bluuebunny/crossref_metadata_2025 huggingface dataset:
8060 SIRT4 Plays a Role in Mammary Gland Development
Authors: deSouza B , Huynh F , Anderson K , Batchvarov I , Capel B , Hirschey M
Published: October 2024

Disclosure: B. deSouza: None. F. Huynh: None. K. Anderson: None. I. Batchvarov: None. B. Capel: None. M. Hirschey: None.

Breastfeeding confers a wealth of benefits to both children and mothers. Breastfeeding can be impaired by metabolic diseases such as diabetes and obesity, which are known to interfere with both normal mammary gland development and lactogenesis, although mechanisms remain unclear. Our lab recently discovered a novel connection between metabolic regulation and mammary development in Sirt4 knockout (Sirt4-/-) mice. SIRT4 is an NAD+-dependent mitochondrial enzyme with strong deacylase activity. It is known to regulate several metabolic pathways including those of fatty acids, glutamine, and leucine. Sirt4 knockout mice are resistant to developing high-fat diet-induced obesity but develop early-onset insulin resistance. We observed that Sirt4-/- females are incapable of nursing their offspring due to impaired mammary ductal branching. Transplantation of wild-type mammary epithelia into SIRT4KO mice fails to rescue mammary development; however, mammary epithelia from SIRTKO mice transplanted into wild-type mice develop normally. SIRT4 action is thus required outside the mammary gland, which led us to explore the effect of SIRT4 on steroid hormone signaling. Treatment of pre-pubertal SIRT4KO mice with progesterone and estradiol, but not estradiol alone, rescued mammary ductal branching. Likewise, transplants of wild-type ovaries into SIRT4KO mice partially rescued the ductal branching defect. Given these findings, we hypothesized that SIRT4 expression in the ovary is necessary for sufficient progesterone biosynthesis and subsequent mammary development. In ovaries of adult mice, SIRT4 is most highly expressed in differentiated granulosa cells of the corpus luteum, a temporary endocrine structure responsible for synthesizing peak levels of progesterone during the diestrus phase of the mouse estrous cycle. Future experiments will compare peak circulating progesterone levels in Sirt4-/- vs. wild-type mice. We will characterize progesterone signaling in SIRT4KO mammary glands, including determining the expression of progesterone receptor isoforms. Additionally, we will characterize SIRT4 function in the ovary, including its effects on corpus luteum formation, steroid hormone biosynthesis, and import vs. de novo synthesis of the steroidogenic precursor, cholesterol. This work could offer new insights into the impairment of breastfeeding due to metabolic diseases.

Presentation: 6/3/2024
8711 The Effect of Testosterone Therapy Upon Bone Remodelling in Testosterone Deficient APOE-/- Mice Fed a High Fat Diet
Authors: Williamson A , Bateman L , LeMaitre C , Jones T H , Aberdein N , Kelly D M
Published: October 2024

Disclosure: A. Williamson: None. L. Bateman: None. C. LeMaitre: None. T.H. Jones: None. N. Aberdein: None. D.M. Kelly: None.

Introduction: Low testosterone can lead to bone loss in males, but the mechanisms are not fully characterised. This study investigates the effects of testosterone depletion, and subsequent testosterone treatment on parameters of bone remodeling in a murine model of cardiometabolic disease. Methods: At 8 weeks of age, high-fat diet-fed ApoE-/- mice were randomised into three groups: sham surgery + placebo treatment (control, n=9), orchidectomy + placebo treatment (n =8), and orchidectomy + testosterone treatment (n=10). 25 week old mice were sacrificed and tissues collected for analysis. Left tibiae were decalcified, paraffin embedded and sectioned prior to immunostaining of bone turnover markers including receptor activator of nuclear factor κB ligand (RANKL), Osteoprotegerin (OPG), runx2, Alkaline Phosphatase (ALP), adiponectin and marrow lipid content. Right tibiae underwent mechanical 3-point bend testing at 0.05mm/s using a CellScale Univert. Results: µCT demonstrated a significant decrease in trabecular bone volume, number, and bone mineral density (BMD) and increased trabecular thickness in orchidectomised mice compared to controls. These parameters returned to control levels in testosterone treated orchiectomised mice. No significant differences were observed in cortical bone. Lipid deposition within the bone marrow was significantly increased in testosterone deficient mice compared to testosterone replete mice. No significant differences in ALP immunopositivity were detected between groups, and runx2 was significantly decreased in orchiectomised mice treated with testosterone compared to controls. The ratio of RANKL/OPG immunopositivity was significantly increased in testosterone deficient mice compared to testosterone replete mice. 3-point bending demonstrated no significant differences in maximal force between groups despite a downward trend in orchiectomised groups compared to controls. Osteoclast number quantified from TRAP-stained sections was not different between groups. Discussion: Testosterone depletion accelerates trabecular bone loss, mediated by increased osteoclastogenesis via the RANKL/OPG pathway and increased bone marrow adiposity, an effect reversed by testosterone treatment. While this study highlights the benefits of testosterone upon trabecular bone health in male mice these changes may not alter fracture risk as 3-point-bend maximal force was not affected.

