Thyroid Peroxidase Research Articles

Thyroid peroxidase antibodies were associated with prevalent carotid intima-media thickness in middle-age and older adults: the ELSA-Brasil cohort.

Understanding the relationship between antithyroperoxidase antibodies (TPOAb) and carotid intima-media thickness (cIMT) could provide insights into the mechanisms linking thyroid autoimmunity and cardiovascular disease. We aimed to explore the association of multiple categories of TPOAb with the increased cIMT at baseline and at follow-up in participants from the ELSA-Brasil Study. This prospective cohort study analyzed data from 9,264 participants (51.5 ± 8.9 years old, 55.9% women) without a history of cardiovascular disease. Fasting serum TPOAb levels were determined. Values of cIMT equal to or above one deviation standard of the sample's mean were classified as increased cIMT at baseline. The increased cIMT after the 8-year follow-up was calculated after excluding participants with increased cIMT at baseline. Multivariate analyses were done using binary logistic and Poisson regression models. The increased cIMT was prevalent in 14.3% of the participants at baseline and its development occurred in 16.8% participants during the cohort. After adjustment for all confounder variables, TPOAb detectability (OR = 1.84, 95%CI = 1.21-2.79), and low detectable (OR = 1.81, 95%CI = 1.18-2.75), high detectable (OR = 2.01, 95%CI = 1.29-3.11) and positive (OR = 1.70, 95%CI = 1.07-2.70) TPOAb were positively associated with increased cIMT at baseline. The associations of low and high detectable TPOAb and increased cIMT at baseline were consistent when excluding those with thyroid dysfunction. There was no statistically significant association between TPOAb levels and increased cIMT at follow-up (p > 0.05), neither for all sample nor for euthyroid individuals. Different levels of TPOAb, including its detectability, were associated with increased cIMT at baseline in the studied sample. We highlight that may be relevant to consider the levels of TPOAb detectability as possible marker of increased cardiovascular risk.

The association between circulating saturated fatty acids and thyroid function: results from the NHANES 2011-2012.

Excessive saturated fatty acids (SFAs) are known to be detrimental to human health. Although the majority of research and dietary guidelines have focused on the intake of SFAs, there has been limited attention to the relationship between circulating SFA levels and hormonal regulation, such as that of thyroid hormones. To explore potential associations, we conducted an investigation with 579 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Subgroup analyses and multivariable linear regression models were used to estimate the relationships between eleven distinct SFA concentrations and various thyroid parameters. For 579 adults, subgroup analysis of thyroid stimulating hormone (TSH) revealed significant differences in nine specific SFAs and the total SFA levels (all p < 0.05). Furthermore, multivariable linear regression analysis identified positive correlations between certain SFAs and various parameters, including TSH, total triiodothyronine (TT3), free triiodothyronine (FT3), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), thyroglobulin (Tg), the ratio of FT3 to free thyroxine (FT4) (FT3/FT4), and the thyrotroph T4 resistance index (TT4RI). Conversely, negative correlations were observed between certain SFAs and total thyroxine (TT4), FT4, the ratio of FT3/TT3, and the thyroid feedback quantile-based index (TFQI) (all p < 0.05). These findings collectively suggest associations between SFAs and thyroid parameters, highlighting the need for future studies to elucidate the underlying mechanisms of these interactions.

5143 Disulfide Bonds of Thyroid Peroxidase Are Critical Elements for Subcellular Localization, Proteasome-Dependent Degradation, and Enzyme Activity

Abstract Disclosure: H. Iwasaki: None. H. Suwanai: None. K. Kanekura: None. N. Satoshi: None. F. Yakou: None. H. Sakai: None. K. Ishii: None. N. hara: None. R. Suzuki: None. Background: Congenital hypothyroidism (CH) is caused by mutations in cysteine residues including Cys655 and Cys825 that form disulfide bonds in thyroid peroxidase (TPO). It is highly likely that disulfide bonds play an important role in TPO activity. However, no study has comprehensively analyzed cysteine mutations that form disulfide bonds in TPO. In this study, we induced mutations in cysteine residues involved in the formation of disulfide bonds and analyzed their effect on subcellular localization, degradation, and enzyme activities to evaluate the importance of disulfide bonds in TPO. Methods: Vector plasmid TPO mutants C655F and C825R in CH patients were transfected into HEK293 cells. TPO activity and protein expression levels were measured by Amplex red assay and western blotting. The same procedure was performed in the presence of proteasome inhibitor MG132. Subcellular localization was determined by immunocytochemistry and flow cytometry. The location of all disulfide bonds within TPO was predicted by in silico analysis. All TPO mutations associated with disulfide bonds were induced. TPO activity and protein expression levels were also measured in all TPO mutants associated with disulfide bonds using the Amplex red assay and western blotting. Results: C655F and C825R showed significantly decreased activity and protein expression compared to the wild-type (P &amp;lt; 0.05). In the presence of a proteasome inhibitor MG132, the protein expression level of TPO was increased to the level comparable with that of the wild-type but its activity did not. The degree of subcellular distribution of TPO to the cell surface in the mutant was lower than that in the wild-type TPO. Twenty-four cysteine residues were involved in the formation of 12 disulfide bonds in TPO, and all TPO mutants harboring an amino acid substitution in each cysteine showed significantly reduced TPO activity and protein expression levels. Furthermore, the differences in TPO activity depended on the position of the disulfide bond. Conclusions: All 12 disulfide bonds play an important role in the activity of TPO. Furthermore, the mutations lead to misfolding, degradation and membrane insertion. Presentation: 6/2/2024

