Search Results (84)

Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging techniques, such as ultrasound and 99mTc-sestamibi scintigraphy, are standard, advanced second-line imaging modalities like 18F-fluorocholine PET/CT (FCH-PET) and four-dimensional computed tomography (4D-CT) have emerged as valuable tools when initial diagnostics are inconclusive. Methods: This article provides an updated review and recommendations of the role of these advanced imaging techniques in localizing parathyroid adenomas. Results: FCH-PET has shown exceptional sensitivity (94% per patient, 96% per lesion) and is particularly useful in detecting small or ectopic adenomas. Despite its higher sensitivity, it can yield false positives, particularly in the presence of thyroid disease. On the other hand, 4D-CT offers detailed anatomical imaging, aiding in the identification of parathyroids in challenging cases, including recurrent disease and ectopic glands. Studies suggest that FCH-PET and 4D-CT exhibit similar diagnostic performance and could be complementary in preoperative planning of most difficult situations. Conclusions: This article also emphasizes a multimodal approach, where initial imaging is followed by advanced techniques only in cases of uncertainty. Although 18F-fluorocholine PET/CT is favored as a second-line option, 4D-CT remains invaluable for its high spatial resolution and ability to guide surgery in complex cases. Despite limitations in evidence, these imaging modalities significantly enhance the accuracy of parathyroid localization, contributing to more targeted and minimally invasive surgery. Full article

Endoscopic surgery is useful and helpful especially to access areas with limited visibility. The combination of this technique with innovative approaches could be the solution to improve quality of surgery and patients’ outcome. This study aimed to illustrate how Endoscopic-Assisted Transoral Approach (EATA) can be used to successfully remove specific extracranial tumors with defined characteristics. Eleven patients with extracranial tumors underwent surgical resection using an EATA between 2003 and 2025. All patients underwent clinical examination and fiberoptic laryngoscopy. Preoperative CT and/or MRI was performed in all cases. All patients were successfully treated utilizing an EATA. Histological examination revealed nine parapharyngiomas, comprising five pleomorphic adenomas, two schwannomas, one ectopic thyroid gland, one lipoma, one masticator space schwannoma, and one nasopharyngeal pleomorphic adenoma. No intra-operative nor peri-operatory complications were observed. The only long-term sequela observed was Horner’s syndrome in the two schwannomas originating from the parapharyngeal-carotid space. The mean hospital stay was 2.6 days, while the mean follow-up duration was 9.8 years. The EATA represents a valid surgical technique for the treatment of benign, encapsulated, and non-vascular parapharyngeal space (PPS) tumors exhibiting posterior displacement of major vessels. This approach may also prove beneficial for the management of other benign, encapsulated, and non-vascular tumors located in the nasopharynx and masticator space. Full article

Thyroid nodules are accidentally found in up to 68% of people undergoing neck ultrasound (US) examination, and fine needle aspiration (FNA) is the current gold standard to discriminate between malignancy and benign lesions. Unfortunately, one-third of FNAs are classified as indeterminate, requiring surgery for definitive diagnosis. This leads to high costs and health risks of unnecessary procedures, since malignancies are observed in less than half of operative specimens. This narrative review aims to describe the most innovative multi-omics approach techniques, including genomics, proteomics, and metabolomics, aimed at making the preoperative evaluation of indeterminate thyroid nodules more accurate. The advantages and disadvantages of the techniques are described in detail, and a SWOT (strengths, weaknesses, opportunities, and threats) analysis of the multi-omic approach is provided. Full article

