bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI165 BIUXX
Authors: Haider Adnan , Sadiq Mehjabeen , Shakesprere Jon , Sidhu Gurmanpreet K
Published: October 2023

Disclosure: A. Haider: None. M. Sadiq: None. J. Shakesprere: None. G.K. Sidhu: None.

Background: Syndrome of inappropriate anti-diuretic hormone (ADH) secretion (SIADH) is characterized by inappropriate ADH secretion causing hyponatremia due to free water retention. Plasma volume expansion leads to renin inhibition by the renal juxtaglomerular complex, resulting in decreased aldosterone secretion with inappropriate natriuresis. However, when autonomous renin-independent aldosterone production is present, natriuresis can be suppressed, causing normal sodium levels despite inappropriately high ADH. Case: 58-year-old male with history of resistant hypertension & bipolar disorder on Oxcarbazepine presented with dizziness, lightheadedness, and severe hypokalemia (2.7 mmol/L, n 3.5-5.0 mmol/L). CT Adrenals revealed an incidental 1.2 cm left-sided adrenal adenoma [HU 6, 40% washout]. Serum aldosterone and plasma renin activity (PRA) were obtained in the supine position via LC/MS/MS assay; concurrent serum K+ was 3.4 mmol/L. Spironolactone was started and titrated to 50 mg BID for blood pressure control due to high suspicion of hyperaldosteronism. The patient was continued on Oxcarbazepine 900 mg BID. A 3 mg Dexamethasone suppression test showed suppressed morning cortisol (1.0 μg/dL, n <1.8 μg/dL). Urine catecholamines and metanephrines were obtained and normal. 3-4 days after starting Spironolactone, the patient developed severe subacute hyponatremia (119 mmol/L, n 135-145 mmol/L) from an admission level of 137 mmol/L. No active renal or GI losses, diuretic use, or untreated hypothyroidism were documented. Serum osmolality was low (262 mOsm/kg, n 275-295 mOsm/kg) with urine osmolality of 357 mOsm/kg (n 50-1200 mOsm/kg) and urine sodium of 92 mEq/L (n >20 mEq/L). Serum aldosterone and PRA levels returned with normal aldosterone (7 ng/dL, n 2-9 ng/dL) but suppressed PRA (0.07 ng/mL/hr, n 0.7-3.3 ng/mL/hr) and elevated aldosterone-renin ratio (100 ng/dL per ng/mL/hr, n ≤ 30 ng/dL per ng/mL/hr). As renin was very low despite mild hypokalemia and active Losartan use at the time of testing, these findings were suggestive of primary aldosteronism. In-hospital 24-hour urine aldosterone collection showed urine aldosterone of 29.3 mcg/24 h (n 5-19 mcg/24 h) with urine sodium of 93 mmol/ 24 h (n 40-220 mmol/24 h). Oxcarbazepine was subsequently tapered off; Spironolactone was intermittently held until complete discontinuation. Fluid restriction and oral salt repletion were started and the patient’s sodium ultimately normalized. Outpatient saline suppression testing and adrenal vein sampling were scheduled. Conclusion: Oxcarbazepine was likely causing high ADH release but co-occurring untreated hyperaldosteronism inhibited natriuresis. Use of Spironolactone unmasked natriuresis by blocking aldosterone activity on the intercalated cells of the renal nephron. Stopping Oxcarbazepine ultimately resulted in hyponatremia resolution.

Presentation Date: Friday, June 16, 2023
OR11-05 High-throughput Screening Identifies TR4 Modulators For Potential Therapeutic Application
Authors: Khowal Sapna , Zhang Dongyun , Damoiseaux Robert , Javaherian Keanu , Heaney Anthony P
Published: October 2023

Disclosure: S. Khowal: None. D. Zhang: None. R. Damoiseaux: None. K. Javaherian: None. A.P. Heaney: None.

Cushing Disease (CD), due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor, leads to excess cortisol and is a life-threatening “orphan disease”. Although surgical removal can be effective, CD frequently recurs. Thereafter, repeat surgery, radiation therapy and/or bilateral adrenalectomy are not always successful and cause significant morbidity. Medical therapy has significantly improved but there is a clear unmet need for efficacious and safe therapies that target the pituitary corticotroph tumor itself to offer biochemical and tumor control. We previously demonstrated that the orphan testicular receptor 4 (TR4) regulates pro-opiomelanocortin gene transcription and ACTH secretion. Herein, we used the Flexi Vector system to identify TR4 modulators by fusing the TR4 LBD (380-615aa) to a 3’ GAL4 DBD to generate a chimeric fusion plasmid, pBIND-TR4-LBD. The pBIND-TR4-LBD construct and an exogenous luciferase reporter construct pGL4.35 (luc2P/9XGAL4UAS), containing 9 copies of a GAL4 responsive upstream activating sequence (UAS), were then transiently transfected into human embryonic kidney (HEK293) cells. Following treatment with TR4 ligands or modulators, our TR4-LBD undergoes a conformational change and recruits additional cofactors and RNA polymerase II to the complex to drive GAL4-directed firefly luciferase expression. In a high throughput screen (HTS) of 27,705 chemicals, we identified several potential “hit” TR4 modulators that induced or inhibited TR4 LBD-directed GAL4UAS-directed luciferase expression by >3 -fold. Compounds from the HTS included ATP-sensitive K+ and calcium channel blockers, steroid hormones and modulators of cell proliferation and inflammation and several agonist and antagonist “hit” compounds induced TR4 >10 fold or inhibited TR4 by 90% respectively with minimal cell toxicity (<10%). In silico analysis of interactions between the TR4 LBD and these potential ligands indicated that the GLU-534 & ARG-565 may be crucial residues involved in TR4 ligand binding. Dose-response curves to calculate EC50 of these potential TR4 hit compounds and mode-of-action characterization are in progress. Our studies have identified several potent TR4 agonistic and antagonistic compounds and lay the framework for the discovery of safe and efficacious lead TR4 ligands that can be further advanced as potential drug therapies for CD and other diseases.

