bluuebunny/crossref_metadata_2025 huggingface dataset:
PSAT323 Ultrasound-guided Percutaneous Ethanol Ablation for the treatment of Benign Cystic Thyroid Nodules: Report of Three Cases on The Initial Ecuadorian Experience
Authors: Naranjo Eddy P Lincango , Garcia Cristhian , Tana Andrea S Cho , Cordero-Garate Juana , Solis-Pazmino Paola , Godoy Richard
Published: November 2022

Introduction

Ultrasound-guided Percutaneous Ethanol Ablation (UPEA) is one of the first-line treatments for benign pure cysts and predominantly cystic thyroid nodules (TN). This non-surgical procedure has been used for years worldwide, however, in Latin America, this was recently adopted. Therefore, the aim of this report is to characterize our initial experience with UPEA in Ecuador.

Clinical cases description: We report on the cases of a woman (F1: 49 y) and two men (M1: 38 y, M2: 69 y) that underwent UPEA for three predominantly cystic TN at ITECC (Instituto de la Tiroides y Enfermedades de Cabeza y Cuello) in Ecuador. All nodules were non-functioning and graded as Bethesda II. Our approach in regards to the total ethanol volume injected was approximately calculated at 1/3 of the TN volume, using 75% ethanol. 10 ml of 2% lidocaine was used for anesthetic purposes. Initial volume and change in TN volume were calculated with the ATA calculator. Patient F1 had a 40 mm (23.5 ml) right lobe TN and underwent needle extraction of 5 ml of cystic fluid before the injection of 6 ml of ethanol. At 1-month follow-up, the nodule reduced 78.1% in volume (28 mm, 5.1 ml). Similarly, patient M1 had a 59 mm (44.8 ml) right lobe TN treated with 6 ml of ethanol after 20 ml of cystic fluid was extracted from the TN. At 3-month follow-up, the nodule reduced 99% in volume (7 mm, 0.1 ml). Finally, patient M2 had a 36 mm (14.5 ml) right lobe TN treated with 5 ml of ethanol. At 6-moth follow-up, the nodule reduced 99% in volume (0.5 mm, 0.04 ml). No patients developed complications and only needed one session.

Conclusions

To the best of our knowledge, we are the pioneers in Ecuador and the fourth country in Latin America that implemented UPEA in the management of cystic TN. In this small report, UPEA seems to be an effective and safe treatment option for cystic TN. Patients had >75% reduction in cyst volume along with symptomatic relief and no complications. Our results are consistent with other series. Data on a longer follow-up are needed to confirm long-term efficacy.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT327 Can Cannabis Use Lead to Central Hypothyroidism
Authors: Farasat Sadaf , Chang Amy
Published: November 2022

Background

Marijuana has been legalized for medical use in 36 states and for recreational use in 18 states. Its effects on thyroid function and hypothalamic-pituitary-thyroid axis in humans is not known.

Clinical Case

72 years old male presented to his primary care physician with occasional difficulty swallowing. He reported fatigue for 4-5 years, trouble falling asleep for 2 months, weight gain 8 pounds over last few weeks, occasional diarrhea, and intermittent episodes of heat intolerance. His past medical history included controlled type 2 diabetes mellitus, recurrent herpes simplex infection, arthritis of hip joints, short-term memory loss, anemia, carpal tunnel syndrome and benign prostatic hyperplasia. Medications included glimepiride, lisinopril, acyclovir, tamsulosin, finasteride, escitalopram. He had been smoking marijuana regularly since he was a teenager. He denied using any other supplements. His physical exam was normal with stable vital signs and normal BMI.

His labs showed a low TSH (0.096 mcIU/mL, n: 0.358-3.8 mcIU/mL), normal free T4 (0.90 ng/dL, n: 0.76-1.46 ng/dL), normal total T3 (70 ng/dL, n: 60-180 ng/dL). Review of his labs showed low TSH for last 4 years progressively getting worse with normal free T4 levels. TSH-receptor antibody and TPO Antibody level were negative. His white cell count, hemoglobin and platelets were normal. His electrolytes, kidney function and liver function tests were also normal.

Thyroid Ultrasound showed 2 small sub-centimeter hypoechoic nodules in the left thyroid lobe. Two years ago, a radioactive Iodine scan showed normal iodine uptake. A recent radioactive iodine uptake scan showed generalized decreased iodine uptake with no evidence of graves’ disease or toxic multinodular goiter.

Conclusion

Currently there are no controlled studies on the effect of marijuana use on thyroid function in humans. A cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012 showed recent marijuana use was significantly associated with lower levels of TSH but was not associated with thyroid dysfunction (1). This study suggests that marijuana use is associated with low TSH levels. This could be due to hypothalamic suppression of TSH or may indicate a protective role against hypothyroidism. Older studies in rodents showed that cannabis exposure may lead to suppression of TSH and hypothalamic function (2).

The data related to human subjects is scarce. Therefore, pathophysiologic mechanisms are speculative, although animal data support potential mechanism of hypothalamic suppression.

