Free Thyroxine Research Articles

Association between air pollutants, thyroid disorders, and thyroid hormone levels: a scoping review of epidemiological evidence.

Over the past two decades, the incidence of thyroid disorders has been steadily increasing. There is evidence to suggest that air pollution may be one of the etiological factors of thyroid diseases. This comprehensive review aimed to examine the evidence related to air pollutants and thyroid disorders and thyroid hormones levels from an epidemiological perspective. The scoping review adopted a systematic approach to search for, identify, and include peer-reviewed articles published in English. We performed a comprehensive search of three databases-PubMed, Embase, and Web of Science to identify relevant literature on the relationship between air pollution [particulate matter, nitrogen oxide, carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2)] exposure and thyroid disorders, including hypothyroidism, congenital hypothyroidism (CH), thyroid nodules, thyroid cancer, autoimmune thyroid diseases, as well as thyroid hormone levels, such as thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4). Articles published until August 1, 2023, were included. A total of 3,373 studies were retrieved, and among them, 25 studies covering eight different air pollutants were relevant. The most frequently studied air pollutants in this review included fine particulate matter (with fine particulate matter (PM2.5), n=21; inhalable particles (PM10), n=10; PM10-2.5, n=1) and nitrogen oxides (with NO2, n=13; NOx, n=3). The thyroid disorders and thyroid hormone levels most commonly associated with evidence of air pollution exposure were hypothyroidism (n=7) and TSH (n=12). Despite variations in study designs and exposure assessments, the findings consistently highlight the substantial health risks that air pollution, particularly PM2.5, poses to thyroid health, especially among vulnerable populations. Given that our study was limited to epidemiological investigations and the increasing prevalence of toxic substances in the environment, there is an urgent need for further research to elucidate the mechanisms by which these pollutants disrupt thyroid function and contribute to the development of thyroid diseases.

Roxadustat has risks of reversible central hypothyroidism in patients undergoing hemodialysis: a single-center retrospective cohort study

Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, has proven efficacy in the treatment of renal anemia; however, evidence indicates that it may cause central hypothyroidism. The prevalence and reversibility of roxadustat-induced central hypothyroidism in patients undergoing hemodialysis remain unclear. Here, we retrospectively analyzed thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels in 51 patients (mean age: 72.3 ± 10.7 years; 58.8% male) undergoing hemodialysis before, during, and after halting roxadustat treatment. TSH levels were significantly decreased from a median of 2.46 (interquartile range:1.60–4.51) mU/L before roxadustat treatment to 1.36 (0.72–2.41) mU/L during treatment (p < 0.001), and improved to 2.56 (1.78–4.63) mU/L after halting roxadustat (p < 0.001). Similarly, FT4 levels decreased from 1.11 (0.97–1.24) ng/dL before roxadustat treatment to 0.92 (0.71–1.03) ng/dL during treatment (p < 0.001) and improved to 1.05 (0.93–1.17) ng/dL after halting roxadustat (p < 0.001). FT3 levels were 2.04 (1.78–2.31) pg/mL before starting roxadustat, 1.97 (1.69–2.27) pg/mL during treatment, and 1.90 (1.63–2.18) pg/mL after halting roxadustat, with no significant difference between each group. Moreover, 2.0% of patients exhibited extremely low TSH levels (≤0.1 mU/L) and low TSH levels (>0.1 mU/L to <0.4 mU/L) before starting roxadustat and that percentage increased to 5.9% and 7.8%, respectively, during treatment. After roxadustat cessation, extremely low or low TSH levels recovered in all patients. Taken together, the results indicate that roxadustat can cause reversible central hypothyroidism in patients undergoing hemodialysis.

Approach to Newborns with Elevated TSH: A Different Perspective from the International Guidelines for Iodine-Deficient Countries.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.

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.

Maternal Thyroid Function and Biochemical Markers of Placental Function in Early Pregnancy.

A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy. Retrospective cohort study. Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aβ). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test. Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aβ 0.62, 95% CI: 0.51-0.76) and higher fT4 (aβ 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aβ 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aβ 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1). In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

7596 Thyroid Function Tests in Breast Cancer Patients Following Immune Checkpoint Inhibitor Treatment: What Happened in a Population with Preexisting Thyroid Dysfunction?

