8800 A Case of Hypopituitarism Due to Sheehan Syndrome

Abstract Disclosure: N. Akabogu: None. S. Dejhansathit: None. F. Marium: None. B. Stanley: None. E.M. Bazuaye: None. L.S. Krusniak: None. L.G. Kurukulasuriya: None. U.Z. Khan: None. Background: Sheehan syndrome, which is also known as postpartum pituitary infarction, refers to the necrosis of the anterior pituitary gland due to postpartum hypovolemia, hemorrhage, shock, resulting in various degrees of hypopituitarism. The pituitary gland enlarges during pregnancy due to estrogen stimulation and becomes hyper-vascular, making it prone to infarction with postpartum hemorrhage. The initial symptoms include hyponatremia, weakness, weight loss, but the most prominent specific symptoms are inability to nurse and postpartum amenorrhea. Depending on the severity of hypopituitarism, symptoms may develop within the first few days to weeks after delivery or may take months to years to develop. Case presentation: 35year-old Caucasian female with a medical history of gestational diabetes, hyperlipidemia, and hypertension, who presented to the hospital with flu-like symptoms, leg pain, abdominal pain, and proximal muscle weakness. The evaluating hospitalist observed that patient appeared sluggish and spoke with a deep coarse voice, which concerned him for hypothyroidism. Thyroid function test revealed undetectable free T4 with inappropriately normal TSH of 1.38 – consistent with secondary hypothyroidism. Additional history from patient uncovered 9 months history of constant fatigue, weight gain, dry skin, hair loss, cold intolerance, and intermittent ankle swelling. There is no history of brain irradiation or head trauma. She has 4 biological children, and her last childbirth 3years ago was complicated by severe bleeding from her incision site, requiring transfusion of 6 units of blood. She has been amenorrheic since and is neither on birth control nor had hysterectomy. Physical exam showed mildly enlarged tongue, diffuse pallor, dry scaly skin on upper arms, scanty eyebrows, and slowed speech. Further work-up for pituitary insufficiency showed secondary adrenal insufficiency, secondary hypogonadism, low prolactin, and growth hormone deficiency. There was no evidence of AVP deficiency. Other lab and clinical findings were hypoglycemia, hyperlipidemia, elevated CK, elevated Cr, pericardial effusion, and diastolic hypertension. Pituitary MRI showed markedly attenuated and flattened pituitary gland with no focal mass. Patient was given stress dose hydrocortisone and thyroid hormone replacement, initially IV then oral. Following hydrocortisone and thyroid hormone replacement, her diastolic BP, hypoglycemia, CK, and Cr improved. Further management plans include initiating estrogen (plus progesterone) for bone health. Conclusion: Although Sheehan syndrome is rare in developed countries, it does occur. This case emphasizes the importance of detailed history taking, to discover the root of patients’ presentation. Even though TSH is the screening test for thyroid disease, when pituitary etiology is suspected, it is important to also check a free T4. Presentation: 6/1/2024

8229 Prevalence of Thyroid Cancer in Patients with Hashimotos Thyroiditis Presenting Concomitant Thyroid Nodular Disease

Abstract Disclosure: M.A. Alvarez Castillo: None. L. Sanchez Arriaga: None. A. Segovia Palomo: None. Introduction: Hashimoto's thyroiditis (HT) is the most frequent autoimmune thyroid disease and the main cause of goiter and hypothyroidism; it induces a process of aseptic autoimmune inflammation. Fibroinflammatory changes lead to the development of thyroid nodules (TN), additionally chronic inflammation is an important player in the development of cancer, although this association is controversial. The prevalence of thyroid cancer (TC) in patients with HT ranges from 0.61-58.4% (25.01%), being higher than in patients with TN without concomitant HT. Objective: To know the prevalence of malignancy in patients with HT who present thyroid nodular disease. Methodology: An observational, descriptive, retrospective, and longitudinal study was carried out. Patients with HT diagnosis were selected by measuring Ab TPO and/or Ab TG who presented an ultrasound diagnosis of TN and FNAB of the thyroid lesion had been performed. Descriptive statistics and linear regression were used. Results: 87 patients: 6 (6.9%) men and 81 (93.1%) women aged 47.9 (12.7) years. 4 (4.5%) required FNAB in 2 TN, for a total of 91 TN studied. 64% had a diagnosis of hypothyroidism and were taking LT4, TSH 4.40 (4.44) mUI/mL, FT4 1.00 (0.27) ng/dL. Mean Ab TPO was 794.7 ± 1354.6. Diagnosis time 19.5 (29.1) months. 39.6% the detection was made by the patient and 35.2% by the doctor. Major axis was 18.8 (12.1) mm. Ultrasound pattern of single TN 58.2% and multinodular 41.8%. Median TIRADS was 4, with a mode of 5. 81.3% reported Bethesda II and 18.7% malignant or suspected, were sent for surgery, malignancy was confirmed in 16/ 17 lesions. 14 (15.3%) were TPC and 2 lymphomas, the main subtypes were classic papillary and NHL, respectively. Mode of ATA risk was intermediate. Multivariate analysis only TIRADS represented risk factor (OR 2.08) Conclusions: The frequency of TC in our population was 15.3%, which reflects a higher prevalence of malignancy in thyroid nodules in patients with chronic thyroiditis, in accordance with what has been reported in other series. Presentation: 6/3/2024