6441 Hyperthyroidism in a patient with Lyme disease

Abstract Disclosure: J. Epstein: None. C. Berman: None. Background: Lyme disease is known to cause inflammation in many organs. There are few case reports in the literature that discuss the association between Lyme disease and thyroiditis. This case underscores the need to further research the association between Lyme disease and thyroid physiology. Clinical Case: A 15-year-old female with a history of polycystic kidney disease is referred to a pediatric endocrinologist for primary amenorrhea and hyperthyroidism. Initial thyroid function tests demonstrated suppressed TSH of 0.03 mIU/L with an elevated free T4 level of 4.0 ng/dL and total T3 of 437 ng/dL. The patient was asymptomatic with normal vital signs, and physical exam was normal without goiter, tremor, tongue fasciculations, or exophthalmos. Thyroid ultrasound demonstrated a mildly heterogenous appearance without nodules. Incidentally, Lyme disease was concurrently diagnosed based on a positive screen confirmed with immunoblot. There was no known tick exposure or rash, but the patient had recently spent time outdoors in upstate New York. Doxycycline was started for the treatment of Lyme disease and repeat thyroid tests one week later showed a decrease in free T4 and total T3 levels, although still elevated. Thyroid antibodies including thyroid peroxidase (TPO), thyroglobulin and thyroid-stimulating immunoglobulin (TSI) were negative. After finishing doxycycline treatment, she developed a hypothyroid state with a TSH of 6.39 mIU/L, free T4 of 0.6 ng/dL, and a normal total T3 of 148 ng/dL. Free T4 has since normalized however TSH remains elevated. The patient continues to be monitored closely without pharmacologic treatment. The evolution of this patient’s thyroid function is consistent with thyroiditis and appears similar to the course of Hashitoxicosis, however antibodies remain negative. There is literature that suggests molecular mimicry between Borrelia proteins and thyroid autoantigens due to amino acid sequence homology. Some Borrelial proteins are found to share antigenic properties with multiple thyroid related proteins, specifically the TSH receptor, TPO, thyroglobulin and sodium iodine symporter, potentially leading to thyroiditis. Three case reports describe adults with hyperthyroidism in the setting of Lyme disease, however in these cases thyroid antibodies (TPO +/- thyroglobulin) were positive. Two of these patients were asymptomatic, similar to our patient. This phenomenon has never been described in a pediatric patient and illustrates the need to consider Lyme disease as a potential cause of destructive, transient, thyroiditis. Presentation: 6/1/2024

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

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

7099 Severe Hypothyroidism from Potassium Iodide Supplements: A Case of Failure to Escape from Wolf- Chaikoff Effect

Abstract Disclosure: M.G. Hamilton: None. A. Kulkarni: None. P. Lekprasert: None. Introduction: The Wolf-Chaikoff effect (WCE) is a physiological response of the thyroid gland to supraphysiologic iodide levels. Failure to escape the WCE can lead to thyroid dysfunction, and we present such a case in a patient with Hashimoto’s thyroiditis taking high-dose potassium iodide (KI). Case Description: A 44-year-old female with hypothyroidism secondary to Hashimoto’s thyroiditis presented with 10-pound weight gain, extremity swelling, fatigue, and abnormal menstruation. She was prescribed Levothyroxine several years ago but stopped taking it shortly after as she felt no improvement. On physical exam, she was bradycardic with heart rate of 58 bpm. There is no goiter but dry skin and edematous lower extremities. Labs revealed TSH of 127 pg/mL (0.35-4.94), free T4 0.1ng/dL (0.8-1.8), TPO Ab 645 (&amp;lt;9) IU/mL in comparison to her labs 2 months ago of TSH 11 pg/mL and free T4 0.9 ng/dL. Suspicion for worsening hypothyroidism from Hashimoto’s was low given this dramatic change on labwork and clinically. On further questioning, she had been taking KI 130 mg/day (Iodine 100 mg, daily requirement 150 mcg/day) as advised by her homeopathic doctor. The supplements were stopped, and she was re-started on Levothyroxine. After 8 weeks, she reported improvement of symptoms and weight loss. TSH is normal at 3.54pg/ml and free T4 1.2 ng/dL. Discussion:The WCE serves as a protective mechanism to decrease thyroid hormone production in the setting of high iodide levels to prevent development of hyperthyroidism. WCE is explained by the formation of Iodopeptides inhibits thyroid peroxidase (TPO) mRNA and protein synthesis resulting in an inhibition of thyroglobulin iodination. WCE is temporary and expected to wane over a few days to weeks and is known as the Wolf-Chaikoff escape due to down regulation of the sodium iodine symporter (NIS) thereby decreasing the intrathyroidal inorganic iodine concentration and permitting normal TPO activity. Rarely, failure to escape WCE can lead to hypothyroidism due to continued suppression of thyroid hormone synthesis. Risk factors include underlying thyroid diseases i.e. Hashimoto’s or other causes of thyroiditis, use of Amiodarone, Lithium or Iodine-containing radiocontrast media and KI supplements. In our case, Hashimotos’ thyroiditis predisposed her to thyroid dysfunction and failure to escape from WCE after taking high-dose KI supplements causing severe hypothyroidism. Thus, this report highlights that in clinical practice, especially in patients with pre-existing thyroid dysfunction, a significant TSH increase, a high suspicion index is needed to investigate for other causes like concurrent use of iodine-containing food/drug leading to the failed escape from WCE apart from verifying compliance to thyroid replacement therapy. Presentation: 6/3/2024

6771 New onset Graves’ Disease in a Patient with Hashimoto's Thyroiditis and Positive Thyroid Peroxidase Autoantibodies. Case Report