Abstract Disclosure: M. Villanova: None. L. Min: None. Introduction: Thyroid dysfunction occurs commonly following immune checkpoint inhibition, but the etiology remains unclear. Immune checkpoint inhibitor (ICI) is not contraindicated in patients with a preexisting thyroid dysfunction, but little is known about the impact of ICI on thyroid function tests (TFTs) in this setting. This study sought to define TFTs abnormalities following ICI treatment in patients with previous thyroid dysfunction. Methods: We performed a retrospective cohort study of thyroid dysfunction in patients with breast cancer undergoing anti-programmed cell death protein-1/ligand-1 therapy from May 2016 to Dec 2023. Results: A total of 30 patients were included with a mean follow-up of 18 ± 12 months. Two patients (7%) had a history of Graves’ disease, 4 patients (13%) had a post ablative hypothyroidism, and 3 patients (10%) had a post-surgical hypothyroidism. The etiology of the hypothyroidism was not further specified in the remain cases (70%). Twenty-three patients (77%) were treated with levothyroxine at baseline at the mean dose of 1.31 ± 0.68 mcg/kg. Baseline TFTs were available in 27 patients (90%). Twenty-four patients (80%) had at least one TFTs abnormality after initiating ICI treatment. Subclinical hypothyroidism (n = 11) was the most common abnormality, followed by overt thyrotoxicosis (n = 10), subclinical thyrotoxicosis (n =7), and overt hypothyroidism (n = 7). Thirteen out of 16 patients with normal baseline TFTs developed at least one TFTs abnormality after initiating ICI treatment. Subclinical hypothyroidism (n = 6) and overt thyrotoxicosis (n =6) were the most common alterations, followed by subclinical thyrotoxicosis (n = 5), and overt hypothyroidism (n = 3). Three patients with post-ablative hypothyroidism had normal baseline TFTs. Among these, one patient developed an overt thyrotoxicosis, one patient developed a subclinical hypothyroidism followed by overt thyrotoxicosis and one patient had no TFTs alterations. One post-operative hypothyroid patient had a normal baseline TFT and developed a subclinical hypothyroidism followed by overt thyrotoxicosis. Twenty-five patients (83%) were on levothyroxine at the last follow-up at the mean dose of 1.41 ± 0.60 mcg/kg. The dose was higher than that at baseline but did not reach statistical difference (Student T test, P = 0.059). Levothyroxine dosage was adjusted in 16 patients (53%) and 25 patients (83%) achieved normal TFTs at the last follow-up. Conclusion: ICI treatment related TFTs abnormalities were common in patients with preexisting thyroid dysfunction. There were multiple distinct phenotypes. The mechanisms underlying the TFTs abnormalities is not clear. Destructive thyroiditis, medication adherence, or interference with TFT assay by ICI are among the possible etiologies. ICI is not contraindicated in this group of patients but their TFTs should be monitored closely. Presentation: 6/1/2024

7385 Prevalence of Central Hypothyroidism in Cushing Syndrome and Thyroid Function Tests After Cushing Treatment

Abstract Disclosure: T. Kunavisarut: None. A. Sriwijitkamol: None. Cushing syndrome can be associated with thyroid dysfunction. We investigated the association between Cushing syndrome and thyroid dysfunction. We conducted a retrospective study at Siriraj Hospital in Thailand and analyzed thyroid function tests in 80 Cushing's patients. The inclusion criteria were patients diagnosed with Cushing syndrome with thyroid function tests recorded at diagnosis of Cushing syndrome. Patients who had an abnormal thyroid function test at diagnosis of Cushing syndrome must have a thyroid function test after treatment of Cushing syndrome. Of the 80 patients, sixty-five patients (81.2%) had normal thyroid function at diagnosis, 12 patients (15%) had central hypothyroidism and three patients (3.8%) had subclinical hyperthyroidism.Interestingly, among 12 patients who had central hypothyroidism, eight patients (66.7%) were diagnosed with Cushing disease. Three patients (25%) were diagnosed with adrenal Cushing syndrome and one patient (8.3%) was diagnosed with ectopic Cushing syndrome. This finding suggested that central hypothyroidism may not be exclusively due to the mass effect of the pituitary tumor on the normal pituitary because adrenal Cushing syndrome and ectopic Cushing syndrome can also cause central hypothyroidism. Among 12 patients with central hypothyroidism at diagnosis of Cushing syndrome, nine patients (75%) normalized their thyroid function after remission of Cushing syndrome without Levothyroxine replacement. Moreover, patients with central hypothyroidism had significantly higher median 24-hour urine-free cortisol levels than euthyroid patients (1030.5 ug/day vs. 404.5 ug/day, p=0.017), indicating a potential correlation between cortisol excess and low FT4 levels. These findings suggest that hypercortisolism in Cushing syndrome can suppress the hypothalamic-pituitary-thyroid axis, but this suppression is often reversible with successful Cushing's treatment. This study highlights the importance of central hypothyroidism, which can occur in all types of Cushing syndrome. If the patients did not have hypothyroid symptoms, Levothyroxine replacement may not be necessary. For patients who already received Levothyroxine and had normal thyroid function tests, Levothyroxine can be carefully tapered and potentially discontinued because successful Cushing syndrome treatment can ultimately normalize thyroid function tests. Presentation: 6/1/2024

7661 Therapeutic Plasma Exchange as a Bridge Therapy to Total Thyroidectomy in Treatment-Resistant Amiodarone-Induced Thyrotoxicosis

