bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI473 Central Hypothyroidism Following Neonatal Graves Presentation
Authors: Metzinger Emily , Halpin Kelsee 
Published: October 2023

Abstract
Disclosure: E. Metzinger: None. K. Halpin: None.
Background: Neonatal Graves’ disease is a rare disorder of neonatal autoimmune hyperthyroidism secondary to the transplacental passage of thyroid-stimulating hormone receptor antibodies. Although neonatal Graves’ disease is transient, it is associated with cardiac dysfunction, intrauterine growth restriction, prematurity, craniosynostosis, and developmental delay and can be life-threatening. Additionally, infants with neonatal Graves’ disease can rarely present with primary or central hypothyroidism later in infancy or childhood. This is suspected to be due to the disruption in the hypothalamic-pituitary-thyroid axis or development of the thyroid gland. Clinical Case: Here we describe a case of neonatal Graves’ disease that has been complicated by persistent central hypothyroidism requiring levothyroxine treatment. This was a preterm infant with tachycardia, biventricular heart failure, and hepatomegaly who was transferred to a higher level of care NICU for cardiac and respiratory failure. Pregnancy was complicated by history of maternal Graves’ disease status post radioiodine ablation. Maternal TRAB and thyroid levels were unavailable. Initial thyroid studies on DOL 1 were notable for suppressed TSH of &lt;0.02mcIU/mL, elevated free T4 6.9ng/dL, and elevated total T4 &gt;24.9mcg/dL. Total T3 was normal at 161ng/dL (50-452ng/dL) on DOL 2, and TSI was elevated at 4.8 (TSI Index, normal &lt;/= 1.3) on DOL 3. For neonatal thyrotoxicosis, the infant was treated with methimazole, potassium iodide (KI), propranolol, and hydrocortisone. Hydrocortisone was discontinued as the infant clinically improved, and KI was discontinued after 1 week. TFTs were closely followed during admission and methimazole dosing was adjusted as needed. He was discharged from the NICU on DOL 19 on methimazole and propranolol with close outpatient lab monitoring and follow-up. Propranolol was discontinued by 1.5 months of life, and methimazole was discontinued by 2 months of life as TFTs normalized. TSI was negative by four months of life. TSH remained low with decreasing free T4 levels. Ultimately, he was started on levothyroxine at 8.5mcg/kg/day at 2.5 months of age for central hypothyroidism. At that time, TSH was 0.06mcICU/mL and FT4 was 0.7ng/dL. TSH remained low through the first 14 months of treatment with normal free T4 levels on levothyroxine. He has been continued on levothyroxine (average 20mcg/day). Conclusion: This case highlights the severity of neonatal Graves’ disease and the possibility of the subsequent development and persistence of central hypothyroidism following neonatal Graves’ diagnosis despite the resolution of hyperthyroidism and normalization of TSI antibody. Due to the risk of the development of hypothyroidism, it may be worthwhile to continue to trend TSH and FT4 to ensure that the infant has not developed hypothyroidism.
Presentation: Friday, June 16, 2023
FRI493 Immune Checkpoint Inhibitors: Effects On Thyroid Nodular Disease
Authors: Maria Bignoli Daniela Laura , Kalara Niketa , Manzano Alex J 
Published: October 2023

Abstract
Disclosure: D.L. Bignoli: None. N. Kalara: None. A.J. Manzano: None.
