Nontoxic Goiter Research Articles

Nodule-specific NRF2-targeted upregulation in patients with KEAP1 mutations and familial nontoxic multinodular goiter.

Kelch-like ECH-associated protein 1 (KEAP1) is associated with nuclear factor erythroid-2 related factor 2 (NRF2) and promotes NRF2 degradation in normal conditions. Genetic abnormality in KEAP1 is a rare disease and presents with familial multinodular goiter. This study assessed the clinical and molecular findings concerning nodular formation in the thyroid gland of patients harboring KEAP1 germline mutations. Next-generation sequencing analysis targeting goiter-associated genes was performed on 39 patients with familial multinodular goiter. The expression of NRF2-targeted genes from surgical thyroid specimens of patients with KEAP1 mutations were analyzed using a whole transcript expression array and immunohistochemistry. We found five probands with pathogenic heterozygous mutations in KEAP1 (p.Q86*, p.L136P, p.V411fs, p.R415C, and p.R483H), which had no meaningful concomitance with mutations of other goiter-associated genes in germline and somatic levels. Their common histopathological features showed multinodular goiters in the entire thyroid gland with few degenerative lesions or complications of malignancy and slow proliferation indicating < 1% at the Ki-67 labeling index. Among 42 NRF2-targeted genes, antioxidant genes were most frequently upregulated (11/12) in the nodule, followed by detoxification genes (6/11). Immunohistochemical analysis showed relatively high expression of glutathione peroxidase 2 and NAD(P)H quinone oxidoreductase 1 (representative NRF2-targeted genes) in the nodules of various patients harboring KEAP1 mutations. KEAP1 germline heterozygous mutations exert excessive NRF2 activity in the thyroid gland and may confer cytoprotective effects even under abundant reactive oxygen species associated with thyroid hormone production, resulting in thyroid hyperplasia with scarce degradation.

7090 The Largest Study on Asymptomatic Primary Hyperparathyroidism (APHPT) Conducted at the Tertiary Care Riga East Clinical University Hospital (RECUH)— Three Years of Data

Abstract Disclosure: D. Stūrīte: None. I. Rasa: None. Background: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder and a leading cause of hypercalcemia in the outpatient setting. The study aimed to assess the characteristics, management and outcomes of pts with APHPT. Methods: A retrospective analysis of data from 168 pts with APHPT, evaluated at RECUH from January 2021 to November 2023 was conducted. Information obtained included medical records, laboratory data, imaging results, surgical protocols, histopathology data. Statistical analysis was performed using IBM SPSS 29.0. Results: From the 168 pts (mean age: 63.7±11.8 years), 86.3% (n=145) were females. Predominantly, 67.3% (n=113) exhibited mild hypercalcemia (2.6-3.0mmol/L), while 22.6% (n=38) had moderate hypercalcemia (3.0-3.49mmol/L), and 4.8% (n=8) -severe hypercalcemia (≥3.5mmol/L). 5.3% (n=9) had normocalcaemic PHPT. The mean preoperative maximal calcium level was 2.9±0.3mmol/L, iPTH level - 247.6±224.9pg/mL, minimal phosphorus - 1.3±6.7mmol/L and 25-OH vitamin D level - 28.3±14.7ng/mL. The mean preoperative eGFR was 90.6±28.2 ml/min/1.73m2, creatinine - 72.5±23.9μmol/L. Parathyroid adenoma sizes ranged from 0.3x0.4cm to 5.3x3.7cm. Calcium levels positively correlated with adenoma cross-sectional area (ρ=0.187, p=0.029) and maximal adenoma dimension (ρ=0.215, p=0.011). Ultrasonography convincingly detected parathyroid adenomas in 63.9% (107/168), SPECT/CT - 68.4% (52/76), 99mTc-sestamibi scintigraphy - 65.6% (61/93), 3D-CT - 70.6% (24/34), contrast-enhanced ultrasonography - 84% (21/25) and MRI in - 40% (2/5) cases. 12.5% (n=21) pts had unlocated parathyroid adenoma. 34.5% (n=58) of pts had osteoporosis, 47.6% (n=80) osteopenia, 12.5% (n=21) had a history of osteoporotic fracture, 17.3% (n=29) had gallstones and 22.0% (n=37) - kidney stones. 80.4% (n=135) of pts had thyroid nodules, 48.2% (n=81) - nontoxic goitre, 24.4% (n=31) - autoimmune thyroiditis, 41.7% (n=70) - hypertension, 10.5% (n=18) - type 2 diabetes. 18.5% (n=31) pts were found to have a diagnosis of malignancy. 61.9% (n=104) of pts underwent parathyroidectomy. Histopathology and radiologic imaging revealed single parathyroid adenoma in 95.2% (n=99), double parathyroid adenomas in 1.9% (n=2), parathyroid hyperplasia in 2.9% (n=3) and parathyroid carcinoma in 1.9% (n=2) pts. The mean maximal postoperative calcium level (n=103) was 2.4±0.1mmol/L, iPTH (n=101) - 63.5±27.7pg/mL, 25-OH vitamin D - 41.5±13.3ng/mL, and the mean minimal phosphorus (n=56) - 1.1±0.2mmol/L. Conclusions: APHPT remains frequently encountered and often showcases bone manifestations. It's crucial to consider the diverse clinical manifestations and associated conditions in patients with APHPT. Presentation: 6/2/2024

