Thyroid Pathology Research Articles

Alleviating effect of whey protein supplementation on oxidative stress in hypothyroidism.

Hypothyroidism is one of the most prevalent thyroid pathologies, which causes oxidative stress by disrupting antioxidant mechanisms. In mammals, the thyroid glands regulate metabolism, development, and growth. Dysfunction of the thyroid gland can result in hypothyroidism, hyperthyroidism, thyroiditis, and thyroid cancer. Whey protein is a widely consumed protein supplement containing abundant sulphur-containing amino acids and bioactive peptides. Here, we analysed the effect of whey protein on oxidative stress in hypothyroidism. In vivo studies were conducted in two phases for 30 and 90 days, respectively. Hypothyroidism was induced in Wistar albino rats by administering 0.05% propylthiouracil (PTU) through drinking water. Five hypothyroid groups and the normal control group were maintained in the first 30 day phase of the study. Among these, one group served as the induced control group, three groups received whey protein at different concentrations (100, 300, and 500 mg per kg body weight), and the last group received L-thyroxine (2 μg per 100 g body weight) as a positive medication. The activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, were analysed, and the levels of total antioxidants, glutathione, and malondialdehyde were determined. Ca2+ ATPase and Na+/K+ ATPase activities were detected by estimating the inorganic phosphate content. Histopathological analysis was carried out on the thyroid and liver tissues of all groups. Antioxidant activity was notably increased for higher doses of whey protein compared to that in the diseased control group (p < 0.05). From this initial study, the dose that achieved the desired therapeutic effect was 500 mg kg-1, which was considered for the next 90 day phase of the study. The 90 day phase of the study was conducted with five groups: normal, whey protein-supplemented, hypothyroid, whey protein-supplemented hypothyroid, and levothyroxine-supplemented hypothyroid. All the PTU-treated groups showed degenerative alterations in thyroid histology. Whey protein supplementation causes a considerable decrease in MDA levels with an increase in the major antioxidant enzyme and ATPase activities, with p < 0.05. As a nutritional supplement, whey protein, at a 500 mg kg-1 dose, effectively boosts antioxidant activity without causing any toxicological concerns in long-term use.

"Atherosclerotic" phenotype of rheumatoid arthritis. What do we know about it?

Several studies have shown that systemic rheumatoid inflammation may cause induction and accelerated progression of atherosclerotic vascular lesions, which in turn may lead to more frequent development of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA) compared to the general population.Objective. To evaluate the presence, nature and role of conventional and RA-specific risk factors for the development of CVD in patients with active RA in real-life clinical practice.Material and methods. Data from 967 patients with confirmed active RA were analyzed. Biologic disease-modifying antirheumatic drugs (DMARDs) or targeted DMARDs were prescribed/switched due to the ineffectiveness of previous therapy. Patients were divided into two groups: with and without CVD. In addition, comparable age subgroups of elderly (60–74 years) and middle-aged (45–59 years) patients were formed in each group. In all patients, clinical and laboratory parameters of RA activity, presence of extra-articular manifestations, the severity and progression of RA and characteristics of pharmacotherapy were analyzed. In addition, concomitant diseases and several traditional risk factors for the development of CVD were analyzed in all RA patients.Results and discussion. In patients with similar RA activity and duration, there is a parallel, tatistically significant accumulation of traditional CVD risk factors with increasing age-related CVD. The incidence of arterial hypertension, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, thyroid pathology, anemic syndrome, dyslipidemia, hyperuricemia and obesity was significantly higher in the group of elderly RA patients with CVD than in the group of middle-aged patients.Conclusion. It seems appropriate to identify a specific variant of RA that is closely associated with atherosclerosis.

Tomographic and ultrasound evaluation of the thyroid gland in pet guinea pigs.

There has been increasing interest in the literature on primary thyroid diseases in guinea pigs, which are believed to be underdiagnosed. This study describes the size and characteristics of the thyroid gland on ultrasound (US) and CT examinations in the guinea pig (Cavia porcellus) without evidence of thyroid pathology and examines the possible use of US as a routine examination for thyroid diseases. This prospective and anatomical study included 20 guinea pigs that underwent CT for dental pathologies and US for thyroid gland (TG) examination. Based on US and CT images, this study evaluated the thyroid lobe dimensions (length, height, and width) and shape. Echogenicity and homogeneity were assessed on US images, and attenuation values (HU) and homogeneity were evaluated on CT images. All animals underwent CT and US examinations under anesthesia. Thyroid lobes appeared more frequently as fusiform on CT (65%) and oval on US scans (67.5%). The attenuation values on CT scans were homogeneous. On the US scans, the TG was more frequently hypoechoic. No statistically significant differences were found between the size of the right and left thyroid lobes, both with CT and US. A statistically significant difference was found between the length values on CT and US. The US and CT thyroid gland dimensions, shape, and appearance were described. Both CT and US are useful techniques for evaluating the TG in guinea pigs.