Abstract Disclosure: M. Maher: None. R. McEvoy: None. V. Farnan: None. D.J. Tansey: None. S. McKenna: None. J. O'Connell: None. R. McQuillan: None. M. Griffin: None. J. Lyne: None. C. Magee: None. C. Traynor: None. A. Hudson: None. M.W. O'Reilly: None. A. Agha: None. M. Sherlock: None. C.M. Moran: None. Background: Amiodarone-induced thyrotoxicosis (AIT) is challenging to manage where conventional medical treatment fails. We report our experience using therapeutic plasma exchange (TPE) to prepare for salvage thyroidectomy. Clinical Cases: A 53-year-old man was diagnosed with AIT type 2 (FT4 45.3pmol/L, RR 12-22; TSH 0.02mU/L, RR 0.27-4.20) whilst on amiodarone, on a background of lamin A/C cardiomyopathy. He remained thyrotoxic despite carbimazole, prednisolone, iodine solution and cholestyramine. TFTs following 4 TPE sessions showed an improvement in TSH (0.03mU/L) and total T4 (129nmol/L, RR 63-151), despite rising FT4 (91.5pmol/L) and FT3 (12.56pmol/L, RR 2.43-6.01).A 47-year-old man was diagnosed with TRAb-negative AIT type 1 (FT4 51.2pmol/L, TSH 0.03mU/L) on a background of atrial fibrillation treated with amiodarone. He became progressively more thyrotoxic despite carbimazole, prednisolone, lithium and cholestyramine. Following 4 TPE sessions, TFTs demonstrated a reduction in FT4 (42.9pmol/L) and FT3 (10pmol/L, RR 3.1-6.8), along with normalisation of total T4 (155nmol/L, RR 66-181).A 56-year-old female was diagnosed with AIT type 2 (FT4 33.9pmol/L, TSH 0.02mU/L), whilst on amiodarone for ventricular fibrillation. She became rapidly and progressively more thyrotoxic despite carbimazole, prednisolone, iodine solution and cholestyramine (FT4 &amp;gt;100pmol/L). After 5 TPE sessions, TFTs showed a persistently elevated FT4 (&amp;gt;100pmol/L), FT3 (13.1pmol/L), and total T4 (318nmol/L). Lastly, a 65-year-old gentleman was diagnosed with AIT type 2 (FT4 &amp;gt;100pmol/L, FT3 18.4pmol/L, Total T4 &amp;gt;320nmol/L, TSH &amp;lt;0.01mU/L) on a background of atrial fibrillation that had been treated with amiodarone. FT3 showed a modest reduction (8.2pmol/L) following treatment with carbimazole and prednisolone; however, FT4 remained &amp;gt;100pmol/L. The patient developed acute decompensated heart failure and underwent TPE as a bridge to emergency thyroidectomy. Following 3 TPE sessions, TFTs demonstrated a reduction in FT4 (67.3pmol/L) and Total T4 (223nmol/L). All 4 patients underwent uneventful thyroidectomy and were subsequently rendered euthyroid with thyroxine. Heparin was administered during TPE in all cases. Conclusion: TPE is beneficial as a bridge to thyroidectomy in treatment-resistant AIT. Our cases demonstrate that the biochemical response is variable. Given the possibility for heparin to cause displacement of bound thyroid hormones, Total T4 may be a better biochemical indicator of response than free thyroid hormone(s) for patients on TPE. Presentation: 6/2/2024

6784 A Case of Euthyroid Hyperthyroxinemia due to Thyroid Binding Globulin Excess Syndrome

Abstract Disclosure: A.S. Iyer: None. Background: Congenital thyroid binding globulin (TBG) excess is a rare phenomenon associated with elevated serum total T3 and total T4 concentrations but normal serum concentrations of free thyroid hormones, with clinically euthyroid patients. While TBG excess can be caused by pregnancy, estrogen-secreting tumors, and estrogen therapy, congenital TBG excess follows an X-linked pattern, with hemizygous males most affected, and heterozygous females showing a spectrum of disease due to random inactivation of one X chromosome. Clinical Case: A 39-year-old Caucasian female presented as a referral from the Gastroenterology clinic due to concern for thyroid resistance syndrome. Symptoms included chronic constipation (improving with Miralax®), gradual weight gain of 8 pounds in one year, fatigue, and palpitations. She reported that her total thyroid hormone levels have always been elevated, with other thyroid labs remaining within normal limits, along with family history of similar labs noted in her two sons, father, and paternal grandmother. Upon initial encounter, TSH was 1.637 (0.430-3.550 uIU/mL), total T4 15.4 (4.8-11.7 ug/dL), total T3 231 (80-200 ng/dL), free T4 0.97 (0.70-1.25 ng/dL), free T3 3.2 (1.7-3.7 pg/mL), and albumin 4.2 (3.5-5.0 g/dL). The patient was not on oral contraceptive pills and she denied any pregnancies in the last three years. Thyroid ultrasound showed a normal-appearing homogeneous thyroid gland with a small cyst with colloid and no cervical lymphadenopathy. Initial differential diagnosis included TBG excess syndrome versus familial dysalbuminemic hyperthyroxinemia. Permission was obtained from the patient to access one of her son’s medical records from age 8-weeks old when he was also evaluated for abnormal thyroid labs. TSH was 2.144 (0.350-6.500 uIU/mL), total T4 28.2 (5.0-12.0 ug/dL), free T4 1.55 (0.8-1.8 ng/dL), and free T3 4.0 pg/mL (no reference available). Thyroid binding globulin was found to be elevated at 81 (12-26 mcg/mL) in her son and found to be elevated to 78.0 (13.5-30.9 mcg/mL) in this patient, confirming a diagnosis of TBG excess syndrome. Conclusions: TBG excess syndrome should be considered in the differential of patients with high total T3 and total T4 levels with normal levels of free T3, free T4, and TSH, especially in individuals who have a known family history and who have minimal or nonspecific symptoms. Definitive diagnosis will make further testing and treatment unnecessary. However, if these patients develop hypo- or hyperthyroidism, then use of TSH and free levels of T4 and T3 is necessary to direct management and avoid confusion. Reference: Pappa, T., and S. Refetoff. “Thyroid hormone transport proteins: Thyroxine-binding globulin, transthyretin, and albumin.” Reference Module in Neuroscience and Biobehavioral Psychology, 2017, https://doi.org/10.1016/b978-0-12-809324-5.03494-5. Presentation: 6/2/2024