7046 Thyroid Storm After Thyroidectomy Without Underlying Hyperthyroidism

Abstract Disclosure: A.J. White-Cotsmire: None. B. Kodali: None. C. McHenry: None. M. Rahhal: None. Background: Thyroid storm is a feared complication of total thyroidectomy; however, this is a rare phenomenon seen primarily in patients with undiagnosed or poorly controlled thyrotoxicosis from Graves’ disease. Preoperative treatment of patients with hyperthyroidism with beta-adrenergic blockers and anti-thyroid medication to ensure that patients are euthyroid prior to thyroidectomy have largely eliminated this risk of thyroid storm. (1) We report a case of thyroid storm caused by release of preformed thyroid hormone, following extensive manipulation and resection of a large retrosternal nontoxic multinodular goiter. To our knowledge, this has not yet been previously described. Clinical Case: A 57yo female underwent a total thyroidectomy with resection of a large benign multinodular goiter with retrosternal extension, which was causing compressive symptoms. She had a nodular goiter for 7 years that was increasing in size. Fine needle aspiration 2 years prior to surgery demonstrated colloid and adenomatoid nodules with Hurthle cell changes. She had no history of hypo- or hyperthyroidism. TSH prior to surgery was 0.576µIU/ml (normal = 0.450-5.330µIU/ml). Extensive manipulation was required to deliver the goiter from beneath the manubrium. Pathology from her thyroid revealed a multinodular goiter without evidence of malignancy. Post-operative course was uncomplicated, and after an overnight stay, the patient was discharged home with 150mcg (1.5mcg/kg) levothyroxine daily. She presented to the emergency department 4 days later and was admitted to the intensive care unit with diffuse abdominal pain, nausea, vomiting, and myalgias, and she was diagnosed with atrial fibrillation with rapid ventricular response. TSH on admission was 0.020 µIU/ml, thyroglobulin levels were &amp;gt;2,250.0ng/mL (n=0.8 – 48.0 ng/mL), thyroglobulin antibodies were negative. Her levothyroxine was stopped, her heart rate was controlled with metoprolol, and she was started on oral anticoagulation with rivaroxaban. She was discharged after a 7-day hospital stay. At 3 weeks follow-up her TSH was 35.67µIU/ml and her thyroglobulin levels were 23.9ng/mL. Her symptoms had resolved, and levothyroxine was resumed at a lower dose of 137mcg daily. Six weeks later her TSH level was 7.785µIU/ml, and her thyroglobulin was 1.8ng/mL. Conclusion: To our knowledge, this is the first case of thyroid storm reported following thyroidectomy in a patient with nontoxic multinodular goiter in a clinically and biochemically euthyroid patient. Massive increase in thyroglobulin postoperatively and rapid resolution of symptoms suggest that the release of preformed thyroid hormone related to vigorous thyroid manipulation was likely the cause. Reference: (1) Christou N, Mathonnet M. Complications after total thyroidectomy. Journal of Visceral Surgery. 2013;150(4):249-256. doi:10.1016/j.jviscsurg.2013.04.003 Presentation: 6/1/2024

8099 Pembrolizumab Induced Autoimmune Diabetes: An Abrupt Virulent Onset

Abstract Disclosure: H.F. Belal: None. N. Shaykh: None. A. Rajesh: None. J.M. Chehade: None. Background: Pembrolizumab is a programmed cell death protein 1 inhibitors (PD-1i) approved for the treatment of many solid cancers. Although thyroid abnormalities are among the most common endocrine adverse effects associated with PD-1i, insulin-dependent diabetes mellitus can also occur in up to 1% of patients treated with PD1-i.[1] Clinical Case: A 70-year-old female with past medical history of non-toxic multi-nodular goiter and surgical hypothyroidism was diagnosed with gastric cancer. She had no pancreatic abnormality on PET scan. Her management included four cycles of neo-adjuvant chemotherapy: fluorouracil, cisplatin, trastuzumab and pembrolizumab. She had no personal history of gestational diabetes. Prior to initiating neo-adjuvant chemotherapy her A1c was 5.9%. She was not prescribed any anti-diabetic medications. Her grandmother had type 2 diabetes mellitus. On exam her BMI was 23.73 kg/m². She had no acanthosis nigrans, skin tags or abdominal striae. Eighteen days after completing her second cycle of neo-adjuvant chemotherapy, she presented to the emergency department with nausea, vomiting, polyuria and confusion and was found to be in DKA. Her A1c during admission was 7.1%. Imaging revealed no pancreatitis. Labs showed suppressed C-peptide &amp;lt;0.1 ng/mL (1.1-4.4) in the setting of blood glucose 283 mg/dL (71-99). Her GAD-65 antibody was elevated at 902 U/mL (0.0-5.0). She was diagnosed with PD-1i induced autoimmune diabetes mellitus (PD-1i DM) and subsequently treated with basal and prandial insulin. Conclusion: The mechanism of PD-1i DM is unclear. A proposed mechanism is aberrant T cell activation towards pancreatic islet cells. One study found that 59% of patients with PD-1i DM presented with DKA.[1] In this study, the median time of PD-1i DM onset was 20 weeks after the first treatment cycle. Additionally, 40% of these patient had at least one positive pancreatic autoantibody. A recent meta-analysis found the relative risk of PD-1i DM to be 1.56 (95% CI = 0.95-2.57, P = 0.08).2 This relative risk increased to 2.06 (95% CI = 0.48-8.86, P = 0.33) when PD-1i were combined with cytotoxic T lymphocyte antigen-4 inhibitors.