Presentation: 6/2/2024
7993 Thienopyrimidine-Based Estrogen Receptor Modulators Adopt Unique Ligand Binding Poses to Elicit Anti-Proliferative Activities in ER+ Breast Cancer Cells
Authors: Fink Emma C , Mateus Sofia Lucia , Meganathan Nandakumar , Sammeta Vamshi K R , Norris John D , McDonnell Donald Patrick , Willson Timothy , Fanning Sean William
Published: October 2024

Disclosure: E.C. Fink: None. S.L. Mateus: None. N. Meganathan: None. V.K. Sammeta: None. J.D. Norris: None. D.P. McDonnell: None. T. Willson: None. S.W. Fanning: None.

One in eight women will be diagnosed with breast cancer in their lifetimes. Estrogen receptor alpha (ER) drives breast cancer pathology and is expressed in approximately seventy percent of tumors. Hormone therapies are used to treat and prevent the metastasis of ER+ breast cancers and these patients have favorable 5-year survivals. However, most breast cancer patient deaths are ER+. While the next generation of antiestrogens have shown promise in the advanced setting, more work needs to be done to fully address these mortalities. ER is a ligand-dependent master transcriptional regulator, whereby ligand-specific ER conformational ensembles redirect multiple programs to produce oncogenic or therapeutic endpoints. To better understand ER structure-activity relationships, we have developed new antiestrogenic small molecules based on a thienopyrimidine scaffold. Comprehensive structural, ER activity, and cancer endpoint profiling shows that these new molecules adopt a unique ligand binding pose, which perturbs new structural elements within the orthosteric hormone binding pocket. These molecules downregulate ER target genes and halt the proliferation of ER+ breast cancer cells.

Presentation: 6/3/2024
5051 Clinical Correlation between TSH levels and TAU Imaging
Authors: Sunil Surya
Published: October 2024

Disclosure: S. Sunil: None.

Background: Tau-PET Scan measures brain tau deposition. TSH levels related to cognitive impairment. We analyzed the correlation of TSH levels to tau-PET imaging in a memory clinic. Hypothesis: Tau-PET positivity correlates with lower TSH values in the clinic patients. Objectives: To assess the correlation of tau-PET positivity to TSH levels in memory clinic patients. Method: Retrospective observational chart review study of patients attending a memory clinic in Boston, MA, with TSH levels and tau-PET scan included for analysis. No stratification based on initial or final diagnosis, severity of cognitive impairment, or tracer used. Baseline TSH levels and a binary PET scan result were analyzed with covariates age, sex and race. Analysis done on ‘R’ v. 2.4.0. Pearson correlation estimated TSH levels to tau-PET status. Kruskal Wallis/Chi square tests for relationship of age, sex, gender and education with TSH levels and tau-PET status. ROC analyses and sensitivity/specificity were obtained. Results: Tau PET positivity did not correlate significantly with TSH levels (r= 0.0655, 95%CI -0.388 to 0.494, p=0.78). Conclusion: Tau PET does not correlate with TSH levels, possibly due to a ceiling effect in the mild impairment subjects.

Presentation: 6/2/2024
8806 A Case of Autoimmune Thyroid Switching
Authors: Case J , Chemitiganti R V , Suravajjala D
Published: October 2024

Disclosure: J. Case: None. R.V. Chemitiganti: None. D. Suravajjala: None.

Autoimmune thyroid disease comprises both hyper- and hypothyroid states including Graves' disease and Hashimoto's thyroiditis, respectively. The predominant antibody activity, demonstrable by thyrotropin receptor antibody, predicts the clinical presentation and treatment; thyrotropin receptor antibodies may act as a stimulatory or inhibitory stimulus upon the thyroid gland recognized as thyroid stimulating antibody(TSAb) and thyroid blocking antibody(TBAb). Rarely patients may transition from a hyperthyroid to a hypothyroid state and vice versa if the predominant antibody activity shifts which may occur due to a variety of mechanisms and characteristics related to each individual patient and treatment course. A 29 year old female presented to establish care for autoimmune thyroiditis. She was diagnosed with Graves' disease at age 19 when pregnant and treated with propylthiouracil; she switched to methimazole for the next six years when her thyroid function normalized and therapy discontinued. Two years later she became concerned with weight gain and her thyroid function was reevaluated demonstrating hypothyroidism and she was treated with levothyroxine 25mcg daily until presentation. Further labwork revealed undetectable TSI, and TPO antibody elevated at 177 u/mL. She became clinically and biochemically euthyroid on levothyroxine 50mcg daily. Switching between hyper- and hypothyroid states is a rare occurrence among patients with may attributable factors. Both antithyroid drugs including methimazole as well as replacement therapy with levothyroxine may alter the antibody milieu and so the predominant ratio and activity among TSAb and TBAb thereby leading to a shift in clinical presentation and thyroid state. Pregnancy may lead to hemodilution contributing to lessening of autoimmune activity which may return following delivery leading typically to a shift from TSAb to TBAb. Uncontrolled hyper- and hypothyroidism may affect dendritic activity leading to altered presentation and increased immune reactivity. The unlikely occurrence of switching from a hyperthyroid to a hypothyroid state based upon autoimmunity as in this patient was likely affected these factors. Recognition of this potential transition and associated factors would lead to beneficial monitoring and possibly development of assays more attuned to this phenomenon with better capability in maintaining a euthyroid state and potentially predicting a transition.

Presentation: 6/3/2024
12238 A Case Of Drug-induced Vasculitis
Authors: Javier Christian , Horani Mohamad Hosam
Published: October 2024

Disclosure: C. Javier: None. M.H. Horani: None.