Presentation: Friday, June 16, 2023
SAT002 Liver-specific Loss Of The Nuclear Receptor Co-regulator ARGLU1 Protects Against Diet-induced Obesity In Female Mice Independent Of Food Intake And Energy Expenditure
Authors: Cash Sarah B , Magomedova Lilia , Tsai Ricky , Cummins Carolyn L
Published: October 2023

Disclosure: S.B. Cash: None. L. Magomedova: None. R. Tsai: None. C.L. Cummins: None.

Arginine and glutamate rich 1 (ARGLU1) has been shown to be a co-regulator for several nuclear receptors including ER, GR and the peroxisome proliferator-activated receptors (PPARs), which are key modulators of nutrient metabolism. We have previously reported that loss of ARGLU1 in the liver protects aged male mice against high-fat diet induced obesity and type 2 diabetes [1]. Here, we assessed the importance of ARGLU1 in lipid and carbohydrate metabolism in aged female mice and used indirect calorimetry to understand the metabolic basis of the resistance to weight gain observed with liver-specific loss of ARGLU1. Aged (11-month-old) female wildtype floxed-Arglu1 mice (Arglu1fl/fl) and liver-specific Arglu1-null mice (Arglu1LKO) were fed a high fat, high cholesterol diet (HFD, 42% calories from fat, TD.88137 Envigo) for 12-weeks (N=7-17). Female mice were housed in Promethion Metabolic Cages (Sable Systems) at room temperature for 5 days during which their food intake, water intake, physical activity, O2 consumption, and CO2 production were measured (N=5-7). Female mice were also subjected to a glucose tolerance test and insulin tolerance test (N=4-8). In agreement with our previous results in male Arglu1LKO mice [1], female Arglu1LKO mice were resistant to diet-induced obesity with final body weights compared to HFD-fed Arglu1fl/fl mice of 30.6 ± 0.9 g vs 35 ± 1 g (P<0.05). Likewise, female Arglu1LKO mice were more glucose tolerant and insulin tolerant compared to HFD-fed Arglu1fl/fl mice. The metabolic cage data showed no change in food intake, locomotor activity or energy expenditure between HFD-fed Arglu1fl/fl and Arglu1LKO mice when accounting for body mass as a covariate (ANCOVA, CalR). Surprisingly, HFD-fed female Arglu1LKO mice had significantly higher water intake compared to HFD-fed Arglu1fl/fl mice (P<0.02). These data support the conclusion that resistance to diet-induced obesity in Arglu1LKO mice is independent of sex. To our surprise, based on the metabolic cage data, we conclude that the mechanism by which Arglu1LKO mice are resistant to diet induced obesity is not due to enhanced energy expenditure or decreased food intake. Future studies will explore whether differential intestinal lipid absorption (independent of food intake) could account for the differences we observed in weight gain between the genotypes. [1] Magomedova, L., Tsai, R., & Cummins, C. L. (2017, April). Hepatic Ablation of the Nuclear Receptor Coactivator, ARGLU1, Is Protective Against the Development of Type 2 Diabetes and Fatty Liver in High-Fat Diet Fed Mice. In 99th Annual Meeting of the Endocrine Society. Endocrine Society.

Presentation: Saturday, June 17, 2023
FRI192 Serum Steroid Biomarkers For The Differential Diagnosis Of Adrenocortical Carcinoma (ACC) And Adrenocortical Adenoma (ACA)
Authors: van Rooyen Desmaré , Scheske Rachel , Lerario Antonio Marcondes , Rainey William E , Auchus Richard Joseph , Hammer Gary D , Else Tobias
Published: October 2023

Disclosure: D. van Rooyen: None. R. Scheske: None. A.M. Lerario: None. W.E. Rainey: None. R.J. Auchus: None. G.D. Hammer: None. T. Else: None.

Background: Adrenal tumors are very common, with the vast majority being benign adrenocortical adenomas (ACA). Adrenocortical carcinomas (ACC) represent only a very small proportion of adrenal tumors. Distinction between the common ACA and rare ACC relies on invasive and costly protocols which are often inconclusive. Research into the use of steroid biomarkers as a non-invasive alternative diagnostic tool has been the focus of various steroid metabolomics studies. In this study, we aimed to identify serum steroid biomarkers to distinguish ACA from ACC. Methods: This study population was comprised of 103 patient samples, including 45 (31 female) and 58 (40 female) respective samples from ACA (age 32-90) and ACC (age 16-77) patients presenting with disease at the time of sampling. No ACC patients studied had been treated with mitotane. Serum steroid levels (4 sulfates and 25 Δ4 steroids) were measured using liquid-chromatography tandem mass spectrometry (LCMS/MS) with comparisons made between steroid profiles in ACA vs ACC and between males and females within each group (ACA and ACC). Data were analyzed to obtain the geometric means with 95% CIs, and statistical significance was determined using a two-tailed Mann-Whitney test. Results: ACC patients were characterized by significantly elevated levels of pregnenolone-sulfate, 17hydroxypregnenolone-sulfate, 11-deoxycorticosterone, 17hydroxyprogesterone, and androstenedione when compared to ACA patients. In addition, steroid levels differed between male and female samples, with dehydroepiandrosterone-sulfate (p<0.01), androstenediol-3-sulfate (p<0.05), 11deoxycortisol (p<0.0001), cortisol (p<0.05) and testosterone (p<0.01) significantly increased in female ACC patients when compared to male counterparts. Conclusion: Significant differences in plasma steroids were observed in ACC vs ACA patients, with more steroids altered in female patients. Serum steroid profiles, particularly steroid sulfates, might serve as an adjunct, easy to obtain diagnostic tool to differentiate ACA and ACC.

