bluuebunny/crossref_metadata_2025_split huggingface dataset:
7768 Hereditary Phaeochromocytoma/Paraganglioma And Aortopathy In A Patient With Known Macroprolactinoma: A Series Of Incidental Findings
Authors: Kelly Jessica R , Soule Steve , Jane Hunt Penelope 
Published: October 2024

Abstract
Disclosure: J.R. Kelly: None. S. Soule: None. P.J. Hunt: None.
Background: The three P association (3PAs) describes the combination of pituitary adenoma and phaeochromocytoma/paraganglioma. Recent case series describe a range of underlying genetic causes, including SDH mutations. We describe a patient with a macroprolactinoma and their subsequent incidental diagnoses of phaeochromocytoma and paraganglioma, with a pathogenic SDHA mutation. Clinical Case: A 58-year-old man had previously received a combination of medical therapy with cabergoline and transsphenoidal debulking surgery for a histologically confirmed macroprolactinoma. Due to a small risk of valvulopathy associated with cumulative doses of cabergoline, screening echocardiogram was requested after seven years of treatment. This showed a calcified bicuspid aortic valve and severe dilatation of the ascending aorta at 58mm. Prior to surgical repair, CT aorta was requested, which showed an incidental left adrenal lesion. Formal adrenal imaging and functional assessment confirmed a 50mm phaeochromocytoma, with a right para-aortic paraganglioma subsequently revealed on Ga-68 DOTATATE-PET scan. He described symptoms of catecholamine excess, with episodic palpitations, chest pain, and increasing anxiety over the previous year, on a background of hypertension. Hereditary phaeochromocytoma/paraganglioma gene panel revealed a pathogenic mutation in SDHA (c.1663+1G&gt;T) – a splicing variant, likely resulting in nonsense decay. Screening was recommended for his three children. He initiated alpha blockade with doxazosin, then beta blockade with metoprolol, prior to open adrenalectomy and excision of paraganglioma. Histology confirmed a left phaeochromocytoma (Ki67 0.1%, PASS score 8, no vascular or capsular invasion) and a paraganglioma. Post-operative plasma normetanephrine normalised (406 pmol/L, pre-operative 6776 pmol/L, normal &lt;1200 pmol/L) and the patient described resolution of symptoms. He subsequently underwent tissue aortic valve replacement and Bentall’s procedure. Histology showed severe atherosclerosis with diffuse medial degeneration of the aorta. Repeat Ga-68 DOTATATE-PET seven months later showed no evidence of residual or recurrent disease. Ongoing management includes cabergoline, annual plasma metanephrine measurement, and intermittent MRI of pituitary and base of skull to coccyx. Conclusion: Macroprolactinomas are relatively common, with only a small proportion associated with underlying genetic abnormalities. This case describes a patient with 3PAs, initially presenting with a macroprolactinoma, with incidental detection of phaeochromocytoma and paraganglioma and subsequent identification of a pathogenic SDHA mutation. In the context of a calcified bicuspid aortic valve and severe aortic dilatation, pre-operative alpha blockade allowed successful surgical management of both potentially life-threatening conditions.
Presentation: 6/3/2024
8477 Medullary Thyroid Carcinoma Masquerading as a Cold Nodule in a Patient With Graves' Disease
Authors: Umashree T , Farooqui K J , Mithal A 
Published: October 2024

Abstract
Disclosure: T. Umashree: None. K.J. Farooqui: None. A. Mithal: None.