Abstract Disclosure: M.M. Eid: None. J.L. Zapater: None. Introduction: Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) are the most common thyroid autoimmune disorders. Transition of GD to HT is common, but transition of HT to GD is rare. Case: A 55 year old, female with depression, HTN and fibromyalgia. She was referred for evaluation of chronic fatigue and reduction in functional capacity. Five years earlier, she had also been evaluated for fatigue. Labs at that time: TSH 3.80 µIU/ml (0.35-3.74 µIU/ml), free T4 0.8 ng/dl (0.76-1.46 ng/dl), thyroid peroxidase antibody (anti-TPO) 605.6 U/ml (0-60 U/ml), and anti-thyroglobulin antibody (anti-TG) 37.2 U/ml (0-60 U/ml). Subclinical hypothyroidism was diagnosed, but no levothyroxine was initiated. Her TSH was found to be normal in 2019 and 2021. At the current clinical encounter, other than fatigue she denies weight/voice change, tremor, palpitation, anxiety, recent flu like illness or radiation exposure, neck swelling/pain, heat intolerance, or difficulty swallowing. Her daily medications are amlodipine 10mg and duloxetine 20mg. She had menopause 2 years ago. She has no known allergy. She has a brother with rheumatoid arthritis. She denies smoking or alcohol consumption. On exam, vital signs are normal, and BMI is 28.1. There is diffuse, firm thyromegaly without a palpable nodule. There is no cervical lymphadenopathy, tremor, neck tenderness, exophthalmos, or lid lag. Creatinine, liver enzymes are normal but hemoglobin is 9gm/dl. Anti-tissue transglutaminase and anti-gliadin antibodies were negative. Her thyroid labs were: TSH &amp;lt;0.008 uIU/ml, free T4 1.06ng/dl, free T3 4.07 pg/ml (2.3-4.2 pg/ml), total T3 1.74 ng/ml (0.60-1.81 ng/ml), anti-TPO antibody 12,414 U/ml, anti-TG antibody 22 U/ml, thyrotropin receptor antibody (TRAB) 15.24 IU/L (0-1.75 IU/L), and thyroid stimulating immunoglobulin (TSI) 331% (&amp;lt;130%). Thyroid uptake scan showed 49% iodine-131 uptake in symmetric and homogenous uptake, and no hot or cold nodules. GD was diagnosed, methimazole 5mg daily was initiated. Conclusion: Our case had subclinical HT with positive anti-TPO antibodies 5 years preceding the onset of GD. Causes of autoimmune conversion are not well understood. Viral infection or radiation exposure in genetic susceptible patients have been assumed as triggers (1). The blocking and stimulating action of TRAB on TSH receptors is considered as a possible mechanism of switching between hypothyroidism and hyperthyroidism. Clinical and biochemical evaluation for possible conversion to GD in patients with HT is recommended (2).

6575 From Tonsils to the Thyroid: A Rare Case of Acute Suppurative Thyroiditis in an Immunocompetent Adult

Abstract Disclosure: F. Sajid: None. A. Mubashir: None. F. Mohsin: None. M. Sattar: None. Introduction: Acute suppurative thyroiditis (AST) is a rare infection of the thyroid gland due to its high vascularity, protective encapsulation, and high iodine content. Most AST cases occur in children with anatomical aberrations or in immunosuppressed adults. Here, we describe a case of AST in an immunocompetent woman. Case: A 54-year-old woman with no medical history presented to the emergency department due to dyspnea, dysphagia, and odynophagia for two days. She reported a four-day history of sore throat, fever, and chills. She was saturating well on room air but was sitting in a tripod position. She had erythema, swelling, tenderness to palpation in the anterior neck with a hoarse voice, and moderate trismus. Nasopharyngoscopy revealed no mass, but the scope could not pass beyond the velum due to edema. The patient’s condition quickly deteriorated, necessitating emergent intubation for acute hypoxic respiratory failure. After intubation, the patient had cardiac arrest with asystole requiring resuscitation and successful ROSC. The initial CT scan showed extensive soft tissue abnormalities in the nasopharynx and parapharyngeal tissues, extending to the thyroid gland and mediastinum with the possibility of developing abscesses. A thyroid ultrasound showed a heterogeneous thyroid gland without nodules or increased vascularity. Treatment commenced with ampicillin-sulbactam. Laboratory results showed Free T4 of 4.74 ng/dL (0.58-1.64), TSH 0.03 MCIU/mL (0.39-4.08), Total T3 1.56 ng/dL (0.72-1.35), WBC 19.3 K/UL (4.8-10.8), and elevated ESR and CRP levels. Thyroid-stimulating Immunoglobulin (TSI), Thyroid Peroxidase (TPO) Antibody, and Thyrotropin Binding Inhibitory Immunoglobulin (TBII) were negative, making AST the top differential. Methimazole was initiated due to concerns of thyroid storm, but it was quickly tapered due to a significant decrease in Free T4 levels and suspicion of AST. A repeat CT scan revealed more defined abscesses along the bilateral pharyngeal walls extending to the thyroid bed. The patient underwent bilateral tonsillectomy and drainage of the abscesses. She was extubated the following day. Cultures from the abscesses grew rare Klebsiella pneumoniae, susceptible to Ampicillin-sulbactam. A barium swallow on day 14 showed no evidence of a pyriform sinus fistula. She was discharged on day 15 with Augmentin for 7 days. On discharge, free T4 decreased to half (2.39 ng/dL), and Total T3 normalized (1.08ng/dL). Conclusion: This case presents a rare instance of AST in an immunocompetent patient without anatomical anomalies, stemming from the spread of peritonsillar and parapharyngeal abscesses into the thyroid bed. AST should be considered in cases of deep neck infections, as it is a potentially life-threatening disease. It is crucial to identify and treat AST early to prevent complications. The primary treatment involves antibiotics, incision, and drainage. Presentation: 6/1/2024