Presentation: Friday, June 16, 2023
FRI525 Gender Differences In Fears Related To Low Risk Papillary Thyroid Cancer And Its Treatment
Authors: Sawka Anna M , Ghai Sangeet , Rotstein Lorne , Irish Jonathan C , Pasternak Jesse D , Gullane Patrick J , Monteiro Eric , Su Jie , Xu Wei , Jones Jennifer M , Gafni Amiram , Baxter Nancy N , Goldstein David P
Published: October 2023

Disclosure: A.M. Sawka: None. S. Ghai: None. L. Rotstein: None. J.C. Irish: None. J.D. Pasternak: None. P.J. Gullane: None. E. Monteiro: None. J. Su: None. W. Xu: None. J.M. Jones: None. A. Gafni: None. N.N. Baxter: None. D.P. Goldstein: None.

Background: It is important to understand the fears of individuals newly diagnosed with papillary thyroid cancer (PTC) to optimize patient counselling and supportive care. Our aim was to explore for potential gender differences in fears experienced by individuals with PTC prior to treatment. Methods: In this prospective study conducted in Toronto, Canada, we enrolled patients with untreated small low risk PTC (< 2 cm in maximal diameter), and offered them the choice of thyroidectomy or active surveillance (Clinicaltrials.gov: NCT03271892). All participants had a surgical consultation prior to assessment. Participants completed Fear of Progression (Short Form) and Fear of Surgery (referring to thyroidectomy) questionnaires, prior to making a decision on PTC management. We also evaluated potential fears that were specific to thyroidectomy (e.g. voice change, thyroid hormone treatment, hypocalcemia, and scar appearance). Total fear scores were calculated for the respective questionnaires. We compared data collected in women and men and explored for factors associated with respective fears using multivariable linear regression analyses. Results: We included 153 women of mean age 50.7 years (standard deviation, SD 15.0) and 47 men of mean age 56.3 years (SD 13.8). There were no significant differences in primary tumor size, marital status, education, parental status, or employment status of women and men. On a scale of 5 to 60 (where 60 is the worst), the mean total fear of disease progression questionnaire score was 26.2 (SD 9.7) in women and 23.0 (SD 9.2) in men (p=0.031). On a scale of 0 to 80 (80 being the worst), the mean total surgical fear questionnaire score was 34.1 (SD 20.3) in women and 22.0 (17.9) in men (p<0.001). Women were also more fearful than men about potential postoperative change in voice (p=0.001), hypocalcemia (p=0.003), and scar appearance (p<0.001). In respective multivariable linear regression analyses, age group (p<0.001) was independently inversely associated with fear of disease progression, whereas being a woman was independently associated with surgical fear (p=0.002). Conclusions: Demographic factors appear to be associated with fears of low-risk PTC patients who are considering primary disease management. Younger patients may have a greater fear of disease progression while women may have a greater fear of the morbidity from thyroidectomy. These factors may be important to consider in patient counselling.

Presentation: Friday, June 16, 2023
FRI532 Thyroid Hormone Resistance: A Possible New Variant In The THRB Gene
Authors: Siddiqui Anood , Khan Zuhaab , Ahmed Taha , Selk Karen
Published: October 2023

Disclosure: A. Siddiqui: None. Z. Khan: None. T. Ahmed: None. K. Selk: None.

Background: Resistance to the Thyroid Hormone (RTH) is caused by reduced target tissue response to thyroid hormone, resulting in the loss of the normal feedback mechanism that suppresses secretion of thyrotropin (TSH). Most cases of RTH are familial, usually inherited in an autosomal dominant manner, with over 100 different pathogenic variants having been described. Clinical Case: A 45-year-old male with history of attention deficit disorder presented for management of hypothyroidism. The patient was Anti-TPO positive, consistent with Hashimoto's thyroiditis and he was treated with varying doses of levothyroxine. Labs on 100 mcg levothyroxine showed a TSH of 7.07 (0.35-4.94 uIU/mL), free t4 1.86 (0.7-1.48 ng/dL), and free t3 4.41 (2.3-4.2 pg/mL). This initially prompted concern for a TSHoma. An alpha subunit level was found to be 0.3 ng/dL and pituitary MRI was within normal limits. Given continued persistent thyroid hormone elevations, further testing for human anti-mouse antibody interference was performed and also unrevealing. The patient continued to report feeling tired and fatigued, with multiple joint pains and inability to focus or concentrate. His levothyroxine was increased to 125 mcg per day. However, even after the adjustment, he still did not notice any change in his symptoms. A trial of addition of liothyronine 5mcg daily was also performed but he self-discontinued this as he did note any improvement. Overall, his findings were highly suspicious for thyroid hormone resistance. Genetic testing for a thyroid hormone resistance beta (THRB) mutation was performed. Direct sequence analysis of the coding region and splice-sites of the THRB gene identified one copy of the c.1368G>T (p.Leu456Phe) variant of uncertain significance. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. However, the THRB c.1368G>T (p.Leu456Phe) variant has not been described in online databases or published literature. It also has not been reported in large, multi-ethnic general populations. Conclusion: This is the first case to our knowledge demonstrating the THRB c.1368G>T (p.Leu456Phe) variant gene as likely giving rise to RTH. Further testing of family members has been recommended to help clarify the clinical significance of this finding.