6641 Observation in Lieu of Surgical Management in Hurthle Cell Neoplasm: Role of Thyroseq V3 Molecular Testing

Abstract Disclosure: R. Kaur: None. L. Kaur: None. T. Chaudhary: None. M. Shrivastava: None. N. Patel: None. The diagnostic utility of fine needle aspiration biopsy with cytology is often confounded in thyroid nodules with predominance of hurthle cells, often interpreted as an oncocytic/hurthle cell lesion with intermediate risk of malignancy, bethesda category (BC) III or IV. With the advent of molecular testing like thyroseq V3, it is helpful in ruling out substantial risk of cancer and considering observation in lieu of surgical management in such difficult cases. We present a case of a 75 year old woman with past medical history significant for type 2 diabetes mellitus and hypothyroidism who was found to have a left lobe complex nodule within a non-toxic multinodular goiter In 2022. Ultrasound of the neck showed a 1.6 x 1.8 x 2 cm intermediate nodule, followed by a fine needle aspiration biopsy which was non-diagnostic and reported as benign, showing only cystic contents and insignificant follicular cells, Bethesda class II. Follow up for the nodule was recommended in one year. Repeat Imaging one year later revealed left nodule without significant changes and repeat fine needle aspiration cytology was advised. The biopsy result was reported as an oncocytic/ Hurthle cell neoplasm, Bethesda class IV. The specimen was also submitted for thyroseq molecular testing and results were awaited. The patient was euthyroid with negative anti thyroid antibodies. There was no family history of thyroid cancer or radiation exposure. The patient denied any active symptoms like shortness of breath, neck pain or pressure, recent voice changes, dysphasia, loss of appetite or weight .On examination the patient was found to have a left thyroid nodule with no signs of tracheal deviation. CT scan of the neck demonstrated a left thyroid nodule with no compression. The patient was followed by both endocrinology and oncology and surgical options were discussed depending upon the biopsy results while awaiting molecular testing report. Molecular testing with thyrosec V3 revealed an absence of gene mutations and reported a low probability of cancer. Depending upon the results observation was considered in lieu of surgical management. Hence It was decided to keep the patient under observation considering the molecular test results in conjunction with all relevant imaging, clinical findings, symptoms, patients family history as well as patients preference. This case report demonstrates the crucial role of molecular Diagnostics specifically thyroseq V3 in the often difficult clinical management of hurthle cell thyroid nodules for ruling out surgical management. Thyroseq V3 shows reliable performance in Hurthle cell cancers with sensitivity of 93% and specificity of 69%. In times of patient guided decision making and ability to narrow down the need of surgery based on pre-operative fine needle aspiration cytology, molecular profiling of thyroid nodules has become increasingly utilized. Presentation: 6/1/2024

Asuhan Keperawatan pada Nn. M dengan Gangguan Sistem Endokrin: Post Op Isthmolobektomi dengan Indikasi Struma Nodusa Non Toksik di Ruang Mawar 2 RSUD dr. Soeselo Kabupaten Tegal

Non-toxic goiter nodusa is an enlargement of the thyroid gland in which one or more nodules are clinically detected without hyperthyroidism (Sari et al., 2021). The purpose of this writing is to find outand provide nursing care to Ms. M with endocrine system disorders: post op isthmolobectomy with indications of non-toxic nodal goiter in mawar ward 2 RSUD dr. Soeselo Tegal Regency in accordance with nursing standards. The method used is a descriptive method in the form of interviews, observation, documentation studies, library and literature studies. From the case review, it was found that the patient’s main comlaint was pain in the surgical wound on the left side to the neck, P:pain worsened when mobilizing, speaking and swallowing, Q: pain like being cut, R: pain on the left side of the neck, S: scale 4, T: disappears. There were three diagnoses found, namely acute pain, knowledge deficit and risk of infection. Intervetions are prepared based on the theory of SDKI, SLKI and SIKI as well as on the client’s condition and can be implemented.

Uncovering a Causal Connection between Gut Microbiota and Six Thyroid Diseases: A Two-Sample Mendelian Randomization Study.