Background: Only a handful of cases of MTC have been reported in the setting of Graves’ disease. Clinical Case: A 38 year old lady presented with symptoms of significant weight loss and palpitations for past six months. Thyromegaly was present, with non tender left lobe enlargement of about 3x3 cm. On further probing it was found that her father had been operated for thyroid cancer 22 years ago, the type of which patient was not aware of. TFTs reflected a thyroxtoxic state (TSH -&lt;0.01mIU/mL [0.34-5.6] FT4 - 3.38 ng/dL [0.58-1.64] FT3 - 8.46 pg/mL [2.6-4.2]) and TRAb was positive (8.74 IU/L [&lt;1.22]). USG neck revealed a hypoechoic lesion of 18x18x13 mm in left lobe thyroid with internal calcifications, with multiple bilateral non-significant lymph nodes. Technetium99 (Tc99) scan showed an enlarged left lobe, with diffuse thyroid uptake at 20 minutes of 4%, and a well-defined photopenic area in left lobe, corresponding to the nodule seen on USG. FNAC of the nodule was suggestive of Hürthle cell neoplasm and patient underwent left hemithyroidectomy. Surprisingly, HPE was consistent with medullary thyroid cancer. Serum calcitonin was raised at 148 pg/mL (N&lt;4.8 for females) and plasma free metanephrines and normetanephrine were normal. F-18 DOPA PET CT showed uptake in residual right lobe of thyroid only, no other abnormal uptake was seen. She underwent completion thyroidectomy with central compartment clearance and is now under regular follow up. Genetic analysis showed RET gene mutation of Cys634Ser, which is heterozygous for MTC. Cold nodules in Graves’ disease should be viewed with suspicion, and while PTC and FTC have been reported more commonly, MTC is extremely rare in this setting. A calcitonin washout of the FNAC may have prevented this patient from undergoing two surgeries. Moreover, Hürthle cell change can also occur in C-cells of the thyroid, not just the follicular cells. Lastly, given the history of thyroid cancer in her father, index of suspicion of MTC should have been higher in this patient. Conclusion: Cold nodules in Graves’ Disease may be malignant, and should always be examined by FNAC. Though MTC is rare, it is not unknown in Grave’s disease.
Presentation: 6/3/2024
8759 Mild Iodine Deficiency During Pregnancy Impairs Hypothalamus-Pituitary-Thyroid Function Programing of the Adult Male Offspring
Authors: Oliveira Mikaeli , Tavares Evelyn , Henrique Guilherme , Anthony Pinto João , Serrano-Nascimento Caroline 
Published: October 2024

Abstract
Disclosure: M. Oliveira: None. E. Tavares: None. G. Henrique: None. J. Pinto: None. C. Serrano-Nascimento: None.
Introduction: Iodine plays a crucial role in the biosynthesis of thyroid hormones and is essential for proper thyroid embryonic development. While severe iodine deficiency during pregnancy and lactation has well-documented deleterious effects, the consequences of mild iodine deficiency (MID) remain not fully understood. MID during pregnancy is a reality in numerous countries, even in regions with seemingly adequate iodine supply in the diet. Previous studies have highlighted the adverse impact of MID on neurological development in offspring, but comprehensive data on thyroid function, particularly in progeny at different developmental stages, are lacking. This study aimed to investigate the repercussions of MID during pregnancy on the programming of thyroid dysfunctions during adulthood. Methods: Female CD1 mice were subjected to iodine-deficient animal chow and iodine-supplemented water, either at normal (NI; 0.2 mg/L) or mild iodine deficiency (MID; 0.8 mg/L) levels during pregnancy. Gene and protein expression in the hypothalamus, pituitary, and thyroid of adult male offspring animals (PND90) were evaluated using qPCR and Western blotting. Additionally, this study explored MID-induced programming of offspring thyroid gene expression through epigenetic mechanisms. Results: Maternal MID exposure led to increased gene and protein expression of thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) in the hypothalamus and pituitary of the offspring animals. Thyroid protein and gene expression of sodium iodide symporter (NIS), TSH receptor (TSHR), thyroid peroxidase (TPO), thyroglobulin (TG), paired box 8 (PAX8), NK2 homeobox 1 (NKX2.1), and monocarboxylate transporter 8 (MCT8) were elevated in the offspring of MID-exposed animals. Epigenetic mechanisms appeared to contribute to the augmented thyroid gene expression in MID-exposed animals, with decreased DNA methyltransferase expression and reduced thyroid DNA global methylation. Additionally, histone 3 hypomethylation and increased acetylation of histones 3 and 4 were observed. Conclusion: The study suggests that MID exposure during pregnancy can be as harmful as severe iodine deficiency in programming the hypothalamus-pituitary-thyroid (HPT) axis, leading to HPT dysfunction during adult life. Consequently, our data suggest that monitoring iodine intake throughout pregnancy is crucial to prevent the occurrence of thyroid disorders in offspring during adulthood.