Title: A Case of Drug-Induced VasculitisChristian Javier, DOMohamad Horani, MD Introduction: Graves’ disease is commonly managed with thionamides. These have rare but serious complications of drug-induced lupus-like syndrome and vasculitis. In patients who present with rheumatologic and inflammatory findings, it is important to consider the possibility of these complications . Case Presentation: We present a 30-year-old female with Graves disease, asthma, and hypertension with concerns for cough, body aches, fatigue, bilateral flank pain, erythema, itching and burning of the hands, in the setting of recent spontaneous miscarriage. She was diagnosed with Graves’ nearly 2 years ago and was started on methimazole, but discontinued due to adverse effects of the medication. She was then started on PTU. The patient had a seizure, and head CT revealed a left-sided 4 cm brain mass in the left frontal lobe. The patient was admitted to the ICU, intubated, and started on IV Decadron. Further imaging showed multiple enlarged lymph nodes in the axilla, mediastinum, and hilum. Her brain mass was biopsied showing acute inflammation with early acute necrosis and multifocal fibrinous vascular necrosis, which has been reported in ANCA vasculitis. She had undetectable TSH (0.35-5.0) and free T4 of 1.54 (4.87-11.72). She was also found to have proteinuria and AKI. At this point, PTU-induced vasculitis and drug-induced lupus were suspected and PTU was discontinued. She was found to have low complement levels (C3 40, C4 6.1), elevated p-ANCA (>1:1280), ANA (1:640), anti-histone IgG (2.3) dsDNA (1:160), SSB La antibodies (70), anti-Smith antibodies (319), anti-RNP antibodies (146). Renal biopsy is pending. After discontinuation of PTU and administration of IV steroids, her symptoms largely resolved and she was extubated and stable for discharge. Conclusion: In patients being treated for Graves’ disease with PTU, there are rare but life-threatening complications associated with this medication including lupus-like state or vasculitis with elevated ANCA antibodies. Common presenting symptoms of drug-induced vasculitis include fever, joint pains, myalgias, skin lesions, glomerulonephritis, cerebral angiitis, and pulmonary hemorrhage. The onset of vasculitis can occur at any time after starting medication, with one study showing an average onset of 36 months after initiation of therapy. Other case reports have demonstrated positive serologies for ANA and anti DS-DNA antibodies in those with PTU-induced lupus. Drug induced lupus can also occur in patients taking PTU, with kidney and CNS involvement being more uncommon. In those with p-ANCA associated vasculitis secondary to PTU, anti-GBM, antiphospholipid, and antinuclear antibodies can also be present.

Presentation: 6/1/2024
8673 Exploring A Case Study On Navigating Complexities In Endocrine Health And Reproductive Challenges
Authors: Yumna Rizvi Syeda , Villanueva Erika
Published: October 2024

Disclosure: S.Y. Rizvi: None. E. Villanueva: None.

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting many reproductive-age women, characterized by irregular menstrual cycles, hirsutism, and challenges with fertility. In this case study, we delve into the medical history of a 24-year-old female presenting with PCOS-related symptoms, hirsutism, and infertility, unraveling the multifaceted aspects of her healthcare journey. Case Description: This patient's diagnostic path began when she received an initial diagnosis of PCOS in her home country due to irregular menstrual periods and clinical signs of hirsutism. Her treatment included metformin, but it was interrupted when she relocated to the United States. Upon her arrival in the U.S., her medical course took an unexpected turn as further evaluations revealed elevated salivary cortisol (++), and a 24-hour urine free cortisol recorded 94.2 mcg (normal 4-50 mcg), indicating hypercortisolism. DHEAS: 730 mcg/dl (normal 18-390 mcg/dl), 17-hydroxyprogesterone: 508 (pre-midluteal: 431), free testosterone: 13 pg/ml (normal 0.1-6.4 pg/ml), with normal CBC, TSH, prolactin, and TPO. CT scan showed large 4.8 cm left adrenal mass. These findings indicated adrenal Cushing's syndrome, leading to referral to a tertiary care hospital's endocrine surgeon. Two months post-adrenalectomy, successful removal of the adrenal mass left the patient with relative adrenal insufficiency. Hydrocortisone replacement therapy was initiated, addressing Cushing's syndrome and revealing a potential factor contributing to infertility. Postoperatively, the patient entered the first trimester unexpectedly, complicating her case. Ensuring proper hydrocortisone levels became crucial for her well-being and the fetus, prompting a collaborative approach with obstetricians and maternal-fetal medicine specialists for optimal pregnancy care. Despite ongoing PCOS effects, including hirsutism, treatment options were limited by pregnancy constraints, deferring Aldactone due to its contraindication during pregnancy. Continuous monitoring included hormonal assessments, metabolic panels, and thyroid tests, aiming to balance adrenal insufficiency, PCOS symptoms, and a healthy pregnancy. Conclusion: This case emphasizes challenges in differentiating PCOS from adrenal Cushing's due to overlapping symptoms. Despite classic symptoms, the initial PCOS misdiagnosis highlights the need for vigilance and comprehensive diagnostics. Complex cases underscore the importance of individualized management and interdisciplinary collaboration. Positive outcomes in complex endocrine disorders and pregnancy are attainable through accurate diagnoses and tailored treatments. The case underscores the critical importance of meticulous evaluation for successful outcomes in challenging medical scenarios.

Presentation: 6/3/2024
6784 A Case of Euthyroid Hyperthyroxinemia due to Thyroid Binding Globulin Excess Syndrome
Authors: Iyer A S , Barghouthi N , Haider A
Published: October 2024

Disclosure: A.S. Iyer: None.