Recent studies have established associations between the gut microbiota (GM) and thyroid diseases (TDs). However, their causal relationships remain elusive. To investigate this causality, we conducted a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data from MiBioGen and FinnGen, with GM as the exposure and six TDs as outcomes. We identified 32 microbial taxa linked to the risk of six TDs. The Clostridium innocuum group, Ruminiclostridium5, and Lachnoclostridium exhibited protective effects against nontoxic diffuse goiter (NDG). Conversely, an increased risk of NDG was associated with Ruminococcaceae UCG002, Alistipes, Methanobrevibacter, Marvinbryantia, and Ruminococcaceae UCG014. Bifidobacterium and Sutterella were protective against nontoxic multinodular goiter (NMG), while the Ruminococcus gauvreauii group and Rikenellaceae RC9 gut group heightened NMG risk. Protective effects against nontoxic single thyroid nodule (NSTN) were observed with Defluviitaleaceae UCG011, Ruminococcus1, and Ruminococcaceae UCG010, whereas increased risk was linked to Alistipes, the Ruminococcus gauvreauii group, and Lachnospiraceae UCG010. Ruminiclostridium9, Victivallis, and Butyricimonas offered protection against thyrotoxicosis with Graves' Disease (GD), while the Eubacterium rectale group, Desulfovibrio, Bifidobacterium, Collinsella, Oscillospira, and Catenibacterium were risk factors. For thyrotoxicosis with Plummer Disease (PD), protective taxa included Butyricimonas and Lachnospira, whereas Dorea, Eggerthella, Odoribacter, Lactobacillus, Intestinimonas, and Phascolarctobacterium increased risk. Lastly, Parasutterella was protective against thyrotoxicosis with toxic single thyroid nodule (TSTN), while increased risk was associated with Sutterella, Oscillibacter, and Clostridium sensu stricto1. Our findings support a causal relationship between specific GM and TDs at the genetic level, laying the foundation for future research into potential mechanisms and the identification of novel therapeutic targets.

Incidental Thyroid Malignancy in Surgical Patients With Benign Thyroid Disease

IntroductionThe rate of incidental thyroid malignancy (ITM) has increased in recent decades. However, the factors associated with ITM remain uncertain. This study analyzes the rate of ITM in patients after surgical resection for benign thyroid disease (BTD) without preoperative suspicion of thyroid malignancy and its associated sociodemographic factors. Materials and methodsA retrospective study of prospectively collected data reviewed data from 2528 patients who underwent initial thyroidectomy for BTD at a tertiary academic medical hospital between 2011 and 2022. Patients were excluded if they had a known history of thyroid cancer, radiation exposure, suspicious thyroid ultrasound features, and/or fine needle aspiration results. ITM rate was analyzed along with patient demographics, body mass index (BMI), tumor size, and invasive features. ResultsAmong 345 patients with BTD (mean 53.6 y, SD = 14.5), 22.9% (79/345) had ITM on final histopathology. Most patients were women (87.0%), White (87.0%), and Hispanic (56.8%), with an average BMI of 29.6 (SD = 6.56). BTD type was associated with ITM (P < 0.001), with nontoxic multinodular goiter exhibiting the highest incidence (36.0%). Higher BMI emerged as a predictor of higher rate of ITM (OR = 1.057, P = 0.007). Other sociodemographic variables did not show significant associations. ConclusionsThe study identified a higher rate of ITM than previously reported as well as an association between higher BMI and increased rate of ITM. This highlights a potential link between obesity and ITM not previously identified. Patients with higher BMI and BTD may benefit from further surveillance.

Manajemen Anestesi Operasi Total Thyroidectomy Pada Pasien Struma Multinodosa: Laporan Kasus

Goiter is an enlargement that occurs in the thyroid gland. Goiter can be classified based on physiology (euthyroidism, hypothyroidism, and hyperthyroisdism), morphology (diffuse and nodular goiter) and clinically (toxic and non-toxic goiter). Multinodular goiter is an enlargement of the thyroid gland with multiple nodules in which the thyroid gland follicles experience changes both morphologically and functionally. The characteristics of nontoxic multinodose goiter are slow, continuous and expanding growth. Surgery is one treatment for most types of goiter. The operation is performed under general anesthesia. Operative procedures performed on the head and neck are high-risk operations that can cause brain damage and result in death. Therefore, it’s necessary to prepare an anesthesia plan as well as appropriate pre-operative, intra-operative and post-operative management to avoid complications that may occur. Mrs. BP, 65 years old, came with complaints that a lump had appeared in his neck since approximately 2 years ago and had grown to approximately 5 cm in the last 1 year. In 2003 the patient underwent partial thyroidectomy under general anesthesia. This case report aims to look at anesthetic management in patients with multinodose goiter, where appropriate anesthetic management also determines the success and prognosis of surgical procedures in these patients.