Introduction: Immune checkpoint inhibitors (ICI) are more recent pharmacologic agents used to treat malignancies, linked to immune related adverse events (irAEs) especially involving the thyroid. Classically, a transient silent thyroiditis occurs followed by hypothyroidism, however the effects on multinodular goiter are not fully recognized. We report a patient with poorly differentiated colon adenocarcinoma, treated with Pembrolizumab and Ipilimumab with significant improvement in the size of her thyroid nodules. Pembrolizumab is a monoclonal antibody directed against PD-1 receptors and Ipilimumab is an anti-CTLA-4 antibody; combination therapy has a higher incidence of irAEs compared with monotherapy (54% versus 24%). Clinical Case: 71-year-old female with a history of nontoxic benign multinodular goiter and Hashimoto’s hypothyroidism began ICI therapy as adjunctive treatment for poorly differentiated colon adenocarcinoma with MSH 2 mutation. She was euthyroid on same dose of levothyroxine for years however developed subclinical hyperthyroidism after starting immunotherapy; reporting anxiety, palpitations, tremors, and anterior neck fullness. TSH then was 0.02 mIU/mL (reference range 0.40-4.50 mIU/mL), free T4 1 ug/dl (reference range 0.9-1.7 ng/dl), and T3 122 ng/dl (reference range 100-200 ng/dl) with positive TPO antibodies. Levothyroxine was stopped and her symptoms subsequently self-resolved at follow-up 4 weeks later. Ultrasonography (US) performed in 2018 prior to starting ICI revealed: left lobe 1.3 x 2.5 x 4.66 cm, right lobe 1.3 x1.4 x 4.6 cm, isthmus 0.7 cm. There were multiple nodules: 0.4 x 0.9 x 0.7 cm, 0.3 x 0.3 x 0.4 cm nodule at right lobe, and 0.9 x 2 x 2.1 cm over right isthmus. The left lobe had four nodules: 0.4 x 0.5 x 0.8 cm, 0.4 x 0.5 x 0.9 cm, 0.8 x 0.8 x 1.36 cm, and 1 x 1.1 x 1.5 cm. Repeat ultrasonography after immunotherapy in October 2022 revealed substantial decrease in thyroid size, and the previously reported isthmus nodule was no longer visualized. The left thyroid lobe measured 0.5 x 1.1 x 3.3 cm, the right lobe 0.92 x 0.6 x 3.4 cm, and isthmus measured 0.2 cm. The right lobe nodule measured 0.40 x 0.33 x 0.86 cm and the left lobe nodule 0.34 x 0.24 x 0.50 cm. TSH was 1.150 mIU/mL, free T4 1.61 ug/dl, T3 96 ng/dl; evidencing a drastic improvement of her multinodular goiter due to ICI therapy. Conclusion: To the best of the author’s knowledge at this point in time, this is one of the few cases demonstrating effects of ICI therapy on nontoxic multinodular goiter. As described, there was a significant change in size and a previously biopsied isthmus nodule was not seen on her last ultrasound. Although irAEs are well established, there is limited literature regarding changes in anatomy and thyroid nodule architecture.
Presentation: Friday, June 16, 2023
FRI189 Alcohol-induced Non-neoplastic Hypercortisolism: Report Of Eight Cases And Review Of The Literature
Authors: Surani Asif , Carroll Ty Brian , Javorsky Bradley Richard , Raff Hershel , Findling James W 
Published: October 2023

Abstract
Disclosure: A. Surani: None. T.B. Carroll: Consulting Fee; Self; Corcept Therapeutics. Research Investigator; Self; Corcept Therapeutics, Recordati. B.R. Javorsky: Consulting Fee; Self; Clarus. Research Investigator; Self; Recordati, Amryt Pharma. H. Raff: Consulting Fee; Self; Cerium Pharmaceuticals, Corcept Therapeutics. Research Investigator; Self; Cerium Pharmaceuticals. J.W. Findling: Consulting Fee; Self; Corcept Therapeutics, Recordati. Research Investigator; Self; Recordati.
Alcohol intake stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Alcohol-induced hypercortisolism (AIH) is an underrecognized clinical phenomenon thought to be of hypothalamic etiology. Patients with alcohol use disorder may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] thus obscuring its diagnosis. We addressed this issue using newer, more accurate biochemical testing for the diagnosis of CS. We evaluated eight patients with AIH referred for possible CS (six for inferior petrosal sinus sampling, one with persistent CS after removal of an adrenal adenoma, and one for pituitary surgery). All patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval (RI) confirming a centrally mediated mechanism. All eight patients had abnormal low-dose dexamethasone suppression test (DST) [post DST serum cortisol 2.2-19.1 mcg/dL (RI&lt;1.8)] and increased late-night salivary cortisol [8.2-71.0 nmol/L (RI&lt;3.2)]. Only one patient had increased urine cortisol excretion. In contrast to patients with pituitary CS, the 5 patients tested had blunted or absent ACTH and cortisol responses to dDAVP. Two patients had adrenal nodules and one patient had abnormal pituitary imaging. Most patients initially underreported their alcohol consumption and one patient denied alcohol use. A marked elevation of blood phosphatidylethanol (PEth) was required in one patient to confirm excessive alcohol use. All the patients had significant elevations of liver function tests (LFTs) with AST&gt;ALT. Review of the literature discovered 37 reported cases of AIH. These cases also had clinical and many biochemical findings that were similar to neoplastic hypercortisolism. Conclusion: AIH is an under-appreciated potentially reversible cause of non-neoplastic hypercortisolism that may be indistinguishable from neoplastic ACTH-dependent CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption may further confound the diagnosis. Elevations of LFTs (AST&gt;ALT) and subnormal ACTH and cortisol responses to dDAVP may be helpful in distinguishing AIH from neoplastic hypercortisolism. Measurement of PEth helps to confirm an alcohol use disorder.