Characteristics of the fetus in pregnant women with thyroid diseases

BACKGROUND: Thyroid dysfunction can cause adverse effects on metabolic changes in the body and disturbances during the gestational period and intrauterine development of the fetus. In developing prevention methods, it is crucial to objectively substantiate and re-confirm theoretical assumptions. AIM: To assess the functional state of the fetus in pregnant women with certain thyroid diseases. MATERIAL AND METHODS: The results of instrumental studies in 118 pregnant women, who were divided into three clinical groups, were analyzed. Group 1 (44 people) consisted of patients with autoimmune thyroiditis (AIT). Group 2 (52 people) included patients with diffuse toxic goiter. Group 3 (control group) consisted of 22 pregnant women who had no somatic pathology and gestational complications. Thyroid diseases were diagnosed by an endocrinologist during a consultation in the third trimester of pregnancy based on laboratory and instrumental data. The functional state of the fetus was assessed using the total result of cardiotocographic and ultrasound studies, for which Partecust (Siemens, Germany) and Aloka-1700 (Hitachi, Japan) were used. Statistical processing of clinical material was performed using StatSoft software (Russia). RESULTS: A comprehensive assessment of the adaptive capabilities of the fetus showed changes in its functional state in pregnant women with thyroid pathology. Prognostically, the most crucial characteristic in pregnant women with autoimmune thyroiditis and diffuse toxic goiter is a decrease to 0–1 point in indicators that determine motor activity and tone, respiratory movements, and reaction to a non-stress test. Among patients with autoimmune thyroiditis and diffuse toxic goiter, a high assessment of the biophysical profile of the fetus occurred 4 and 3.4 times, respectively, less often than among women with a normal pregnancy (among pregnant women without somatic pathology and gestational complications). CONCLUSION: Disturbances in thyroid gland function during the gestational period can have an adverse effect on the development of the fetus, which is a theoretical basis for the development of treatment and preventive methods aimed at improving perinatal outcomes in this group of patients.

6688 Clinical Presentation and Management of Highly Differentiated Follicular Carcinoma Arising from Struma Ovarii with DICER1 Mutation: A Case Report

Abstract Disclosure: S.M. Seav: None. J. Shah: None. C. Dosiou: None. Background: Struma ovarii (SO) is a rare type of ovarian teratoma comprised of &amp;gt; 50% thyroid tissue. Extra-ovarian spread of SO, called peritoneal strumosis, was previously considered benign given the lack of histological malignant features. The 2020 WHO Classification of Female Genital Tumors has reclassified this as highly differentiated follicular carcinoma arising from struma ovarii (HDFCO), highlighting its low-grade malignant potential.[1] We report a case of HDFCO with extensive peritoneal disease and discuss its management. Clinical Case: A 38-year-old female presented to her OBGYN for irregular menses. Pelvic MRI showed an 8 cm right ovarian mass. Right salpingo-oopherectomy and pelvic peritoneal biopsies revealed well-differentiated thyroid tissue. Thyroid ultrasound demonstrated a multinodular goiter with ATA high risk nodules; 4 of 5 biopsied with benign results. Her thyroglobulin (Tg) was 170 ng/mL (normal 2 – 35 ng/ml). No further intervention was recommended. Two years later she was referred to our clinic. CT of abdomen/pelvis showed multifocal residual disease. We recommended more aggressive management, given the diagnosis of HDFCO. All visible disease was resected in a diagnostic laparoscopy with pelvic and omental biopsies. Pathology showed well-differentiated thyroid tissue. Molecular testing for the FGFR4 mutation associated with HDFCO was negative, but there was a DICER1 mutation c.5428 G&amp;gt;T of undetermined significance. DICER1 mutations are associated with thyroid cancers2. A total thyroidectomy and radioactive iodine ablation (RAI) were recommended. Thyroid pathology was benign. Tg was 9 ng/mL one month post-op. MRI six months post-laparoscopy revealed only one 6 mm omental lesion. Withdrawal I-123 whole body scan (WBS) showed multiple peritoneal implants. Tg was 214 ng/mL and TSH was 72 ulU/mL. The patient was treated with 157 mCi of oral I-131. Given the extensive peritoneal disease, she received prophylactic oral dexamethasone for 2 weeks after RAI to decrease the risk of peritoneal inflammation and bowel obstruction potentially mediated by local inflammation from radiation-related tissue injury. Her Tg three months post-RAI was 4 ng/mL. The surveillance plan is to alternate between RAI WBS and MRI abdomen/pelvis every 6 months. Conclusions: Peritoneal strumosis, previously considered benign, has recently been reclassified as HFDCO, an extremely rare low-grade malignancy with no standardized treatment. We report the first case of extensive HFDCO with a DICER1 mutation. Given the significant peritoneal involvement, our case was treated with total thyroidectomy, surgical excision of all implants, RAI, and prophylactic steroids post-RAI. Further research into the prognostic factors and optimal treatment of HFDCO is needed. Reference: [1]Giovanopoulou et al. Curr Oncol. 2022; 29(12): 9105-9116. 2Sauer et al. Head Neck Pathol. 2022; 16(1): 190–199. Presentation: 6/1/2024