References

1. Malhotra S, Heptulla RA, Homel P, Motaghedi R. Effect of Marijuana Use on Thyroid Function and Autoimmunity. Thyroid. 2017;27(2): 167-173. 2. Hillard CJ, Farber NE, Hagen TC, Bloom AS. The effects of delta 9-tetrahydrocannabinol on serum thyrotropin levels in the rat. Pharmacol Biochem Behav. 1984;20(4): 547-550.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT335 Histopathological changes of the thyroid may be subtle yet important in Amiodarone induced thyrotoxicosis (AIT).
Authors: Gaballa Salem , Naser Nejat , Paal Edina , Sabyasachi Sen
Published: November 2022

Background

Amiodarone is an effective antiarrhythmic for several cardiac arrhythmias. Due to its high iodine content and long half-life with direct toxic effects on the thyroid gland, it is known to cause a spectrum of thyroid dysfunction. AIT type 1, a form of iodine-induced hyperthyroidism, and AIT type 2, a drug induced destructive thyroiditis, pose a diagnostic and therapeutic challenge. Since the physical and psychological consequences of long-term therapy with either condition are too large to ignore, it is crucial to differentiate between the two types. Histopathologic findings in AIT includes disrupted follicles filled with desquamated vacuolated epithelial cells, foamy macrophages, scattered lymphocytes, involution changes and fibrosis. However, these changes may be subtle in patients who have been treated with long term high dose steroids, but helpful in establishing either AIT 1 or 2.

Case

A 56-year-old man with a history of cardiomyopathy with an ejection fraction of 30% and atrial flutter treated previously with six months of amiodarone, presented for a routine appointment found to be in atrial flutter with rapid ventricular rate. The patient was off amiodarone therapy for ∼ 6 months prior to current presentation. The patient was referred to the ER where initial vital signs were remarkable for heart rate in the 140s. Exam was remarkable for mild tremor of the outstretched bilateral hands. Labs were remarkable for TSH of 0.01 ulU/ml (0.27-4.20), Free T4 of 2.2 ng/dl (0.93-1.70), Free T3 of 5.9 pg/ml(2.3-4.2). Thyroid ultrasonography revealed a heterogeneously enlarged thyroid gland with no increased vascularity, and 2.4 cm isthmus nodule of a TI-RAD-3. Thyroid stimulating immunoglobulins (TSI) of 96 (<140%), and thyroid peroxidase (TPO) of 2IU/ml (<9). Thyroid radioactive iodine uptake (RAIU) revealed a severely decreased uptake in the setting of amiodarone use. Mixed AIT was suspected and patient was placed on titrated dose of Methimazole (MMI) and Prednisone. Approximately three weeks later, patient was discharged on MMI 40 mg TID and Prednisone 60 mg daily. He had a close outpatient follow up with further titration of prednisone to 80 mg daily. Due to prolonged nature of disease, he was subsequently referred for total thyroidectomy. Histological examination revealed subtle changes including desquamated follicular epithelial cells and intrafollicular foamy macrophages. The thyroid architecture was maintained and no inflammatory infiltrates of fibrosis were noted. These findings are consistent with AIT type 2.

Conclusion

AIT is a challenging diagnosis, and in medically refractory cases, total thyroidectomy is a curative option. The pathological findings in a patients treated with prolonged steroids may dampen inflammation of AIT2, and therefore careful histologic examination and monitoring of inflammatory markers may help to consolidate diagnosis.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT341 Hashimoto's Thyroiditis After Allogenic Bone Marrow Transplantation
Authors: Melhim Abdullah , Arnason Jon , Gavrila Alina
Published: November 2022

Introduction

Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is a common autoimmune-mediated thyroid disease triggered by an inappropriate T and B cells response. We present a case of a female without personal or family history of autoimmune disease, who developed Hashimoto's thyroiditis with severe hypothyroidism after undergoing bone marrow transplant (BMT).

Clinical Case

A 57-year-old woman with hypoplastic myelodysplastic syndrome (MDS) was initially started on immunosuppressive therapy, complicated by autoimmune hemolytic anemia and thrombocytopenia. Three years after diagnosis, she underwent allogenic BMT from a matched unrelated donor. A year later, she presented with weight gain, fatigue, cold intolerance, insomnia, eye puffiness and lower extremity weakness, developed over a month. Exam was notable for periorbital edema and delayed DTRs. Laboratory workup revealed an elevated TSH at 302 µIU/mL (0.27-4.2) with undetectable free T4 and total T4 levels and elevated anti-thyroglobulin antibodies of 2698 IU/mL (0-40) and antiTPO antibodies of 90 IU/mL (0-35). Cortisol was normal at 14 µg/dL. TSH was normal prior to the BMT. Thyroid ultrasound revealed a normal-sized thyroid with a slightly heterogeneous echotexture, suggestive of thyroiditis without distinct nodules. Myxedema coma was ruled out at the time of diagnosis. The patient was started on levothyroxine and noticed a significant improvement of her symptoms within few weeks.

Our patient does not have a personal or family history of thyroid disease or other autoimmune disorders. She did not receive radiation treatment or steroid treatment prior to her hypothyroidism diagnosis. She had an RSV upper respiratory infection two months prior to the diagnosis of hypothyroidism without associated neck pain. The clinical and biochemical picture suggest that her hypothyroidism could be related to her allogenic BMT. The presumed mechanism for the autoimmune thyroid dysfunction noted in this patient is the transfer of autoantibodies and donor lymphocytes during BMT.

Conclusion

Adoptive autoimmune hypothyroidism can occur post-BMT, especially if the donor has genetic susceptibility. It is now accepted that autoimmune thyroiditis can be transferred from donors to recipients during BMT.