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

12233 Weight Gain Following Thyroidectomy For Benign Conditions

Abstract Disclosure: A. Krueger: None. A. Chiu: None. S. Pabich: None. S. Syed: None. A. Poloju: None. S. Holoubek: None. Background: Weight gain is a common complaint of patients with hypothyroidism irrespective of etiology that causes dissatisfaction and decreased quality. Patients often report thyroidectomy as the precipitating event leading to subsequent weight gain and resistance to weight loss. Reported data on body weight changes following surgery are conflicting and there is limited literature on patients with benign pathologies. The average weight gain in the general population has been reported as 0.5/year. The primary outcome of this study was to determine if patients undergoing thyroidectomy for benign conditions experienced greater than expected weight gain compared to the general population when TSH values were controlled. Secondary outcomes assessed were whether pre-operative disease pathology or antibody status affected weight changes. Methods: A retrospective review was performed on 325 patients undergoing total thyroidectomy for benign conditions from January 2015 to December 2020 using the University of Wisconsin Thyroid Surgery Database. The weight change was determined from the time of surgery to the following intervals: 1-2 years, 2-5 years, and >5 years. Study groups were then compared by pathology and presence of antibodies. Exclusion criteria included age <18 years, thyroid cancer, pregnancy within one-year post-surgery, incomplete weight or TSH data, post-operative gastric-bypass surgery, and patients who were not euthyroid pre- and post-op. Results: Our patient population (n=219) gained a mean of 1.58 kg at the 1-2 year interval. There was no significant difference in weight gain based on pathology or antibody status. At the 2-5 year interval, the average weight gain was 2.05 kg and those with antibodies had significantly higher weight gain. Patients with TPO antibodies (n=34) gained a mean weight of 4.58 kg, and those with TRAB and or TSI antibodies (n=17) gained a mean weight of 4.67 kg. Those with both types of antibodies (n=10) did not have any significant weight gain. Conclusion: Conservatively, the expected weight gain of the general population over 2-5 years is 2.5 kg. Using a logistic regression model, patients with autoimmune thyroid disease had twice the odds of gaining more weight than expected by 2-5 years. The presence of auto-immune thyroid antibodies may serve as a target population for intensive weight management programs following surgery. Presentation: 6/1/2024