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

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

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

8630 Cardiorespiratory Failure in Thyroid Storm After C-section in a Patient with Untreated Hyperthyroidism

Abstract Disclosure: I.C. Arroyo: None. M. Ramirez: None. M. Alvarado: None. L.R. Sepulveda-Garcia: None. L. El Musa Penna: None. W. Medina-Torres: None. Z. Maisonet -Feliciano: None. J. Segarra-Villafane: None. Unrecognized hyperthyroidism during pregnancy increases the risk of maternal and fetal complications, including miscarriage, pre-eclampsia, maternal congestive heart failure, and intrauterine growth restriction (IUGR). Thyroid storm is a rare but life-threatening complication that can occur as well. Furthermore, it can present with cardiopulmonary failure which increases risk of death. Recognizing it early and providing intensive and ongoing therapy is imperative for a positive outcome.We report a case of a 29-year-old female G4P2A0 with triplet pregnancy who developed thyroid storm after an emergency C-section at 27 weeks of gestation due to sinus tachycardia and IUGR in one of the fetuses.Past medical history was remarkable for hyperthyroidism diagnosed on first pregnancy that did not require treatment.Upon questioning, she referred unintentional weight loss, palpitations, tremors, and heat intolerance in the past months.Physical examination showed sinus tachycardia, fine hand tremors, non-tender goiter, and thin/brittle hair.One day after C-section thyroid function tests (TFT) were remarkable for suppressed TSH &amp;lt;0.008uIU/mL, FT4 at 4.30 (0.89-1.76ng/dL) and positive thyroid stimulating antibodies. Burch-Warsofsky Point Scale (BWPS) for Thyrotoxicosis of 20 points didn’t indicate current or impending thyroid storm. Methimazole and propranolol were started. Two days after C- section patient developed worsening FT4 at 5.63ng/dl, worsening sinus tachycardia, increased temperature and respiratory failure requiring mechanical intubation. 2 D echocardiogram showed right ventricular overload with pulmonary hypertension, while CT angiogram of thorax suggested thyrotoxic cardiomyopathy. BWPS was now at 45 points compatible with thyroid storm (positive criteria for temperature of 38.4, heart rate of 117 bmp and heart failure). At this time methimazole was switched to propylthiouracil (PTU), propranolol was adjusted, and hydrocortisone, in addition to cholestyramine, were started. After these changes in therapy, TFTs improved markedly and a stable clinical state was achieved, with successful extubation.Untreated hyperthyroidism during pregnancy and post-partum period poses significant risks, including thyroid storm. Our patient had a C-section with worsening TFTs despite methimazole therapy, developing thyroid storm with cardiopulmonary failure. Cardiopulmonary failure is a rare, but deadly presentation of thyroid storm. In this case C-section was identified as a stressor for thyroid storm and cardiorespiratory failure as a complication. Prompt recognition and aggressive treatment of this potentially lethal condition is warranted to improve survival in thyrotoxic cardiomyopathy. Presentation: 6/1/2024

7915 A Case of Severe Hypothyroidism in a Patient with Nephrotic Syndrome presenting with Rhabdomyolysis requiring Levothyroxine and Liothyronine combination therapy

