Lymphocytic Thyroiditis Research Articles

Warthin-like Papillary Thyroid Carcinoma: A Case Report and Review of the Literature.

Warthin-like subtype of papillary thyroid carcinoma (WLPTC) is a rare subtype of papillary thyroid carcinoma. This PTC subtype shows some pattern resemblance to Warthin tumors of the salivary gland, which confers its name but is a not genetically similar to salivary Warthin tumor, with the most frequent genetic change in WLPTC being BRAF p.V600E, the most frequent genetic driver of PTC. Warthin-like subtype of papillary thyroid carcinoma is found to have a favorable prognosis. We report a 44-year-old woman who presented with anterior neck swelling and elevated levels of antithyroid peroxidase antibodies. Fine-needle aspiration cytology showed features of papillary thyroid carcinoma and lymphocytic thyroiditis. On histopathological examination, thyroid follicular cells have oncocytic cytoplasm with infiltration of the tumor and fibrovascular cores by a dense lymphoplasmacytic infiltrate. Numerous multinucleated giant cells in the tumor are a notable feature. The final diagnosis is Warthin-like papillary thyroid carcinoma arising in association with chronic lymphocytic (Hashimoto) thyroiditis. Along with this case report, we perform a literature review of WLPTC between 2010 and 2024.

Thyroid hormones in female and male reproduction with special reference to dogs and cats

Thyroid hormones have an important function in numerous physiological processes in humans and animals, including the regulation of metabolism, growth and development of individual and reproductive function. The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), have a direct effect on the reproductive organs and an indirect effect in interaction with other hormones. Thyroid hormones influence the reproductive system by regulating metabolism and tissue development of the ovaries, uterus and placenta. Changes in the serum concentrations of T3 and T4 lead to disturbances in overall body function. Thyroid dysfunction, including hypothyroidism and hyperthyroidism, can lead to significant reproductive problems. The aim of this review was to describe the functions of thyroid hormones and the effects of hypothyroidism and hyperthyroidism on the animal reproductive system. Hypothyroidism is often caused by autoimmune diseases such as lymphocytic thyroiditis, and is associated with later puberty, reduced fertility and abnormalities in reproductive organ development. Hypothyroidism can lead to a prolonged interval, absent cycles, silent oestrus cycles, prolonged oestrus bleeding, and a lack of libido, with the occurrence of infertility, miscarriages, stillbirths and mummified foetuses. In males, hypothyroidism leads to a decrease in libido, semen quality, ejaculate volume, testicular atrophy, hypospermia and azoospermia. Hyperthyroidism, on the other hand, is usually the result of thyroid cancer, which produces excessive amounts of thyroid hormones. Increased concentrations of thyroid hormones lead to disturbances in the physiological balance of reproductive hormones, irregular oestrus cycles, anovulation and reduced fertility, as well as a decrease in the weight of the ovaries and the number of healthy follicles, with a simultaneous increase in the number of atretting follicles. The effects of hyperthyroidism on male fertility include disorders of spermatogenesis, changes in sex hormone levels and changes in sperm quality, such as hypospermia, oligozoospermia, asthenozoospermia and teratozoospermia. It is important to diagnose and treat thyroid disorders in time in order to prevent negative effects on fertility and reproduction in animals.

Diagnostic significance of ultrasound characteristics in discriminating follicular thyroid carcinoma from adenoma

BackgroundFollicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland and has a greater propensity for haematogenous metastasis. However, the preoperative differentiation of FTC from follicular thyroid adenoma (FTA) is not well established. Certain ultrasound characteristics are associated with an increased risk of thyroid malignancy, but mainly for papillary thyroid cancers and not for FTC.ObjectivesThis retrospective study aimed to evaluate the ultrasound characteristics of FTC and the value of ultrasound characteristics in differentiating FTC from FTA.MethodsA total of 96 patients with pathologically confirmed FTC or FTA who underwent preoperative thyroid ultrasound were included in this study. The ultrasound and pathological characteristics were evaluated.ResultsOur data revealed that the incidences of lesions with tubercle-in-nodule, spiculated/microlobulated margins, mixed vascularization, egg-shell calcification, central stellate scarring, extension toward the capsule and chronic lymphocytic thyroiditis were significantly higher in the FTC group (all p < 0.05). After adjusting for confounding factors, lesions with mixed vascularization (odds ratio [OR]: 2.038, P = 0.019), central stellate scarring (OR: 87.992, P = 0.007), extension toward the capsule (OR: 22.587, P = 0.010), and chronic lymphocytic thyroiditis (OR: 9.195, P = 0.006) were independently associated with FTC. Furthermore, combined with chronic lymphocytic thyroiditis, mixed vascularization, central stellate scarring, and extension toward the capsule showed high discriminatory accuracy in predicting FTC (AUC: 0.914; sensitivity: 96.5%; specificity: 71.8%; p < 0.001).ConclusionsIn combination with chronic lymphocytic thyroiditis, mixed vascularization, central stellate scarring, and extension toward the capsule have greater accuracy in differentiating FTCs from FTAs.