Presentation: Friday, June 16, 2023
FRI554 Pretibial Myxedema Associated With Hashimoto Thyroiditis Treated With Teprotumumab
Authors: Marta Niedzialkowska Ewelina , Ajaz Banka , Pokharel Ashbita
Published: October 2023

Disclosure: E.M. Niedzialkowska: None. B. Ajaz: None. A. Pokharel: None.

Introduction: Pretibial myxedema (PTM) is a localized thyroid-associated dermopathy characterized by local thickening of the skin of the lower extremities. It mostly develops after the onset of thyroid eye disease (TED). Majority of the cases are associated with Graves disease (GD) but infrequently it can occur in Hashimoto thyroiditis (HT) in the presence of thyroid stimulating immunoglobulins (TSIs). Orbital fibroblasts and the pretibial dermis share antigenic sites that underlie autoimmune thyroid disease. IGF-1 has been reported to potentiate the effects of TSH and TSI on TSHR signaling and fibroblast proliferation. Teprotumumab, a novel monoclonal antibody that blocks IGF-1R receptors, is registered for TED treatment. It is plausible it also improves outcomes in PTM through the same mechanism. Clinical case: 52 year old female reported to our Endocrinology clinic with proptosis and myxedema. The patient was diagnosed with hypothyroidism at the age of 21 and was on substitutional dose of levothyroxine, 125 mcg daily. She developed TED 7 years prior with bilateral exophthalmos with medial rectus muscle infiltration. She underwent 5 decompression surgeries and steroid courses due to concern for optic nerve compression. 4 years prior to the visit she developed bilateral, erythematous pitting edema of the lower extremities with involvement of the pretibial areas, ankles and toes and underwent excess left toe callus excision. Despite multiple courses of intralesional steroid injections and topical ammonium lactate use the patient reported persistent edema, pruritus, and restriction of motion. Laboratory results were significant for TSH of 1.73 uIU/mL (n 0.40 - 4.50 uIU/mL), TRAB >40 IU/L (0.00 - 1.75 IU/L), TSI 4.95 (n <0.10 IU/L), TPO antibody <=35 IU/mL, free ft3 2.5 pg/ml (1.7 - 3.7 pg/mL), free ft4 1.0 (0.7 - 1.5 ng/dL). The patient underwent thyroidectomy with pathology results consistent with Hashimoto thyroiditis (thyroiditis with thyroid follicles, Hurthle cell change, marked lymphoid and fibroadipose tissue). Following the procedure she experienced PTM and TED flare up. Subsequent orbital decompression and orbital steroid injections provided minimal improvement. The patient was started on Teprotumumab (8 infusions every 3 weeks) with marked improvement of orbitopathy (CAS reduction from 6/10 to 1/10) and significant reduction of lower extremity edema and rash. Conclusion: We present the case of Hashimoto thyroiditis associated with TED with PTM successfully treated with Teprotumumab. In TED, TSI binds to IGF-1R creating a complex that promotes orbital inflammation. Teprotumumab is believed to degrade antibody-receptor complex and downregulate fibroblast activation and glycosaminoglycans deposition. We postulate the same process may occur in dermal fibroblasts in the light of PTM improvement after teprotumumab treatment.

Presentation: Friday, June 16, 2023
FRI197 Patient Suffering From Resistant HTN For 15 Years With Negative CT Diagnosed With Hyperaldosteronism Due To Adrenal Cortical Adenoma
Authors: Seidenberg Jacob , Uddin Ansari Mohammad Jamal
Published: October 2023

Disclosure: J. Seidenberg: None. M.J. Ansari: None.

Background: Resistant HTN, blood pressure remaining above goal despite concurrent use of three antihypertensives of different classes at maximum doses is a common presentation in both endocrinology and primary care settings. Patients can often be prescribed multiple max-dosed antihypertensives with varying results and adverse effects and still spend years with uncontrolled HTN leading to long term health concerns. Hyperaldosteronism is diagnosed for resistant HTN in 4% of primary care patients and 10% endocrinology-referred patients. Adrenal adenomas account for 40% of all cases characterized by high aldosterone/renin activity ratio, hypokalemia, mild hypernatremia and hypomagnesemia commonly diagnosed with a mass found in the adrenals on CT. Clinical Case: Patient is a 39 year old Female who presented to the endocrinology office due to elevated urine metanephrine levels, BP 159/100. Patient had resistant HTN since her early 20s treated currently with labetalol and nifedipine, and hypokalemia treated with potassium supplements. Lab results revealed potassium 3.4 mmol/L (3.6 -5.2 mmol/L), normetanephrines 787 mcg/g (0-145 mcg/g) , aldosterone 11 ng/dL (2-9 ng/dL) , renin 0.2 ng/mL/h (0.7- 3.3 ng/mg/hr), aldosterone/renin activity ratio 55 (<25) . Renal US showed no renal artery stenosis. The patient was suspected of having hyperaldosteronism using cutoff ratios aldosterone renin ratio >30, and 15 years of potassium levels between 3.0 and 3.5. CT of the adrenals revealed no masses. Patient underwent IR guided venous sampling which indicated R adrenal gland producing 45x more aldosterone than the L adrenal gland. Patient underwent R sided adrenalectomy for definitive management of primary hyperaldosteronism. Pathology showed cortical adenoma. Patient was continued on chlorthalidone, losartan and nifedipine, and within 3 months her BP averaged 120/70 mmHg, with potassium within normal limits, Aldosterone 13 ng/dL, renin 1.25 ng/mL. Conclusion: Concurrent hyperaldosteronism with essential HTN is an uncommon but potential cause of resistant HTN. Patients with resistant HTN, prescribed multiple max-dosage antihypertensive medications while also having negative renal artery US result should undergo aldosterone and renin lab work. CT scans can have low sensitivity for adrenal adenoma. Concerning lab work should be followed up by IR-guided venous sampling for evaluation of an adrenal cortical adenoma, which can be treated surgically. Underlying essential HTN will still require treatment, but at significantly decreased medication dosages. Patients with resistant HTN should be evaluated for hyperaldosteronism early in their disease course regardless of a negative CT to prevent sequelae of untreated hyperaldosteronism including cardiac hypertrophy, arrhythmias, nephrogenic diabetes insipidus and neuromuscular symptoms.