Reference

Buxbaum NP, Pavletic SZ. Autoimmunity Following Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2020 Aug 25;11: 2017.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT345 Neonatal Graves (NG) Affecting 3 Newborns of a Mother Treated with Radioactive Iodine (RAI) for Graves’ Disease (GD)
Authors: Ali Dalal S , Mohamed Medina
Published: November 2022

Background

Elevated serum thyrotropin receptor antibody (TRAb) levels often return to baseline one year post RAI therapy but can sometimes take a few years to normalize. Remission rates of TRAb autoimmunity in GD is higher in patients taking antithyroid medications and who have undergone a thyroidectomy compared to RAI(1). The incidence of neonatal hyperthyroidism in mothers treated with RAI is estimated to be 3.6% 18-24 months post RAI.(2)

Clinical case

A 31-year-old female G4A1L3 diagnosed with GD at 24 years old treated with RAI at age 25 and remained on L-thyroxine replacement for hypothyroidism. First pregnancy (P1) age 24: terminated at 11wks gestation. P2 (age 28): Spontaneous vaginal delivery (SVD) induced at 38+4wks due to vaginal bleeding, birth weight (BW) 3750g, APGARS 9/9. Baby had NG and was admitted to NICU. On day 3, her heart rate (HR) was greater than140bpmin and she has lost 9.5% weight below her BW. Blood work showed TSH <0.01mIU/L (N: 0.71-31.5), FreeT4 >64.0pmol/L (N: 13.5-41.3), FreeT3 40.4pmol/L (no neonatal reference range), TRAb 206U/L (<10). Methimazole (MMZ) (0.5mg/kg/day) and propranolol (1mg/kg/day) were initiated. Therapy was discontinued at 5 months postpartum. Maternal TRAb was 405U/L (N <10) in first trimester (T1) and dropped to 248U/L in third trimester (T3). P3 (age 31): C-section at 36+2wks, dichorionic diamniotic twin pregnancy, serial US showed good growth and normal dopplers. Both twins developed NG and required NICU admission. Baby A, 3100g, APGARS 7/8/8, had TSH <0.02mIU/L(N: 0.71-3,1.5), FT4 at ∼54h of life of >90pmol/L(N: 12.4-72.4), FT3 23.7pmol/L, TRAb 25.9IU/L(N: <=1.8), HR 162bpmin. Started on MMZ 0.75 mg BID. TSH normalized 3 months postpartum 1.30 mIU/L, FT4 11.4pmol/L. Baby B, 2850g, APGARS 9/9, had jaundice with elevated bilirubin 182umol/L(N: 10-180). HR 130-150bpmin, TSH <0.02mIU/L(N: 0.71-3,1.5), FT4 >90 pmol/L(N: 12.4-72.4), FT3 19.5pmol/l. TRAB 21.9IU/L(N<=1.8). Recovered after 3 months of therapy with MMZ. Maternal TRAb was 60.5 IU/L in second trimester (T2) and 43 IU/L in T3.

Conclusion

Women with GD who were previously treated with RAI need to be closely monitored for TRAb activity throughout pregnancy. When TRAb Ab levels remain elevated in the T3, close monitoring and assessment of the fetus is critical. Obstetricians and neonatologists need to be involved in the management of these women.

References

1. Laurberg P, Wallin G, Tallstedt L, Abraham-Nordling M, Lundell G, Tørring O. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. European Journal of Endocrinology. 2008-01-01 2008;158(1): 69-75. 2. Yoshihara A, Iwaku K, Noh JY, Watanabe N, Kunii Y, Ohye H, et al. Incidence of neonatal hyperthyroidism among newborns of graves’ disease patients treated with radioiodine therapy. Thyroid. 2019;29(1): 128-34.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT379 Performance of a Raman Fingerprint in Thyroid Nodules with Indeterminate Cytology: A Prospective Blinded Monocentric Study
Authors: Palermo Andrea , Sodo Armida , Naciu Anda Mihaela , Gioacchino Michael D , Paolucci Alessio , Masi Alessandra D , Maggi Daria , Crucitti Pierfilippo , Longo Filippo , Perrella Eleonora , Taffon Chiara , Verri Martina , Ricci Maria Antonietta , Crescenzi Anna
Published: November 2022

Background

Molecular analysis of thyroid fine-needle aspiration biopsy (FNA) was proposed to improve indeterminate nodules management. However, sensibility and specificity as well as the cost of molecular diagnostics require to be improved to increase their cost-effectiveness for medical practice setting. Raman spectroscopy (RS) demonstrated ability in separating benign from malignant thyroid lesions in surgically removed tissues, based on specific RS profile. This study aimed to investigate the diagnostic performance of RS on cytological samples obtained by thyroid FNA.

Methods

In this prospective, blinded monocentric study, we enrolled 123 patients with indeterminate or worse cytological diagnosis, candidate to surgery according to international guidelines, and submitted to RS analysis of FNA samples. Cytology specimens were evaluated in agreement to Italian Reporting System for Thyroid Cytology1 as follows: TIR1 (non-diagnostic), TIR1C (non-diagnostic-cystic), TIR 2 non-malignant/benign, TIR3A (low-risk indeterminate lesion), TIR3B (high-risk indeterminate lesion), TIR 4 (suspicious of malignancy), or TIR 5 (malignant). As previously published2, the two diagnostic subcategories referred to indeterminate nodules with low (TIR3A) and high risk (TIR3B) of malignancy, may be respectively compared to the class III and Class IV of The Bethesda System for Reporting Thyroid Cytopathology.

We compared RS, cytology and final histology, as reference standard, using various statistical approaches.

Findings: Our study population included 37 TIR3A, 32 TIR3B, 16 TIR4 and 38 TIR5; the 30.9% of patients had benign histological diagnosis after surgery. In particular, 72.9% of patients classified TIR3A and 31.3% TIR3B had benign histological diagnosis. RS analysis of FNA samples had overall specificity of 86.8% in predicting thyroid malignancy. In indeterminate cytological categories, RS specificity was 86.5%. In patients with TI-RADS score four or five, the specificity of RS increased to 87.5% for TIR3A and reached 100% in TIR3B.; if considering RS positive test, unnecessary surgery was reduced to 7.4% in the whole sample, 33.3% in TIR3A, and 6.7% in TIR 3B.

Interpretation: We demonstrated for the first time that RS represents a valuable tool for thyroid cytology and a valid alternative to molecular analyses, able to improve management and reduce unnecessary surgery in indeterminate nodules.