8049 Beyond Metastasis: Parasitic Thyroid Tissue Mimicking Thyroid Cancer

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. N.A. Mungo: None. This case study details a complex clinical scenario involving a patient with diaphoresis and a familial history of thyroid cancer. Initial suspicions of functionally active metastatic thyroid cancer led to a thyroidectomy and cervical lymph node dissection, only to reveal unexpected parasitic thyroid tissue. This case highlights the importance of meticulous evaluation and follow up similar presentations, shedding light on the rarity of this phenomenon.The patient, experiencing a year of diaphoresis unresponsive to estradiol therapy, underwent imaging revealing multiple thyroid nodules. A left superior nodule (TI-RADS 4) and a more concerning right mid-posterior nodule (TI-RADS 5) prompted fine needle aspiration (FNA). FNA of the right thyroid nodule exhibited Bethesda category III atypia, no molecular samples were taken at that time, while cervical lymph node FNA yielded nondiagnostic results.Subsequent ultrasound showed no interval change in the right thyroid nodule but raised concerns about increased solid components and decreased echogenicity in other nodules. Due to patient concerns of positive family history of thyroid cancer, the lymph node was biopsied. The result yielded a low cellular sample, but follicular thyroid tissue was present. The patient elected to undergo thyroidectomy as she did not want to continue monitoring. Pathology revealed parasitic thyroid tissue in the lymph node and nodular follicular thyroid disease, with no evidence of papillary thyroid carcinoma in the gland. Notably, the patient had no history of thyroid surgeries, ruling out traumatic rupture or implantation from a follicular adenoma. However, the possibility of follow-up metastatic follicular carcinoma cannot be entirely excluded on histologic grounds.Follow-up tests were recommended, encompassing mutational analysis, whole-body scans, and thyroglobulin (Tg) monitoring. Molecular analysis did not favor cancer. Tg levels remained at (18 ng/ml, n< 35ng/ml) of initial evaluation six weeks post surgery and repeat testing is pending. Ablative radioactive iodine therapy may be appropriate as resection of all parasitic thyroid tissue can prove difficult.This case emphasizes the diagnostic challenges posed by the rare occurrence of parasitic thyroid tissue, often mistaken for metastatic thyroid cancer. The findings contribute to our understanding of uncommon thyroid pathologies. The clinical implications of this case extend to the importance of heightened clinical suspicion in intricate endocrine cases. Presentation: 6/3/2024

7053 Sex Differences in Endocrine-Related Pre-existing, COVID-19- and COVID-19 Vaccine-Related Health Conditions and Adverse Events

Abstract Disclosure: J. Knapp: Other; Self; Co-founder, Aseesa Inc. R. Karumanchi: None. C. Fee: None. S. Inslicht: None. A. Bhargava: Other; Self; Co-Founder, Aseesa Inc. COVID-19 illness-related symptoms and outcomes are highly variable, with reported sex differences. mRNA vaccines were deployed for the first-time on a large scale for COVID-19, and the endocrine effects of Pfizer’s and Moderna’s mRNA vaccines, remain to be elucidated. Associations between COVID-19 illness and/or COVID-19 vaccines and reproductive disturbances have been reported based on large nation-wide surveys and targeted studies. Yet, none of the studies have directly ascertained similarities and differences between reproductive adverse outcomes from COVID-19 illness in unvaccinated individuals versus COVID-19 mRNA vaccines in individuals without COVID-19 illness. Here, we report preliminary findings on endocrine systems from a global survey of ∼8,000-10,000 participants collected between February 2022 and October 2023. Approximately 62.5% of the participants were from the United States, and the remaining were international. Nearly 1.49% of respondents reported hospitalization after COVID-19, whereas 5.69% of the respondents reported hospitalization after vaccination in our cohort. SARS-CoV-2-related severe symptoms were reported by ∼9.3% of COVID-19 vaccinated versus 6.7% of unvaccinated individuals (p<0.001). Women reported more vaccine-related adverse events (AEs) than men; 30% of men and 19% of women reported no AEs after any vaccination dose. After the first dose, 60% women and 48% of men reported some AEs, whereas after the second dose, 46% of women and 40% of men reported experiencing several AEs. Sex differences were present in endocrine and autoimmune pre-existing health conditions, including thyroid disease (13%F vs 3%M), osteoporosis (6%F vs 1%M), elevated cholesterol (M>F), and hypertension (M>F). Nearly 5% of women reported pre-existing irregular menstrual cycle irregularities and hormonal changes, whereas only 2% of men reported hormonal irregularities. In unvaccinated individuals, after COVID-19 illness, nearly 6% of women reported experiencing hot flashes, whereas 7.5% reported irregular menstrual cycles. In COVID-19 vaccinated individuals without SARS-CoV-2 infection, 94.6% of men and 62.5% of women respondents reported no reproductive changes. Of those reporting reproductive AEs included hormonal changes in 5% of women and 3.5% men, hot flashes in 8.5% women and 1.9% men, heavy periods and/or dysmenorrhea in 16.7% of women, and irregular periods in17.1% of women. In summary, reproductive AEs in vaccinated individuals without COVID-19 illness were more frequent than in unvaccinated individuals with COVID-19 illness. A detailed and thorough follow-up is needed to better understand if pre-existing health conditions exacerbated vaccine-associated AEs. Presentation: 6/3/2024