Background: Congenital thyroid binding globulin (TBG) excess is a rare phenomenon associated with elevated serum total T3 and total T4 concentrations but normal serum concentrations of free thyroid hormones, with clinically euthyroid patients. While TBG excess can be caused by pregnancy, estrogen-secreting tumors, and estrogen therapy, congenital TBG excess follows an X-linked pattern, with hemizygous males most affected, and heterozygous females showing a spectrum of disease due to random inactivation of one X chromosome. Clinical Case: A 39-year-old Caucasian female presented as a referral from the Gastroenterology clinic due to concern for thyroid resistance syndrome. Symptoms included chronic constipation (improving with Miralax®), gradual weight gain of 8 pounds in one year, fatigue, and palpitations. She reported that her total thyroid hormone levels have always been elevated, with other thyroid labs remaining within normal limits, along with family history of similar labs noted in her two sons, father, and paternal grandmother. Upon initial encounter, TSH was 1.637 (0.430-3.550 uIU/mL), total T4 15.4 (4.8-11.7 ug/dL), total T3 231 (80-200 ng/dL), free T4 0.97 (0.70-1.25 ng/dL), free T3 3.2 (1.7-3.7 pg/mL), and albumin 4.2 (3.5-5.0 g/dL). The patient was not on oral contraceptive pills and she denied any pregnancies in the last three years. Thyroid ultrasound showed a normal-appearing homogeneous thyroid gland with a small cyst with colloid and no cervical lymphadenopathy. Initial differential diagnosis included TBG excess syndrome versus familial dysalbuminemic hyperthyroxinemia. Permission was obtained from the patient to access one of her son’s medical records from age 8-weeks old when he was also evaluated for abnormal thyroid labs. TSH was 2.144 (0.350-6.500 uIU/mL), total T4 28.2 (5.0-12.0 ug/dL), free T4 1.55 (0.8-1.8 ng/dL), and free T3 4.0 pg/mL (no reference available). Thyroid binding globulin was found to be elevated at 81 (12-26 mcg/mL) in her son and found to be elevated to 78.0 (13.5-30.9 mcg/mL) in this patient, confirming a diagnosis of TBG excess syndrome. Conclusions: TBG excess syndrome should be considered in the differential of patients with high total T3 and total T4 levels with normal levels of free T3, free T4, and TSH, especially in individuals who have a known family history and who have minimal or nonspecific symptoms. Definitive diagnosis will make further testing and treatment unnecessary. However, if these patients develop hypo- or hyperthyroidism, then use of TSH and free levels of T4 and T3 is necessary to direct management and avoid confusion. Reference: Pappa, T., and S. Refetoff. “Thyroid hormone transport proteins: Thyroxine-binding globulin, transthyretin, and albumin.” Reference Module in Neuroscience and Biobehavioral Psychology, 2017, https://doi.org/10.1016/b978-0-12-809324-5.03494-5.

Presentation: 6/2/2024
6601 A Case of Recurrent Painless Thyroiditis and Discussion of Management
Authors: Slack Margaret Carolyn , Grock Shira
Published: October 2024

Disclosure: M.C. Slack: None. S. Grock: None.

Introduction: Painless (silent) thyroiditis is characterized as a subacute and generally self-limited disease process in which patients develop transient thyrotoxicosis, which is often followed by a hypothyroid phase before entering the recovery euthyroid phase. Given high frequency of positive thyroid antibodies, it may be autoimmune-mediated; recurrence is rare. Here we present a case of recurrent painless thyroiditis and discuss management options. Clinical Case: A Korean woman was followed by endocrinology from age 38 to 60 and experienced at least seven episodes of painless thyroiditis over this time. The episodes occurred without an identifiable trigger and were not preceded by viral illness. During episodes she developed palpitations, hair loss, and dyspnea on exertion and biochemical evidence of thyrotoxicosis with TSH suppressed to <0.2 mIU/mL (normal 0.3-4.7) and elevated free T4 levels as high as 5.4 ng/dL (normal 0.8-1.7). TSI, TPO, and TSH receptor antibodies were checked during multiple episodes and resulted negative, though thyroglobulin antibody was significantly elevated. A radioactive iodine uptake scan was obtained during an active episode of thyroiditis and revealed diffusely low uptake. The patient’s episodes lasted approximately two to three months before normalization of her TSH and FT4. She had at least one instance of transient hypothyroidism after thyrotoxicosis with a TSH of 13.2 and FT4 of 0.6 which subsequently normalized 6 weeks later. The patient did not have known cardiovascular disease and DXA scans revealed mild osteopenia with the lowest T-score -1.3. RAI was considered for the patient based on the total number and increasing frequency of her episodes. She ultimately declined treatment with RAI and continues to follow with endocrinology. Clinical Lessons: While the deleterious effects of prolonged hyperthyroidism (e.g. osteoporosis, arrhythmia, cardiovascular disease) are well known, it is unclear what risk recurrent painless thyroiditis episodes pose. As there are no guidelines regarding treatment, clinical gestalt incorporating frequency and duration of episodes, as well as symptoms, is often used to determine if definitive management is indicated. There are case reports in the literature of treatment of recurrent thyroiditis with RAI ablation performed during a euthyroid state, which eliminated recurrence of episodes but did lead to permanent hypothyroidism necessitating hormone replacement. Surgical thyroidectomy may also be considered in select patients. This case highlights the challenges in treating rare cases of recurrent painless thyroiditis given the lack of research or established guidelines. It is reasonable to consider the frequency, severity, and total number of episodes, as well as patient risk factors, symptoms, and preferences when making recommendations regarding management.