7504 A Case of Methicillin Sensitive Staphylococcus Aureus Thyroiditis

Abstract Disclosure: K. Patel: None. P. Kachhadia: None. S. Khan: None. F. Akanbi: None. A. Abu Limon: None. S.A. Aldasouqi: None. Introduction: Acute suppurative thyroiditis refers to bacterial infection of the thyroid gland. It is rare as the thyroid gland is typically protected from infection due to isolation of the gland from neighboring structures as well as its rich blood supply and adequate lymphatic drainage. It shares characteristics with subacute and autoimmune thyroiditis which make for difficult diagnosis. Here we present a case of acute suppurative thyroiditis in the setting of methicillin sensitive staphylococcus aureus (MSSA) bacteremia. Case Presentation: We have a 45 year old gentleman with a history of polysubstance abuse who was admitted after a drug overdose. He was being treated for rhabdomyolysis and approximately ten days after admission he became febrile with Tmax 103.3 Farenheit with a sore throat and dysphagia. Workup showed leukocytosis, ESR 86 mm/h [0-15], CRP 45.5 mg/dL [0-1], blood cultures with MSSA, negative viral upper respiratory panel, throat culture, Syphilis and HIV testing. He had a positive Hepatitis C antibody without a detectable viral load. Echocardiogram ruled out vegetations. He was treated with cefazolin. CT neck was obtained and showed thyroid enlargement. Subsequent ultrasound showed heterogeneous echotexture and increased color flow and a left inferior pole nodule 2.3 x 2.1 x 2.0 cm. Thyroid labs showed TSH 0.16 [0.35 - 4.01 u[IU]/mL,] Free T4 3.91 ng/dL [0.61 - 1.37], TPO &amp;lt;0.3. The nodule was biopsied and endocrinology was consulted. On exam thyroid was nontender. He was started on beta blockers and thyroid labs were monitored. TSI and TRAB were negative. TSH, Free T4 and Free T3 improved to normal range. Nodule biopsy results showed benign follicular cells with abundant acute inflammation suggestive of an abscess. Metronidazole was added after biopsy results. Post antibiotic therapy, CRP improved to 1.7 mg/dL. Discussion/Conclusion: Incidence of acute suppurative thyroiditis has been published as occurring &amp;lt;1% of all thyroid diseases. One systematic review found 200 cases reported from January 2000 to January 2020. Prior case reports have described acute suppurative thyroiditis in adult patients with prior thyroid gland pathology or an immunocompromised state and some demonstrated a correlation with intravenous drug users. The most common culprits include Staphylococcus spp, Streptococcus spp, Salmonella spp, Escherichia spp. Management includes antimicrobial therapy and/or needle aspiration. Non-responders can undergo incision and drainage of abscess or thyroidectomy. Mortality was reported in about 8% of the reported 200 cases. In our patient, his history of drug use and Hepatitis C likely made him prone to infection. Although there was no description of pus during biopsy, pathology suggested acute inflammation. This along with elevated inflammatory markers led to the diagnosis. This case highlights an uncommon but potential cause of thyroiditis. Presentation: 6/3/2024

6770 Graves’ disease induced by COVID-19 infection in a 49 year old male

Abstract Disclosure: N. Al-hosainat: None. A. Al Najada: None. T. Salar: None. S. Iqbal: None. K. Abdel Gadir: None. Introduction: Graves’ disease is an autoimmune disease causing hyperthyroidism, characterized by elevated thyrotropin-receptor antibodies. COVID-19 infection has been increasingly reported as a trigger of thyroid illness including Graves’ disease. We present a unique case of 49-year-old patient who was diagnosed with Graves’ disease after COVID-19 infection. Case description: A 49-year-old male patient with history of prediabetes presented with complaints of tremor, fatigue, generalized itching, and unintentional weight loss (30 Ibs in 6 months). He had COVID-19 infection 3 months prior. The remainder of review of systems was negative. No family history of thyroid disease. On exam, the patient had sinus tachycardia with otherwise normal vital signs. Diffuse thyromegaly was noted along with an intermittent fine tremor of the extremities. Blood work was notable for low TSH &amp;lt;0.01 uIU/mL, elevated free T4 (3.4 ng/dL), free T3 (17.6ng/dL), and TSH receptor antibody (12 IU/L). Thyroid ultrasound showed mild goiter with 2 nodules, one of which was TIRADS 4 and 1.5cm. This nodule was biopsied and found to be benign. Radioactive iodine uptake scan revealed homogeneous diffuse increased thyroid uptake. The diagnosis of Graves’ disease was made, and the patient was started on propranolol and methimazole with significant improvement of his symptoms and his laboratory tests normalizing. Discussion: Graves' disease is an autoimmune disease, characterized by hyperthyroidism, goiter, occasional orbitopathy and dermopathy. Caused by antibodies against thyroid-stimulating hormone receptors which stimulate thyroid hormone secretion and thyroid growth. Treatment is aimed to decrease thyroid hormone synthesis by either a Thionamide, radioiodine ablation, or surgery. Remission rates with antithyroid drugs average under 40 percent after one to two years of treatment and could exceed 80 percent after 5 to 10 years of treatment. COVID-19 is a multi-system disease, caused by SARS-CoV-2 virus, transmitted by large droplets and small particle aerosols, was declared a pandemic in 2020 and affected millions of people worldwide. There is emerging data showing the association of COVID-19 with various thyroid diseases including thyroiditis and relapse of known Graves' disease after the infection. We present a case of newly diagnosed Graves’ disease after COVID-19 infection in a patient with no personal or family history of such disease which raises the concern of autoimmune pathway activation induced by the infection. The onset of Graves’ disease after COVID-19 infection does not depend on the presence of pre-existing thyroid pathology and in this case responded well to antithyroid medication. Conclusion: COVID-19 can lead to the development of a range of medical illnesses. In patients who develop symptoms of thyrotoxicosis, Graves’ disease should be suspected, investigated, and treated appropriately Presentation: 6/3/2024