12233 Weight Gain Following Thyroidectomy For Benign Conditions

Abstract Disclosure: A. Krueger: None. A. Chiu: None. S. Pabich: None. S. Syed: None. A. Poloju: None. S. Holoubek: None. Background: Weight gain is a common complaint of patients with hypothyroidism irrespective of etiology that causes dissatisfaction and decreased quality. Patients often report thyroidectomy as the precipitating event leading to subsequent weight gain and resistance to weight loss. Reported data on body weight changes following surgery are conflicting and there is limited literature on patients with benign pathologies. The average weight gain in the general population has been reported as 0.5/year. The primary outcome of this study was to determine if patients undergoing thyroidectomy for benign conditions experienced greater than expected weight gain compared to the general population when TSH values were controlled. Secondary outcomes assessed were whether pre-operative disease pathology or antibody status affected weight changes. Methods: A retrospective review was performed on 325 patients undergoing total thyroidectomy for benign conditions from January 2015 to December 2020 using the University of Wisconsin Thyroid Surgery Database. The weight change was determined from the time of surgery to the following intervals: 1-2 years, 2-5 years, and >5 years. Study groups were then compared by pathology and presence of antibodies. Exclusion criteria included age <18 years, thyroid cancer, pregnancy within one-year post-surgery, incomplete weight or TSH data, post-operative gastric-bypass surgery, and patients who were not euthyroid pre- and post-op. Results: Our patient population (n=219) gained a mean of 1.58 kg at the 1-2 year interval. There was no significant difference in weight gain based on pathology or antibody status. At the 2-5 year interval, the average weight gain was 2.05 kg and those with antibodies had significantly higher weight gain. Patients with TPO antibodies (n=34) gained a mean weight of 4.58 kg, and those with TRAB and or TSI antibodies (n=17) gained a mean weight of 4.67 kg. Those with both types of antibodies (n=10) did not have any significant weight gain. Conclusion: Conservatively, the expected weight gain of the general population over 2-5 years is 2.5 kg. Using a logistic regression model, patients with autoimmune thyroid disease had twice the odds of gaining more weight than expected by 2-5 years. The presence of auto-immune thyroid antibodies may serve as a target population for intensive weight management programs following surgery. Presentation: 6/1/2024

8534 Comorbid Autoimmune Thyroid Disease in a Parent-Child Pair with Resistance to Thyroid Hormone Beta

Abstract Disclosure: A.H. Smith: None. E. Grethen: None. Resistance to Thyroid Hormone Beta (RTHβ) is an inherited disorder caused by mutations in the gene encoding the thyroid hormone receptor beta protein, resulting in decreased binding affinity to triiodothyronine in certain tissues. An asymptomatic individual with RTHβ may demonstrate abnormalities in serologic evaluation of thyroid hormone markers. When other thyroid pathologies present with RTHβ, however, the diagnosis and management can quickly become complex. Below we discuss two cases, a parent-child pair, with different presentations of presumably the same RTHβ gene. Patient 1 is a 61-year-old male with a history of autoimmune thyroiditis several years ago, presenting for continuation of care; he has had levothyroxine doses gradually uptitrated to over 3 mcg/kg to normalize TSH despite persistently high free T4 levels. He also has a family history notable for six out of seven siblings with autoimmune thyroid disease. Patient 2 is a 44-year-old male who was evaluated for hypothyroidism and difficulty with levothyroxine titration. Prior to consultation, he underwent radioactive iodine ablation for presumed Grave’s disease, followed by total thyroidectomy due to persistent symptoms. Post-operatively, he required high doses of levothyroxine to maintain normal TSH levels; however T4 and T3 levels remained high. Both patients confirmed proper levothyroxine supplementation. Further analysis of both patients demonstrated mildly elevated TBG and normal alpha subunit. Patient 2 pursued genetic testing while patient 1 declined, revealing a heterozygous R320S mutation in the TR-beta protein. Further testing and genetic counseling were offered to other family members. Propranolol and levothyroxine supplementation were titrated accordingly; triiodothyronine administration was attempted but did not alleviate symptoms. These two cases demonstrate the increased risk of autoimmune thyroid disorders in patients with RTHβ and the unique challenges they pose in accurate diagnosis. Autoimmune thyroiditis in RTHβ, with goiter, elevated T4 and elevated T3 levels, can be easily confused with Grave’s disease, especially when TSH is suppressed during active thyroiditis. Timely diagnosis can aid in targeted management of sequelae, prevent ineffective treatments for comorbid conditions which may mimic other diseases, and provide anticipatory/preventive guidance for family members to help with screening. Presentation: 6/1/2024