Abstract Disclosure: S.S. Mohammed: None. E.T. Ngo: None. S. Tadisina: None. B.M. Drees: None. Background: Nephrotic syndrome is known to worsen hypothyroidism via urinary loss of thyroid binding globulin, transthyretin, albumin and other proteins, often requiring escalating levothyroxine doses. Severe uncontrolled hypothyroidism can result in rhabdomyolysis, although this presentation is quite rare. Clinical case: We present a case of a 50-year-old male with long-standing Hashimoto’s hypothyroidism, biopsy-proven minimal change disease with nephrotic syndrome, dyslipidemia, and hypertension, who was admitted for generalized myalgia, weakness, and progressive swelling of bilateral hands and feet for one month. He had been off levothyroxine 3 months prior to presentation. He previously required large doses of oral levothyroxine, as high as 350mcg daily, but never achieved a euthyroid state despite reported adherence to therapy with the high levothyroxine doses.Laboratory workup showed severe hypothyroidism (free thyroxine &amp;lt;0.25ng/dL [0.6-1.6ng/dL] with markedly elevated thyroid stimulating hormone 282.03 mIU/mL [0.3-5.6mIU/mL]), along with acute kidney injury and rhabdomyolysis (Creatine kinase 4882 U/L[38-234U/L]). He was hemodynamically stable with intact mentation and was not deemed to be in myxedema coma. Physical examination was consistent with hypothyroidism with periorbital swelling, dry skin, deep hoarse voice, bilateral hand and feet edema, and delayed deep tendon reflexes. Thyroid function tests and clinical symptoms failed to improve after 8 days, despite high doses of levothyroxine IV (200mcg). Creatine kinase remained high at 4994 U/L [38-234U/L] despite adequate fluid hydration. Liothyronine 5mcg orally was started in addition to levothyroxine 200mcg IV. Repeat thyroid function tests after 2 days of combined IV levothyroxine and oral liothyronine therapy showed significant downtrend in TSH to 154.12 uIU/ml [0.3-5.6mIU/mL] and increase in free thyroxine to 0.44ng/dl [0.6-1.6ng/dL]. Creatine kinase also down trended to 3181U/L[38-234U/L] on D4 of IV levothyroxine 200mcg IV with liothyronine 5mcg daily. He was discharged stable and clinically improved on oral levothyroxine and liothyronine. Laboratory evaluation 10 days later showed further improvement in TFTs (TSH 66.0[0.3-5.6mIU/mL]), free thyroxine 0.6 [0.6-1.6ng/dL] Conclusion: This case presents a unique and unusual clinical course in symptomatic primary hypothyroidism with rhabdomyolysis and AKI. Rhabdomyolysis due to hypothyroidism, without an obvious precipitating factor, has been previously reported, but is very rare. There is limited evidence regarding combination treatment with levothyroxine and liothyronine in primary hypothyroidism; however, as demonstrated in this patient, combination therapy resulted in clinical and biochemical improvement of thyroid function. Presentation: 6/2/2024

7617 Two Cases of Severe Beta-hCG-Mediated Hyperthyroidism with Gestational Trophoblastic Disease

Abstract Disclosure: A. Morvant: None. M. Mashayekhi: None. Introduction: Hyperthyroidism is most commonly caused by Graves’ disease and toxic nodules and affects 2.5% of the world’s population. Hyperthyroidism due to elevations in beta-hCG (b-hCG), which has thyroid-stimulating activity due to homology with TSH, is a rare process that requires high clinical suspicion. We present two cases of hyperthyroidism caused by severely elevated b-hCG due to gestational trophoblastic disease (GTD), with rapid resolution of hyperthyroidism after treatment of the underlying conditions. Clinical Cases Case 1: A 35-year-old at 28-weeks gestation presented with dyspnea, palpitations, and 6-pound weight loss over the prior month. Labs revealed b-hCG 5.2 million (0-5 mIU/mL), TSH &amp;lt;0.015 (0.35-3.6 mcU/mL), and free T4 2.42 (0.7-1.37 ng/dL). Imaging revealed extensive pulmonary lesions concerning for metastatic disease and a 2.4 cm ovarian mass. Due to worsening respiratory distress and the need to start chemotherapy urgently, she underwent Cesarean section to deliver the viable infant and take out the ovarian mass. Pathology confirmed choriocarcinoma. Methimazole was started post-operatively, and she started chemotherapy. Labs after cycle one of chemotherapy showed b-hCG 1.3 million, TSH &amp;lt;0.015, and free T4 1.46. The methimazole dose was decreased and ultimately stopped as free T4 levels decreased with subsequent chemotherapy cycles. After three cycles, labs showed b-hCG 4,652, TSH 1.55, and free T4 0.68. She was discharged without thyroid-targeting therapy. Case 2: A 33-year-old woman at 12-weeks gestation presented with nausea, vomiting, and 10-pound weight loss over 1 month. Labs showed TSH &amp;lt;0.015, free T4 2.39, and total T3 351 (58-160 ng/dL), which were thought to be due to hyperemesis gravidarum. Two months later she presented with vaginal bleeding and imaging showed an enlarged placenta with a moth-eaten appearance and theca lutein cysts concerning for partial molar pregnancy. Beta-hCG level was 3.3 million, TSH &amp;lt;0.015, free T4 1.76, and total T3 289. She underwent dilation and evacuation and pathology confirmed partial hydatidiform mole. Beta-hCG level decreased to 1.8 million and free T4 normalized after surgery, with b-hCG 3,300, normal TSH, and normal total T3 one month later. Conclusion: These cases highlight the importance of considering possible GTD when evaluating a patient with hyperthyroidism, particularly in women of childbearing age and cases of early pregnancy when the degree of hyperthyroidism seems out of proportion to that expected. Clinicians should consider checking a b-hCG level in consultation with an obstetrician when indicated. Treatment is aimed at the GTD and can yield rapid resolution of hyperthyroidism.