7355 A Case of High-Risk Thyroid Tumor Markers Found in Subcutaneous Thyroid Implants in a Patient with Benign Thyroid Pathology

Abstract Disclosure: J. Fedorko: None. S. Fatima: None. A.P. Amblee: None. C.A. Poku: None. Background: While fine needle aspiration (FNA) remains the primary diagnostic tool for thyroid malignancies, the utilization of molecular markers has become increasingly common in the workup of thyroid nodules. They play a useful role in distinguishing between malignant and benign pathology when cytology is indeterminate and in formulating treatment plans. The vast majority of research for these genetic markers is conducted in cases with thyroid malignancy. However, there have been numerous cases where these genetic markers were identified in benign thyroid tissue. Case: A 73-year-old male with left hemithyroidectomy (benign left nodule) presented 6 years later with new superficial neck nodules along the midline, left thyroid bed and R thyroid lobe. FNA of the right thyroid nodule was benign. Three months later the patient underwent an excision of the midline neck nodules which revealed thyroid tissue arranged in nests of fibrotic tissue without definite features of papillary thyroid carcinoma. Molecular analysis (Thyroseq) was positive for HRAS, E1F1AX and TERT mutations thus metastatic follicular carcinoma was suspected. The patient underwent complete thyroidectomy. Pathology revealed normal thyroid tissue and a diagnosis of thyroid neck implants was made. Given the benign pathology, the plan was for close follow-up with neck imaging every 6 months. Discussion: Thyroid tissue implants can rarely be caused by previous surgical interventions, especially partial thyroidectomy. There is literature documenting similar clinical cases in which subcutaneous thyroid implants are found in patients after undergoing total or subtotal thyroidectomy. In one case series, there were cases in which thyroid implants were discovered 26 years post-surgery, with most of the cases reporting benign pathology. Given our patient’s presentation and clinical history, the possibility remains that his subcutaneous tissue findings were caused by his prior partial thyroidectomy. A recent article reviewed 60 publications and &amp;gt;8000 patients for the prevalence of high-risk tumor markers (RAS mutation, RET/PTC, and PAX8/PPAR-gamma chromosomal rearrangements) in benign thyroid tissue. They concluded that prevalence findings were highly variable, warning providers to exercise caution when using these genetic markers to guide diagnosis and treatment decisions. Conclusion: While certain high-risk genetic tumor markers are increasingly used to help identify thyroid malignancies, it is important to keep in mind that these genetic markers are not exclusively found in cancerous tissue, and should not be used as the sole diagnostic tool for diagnosis and treatment. While it is imperative that metastatic disease is ruled out, it is essential to consider other pathologies when evaluating recurrent thyroid and neck masses in patients with a history of benign thyroid lesions. Presentation: 6/3/2024

8049 Beyond Metastasis: Parasitic Thyroid Tissue Mimicking Thyroid Cancer

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. N.A. Mungo: None. This case study details a complex clinical scenario involving a patient with diaphoresis and a familial history of thyroid cancer. Initial suspicions of functionally active metastatic thyroid cancer led to a thyroidectomy and cervical lymph node dissection, only to reveal unexpected parasitic thyroid tissue. This case highlights the importance of meticulous evaluation and follow up similar presentations, shedding light on the rarity of this phenomenon.The patient, experiencing a year of diaphoresis unresponsive to estradiol therapy, underwent imaging revealing multiple thyroid nodules. A left superior nodule (TI-RADS 4) and a more concerning right mid-posterior nodule (TI-RADS 5) prompted fine needle aspiration (FNA). FNA of the right thyroid nodule exhibited Bethesda category III atypia, no molecular samples were taken at that time, while cervical lymph node FNA yielded nondiagnostic results.Subsequent ultrasound showed no interval change in the right thyroid nodule but raised concerns about increased solid components and decreased echogenicity in other nodules. Due to patient concerns of positive family history of thyroid cancer, the lymph node was biopsied. The result yielded a low cellular sample, but follicular thyroid tissue was present. The patient elected to undergo thyroidectomy as she did not want to continue monitoring. Pathology revealed parasitic thyroid tissue in the lymph node and nodular follicular thyroid disease, with no evidence of papillary thyroid carcinoma in the gland. Notably, the patient had no history of thyroid surgeries, ruling out traumatic rupture or implantation from a follicular adenoma. However, the possibility of follow-up metastatic follicular carcinoma cannot be entirely excluded on histologic grounds.Follow-up tests were recommended, encompassing mutational analysis, whole-body scans, and thyroglobulin (Tg) monitoring. Molecular analysis did not favor cancer. Tg levels remained at (18 ng/ml, n&amp;lt; 35ng/ml) of initial evaluation six weeks post surgery and repeat testing is pending. Ablative radioactive iodine therapy may be appropriate as resection of all parasitic thyroid tissue can prove difficult.This case emphasizes the diagnostic challenges posed by the rare occurrence of parasitic thyroid tissue, often mistaken for metastatic thyroid cancer. The findings contribute to our understanding of uncommon thyroid pathologies. The clinical implications of this case extend to the importance of heightened clinical suspicion in intricate endocrine cases. Presentation: 6/3/2024