7504 A Case of Methicillin Sensitive Staphylococcus Aureus Thyroiditis

Abstract Disclosure: K. Patel: None. P. Kachhadia: None. S. Khan: None. F. Akanbi: None. A. Abu Limon: None. S.A. Aldasouqi: None. Introduction: Acute suppurative thyroiditis refers to bacterial infection of the thyroid gland. It is rare as the thyroid gland is typically protected from infection due to isolation of the gland from neighboring structures as well as its rich blood supply and adequate lymphatic drainage. It shares characteristics with subacute and autoimmune thyroiditis which make for difficult diagnosis. Here we present a case of acute suppurative thyroiditis in the setting of methicillin sensitive staphylococcus aureus (MSSA) bacteremia. Case Presentation: We have a 45 year old gentleman with a history of polysubstance abuse who was admitted after a drug overdose. He was being treated for rhabdomyolysis and approximately ten days after admission he became febrile with Tmax 103.3 Farenheit with a sore throat and dysphagia. Workup showed leukocytosis, ESR 86 mm/h [0-15], CRP 45.5 mg/dL [0-1], blood cultures with MSSA, negative viral upper respiratory panel, throat culture, Syphilis and HIV testing. He had a positive Hepatitis C antibody without a detectable viral load. Echocardiogram ruled out vegetations. He was treated with cefazolin. CT neck was obtained and showed thyroid enlargement. Subsequent ultrasound showed heterogeneous echotexture and increased color flow and a left inferior pole nodule 2.3 x 2.1 x 2.0 cm. Thyroid labs showed TSH 0.16 [0.35 - 4.01 u[IU]/mL,] Free T4 3.91 ng/dL [0.61 - 1.37], TPO <0.3. The nodule was biopsied and endocrinology was consulted. On exam thyroid was nontender. He was started on beta blockers and thyroid labs were monitored. TSI and TRAB were negative. TSH, Free T4 and Free T3 improved to normal range. Nodule biopsy results showed benign follicular cells with abundant acute inflammation suggestive of an abscess. Metronidazole was added after biopsy results. Post antibiotic therapy, CRP improved to 1.7 mg/dL. Discussion/Conclusion: Incidence of acute suppurative thyroiditis has been published as occurring <1% of all thyroid diseases. One systematic review found 200 cases reported from January 2000 to January 2020. Prior case reports have described acute suppurative thyroiditis in adult patients with prior thyroid gland pathology or an immunocompromised state and some demonstrated a correlation with intravenous drug users. The most common culprits include Staphylococcus spp, Streptococcus spp, Salmonella spp, Escherichia spp. Management includes antimicrobial therapy and/or needle aspiration. Non-responders can undergo incision and drainage of abscess or thyroidectomy. Mortality was reported in about 8% of the reported 200 cases. In our patient, his history of drug use and Hepatitis C likely made him prone to infection. Although there was no description of pus during biopsy, pathology suggested acute inflammation. This along with elevated inflammatory markers led to the diagnosis. This case highlights an uncommon but potential cause of thyroiditis. Presentation: 6/3/2024