Presentation: Friday, June 16, 2023
SAT453 Endocrine Related Adverse Events Of Immune Checkpoint Inhibitors In Cancer Patients Visiting Tertiary Care Center In Saudi Arabia
Authors: Mohammed Alqahtani Ali , Saad Alghassab Abdulmohsen , Ahmed Alghamdi Lamia , Almalki Mussa
Published: October 2023

Disclosure: A.M. Alqahtani: None. A.S. Alghassab: None. L.A. Alghamdi: None. M. Almalki: None.

Introduction: Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a different types of cancers. Those agents may result in exaggerated immune response leading to numerous toxicities referred to as immune-related adverse events particularly endocrinopathies affecting most commonly the thyroid and pituitary glands. Methods: We carried out a retrospective analysis of endocrine dysfunction in cancer patients receiving immune checkpoint inhibitors therapy namely pembrolizumab, nivolumab and ipilimumab between July 2018 and July 2022. A total of 123 patients were included in this analysis. We reviewed pituitary-, thyroid-, and adrenal-related hormone test results, as well as the clinical perspective of patients, to identify and characterize cases of hypophysitis, hypothyroidism, thyroiditis, and adrenal dysfunction. Results: A total of 123 patients were included in our study. Among them, Female participants were 67 (54.5%) and males were 56 (45.5%) with mean age of 53.7 years. Majority of the included patients (91.1%) received single agent and only 8.9% received combination therapy. The most used ICI in our cohort was pembrolizumab 73.9% followed by nivolumab 17.8% and the combination of either one of them (beside ipilimumab) was used in 8.9% of the time. The most frequent indication for ICIs was breast cancer (27.6%) followed by lung cancer (19.5%) and metastatic renal cell carcinoma (8.9%). The average number of cycles was 12 cycles, and the average duration of treatment was 12 months. The total incidence of all endocrinopathies was 22.7%. Out of 123 patients, 24 patients developed thyroid dysfunction in term of thyroiditis (1), subclinical hypothyroidism (7) or overt hypothyroidism (16). Hypophysitis occurred in one patient only. There was no occurrence of new onset diabetes mellitus in all groups. Pembrolizumab is thought to be the culprit in 18 patients of thyroid dysfunction and the patient who developed hypophysitis. Nivolumab was responsible about 4 cases of thyroid dysfunction. The rest of the cases were attributed to the combination therapy. The mean TSH level at the time of hypothyroidism diagnosis (overt hypothyroidism and subclinical hypothyroidism) was 95.8 mIU/L. And the mean free thyroxine level in overt hypothyroidism group was 6.3 pmol/L. Conclusion: Our cohort demonstrated an increased risk of thyroid dysfunction among cancer patients who receive immune checkpoint inhibitors. Pituitary dysfunction is infrequent adverse effect of these agents. Endocrine assessment is recommended prior to initiation of therapy and periodically afterward. Special attention should be given to pituitary dysfunction as it might be overlooked due to non-specific symptoms.

Presentation: Saturday, June 17, 2023
SAT478 A Rare Case of Thyrotoxic Periodic Paralysis in a Patient with Concomitant Methimazole-Induced Agranulocytosis
Authors: Wei Kevin S , Cannon Sophie M , Angell Trevor E
Published: October 2023

Disclosure: K.S. Wei: None. S.M. Cannon: None. T.E. Angell: None.

Introduction: Thyrotoxic state may precipitate sudden-onset unilateral or bilateral extremity weakness brought on by transient hypokalemia requiring specific management. Clinical Case: A 48-year-old woman presented to our hospital with fevers, sore throat, and sudden-onset bilateral leg weakness. Ten weeks prior, she was started on methimazole 20mg daily for a new diagnosis of Graves’ disease. Two days prior to presentation, she had consumed a carbohydrate-heavy meal and that night experienced acute-onset lower extremity weakness rendering her unable to walk. She also had been experiencing sore throat, odynophagia, and intermittent fevers. On admission, the patient was found to be febrile, tachycardic, and in shock with WBC <0.5 (ref: 4.5-10 K/cumm), potassium 2.6 (3.5-5.1 mmol/L), lactate 4.1 (0.5-2.2 mmol/L), TSH <0.01 (0.27-4.2 uIU/mL), fT4 4.04 (0.93-1.7 ng/dL) and was admitted to the ICU for neutropenic fever and septic shock. Computed tomography (CT) imaging of the thorax showed right lung consolidation suggesting pneumonia. Magnetic resonance imaging of the spine and CT head did not demonstrate an etiology for her weakness. She was diagnosed with thyrotoxic periodic paralysis (TPP) and treated with potassium. For severe hyperthyroidism with methimazole contraindication, she received broad spectrum antibiotics, lithium 300mg orally every 8 hours, and propranolol 10-20mg every 8 hours. Given minimal improvement in both weakness and hypokalemia after 48 hours of therapy, she was also diagnosed with refeeding syndrome and potassium repletion was intensified. The patient’s shock resolved, with slow improvement of lower extremity weakness over a two-week period and resolution of agranulocytosis and fevers. Conclusion: This rare presentation offers several distinct points regarding the patient’s care. Firstly, TPP is a rare hyperthyroidism-related hypokalemia that can cause weakening of the extremities due to a rapid intracellular shift of potassium (1) and is an important syndrome to consider on the differential for any thyrotoxic patient presenting with sudden-onset weakness. Secondly, gentle potassium repletion is recommended to prevent rebound hyperkalemia. However, our patient had both total body loss of potassium from refeeding syndrome and intracellular shift from TPP, requiring more aggressive potassium repletion to treat her paralysis than is typical for TPP alone. In settings where weakness and hypokalemia do not improve with beta blockade and gentle potassium repletion, it is important to investigate other causes of hypokalemia and consider concurrent overlapping diagnoses. Lastly, patients with methimazole-induced agranulocytosis may require alternative treatments, such as lithium to control hyperthyroidism. 1) Lin, Shih-Hua. Thyrotoxic Periodic Paralysis. Mayo Clin Proc. 2005;80(1):99-105.