A study of autoimmune thyroid disease in pregnant women and its effect on fetal and maternal outcome

ABSTRACT Introduction: Anti-thyroid antibodies not only cause thyroid dysfunction but have independent adverse outcomes in the fetus and mother during pregnancy and after birth. Chronic lymphocytic thyroiditis as a presentation of immune system deregulation may be associated with a generalized activation of the immune system at the fetus–maternal unit, the placenta. This interference could be associated with pregnancy morbidities in m o t h e r a n d fetus. This study was done to find out the frequency of autoimmune thyroid disease and its effect on maternal and fetal outcomes in a tertiary care facility in Jharkhand. Method: This is an Observational Prospective Study done during an 18-month period on 254 pregnant women in their second trimester who came to the antenatal clinic (ANC) clinic with singleton pregnancy at RIMS Ranchi. Result: 222 (87.4%) out of the 254 pregnant women had anti- TPO antibodies less than 35 IU/ml. Anti-thyroid peroxidase (anti-TPO) antibody positivity with values greater than 35 IU/ml was found in 32 patients (12.6%). Anti-TPO antibody mean value was 22.54 ± 19.67 IU/ml. Among the 222 individuals who tested negative for the anti-TPO antibody, 7 (3.3%) had miscarriages, 182 (88.3%) gave birth vaginally, and 33 (14.9%) underwent a cesarean section. Of the 32 individuals who tested positive for the anti-TPO antibody, 2 (6.3%) had miscarriages, 24 (75.0%) had vaginal deliveries, and 6 (18.8%) had cesarean sections. Using the Chi-square test, a P value of 0.549 was calculated, indicating statistical insignificance (Pearson Chi-square test value = 0.200a). Conclusion: Anti-TPO antibody positivity was significantly related to miscarriage and anemia. Other complications like preterm delivery, pre-eclampsia, and low birth weight were higher in anti-TPO antibody-positive patients as compared to anti-TPO antibody-negative patients. However, these findings were not statistically significant.

Chronic Lymphocytic Thyroiditis is a Protective Factor for Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Propensity Score Matching Analysis.

Aims/Background The connection between lymph node (LN) metastases in papillary thyroid carcinoma (PTC) and chronic lymphocytic thyroiditis (CLT) has been examined in a number of prior investigations. However, there is ongoing debate over the effect of CLT on LN metastasis in PTC. In order to explain the relationship between CLT and LN metastasis more convincingly, we aimed to retrospectively review clinical data to investigate the correlation between CLT and LN metastasis in PTC using propensity score matching (PSM). Methods Data on PTC patients at Wenzhou Central Hospital were collected retrospectively between 1 January 2018, and 31 March 2022. The patients were split into two groups based on whether they had CLT or not. The clinicopathological characteristics of the two groups were compared using a PSM analysis. The relationship between CLT and LN metastases was analyzed using logistic regression analysis. Results Among the 773 PTC patients collected and examined, 213 showed simultaneous CLT. Prior to PSM, patients with CLT displayed a significantly lower incidence of LN metastasis (34.3% VS 44.8%, p = 0.008), a lower metastatic LN ratio (0 (0, 0.17) VS 0 (0, 0.38), p = 0.011), and a greater number of LNs dissected (7 (5, 11) VS 5 (3, 7), p < 0.001). These differences persisted after the PSM of 208 pairs. After PSM, patients with CLT displayed a significantly lower incidence of LN metastasis (35.0% VS 44.7%, p = 0.045), a lower metastatic LN ratio (0 (0, 0.17) VS 0 (0, 0.33), p = 0.038), and a higher number of dissected LNs (7 (5, 11) VS 5 (3, 7), p ≤ 0.001). Additionally, the multivariate logistic regression analysis indicated that CLT had a protective role against LN metastasis in both the matched group (odds ratio (OR), 0.62; 95% confidence interval (CI): 0.39-0.96; p = 0.032) and the unmatched group (OR, 0.63; 95% CI: 0.44-0.91; p = 0.014). Conclusion Our data indicate that CLT may protect against LN metastases in patients with PTC. Patients having PTC with coexisting CLT have fewer LN metastases, a greater number of LNs dissected, and a lower metastatic LN ratio.

Evaluation of spexin levels in euthyroid patients with Hashimoto thyroiditis and its relation to autoimmunity.