12393 Myxedema Presenting With Impending Cardiac Tamponade : A Case Report

Abstract Disclosure: A. Hoskote: None. V. Gupta: None. J. Seidenberg: None. The widespread availability of thyroid stimulating hormone (TSH) assays, routine screening and affordable replacement therapy has resulted in decreased prevalence of complications of untreated hypothyroidism. “Myxedema heart” is a rare syndrome that results in bradycardia, cardiomyopathy and pericardial effusion. We present a rare case of cardiac tamponade due to myxedema in a patient with unidentified hypothyroidism. A 49-year-old male was brought to the ER by his family for several weeks of cognitive slowing, weakness and inappropriate behavior involving defecating on himself eating old food and barricading in his room. The patient denied past medical or psychiatric history, medication use or recent physician evaluation. On exam he had macroglossia, was disheveled, forgetful but alert with slow speech, ataxia and muscle wasting. He was afebrile and hemodynamically stable. EKG showed sinus bradycardia. Labs were notable for sodium 133, hemoglobin 8.8g/dL and TSH was incidentally &amp;gt;100U. Levothyroxine was begun. The next day, he was noted to have increased lethargy, bradycardia and hypoglycemia and was transferred to the intensive care unit with concern for myxedema coma. Free T4 was &amp;lt;0.3 ng/dL (0.6-1.6) and free T3 was 1.6pg/mL (2.5-3.9). An echocardiogram revealed a large circumferential pericardial effusion with right atrial and ventricular collapse with tamponade. Treatment with 5 mcg liothyronine, intravenous levothyroxine and stress dose hydrocortisone was begun. A pericardial drain was placed, draining 980mL of sanguineous fluid. After clamping trials, the drain was removed 48 hours later. Labs revealed thyroglobulin &amp;lt;0.1ng/mL (1.6-50), thyroid peroxidase (TPO) antibody 574 IU/mL (&amp;lt;9), thyroglobulin antibody &amp;gt;2500 (&amp;lt;4) and thyroid ultrasound showed a normal sized thyroid gland with heterogenous echogenicity confirming a diagnosis of Hashimoto’s thyroiditis. Serial echocardiograms during the admission and a follow-up two months later showed a stable posterior effusion with no recurrence of the anterior pericardial effusion. Gradually mentation, hemodynamics and electrolyte derangements improved, and he was discharged on oral levothyroxine. TSH values showed sequential improvement to 48U in 15 days and to 11U in 2 months. Myxedema is a manifestation of severe hypothyroidism. The pericardium, a collagen-rich structure, is susceptible to myxedematous infiltration, leading to pericardial effusion. While small pericardial effusions are common with chronic hypothyroidism, a large pericardial effusion with tamponade is a rare life-threatening complication that requires prompt recognition and management. Clinicians must promptly identify myxedema and replace thyroid hormone to prevent progression of pericardial effusion to tamponade, maintaining especially high suspicion in those at risk of poor access to healthcare or inadequate health literacy. Presentation: 6/3/2024

8454 Iron deficiency as a cause of euthyroid syndrome

Abstract Disclosure: O.V. Samburskaya: None. S. Kalinchenko: None. L. Vorslov: None. Annotation: The prevalence of euthyroid pathology syndrome is increasing, and the cause of its occurrence remains unknown, despite the decrease in the quality of life of these patients, there is no treatment for this pathology. One of the reasons may be iron deficiency, which not only reduces the activity of thyroid enzymes, but also disrupts the feedback between a decrease in triiodothyronine and the level of thyroid-stimulating hormone (TSH). Materials and methods: There are 6 patients under observation, aged from 25 to 55 years, average age 38.4±12.67 years, gender distribution: 4 women 67% and 2 men 33%, who are undergoing treatment to compensate for iron deficiency and simultaneously control thyroid function. The analysis of iron deficiency is performed according to blood test parameters: total blood count, total serum iron binding capacity, transferrin, ferritin, serum iron. The function of the thyroid gland is determined by blood test parameters: T4 free, T3 free, TSH.The received data. According to the results of the data obtained, latent iron deficiency was found in all 6 patients. All patients have a decrease in thyroid hormone levels: T3 free 3.87±0.45 pmol/l (reference range 3.69-8.46 pmol/L) and T4 free 14.17±1.23 pmol/L (reference range 12.3-22.8 pmol/L) is closer to the lower limit of normal, but TSH is also closer to the lower limit of the norm is 1.46±0.33 µm/ml (reference range 0.70-5.9 µm/ml). Discussion: The existing iron deficiency leads to the development of chronic hypoxia, which leads to a violation of the functioning of many endocrine glands, including a violation of the work of thyroid enzymes: thyroid peroxidase and deiodinases, with a decrease in the synthesis of thyroid hormones (T4 and T3), and according to the feedback principle, an decrease in the level of thyroxine and triiodothyronine is expected raising the level of TSH. However, with chronic hypoxia, iron deficiency, hypoxic dysfunction develops not only of the peripheral endocrine glands, but also hypoxic hypothalamic-pituitary dysfunction, which leads to an inadequate response of the pituitary gland, i.e. the absence of an increase in TSH in response to a decrease in thyroid hormones. Conclusion: All patients with euthyroid syndrome need to evaluate the biochemical parameters of the body's iron supply, and the elimination of deficiency of which may be the necessary treatment for patients with euthyroid pathology. Presentation: 6/2/2024

8759 Mild Iodine Deficiency During Pregnancy Impairs Hypothalamus-Pituitary-Thyroid Function Programing of the Adult Male Offspring