Presentation Date: Saturday, June 17, 2023
SAT479 A Case of Thyroiditis Cause by Cabozantinib
Authors: Bulchandani Sheetal , Janicic-Kahric Natasha
Published: October 2023

Disclosure: S. Bulchandani: None. N. Janicic-Kahric: None.

Introduction: Thyroiditis is an inflammatory disease of the thyroid; the cause can be autoimmune, infectious or drug induced. Patients can have an initial phase of hyperthyroidism (thyrotoxicosis) attributed to the release of preformed thyroid hormone from damaged thyroid cells. This can be followed by hypothyroidism, when the thyroid stores are depleted, and then eventual restoration of normal thyroid function. Some patients may develop permanent hypothyroidism.1 We report a case of thyroiditis caused by cabozantinib. CASE REPORT: 39-year-old female presented with abdominal pain, vomiting and palpitations. Past medical history was significant for metastatic clear cell renal carcinoma. Eight weeks before the presentation, she had started on cabozantinib 60 mg daily as part of therapy for her renal carcinoma. On presentation, the patient’s temperature was 36.6 Celsius, heart rate was 118 beats/minute, blood pressure was 114/84 mm Hg and oxygen saturation was 100% on room air. Laboratory evaluation was notable for white blood cell count of 12.3 k/uL, Hemoglobin of 16.5g/dl, Platelet count of 573 k/uL bicarbonate level of 13 mmol/L, anion gap 24 mmol/L, Total bilirubin of 0.6 mg/dl, Aspartate aminotransferase of 36 units/L, Alanine aminotransferase of 30 units/L, Alkaline phosphatase of 121 units/L. Thyroid function tests revealed thyroid stimulating hormone (TSH) which was low at 0.045 uIU/ml and free thyroxine level (Free T4) which was elevated at 4.29 ng/dl. Thyroid function tests performed eight weeks prior to presentation showed TSH of 6.9 uIU/ml, attributed to immunotherapy that the patient received 1 month prior. She was admitted and received intravenous fluids. Prednisone at 40 mg orally daily was initiated. Labs demonstrated a decrease in Free T4 level. She was discharged on a tapering course of prednisone. Free T4 one week later was normal at 1.35ng/dl. Repeat laboratory evaluation three weeks later revealed that the patient had developed hypothyroidism with TSH level of 8.7 uIU/ml and she was started on 50 micrograms of levothyroxine. Cabozantinib was discontinued. Discussion: Tyrosine Kinase inhibitor therapy can result in clinically significant thyroid dysfunction. Cabozantinib treatment can result in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and close follow-up are essential to provide adequate management2

Presentation Date: Saturday, June 17, 2023
SAT487 A Case of Mistaken Identity: A Rare Presentation of Ectopic Thyroid Tissue
Authors: Doshi Nirmita , Azimzade Rizvan , Rajpal Aman
Published: October 2023

Disclosure: N. Doshi: None. R. Azimzade: None. A. Rajpal: None.

Background: Ectopic thyroid tissue (ETT) lateral to the midline is very rare, and its presence at the carotid bifurcation is exceedingly unique. Paraganglioma is the most common primary tumor at the carotid bifurcation, often called a carotid body tumor. We hereby present a case of lateral ETT with radiological features similar to paraganglioma. Case Description: A 72-year-old female with history of GERD was referred to us for evaluation of a well-circumscribed, slightly tender left neck mass. She has had the mass for approximately 15 years with previous evaluation with ultrasound in Yemen, where she was told to undergo surgery to remove it. She did not pursue surgery at that time. She moved to the U.S. one year ago and was re-evaluated for the neck mass. On examination, a firm mass was noted on the left side of the neck, followed by an ultrasound which demonstrated a 4.5 cm mass at the left carotid bifurcation and an enlarged right thyroid lobe of the same echogenicity with no tissue in the left thyroid bed. She had no clinical symptoms suggesting of hypo or hyperthyroidism. Laboratory examination showed suppressed TSH with elevated T3 suggesting thyrotoxicosis. CT neck was obtained for further characterization of the left neck mass which showed a hyper-enhancing, lobular soft tissue mass at the carotid bifurcation extending from the mandible to the level of the thyroid isthmus, concerning for carotid body paraganglioma or schwannoma. An I-123 scan demonstrated 24% (increased) uptake in the right thyroid lobe and minimal uptake in the carotid bifurcation tissue. The patient is currently being treated medically for thyrotoxicosis. Based on its ultrasonographic appearance, mild uptake on the I-123 scan, and no clinical suggestion of paraganglioma, the left neck mass is presumed to be ETT and no surgical intervention is being pursued. It is possible that the right lobe is thyrotoxic, suppressing iodine uptake in the ectopic tissue. Conclusion: This case demonstrates a unique presentation of ETT in the left carotid bifurcation with a thyrotoxic right lobe. It is difficult to distinguish the precise composition of neck masses at the carotid bifurcation, which has important implications for management. Often, an official diagnosis of thyroid tissue is made with histopathology only after the mass is surgically excised. Most ETT is benign in nature, and many times it is the only thyroid tissue available, thus surgery is not indicated. It is especially difficult to distinguish between ETT and paraganglioma on imaging itself. Somatostatin receptor scintigraphy, Ga-68/PET scanning, or iodine uptake scan can be useful to distinguish ETT from paraganglioma. Despite its rarity, lateral ETT must be included in the differential diagnosis of carotid body paraganglioma.