Hashimoto thyroiditis (HT) is chronic lymphocytic thyroiditis. Cytokines and chemokines such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-1 beta originating from immune cells are involved in the etiopathogenesis of HT. Spexin (SPX) is a recently identified novel peptide hormone consisting of 14 amino acids and has been demonstrated in follicle epithelial cells in thyroid tissue. SPX has been shown to affect the inflammatory response and play a role in its regulation in various diseases. There is a need for markers for diagnosis and treatment of HT patients with negative antibody levels. We found that there is no study in the literature that investigates the HT and the role of spexin in this inflammatory process. Forty-five patients aged 18 to 70 years with HT or newly diagnosed HT and 42 healthy subjects as the control group were included in the study. Patients in the HT group were divided into 3 categories according to ultrasound findings. Mild heterogeneity was called grade 1 (G1), moderate heterogeneity was called grade 2 (G2), and high heterogeneity was called grade 3 (G3). Laboratory parameters and anthropometric measurements of all patients participating in the study were performed, and SPX was measured by the ELISA method. There was no significant difference between the HT and control groups in terms of SPX levels (P = .27). In HT subgroup analysis, SPX levels were found to be borderline statistically significantly higher in the G2 group, where antibody levels were higher compared to other groups (P = .061). In our study, we evaluated SPX levels in HT patients, which has never been done before in the literature. We found high SPX levels in HT patients with high antibody levels. Multicenter studies with high case series, especially at the tissue level, are needed to fully explain the role of SPX in HT immunoetiopathogenesis and to understand immune-checkpoint pathways more clearly.

Molecular Profiling and Surgical Outcomes in Indeterminate Thyroid Nodules: Experience from a Tertiary Care Center

Abstract Introduction/Objective This study examines molecular results(MR) and surgical follow-up(SFU) of cytologically- indeterminate thyroid nodules. Methods/Case Report Atypia-of-undetermined significance/suspicious-for-follicular-neoplasm cases that underwent Quest/ThyroSeq molecular testing between 2015-2022 were analyzed for MR, SFU and lymph node metastasis(LNM). Results (if a Case Study enter NA) 417 cases(Quest=192, ThyroSeq=225). 59% had SFU. 43% malignancy rate.SFU for Quest(49%): non-neoplastic(NNP)=20%, neoplastic(NP)=80%. MR in these cases:NRAS=48, HRAS=19, BRAF=15, KRAS=8, RET/PTC=3, PAX8=2. SFU: papillary thyroid carcinoma(PTC)=35, non-invasive-follicular-thyroid- papillary-neoplasm with papillary-like nuclear features(NIFTP)=20, thyroid nodular follicular disease(TFND)=18, follicular adenoma(FA)=10, follicular carcinoma(FC)=5, oncocytic carcinoma(OC)=1, lymphocytic thyroiditis(LT)=1. Surgical-molecular correlation(SMC): PTC in 3/3 RET/PTC-mutated, 14/15 BRAF-mutated cases. 1 TFND was BRAF- positive. RAS-mutated category: NIFTP=20,PTC=18,TFND=17,FA=9, OA=5, FC=5, LT=1. In RAS-mutated PTCs, NRAS was most common(n=13), followed by HRAS(n=4) and KRAS(n=1). 2 PAX8-mutated cases showed FA and OC. 9/41 malignant cases, all PTC, had LNM, MR:BRAF=6, HRAS=2, RET/PTC=1.SFU for ThyroSeq(68%): NN=10%, NNP=90%. MR:NRAS=34, copy number alterations(CNAs)=25, HRAS=14, BRAF=13, KRAS=11, gene expression alterations(GEA)=7, THADA+IGF2BP3=7, CNAs Hurthle cell type(HCT)=6, EIF1AX=6, DICER1=4, PAX8- PPARG fusion=4, CNAs+GEA=3, NTRK3=3, TERT=2, RAS+EIF1AX=2, TERT+CNAs=2, EIF1AX=1, EZH1=1, RET/PTC1 fusion=1, ALK=1, BRAF K601E=1,RAS+TERT=1, RAS+TERT+PTEN+EIF1AX=1, TERT+BRAF=1, TERT+EIF1AX=1,TP53+CNAs=1. SFU:PTC=39, NIFTP=31, OA=21, FA=20, papillary microcarcinoma(PMiC)=13, TFND=10, OC=7, LT=6, FC=5, poorly differentiated carcinoma(PdC)=1.10/13 BRAF-mutated cases were PTC, other 3 PMiC. SFU of RAS-mutated cases(n=59):TFND=6, LT=4, NIFTP=19, FA=8, OA=4, PTC=13, PMiC=2, FC=2. RAS mutations in PTC: KRAS=6, HRAS=4, NRAS=3. SFU of CNAs-HCT: OA=3, OC=2, TFND=1. Infrequently detected mutations with SFU of PTC:RET/PTC(1/1), ALK(1/1), RAS+TERT(1/1), TERT+BRAF(1/1), BRAF K601E(1/1), RAS+EIF1AX(1/2). SFU of RAS+TERT+PTEN+EIF1AX:PdC. 11/65 malignant cases, all PTC had LNM:BRAF=5, KRAS=3, CNAs=1, EIF1AX=1, TERT+BRAF=1. Conclusion Substantial proportion of cases with positive MR underwent surgical resection. BRAF-positive and CNAs- HCT correlated with PTC and oncocytic neoplasms, respectively. BRAF-positive PTCs had a higher incidence of LNM compared to wild-type cases(46% vs.18%).