8385 Coexistence of Parathyroid Adenoma & Papillary Thyroid Cancer: A Rare Case Report

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. M. Roy: None. S. Rathore: None. Prevalence of primary hyperparathyroidism (pHPT) ranges from 0.1- 0.4% in general population. Nodular thyroid disease is an increasingly common incidental diagnosis due to widespread use of ultrasound. Papillary thyroid cancer (PTC) is the most common cancer of thyroid gland. Here we report a 53 year old post-menopausal woman presented with weight loss, generalised body aches, arthralgia, myalgia, and proximal muscle weakness. She was hypertensive and clinically euthyroid. Physical examination revealed generalized tenderness all over the body but no thyroid or parathyroid nodules on palpation. Biochemical evaluation showed hypercalcemia 12.1mg/dl (8.4-10.2mg/dl), PTH>2000pg/ml (14-72pg/ml), ALP-1855 U/L (40–125 U/L), decreased phosphorous of 2.4mg/dl (25-4.6 mg/dl), and vitamin-D of 46 nmol/L ( 75-250 nmol/L). USG neck revealed a heterogeneous lesion at the lower pole of right lobe of thyroid gland & two small hypoechoic nodules seen in the right lobe of thyroid gland. FNAC from nodules was inconclusive. USG abdomen revealed nephrocalcinosis. DEXA scan showed severe osteoporosis. Tc99mSestamibi SPECT-CT showed uptake at lower pole of right lobe of thyroid. On exploration, two nodules were palpated in the right lobe of the thyroid and simultaneous right hemi-thyroidectomy was performed. Histopathologic report confirmed parathyroid adenoma (figure 1) as well as presence of carcinoma in the two nodules: one was a papillary thyroid cancer (Classic variant) and the other a follicular variant of papillary thyroid carcinoma (figure 2). Margins were negative for malignancy. She was treated with levothyroxine to maintain TSH <0.1U/L and followed up with annual ultrasound screening. At 2 year follow up, patient was symptom free with improved T score on DEXA scan and no nodule over residual thyroid gland. Discussion: Co-existence of pHPT and PTC ranges from 2.3-4.3%. The use of ultrasound neck as a routine imaging modality for localisation of parathyroid adenoma allows detection of thyroid nodules. Benign and/or malignant thyroid nodules are commonly seen in patients with pHPT and this can range from 2-15%. Women have higher risk for co-existence. The relationship between the two diseases is thought to be incidental. Some authors have suggested possible role of shared genes, embryological factors, transcription factors, vitamin-D deficiency and hyperparathyroidism that could lead to activation of angiogenic factors and carcinogenesis. Fig. 1. Parathyroid adenoma. (a)Tc99m sestamibi scan showing right inferior parathyroid adenoma (b) Parathyroid adenoma (400x high power) comprising predominantly of Chief cells with mild pleomorphism. Fig. 2. Histopathology of PTC. (a)Papillary Carcinoma thyroid. 10xPhotomicrograph showing areas of calcification. (b) Papillary Carcinoma thyroid. Photomicrograph showing thyroid with papillary pattern with areas of infiltration. Presentation: 6/1/2024

12602 The Effect of Three-Month Semaglutide Treatment on Serum TSH and Thyroid Hormones in Individuals with Obesity

Abstract Disclosure: P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. A.J. Kretowski: None. L. Szczerbinski: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) play a crucial role in managing obesity and diabetes, significantly influencing glycemic control and weight management. Previous studies showed that GLP-1 RAs therapy affects thyroid-stimulating hormone (TSH) levels; however, they were limited by small sample sizes and did not extensively cover newer agents like semaglutide. Thus, the aim of this study was to assess the impact of a three-month semaglutide treatment on thyroid hormones and TSH levels in individuals with obesity, without diabetes, and examine the relationship of these changes with weight loss. Methods: We analyzed data from 290 patients participating in the GAROS study, excluding those on medications affecting thyroid function or with a known history of thyroid disease. All participants underwent a three-month treatment with oral semaglutide, followed by a three-month discontinuation phase. Measurements of TSH, free triiodothyronine (fT3), free thyroxine (fT4), and body weight were taken at baseline, at the end of the treatment period, and three months post-treatment discontinuation. To compare changes in TSH, fT3, and fT4 levels, as well as weight, across the study timelines we used non-parametric tests due to the non-normal distribution of the data. We also employed multiple linear regression models to evaluate the association between thyroid hormone changes and weight loss, both in the aggregate and stratified by sex. Results: Initial fT3, fT4, and TSH levels were 3.13 pg/ml (SD=0.38), 0.94 ng/dl (SD=0.10), and 1.64 mIU/l (SD=0.82), respectively. Post-treatment, fT3 decreased on average by 0.33 pg/ml (p<0.001), TSH by 0.32 mIU/l (p<0.001), and fT4 increased by 0.06 ng/dl (p<0.001). Upon discontinuation, fT3 and fT4 levels did not fully return to baseline values but showed a significant shift in that direction (p<0.001 for fT3 and p=0.006 for fT4, compared to baseline). Conversely, TSH levels adjusted back to their baseline values (p=0.26). Notably, changes in fT4 levels, unlike fT3 and TSH, were significantly negatively associated with weight changes during (p=0.030) and post-treatment (p=0.008), across sex-stratified analyses. Conclusions: Semaglutide treatment significantly alters thyroid hormones and TSH levels in patients with obesity, with some effects reversible post-discontinuation. Except for fT4, these hormonal changes appear to be independent of the weight loss effects of semaglutide. Although the magnitude of these alterations might not be clinically significant, they do imply that GLP-1 RAs may have additional physiological effects. The exact nature of the interaction between semaglutide and thyroid function, however, remains to be fully elucidated, highlighting the need for further research to clarify these mechanisms. Presentation: 6/2/2024