Abstract Disclosure: M. Oliveira: None. E. Tavares: None. G. Henrique: None. J. Pinto: None. C. Serrano-Nascimento: None. Introduction: Iodine plays a crucial role in the biosynthesis of thyroid hormones and is essential for proper thyroid embryonic development. While severe iodine deficiency during pregnancy and lactation has well-documented deleterious effects, the consequences of mild iodine deficiency (MID) remain not fully understood. MID during pregnancy is a reality in numerous countries, even in regions with seemingly adequate iodine supply in the diet. Previous studies have highlighted the adverse impact of MID on neurological development in offspring, but comprehensive data on thyroid function, particularly in progeny at different developmental stages, are lacking. This study aimed to investigate the repercussions of MID during pregnancy on the programming of thyroid dysfunctions during adulthood. Methods: Female CD1 mice were subjected to iodine-deficient animal chow and iodine-supplemented water, either at normal (NI; 0.2 mg/L) or mild iodine deficiency (MID; 0.8 mg/L) levels during pregnancy. Gene and protein expression in the hypothalamus, pituitary, and thyroid of adult male offspring animals (PND90) were evaluated using qPCR and Western blotting. Additionally, this study explored MID-induced programming of offspring thyroid gene expression through epigenetic mechanisms. Results: Maternal MID exposure led to increased gene and protein expression of thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) in the hypothalamus and pituitary of the offspring animals. Thyroid protein and gene expression of sodium iodide symporter (NIS), TSH receptor (TSHR), thyroid peroxidase (TPO), thyroglobulin (TG), paired box 8 (PAX8), NK2 homeobox 1 (NKX2.1), and monocarboxylate transporter 8 (MCT8) were elevated in the offspring of MID-exposed animals. Epigenetic mechanisms appeared to contribute to the augmented thyroid gene expression in MID-exposed animals, with decreased DNA methyltransferase expression and reduced thyroid DNA global methylation. Additionally, histone 3 hypomethylation and increased acetylation of histones 3 and 4 were observed. Conclusion: The study suggests that MID exposure during pregnancy can be as harmful as severe iodine deficiency in programming the hypothalamus-pituitary-thyroid (HPT) axis, leading to HPT dysfunction during adult life. Consequently, our data suggest that monitoring iodine intake throughout pregnancy is crucial to prevent the occurrence of thyroid disorders in offspring during adulthood. Presentation: 6/1/2024

8471 A Rare Case of Graves' Disease in a Three-Year-Old

Abstract Disclosure: A. Rajesh: None. A. Ravari: None. L.E. Kimball-Ravari: None. H. Roan: None. Graves’ Disease (GD) is an autoimmune disease that causes hyperfunctioning of the thyroid gland which may be triggered by environmental factors such as infection or stress. Though the leading cause of hyperthyroidism in both adult and pediatric populations is GD, it is extremely rare in children under the age of four years old. Some studies show the incidence to be 1 per 1,000,000 cases[1],2. Detecting GD in children early is very important as untreated GD poses a risk for failure to thrive. There have also been cases of young children suffering from psychomotor delays, craniosynostosis, and language delays because their suspected diagnosis of GD had not been detected for one to two years. In this article, we report the case of a previously healthy three-year-old Caucasian female who presented to the pediatric endocrinologist after collapsing from an episode of hypoglycemia; plasma glucose 47 mg/dL (71-180) . The patient was diagnosed with Graves’ Disease due to her significantly elevated free T3 and T4, decreased TSH, positive thyroid peroxidase (TPO) antibodies, and elevated TSIg. She was started on methimazole treatment; however, she did not respond after six months of ATD and underwent total thyroidectomy. Her hypoglycemia was attributed to abnormal proinsulin processing and glucose metabolism, which has been associated with hyperthyroidism; thyroid hormones can produce increased GLUT2 transporters3. This case report demonstrates the importance of recognizing the signs and symptoms of GD early, as well as discuss the importance of increasing the recognition of autoimmune diseases in the pediatric population.

7824 Orbital Lymphoma masquerading as Thyroid Eye Disease

Abstract Disclosure: S. Ganawa: None. S. Joseph: None. C. Anshuman: None. D. Luciane L: None. A. Sajid: None. C. Anne: None. S. Dhage: None. Thyroid eye disease (TED) is the most common extrathyroidal manifestation in Graves’ disease (GD). In this case report, we present a case of a 64 years old lady, who was initially diagnosed with thyroid eye disease about 9 years ago. However, she was clinically and biochemically euthyroid. She was offered an orbital decompression surgery by local ophthalmology team. Patient wasn’t keen on the surgery at this stage.Recently she experienced increased swelling of her eyes, with conjunctival redness, oedema, and diplopia bilaterally, more evident on the left side. She was initiated on intravenous methylprednisolone (IVMP) weekly, by local ophthalmology team and was referred to our specialist thyroid eye clinic for further management.On presentation to us, her clinical activity score (CAS) was 5/7, but she was euthyroid clinically and biochemically. She was continued on weekly IVMP and oral mycophenolate mofetil (MMF) was added on as per the latest EUGOGO guidelines published in 2021. Her treatment was reviewed after the anti thyroperoxidase (TPO) and anti-Thyroid Stimulating Hormone receptor (TSH) antibodies were reported as negative and her eyes worsened despite the treatment with IVMP and MMF.Her repeat MR orbit at this stage showed possible orbital lymphoma. Her immunosuppressive medications were discontinued at this stage. After further discussions at regional thyroid eye MDT and radiology MDT, an orbital biopsy was arranged for, which confirmed Extra nodal Marginal Zone lymphoma, with no high-grade component. She has been referred to the oncology unit for further assessment and management.This case highlights the importance of considering alternative differential diagnosis in certain patients with atypical features or those who are non-responders to the first line immunosuppressive therapies for thyroid eye disease. Details of this case and relevant literature will be reviewed in this report. 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 &amp;lt;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: &amp;lt; 0.55), thyroglobulin antibody of 351 IU/ml (&amp;lt; 0.9) and anti-TPO Ab &amp;gt;600 IU/ml (ref&amp;lt; 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