Mitophagy Defects Exacerbate Inflammation and Aberrant Proliferation in Lymphocytic Thyroiditis.

Background: Mitochondrial dysfunction in the thyroid due to defective mitophagy has been observed in lymphocytic thyroiditis (LT). However, the effect of impaired mitophagy on the pathogenesis of LT is not well understood. The aim of this study is to investigate the role of mitophagy dysregulation in the thyroid gland. Methods: We analyzed RNA sequencing data of human thyroid glands with/without LT from Genotype-Tissue Expression (GTEx; n = 653) and performed RNA sequencing in thyroid glands of phosphatase and tensin homolog-induced putative protein kinase 1 (Pink1) knock-out and wild-type mice. We evaluated the phenotypic and histopathologic characteristics of the human (n = 16) and mouse thyroids. Additionally, we assessed cell proliferation, reactive oxygen species (ROS) production, and cytokine secretion of human thyroid epithelial cells (HTori-3) treated with PINK1 siRNA or a mitophagy inhibitor. Results: We found that expression of PINK1, a key regulator of mitophagy, was compromised in human thyroids with LT. Thyroid glands of Pink1-deficient mice exhibited increased inflammatory responses and nodular hyperplasia. Furthermore, mitophagy defects led to the production of pro-inflammatory cytokines and ROS in thyroid cells, resulting in immune cell recruitment. Notably, these mitophagy defects upregulated both the RNA expression and protein secretion of amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, in thyroid cells, while decreasing the protein expression of cAMP response element-binding protein (CREB), a transcription factor that suppresses AREG transcription. Finally, we demonstrated that aberrant cell proliferation in thyroid cells, driven by mitophagy defects, was mitigated after treatment with cetuximab, an EGFR inhibitor. Conclusions: In this study, we observed that mitophagy defects in the thyroid not only intensify inflammation through the accumulation of ROS, cytokine production, and immune cell recruitment but also contribute to hyperplasia via the EGFR pathway, facilitated by increased secretion of AREG from thyroid cells.

7923 Latent Autoimmune Diabetes of Adulthood (LADA) Complicating Common Variable Immunodeficiency (CVID)

Abstract Disclosure: L. Pathak: None. M.G. Jakoby: None. Introduction: CVID is caused by defective B-lymphocyte maturation that results in immunoglobulin deficiency. Patients with CVID are predisposed to both infections and autoimmune disorders, with approximately 20% experiencing at least one autoimmune complication. We present a patient with LADA complicating CVID. Case A 31-year-old woman was referred for newly diagnosed diabetes mellitus (DM). Medical history was notable for primary hypothyroidism and apparent chronic lymphocytic thyroiditis. A presumptive diagnosis of type 2 DM was made due to obesity, and the patient was treated with metformin. However, she could not tolerate the medication due to diarrhea. Semaglutide was substituted and tolerated without adverse effects. During the first six months of treatment with semaglutide 0.5 mg weekly, HbA1c improved from 6.4 to 5.6%. However, in the next six months, HbA1c increased to 6.6% despite full compliance with medication and stable weight. Anti-glutamic acid decarboxylase (GADA) titer was unequivocally elevated at 69.8 IU/mL (0.0-5.0), though anti-insulin and islet antigen-2 (IA-2) antibodies were undetectable. Insulin glargine was added to the patient’s diabetes regimen, and HbA1c improved to 5.5% three months later. Discussion This patient meets Immunology of Diabetes Society diagnostic criteria for LADA, namely diabetes diagnosed in adulthood (≥ 30 y), elevated diabetes-associated autoantibody titer, and insulin independence for at least six months after diagnosis. Patients with high-titer GADA tend to be younger and have more rapid and significant loss of β-cell function than patients with low GADA titers, and this patient’s rapidly waning glycemic response to semaglutide conforms with this observation. Until recently, autoimmune diabetes in the setting of CVID was thought to be an unusual complication, though the prevalence of type 1 diabetes among CVID patients in the European Society for Immunodeficiency registry is 1.6%, approximately four-fold higher than the general European population. LADA shares genetic features linked to childhood-onset type 1 DM, making it possible or evenly likely that LADA has occurred in cases of CVID, though a careful search of PubMed failed to identify reported cases. This patient illustrates the importance of considering LADA in CVID, particularly with abrupt loss of glycemic response to noninsulin therapeutic agents. Presentation: 6/1/2024