8295 Development of Type 1 Diabetes and Primary Adrenal Insufficiency Secondary to Immunotherapy Treatment for Chordoma in a Patient With Hypopituitarism

Abstract Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None. Background: Cranio-cervical chordomas are rare locally aggressive, invasive, and slow-growing bone neoplasms. Treatment involves a combination of excision and radiation therapy, and sometimes immunotherapy for recurrent disease. Endocrine-related toxicities from immune checkpoint inhibitors are well recognized and include autoimmune thyroid disease, hypophysitis, and less commonly, type 1 diabetes mellitus (T1DM) and primary adrenal insufficiency (PAI). We present a case of a patient with hypopituitarism secondary to a recurrent and aggressive skull base chordoma with leptomeningeal spread who developed T1DM and PAI after treatment with nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody. Diagnosis of PAI was delayed because patient was on hydrocortisone replacement for secondary adrenal insufficiency. Case Report: A 38 year old male with history of primary hypothyroidism underwent endoscopic endonasal transsphenoidal resection and adjuvant proton beam radiation therapy for a sellar chordoma after presenting with diplopia. Testing was consistent with hypopituitarism and the patient was started on hydrocortisone, levothyroxine, and testosterone replacement. Due to recurrent disease and leptomeningeal spread, he subsequently underwent three additional surgeries and two courses of gamma knife radiosurgery. Five months after starting systemic therapy with nivolumab, the patient developed insulin dependent diabetes presumed to be T1DM secondary to immunotherapy. He was continued on nivolumab, and six months into treatment developed hyperkalemia and hyponatremia requiring inpatient admission. He was treated with diuretics and fluid restriction initially without improvement in his electrolyte abnormalities although he remained relatively asymptomatic. Laboratory evaluation showed a renin activity of 66 ng/mL/H and aldosterone < 4.0 ng/dL (<= 21) with sodium of 128 mmol/L (135-145) and potassium 5.8 mml/L (3.3-4.9). Due to suspicion for PAI secondary to checkpoint-inhibitor induced adrenalitis, 21-hydroxylase antibody was checked and was positive. It was felt that the patient had not had other signs or symptoms classic for PAI such as nausea and/or vomiting because he had already been on glucocorticoid replacement for his hypopituitarism. Ultimately, the patient was started on fludrocortisone, with resolution of his hyponatremia and hyperkalemia. Conclusion: Adrenal insufficiency from immunotherapy is most commonly caused by hypophysitis. T1DM and PAI due to adrenalitis are less common. In patients on steroid replacement for hypopituitarism, the development of electrolyte abnormalities with or without symptoms in a patient on immunotherapy should raise the suspicion for rarer endocrine side effects such as primary adrenal insufficiency. Presentation: 6/3/2024

7729 Autoimmune Thyroid Disease And Risk of Premature Ovarian Failure - A Comprehensive Analysis Combining Observational Studies, Two-sample Mendelian Randomization Study, And Targeted Drug Forecast

Abstract Disclosure: R. Wang: None. T. Dou: None. L. Guan: None. X. Qi: None. X. Wang: None. C. Yu: None. Q. Guan: None. Premature ovarian failure (POF), a condition impacting women's fertility and physical well-being. Specifically, autoimmune thyroid disease (TAI) is recognized as an organ-specific autoimmune condition that may co-occur with POF in clinical scenarios, yet the precise nature of their relationship remains uncertain. The objective of this study is to investigate the influence of TAI on ovarian function, identify shared pathogenic genes, predict potentially effective drugs, and establish a foundation for clinical interventions. Firstly, a case-controlled study was conducted using the Nationwide Readmissions Database (NRD) in the United States. This involved identifying patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) as the study group, and those without deficiency as the control group, to explore the correlation with POF. Additionally, an Asian population-based case group comprising 897 patients with POF and a control group of 897 healthy women were gathered to analyze the association of POF with TAI-related antibodies, namely TGAb and TPOAb. Furthermore, a two-sample Mendelian randomization(MR) study was undertaken in European populations to investigate the causal relationship between TAI and POF. Lastly, genes associated with HT, GD, and POF were compiled from the GEO, GeneCards, and DisGeNET databases, and common genes were identified through intersection. Subsequent gene ontology and pathway enrichment analyses, protein-protein interaction analyses, and candidate drug predictions were performed based on the shared genes. The findings revealed a significant association between TAI and POF in the NRD, with patients exhibiting TAI being notably more prone to POF compared to the control group (OR 1.78, 1.34-2.35, P<0.001). Subgroup analysis further demonstrated an increased risk of POF in patients with HT (OR 1.51, 1.02-2.22, P<0.05) and GD (OR 2.18, 1.45-3.29, P<0.05). In the Asian population, a retrospective analysis indicated a positive correlation between TPOAB positivity and POF (OR 1.76, 1.24-2.51, P<0.05). MR analysis unveiled a causal relationship between GD and POF. Through a comprehensive examination of multiple gene databases, 47 common genes were identified between HT and POF, and 20 common genes between GD and POF. Enrichment analysis demonstrated relative similarities in cytokines and signal transduction, apoptosis, inflammatory response, and other aspects between HT and POF. GD was found to potentially influence ovarian function through pathways such as the PI3K-Akt signaling pathway and adhesive plaques. Dexamethasone, rapamycin, and other drugs emerged as potential therapeutic options for both diseases. In summary, our study suggests that TAI, particularly GD, may elevate the risk of POF. Additionally, we predict potential therapeutic drugs, and shed light on the potential biological mechanisms linking HT/GD and POF. Presentation: 6/3/2024