12243 The Case of a Metastatic Papillary Thyroid Cancer Presenting as an Unresectable Pelvic Mass

Abstract Disclosure: M. Tucktuck: None. Y. El Soufi: None. O.G. Adeniran: None. A.A. Gliwa: None. Background: Papillary thyroid cancer (PTC) represents around 85% of all thyroid cancers, of which 2-10% of patients will present with metastasis distant to the neck. The frequency of bone metastasis in PTC occurs in only 1-4% of patients. Studies have shown that distant and multi-organ metastasis is associated with higher mortality rates. Clinical case: A 69-year-old woman with diabetes mellitus, cerebrovascular accident, and right lower extremity deep venous thrombosis, presented with right foot and hip pain for 1 week after a mechanical fall. She had a 50 pound weight loss over a year without personal or family history of thyroid cancer or disease or radiation exposure. A soft and nontender mass in the right lower abdomen was noted during a physical exam. Imaging revealed a large heterogeneous lesion (16.3 x 13.3 x 15.5 cm) in the right bony pelvis with internal necrosis, destructing the right iliac bone, and extending into the right sacrum, acetabulum, and musculature, with mass effect on the surrounding vasculature, and enlarged lymph nodes suspicious for metastasis. Thyroid imaging showed a hypervascular hyperechoic 1.3 cm nodule within the right thyroid gland and a large 2 cm left thyroid nodule with scattered microcalcifications. Thyroid function tests were within normal limits. The patient underwent an initial ultrasound guided biopsy of the pelvic mass with indiscriminate results, and later a laparoscopic excisional biopsy of the pelvic mass showed neoplastic papillary proliferation with typical nuclear features, without necrosis or associated ovarian tissue. The immuno-histopathological profile was positive for PAX-8, TTF-1, thyroglobulin, and CK7, and the Ki-67 proliferation index was ∼20-30%. The patient was diagnosed with papillary thyroid cancer with metastasis to the pelvic bone, and was classified as stage IV, cT1bN0M1. As the pelvic mass was inoperable, the patient completed total thyroidectomy and was started on hormone replacement therapy. Subsequent thyroid pathology report was negative for papillary carcinoma. Further review of imaging did not show ectopic thyroid tissue in the neck or an ovarian pathology. Before the patient’s next visit to evaluate for struma ovarii, she passed away. Conclusion: Thyroid cancer is usually treated through thyroidectomy or lobectomy, with radioiodine (RAI) therapy as an effective treatment for differentiated cancers. Our patient, who presented with extremity pain revealing a distant metastasis, completed thyroidectomy with plans to undergo RAI therapy. Our case highlighted the importance of recognizing musculoskeletal presentations as an initial and possibly only finding of a distant metastasis. It also emphasized the utility of multidisciplinary collaboration in detecting and recognizing PTC as a primary thyroid cancer, as early management can reduce mortality and lead to more favorable outcomes. Presentation: 6/2/2024

8534 Comorbid Autoimmune Thyroid Disease in a Parent-Child Pair with Resistance to Thyroid Hormone Beta

Abstract Disclosure: A.H. Smith: None. E. Grethen: None. Resistance to Thyroid Hormone Beta (RTHβ) is an inherited disorder caused by mutations in the gene encoding the thyroid hormone receptor beta protein, resulting in decreased binding affinity to triiodothyronine in certain tissues. An asymptomatic individual with RTHβ may demonstrate abnormalities in serologic evaluation of thyroid hormone markers. When other thyroid pathologies present with RTHβ, however, the diagnosis and management can quickly become complex. Below we discuss two cases, a parent-child pair, with different presentations of presumably the same RTHβ gene. Patient 1 is a 61-year-old male with a history of autoimmune thyroiditis several years ago, presenting for continuation of care; he has had levothyroxine doses gradually uptitrated to over 3 mcg/kg to normalize TSH despite persistently high free T4 levels. He also has a family history notable for six out of seven siblings with autoimmune thyroid disease. Patient 2 is a 44-year-old male who was evaluated for hypothyroidism and difficulty with levothyroxine titration. Prior to consultation, he underwent radioactive iodine ablation for presumed Grave’s disease, followed by total thyroidectomy due to persistent symptoms. Post-operatively, he required high doses of levothyroxine to maintain normal TSH levels; however T4 and T3 levels remained high. Both patients confirmed proper levothyroxine supplementation. Further analysis of both patients demonstrated mildly elevated TBG and normal alpha subunit. Patient 2 pursued genetic testing while patient 1 declined, revealing a heterozygous R320S mutation in the TR-beta protein. Further testing and genetic counseling were offered to other family members. Propranolol and levothyroxine supplementation were titrated accordingly; triiodothyronine administration was attempted but did not alleviate symptoms. These two cases demonstrate the increased risk of autoimmune thyroid disorders in patients with RTHβ and the unique challenges they pose in accurate diagnosis. Autoimmune thyroiditis in RTHβ, with goiter, elevated T4 and elevated T3 levels, can be easily confused with Grave’s disease, especially when TSH is suppressed during active thyroiditis. Timely diagnosis can aid in targeted management of sequelae, prevent ineffective treatments for comorbid conditions which may mimic other diseases, and provide anticipatory/preventive guidance for family members to help with screening. Presentation: 6/1/2024