Presentation: Friday, June 16, 2023
FRI494 Ischemic Stroke After Radioactive Iodine Therapy In Graves Disease
Authors: Rave Talia , Giunta Judy 
Published: October 2023

Abstract
Disclosure: T. Rave: None. J. Giunta: None.
Hyperthyroidism is defined as excess thyroid hormone, most commonly due to Graves Disease. Thiomides are first line therapy, however more definitive options are radioactive iodine (RAI) or thyroidectomy. RAI enters thyroid follicular cells and destroys the thyroid tissue with beta ray emissions. Patients with Graves disease, toxic multinodular goiter, and thyroid cancer can benefit from RAI, but it is contraindicated in pregnancy, breast feeding, and severely uncontrolled thyrotoxicosis. Early side effects are pancytopenia, thyrotoxicosis, and later complications are bone marrow suppression and cancer. There are several reports of cerebral vascular accidents (CVA) after RAI therapy, however, there is limited research demonstrating whether CVA is a direct consequence of RAI or secondary to thyrotoxicosis. This case describes a possible RAI-induced CVA. A 60-year-old female with a past medical history of type 2 Diabetes Mellitus, hypertension, obesity, and Graves disease presented with altered mental status and gait instability for 1 day. She received RAI therapy 1 day prior to symptom onset for uncontrolled Graves disease. She was previously on Methimazole and PTU, however, both were discontinued due to an intolerable rash. As a result, she was maintained on a beta blocker prior to RAI. On presentation, she was afebrile, normotensive with a heart rate of 79. She was oriented only to person and place and had an unbalanced gait. Her Burch-Wartofsky score was 30, which was concerning for thyrotoxicosis. Her TSH was undetectable and EKG showed normal sinus rhythm. She was placed on atenolol, PTU and hydrocortisone. Her CT head was negative for acute disease, however, her MRI brain diagnosed an acute ischemic stroke. During admission, she had episodes of atrial fibrillation with rapid ventricular response. This patient presented with thyrotoxicosis after RAI therapy complicated by a CVA. It is important to note that on presentation she was reliably taking a beta blocker outpatient and her EKG was normal sinus rhythm making atrial fibrillation a less likely culprit of her CVA. Research has found that hyperthyroidism alone can lead to a prothrombotic state, however, additional literature reports that both hyperthyroid and euthyroid patients have an increased risk of CVA following RAI. Whether a CVA is secondary to thyrotoxicosis or a direct effect of RAI, this potentially life-threatening complication should be discussed with patients prior to treatment.
Presentation: Friday, June 16, 2023
FRI521 Low FT3 And Decline In FT3 Levels Are Associated With Mortality; A Big-data Study
Authors: Strich David M , Israel Ariel , Joseph Gillis David 
Published: October 2023

Abstract
Disclosure: D.M. Strich: None. A. Israel: None. D.J. Gillis: None.
Importance : If low free triiodothyronine levels could detect people at risk for early mortality, this could be helpful in focusing preventive medicine efforts on those who are in most need. Objectives: Thyroid hormone levels characteristic of "euthyroid sick syndrome" are seen in acute illness. Lower levels of free tri-iodothyronine and free thyroxine are seen with increasing age. We aimed, adjusting for normal age-associated decline of these hormones, to determine whether thyroid hormone levels could predict long-term survival. Design & Setting: This is a "big-data" study based on thyroid function tests from samples taken between 2008-2014. Data were crossed with electronic health records for morbidity and national death registry for mortality. Excluded: age below 18 years or above 95 years, taking thyroid or anti-thyroid drugs. We converted each measurement to an Age and Gender Adjusted Percentile (AGAP). We assessed survival according to ranges of initial AGAPs of Free Triiodothyronine (FT3), Free Thyroxine (FT4), and Thyrotropin (TSH) up to 8 years prior to death for two subgroups: "not healthy" - subjects with at least one of five chronic conditions registered in their electronic health chart; "healthy" - all others. The hazard ratio for death of various AGAPs was defined for the entire cohort and the subgroups separately. Results: Thyroid function tests were taken from 365,965 patients. 258,695 remained after exclusion criteria: 151,868 "not healthy" and 106,827 "healthy". After a median follow-up of 6.8 years, 5,865 /151,868 (10.4%) of the "not healthy" had died and 2,504/106,827 (2.3%) of "healthy" participants. The lowest 5th percentile initial FT3 AGAPs survival compared to the 95th percentile was for "not healthy" hazard ratio 5.71 (CI - 5.23 to 6.26, p&lt;0.001), for "healthy" - hazard ratio was 3.92 (CI - 3.06 to 5.02, p&lt;0.001)). Eight year survival associated with decline in FT3 AGAPs for 34,129 individuals was lowest for those with greater that 50%, decline: 86% of "not healthy" subjects and 95.5% of "healthy" subjects with such a decline survived 8 years. Conclusion and relevance: Lower age-adjusted values of FT3 were associated with decreased survival. This marker may potentially be used for focusing patients with expected reduced survival.