Presentation: 6/1/2024
8307 Molecularly Targeted Therapy in Oncogene-Driven Human Thyroid Cancer Cell Models: Assay Selection and Response Assessment
Authors: Yang Adeline T , Laetsch Theodore W , Franco Aime T 
Published: October 2024

Abstract
Disclosure: A.T. Yang: None. T.W. Laetsch: Consulting Fee; Self; Cellectis, Deciphera, GentiBio, Jazz Pharmaceuticals, Jumo Health, MassiveBio, Novartis Pharmaceuticals, Pyramid Biosciences, Y-mAbs Therapeutics, Advanced Microbubbles, AI Therapeutics, Bayer, Inc.. A.T. Franco: None.
Background: The most common types of pediatric thyroid cancer (TC) demonstrate kinase-activating genomic alterations that are clinically inhibitor responsive – however, optimal integration of molecular therapy into practice remains uncertain. Human TC cell models can facilitate evaluation of combination therapies. However, prior studies vary from using traditional cell counts to newer reaction-based assays; we assessed whether a linear relationship between cell count and alternative assays exist for human TC cell models. Methods: Standardized curves for Cell TiterGlo (CTG; measures total ATP using luciferase-based luminescence) and NucBlue (DAPI; binds to DNA with nuclear fluorescence) were generated using TC cells seeded at escalating concentrations (5k to 300k cells/well). A linear equation was fitted to the CTG data and used to estimate cell count. DAPI counts were obtained with EVOS automation. Human TC cell lines TPC1 (RET fusion) / CUTC5 (BRAF V600E) were seeded at low (1.5k/2k) and high (3k/4k) cells per well, exposed for 3 days to 0-256 nM selpercatinib (RET inhibitor) or 0-192 nM dabrafenib (BRAF inhibitor), respectively, and response was measured using CTG and DAPI. All were measured in triplicate. Results: Standardized curves of CTG and DAPI demonstrated a 9-23% difference between known and measured cell counts. CTG was accurate within 20k-40k cells/well; DAPI showed linearity within 10k-80k cells/well. TC cells exhibited different IC50 depending on the assay and seeding concentration. Prior studies for selpercatinib and dabrafenib reported in vitro IC50 of 0.4-67 nM and 0.5-6 nM, respectively. In this study, IC50 for CTG/DAPI were closer at higher cell counts: TPC1 was 6.1 / 8.2 nM respectively; CUTC5 was 10.6 / 5.1 nM. Wells seeded at lower counts demonstrated larger inter-assay difference: IC50 for TPC1 was 10.1 / 5.9 nM respectively; CUTC5 was 38.4 / 5.9 nM. Conclusion: IC50 values varied by cell seeding concentrations and assay used, with a two to six fold difference at lower seeding and loss of linearity between luminescence measurements and cell count. This variability complicates evaluating the concordance among data from different laboratories, and in vitro and clinical response. Alternative assays intended to assess viability of inhibitor-exposed human TC cell models may require additional evaluation to ensure measured values demonstrate the expected relationship to the intended measure (ie cell number) and ultimately clinical outcome.
Presentation: 6/3/2024
6668 Myxedema Coma and Takotsubo Cardiomyopathy
Authors: Skariah Annie M , Jain Sumeet 
Published: October 2024

Abstract
Disclosure: A.M. Skariah: None. S. Jain: None.