Prognostic factors for the development of obstetric and perinatal pathology in pregnant women under conditions of iodine deficiency

According to the World Health Organization (WHO), iodine deficiency is the main cause of mental retardation in children, and at the same time, it significantly affects the pathological course of pregnancy and childbirth. The problem is complicated by the fact that more than 100.000 children with cretinism are born annually in the world. In recent years, there has been a significant increase in endemic thyroid diseases in Ukraine, the main cause of which is insufficient iodine consumption. Iodine deficiency conditions are aggravated by socio‑economic, ecological and radiological factors, while at the same time mass and group iodine prophylaxis is carried out improperly on the state level. Objective. To determine prognostic factors for the development of obstetric and perinatal pathology in pregnant women under conditions of iodine deficiency. Materials and methods. To compile a diagnostic table of prognostic factors of the threat of miscarriage, the analysis has been performed of 185 cases of threatened abortion (111 in the first trimester, 56 in the second, 18 in the third) and 223 control observations (without the threat of miscarriage). A diagnosis was considered as confirmed if it was established using all applicable methods of examination of pregnant women. Results. The risk factors of the occurrence of perinatal pathology include hypothyroxinemia (DC=–2.5) and ioduria in pregnant women less than 100 mg/l (DC=–1.9). In the intranatal period, a negative impact is exerted by the lack of coordination and weakness of labor activity (DC=–8.1). Levels of thyroid‑stimulating hormone (TSH) in umbilical cord blood &gt;10 mIU/ml (DC=–4.6) are the prognostically favorable factors for the postnatal adaptation of the newborn, especially TSH levels &gt;20 mIU/ml (DC=–8.3). Conduction of iodine prophylaxis (DC=7.7) and ioduria in pregnant women 200—400 mg/l (DC=5.1) contribute to the improvement of perinatal outcomes. Conclusions. A retrospective review of the prognostic significance of the diagnostic table in 188 patients with diffuse nontoxic goiter revealed its sensitivity (76%) and specificity (68%). On the basis of the conducted research, we established risk factors for the development of obstetric and perinatal complications, and assessed their informativeness. The developed algorithm is represented by a diagnostic table for the prediction of complications of pregnancy, childbirth and adverse perinatal outcomes in women with endemic thyropathies.

Topical Use of Cannabis in Inflammatory Diseases in patients of the IPS Salud Social in Barranquilla, Colombia

To relate the topical use of cannabis as an analgesic therapeutic alternative in patients with some inflammatory diseases in Salud Social I.P.S during May to July 2023. An analytical, retrospective study was carried out. The population from which the sample was obtained corresponds to patients diagnosed with Arthrosis, Unspecified, Non-Toxic Multinodular Goiter, Epilepsy, Unspecified Type Venous Insufficiency (Chronic) (Peripheral), Unspecified Lumbago, Secondary Gonarthrosis, Rotator Cuff Syndrome, Carpal Tunnel Syndrome, in Salud Social I.P.S of Barranquilla, Atlántico. A sample of 23 patients diagnosed with these pathologies was obtained by non-probabilistic convenience sampling. All patients showed pain relief after two months of follow-up, two experienced adverse effects. Some studies suggest that cannabinoids present in cannabis, such as CBD and THC, may have analgesic and anti-inflammatory properties that could alleviate pain and inflammation associated with these conditions. This is consistent with the present study. Topical cannabis is presented as a therapeutic alternative in inflammatory diseases, however, it is important to highlight that research on the use of cannabis in these diseases is limited and more studies are needed to fully understand its effects and potential benefits.

Predictive factors for the outcome of radioiodine therapy in patients with benign thyroid diseases.

Radioiodine therapy (RIT) of benign thyroid diseases is an established therapy. This study aimed to identify factors predictive for outcome in patients with non-toxic goiter (NTG), unifocal (UFA), multifocal (MUFA) or diffuse autonomy (DISA) and Graves' disease (GD). Retrospective analysis of 205 patients with benign thyroid disease (54 NTG, 46 MUFA, 24 DISA, 26 UFA, 55 GD) who underwent RIT. Follow up time was 12 months for determining treatment outcome. The type of disease was predictive for volume reduction after 12 months (NTS 66%, DISA 67%, MUFA 58%, UFA 51%, GD 71%, p<0.001) and post-treatment hypothyroidism (NTS 48%, DISA 33%, MUFA 15%, UFA 15%, p=0.006). Initial volume, intra-therapeutic uptake and intra-therapeutic half-life were independent prognostic factors for volume reduction 12 months after RIT. In patients with NTG, UFA, MUFA, DISA post-treatment hypothyroidism was significantly correlated with extent of volume reduction 12 months after RIT, achieved dose, higher pre-therapeutic TSH values and younger age. Two different strategies for pre-therapeutic dosimetry used in MUFA showed no differences regarding the therapeutic outcome. In GD, effective half-life, initial volume and Graves' ophthalmopathy were predictive for treatment failure. Reduction of thyroid volume and the percentage of hypothyroid patients one year after RIT was primarily dependent on the type of disease. In MUFA and DISA we could identify volume reduction after 3 months as a reliable predictor for hypothyroidism while in patients with GD a short intra-therapeutic half-life, a large pre-therapeutic volume and active Graves' ophtalmopathy were relevant predictors for treatment failure suggesting an intensified follow-up scheme in these patients.