8176 An Unusual Case of Thyroid Eye Disease (TED) Occurring in Autoimmune Hypothyroidism

Abstract Disclosure: K. Prasongdee: None. C.M. Tessier: None. Background: It is unusual for TED to present in patients with autoimmune thyroid disease who are euthyroid or hypothyroid. Clinician recognition of this rare presentation is important in ensuring proper treatment and improving patient outcomes. Clinical Case:Our patient is a 57-year-old female with a past medical history of COPD, hypothyroidism presenting with several months of blurry vision. She reports double vision when looking down, and eye pain at rest and with eye movement. She was diagnosed with hypothyroidism one year prior to presentation, and her TSH subsequently normalized after titration to levothyroxine of 112 mcg daily. She reported no history of head or neck radiation. No family history of thyroid disease. She smoked for 30 pack years but stopped 2 years prior. Physical exam showed eye lid swelling and redness, pain and diplopia on end-lateral gaze, no chemosis, no conjunctival injection, or inflammation of the caruncle, lids closed completely, proptosis with Hertel ophthalmometer measured 23 mm on the right eye and 22 mm in the left eye (normal range &amp;lt; 18 to 20 mm for Caucasians), thyroid not enlarged with no palpable nodules, no thyroid bruits. The initial Clinical Activity Score (CAS) was 4, which indicated active TED. A thyroid ultrasound showed Inhomogeneous echogenicity with increased vascularity consistent with autoimmune thyroiditis. An MRI of the orbits revealed diffuse extraocular muscle enhancement and enlargement with tendinous insertion sparing, increased T2 hyperintensity findings which favored thyroid eye disease. Further laboratory testing confirmed the presence of multiple thyroid autoantibodies: Thyrotropin binding inhibitory immunoglobulin 2.76 IU/L (normal range &amp;lt; 1.75 IU/L), Thyroid peroxidase antibody 1135 IU/mL (normal range &amp;lt;9 IU/mL), Thyroglobulin antibodies 157 IU/mL (normal range &amp;lt; 116 IU/mL), thyroid-stimulating immunoglobulin 447% (normal range &amp;lt;140 % Baseline). She was referred to ophthalmology for management of TED and was started on teprotumumab. Her CAS improved to 0 and her diplopia resolved. Her proptosis remained stable. This case illustrates an unusual clinical course in a patient who initially presented with autoimmune hypothyroidism, later developed Thyroid Eye Disease. A study by Kahaly GJ et al showed that in Hashimoto’s thyroiditis (HT), thyroid-stimulating autoantibodies are highly correlated with thyroid eye disease (TED) with positive thyroid-stimulating autoantibodies detected in 5.5% of the patients with HT and 68.2% in the patients with HT and TED. Even though it is less common, up to 6% of patients with HT may be affected by TED. Rare presentations such as this case emphasizes the need to be vigilant when evaluating eye symptoms in patients with autoimmune thyroid disease. Teprotumumab that showed improvement in patients with Grave’s and thyroid eye disease, was also successful in treating our patient symptoms. Presentation: 6/3/2024

7314 The Thyroid Tetralogy: Hypothyroidism, Graves' Disease, AFTN, and Thyroid Cancer in a Single Patient

Abstract Disclosure: F. Sajid: None. F. Mohammadrezaei: None. K. Tiwari: None. J. Shapiro: None. F. Mohsin: None. T. Lin: None. Introduction: In this case, we explore a rare and complex situation involving a patient's shift from hypothyroidism to hyperthyroidism. This transition led to the diagnosis of Marine Lenhart Syndrome (MLS), an uncommon condition characterized by the coexistence of Graves' disease and autonomously functioning thyroid nodules (AFTNs). Adding to the complexity of the case, the patient was also diagnosed with papillary thyroid carcinoma (PTC). Case Presentation: A 47-year-old woman with a history of hypothyroidism, treated with levothyroxine for 14 years, presented with palpitations, weight loss, and insomnia for a few months. Her levothyroxine dose was gradually reduced and eventually discontinued by her primary care physician due to low TSH and high free T4 levels. Post-discontinuation, her symptoms were improving. Laboratory tests showed TSH 0.01 mIU/mL (0.39-4.08), Thyroglobulin (TG) 72 ng/mL (3-40), Free T4 2.5 ng/dL (0.8-1.8), Free T3 11.5 ng/dL (0.2-0.5ng/dL). Furthermore, Thyrotropin Receptor Antibody (TRAb), and Thyroid Peroxidase Antibody (TPO Ab) were positive leading to a diagnosis of Graves' Disease and initiation of Methimazole. After three months on Methimazole, her TSH remained suppressed with normalized free T4 and T3 levels. A thyroid ultrasound revealed bilateral nodules, with a calcified well-circumscribed nodule in the right mid-pole. A Radioactive iodine uptake (RAIU) scan showed a hyperfunctioning right mid-pole thyroid nodule. Fine-needle aspiration biopsy was consistent with Bethesda V, suggestive of possible malignancy. Consequently, she underwent a total thyroidectomy, with pathology confirming multifocal classic PTC, stage pT1bN0. Post-surgery, she developed hypothyroidism and was started on levothyroxine. Four weeks later, her TSH remain suppressed, other thyroid function tests and calcium levels were within normal range: TSH 0.01 mIU/mL, Free T4 1.0 ng/dL, TG 4.6 ng/mL, Thyroglobulin antibodies 1 IU/mL (less than or equal to 1), PTH intact 43 pg/mL (16-77), and Calcium 8.9 mg/dL (8.6-10.2). Conclusion: This case represents a complex and unusual medical scenario where a patient transitioned from hypothyroidism to hyperthyroidism, ultimately leading to the diagnosis of MLS in conjunction with PTC. The exact mechanism behind this transition is not fully understood. In the management of hypothyroidism, adjustments in thyroxine dosage are common, but significant tapering of the dose should prompt further investigation. The presence of PTC in AFTNs is considered rare, as AFTNs are typically characterized as hot nodules, implying they are hyperfunctioning and generally considered to be less likely malignant compared to cold nodules. This case underscores the need for comprehensive evaluation and follow-up in patients with thyroid disorders, especially when there is a change in thyroid function or the presence of nodules. Presentation: 6/3/2024