Funding: This study was supported by Ministero della Salute, through TIRAMA project (RF-2018-12366568).

1 J Endocrinol Invest. 2014;37(6): 593-599. doi: 10.1007/s40618-014-0062-0

2Cytopathology. 2021;32(6): 714-717.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT381 Rising Preoperative TPO Titers Decrease the Risk for Differentiated Thyroid Cancer in a Linear Fashion: A Retrospective Analysis of 1620 Consecutive Thyroid Surgeries
Authors: Paparodis Rodis , Livadas Sarantis , Karvounis Evangelos , Bantouna Dimitra , Zoupas Ioannis , Imam Shanawaz , Jaume Juan
Published: November 2022

Introduction

Chronic lymphocytic thyroiditis is an important risk factor for differentiated thyroid cancer (DTC) in surgical series, but the role of thyroid peroxidase antibodies (TPO) seems less clear in that regard. We designed the present study to evaluate that effect in our large patient population.

Methods

We recruited subjects operated with total thyroidectomy in 4 sites (USA: 1, Greece: 3) during a period of 14 consecutive years. We gathered data on TPO antibodies titers measured with commercially available radioimmunoassays, and reviewed data on surgical pathology. TPO≥34IU/ml was deemed high (TPO+). Odds ratios (OR) for DTC were calculated with Fischer's exact test. p<0.05 was deemed significant.

Results

We reviewed data on 8,425 thyroid surgeries, and TPO titers were available for 1,620 subjects: DTC n=702 (43.3%), benign pathology (BEN) n=918 (56.7%), TPO+ n=524 (32.3%) and TPO- (<34IU/ml) n=1096 (67.7%). DTC was found with a lower frequency in TPO+ (183/524, 34.9%) compared to TPO- (519/1096, 47.4%) subjects, OR 0.60 (0.48-0.74, p<0.0001). Subjects with the lowest TPO titers had the highest rate of DTC: TPO< 10IU/ml n=338/635 (49.3%), TPO 34-100IU/ml n=69/162 (42.6%), TPO 100-500IU/ml n=70/168 (41.7%), TPO 500-1000IU/ml n=16/50 (32.0%), TPO >1000IU/ml n=28/144 (19.4%), p<0.0001.

Conclusions

High TPO Antibodies appear protective against DTC in our large multicentre cohort of patients operated with a total thyroidectomy. Rising preoperative TPO titers confer linearly increasing protection against DTC in the surgical specimen. More research is needed to fully understand the role of thyroid autoimmunity in the genesis of DTC.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT384 Familial Non-Medullary Thyroid Cancer — Does The Number Of Alanine Residues In The FOXE1 Gene Play A Role?
Authors: Trofimiuk-Muldner Malgorzata , Domagala Bartosz , Koziara Michal , Skalniak Anna , Hubalewska-Dydejczyk Alicja
Published: November 2022

Familial non-medullary thyroid cancer (FNMTC) constitutes about 3–9% of all thyroid cancers. One of the genes believed to predispose to non-syndromic FNMTC is FOXE1. It contains a polyalanine tract (polyAla) with a variable number (11–22) of alanine residues. This length polymorphism could lead to changes in the FOXE1-encoded protein (FOXE1 transcription factor) structure and predispose to papillary thyroid cancer (PTC).

The aim of the study was to investigate the relationship between the length of the polyAla tract and the stage of PTC at diagnosis (according to AJCC 8th edition) in patients with FNMTC.

The study included 27 patients (from twenty families) with familial PTC (at least two family members were diagnosed with the disease). The length of the polyAla tract of the FOXE1 gene was analyzed. The following numbers of polyAla variants were detected: 11-Ala – 2, 12-Ala – 1, 14-Ala – 23, 16-Ala – 28 alleles. The staging at diagnosis was compared in two groups: less than 16-Ala and at least 16-Ala. The stages of pT1a and pT1a (m) were found in 20 alleles in the less than 16-Ala group, whereas in 16 alleles of the at least 16-Ala group, pT1b-pT2(m) was the most common (p = 0.039). Lymph node metastases were found more frequently in the less than 16-Ala group than in the at least 16-Ala group but this difference was not statistically significant (10 vs. 3 respectively; p = 0.680).

Conclusions

The analysis of the length of the polyAla tract may be a useful diagnostic tool in predicting the course of PTC in patients with a positive family history.

The research was funded by the Jagiellonian University Medical College grant No N41/DBS/000087.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSUN36 Subacute Thyroiditis Following mRNA Vaccine for COVID-19 in a 40-Year-Old Male Patient
Authors: Munir Kashif , Ahmed Amiya , Kim Yoon Kook , Siddiqi Muhammad , Malek Rana
Published: November 2022

Background

Subacute thyroiditis typically occurs a few weeks after a viral infection and is the most common cause of painful thyrotoxicosis. Cases of subacute thyroiditis have been reported following both inactivated and live-attenuated vaccines, such as the influenza vaccine. We describe a case of subacute thyroiditis in the setting of the Pfizer-BioNTech mRNA COVID-19 vaccination.