7633 Novel CASR Gene Mutation in a patient with Familial Hypocalciuric Hypercalcemia and Papillary Thyroid Cancer

Abstract Disclosure: A. Parihar: None. E.S. Nylen: None. S.M. Gandhi: None. Familial Hypocalciuric Hypercalcemia (FHH) is predominantly caused by loss-of-function mutations in the calcium-sensing receptor (CaSR) characterized by a benign elevation in calcium and PTH which can be mistaken for primary hyperparathyroidism (PHPT). Missense mutations in the CaSR gene causing FHH have been documented but not much is known regarding their clinical significance. We describe a patient with FHH found to have a novel variant mutation. A 37-year-old male with hypogonadism and fatty liver was incidentally found to have hypercalcemia suggestive of PHPT with elevated PTH (102-114 pg/ml), normal vitamin D, and Fractional Excretion of Calcium (FECa) of 0.014. His father also had hypercalcemia and had undergone parathyroid surgery. The patient denied kidney stones and had a normal bone density. Subsequent Sestamibi and 4D CT scan suggested parathyroid adenoma on the left mid-lower pole of the thyroid. Neck ultrasound also showed a left 1.2 x 1 x 1 cm thyroid nodule as well as a left neck mass with calcifications. Fine needle aspiration was positive for metastatic Papillary thyroid cancer(PTC) in the left neck mass and patient underwent total thyroidectomy along with subtotal parathyroidectomy and lateral neck dissection. Thyroid pathology confirmed multifocal PTC with lymph node involvement that were BRAF V600 positive. Parathyroid pathology was benign hyperplasia. The PTH level decreased appropriately intraoperatively (69%), but postoperatively a rise was noted with levels remaining 70-90 pg/ml with normal calcium levels. Repeat FECa was 0.007, supporting the diagnosis of FHH. Given patient’s father also had hypercalcemia, genetic testing was pursued. This revealed CaSR gene missense mutation (c.1382T&amp;gt;C p.Leu461Pro, heterozygous). This variation is not present in population databases and has been classified as a variant of uncertain significance. It can be difficult to distinguish PHPT from FHH based on FECa as in this case. The patient also had PTC which is not known to be associated with FHH. Due to uncertain significance of this novel CaSR missense mutation, long term follow-up and further familial genetic testing will help better understand clinical implications. Presentation: 6/2/2024

Utility of Sonoelastography and Magnetic Resonance Imaging in Characterization of Thyroid Nodules.

To evaluate thyroid nodules with sonoelastography and magnetic resonance imaging (MRI). The study included 28 patients with 40 thyroid nodules. Clearance was obtained from the institute's ethical clearance committee. Patients with pure cystic nodules or nodules with eggshell calcification, diffuse thyroid pathology (such as Graves' disease, Hashimoto's thyroiditis, De Quervain thyroiditis, and Riedel's thyroiditis), inaccessible nodules via fine needle aspiration cytology (FNAC), or patients with a history of thyroid gland surgery were excluded from the study. Strain elastography was performed on a Phillips iU22 machine, producing qualitative color-coded strain maps (graded using the Rago 5-point system) and semiquantitative strain ratios. MRI was performed on a Phillips ACHIEVA 1.5T magnet with a head and neck coil. Rago scores statistically correlated (χ2 = 18.052, p < 0.001) with malignant nodules, and using the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUROC) for the mean strain ratio predicting malignant outcomes was 0.88 [95% confidence interval (CI): 0.767-0.992], which was also statistically significant (p < 0.001). A cutoff of mean strain ratio ≥2.48 predicted malignant outcomes with 100% specificity. T2 signal intensity ratio (SIR) and apparent diffusion coefficient (ADC) values were not statistically significant in predicting malignant outcomes. Kinetic curves were statistically significant for Rago scores (χ2 = 11.356, p = 0.045); however, no significant difference was found in predicting malignant outcomes. We concluded that sonoelastography, along with grayscale ultrasound, is a useful noninvasive technique for predicting histological outcomes. However, MRI should largely be reserved as a problem-solving tool rather than a standalone imaging modality. The kinetic curves show some degree of overlap between histologically distinct diseases, and thus large-scale multicenter trials are needed for further standardization.

Tight Junctions and Cancer: Targeting Claudin-1 and Claudin-4 in Thyroid Pathologies.