5039 Chronic Painful Hashimoto's Thyroiditis

Abstract Disclosure: S. Ahmed: None. M. Vahidi Rad: None. S.A. Westphal: None. M.D. Whitaker: None. Introduction: Painful Hashimoto thyroiditis is a rare variant of Hashimoto thyroiditis that mostly affects women. Most cases are empirically treated as subacute thyroiditis with corticosteroids, levothyroxine, or nonsteroidal anti-inflammatory drugs. However, no medical treatment may provide sustained pain resolution, so optimal treatment remains unclear. We describe the case of a 40-year-old female with longstanding throbbing anterior neck discomfort that failed medical therapy and her symptoms completely resolved with total thyroidectomy. Case Report: A 40-year-old lady with anterior neck pain centered over the thyroid for more than 16 years, shortly after she delivered her last child. The pain is described as intense, it tends to wax and wane but there is a constant throbbing with occasional radiation to the angle of the jaw. Over the years the pain has gradually worsened and during its flares, the thyroid itself is very tender to the point where she experiences difficulty in swallowing and hoarseness of voice. Complicating the issue is her underlying diagnosis of fibromyalgia, as she tends to experience discomfort in many other areas of her body. However, the neck pain appears to be of a different character. No symptoms of hyper or hypothyroidism. The anterior neck pain has been difficult to alleviate, she has used chronic opioids for it which seems to have helped to some extent, in the past she was on prednisone for 1 month however this made no difference to it. On examination, the thyroid is tender and somewhat firm without lymphadenopathy. Thyroid levels have been consistently normal and the most recent of which was a TSH: 1.48, FT4: 1.4, FT3: 3.5 with negative TPO and thyroid stimulating antibodies. ESR and CRP were unremarkable. Thyroid ultrasound showed mildly heterogeneous parenchyma with no solid nodules or lymphadenopathy. Interestingly she had an elevated thyroid uptake in her scan dated April 1st 2022, 4 hour and 24-hour uptakes were abnormal at 23% and 49% respectively which can be seen with Hashimoto's. She underwent total thyroidectomy and her surgical pathology showed benign thyroid tissue with multiple foci of chronic lymphocytic thyroiditis and hyperplastic nodules. Her pain completely resolved after total thyroidectomy. Discussion: Painful Hashimoto thyroiditis is a rare diagnosis and optimal treatment remains unclear. The painful variant of Hashimoto's thyroiditis should be considered in the differential diagnosis of pain and tenderness of the thyroid which can be managed successfully by surgical treatment. Thyroidectomy not only can lead to alleviation of symptoms but also provides the definitive diagnosis. The risks of surgical intervention must be taken into consideration, especially because painful Hashimoto thyroiditis can be associated with a small fibrous gland; hence, the importance of access to highly skilled, experienced surgeons cannot be overemphasized. Presentation: 6/1/2024

7008 Challenges in the Management of Thyroid Lymphoma - Case Report

Abstract Disclosure: F. Toloza Bonilla: None. P. Veeraraghavan: None. R. Lakhotia: None. M. Roschewski: None. N. Nilubol: None. S. Gubbi: None. J. Klubo-Gwiezdzinska: None. Introduction: Primary thyroid lymphoma is an extremely rare thyroid malignancy accounting for less than 5% thyroid malignancies. The management depends on the histological subtype and tumor staging, typically involving chemotherapy alone or combined with radiotherapy. Although, surgical intervention is generally not recommended, given the potential surgical risks and the absence of additional benefits compared to chemoradiation therapy, it is reserved to obtain tissue diagnosis and to treat compressive symptoms. Clinical Case: A 66-year-old Caucasian female presented with dysphagia to solid food and acute neck swelling for a few weeks. History was negative for fever, weight loss or nocturnal diaphoresis. The patient had a history of primary hypertension, pre-diabetes, and Hashimoto’s hypothyroidism. A neck computed tomography (CT) scan showed a thyromegaly (8.3 x 5.8 cm) and bilateral cervical lymphadenopathy. Thyroid ultrasound showed sub centimeter nodules in the right mid-gland and a heterogeneous and irregular left thyroid lobe. TSH was normal (0.87 mcIU/mL [0.27-4.2]). She was treated for suspected subacute thyroiditis with prednisone for two weeks, showing initial clinical improvement, but symptoms recurred after steroids were stopped. Subsequently, a CT neck and fludeoxyglucose F18 (FDG) positron emission tomography (PET) scan demonstrated FDG avid thyroid enlargement with local adenopathy and rightward tracheal deviation. Lymph node, FNA, core biopsies and molecular testing were consistent with stage IIE MYC/BCL6 rearranged diffuse large B-cell lymphoma as she had no bone marrow or central nervous system (CNS) involvement. The patient’s treatments included four cycles of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab with ibrutinib added after the first cycle and intrathecal methotrexate with cycles 3-6, to reduce the risk of CNS involvement. A 6-month post-therapy follow-up showed complete response (CR) on imaging with symptoms resolution. Four months later, she experienced worsening symptoms, including dysphagia with solids and liquids, and hoarseness despite CR to therapy and stable CT imaging. Laryngoscopic evaluation noted left vocal cord paralysis and extrinsic compression of the tracheoesophageal groove. Patient opted for a left hemithyroidectomy, experiencing excellent symptom relief. Surgical pathology showed findings consistent with a necrotic tumor and residual areas of lymphocytic thyroiditis. No active DLBCL was appreciated. The patient remains in remission and continues to be symptoms-free 24 months post-thyroid lymphoma treatment. Conclusion: While thyroidectomy is not typically recommended as the initial treatment for primary thyroid lymphoma, it emerges as a potentially effective option to manage recurrent or persistent compression symptoms following the completion of medical therapy. Presentation: 6/3/2024