Clinical Case

A 40-year-old man with no significant medical history presented with signs and symptoms of thyrotoxicosis after receiving the Pfizer COVID-19 vaccine. Symptoms began 3 days after receiving the second vaccine dose and included 9 kg unintentional weight loss, arthralgia in both knees, palpitations, fatigue, bilateral thigh weakness, and diffuse neck swelling, pain, and tenderness. Initial treatment with antibiotics for presumed upper respiratory infection did not improve symptoms, and PCR testing for COVID-19 infection was negative. Thyroid ultrasound obtained 15 days after symptoms onset revealed a 4 cm nodule in the left lobe of the thyroid gland. Testing 30 days after onset of symptoms demonstrated TSH<0.005 uIU/mL (ref: 0.45-4.50 uIU/mL), elevated free T4 of 2.53 ng/dL (ref: 0.82-1.77 ng/dL), and elevated erythrocyte sedimentation rate of 42 mm/hr (ref: 0-15 mm/hr). Repeat labs and imaging 9 days later demonstrated improvement with a TSH of 0.071 uIU/mL and free T4 of 1.04 ng/dL as well as decreased nodule size (2.5 cm). At this time, the patient reported resolution of all symptoms and return to baseline weight. Thyroid ultrasound obtained 3 months after symptoms onset demonstrated normal thyroid without detectable nodules or enlargement, and complete normalization of TSH and free T4 levels to 4.250 uIU/mL and 1.22 ng/dL, respectively.

Conclusion

This is the second documented case of subacute thyroiditis following the Pfizer-BioNTech vaccine for COVID-19 in a male patient. A literature review demonstrates 12 other cases of subacute thyroiditis following the Pfizer-BioNTech mRNA COVID-19 vaccine, 3 cases following the Moderna mRNA COVID-19 vaccine, 8 cases following the AstraZeneca recombinant COVID-19 vaccine (one male patient), 4 cases following the CoronaVac inactivated SARS-CoV-2 COVID-19 vaccine, 1 case following the Covaxin inactivated SARS-CoV-2 COVID-19 vaccine, and 3 cases following the Janssen viral vector SARS-CoV-2 COVID-19 vaccine. Albeit uncommon, providers should be aware that transient thyrotoxicosis following COVID-19 vaccination may occur. Similar to subacute thyroiditis due to viral infection, the clinical course is generally self-limited with patients returning to a euthyroid state within a few months. Usual management of subacute thyroiditis with symptomatic management and watchful waiting is appropriate.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN39 A rare presentation of autoimmune thyroid diseases and myasthenia gravis: A clinical case report
Authors: Udorji Ogochukwu , Trikudanathan Subbulaxmi , Desantis Anthony
Published: November 2022

We report a case of a 37-years-old female that presented with a three-week history of diplopia, ptosis, muscle weakness, difficulty chewing, tachycardia, and fatigue; these clinical symptoms were concerning for acute myasthenia gravis crisis. The diagnosis of Myasthenia gravis was further confirmed by a positive immunology workup. Chest CT imaging during her assessment showed anterior mediastinal mass/enlarged thymus indicative of thymic hyperplasia. Medical therapy with intravenous immune globulin, pyridostigmine and further treatment with high-dose steroid. She had a positive response to treatment but still reported persistent symptoms of fatigue, tachycardia, and intermittent diplopia, raising suspicions for underlying Graves’ thyrotoxicosis. Thyroid function testing was performed which showed a very suppressed thyroid-stimulating hormone (TSH) and elevated Free t4 levels. Further workup for Graves thyroid autoimmune antibodies indicative of extremely elevated thyroid stimulating hormone receptor autoantibodies consistent with Graves’ disease. We initiated medical therapy for Graves’ disease with a beta-blocker and thioamide (methimazole). She endorsed progressive improvement in her symptoms following treatment for Grave's disease. She was discharged with high dose steroids, pyridostigmine, and appropriate therapy for Graves’ disease. She did well after her discharge from the hospital and six months afterwards she returned to the hospital for a robot-assisted right thymectomy. Final pathology report indicative of non-thymomatous myasthenia gravis. She continued to follow up with us in the endocrinology outpatient clinic. Her steroid therapy was tapered off and medical therapy for Graves’ disease was continued accordingly. She demonstrated a positive response to medical therapy with remarkable improvement in the remaining of her symptoms, especially her neurological and ocular symptoms after initiation of treatment for Graves’ disease.

Conclusion

we report two rare concomitant autoimmune diseases, myasthenia gravis, and Graves’ disease. Both conditions have similar overlapping clinical features making diagnosis and treatment challenging in clinical practice. It is well reported in clinical literature and studies that hyperthyroidism may worsen symptoms of MG and management of hyperthyroidism in the setting of MG may lead to worsening of myasthenia symptoms; hence, certain precautions should be taken to avoid worsening symptoms of myasthenia gravis. Therefore, we call for more case-control, case series and clinical trials to explore more clinical knowledge about the association between the two conditions and formulate better management strategies.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF11 | PSAT368 The role of thyroid peroxidase antibodies on the risk of thyroid cancer: a systematic review and meta-analysis of surgical cohort studies.
Authors: Anagnostis Panagiotis , Imam Shahnawaz , Jaume Juan , Paparodis Rodis , Livadas Sarantis , Karvounis Evangelos , Bantouna Dimitra
Published: November 2022

Introduction

Hashimoto's thyroiditis raises the risk for differentiated thyroid cancer (DTC) in surgical series, but the role of thyroid peroxidase antibodies (TPO) remains controversial in that regard. We designed the present study to evaluate the effect of preoperative TPO titers in the risk of DTC.

Methods

A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases in November 2021 for the terms "thyroid cancer" and "TPO" or "peroxidase antibodies". We characterized the differential risk found in patients with high titers of TPO (TPO+), as compared to those with low or undetectable titers (TPO-) with regard to DTC. Data are expressed as odds ratio (OR) with 95% confidence interval (CI).