Presentation: 6/1/2024
7915 A Case of Severe Hypothyroidism in a Patient with Nephrotic Syndrome presenting with Rhabdomyolysis requiring Levothyroxine and Liothyronine combination therapy
Authors: Mohammed S S , Ngo E T , Tadisina S , Drees B M
Published: October 2024

Disclosure: S.S. Mohammed: None. E.T. Ngo: None. S. Tadisina: None. B.M. Drees: None.

Background: Nephrotic syndrome is known to worsen hypothyroidism via urinary loss of thyroid binding globulin, transthyretin, albumin and other proteins, often requiring escalating levothyroxine doses. Severe uncontrolled hypothyroidism can result in rhabdomyolysis, although this presentation is quite rare. Clinical case: We present a case of a 50-year-old male with long-standing Hashimoto’s hypothyroidism, biopsy-proven minimal change disease with nephrotic syndrome, dyslipidemia, and hypertension, who was admitted for generalized myalgia, weakness, and progressive swelling of bilateral hands and feet for one month. He had been off levothyroxine 3 months prior to presentation. He previously required large doses of oral levothyroxine, as high as 350mcg daily, but never achieved a euthyroid state despite reported adherence to therapy with the high levothyroxine doses.Laboratory workup showed severe hypothyroidism (free thyroxine <0.25ng/dL [0.6-1.6ng/dL] with markedly elevated thyroid stimulating hormone 282.03 mIU/mL [0.3-5.6mIU/mL]), along with acute kidney injury and rhabdomyolysis (Creatine kinase 4882 U/L[38-234U/L]). He was hemodynamically stable with intact mentation and was not deemed to be in myxedema coma. Physical examination was consistent with hypothyroidism with periorbital swelling, dry skin, deep hoarse voice, bilateral hand and feet edema, and delayed deep tendon reflexes. Thyroid function tests and clinical symptoms failed to improve after 8 days, despite high doses of levothyroxine IV (200mcg). Creatine kinase remained high at 4994 U/L [38-234U/L] despite adequate fluid hydration. Liothyronine 5mcg orally was started in addition to levothyroxine 200mcg IV. Repeat thyroid function tests after 2 days of combined IV levothyroxine and oral liothyronine therapy showed significant downtrend in TSH to 154.12 uIU/ml [0.3-5.6mIU/mL] and increase in free thyroxine to 0.44ng/dl [0.6-1.6ng/dL]. Creatine kinase also down trended to 3181U/L[38-234U/L] on D4 of IV levothyroxine 200mcg IV with liothyronine 5mcg daily. He was discharged stable and clinically improved on oral levothyroxine and liothyronine. Laboratory evaluation 10 days later showed further improvement in TFTs (TSH 66.0[0.3-5.6mIU/mL]), free thyroxine 0.6 [0.6-1.6ng/dL] Conclusion: This case presents a unique and unusual clinical course in symptomatic primary hypothyroidism with rhabdomyolysis and AKI. Rhabdomyolysis due to hypothyroidism, without an obvious precipitating factor, has been previously reported, but is very rare. There is limited evidence regarding combination treatment with levothyroxine and liothyronine in primary hypothyroidism; however, as demonstrated in this patient, combination therapy resulted in clinical and biochemical improvement of thyroid function.

Presentation: 6/2/2024
12575 Exploring Patient And Parent Perceptions Of Administering Hydrocortisone Injection During Adrenal Crisis: A Cross-Sectional Study
Authors: Llahana S V , Anhony J
Published: October 2024

Disclosure: S.V. Llahana: None. J. Anhony: Employee; Self; Solution Medical LLC.

Background: Adrenal insufficiency (AI) necessitates lifelong glucocorticoid replacement therapy for most patients, with parenteral hydrocortisone crucial for managing adrenal crisis, a potentially life-threatening complication. Despite this, approximately 1 in 6-12 patients are hospitalised at least once a year, while 1 in 200 patients die from a potentially preventable adrenal crisis. While timely self-administration of hydrocortisone mitigates these risks, the complexity of current injection devices, requiring up to 20 steps to administer, often impedes effective self-treatment. Evidence shows that although 70% of patients possess emergency hydrocortisone injection kits, only 19% have received training for self-administration. Aim: This study aimed to investigate the experiences and perceptions of patients with AI and their caregivers regarding the usage of Solu-Cortef Act-O-Vial (parenteral hydrocortisone) for adrenal crisis management. Methods: A cross-sectional online survey was conducted, involving participants recruited through USA-based patient advocacy groups, CARES Foundation and Adrenal Insufficiency United. Participants provided insights into factors influencing their ability to manage adrenal crisis using Solu-Cortef Act-O-Vial. Content analysis generated themes, which were quantitatively analyzed using SPSS descriptive statistics and correlations. Results: The survey encompassed 689 patients and caregivers. Content analysis revealed eighteen themes across three domains: patient-based factors, external influences, and emotional aspects. Predominant themes, identified by over 80% of participants, included the complexity of the hydrocortisone device, the necessity for assistance during adrenal crisis episodes, and emotional distress due to fear associated with injection. Conclusion: This study underscores the necessity for a simpler injection device to enhance patient self-confidence and self-administration ability. Heightened awareness among healthcare professionals and the public regarding adrenal crisis is imperative for timely management and prevention of avoidable hospital admissions.