7007 Analytical & Clinical Performance of a Novel Sensitive Rapid Bioassay for Thyrotropin Receptor Antibodies

Abstract Disclosure: P.D. Olivo: Consulting Fee; Self; QuidelOrtho, CA USA. H. Kim: Employee; Self; QuidelOrtho. L. Miao: Employee; Self; QuidelOrtho. J. Houtz: Employee; Self; QuidelOrtho. M. Luffy: None. J. Wolf: None. G.J. Kahaly: Grant Recipient; Self; QuidelOrtho, USA. Background: The role of stimulatory anti-TSH-R-Ab in the pathogenesis of autoimmune hyperthyroidism is well established. A novel and rapid cell-based bioassay, referred to as Turbo TSITM, for measurement of thyroid-stimulating autoantibodies (TSAb) was recently developed. An assessment of the analytical & clinical performance of this bioassay is described herein. Methods: Turbo TSI greatly reduces the complexity and time required to measure TSAb. It avoids the need for cell culture, has no wash or lysis steps, and has a total turn-around-time of less than 90 minutes. Thawed cells from Turbo TSI kits were treated with different concentrations of a World Health Organization (WHO) international standard (IS) TSI or TSAb-positive serum. TSAb was measured as a function of luciferase activity measured as relative light units (RLU) and converted into international units per liter (IU/L). Two users at two sites performed analytical performance studies on numerous samples, over multiple days. Results: The limit of blank, limit of detection and limit of quantitation were determined to be 0.007 IU/L, 0.014 IU/L, and 0.021 IU/L, respectively. Receiver operator characteristics (ROC) analysis determined the cut-off to be 0.0241 IU/L with an area under the curve of 0.984. The linear range was shown to be from 0.015 to 11.958 IU/L. The intra-laboratory precision was ≤15 percent CV. The overall reproducibility of the assay was ≤20 percent CV for five concentrations (0.06 to 5.16 IU/L). Interference and cross reactivity studies with a variety of substances showed that the assay was robust. Turbo TSI demonstrated 95.2% (95% CI 83.3-98.1) sensitivity and 94.8% (95% CI 90.9-97.1) specificity when compared with an FDA-cleared bioassay (Thyretain® TSI) using serum from 295 patients with autoimmune thyroid disease (AITD). When testing 172 unselected, consecutive TSAb+ AITD patients, a US based, prospective, multicenter, blinded study showed a 98% concordance between Turbo TSI and Thyretain® TSI. When comparing Turbo TSI, Thyretain TSI and a TSH-R-Ab binding immunoassay (Cobas) in 670 unselected, consecutive, treated and untreated AITD subjects, sensitivity was 83%, 79% and 68%, respectively (Turbo vs. Cobas, P<0.001). Furthermore, testing 84 patients with naïve, untreated Graves’ hyperthyroidism, detection of TSH-R-Ab was 100%, 98% and 92%, respectively (Turbo TSI vs binding assay, P<0.01). Finally, 95% vs. 73% of 332 patients with Graves’ orbitopathy were TSH-R-Ab+ with Turbo TSI vs. binding assay (P<0.001). Conclusions: The Turbo TSI bioassay exhibits excellent analytical & clinical performance, a high level of reproducibility, and compares well with the FDA-cleared Thyretain® TSI. Presentation: 6/1/2024