Background: Takotsubo cardiomyopathy (TCM) also know as broken heart syndrome is a transient decrease in systolic cardiac function in the absence of obstructive CAD. TCM is likely related to hyperadrenergic conditions leading to increased cardiac sensitivity to catecholamine surge leading to cardiomyopathy. TCM is more associated with hyperthyroidism. Case presentation: Patient is an 84-year-old female with PMH of celiac disease,hypertension,prediabetes, and atrial fibrillation s/p cardioversion, on amiodarone. She was brought to the ER after having an unwitnessed fall. She was hypotensive 76/56 mm of Hg, hypothermic 35.5 degree C, HR 90 beats/min; labs significant for hyponatremia, macrocytic anemia, TSH 65.47uIU/ml, FT4 &lt;0.4 ng/dl and mild QTC prolongation of 469ms. Family mentioned history of constipation, progressive weakness, poor oral intake, memory problems and cold sensitivity for a couple of months. Started on 1 pressor, 3 units of PRBC and 2 liters of IVF; BP improved; labs and history suggestive of myxedema coma with myxedema coma Popoveniuc score 85 suggestive of high suspicion for myxedema coma.She had TSH 50.39 uIU/ml and FT4 of 0.4 ng/dl for her memory issues workup 2 months prior to presentation but was not started on medication. Upon admission, started stress dose steroids followed by IV levothyroxine 100 mcg. Not started on LT3 given her old age and atrial fibrillation history. Received additional dose of LT4 100 mcg within few hours. TFT improved with TSH 35 uIU/ml and FT4 1 ng/dl after 2 doses. Later same day, shock worsened, and patient was on 3 pressors along with stress dose of steroids. Cardiology was consulted; recommended an Echocardiogram.Echo was done on day 2; EF 55-60 % with severe hypokinesis of apical myocardium consistent with TCM. Normal echocardiogram studies 4 months ago.Started on weight-based regimen of LT4 75 mcg IV on day 3 and switched to 100 mcg oral when patient tolerated pills.Patient was down to 2 pressors on day 3 and gradually off pressors by day 6. Repeat TFT -showed improvement TSH 12 uIU/ml and FT4 0.7 ng/dl—day 5. Eventually her mentation improved and was discharged on oral LT4. Conclusion: TCM is rare complication of treatment of myxedema coma. Our patient developed shock requiring 1 pressor which unexpectedly worsened to 3 pressors requirement after initial LT4 treatment. High doses of LT4 and LT3 which is part of myxedema coma treatment sensitizes myocardial tissue to catecholamines by increasing expression of beta adrenoreceptors in cardiac myocytes with subsequent ionotropic and chronotropic effects. This may contribute to cardiac stunning and TCM. It’s beneficial to evaluate patients with myxedema coma who develop worsening cardiac status after initiation of high dose of thyroid hormone replacement for TCM.
Presentation: 6/2/2024
8089 Myxedema Coma Presenting with Reversible Cardiomyopathy and Acute Renal Failure
Authors: Mubashir A , Sajid F , Sattar M 
Published: October 2024

Abstract
Disclosure: A. Mubashir: None. F. Sajid: None. M. Sattar: None.