Presentation: 6/3/2024
8087 A Case Series on Thyroid Eye Disease Precipitated by the COVID Vaccine in Patients with Long-Standing Primary Hypothyroidism
Authors: Hassan R , Islam J
Published: October 2024

Disclosure: R. Hassan: None. J. Islam: None.

Background: Thyroid eye disease (TED) is an autoimmune disease characterized by progressive inflammation and damage to the tissues around the eyes, especially extraocular muscle, connective, and fatty tissue. It is most commonly seen in patients with Graves' disease. Less commonly, TED may occur in patients with hypothyroidism. Case Discussion We are presenting a case series on TED precipitated by the COVID vaccine in three patients with known cases of long-standing hypothyroidism. References ranges:TPO Ab: (Ref range: <9.0 IU/mL)TSI: (Ref range: <=1.3 TSI index)TRAb : (Ref range: 0.00-1.75 IU/L)TSH: (Ref range: 0.450-4.500 uIU/mL)Free T4: (Ref range: 0.82-1.77 ng/dL)T3: (Ref range: 87.00 - 178.00 ng/dL) CASE 1: 59 year-old female patient with 18-year history of primary hypothyroidism on levothyroxine who presented with a 5 month history of progressive ocular symptoms of double vision and “puffy eyes” along with other thyrotoxic symptoms. These occurred after receiving her second COVID-19 vaccine. Labs showed elevated TSI and TRAb (3.0, 6.32). TPO antibody was within normal limits at 0.5. Patient had undetectable TSH and free T4 within normal range (162, 1.08). CASE 2: 70 year-old female patient with 25-year history of primary hypothyroidism on levothyroxine who presented with a 4 month history of eye discomfort, eyelid blistering and ocular swelling after she receiving her first dose of COVID-19 vaccine. She was found to have increased ocular pressure per her ophthalmologist. On lab work, she was found to have elevated TSI and TRAb (7.1, 2.60). TPO antibody was within normal limits at 0.8. TSH was undetectable and free T4 were within normal range (159.76, 1.49). CASE 3: 82 year-old female with 30-year history of primary hypothyroidism on levothyroxine who started developing diplopia and proptosis over a 6 month course after she received her first COVID-19 vaccine.Labs showed elevated TSI and TRAb (5.1, 17). Her TPO antibody was within normal limits at 0.4. Her TSH was undetectable, and free T4 was within normal limits (71.76, 1.32). All three patients were started on low-dose methimazole, prednisone, and completed an eight week infusion course of Teprotumumab (Tepezza) with subsequent improvement of proptosis and diplopia. Conclusion Providers should be aware that patients with long standing hypothyroidism, who suddenly require less to no thyroid hormone replacement along with new onset ocular symptoms could be developing TED. This had previously been thought to be solely associated with Graves’ Disease but now has been seen with an uptick in incidence in patients with chronic hypothyroidism during the COVID pandemic. This is likely related to immune response that been associated with vaccines.

Presentation: 6/3/2024
6689 A Multicentric Study for Validation of the Diagnostic Accuracy of ACR-TIRADS in a Mexican population
Authors: Romero Ibarguengoitia M , Villarreal-Ondarza I A , Mercado Basurto J , González Cantu A
Published: October 2024

Disclosure: M. Romero Ibarguengoitia: None. I.A. Villarreal-Ondarza: None. J. Mercado Basurto: None. A. González Cantu: None.

The diagnostic performance of ultrasonographic ACR-TIRADS classification to evaluate thyroid nodules is poorly studied in a Mexican population. The aim was to assess the diagnostic accuracy of ACR-TIRADS classification for identifying malignant thyroid nodules in adults aged >18 years. This retrospective research study was conducted in 4 medical centers in Northern Mexico from 2022 to 23 to obtain ACR-TIRADS classification of nodules from thyroid ultrasound. Information about Bethesda classification after fine needle aspiration and cytology from thyroidectomy was analyzed for diagnostic performance tests. A total of 160 patients were included. Thyroid nodules were classified as TIRADS 3 in 12%, TIRADS 4 in 44%, and TIRADS 5 in 41%. Twenty-six (16%) were classified as Bethesda 1, 39 (24%) were classified as Bethesda 5, and 30 (19%) were classified as Bethesda 6. The sensitivity (S) of TIRADS 4 was 41%, specificity (E) was 50%, positive predictive value (PPV) was 59%, negative predictive value (NPV) was 32%, and accuracy was 44%. The S of TIRADS 5 was 51%, E 77%, PPV 80%, NPV 47%, and accuracy of 61%. When comparing with other populations, the performance was the same as the Turkish (their accuracy was 59.93%) population but lower than a population from China (their accuracy was 86%) and Germany (PPV 100% for TIRADS 5). The proportion of malignancy in our sample compared with a reference sample from Germany was lower, 36 vs. 85% for TIRADS 3, 59 vs. 85% for TIRADS 4, and 80% vs. 100%, p< 0.001. Concerning Bethesda's classification, the proportion of malignancy was the same according to the reference sample from the American Thyroid Association. In conclusion, there was a moderate accuracy of the ACR-TIRADS classification system in our population, the same in comparison with the Turkish population; slightly lower than what is reported in a population from Germany and China.