8578 Papillary Thyroid Carcinoma in Autonomous Nodule with Low Risk Characteristics in Adolescent

Abstract Disclosure: A. Aponte Velez: None. M.M. Mangual Garcia: None. Thyroid nodules in children are uncommon but are known to carry a greater risk of malignancy than adult thyroid nodules. Additionally, differentiated thyroid cancer (DTC) in children is more commonly found with extrathyroidal extension and metastases which makes the approach and treatment similar but with important differences. The incidence of DTC in children is increasing, making a personalized evaluation of thyroid nodules in pediatric patients even more valuable. Guidelines recommend evaluation of nodules based on sonographic characteristics rather than size of nodule. However, not having worrisome sonographic characteristics may not be as reassuring as in adult patients. A 13 year old female patient presented with a palpable non tender right sided solid thyroid mass. She had no family history of thyroid cancer or history of irradiation. Thyroid function tests were remarkable for TSH:0.017 and positive thyroid stimulating immunoglobulin. Thyroid Ultrasound findings described heterogenous parenchyma with multiple discrete lesions on right thyroid lobe with a dominant solid isoechoic nodule at upper lobe measuring 2.1 x 3.5 x 1.9cm and a smaller nodule in lower lobe. Thyroid scan demonstrated a large functional hot nodule occupying most of right thyroid lobe with suppression of rest of thyroid parenchyma. Ultrasound guided FNA was performed of this lesion and results were negative for malignancy. Patient underwent total thyroidectomy with pathology report revealing right thyroid nodule encapsulated classical variant of papillary thyroid carcinoma. No lymph node metastases were identified. Non neoplastic thyroid parenchyma revealed chronic lymphocytic thyroiditis. Patient underwent radioiodine therapy with Whole Body Scan post radioiodine therapy demonstrating focal increased radionuclide localization at in region of neck consistent with functional thyroid tissue. There was no evidence of metastatic disease. In children, risk of malignancy is underestimated in ultrasonography and cytology. In this patient, papillary thyroid carcinoma was identified despite being stratified as having low risk of malignancy based on ultrasonography characteristics, hyperfunctioning nodule in scintigraphy study along with negative FNA results. Hyperfunctional nodules are usually reassuring for low risk of malignancy but rarely DTC can be found as in our patient. Guidelines agree that FNA is not recommended in functional nodules as surgical resection is the main therapy in children. However, surgery may be deferred if subclinical hyperthyroidism and low risk sonographic characteristics are present such as in our patient. If surgery had been deferred, based on low risk of malignancy, the risk of progression of disease would have been higher. Prognosis of DTC in children is good but the recurrence rate along with morbidity at such a young age may improve with more studies of DTC in children. Presentation: 6/2/2024

Scary But Innocent Cells—Potentially Helpful Diagnostic Feature for Chronic Lymphocytic Thyroiditis

Scary But Innocent Cells—Potentially Helpful Diagnostic Feature for Chronic Lymphocytic Thyroiditis

The intratumoral infiltration of macrophages is associated with concomitant lymphocytic thyroiditis and possibly worse prognosis in patients with medullary thyroid carcinoma

The intratumoral infiltration of macrophages is associated with concomitant lymphocytic thyroiditis and possibly worse prognosis in patients with medullary thyroid carcinoma

Efficacy of Follicular Cell Pattern Analysis in Thyroid Fine-needle Aspiration Cytology Evaluation.

Fine-needle aspiration cytology (FNAC) is widely utilized for thyroid lesion diagnosis but faces challenges such as sample inadequacy and overlapping cytological features. This study examines how accurately these patterns correlate with histopathological diagnoses, shedding light on FNAC's limitations and diagnostic potential. To study the application of the architectural pattern of follicular cells in the interpretation of thyroid lesions and to demonstrate the diagnostic accuracy (DA) of FNAC. Cross-sectional study carried over 1 year. A total of 110 cases were reviewed by the cytopathologists. The prominent follicular cell architecture, namely macrofollicular, microfollicular, papillary, trabecular, three-dimensional clusters, and dispersed cells, was described in each case. In addition to these patterns, cellular morphology and background features were also noted, and a final cytological diagnosis was established. The cytology diagnosis was correlated with the histopathological diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, DA of FNAC in diagnosing nonneoplastic and neoplastic lesions. Macrofollicular pattern was seen in 80.26% of colloid goiter cases. Microfollicular pattern was observed in 72.2% of follicular neoplasm. About 62.5% of papillary thyroid carcinomas showed a papillary pattern. The trabecular pattern was seen in 42.86% of chronic lymphocytic thyroiditis and 16.67% of follicular neoplasms. The sensitivity and specificity of FNAC in diagnosing neoplastic lesions was 92.59% and 97.59%, respectively. FNAC is a simple, rapid, definite, and cost-effective primary diagnostic tool for thyroid evaluation. Cell architecture pattern is a simple and appropriate approach that complements cell morphology and background details in arriving at the final cytological diagnosis of thyroid lesions.