6423 The Storm in a Healthy 26-year-old Hispanic Female

Abstract Disclosure: P.M. Reyes-Torres: None. M. Hernandez-Hernandez: None. Uncontrolled hyperthyroidism can cause thyrotoxicosis and lead to end-organ dysfunction known as thyroid storm. The incidence is .20 and .76 per 100,000 persons per year, with an incidence of 4.8–5.6 per 100,000 hospitalized patients. Of those hospitalized with thyrotoxicosis in the U.S., thyroid storm is diagnosed in 16%. Most commonly affects females, middle-aged patients, and Caucasians. Can be precipitated by acute illnesses, surgery, or non-compliance with medications. Symptoms are characterized by fever, cardiac and gastrointestinal dysfunction, and altered mentation along with impaired thyroid function tests.A 26-year-old Hispanic female presented to our ER complaining of palpitations, general malaise, dysphagia, and fevers after attending a social event 3 days before. Physical examination revealed a fever of 101F, restless patient with pressured speech, and diffusely enlarged non-tender thyroid without discrete nodules. Labs were remarkable for WBC: 12 000, urinalysis, b-HCG, and CXR were all negative. Burch-Wartofsky Point Scale: 55 and biochemical tests (TSH: 0.005 ml/UL, free T4 &amp;gt;5 ng/dL, Total T3: 8.5 ng/mL, Total T4: 28.87 uG/DL, Thyroglobulin 34.81 ng/mL) for which diagnosis of thyroid storm was made. She was transferred to the ICU and treatment was initiated with fluids, Propranolol 60 mg PO q4hrs, PTU 250 mg PO q4hrs, and Hydrocortisone 300 mg IV as loading dose then 100mg IV q8hrs. TSI and TRAb were ordered. Thyroid US remarkable for bulky thyroid gland with heterogeneous, increased vascularity, no obvious cystic/solid lesions seen. Repeated tests showed a decreasing trend of free T4: 4.71 ng/dL and Total T3: 2.42ng/dL for which PTU was discontinued and Methimazole 15 mg PO BID was started. Five days after treatment started, the patient continued symptom-free and was discharged with Propranolol 60 mg PO q6hrs and Methimazole 15 mg PO BID. TSI and TRAb samples were obtained but results were pending before discharge. Follow-up was scheduled in 2 weeks with routine labs but the patient was lost to follow-up.This case highlights the importance of early recognition and treatment of thyroid storm in Hispanics, undiagnosed patients given the presenting nonspecific, life-threatening symptoms. We conclude that our patient's cause of thyrotoxicosis was an undiagnosed case of Graves Disease and the storm was most likely triggered by an upper viral respiratory tract infection. This case could potentially help physicians identify hyperthyroidism in an earlier phase, reducing incidence, mortality, and hospitalizations of thyroid storm since a variety of mimics make the diagnosis challenging. Furthermore, we could contribute to updated statistical knowledge regarding the risk of patients with thyrotoxicosis developing thyroid storm which despite advancements in technology, are currently lacking. Presentation: 6/1/2024

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

6874 A Rare Case Of Hereditary 1,25 (OH)2D Resistant Rickets

Abstract Disclosure: G. Umarji: None. F. Thelmo: None. S.A. Jabbour: None. Vitamin D-dependent rickets type 2A (VDDR2A) also known as hereditary 1,25 (OH)2D resistant rickets is due to biallelic loss-of-function mutations in the gene encoding vitamin D receptor on chromosome 12q13.11, thus, it represents a true form of tissue resistance to vitamin D. It is a scarce form of rickets with approximately only 120 cases reported. A 37-year-old male was referred to endocrinology by neurosurgery for evaluation of metabolic bone disease. Seven years ago, he was in a car accident which resulted in a lumbar spine injury causing radiculopathy and severe low back pain leading to lumbar spine decompression/fusion. However, he suffered from nonunion of bones and had to undergo another surgery a year later with recurrent postoperative nonunion of bones. During the operation, the surgeon noticed that his spine seemed demineralized. He had a history of multiple minor fractures in childhood, decreased hearing in left ear for two years, fragile teeth for many years, and some hair loss since age 30. Physical exam showed a height of 1.82 m, weight 89.3 kg with body mass index of 26 kg/m2, broken teeth, no leg bowing and normal stance. Laboratory results showed normal renal function, thyroid function tests and testosterone level, corrected calcium 8.3 mg/dL (8.7-10.2), 25-OH-vitamin D 54 ng/mL (30-100), phosphorus 2.8 mg/dL (2.8-4.1), intact parathyroid hormone 65 pg/mL (15-65), bone-specific alkaline phosphatase 21 mcg/L (4-27), 24-hour urine calcium 156 mg/day (100-300), 24-hour urine phosphorus 1,752 mg/day (390-1,425), FGF-23: 93 RU/mL (44-215) and 1,25 (OH)2D 92 pg/mL (24-81.5). Dual absorptiometry of the lumbar spine and hip showed osteopenia with Z scores of -2.2 and -1.2 respectively. Genetic testing for metabolic bone disease panel showed heterozygous mutation in VDR gene at nucleotide position c.146+9dup associated with autosomal recessive VDDR2A. We present a very rare form of vitamin D resistant rickets. As many patients with VDDR2A are unable to respond to any form of vitamin D, it is suggested that VDDR2 be more appropriately described as hereditary 1,25 (OH)2D resistant rickets (HVDRR), hereditary resistance to 1,25 (OH)2D, or even pseudovitamin D-deficiency type IIA (PDDR IIA). Clinical features include severe rickets, bone pain, hypotonia, dental caries and alopecia. Biochemical features include hypocalcemia, hypophosphatemia, normal to elevated alkaline phosphatase, normal 25(OH)D and importantly, elevated 1,25-(OH)2D levels. Management is with high doses of calcium and vitamin D therapy. While rare, this disease highlights the need for a comprehensive evaluation of metabolic bone diseases and a thorough understanding of calcium and vitamin D metabolism. Presentation: 6/2/2024