Myxedema Coma is a life-threatening complication of hypothyroidism and often presents with multi-organ failure. However, reversible cardiomyopathy and acute renal failure are rare. Here, we present a case of iatrogenic hypothyroidism leading to myxedema coma with reversible organ failure. Case Presentation: A 58-year-old male with a past medical history of iatrogenic hypothyroidism after total thyroidectomy for follicular thyroid cancer, noncompliant with levothyroxine for the past three years, was brought to the hospital due to worsening mental status, low energy, and cold extremities for three days. On admission, vital signs were within normal limits. Laboratory studies revealed Random Glucose 113 (74-200 mg/dl), Na 134 (135-149 mmol/l), TSH: 217 (0.39-4.08 MCIU/ml), Free T4 &lt;0.25 (0.58-1.64 ng/dl), Free T3 1.01 (2.53-3.87 pg/ml), BUN 53.3 (7-21 mg/dl), Creatinine 4.9 (0.5-1.3mg/dl). Urinalysis was positive for protein of 300 mg/dl (negative). Urine studies showed hematuria, total protein/cr 3.18 (&lt;0.10), with increased total protein of 60/24 hours (0-12 mg/dl), suggesting glomerular etiology. Additionally, Bence Jones protein and monoclonal band were negative, interpreted as mild glomerular proteinuria. FeNa &gt;2%, Urine sodium of &gt;40 (20-40mmol/l) suggest acute tubular necrosis. EKG showed normal sinus rhythm with low voltage. To rule out diastolic dysfunction, an echocardiogram was performed, which revealed depressed systolic function with an ejection fraction of 31-35% and a large pericardial effusion with echocardiographic features of tamponade. He also had global cardiomyopathy with akinesis, especially in the inferior segments. He was treated with IV levothyroxine. Repeat imaging in one month showed an increase in ejection fraction to 55% with moderate-sized pericardial effusion and no echocardiographic features of tamponade. Global cardiomyopathy had also resolved. However, left ventricular systolic function was borderline, with delayed diastolic expansion of the right ventricle. Repeat creatinine was 2mg/dl. The patient’s condition greatly improved, and he was discharged with follow-up with endocrinology, nephrology, and cardiology. Discussion: In the available literature, diastolic dysfunction is associated with severe hypothyroidism. However, reversible global cardiomyopathy with decreased systolic function is rare. The pathogenesis of this myopathy is not well understood. Similarly, known mechanisms of renal injury in hypothyroidism include renal hypoperfusion, rhabdomyolysis, decreased kidney-to-body weight ratio, truncated tubular mass, and altered glomerular architecture. While the need to perform a renal biopsy or the use of goal-directed therapy for dilated cardiomyopathy remains questionable in such cases, reversible complications of severe hypothyroidism should be investigated in patients with suspected myxedema.
Presentation: 6/2/2024
12393 Myxedema Presenting With Impending Cardiac Tamponade : A Case Report
Authors: Hoskote Abhinav , Gupta Vishal , Seidenberg Jacob 
Published: October 2024

Abstract
Disclosure: A. Hoskote: None. V. Gupta: None. J. Seidenberg: None.
The widespread availability of thyroid stimulating hormone (TSH) assays, routine screening and affordable replacement therapy has resulted in decreased prevalence of complications of untreated hypothyroidism. “Myxedema heart” is a rare syndrome that results in bradycardia, cardiomyopathy and pericardial effusion. We present a rare case of cardiac tamponade due to myxedema in a patient with unidentified hypothyroidism. A 49-year-old male was brought to the ER by his family for several weeks of cognitive slowing, weakness and inappropriate behavior involving defecating on himself eating old food and barricading in his room. The patient denied past medical or psychiatric history, medication use or recent physician evaluation. On exam he had macroglossia, was disheveled, forgetful but alert with slow speech, ataxia and muscle wasting. He was afebrile and hemodynamically stable. EKG showed sinus bradycardia. Labs were notable for sodium 133, hemoglobin 8.8g/dL and TSH was incidentally &gt;100U. Levothyroxine was begun. The next day, he was noted to have increased lethargy, bradycardia and hypoglycemia and was transferred to the intensive care unit with concern for myxedema coma. Free T4 was &lt;0.3 ng/dL (0.6-1.6) and free T3 was 1.6pg/mL (2.5-3.9). An echocardiogram revealed a large circumferential pericardial effusion with right atrial and ventricular collapse with tamponade. Treatment with 5 mcg liothyronine, intravenous levothyroxine and stress dose hydrocortisone was begun. A pericardial drain was placed, draining 980mL of sanguineous fluid. After clamping trials, the drain was removed 48 hours later. Labs revealed thyroglobulin &lt;0.1ng/mL (1.6-50), thyroid peroxidase (TPO) antibody 574 IU/mL (&lt;9), thyroglobulin antibody &gt;2500 (&lt;4) and thyroid ultrasound showed a normal sized thyroid gland with heterogenous echogenicity confirming a diagnosis of Hashimoto’s thyroiditis. Serial echocardiograms during the admission and a follow-up two months later showed a stable posterior effusion with no recurrence of the anterior pericardial effusion. Gradually mentation, hemodynamics and electrolyte derangements improved, and he was discharged on oral levothyroxine. TSH values showed sequential improvement to 48U in 15 days and to 11U in 2 months. Myxedema is a manifestation of severe hypothyroidism. The pericardium, a collagen-rich structure, is susceptible to myxedematous infiltration, leading to pericardial effusion. While small pericardial effusions are common with chronic hypothyroidism, a large pericardial effusion with tamponade is a rare life-threatening complication that requires prompt recognition and management. Clinicians must promptly identify myxedema and replace thyroid hormone to prevent progression of pericardial effusion to tamponade, maintaining especially high suspicion in those at risk of poor access to healthcare or inadequate health literacy.