Results

We retrieved and reviewed 408 records; 21 retrospective cohort studies (2006-2022) from 7 countries and n=30,5536 subjects, fulfilled the eligibility criteria: 15 studies in East Asia with n=25,125 subjects (82.2%) and 6 studies in the Western world with n=5,428 subjects (17.8%)]. These comprised n=17,684 subjects with benign disease (57.9%) and n=12,869 with DTC (42.1%). The reference used for TPO+ was 23.6±18.8 (Range 5.1-60.0 IU/ml); n=6,307 patients were TPO+ (20.6%) and n=24,246 were TPO- (79.4%). DTC was present in n=2,960 TPO+ patients (46.9%) and n=9,909 TPO- patients (40.9), OR 1.28, (95%CI 1.21-1.35), p<0.001.

A high titer of TPO was associated with increased risk for DTC in both Asian cohorts, [OR 1.36 (1.28-1.45, p<0.001)] and Western world alike, [OR 1.15 (1.02-1.31), p=0.025]. That risk was statistically significantly higher in the Asian world cohorts as compared to the Western World cohorts, p<0.001.

Conclusions

Thyroid peroxidase antibodies are an integral part of Hashimoto's thyroiditis, which is a well characterized risk factor for thyroid cancer and seem to increase that risk as well. That effect seems significantly higher in East Asia as compared to the Western World region. Further studies are needed to characterize the effects of the immune response, with regard to thyroid cancer risk.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m.
RF11 | PSAT369 CDK7 and CDK9 Inhibition Induces RNA Polymerase II Ubiquitination and Proteasome Degradation in Thyroid Cancer Cells
Authors: Rajan Neel , Khanal Tilak , Adik Amy , Porter Kyle , Ringel Matthew
Published: November 2022

"Superhenhanced" transcription of specific oncogenes by aberrant looping of upstream enhancer elements to marked transcriptional regulatory regions is a mechanism of oncogene overexpression. Therefore, compounds that target key positive regulators of RNA polymerase II (RNAPII) activity, such as CDK7 and CDK9, can relatively selectively reduce expression of such superenhanced oncogenes and are in clinical trials. We have previously reported activity of the CDK7 inhibitor THZ1 in medullary thyroid cancer (MTC) along with identification of a superenhancer in RET. CDK7 inhibitors also are reported to be active in anaplastic thyroid cancer cell lines. In the present study, we extend this work to both CDK7 and CDK9 inhibitors, and to a more extensive set of thyroid cancer cell lines. We selected 8 thyroid cancer cell lines (TPC1, FTC133, BCPAP, SW1376; K1, THJ-16T, C643, and 8505C) from a variety of histological subtypes with different driver mutations for treatment with a CDK7 (THZ1) or CDK9 (AZD4573) inhibitors. Cell viability assays were performed to determine IC50 and Western blots were performed for target validation. IC50 values ranged from 5-100 nM for both compounds for all cell lines demonstrating broad activity and robust activity. Unexpectedly, both compounds inhibited both CDK7 RNAPII phosphorylation (Ser5) and CDK9 RNAPII phosphorylation (Ser2) due to a loss of total RNAPII protein levels in all cell lines. Further time course studies two cell lines, 8505C (BRAFV600E) and TPC1 (RET/PTC) showed the loss off RNAPII occurred rapidly (1-3 hours) with stable RNAPII mRNA levels by qRTPCR. We therefore hypothesized that RNAPII stalling induced by inhibition of CDK7 may cause loss of RNAPII protein stability through ubiquitination and proteasome-mediated degradation. Immunoprecipitation-Western blots demonstrated variable baseline levels of RNAPII ubiquitination in 8505C (low) and TPC1 (high) cells. THZ1 treatment induced ubiquitination of RNAPII in 8505C cells signficantly, while a modest increase beyond the higher baseline occurred in TPC1. Bortezomib (proteasome inhibitor) treatment rescued THZ1-reduced RNAPII protein levels in both cell lines. In summary, human thyroid cancer cell lines are broadly sensitive to CDK7 and CDK9 inhibitors. CDK 7 and 9 inhibitors reduce RNAPII levels and THZ1 induces RNAPII ubiquitination and proteasome degradation demonstrating a new mode of action for the reduced RNAPII activity induced by these inhibitors.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:42 p.m. - 1:47 p.m.
RF11 | PSAT370 I-PET Score: Combining Whole Body Iodine Scan and 18 Fluorodeoxyglucose Positron Emission Topography to Predict Progression in Thyroid Cancer
Authors: Wijewardene Ayanthi , Hoang Jeremy , Maw Aung Min , Gild Matti , Tacon Lyndal , Roach Paul , Schembri Geoffrey , Chan David , Clifton-Bligh Roderick
Published: November 2022

Introduction

A well-known 'flip flop' phenomenon exists between whole-body scans (WBS) and 18FFDG PET imaging in differentiated thyroid cancer (DTC) such that cancer progression is typically associated with reduced iodine uptake and increased FDG avidity. Patients with FDG avidity have a poor clinical outcome while those with iodine avid lesions are more responsive to radioactive iodine therapy (RAI) and have a better prognosis. A spectrum however exists, as thyroid cancers become less well differentiated, when they will be both iodine and FDG avid. Current scoring systems in thyroid cancer are limited to a single imaging data set. We propose a new scoring system (I-PET) combining WBS and FDG findings to identify patients more likely to be refractory to RAI, and who may be ideal candidates for 're-differentiation' before RAI treatment.

Methods

Retrospective analysis of 142 patients age > 18 with differentiated thyroid cancer who had a 18FFDG PET and WBS within a 6 month period of each other between 2010 and 2020. Initial pair of 18F FDG PET and WBS were reviewed by two independent nuclear medicine physicians and an IPET score was assigned: IPET [0]: Iodine –ve, FDG –ve, IPET [1]: Iodine +ve, FDG –ve, IPET [2]: Iodine +ve, FDG +ve and IPET [3]: Iodine –ve, FDG +ve. Patients with FDG +ve lesions (I-PET 2 and I-PET 3) were further classified into group 'a' and 'b' if SUVmax was less than or greater than 5 respectively. Follow-up data was obtained by chart review. Progression was defined as either structural recurrence as per RECIST 1.1 or equivalent clinical assessment, or biochemical incomplete response with an unstimulated Tg > 1ug/L. The study was approved by IRB (ETH00674/ STE01494).