6415 Resistance to Thyroid Hormone -A Challenge to Manage

Abstract Disclosure: A. Altaf: None. F. Iqbal: None. E. Hamoudeh: None. C. Coyne: None. K. Anne: None. L. Buckley: None. Background: Resistance to thyroid hormone (RTH) or Refetoff syndrome was first introduced in 1967. It is an autosomal dominant or recessive genetic disease with a mutation in the thyroid hormone receptorβ (THR-β) gene or the thyroid hormone receptorα (THR-α) gene. The distinguishing biochemical feature of RTHβ is an elevated level of circulating free thyroid hormones with normal or high TSH concentration and decreased peripheral tissue response to thyroid hormone. Common signs and symptoms in patients with RTHβ are short stature, attention deficit disorder, and resting tachycardia and many patients might be asymptomatic. Case: We report a case of a 36-year-old patient with past medical history of congenital bilateral hearing loss, atrial fibrillation, CHF, and slow learning/comprehending who presented to the ER with shortness of breath and atrial fibrillation with tachycardia. Admission labs revealed elevated TSH 3.9, elevated fT4 3.28, and elevated TT3 205. He reported that for the past year, he has been on levothyroxine 50mcg for abnormal TSH. Levothyroxine was stopped and the patient was discharged on methimazole 10mg daily. Further workup revealed negative thyroglobulin and thyroid peroxidase antibodies. Thyroid ultrasound with Doppler demonstrated a mildly hypervascular thyroid gland without evidence of nodules. Brain MRI was negative for any pituitary abnormalities. HAMA testing continued to show elevated TSH. Patient was followed by cardiology and due to continued atrial fibrillation, had multiple cardioversions and was managed on a beta blocker. Due to his atrial fibrillation, endocrinology service continued his methimazole till his genetic testing came positive for an autosomal dominant heterozygous pathogenic mutation in THRB c.1373 T&amp;gt;C (p. Val458Ala). His thyroid hormones and TSH continue to be elevated. Currently, he is not on thyroid medication and getting monitored. The need for multiple cardioversions for atrial fibrillation in this patient makes resistance to thyroid hormone management challenging. Discussion: Hyperthyroidism is commonly mistaken for RTH. However, the lack of TSH suppression should be further investigated. Most patients with RTHβ are adequately compensated by the increased endogenous supply of thyroid hormone showing increased serum fT3 and fT4 levels and normal or near normal TSH levels. Beta Blockers like atenolol cannot inhibit the conversion of T4 to T3 and can be used for RTHβ with tachycardia. Triiodothyroaceticacid (TRIAC) or dextrothyroxine (DT4) have also been used to treat thyrotoxicosis. In summary, treatment for RTHβ remains a challenge for clinicians, especially in patients with atrial fibrillation and many patients are misdiagnosed and managed as hyperthyroidism. Presentation: 6/3/2024

7527 Subacute Thyroiditis in First Trimester of Pregnancy: Rare Cause of Thyrotoxicosis

Abstract Disclosure: K. Wilcher: None. A. Gupta: None. Background: Subacute thyroiditis (SAT) is extremely rare in pregnancy with only 8 prior cases reported in the literature. SAT can result in maternal and fetal complications. In this case report, we describe a case of subacute thyroiditis presenting in the first trimester of pregnancy. Case Presentation: A 38-year-old female with past medical history of stillbirth presented with thyrotoxicosis in gestational week 10 of her pregnancy. The patient has a history of stillbirth in gestational week 38 of her first pregnancy requiring cesarean section one year prior to presentation. She was in the process of getting in vitro fertilization (IVF) and had an egg retrieval. During the process, she started on thyroxine 50 mcg daily for blood thyroid-stimulating hormone (TSH) 3.77 mcIU/mL. She became pregnant without the help of IVF and stopped thyroxine. One month later, labs showed low TSH 0.022 mcIU/mL (reference range: 0.4-4.5 mcIU/mL) and high blood free thyroxine (FT4) 1.87 ng/dL (reference range: 0.7-1.8 ng/dL). Repeat labs two weeks later showed low blood TSH 0.012 mcIU/mL, high FT4 2.08 ng/dL, and high blood free triiodothyronine (FT3) 5.2 pg/mL (reference range: 2.3-4.2 pg/mL). She was referred to endocrinology for evaluation. She reported mild intermittent right sided neck pain since diagnosis of pregnancy. She denied any history of viral infection, cough, or fever. She reported symptoms of severe nausea, mild constipation, and mild anxiety. She denied diarrhea, tremors, changes in voice, palpitations, or weight loss. Her family history is significant for hypothyroidism in her father. Physical exam demonstrated a non-tender, symmetric thyroid without enlargement or nodules. Ultrasound showed heterogenous thyroid with an ill-defined heterogenous area in the right lobe appearing pseudo-nodule, and increased vascularity. At this time, the patient was diagnosed with mild gestational hyperthyroidism with a plan to monitor thyroid hormone levels. Repeat labs two weeks later showed low blood TSH 0.005 mcIU/mL, high FT4 2.35 ng/dL, and high FT3 6.4 pg/mL. TSH-receptor antibodies, thyroid stimulating immunoglobulin, and thyroid peroxidase antibodies were normal on testing. In gestational week 16, labs showed normal TSH 2.76 mcIU/mL, low FT4 0.56 ng/dL, and low FT3 2.1 pg/mL. At that time, she started on levothyroxine 75 mcg daily and was diagnosed with subacute thyroiditis. Follow up labs in gestational weeks 18, 20, and 24 showed improvement in TSH and FT4 on thyroid hormone supplementation. Conclusion: This case report discusses the findings of SAT in first trimester pregnancy. Currently, she is in gestational week 28 and still requiring thyroid hormone supplementation. SAT in pregnancy is very rare. This case report significantly contributes to the literature and current knowledge of the prevalence, presentation, and disease process of subacute thyroiditis in first trimester pregnancy. Presentation: 6/2/2024