Retrospective Diagnosis of Ca Thyroid on Thyroid Pertechnetate Scan -A part of Routine Post Thyroidectomy Work up For Nontoxic Multi Nodular Goiter.

Unsuspected thyroid cancer can be detected in multinodular goiter (MNG) where the risk of malignancy is 7-9%. Fine needle aspiration (FNAc) is performed in case of suspicious findings on ultrasound. With benign FNAC results there is no need for surgery unless the patient has pressure symptoms or cosmetic concerns, but the risk of overlooked malignancy is always present. We present the case of a patient with unexpected detection of papillary thyroid cancer on thyroid scan.

AMERICAN COLLEGE OF RADIOLOGY THYROID IMAGING REPORTING AND DATA SYSTEM IN SOLITARY THYROID NODULES – A COMMUNITY-BASED SINGLE CENTRE REAL WORLD EXPERIENCE

Introduction: A solitary thyroid nodule (STN) is a palpable enlargement in a normally functioning thyroid. Diagnosing and treating STN requires a holistic approach. Ultrasonography (USG) is a standard screening tool to identify high-risk nodules that may require fine needle aspiration cytology (FNAC) (benign/malignant). Hence, the current analysis aimed to access the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) with the malignancy and the management of STN in routine clinical practice. Methods: The study was a retrospective analysis of STN patients electronic medical records (EMR) database and USG recorded from 2014 to 2022. We queried a single-center EMR database with the search terms “solitary thyroid nodule”, “autonomously functioning thyroid nodule” and “nontoxic multinodular goiter”. A total of 213 records were identified with STN diagnosis, 161 records have one USG report, and of which a 5-year follow-up of 88 records having at least 2 USG reports with at least 1-year time interval of follow-up data. To better identify benign and malignant nodules and optimize clinical management, ACR-TIRADS and The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was adapted in clinic from 2017. Descriptive statistics was used to report the statistical analysis of data. Results: A total of 213 patients were identified with STN. The mean (SD) age is 45.2 (13.8) years. Of these, majority were female, 158 (75%) than male, 54 (25%). Of the total of 160 patients who had ACR TIRADs, 2 (1%) patients had score of 1, 97 (67%) had score 2, 46 (26%) had score 3, 16 (10%) had score 4, 3 (2%) had score 5. Ninety six (45%) patients had Bethesda categorization of nodule and it is observed in 3 (3%), 82 (82%), 8 (8%), 2 (2%), 1 (1%) belonged to class 1, 2, 3, 4, 5, respectively. At follow-up, 67 (76%) patients had no change in the ACR TIRAD nodule score, in 14 (16%) patients score decreased and in 7 (8%) patients increase in score. At baseline the mean (median) nodular volume is 24.2 (8.2) and at follow up 22.2 (6.7), percent change in the nodule volume is -17.7% (-16.0%). Further, of the 88 patients, 7 (9%) of patients had shown &gt;50% increase in the nodular volume. Conclusion: In this real-world data analysis of STN, we observed that the majority of the nodules are benign and nonprogressive, and very few patients had the risk of malignancy, indicating better treatment approaches to control the progression of this condition.

FRI493 Immune Checkpoint Inhibitors: Effects On Thyroid Nodular Disease

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

THU587 High Prevalence Of Primary Aldosteronism Diagnosis In Patients With Papillary Thyroid Cancer And Hypertension: A Cross-sectional Case-control Study