Purpose: Claudins are tight junction proteins partaking in epithelial-mesenchymal transition and cancer progression. In this study, we investigated the expression patterns of claudin-1 and claudin-4 in thyroid pathologies, discussed their links with the pathogenesis of thyroid cancers, and reviewed the therapeutic potential of targeting claudins in cancers. Methods: The research group 162 cores of thyroid samples from patients (70 female and 11 male) diagnosed with thyroid adenoma, goiter, papillary, medullary, and anaplastic thyroid cancers. All samples were stained for the expression of claudin-1 and claudin-4, and the analysis of IHC was performed. Results: Goiter samples showed negative claudin-1 and mostly positive expression of claudin-4. Papillary thyroid cancer and thyroid adenoma showed positive expression of claudin-1, while claudin-4 was positive in papillary thyroid cancers, goiters, and adenomas. In The Cancer Genome Atlas cohort, claudin-1 and claudin-4 were overexpressed in papillary thyroid cancer compared to normal thyroid tissues. Patients with high claudin-1 expression had significantly lower 5-year overall survival than patients with low claudin-1 levels (86.75% vs. 98.65, respectively). In multivariate analysis, high claudin-1 expression (HR 7.91, CI 95% 1.79-35, p = 0.006) and advanced clinical stage remained statistically significant prognostic factors of poor prognosis in papillary thyroid cancer. Conclusions: The pattern of claudin-1 staining was pathology-specific and changed between cancers of different histology. This phenomenon may be associated with the different pathogenesis of thyroid cancers and early metastasis. The loss of claudin-1 and claudin-4 characterized more aggressive cancers. Several studies have shown the benefits of targeting claudins in cancers, but their implementation into clinical practice requires further trials.

Influence of stress on cellular immunity in patients with autoimmune thyroid pathology

Influence of stress on cellular immunity in patients with autoimmune thyroid pathology

Cytological Features and Mimickers of Thyroid Gland Sarcomas: A Case-Based Study.

Sarcomas of thyroid glands represent a distinctive subset of rare and perplexing anomaly that present a challenges in the field of thyroid pathology. Thyroid sarcomas, primary or secondary, are exceptionally rare with only a handful of case reports documented so far. The challenges lie in the fact that certain primary thyroid malignancies of epithelial origin may exhibit spindle cell morphology, making them difficult to differentiate from thyroid sarcomas. Despite the morphological similarities, discerning between these entities is crucial due to their distinct treatment and management implications. This report documents a series of unusual types of sarcoma in the thyroid gland. The aim is to explore the peculiarities of these lesions, the diagnostic challenges faced as well to study the potential implications for both clinicians and patients.

Complicações pós tireoidectomias: revisão narrativa

Introduction: Thyroid disorders are one of the most prevalent endocrine disorders, with thyroidectomy being the most common endocrine surgery for malignant and benign thyroid diseases. Thyroidectomy, despite its effectiveness, is a delicate procedure due to the proximity to important structures, such as the nerves, the lymph nodes and the parathyroid glands. Thus, the incidence of surgical complications is influenced by the extent of the surgery, the thyroid pathology, the anatomical differences, in addition to the surgeon's experience and the association with other procedures. Objective: To carry out a survey regarding the main complications after thyroidectomy and the factors related to the manifestations. Methodology: The literature review was carried out over the months of January and March 2023, through the PubMed, BVS and LILACS databases, using the terms validated by the DeCS “Thyroidectomy”, “Postoperative Complications” and “Postoperative Period”. Results: Eighteen studies were used in the writing of this article after applying the inclusion and exclusion criteria and, subsequently, a table was made with their main findings. Hypocalcemia, hypoparathyroidism and recurrent laryngeal nerve injury are the most common complications after thyroidectomy, the latter being the most serious, with different incidences, causes and prevention. Regarding risk factors, female gender, involuntary parathyroidectomy, parathyroid autograft, surgical extension, and central lymph node dissection were related to a higher incidence of complications. The parathyroid hormone levels were used with predictive value for hypocalcemia and hypoparathyroidism. Conclusion: Thyroidectomy is characterized as a well-established procedure in the medical community, however its approach can bear complications. Studies emphasize hypocalcemia, hypoparathyroidism and recurrent laryngeal nerve injury as the most prevalent, in addition to addressing their causes and risk factors. However, further studies are needed to validate means of prevention to ensure the maintenance of patients' quality of life.

Risk of malignancy in thyroid nodules with increased 11C-Choline uptake detected incidentally on PET/CT: A diagnostic accuracy study.

The purpose was to evaluate the pathological nature of focal thyroid uptake seen in 11C-Choline PET/CT performed for prostate cancer. The study was IRB-approved. All 11C-Choline PET/CT exam reports for studies performed between January 01, 2018, and July 30, 2021, in male patients with prostate cancer in our institution were retrospectively reviewed. Exams with "focal thyroid uptake" on their final report were selected. Patients with surgery or ablation in the thyroid prior to the PET/CT, proven parathyroid adenomas or absent thyroid ultrasound were excluded. Repeated PET/CT exams of same patient were excluded. PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) of the focal thyroid uptake. Available thyroid ultrasound images, cytology and pathology reports were reviewed. Statistical analyses were performed. Out of 10,047 sequential 11C-Choline PET/CT studies, 318 reports included "focal thyroid uptake." About 128 of these studies were repeat exams and were excluded. Additional 87 patients were excluded, because the uptake was determined to be adjacent, rather than confined to the thyroid gland. Out of the remaining 103 patients, 74 patients had focal thyroid uptake and concurrent thyroid sonographic evaluation. Out of the 74 focal uptakes evaluated with ultrasound, 21 were presumed benign thyroid nodules based on the ultrasound and 53 had further evaluation with biopsy. Sixty three nodules were benign (21 presumed benign on ultrasound and 42 cytology or surgical pathology-proven), 9 nodules were malignant and 2 remained indeterminate. There was no significant difference between the SUVs of the benign and malignant groups (P > .3). In this retrospective study of patients with prostate cancer who underwent 11C-Choline PET/CT, we identified a group of patients who underwent thyroid ultrasound for incidental finding of focal 11C-Choline thyroid uptake. Incidence of malignancy in this group was 12%. Therefore, further investigation with ultrasound and possibly ultrasound-guided biopsy may be warranted when a choline avid thyroid nodule is found incidentally on choline PET.