6812 A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait Due to Subacute Combined Degeneration of the Spinal Cord Associated with Pernicious Anemia

Abstract Disclosure: F. Mohammadrezaei: None. F. Sajid: None. C.A. Resta: None. J.G. Karam: None. A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait due to Subacute Combined Degeneration of the Spinal Cord associated with Pernicious Anemia Background: The coexistence of Hashimoto's thyroiditis and pernicious anemia is well established and is recognized as Polyglandular Autoimmune Syndrome (PAS) Type 3B [1]. We describe a rare case of a patient presenting with subacute combined degeneration of the spinal cord leading to the diagnosis of PAS Type 3B. Case Presentation: A 37-year-old man with no known medical history presented to the Emergency Department after a fall in the subway station. On history, he complained of progressive bilateral lower extremity weakness of 10 months duration, necessitating assistance with ambulation, and significant weight gain, described as an increase in his pants size from 40 to 56. His physical examination was relevant for weight of 145kg, BMI of 46.5, normal motor strength and sensation of the upper extremities, decreased strength at 4 out of 5 of bilateral hip flexion and extension, and decreased vibration sensation of bilateral lower extremities. He could not fully stand or walk due to imbalance and weakness. Blood testing revealed a hemoglobin level of 11.4 gm/dl (14-18), MCV of 108.8 FL (80-94), a significantly low vitamin B12 at 89 pg/ml, and normal folate level. His TSH level was 9.26 MCIU/ML (0.39-4.08), with a free T4 of 0.74 ng/dl (0.8-1.8) and significantly elevated Thyroid Peroxidase Antibody titer at 4320 IU/ml (&amp;lt; 34.9). Intrinsic factor antibody and parietal cell antibody tests both came back elevated at 13.4 AU/mL (0.0-1.1) and 1.8 (&amp;lt;1.2), respectively. A head CT scan showed no acute pathology, but MRI spine with contrast revealed abnormal T2 hyperintensity, primarily affecting the lateral columns throughout the cervical and thoracic cord, likely indicative of subacute combined degeneration. The patient was diagnosed with autoimmune Hashimoto's thyroiditis, pernicious anemia, and subacute combined degeneration of the spinal cord due to vitamin B12 deficiency. He was treated with daily vitamin B12 1000mcg muscular injections, levothyroxine 75mcg orally daily (after ruling out adrenal insufficiency), and physical therapy. Conclusion: This case highlights the complexity of polyglandular autoimmune syndromes and the importance of recognizing atypical presentations early in the history of disease. Comprehensive evaluation and timely intervention are essential to mitigate the progression of these conditions and improve patients' quality of life. Reference: (1) Betterle C, Furmaniak J, Sabbadin C, Scaroni C, Presotto F. Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy. J Endocrinol Invest. 2023 Apr;46(4):643-665. Presentation: 6/1/2024

8105 Radiation-Induced Hyperthyroidism in the Context of Palliative Radiation Therapy

Abstract Disclosure: A. Randhawa: None. G. Palaguachi: None. J.G. Karam: None. Introduction: Palliative radiotherapy, designed to alleviate focal symptoms in advanced, incurable cancer, aims to enhance quality of life with minimal treatment burden. The thyroid gland's susceptibility to neck radiation is known, primarily leading to hypothyroidism. However, hyperthyroidism is a much less frequently reported adverse effect that is poorly understood. This case report highlights an unusual instance of radiation-induced hyperthyroidism. Case Presentation:The patient is a 53 years-old woman with history of Ewing’s sarcoma of the sacrum diagnosed in August 2022, treated initially with chemotherapy (cyclophosphamide, vincristine, etoposide and ifosfamide), but diagnosed with leptomeningeal metastasis and T12/L1 mass in October 2023 when she presented with lower extremities weakness and urinary incontinence. She underwent T12-L1 laminectomy, resection of tumor and fusion, and was started on palliative intent radiation therapy for the brain and C-spine. A month later, she was admitted for altered mental status and was found to be persistently tachycardic at 140 bpm. Thyroid function testing was sent and revealed hyperthyroidism with TSH of 0.07 mIU/L (0.39-4.08), Free T4 of 1.74 ng/dl (0.58-1.64), T4 of 10.7ug/ml (4.4-9.5), T3 of 0.54 ng/ml (0.72-1.35), with undetectable Thyroid Peroxidase Antibodies and Thyroid Stimulating Immunoglobulin level. Thyroid Ultrasound showed a small and homogenous thyroid gland with no discrete nodules. Radioactive Iodine uptake and scan was not obtained because of exposure to iodized contrast during hospital stay. The patient had no available baseline thyroid function tests. She had no recent fever or viral illness. Unfortunately, her clinical condition deteriorated rapidly, and she passed away on the seventh day of admission. Conclusion: While hypothyroidism is a well-established consequence of high-dose irradiation, the mechanisms behind the rarer radiation-induced hyperthyroidism remain unclear. Speculation includes the release of autoantigens from damaged thyroid glands, triggering an immune response and potentially leading to Graves' hyperthyroidism. However, our case more likely represents a hyperthyroid phase in the triphasic sequence of destructive subacute thyroiditis, given the absence of elevated thyroid antibodies, thyroid nodules, and other causes of thyroiditis. Increasing awareness of radiation-induced hyperthyroidism, unraveling its mechanisms, and refining diagnostic strategies such as obtaining baseline and monitoring thyroid function testing are crucial, particularly in the context of palliative therapy, where striking the delicate balance between efficacy and minimizing toxicity is paramount. Presentation: 6/3/2024