Presentation: 6/3/2024
12337 Nivolumab Induced Secondary Adrenal Insufficiency And Hypothyroidism In A Patient With Graves’ Disease: A Case Report
Authors: Sajid Fatima , Kaur Jasveen , Zatsepina Alina , Khan Muzammil , Resta Christine A 
Published: October 2024

Abstract
Disclosure: F. Sajid: None. J. Kaur: None. A. Zatsepina: None. M. Khan: None. C.A. Resta: None.
Introduction: We present a case of a patient with Graves’ disease who developed concurrent secondary adrenal insufficiency (SAI) and primary hypothyroidism while undergoing treatment with nivolumab for non-small cell lung cancer (NSCLC). This case sheds light on the immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy. Case Presentation: A 63-year-old woman with a history of Graves’ disease and NSCLC undergoing neoadjuvant chemoimmunotherapy was admitted with hyponatremia. She was diagnosed with Graves’ disease a year before and was treated with methimazole (MMI). When she was diagnosed with Graves’ disease, her TSI was 1.64 IU/L (&lt;0.55). Before starting nivolumab, TSH had normalized at 0.5 MCIU/mL on MMI therapy. She started nivolumab 3 months before admission. One month after starting nivolumab, her TSH was &lt;0.01. By the time she was admitted, she had severe hypothyroidism and SAI with sodium 116 mmol/L (135-149), TSH 40.34 mIU/mL (0.39-4.08), free T4 &lt;0.25 ng/dL (0.8-1.8), TSI 21.2 IU/L (0.00-0.55) Total Cortisol 0.4 ug/dL (6.7-27.6), AM Cortisol 0.6 ug/dL, ACTH &lt;1.5 pg/mL (7.2-63.3), LH 75.5 IU/L (7.7-58.5), and FSH 179 IU/L (25.8-134.8). MMI was discontinued due to hypothyroidism. She was started on replacement therapy with levothyroxine and hydrocortisone. Subsequent sodium levels normalized. Discussion: Nivolumab has emerged as a promising immunotherapy for NSCLC. Our patient developed irAEs following nivolumab treatment. Notably, this case represents only the third documented case to our knowledge of both primary hypothyroidism and secondary adrenal insufficiency occurring post-nivolumab treatment. Workup for our patient revealed two irAE’s. She developed primary hypothyroidism and isolated ACTH deficiency with other pituitary function remaining normal. The pattern of thyroid profile over time was consistent with thyroiditis due to ICI therapy. TSI increased, ruling out remission from Graves’ disease. Even after discontinuing methimazole, she remained hypothyroid. Hence, in this case, ICI effectively acted as definitive therapy for her Graves’ disease. Conclusion: This case sheds light on the intricate interplay between nivolumab therapy, pre-existing autoimmune conditions such as Graves’ Disease, and the emergence of irAEs. This case underscores the importance of vigilant monitoring of serum sodium levels, and thyroid and pituitary function tests in patients undergoing immunotherapy.
Presentation: 6/1/2024