Results

Of the 142 patients included in the study 121 patients had follow up data available for review. At baseline, 49 patients were classified as IPET [0], 10 as IPET [1], 16 as IPET [2] and 46 as IPET [3]. Progression was identified in 49% (59/121) patients; of which 54 were structural and 5 biochemical. Patients classified as [2b] and [3b] had a recurrence rate of 88% (7/8) and 78% (25/32) respectively, while IPET [0] patients had 22% (11/49) recurrence (p < 0.001). Patients classified as IPET [3b] were 10.4 times more likely to commence on tyrosine kinase inhibitor therapy (p=0.005) and had a 8.1 times greater mortality rate (p=0.02) than patients in the other IPET groups.

Conclusion

IPET score is a novel scoring system incorporating WBS and 18FFDG PET imaging which predicts progression and death in patients with FDG avid thyroid cancer.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:48 p.m. - 1:53 p.m.
RF23 | PSAT365 An Open-Label Therapeutic Efficacy Study of Tirosint (Levothyroxine Sodium) Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors
Authors: Sachmechi Issac , Burman Kenneth D , Mautone Giuseppe , Lanzi Gabriele , Moriarty Patricia L , Scarsi Claudia , Wartofsky Leonard
Published: November 2022

Levothyroxine sodium (LT4) absorption is known to be affected by proton pump inhibitors (PPIs). Normal gastric acid secretion is important for the subsequent intestinal absorption of LT4. A reduced gastric acidity may diminish the dissolution of the LT4 tablet in the stomach and the release of LT4 to the gut. The dissolution profile of LT4 soft capsules has been reported to be less affected by pH than that of tablets. Previous studies in healthy subjects administered with LT4 and PPIs, as well as in hypothyroid patients with atrophic gastritis confirmed little or no impact of increased gastric pH on LT4 absorption when administered in soft capsule formulation. The present study was aimed at evaluating whether LT4 soft capsules may provide better control of thyroid stimulating hormone (TSH) in thyroidectomized patients undergoing chronic replacement therapy with LT4, who were also on chronic use of PPIs.Forty-seven (47) patients were enrolled in this multicenter study. Upon switching to Tirosint capsules at the same previous dose of LT4 tablets and while maintaining the same dose of PPI, TSH (when measured on week 12 of treatment) was significantly reduced from a mean±SD of 1.34±1.51 mIU/L to 0.75±1.08 mIU/L (p<0.0001) in the Intention-To-Treat population analysis on original data. No significant changes were detected in the level of free and total thyroxine (T4), while slight but significant (p<0.05) increases were measured in free and total triiodothyronine (T3). The measured extent of TSH decrease is consonant with the extent of TSH increase previously reported by other authors upon start of PPI therapy in hypothyroid patients treated with LT4 tablets.In conclusion, these data confirm previous reports that LT4 soft capsules absorption is not affected by increased gastric pH due to PPIs. This may be relevant to improve TSH stabilization in patients who take PPIs intermittently or those with gastric pH altered by concomitant pathologies.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.
RF35 | PSAT257 The Severity of Subacute Thyroiditis Depends on Its Causative Agent
Authors: Brancatella Alessandro , Viola Nicola , Sgrò Daniele , Casula Mauro , Santini Ferruccio , Latrofa Prof Francesco
Published: November 2022

We retrospectively evaluated 402 patients referred to of the University Hospital of Pisa because of a SAT from January 2011 to December 2020. Neck pain was present in all patients; in 92 patients it was bilateral. A previous symptomatic involvement of the upper airways was reported by 97 patients. 32 patients did not receive pharmacological treatments, 16 were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and 354 with glucocorticoids; the most common initial dose of prednisone was 25 mg (in 286 patients); the majority (n. 277 patients) were treated for 90 days. 88 patients experienced permanent hypothyroidism. Free thyroxine (FT4) values ​​correlated with those of the C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and thyroglobulin (Tg) ​​(p <0.001 for all). Tg values ​​correlated with the severity of thyrotoxicosis and the levels of inflammatory markers. Values ​​of FT4, Tg, ESR and CRP in patients experiencing hypothyroidism were higher compared to those observed in patients who remained euthyroid after SAT. Values ​​of FT4, Tg, and CRP and incidence of hypothyroidism were higher in patients with bilateral neck pain compared to those experiencing unilateral neck pain. Similar differences were observed comparing patients who had respiratory symptoms prior to SAT to those who did not. Glucocorticoid treatment was associated with a shorter duration of neck pain (14 days) compared to those treated with NSAIDs (28 days) and those left untreated (28 days) (p <0.001). The initial dose of 25 mg (lower than that recommended by the recent guidelines of the American Thyroid Association - 40 mg/day) was sufficient to control the pain. The annual incidence of SAT was similar throughout the entire period of observation. The third quarter of the year was characterized by the highest number of cases compared to the other quarters in all years except 2012 and 2015, when there was a higher incidence in the first quarter, and in 2020, when most of the SAT cases occurred in the second and fourth quarters. In these peculiar periods thyrotoxicosis and inflammatory markers were higher and permanent hypothyroidism more common. The clusters of SAT in 2020 occurred within a month of the Covid-19 waves, while in the winter seasons 2011-12 and 2014-15 in Italy there was a higher incidence of the influenza virus A.H3N2. In conclusion, the severity of SAT depends upon the causative virus.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:06 p.m. - 1:11 p.m.
OR29-2 Comprehensive Steroid and Global Metabolome Analysis by Mass Spectrometry and Machine Learning to Understand Metabolic Risk in Benign Adrenal Tumours With Mild Autonomous Cortisol Secretion
Authors: Prete Alessandro
Published: November 2022