Presentation Date: Saturday, June 17, 2023
SAT489 Grave’s Disease Secondary To Alemtuzumabuse
Authors: Gong Michael Shifeng , Lee David , Arceo-Mendoza Rod Marianne
Published: October 2023

Disclosure: M.S. Gong: None. D. Lee: None. R. Arceo-Mendoza: None.

Introduction: We present a case of alemtuzumab-induced autoimmune thyroid disease in a patient with Multiple Sclerosis (MS). Clinical Case: A 42/F was evaluated by endocrine inpatient service for hyperthyroidism. She presented with tremors, dyspnea, and ataxic gait. She has known MS and was treated with Alemtuzumab (ALZ) in 2018 and in 2019, with her initial infusion being 4 years prior to this admission. Lab tests on admission showed TSH of <0.01 uIU/mL with elevated Free T3 and Free T4 of 1987 pg/dL (NV:171-371 pg/dL) and 3.9 ng/dL (NV:0.7-1.5 ng/dL) respectively. Her Thyroid Stimulating Immunoglobulin and TSH receptor binding antibody were elevated. Baseline TSH prior to starting ALZ and a follow up TSH in 2020 were in the normal range. She denies personal or family history of thyroid disease. Hospital course was further compounded by ongoing leukopenia, with a WBC of 2.3 and ANC of 1.1. Initiation of thionamide therapy was discussed however patient declined to start methimazole when risk of agranulocytosis, albeit low, was explained. She had opted to proceed with RAI therapy for definitive management but then changed her mind. We were just initially able to treat her with prednisone, beta blocker and cholestyramine with close biochemical monitoring as an outpatient. Her Grave’s hyperthyroidism was refractory to medical management hence she was eventually admitted again for medical optimization and surgical evaluation. Her hospital course upon readmission was complicated by worsening hemoptysis and a diagnosis of pulmonary embolism. At this point, it was decided she is not a good surgical candidate for thyroid surgery given comorbidities. She eventually agreed to start methimazole after undergoing bone marrow biopsy for worsening leukopenia and cleared by hematology to start the antithyroid drug. At this time, she remains to be on methimazole as an outpatient. Clinical course however, is unfortunately complicated by patient’s ongoing poor compliance to clinic follow up. Clinical Lesson: ALZ is an anti-CD52 monoclonal Ab which induces depletion of B and T lymphocytes causing lymphopenia and immunosuppression. It is an effective treatment for MS but is linked to a number of autoimmune adverse event. Thyroid autoimmune dysfunction may occur in 20-30% of patients, and Grave’s disease accounts for 60-70% of cases. The ALZ product label recommends TFT monitoring every 3 months for at least 48 months after the last infusion. Our patient presented with Grave’s disease in 4 years following initial ALZ administration. To our knowledge, there is no published case with reported ALZ-induced Grave’s disease with this length of interval since infusion. Our case highlights not only the importance of pretreatment screening but continued vigilance and close thyroid function monitoring in patients treated with ALZ even several years after therapy.

Presentation Date: Saturday, June 17, 2023
SAT492 Hypothyroidism Induced Psychosis: A Rare Initial Presentation Of Severe Hypothyroidism
Authors: Shaukat Mishal , Mack Margaret , Galarza Emma , Saeed Rehan , Arzeno-Tejada Luis E
Published: October 2023

Disclosure: M. Shaukat: None. M. Mack: None. E. Galarza: None. R. Saeed: None. L.E. Arzeno-Tejada: None.

Introduction: Hypothyroidism presents as slowing of bodily functions that become more severe as the disease progresses. Common presentations of hypothyroidism are lethargy, constipation, hair and skin changes and mental slowing. We present a rare presentation of hypothyroidism induced psychosis, also called myxedema psychosis or more commonly, myxedema madness, triggered by lenalidomide. This, per our review, has only been reported a handful of times in prior literature. Case Description: 64-year-old male with a history of follicular Non-Hodgkins Lymphoma, currently on rituximab/lenalidomide who was brought to the Emergency Department (ED) for concerns of hallucinations, paranoia and manic episodes for three days. In the ED, his vitals were stable. Computed Tomography (CT) head was normal. Lab work revealed an elevated TSH at 51.70 uIU/ml (normal 0.30-5.0 uIU/ml), free T3 <0.1 pg/ml (normal 2.0-4.4 pg/ml) and free T4< 0.1 ng/dL(normal 0.7-1.7 ng/dL). Thyroid peroxidase antibody was 9 IU/ml (normal <34.0 IU/ml). He was started on intravenous levothyroxine and as needed haloperidol to which he responded well in about forty-eight hours. During this time, he got a MRI of his brain that was normal. He was examined by neurology who did not recommend any further neurological workup. He continued IV therapy for 4 weeks after which he was switched to oral levothyroxine. His chemotherapy regimen has been changed to bendamustine/rituximab and he was discharged to a psychiatric facility for two weeks. He continues to be on oral levothyroxine and is currently doing well. Discussion: Hypothyroidism is described as decreased activity of the thyroid gland that results in retardation in growth and development of children and adults and common initial presentations of hypothyroidism include lethargy, hair loss, skin changes, cold sensitivity, weight gain and constipation. The most common psychiatric association of hypothyroidism is depression. Studies have also shown that there is an association between hypothyroidism and bipolar disorders. Other psychiatric manifestations include loss of memory, labile emotions and forgetfulness. However, in around 5 to 15 percent of the patients, the initial presentation of hypothyroidism is psychosis, also termed myxedema psychosis. The exact mechanism is uncertain, and the evidence is based on experimental animal models, but it is believed that the effects on the brain are due to increased dopamine levels and tyrosine hydroxylase activity in hypothyroid patients, mostly in the limbic system where most emotional and behavioral responses are processed. Prompt diagnosis with thyroid function tests along with removal of the offending agent is important in these cases since the cause of psychosis is reversible and early treatment has promising results.