Presentation: Friday, June 16, 2023
FRI529 Hypothyroidism And Systemic Lupus Erythematosus: A Nationwide Analysis
Authors: Sami Faria , Ahmed Sami Shahzad , Razok Almurtada , Ayub Tooba , Olafimihan Ayobami 
Published: October 2023

Abstract
Disclosure: F. Sami: None. S. Sami: None. A. Razok: None. T. Ayub: None. A. Olafimihan: None.
Background: Hypothyroidism is the most common thyroid disease in Systemic Lupus Erythematosus (SLE) and more prevalent in SLE than the general population. Our aim is to study the prevalence, epidemiology and likelihood of hypothyroidism with SLE as well as impact on outcomes and healthcare burden. Methods: The National Inpatient Database from 2016-2019 was used to extract patient populations. Data was stratified to reflect national estimates. Adult patients with principal diagnosis of SLE and hypothyroidism as a primary or secondary diagnosis were identified. Epidemiology was compared. We analyzed mortality rates, hospital charges (THC) and length of stay (LOS). Secondary outcomes included sepsis, congestive heart failure (CHF), renal and respiratory failure, stroke and myocardial infarction (MI). Statistical analysis was performed with STATA17. Univariate and multivariate regression analyses adjusted for confounders. Results: Among 721,090 adult SLE patients, 17.64% had hypothyroidism. In SLE-hypothyroid group, there were more females (93.46% vs 87.35%, odds ratio 2.01) and whites ( 65.82%vs 33.53%, OR 2.37). The mean age was higher (59.95 SD 15.56 vs 50.91 SD 16.94, P-value 0.000) with significantly more patients in 60-80 years group (44.64% vs 28.56%) and less in 18-40 year age group (1.68% vs 29.01%). African-Americans and Hispanics were significantly less in hypothyroid group with OR 0.34 and 0.87 respectively. Charlson comorbidity Index was ssignificantly high (3.2 vs 2.97). Hypothyroidism was significantly more among higher socioeconomic class of SLE patients (20.62% vs 16.7%) and less prevalent among the low socioeconomic class (28.88% vs 35.36%) based on annual income. There was no significant rise in mortality when adjusted for confounders (1.93% vs 1.97%, P-value 0.702), mean length of stay (5.41 vs 5.46, P-value 0.284), or total hospital charges ($63372 vs 64065, P-value 0.273) between two groups. There was a significantly higher prevalence of MI (3.21% vs 2.9%, P-value 0.01,OR 1.11) and CHF (5.94% vs 5%, P-value 0.00,OR 1.2). Prevalence of sepsis (8.92% vs 8.77%, P-value 0.449), renal failure (37.94% vs 37.79%), respiratory failure (37.63% vs 37.84%) and stroke (0.88% vs 0.93%,) was comparable with no significant difference. Odds ratio for hypothyroidism in SLE was 1.5, p-value 0.000. Conclusion: SLE patients with hypothyroidism are more females, Caucasians, of higher mean age, between 60-80 years of age, and from higher socioeconomic status. There is no effect on mortality, LOS and THC, rate of sepsis, stroke, renal and respiratory failure with hypothyroidism. There is a significantly higher risk of MI and CHF. SLE patients have 1.5 times increased risk of developing hypothyroidism. This emphasizes screening at-risk individuals when suspicion arises, for timely diagnoses and improving outcomes.
Presentation: Friday, June 16, 2023
FRI531 IgG4 Related Mass -forming Thyroid Disease: Two Case Reports
Authors: Sarah Braham Rim , Droumaguet Céline , Vitellius Manuel , Tran-van-nhieu Jeanne , Béquignon Emilie , Desgranges Pascal , Limal Nicolas , Mahevas Matthieu , Godeau Bertrand 
Published: October 2023

Abstract
Disclosure: R.S. Braham: None. C. Droumaguet: None. M. Vitellius: None. J. Tran-van-nhieu: None. E. Béquignon: None. P. Desgranges: None. N. Limal: None. M. Mahevas: None. B. Godeau: None.