Abstract Disclosure: A.W. Maciel: None. T. Freitas: None. D.L. Danilovic: None. G.F. Fagundes: None. F. Freitas-Castro: None. L. Santana: None. A. Guimaraes: None. A. Pio-Abreu: None. J. V. Silveira: None. F. Consolim-Colombo: None. L. Bortolotto: None. M.C. Fragoso: None. A. Latronico: None. L. Drager: None. B.B. Mendonca: None. A.O. Hoff: None. M.Q. Almeida: None. Introduction: Aldosterone excess can cause oxidative stress leading to DNA damage in vitro and in vivo. Single case reports demonstrated a coincidence of primary aldosteronism (PA) with different malignancies. A higher prevalence of thyroid nodules and non-toxic multinodular goiter was described in patients with PA compared to those with essential hypertension (HT). A single study showed an association between PA and papillary thyroid cancer (PTC), but without a paired control group. Objective: To assess PA prevalence in a transversal cohort of patients with PTC and HT compared to a paired control group with HT. Methods: In this cross-sectional case-control study, PA was investigated in all patients with PTC and HT (n= 114), regardless of HT severity, under active surveillance at a cancer institute from 2019 to 2022. The control group included 228 (2:1) age-, sex- and body mass index (BMI)-matched individuals from a retrospective cohort of HT previously investigated for PA from 2011 to 2022. Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone ≥10 ng/dL and aldosterone to renin ratio ≥2 ng/dL/μUI/mL. Results: Age, sex and BMI were not statistically different between PTC and control groups, respectively (age 59.8 ± 12 vs. 58.9 ± 12.3 yrs, p= 0.67; 79% vs. 81% women, p= 0.67; BMI 30.7 ± 5.8 vs. 30.8 ± 6.5 Kg/m2, p= 0.98). PA was diagnosed in 35 out of 114 PTC patients with HT. The prevalence of PA in the PTC group (30.5%, confidence interval (IC) 22.6%-40.1%) was significantly higher when compared to the paired control group with HT (11.84%, CI 8.08%-16.93%; p&amp;lt; 0.0001). Although PA prevalence was higher in the PTC group, only 20.2% had stage 3/resistant HT (vs. 38% in the control group, p= 0.003). The number of anti-hypertensive medications was lower in the PTC group compared to controls (2 drugs, 1 to 3 vs. 4 drugs, 3 to 5, respectively; p&amp;lt; 0.001). When analyzing only PA patients in both groups, frequency of stage 3/resistant HT and number of medications were lower in the PTC group (p&amp;lt; 0.001 and p&amp;lt; 0.001, respectively). Although HT was more severe in PA patients without PTC, aldosterone and renin levels were not different in PA patients from PTC and control groups, respectively (p= 0.15 and p= 0.34). Conclusion: PA prevalence was strikingly high among patients with PTC and HT, supporting the recommendation of PA screening in this patient group, regardless of HT severity. Presentation: Thursday, June 15, 2023

SAT571 When Two Is Too Few: Bethesda IV Pathology On Repeat Thyroid Fine Needle Aspiration

Abstract Disclosure: C.M. Godar: None. A.J. Spiro: None. M.K. Shakir: None. T.D. Hoang: None. Background: The 2015 American Thyroid Association Guidelines for Adult Patients with Thyroid Nodules provide a strong recommendation against routine ultrasound surveillance of thyroid nodules for which two benign fine needle aspiration (FNA) cytology results have been previously obtained. Strict adherence to these guidelines may hinder detection of malignancy, especially in large nodules where there is potential to miss heterogeneous pathology based on sampling technique. Clinical Case: A 36-year-old female was evaluated for surveillance of a large non-toxic multinodular goiter. Thyroid ultrasound demonstrated a dominant right thyroid nodule greater than 7 centimeters in size. The patient had undergone FNA of this nodule in 2014 and 2019 with Bethesda II (benign) cytopathology results. A chest x-ray showed tracheal deviation without evidence of narrowing. She noted a sensation of neck pressure without dysphagia or shortness of breath. She denied fatigue, heat or cold intolerance, hand tremor, or pretibial myxedema. She denied a family history of thyroid cancer or any history of neck irradiation. Due to new compressive symptoms a repeat FNA was performed. Three passes were performed with adequate samples, and the final FNA cytopathology demonstrated a Hurthle cell oncocytic-type follicular neoplasm with Bethesda IV classification. The sample was submitted for ThyGeNEXTTM and ThyraMIRv2TM molecular testing, which returned with NRAS q61R mutation of moderate-to-high risk of malignancy (65-75%). The patient was subsequently referred for total thyroidectomy with pending surgery date. Discussion: The current ATA guidelines offer a cost-effective surveillance strategy for the vast majority of patients with thyroid nodules. False negative FNA results are rare and are reported to occur in about 1% of cases1. As in this vignette, it is reasonable to perform an additional FNA after two consecutive Bethesda II results in nodules with clinically significant growth, new compressive symptoms, or if there is concern for incomplete sampling in nodules of large size. During an FNA, care should be taken to gently move the needle at various angles to capture follicular cells from different areas within a nodule. Large nodules should be sampled via multiple, separate skin entry points when feasible. Judicious use of repeat FNA along with these sampling techniques may help to prevent under-diagnosis in nodules containing multifocal areas of heterogeneous pathology. Reference: 1) Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S, Attard M, Lamartina L, Nicolucci A, Filetti S. 2015. The natural history of benign thyroid nodules. JAMA 313:926-935 Presentation: Saturday, June 17, 2023