Presentation Date: Saturday, June 17, 2023
FRI203 A Case Of Pseudoadrenal Tumor Mimicking Left Adrenal Pheochromocytoma
Authors: Tanabe Akiyo , Sugito Erika , Kajio Hiroshi
Published: October 2023

Disclosure: A. Tanabe: None. E. Sugito: None. H. Kajio: None.

Approximately 50% of adrenal incidentalomas are non-functional cortical adenomas, and 25% are adrenocortical hormone-secreting adenomas and pheochromocytomas. Adrenocortical carcinomas, and pheochromocytomas which have malignant potential, need to be differentiated and removed even if the tumors are hormonally inactive. In addition to these adrenal origin tumors, anatomic structures and tumors that develop in tissues neighboring the adrenal glands (pseudoadrenal tumors) may be confused with primary adrenal tumors. The larger the tumor, the more difficult it is to determine continuity with the adrenal glands. Herein we report a patient with gastrointestinal stromal tumor (GIST) that mimicked a left adrenal pheochromocytoma. A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. The mass appeared to be in the tip of the lateral limb of the left adrenal gland and was located between the left adrenal gland and the posterior wall of the stomach. The patient had no abnormal findings other than general obesity. The blood pressure was 106/72 mmHg with antihypertensive agents. The plasma corticotropin and cortisol concentrations were normal and suppressed normally after a 1-mg overnight dexamethasone suppression test. The plasma aldosterone concentration and renin activity were increased with angiotensin receptor blocker and diuretic therapy. The 24-h urine fractionated metanephrines levels were at the upper limit of the reference range. Because the tumor showed unenhanced computed tomography (CT) attenuation of 40-50 Hounsfield units, hormonally-inactive adrenocortical carcinoma or pheochromocytoma had to be differentiated. I-123-metaiodobenylguanidine (I-123-MIBG) scintigraphy showed tumor avidity consistent with a pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal CT postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a GIST. Although it has been reported that I-123-MIBG may accumulate in tumors other than neuroendocrine tumors, reports on GISTs are rare. Lessons learned from our case include the importance of clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathologic analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies.

Presentation: Friday, June 16, 2023
SAT537 Thyroid Cancer Mimicking Acute Coronary Syndrome
Authors: Rodrigues Nimmy M , Alexander Blesset , Palacios Merchan Juan Diego
Published: October 2023

Disclosure: N.M. Rodrigues: None. B. Alexander: None. J. Palacios Merchan: None.

Background: The use of thyrotropin –alpha for preparation of remnant ablation is associated with superior short-term quality of life and similar rates of remnant ablation as thyroid hormone withdrawal. Usually treatment with thyrotropin-alpha is well tolerated, but we need to be aware of the potential side effects. Clinical case: 61-year-old Hispanic female with multinodular goiter, underwent total thyroidectomy for compressive symptoms. The pathology report showed 4 cm invasive papillary carcinoma, well-differentiated follicular variant, with invasion of an adjacent parathyroid gland. The margins were negative, and no nodal involvement was noted. Due to the extra thyroidal extension, the plan was to undergo radioactive iodine ablation. She received two doses of thyrotropin-alpha. On the following day, 24 hours after the second thyrotropin-alpha, she complained of severe left sided chest pain and went to the emergency room. Initial workup for acute coronary syndrome was negative. CT angiography done to rule out aortic dissection showed diffuse multifocal bilateral pulmonary nodules and a 2.4 cm lytic lesion on the superior aspect of the manubrium suggesting osseous metastasis. She had severe tenderness to palpation of her chest - mostly of the sternum. We decided to perform a whole-body scan to determine if the lesions were iodine avid. Due to down trending TSH at 25 microIU/mL, she received another dose of thyrotropin-alpha. Her TSH subsequently increased to 209.4 microIU/mL with a thyroglobulin level of 2250 ng/mL. Whole body scan showed evidence of metastatic disease to the lungs bilaterally and bone metastatic lesions in the manubrium and left proximal femur. . The pain did not improve with morphine but responded well to oral diclofenac. One week later, she again received two doses of thyrotropin-alpha in preparation for radioactive iodine ablation with 200 mCi of I-131 due to the metastatic lesions. She started taking prednisone 50 mg daily for 1 week before the thyrotropin- alpha injection and continued prednisone 25 mg for five additional days. She remained asymptomatic during the radioactive iodine treatment. Conclusion: Thyrotropin-alfa has a manufacturer warning that it can lead to an increase in tumor burden resulting in severe pain and inflammation, especially at the metastatic sites. Even though imaging to look for metastasis is usually not part of the protocol before radioactive iodine ablation, it could be considered in patients with high-risk features on the surgical pathology report. This could prevent possible complications related to thyrotropin-alpha by identifying patients at risk. It is recommended that patients with cancer near their trachea, in their central nervous system, or in their lungs receive treatment with glucocorticoids to reduce inflammation. This pretreatment is shown to be very effective in preventing these complications.

Presentation Date: Saturday, June 17, 2023