Presentation: 6/1/2024
8549 A Pre-ablative Stimulated Thyroglobulin Value That Predicts ATA High Risk Patients and Their Treatment Response
Authors: Gondaliya H , Nangadda N , Bhat D , Khadilkar K s , Kumbenahalli Siddegowda S , Sooragonda B G , Shetty A , Kannan S
Published: October 2024

Disclosure: H. Gondaliya: None. N. Nangadda: None. D. Bhat: None. K.S. Khadilkar: None. S. Kumbenahalli Siddegowda: None. B.G. Sooragonda: None. A. Shetty: None. S. Kannan: None.

In ATA risk stratification system for differentiated thyroid cancer (DTC), one of the variables placing patients in ATA high risk category is thyroglobulin (Tg) suggestive of distant metastases. However there is no defined cut-off Tg level for guiding the clinicians. We aimed to determine pre-ablative stimulated Tg (psTg) value that predicts ATA high risk patients (based on non-Tg parameters) and their treatment response on follow up. This was an ambispective observational study of 285 patients with DTC treated at our centre from April 2017 to November 2022. psTg was measured in all patients 3-4 weeks after surgery and they were subjected to RAIA depending on clinician’s discretion and followed up using the ATA dynamic risk stratification every 6 months. The cohort was divided into two groups: ATA high risk and ATA non-high risk (Low and intermediate risk). Patients among high risk group were divided based on response to treatment into structural incomplete group and non-structural incomplete group (Excellent, Indeterminate and Biochemically incomplete response). The mean age of the study population was 41±15 years and 68% (n=194) were female and 87% (n=249) were papillary thyroid cancer (PTC) and 13% (n=36) were Follicular Thyroid Cancer (FTC). Median duration of follow up was 2.95 years (IQR: 1.42 - 5.12). Among those with PTC, 75% were Classic, 15% Follicular variant and 10% aggressive variants that included tall cell, hobnail, diffuse sclerosing and columnar variant. On ATA risk stratification, 81.75% (n=233) patients were in non-high risk group with median psTg 3.4 ng/ml (IQR 0.5-12.2) and 18.25% (n=52) were in high-risk group with median psTg 150.5 ng/ml (IQR 7.15-439.5). On ROC analysis of all the patients, a psTg value >53.3 ng/ml was predictive of ATA high risk group with PPV of 64%; NPV of 93.5% and AUC 0.81. In ATA high-risk group, there were 73% (n=38) of patients with structural incomplete response on follow up and their median psTg was 287 ng/ml (IQR 95-500) and there were 27% (n=14) with non-structural incomplete response and their median psTg level of 6.2 ng/ml (IQR 2.3-110). A psTg value >53 ng/ml discriminated structural incomplete from non-structural incomplete response with PPV of 77%; NPV 87% and AUC 0.83. A psTg value >53 ng/ml not only predicts ATA high risk patients but also indicates those who are likely to remain with structural residual disease at follow up of 3 years.

Presentation: 6/1/2024
12382 A Prospective Analysis of De Novo Thyroglobulin Antibodies in Patients with Differentiated Thyroid Cancer Using the Italian Thyroid Cancer Observatory Repository
Authors: Neutel Bradley Sean , Grani Giorgio , D’elia Silvia , Durante Cosimo , Gianoukakis Andrew George
Published: October 2024

Disclosure: B.S. Neutel: None. G. Grani: None. S. D'elia: None. C. Durante: None. A.G. Gianoukakis: None.

The prevalence and significance of newly developed (de novo) thyroglobulin antibodies (dnTgAb) in patients with differentiated thyroid cancer (DTC) who were initially thyroglobulin antibody (TgAb) negative, is not well established. We sought to examine the phenomenon of dnTgAb using the Italian Thyroid Cancer Observatory (ITCO) database. Beginning in 2013, the ITCO repository prospectively collected clinical data on DTC management in a consecutive series of newly diagnosed patients treated in large academic centers distributed across Italy. Patients were managed by treating physicians based on perceived best practice. Pre-specified parameters were collected. Clinical status, investigations, and treatments were updated periodically. We formulated inclusion and exclusion criteria to mirror previously published literature studying dnTgAb. Patients included in the analysis were initially TgAb negative at their first postoperative check and had no evidence of persistent disease at their 1 year follow up visit. The dnTgAb group included patients who were initially TgAb negative and then developed TgAb on at least one measurement from the second postoperative check or later. All patients included in the study had at least 3 years of follow up and 3 TgAb measurements. At the time of analysis, 5360 patients were without persistent disease at 1 year. 2107 of these patients had a least 3 years of follow up and 3 TgAb measurements. 334 patients with positive TgAb at their first lab check and an additional 124 patient with incomplete data were excluded. 1649 patients met criteria for inclusion. Median follow up time was 1.85 years. DnTgAb occurred in 4.3% of patients (n=71). We found no statically significant difference in gender, tumor size, tumor focality, extrathyroidal extension, AJCC stage and ATA risk level between the persistently negative TgAb group and the dnTgAb group. Only primary tumor vascular invasion occurred at a higher rate in patients within the dnTgAb group when compared to the persistently negative group (p=0.012). Structural DTC recurrences occurred in 1.4% (n=22) of persistently TgAb negative patients and 5.6% (n=4) of patients with dnTgAb (p=0.02).This is the largest and first prospective cohort used to evaluate the prevalence and clinical significance of dnTgAb. DnTgAb occurred at a clinically relevant rate and there was a statistically significant relationship between detection of dnTgAb and structural DTC recurrence. The study is limited by the small overall recurrence rates and the exclusion of patients with less than 3 years of follow up.