The effect of vitamin D on the development of Hashimoto's disease and the reduction of the inflammatory process in its course - review

Introduction Hashimoto's disease is an autoimmune chronic lymphocytic thyroiditis. It is a common condition, more frequent in women. Its diagnosis is based on the presence of specific antithyroid antibodies in the patient's blood which lead to the destruction of the thyroid gland. This can result in the development of hypothyroidism, requiring levothyroxine replacement therapy. Aim of the review A summary of the information gathered so far on the involvement of vitamin D in the development and course of Hashimoto's disease. Results The articles analyzed have mixed results. Most of them show a positive correlation between vitamin D and Hashimoto's disease, paying particular attention to the contribution of vitamin D in moderating the inflammatory process in HT. Other studies show significant differences in vitamin D levels between groups with different HT severity. Others show a negative correlation between vitamin D levels and the development of Hashimoto's disease. Conclusions Large well-controlled randomized double blind trials are needed in order to determine the exact role of vitamin D in Hashimoto’s disease.

Mucoepidermoid Carcinoma of the Thyroglossal Duct: Two Rare Entities in a Unique Case Report.

Mucoepidermoid Carcinoma (MEC) of the thyroid represents less than 0.5% of all thyroid neoplasms. Thyroglossal duct cyst carcinoma is a rare condition with only approximately 300 cases reported. A 34-year-old pregnant woman at 37 weeks gestation presented to an endocrinological center for primary autoimmune hypothyroidism. The thyroid ultrasound revealed a pseudonodular pattern. The patient was followed up after two years. She reported a full-term delivery without complications. A new thyroid ultrasound was performed, showing a cystic lesion in the median suprathyroid area, measuring 6 x 9 x 10 mm, not previously reported. After 4 months, the suprathyroid cystic lesion was confirmed by thyroid ultrasound, measuring 6 x 11 x 12 mm. The patient was referred for fine-needle aspiration cytology. Cytological examination showed lymphocytes, red blood cells, and some epithelial aggregates with large cytoplasm and nuclear polymetrism with oxyphilic aspects. The patient underwent the Sistrunk procedure for the suprathyroid lesion. The histological examination revealed lymphocytic thyroiditis in heterotopic thyroid tissue with solid cell nest, epidermoid epithelium, and mucus-secreting cells suggestive of low-grade mucoepidermoid carcinoma. The immunohistochemistry study was positive, exhibiting thyroid transcription factor 1 and cytokeratin-19. No positivity was observed for thyroglobulin, calcitonin, galectin-3, and Hector Battifora mesothelial antigen 1. The recent follow-up examination, 13 months after the surgery, has been found negative for disease recurrence. This is the first case of an MEC occurring within a thyroglossal duct. Considering the age of the patient, the histological diagnosis, and the absence of thyroid nodules and metastasis, we decided on the Sistrunk procedure without total thyroidectomy.

Can thyroid histomorphology identify patients with PTEN hamartoma tumour syndrome?

The phosphatase and tensin homologue (PTEN) hamartoma tumour syndrome (PHTS) is a genetic disorder with variable clinical presentation and increased lifetime risk of multiorgan malignancies. The thyroid gland is commonly affected with follicular nodular disease (FND) and follicular cell-derived carcinomas. Histopathological and immunohistochemical assessment of thyroid disease in PHTS is essential to identify patients at-risk. In all, 30 PHTS patients with available thyroidectomy specimen material (2000-2023) and 31 control patients with FND and "adenomatous nodules" were retrieved. Histologic criteria, including the frequency of adenomatous-type nodules versus hyperplastic-type nodules, background and nodular lipomatous metaplasia, chronic lymphocytic thyroiditis, cytoplasmic clearing of follicular cells in nodules, nodule-in-nodule appearance, and spectrum of nuclear atypia between nodules were evaluated in both cohorts and a Thyroid Histomorphologic PHTS Score (THiPS) system was established with a cutoff of 4 points or higher being considered concerning for PHTS. In all, 27 PHTS (90%) and five control (16.1%) cases had THiPS ≥4. A PTEN immunohistochemical stain was evaluated in 25 cases of each cohort and showed nuclear and cytoplasmic loss of expression in all or most of the nodules of 24/25 PHTS cases. In 3/25 control cases, two with THiPS ≥4, had loss of expression in one to multiple nodules. Conventional papillary thyroid carcinomas in PHTS patients retained PTEN cytoplasmic expression. Our study supports that, although not specific, the finding of multiple histologic features is found more frequently in patients with PHTS compared to the non-PHTS control group. The THiPS system has high sensitivity for thyroid specimens from patients with PHTS.