Enhanced Differentiation of Amiodarone-Induced Thyrotoxicosis Types Using Semi-Quantitative 99mTc-MIBI Uptake Analysis: A Pilot Study.

BACKGROUND Technetium (99mTc)-labelled Methoxy-2-Isobutylisonitrile (MIBI) is a diagnostic lipophilic cationic radiotracer used to evaluate the cardiac, breast, thyroid, and parathyroid pathology. This study aimed to evaluate the role of MIBI combined with Tc-99m pertechnetate thyroid scintigraphy, thyroid ultrasonography, and measurement of thyrotropin, thyroid hormones, and autoantibodies to subtype amiodarone-induced thyrotoxicosis (AIT) and the contribution of semi-quantitative analysis of MIBI uptake. MATERIAL AND METHODS This cross-sectional study included 36 patients with AIT who underwent thyrotropin, thyroid hormone, and autoantibody analysis using chemiluminescent method, ultrasonography, pertechnetate, and MIBI thyroid scintigraphy with semi-quantitative uptake, including calculation of the target-to-background ratio (TBR) with 2 different background regions. The MIBI washout rate (WR) was analyzed in all groups. Statistical analysis was performed using descriptive statistics, correlations, and the receiver operating characteristic curve - area under the curve (ROC-AUC). The results were compared with the control group. RESULTS Based on visual and semi-quantitative analyses, patients were successfully categorized into AIT groups (AIT-1, AIT-2 and AIT-3) but the latter method enabled better differentiation of MIBI uptake between all groups. Additionally, ROC-AUC analysis determined cutoff values which enabled discerning between AIT-1 and AIT-2 groups, and AIT-1 and AIT-3 groups. WR showed no significant difference between all AIT groups and controls (P>0.05). CONCLUSIONS Visual MIBI analysis enabled differentiation between AIT-1 and 2 groups, but the method was substantially improved with semi-quantitative analysis, especially in defining AIT-3 group. However, multicenter collaboration with larger studies is needed to standardize the method and obtain more accurate and consistent results.

MULTIFRACTAL ANALYSIS OF POLARIZATION MAPS OF ELLIPTICITY OF MICROSCOPIC IMAGES OF BLOOD SMEARS AND DIFFERENTIAL DIAGNOSIS OF THYROID GLAND PATHOLOGY

Among the numerous biomedical diagnostic applications of the soft matter structure,Mueller- matrix polarimetry of the optical anisotropy of biological tissues occupies animportant place. Various Mueller- matrix polarimetry systems have been developed toimplement the diagnostic tasks.The aim of the study – to conduct a comparative analysis of the effectiveness of themultifractal processing method of polarization ellipticity maps of digital microscopicimages of supramolecular protein networks of polycrystalline blood smears in orderto determine new objective criteria (markers) of digital laser histological differentialdiagnosis of the thyroid gland pathology.Material and methods. Four observation groups were formed: 1. Control group – healthydonors (51 people). 2. Patients with nodular goiter (51 patients). 3. Patients with autoimmunethyroiditis (51 patients). 4. Patients with papillary cancer (51 patients). A comparative analysisof the effectiveness of the statistical and multifractal processing methods of polarizationellipticity maps of digital microscopic images of supramolecular protein networks ofpolycrystalline blood smears was carried out in order to determine new objective criteria(markers) of digital laser histological differential diagnosis of the thyroid pathology. Results. A comprehensive statistical and multifractal analysis of polarization ellipticitymaps of experimental blood samples of donors and patients with nodular goiter,autoimmune thyroiditis, and papillary cancer was performed. Objective statistical andmultifractal markers for differential diagnosis of the thyroid gland pathology weredetermined. An excellent level (~96 %-98 %) of the balanced accuracy of the multifractalanalysis method of polarization maps of blood for minimally invasive differentiation ofpathological conditions has been demonstrated.Conclusions. 1. The most optimal statistical markers of the method of mapping ellipticitymaps of polarization of digital microscopic images of blood smears were found to bethe most optimal, and a good diagnostic capacity of diagnosis (~87.3 %-88.3 %) anda satisfactory level (~78.4 %-81.4 %) of differentiation of thyroid pathology wereestablished. 2. Multifractal markers of the mapping ellipticity maps method of polarizationof digital microscopic images of blood smears were found to be the most optimal and anexcellent level (~96 %-98 %) of the balanced accuracy of differential diagnosis of thethyroid gland pathologies was established.