Presentation: 6/3/2024
6594 A Rare Case of Clomiphene Induced De Quervain’s Subacute Thyroiditis
Authors: Abdelhameed Aya , Mortagy Mohamed , Elsandouby Ahmed , Ghaffar Adeel
Published: October 2024

Disclosure: A. Abdelhameed: None. M. Mortagy: None. A. Elsandouby: None. A. Ghaffar: None.

Introduction: Clomiphene is a selective estrogen receptor modulator that stimulates LH release by inhibiting negative feedback on the hypothalamic-pituitary axis. De Quervain’s subacute granulomatous thyroiditis is usually caused by viral infections and less often is drug-induced. We present a case of possible subacute thyroiditis induced by clomiphene. To the best of ourknowledge, this association has not been reported before. Case presentation: A 35-year-old female with a past medical history of unexplained infertility presents to the general medicine clinic with severe neck pain for the last 5 days. Her neck pain started 2 days after the completion of the clomiphene course for induction of ovulation (50 mg daily for 5 days). She denied upper respiratory symptoms. She had an extremely tender thyroid with no palpable nodules. Throat was clear. She was clinically euthyroid with no rash or itching. TSH was 3.9 mIU/L (TSH was normal 6 months prior). ESR was 40 mm/hr. Thyroid ultrasound was unremarkable. She was treated with Ibuprofen for subacute thyroiditis. In the first 2 weeks, the patient complained of increased anxiety. In the next month, she had a missed menstrual cycle. Her pain and tenderness resolved after 50 days. Repeat TSH was 2.4 mIU/L. The patient was advised not to retake clomiphene. Discussion: This is a typical presentation of subacute thyroiditis as persistent thyroid pain and tenderness with elevated ESR. The patient didn’t have the classical symptoms of preceding viral infection. However, her symptoms began immediately after completion of clomiphene course suggesting a temporal relation. The patient didn’t have any history of thyroid problems. She had increased anxiety initially followed by a missed period which suggests clinical thyroid dysfunction.Clomiphene has been associated in the literature with an increased risk of thyroid cancer. Uncontrolled thyroid dysfunction is a contraindication for clomiphene use. This might suggest an interaction between clomiphene and thyroid homeostasis. Subacute thyroiditis could be caused by drugs (e.g., lithium and amiodarone). This suggests that other drugs could lead to subacute thyroiditis such as clomiphene in our case. Conclusion: Clinicians should be aware that clomiphene could be associated with thyroid disorders such as subacute thyroiditis. It is also important to note that thyroid dysfunction is a contraindication for clomiphene use.

Presentation: 6/3/2024
8194 Extramedullary Hematopoiesis Involving Bilateral Adrenal Glands In A Patient With Sickle Cell Anemia
Authors: Pham Vi T , Sendos Lavanya N
Published: October 2024

Disclosure: V.T. Pham: None. L.N. Sendos: None.

Title: Extramedullary hematopoiesis involving bilateral adrenal glands in a patient with sickle cell anemia Background: Extramedullary hematopoiesis refers to blood cell production occurring outside the bone marrow. It is a reactive process caused by inadequate production or excessive destruction of blood cells typically seen in patients with hereditary anemias or infiltrative bone marrow disorders. Extramedullary hematopoiesis usually occurs in the spleen, liver and lymph nodes, but it can also very rarely arise from the adrenal glands. Case Presentation:We present a case of a 42-year-old male with a history of sickle cell anemia who presented with chest pain and shortness of breath and had a chest CT angiography which incidentally showed a 5.6 x 3.8 cm left adrenal mass and a 2.9 x 2.1 cm right adrenal mass. Further evaluation with an MRI abdomen with and without contrast revealed a 5.5 cm lobulated left adrenal mass with patchy areas of microscopic fat and faint delayed heterogeneous enhancement as well as a 2.2 cm right adrenal nodule. The nodules were described as markedly T2 hypointense with heterogeneous T1 hyperintense/isointense signal on MRI with a broad differential diagnosis including extramedullary hematopoiesis in bilateral adrenal glands, lipid poor adenoma or neoplasm. Regarding his sickle cell disease history, the patient was diagnosed as an infant and had very rare episodes of sickle cell pain crisis as a child. However, once he entered adulthood, he began to have multiple episodes of sickle cell pain crisis requiring hospitalizations and transfusions. On further review of patient’s prior imaging scans during these previous hospitalizations, he was first noted to have bilateral sub centimeter adrenal nodules on a CT Abdomen without contrast done almost a decade prior to his current presentation. We ordered biochemical evaluation which did not show any evidence of adrenal hormonal hypersecretion. His case was discussed at our multidisciplinary conference with the radiology and surgery team and it was concluded that the imaging characteristics were most consistent with extramedullary hematopoiesis in the setting of bilateral adrenal gland involvement and patient’s history of sickle cell anemia. Therefore, no immediate surgical resection was recommended. Given the size of the left adrenal mass being greater than 4 cm in size, we advised follow-up imaging for surveillance. Discussion:There has been a rise in detection of adrenal incidentalomas due to the increased use of advanced diagnostic imaging in healthcare settings. When patients with hematologic diseases are found to have adrenal incidentalomas, it is important to consider extramedullary hematopoiesis in the differential diagnosis to avoid unnecessary invasive procedures and surgeries.

Presentation: 6/2/2024