FRI570 Repatha Induced Thyroid Storm

Abstract Disclosure: L.R. Sepulveda-Garcia: None. L.N. Madera Marin: None. L. El Musa Penna: None. W. Medina-Torres: None. M.A. Ortiz-Rivera: None. A. Rosado-Burgos: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. Introduction: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are an effective medical therapy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol ability of statins. In 2020, a case of transient hyperthyroidism secondary to evolocumab was reported. We present a case of impending thyroid storm after a patient received evolocumab. Patient description: 60 y/o female patient with medical history remarkable for hyperlipidemia, anti-TPO positive non-toxic multinodular goiter, hypertension, fibromyalgia, and coronary artery disease who presented with heat intolerance, palpitations, tremors, and insomnia after second dose of evolocumab. At physical exam found with tachycardia, hypertension, anxious mood, tremors, leg pitting edema +1 bilateral, and deep tendon reflexes +3 in lower extremities, although no palpable or painful goiter. Laboratories compatible with hyperthyroidism [TSH &amp;lt; 0.008 uIU/mL (0.3 – 3.0 uIU/mL), Free T4 4.29 ng/dL (0.89 – 1.76 ng/dL), Total T4 20.03 ug/dL (4.5-12 ug/dL)] and clinically with severe thyrotoxicosis. Patient was sent to ED for further evaluation and management. Case outcomes: Upon admission patient presented with a tonic-clonic seizure with short post ictal state. Burch-Wartofsky scale Point Scale 35, consistent with impending thyroid storm. Thyrotoxicosis management given requiring high doses of PTU, hydrocortisone and propranolol, including the need to add cholestyramine to the regime. By day 9 of therapy, patient was transitioned to methimazole 30mg daily with discontinuation of hydrocortisone and cholestyramine. Upon discharge, 2 weeks later, thyroid function tests had normalized to a FT4 of 1.39 ng/dL and a Total T4 of 9.6 ug/dL. Case discussion: A case of transient hyperthyroidism with PCSK9 inhibitor was previously reported requiring only symptomatic treatment. In this case a patient presented with severe thyrotoxicosis after she received her second dose of evolocumab. PCSK9 inhibitor therapy immunological influence on thyroid remains unknown. This case shows the importance of thyroid function test follow up in patients on PCSK9 inhibitor therapy and the possibility of immunological influence on the thyroid. Presentation: Friday, June 16, 2023

Structural and morphologic characteristics of nodular goiter in chronic iodine deficiency status

OBJECTIVES. Diffuse and nodular goiter are the most common thyroid gland (thyroid) diseases in children and adults living in iodine-deficient regions. Thyroid hormone potentiates progressive hypertrophy and hyperplasia of thyrocytes, with uneven proliferation of thyroid cells leading to nodule formation. Iodine deficiency, which promotes replication of thyroid follicular cells, also increases the incidence of TSH Receptor mutations, leading to receptor activation and autonomous functioning of follicles.AIM. To evaluate and describe ultrasound and cytologic thyroid nodes in the regions in Russia with proven iodine deficiency.MATERIALS AND METHODS. The study was conducted in regions with proven iodine deficiency in the Central and North Caucasian Federal Districts. Population of conditionally healthy adult volunteers (mean age — 47.5 years) was recruited as part of visiting events to screen for the occurrence of thyroid nodes.RESULTS. The results obtained indicate a high prevalence of multinodular colloid goiter in adult patients living in conditions of chronic iodine deficiency. In the Chechen Republic, the prevalence of nodular thyroid pathology was found in 64.5% (205/318) of cases, and in the Tula region — in 40.6% (116/286). In the studied sample the results of cytologic examination confirmed the presence of colloid thyroid masses in 97% (60/62) — Bethesda category II; in 3% (2/62) of patients nodular masses had Bethesda IV. Diffuse goiter prevalence in the examined population was 20.8%.CONCLUSIONS. A study indicates a high prevalence of iodine-deficient thyroid disease — multinodular colloid goiter in regions with proven chronic iodine deficiency. The wide prevalence of goiter with colloid and cystic components is confirmed by the cytologic examination with different ultrasound characteristics according to the EU-TIRADS classification. The obtained data correspond to the official statistics demonstrating high prevalence of nontoxic goiter in adults in the examined regions, which is an important argument confirming the need for systemic iodine prophylaxis.

Study of the Relation between 8_Hydroxy-2′-deoxyguanosin (8_OHDG) and Suspicious Thyroid Nodule in a Patients with Multinodular Goiter

Abstract Background Nodular disease of the thyroid gland is prevalent. The lifetime risk for developing a palpable thyroid nodule is estimated to be 5-10%, however, high resolution ultrasound has revealed thyroid nodules in 19-68% of randomly selected individuals. The condition affects more women than men. Aim of the Work In this study we aimed to study the relation between 8_Hydroxy-2'deoxyguanosin (8_OHDG) and Suspicious Thyroid nodule in a Patients with Multinodular Goiter. Patients and Methods The present study was a case-control study that was conducted on 60 subjects patients presented with MNG at Ain Shams University hospital during the period from January to December 2019. Results The results of our study demonstrated that plasma 8_OHDG levels were higher in patients with Multinodular goiter than in control group, and were higher in MNG patients with cancer than MNG without cancer. Which confirms the presence of oxidative stress in patients with non-toxic multinodular goiter and 8-OHDG levels may be markers of the carcinogenic potential of Multinodular goiter. Conclusion Our study confirms the presence of oxidative stress in patients with non-toxic multinodular goitre. The plasma 8-OHDG levels may be markers of the carcinogenic potential of multinodular goiter and could be used for early detection of different cancer types, including thyroid cancer. This warrants nutritional support with antioxidant agents in patients with non-toxic multinodular goiter. Further studies are warranted for better understanding of underlying pathogenic mechanism of oxidative stress in non-toxic Multinodulargoitre.