Background

Benign adrenal tumours are found in 3-10% of adults and can be non-functioning (NFAT) or associated with adrenal hormone excess. Analysing 1305 prospectively recruited patients with benign adrenal tumours, we recently demonstrated that 45% of patients had mild autonomous cortisol secretion (MACS), i.e. biochemical evidence of cortisol excess without distinct signs of Cushing syndrome (CS). We found that MACS increases the prevalence and severity of type 2 diabetes and hypertension and primarily affects women (Ann Int Med. 2022 Doi: 10.7326/M21-1737). Here we analysed the cohort's steroid metabolome and non-targeted global metabolome to reveal underlying metabolic processes.

Methods

We analysed 24-h urine samples from 1305 patients (649 NFAT, 591 MACS, 65 CS) using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) multi-steroid profiling assay. In addition, we performed non-targeted serum metabolome analysis in a representative sub-cohort (104 NFAT, 140 MACS, 47 CS) employing two complementary LC-MS assays, HILIC and C18-lipidomics. The steroid and global metabolome data were analysed by two supervised machine learning approaches, generalized matrix learning vector quantization and ordinal regression, to identify the most relevant metabolic changes.

Findings

Urine steroid metabolome analysis revealed an increase in glucocorticoid excretion from NFAT over MACS to CS, whereas androgen excretion decreased. Increased glucocorticoid metabolites were also the major differentiators between MACS patients with and without type 2 diabetes and hypertension, respectively. Lipidome analysis by machine learning identified glycerophospholipids, lysoglycerophospholipids, triacylglycerides, ceramides, sphingolipids, and acylcarnitines as the most relevant metabolite classes exhibiting gradually progressive changes with increasing cortisol excess (NFATInterpretation: We show a gradual change in the lipidome towards lipotoxicity with increasing cortisol excess. MACS patients with type 2 diabetes and hypertension had higher glucocorticoid output than other MACS patients, suggestive of a causative contribution of cortisol excess to their increased cardiometabolic burden. Observed changes may hold promise for risk stratification in MACS, a highly relevant and previously largely overlooked metabolic risk condition.

Presentation: Tuesday, June 14, 2022 10:00 a.m. - 10:15 a.m.
RF35 | PSAT263 Efficacy of Teprotumumab for Thyroid Eye Disease in Hypothyroid Patients
Authors: Smith Terry J , Choudhary Chitra , Bhattacharya Rajib J , Holt Robert
Published: November 2022

Background

Thyroid eye disease (TED) is an autoimmune inflammatory process that can lead to eye-bulging (proptosis) and double-vision (diplopia). Teprotumumab, an insulin-like growth factor-I receptor inhibitory antibody, has demonstrated improvements in proptosis and diplopia. Thyroid dysregulation has been linked to increased TED severity1 and may trigger TED flares,2 thus, treatment efficacy of hypo- or hyperthyroid patients with teprotumumab is of interest. This post-hoc analysis of pooled phase 2 and 3 trial data3 examined teprotumumab efficacy in patients with low baseline FT4 levels.

Methods

Patients from Phase 2 and 3 teprotumumab trials with low baseline FT4 (≤11.5 pmol/L) were included. Patients received teprotumumab or placebo for 24 weeks (8 infusions). Proportions of proptosis (≥2 mm reduction), clinical activity score (CAS, 7-point scale, CAS 0 or 1), and diplopia (≥1 Gorman diplopia scale grade improvement) responders were determined at Week 24. Additionally, the Graves’ ophthalmopathy- quality of life (GO-QOL) questionnaire measured quality of life.

Results

Nine teprotumumab-treated patients (6 female [67%], 54.6±10.7 years old) and 8 (6 female [75%], 50.0±14.9 years old) patients made up the teprotumumab and placebo groups, respectively. Mean baseline proptosis in the study eye was 25.1±3.9 mm in teprotumumab patients and 21.9±3.8 mm in placebo patients. At Week 24, 78% (7/9) teprotumumab-treated vs. 38% (3/8) placebo-treated patients were proptosis responders. Further, mean proptosis reduction was 2.9±0.6 mm with teprotumumab vs. 1.2±0.7 mm with placebo. 67% (6/9) vs. 13% (1/8) of teprotumumab vs. placebo patients were CAS responders at Week 24. Of those with baseline diplopia, 86% (6/7) vs. 40% (2/5) were diplopia responders, respectively. In the teprotumumab group, the least square mean change from baseline in overall GO-QOL score improved by 23.4±6.4, which was a large clinical change. In contrast, the placebo group improved by 6.9±7.4.

Conclusions

After 24 weeks, responses to teprotumumab were greater versus placebo in patients with low baseline FT4 in two clinical trials. Responses in these mildly hypothyroid patients in this study were consistent with those in the overall pooled population as follows: Proptosis response: 78% and 77%, respectively; mean proptosis reduction: 2.9 mm and 3.14 mm; diplopia response 86% and 70%; CAS response 67% and 62%, respectively. Thus, pretreatment hypothyroid status does not affect clinical responses to teprotumumab in TED.

References

Bartalena L. Best Pract Res Clin Endocrinol Metab 2012; 26: 371-379. Patel P, et al. Ophthalmic Plast Reconstr Surg 2015; 31(6): 445-448. Kahaly et al. Lancet Diabetes and Endocrinol 2021; 9(6): 360-372

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:26 p.m. - 12:41 p.m.