The Association between Lymphocytic Thyroiditis and Papillary Thyroid Cancer Harboring Mutant BRAF: A Systematic Review and Meta-Analysis.

Background: Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harboring BRAFV600E (PTC-BRAF) confers a worse prognosis, but it is unclear if LT alters prognostic features and recurrence of PTC. Objective: We compared the prevalence of PTC-BRAF with and without LT. The risk of adverse pathological features in (i) PTC in the presence and absence of BRAF mutation, irrespective of LT status, was compared to (ii) PTC in the presence and absence of LT, irrespective of BRAF status. Methods: We searched PubMed, Embase, and Web of Science Core Collection for observational studies published from 2010 to June 2023 on adult patients with PTC. The search strategy yielded 47 studies with relevant data. Data of baseline characteristics, clinicopathological features, and the quality assessment tool were extracted by two reviewers. The study was registered with PROSPERO (CRD42023437492). Results: Of the 47 studies, 39 studies with a total cohort of 28 143, demonstrated that the odds of PTC-BRAF were significantly lower in the presence of LT compared to its absence (odds ratio [OR] 0.53, 95% confidence interval [CI]: 0.48-0.58, p < 0.00001). In PTC-BRAF patients, there was a positive association of central neck nodal disease (CNND), PTC > 1 cm, extra-thyroidal extension, American Joint Committee on Cancer (AJCC) Stage 3-4, and multifocality with pooled ORs of 1.54 (95% CI: 1.16-2.04), 1.14 (95% CI: 0.82-1.58), 1.66 (95% CI: 1.40-1.97), 1.53 (95% CI: 1.35-1.75), and 1.24 (95% CI: 1.11-1.40) respectively, compared to wild-type PTC, irrespective of LT status. In the same studies, PTC with LT patients had lower pooled ORs of 0.64 (95% CI: 0.51-0.81) for CNND, 0.83 (95% CI: 0.73-0.95) for PTC > 1 cm, 0.71 (95% CI: 0.58-0.86) for ETE, 0.84 (95% CI: 0.75-0.94) for AJCC Stage 3-4 compared to PTC without LT, irrespective of BRAF status. PTC recurrence was not affected by BRAF or LT, with pooled ORs of 1.12 (95% CI: 0.66-1.90, p = 0.67) and 0.60 (95% CI: 0.28-1.30, p = 0.20) respectively. Similar results were seen with recurrence expressed as hazard ratio in this limited data-set. Conclusion: The odds of PTC-BRAF are significantly lower in the presence of LT than without. PTC with LT, irrespective of BRAF status, was significantly associated with better prognostic factors. Further studies are required to evaluate if LT inhibits PTC-BRAF, and whether this is relevant to the role of immunotherapy in advanced thyroid cancer.

Iron and ferritin deficiency in women with hypothyroidism and chronic lymphocytic thyroiditis - systematic review.

Iron is one of the essential microelements necessary for maintaining the body's homeostasis. It serves various roles, including being a crucial component in the proper structure of many enzymes and supporting the transport of oxygen and electrons. Its deficiency can lead to anaemia, which is a common clinical condition often associated with thyroid diseases. Iron deficiency is one of the most common nutritional deficiencies, and its prevalence is strongly associated with socioeconomic status. It is the primary cause of anaemia in 42% of children and 50% of women. Importantly, iron deficiency is placed among the top 5 causes of disability in women. Thyroid peroxidase (TPO) is an enzyme essential for the production of thyroid hormones, and iron is a key factor in its proper functioning. Therefore, in the case of iron deficiency, the activity of this enzyme is also reduced. Iron is also a factor that is important in epigenetic modification processes, and its deficiency may contribute to genomic changes potentially promoting the development of autoimmune thyroid diseases. Adequate supplementation in patients with Hashimoto's disease is one of the crucial elements of effective therapy. In addition to iodine, selenium, and magnesium supplementation, attention should be paid to proper iron intake. Iron is an element that is a component of the heme enzyme- thyroid peroxidase, which owes its activity to the binding of haem, and its function is the production of thyroid hormones. Iron can be delivered to the body in haem and non-haem forms. The haem form is found particularly in haemoglobin-rich red meat, but also in eggs, fish, and poultry. On the other hand, non-haem iron can be found in legumes, grains, fruits, and vegetables. Our study aimed to gather and summarise knowledge from scientific literature regarding iron deficiency anaemia and its association with hypothyroidism in women, as well as the possible mechanisms and pathogenesis of these conditions. The paper also aims to highlight that considering the high risk of iron deficiency, assessing iron status along with ferritin should be an integral part of additional diagnostic measures in cases of hypothyroidism, particularly Hashimoto's disease.