5103 Synthroid Absorption Conundrum: A Case Deciphered

Abstract Disclosure: H. Nadeem: None. O. Alzohaili: None. Hypothyroidism is a disorder requiring lifelong Synthroid therapy. Untreated patients have high morbidity rate and suffer from weight gain, cold intolerance, fatigue and constipation. Inadequate therapeutic outcomes may result in the case of malabsorption, like GI tract conditions, medication interactions and dietary ingredients. Here, we describe the case of a 50-year-old woman who despite compliance to therapy, had refractory hypothyroidism. Complexity of unexplained Synthroid malabsorption is highlighted, emphasizing the importance of managing and optimizing thyroid hormone replacement therapy. A 50-year-old woman with a history of papillary carcinoma s/p thyroidectomy and radioactive iodine therapy came in with fatigue, weight gain and constipation. Despite taking Synthroid 150 mcg, thyroid function tests (TFTs) remained high with TSH 150 uIU/mL and fT4 0.25 ng/dL. Her dose was gradually increased until it reached 1800 mcg yet repeat TFTs showed refractory hypothyroidism with TSH 179 uIU/mL, fT4 0.8 ng/dL. Compliance was addressed to which she demonstrated strict adherence, while avoiding concurrent intake of food, supplements or medications interfering with the absorption. Autoimmune conditions were ruled out and no dietary patterns affecting absorption were identified. A thyroid absorption test was then performed, during which 2100 mcg of Synthroid were given orally in the AM, and thyroid hormones were measured for 8 hours. She was found to have a TSH in 200s uIU/mL and fT4 &amp;lt;0.10 ng/dL, deeming her to have refractory hypothyroidism. She was seen by GI and had an EGD/ colonoscopy, revealing no abnormalities. In a follow up visit, she was still complaining of the same symptoms, periorbital edema, and mild confusion. Her TSH was still elevated at 225 uIU/mL. She was then started on IV 500 mcg of weekly Synthroid infusions and after several weeks, she reported symptoms improvement. Subsequent TFTs showed a progress in TSH, now 26.6 uIU/mL, with fT4 1 ng/dL, indicating successful management of Synthroid malabsorption. During this process, she had a nutritional assessment and was consistently having hyperlipidemia with LDL 243 mg/dL. She was compliant with Praluent and max dose of atorvastatin 80 mg, but LDL only decreased to 134 mg/dL after adjusting her thyroid hormone levels. With nonadherence being the top cause of medication non responsiveness, ruling out causes of malabsorption is vital. In this case, compliance, nutritional assessment, medication interactions, GI abnormalities, autoimmune conditions were all addressed and no interfering factors were identified. IV treatment with unexplained thyroid hormone malabsorption was the effective treatment, ultimately improving outcomes. With the hope to transition her to oral medication, the possibility of it happening is still not clear. More research is necessary to discover the underlying causes in such an exceptional case. Presentation: 6/2/2024