IgG4 thyroiditis is an invasive fibrotic process involving the thyroid in a systemic disease. It is a rare inflammatory autoimmune disease with insidious presentation and nonspecific symptoms.We describe two unusual cases of mass forming IgG4 thyroiditis that were diagnosed recently in our department. The first case is about a 42-year-old woman who has a history of Hashimoto thyroiditis with hypothyroidism presenting with a rapid goiter growth, neck pain, dysphagia and hoarseness. A lymphoma was suspected. Ultrasonography shows heterogeneous hypoechoic lesions that may infiltrate the perithyroid muscles. Fine-needle aspiration (FNA) was suspicious of IgG4 infiltrative disease which was confirmed by microbiopsy. Only the thyroid was hypermetabolic on fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) Scan. No improvement under corticosteroid treatment and Rituximab. Surgery was planified to relieve pressure symptoms. The thyroid surgery was very difficult because of the extensive fibrosis and only a biopsy was performed, confirming the diagnosis and excluding malignancy. The second case is about a 68-year-old woman with a history of hypertension and Graves disease presented with a neck right mass that was suspected to be a paraganglioma, hypermetabolic on FDG PET scan with no other localisation. This mass was surrounding the right primitive carotid artery, associated with thrombi of the internal jugular vein. FNA and microbiopsy found a fibrotic non specific tissue. Thyroidectomy and surgical biopsy of the neck mass were performed with histopathology confirming IgG4 disease on the thyroid gland with fibrosis. There were no hypocalcemia in the two cases and no other localisation. IgG4 related mass-forming thyroiditis is an extremely rare disease. It is now a recognizable pattern of IgG4 thyroiditis, and has as differential diagnosis Hashimoto’s thyroiditis, Graves disease and thyroidal carcinoma.We will discuss through these cases the different clinical presentation of this rare disease, the diagnostic tools, the treatment and the long term follow up.
Presentation: Friday, June 16, 2023
FRI533 A Novel Cre-loxP Based Mouse Model For Graves' Disease
Authors: Kim Daham , Bao Yaru , Jeong Kang Min , Hee Cho Yoon , Kim Youngsook , Hwang Yoon-a , Ryong Ku Cheol , Jig Lee Eun 
Published: October 2023

Abstract
Disclosure: D. Kim: None. Y. Bao: None. M. Kang: None. Y. Cho: None. Y. Kim: None. Y. Hwang: None. C. Ku: None. E. Lee: None.
Objectives: Over years, various approaches have been used to model human Graves’ disease in mice, including transfected fibroblasts, and plasmid or adenoviral immunizations with the extracellular A subunit of the human thyrotropin receptor (hTSHRa). However, these models require a lot of effort for multiple dosing over several months and the results are very heterogeneous, limiting their use as a platform for the development of new therapeutics. Thus, we developed a novel Cre-loxP based mouse model for Graves' disease. Methods: To overcome the limitation of existing animal models, we made ESC-derived KI mouse expressing hTSHRa that will act as an antigen in a conditional manner by inserting the CAG-loxP-STOP-loxP-hTSHRa cassette into the mouse Rosa26 locus. TAT-Cre, a recombinant cell-permeant fusion cre-recombinase protein, was used for site-specific recombination to avoid leaky expression which may induce immune tolerance. Various concentrations of TAT-Cre were tested to avoid neutralization and produce adequate hyperthyroidism. Serum TSHR Ab and T4 levels were measured. Immunohistochemical examinations of the thyroid gland and orbits were performed. Results: Treatment with TAT-Cre within the range of 250-750U produced the most efficient TSHR Ab and significantly increased T4. Four weeks after TAT-Cre 500U administration, TSHR Ab levels were already significantly produced in all mice and T4 levels started to increase. At 8 and 12 weeks, TSHR Ab levels were produced at a very high levels in all mice and T4 levels were increased to a very high levels in over 80% of mice. After 3 months, MRI images did not show any significant protrusion. However, there was an enlargement in the volume of the orbital muscles. We also found thyroid enlargement and hypertrophy, orbital macrophage infiltration and fibrosis in Immunohistochemical examinations. Conclusions: A new mouse model for Graves' disease was successfully established by using the Cre-loxP system. After being optimized for orbitopathy induction, this model can be used as a platform for the development of novel therapeutics.
Presentation: Friday, June 16, 2023