12243 The Case of a Metastatic Papillary Thyroid Cancer Presenting as an Unresectable Pelvic Mass

Abstract Disclosure: M. Tucktuck: None. Y. El Soufi: None. O.G. Adeniran: None. A.A. Gliwa: None. Background: Papillary thyroid cancer (PTC) represents around 85% of all thyroid cancers, of which 2-10% of patients will present with metastasis distant to the neck. The frequency of bone metastasis in PTC occurs in only 1-4% of patients. Studies have shown that distant and multi-organ metastasis is associated with higher mortality rates. Clinical case: A 69-year-old woman with diabetes mellitus, cerebrovascular accident, and right lower extremity deep venous thrombosis, presented with right foot and hip pain for 1 week after a mechanical fall. She had a 50 pound weight loss over a year without personal or family history of thyroid cancer or disease or radiation exposure. A soft and nontender mass in the right lower abdomen was noted during a physical exam. Imaging revealed a large heterogeneous lesion (16.3 x 13.3 x 15.5 cm) in the right bony pelvis with internal necrosis, destructing the right iliac bone, and extending into the right sacrum, acetabulum, and musculature, with mass effect on the surrounding vasculature, and enlarged lymph nodes suspicious for metastasis. Thyroid imaging showed a hypervascular hyperechoic 1.3 cm nodule within the right thyroid gland and a large 2 cm left thyroid nodule with scattered microcalcifications. Thyroid function tests were within normal limits. The patient underwent an initial ultrasound guided biopsy of the pelvic mass with indiscriminate results, and later a laparoscopic excisional biopsy of the pelvic mass showed neoplastic papillary proliferation with typical nuclear features, without necrosis or associated ovarian tissue. The immuno-histopathological profile was positive for PAX-8, TTF-1, thyroglobulin, and CK7, and the Ki-67 proliferation index was ∼20-30%. The patient was diagnosed with papillary thyroid cancer with metastasis to the pelvic bone, and was classified as stage IV, cT1bN0M1. As the pelvic mass was inoperable, the patient completed total thyroidectomy and was started on hormone replacement therapy. Subsequent thyroid pathology report was negative for papillary carcinoma. Further review of imaging did not show ectopic thyroid tissue in the neck or an ovarian pathology. Before the patient’s next visit to evaluate for struma ovarii, she passed away. Conclusion: Thyroid cancer is usually treated through thyroidectomy or lobectomy, with radioiodine (RAI) therapy as an effective treatment for differentiated cancers. Our patient, who presented with extremity pain revealing a distant metastasis, completed thyroidectomy with plans to undergo RAI therapy. Our case highlighted the importance of recognizing musculoskeletal presentations as an initial and possibly only finding of a distant metastasis. It also emphasized the utility of multidisciplinary collaboration in detecting and recognizing PTC as a primary thyroid cancer, as early management can reduce mortality and lead to more favorable outcomes. Presentation: 6/2/2024

7078 Diagnostic Obstacles in Thyroid-Stimulating Hormone-Secreting Pituitary Adenoma (TSH-oma): A Case Report

Abstract Disclosure: V.A. Mendpara: None. P.P. Rao: None. M.D. Lundholm: None. Background: Thyroid-stimulating hormone-secreting pituitary adenoma (TSH-oma) is a rare cause of hyperthyroidism, forming 0.5-3% of all functioning pituitary tumors and &amp;lt;1% of hyperthyroid cases. Here, TSH secretion is autonomous and unresponsive to the normal negative feedback of thyroid hormones, leading to inappropriate TSH, T4 and T3 elevation. In the absence of clinical symptoms it can be difficult to distinguish between thyroid hormone resistance (THR) and lab errors. Clinical Case: A 44-year-old Swahili-speaking female with a history of type 2 diabetes was admitted for hypoglycemia requiring insulin adjustment. In her workup, thyroid function tests were obtained, revealing normal or low TSH (0.28 mIU/L) and high free T4 levels (2.7 ng/dL). At outpatient follow-up, repeat labs showed elevated TSH, T3 and FT4 (5.22 mIU/L, 377 ng/dL and 4.7 ng/dL, respectively). She reported weight loss, occasional palpitations, and chronic insomnia but denied other symptoms. Graves' antibodies (TSI, TSHR Ab) were negative. On exam, she had a 30-40 gm, smooth, non-tender thyroid without adenopathy, and a BMI of 23 kg/m2. The initial differential diagnosis included TFT lab error, THR or TSH-oma. A FT4 by equilibrium dialysis was high at 7.8 ng/dL (1.1-2.4 ng/dL). N-telopeptide (NTX) and sex hormone-binding globulin (SHBG) were elevated, consistent with a true hyperthyroid state. Genetic testing for THR posed time and cost barriers. Elevated alpha-subunit levels (87 ng/mL, normal ≤1.8 ng/mL) with normal levels of other pituitary hormones prompted a pituitary MRI, unveiling a 4.7 cm suprasellar bilobed pituitary mass abutting the optic chiasm and invading the cavernous and sphenoidal sinuses. She denied peripheral vision loss or headaches. Hyperthyroidism was managed with methimazole until surgical intervention for the TSH-oma. A transsphenoidal resection was performed with histopathological confirmation of a TSH-staining pituitary adenoma. She was started on levothyroxine for central hypothyroidism thereafter. Discussion: It is challenging to find the cause of abnormal TFTs when patients are asymptomatic and the differential includes THR, lab errors or TSH-oma. Inaccurate diagnosis can lead to delays in care or unnecessary thyroid ablation or pituitary surgery. Conversely, early identification and appropriate treatment of TSH-omas can prevent neurological and endocrinological complications, such as optic chiasm compression, visual disturbances, headache and hypopituitarism. Despite a lack of convincing symptoms of hyperthyroidism, we used confirmatory labs (NTX, SHBG) to rule in biochemical hyperthyroidism along with alpha-subunit testing and pituitary MRI to solidify the TSH-oma diagnosis, leading to surgical intervention. This case highlights the vital steps in the diagnosis of a TSH-oma, emphasizing the need for logical evaluation and differentiation of this rare condition. Presentation: 6/1/2024