Identifying parathyroid glands during surgery is challenging and time-consuming due to their small size (3–5 mm) and camouflaged appearance in the background of the thyroid, lymph nodes, fat, and other neck structures. For the gland itself, it is also important to differentiate abnormal ones from normal ones. Accidental damage or removal of the normal glands can result in complications like hypocalcemia, which may necessitate lifelong medication dependence, and, in extreme cases, lead to death. The study of autofluorescence optical properties of normal and abnormal parathyroid glands and the surrounding tissue will be helpful for developing non-invasive detection devices. The near-infrared (NIR) autofluorescence characteristics of parathyroid and thyroid tissues have been studied extensively and are now used for parathyroid gland detection during surgery. Additionally, there have been a few reports on the UV-visible light-excited autofluorescence characteristics of these tissues with a focus on spectroscopy. However, there is a lack of high-resolution, side-by-side autofluorescence imaging comparisons of both tissue types under various excitation wavelengths, ranging from visible to NIR. We developed a standalone tabletop autofluorescence imaging system to acquire images of ex vivo specimens in the operating room under different excitation wavelengths: visible 405 nm, 454 nm, 520 nm, 628 nm, and NIR 780 nm. Autofluorescence imaging features of parathyroid adenomas for each excitation wavelength were described and compared. It was found that visible light excites much stronger autofluorescence from parathyroid adenoma tissue compared to NIR light. However, NIR excitation provides the best intensity difference/contrast between parathyroid adenoma and thyroid tissue, making it optimal for differentiating these two tissue types, and detecting parathyroid adenoma during surgery. The high fluorescent site under the NIR 780 nm excitation also generates high fluorescence under visible excitation wavelengths. Heterogeneous fluorescence patterns were observed in most of the parathyroid adenoma cases across all the excitation wavelengths. Full article

Background: Parathyroid neoplasia is a heterogeneous group of tumors, including parathyroid adenoma (PA), atypical parathyroid tumors (aPTs), and parathyroid carcinoma (PC). Differential diagnosis, especially preoperatively, between parathyroid carcinoma and the other two entities is challenging. The purposes of this study were to highlight the main differences between different parathyroid tumors and to evaluate how combined PC suspicion and intraoperative adjuncts can influence surgical decision-making and outcome-related issues. Methods: We performed a retrospective study of a database of patients diagnosed with parathyroid tumors who underwent surgical treatment at our endocrine surgery referral center between June 2019 and July 2024. Demographic, clinical, biochemical, imaging, intraoperative, immunohistochemical, and follow-up data were analyzed. Results: A total of 83 cases were included in our study, divided for analysis into PA (n = 67), aPT (n = 9) and PC (n = 7) subgroups. The clinical profile of the cohort showed a significant difference (p < 0.05) between the PA, aPT, and PC subgroups regarding the presence of palpable tumors (0% vs. 11.11% vs. 14.29%), both bone and kidney involvement (14.93% vs. 44.44% vs. 85.71%), and extensive disease beyond bone and kidney involvement (4.48% vs. 44.44% vs. 71.43%). PTH levels over five times the normal value were present at significantly different rates (p < 0.001), with higher rates in the aPT and PC subgroups (55.56% and 85.71%, respectively) compared with the PA subgroup (7.46%). Also, a significant difference (p < 0.001) was observed when analyzing extreme albumin-corrected serum calcium elevations over 14 mg/dL, with much higher rates in the PC subgroup (71.43%) compared to PA (1.49%) and aPT (33.33%). On preoperative ultrasonography, a significantly higher number of PCs presented diameters ≥ 3 cm (p < 0.001), depth-to-width ratios (D/W) ≥ 1 (p = 0.003), suspicious delineation (p < 0.001), and suspicious echotexture features (p < 0.001), compared to PAs. On preoperative US performed by the surgeon, suspicious features for thyroid cancer were identified in five more patients compared to the four identified by the initial US evaluation, and all (10.84% of all patients) were confirmed on final histopathology as papillary thyroid cancers. Intraoperatively, a significant difference (p < 0.001) regarding parathyroid macroscopic suspicious features, including adhesions to the thyroid gland, was seen between subgroups. When analyzing only cases with en bloc resection, we found that, in all PC cases, a combined preoperative suspicion was present, and in five cases an intraoperative suspicion was raised. Immunohistochemical data showed significantly different median Ki-67 indices between subgroups (1, 2, and 5; p = 0.008) and a different parafibromin staining profile between PC and aPT. Regarding intraoperative neuromonitoring use, a significantly lower incidence of voice changes related to the external branch of the superior laryngeal nerve was observed in the monitoring vs. non-monitoring group (57.14% vs. 12.5%, p = 0.019). Conclusions: Our findings confirm that, in a multimodal and combined diagnostic approach, early pre- and intraoperative PC suspicion can be raised in order to optimize surgical treatment and, thus, favorably influence the outcome. Utilizing all resources available, including intraoperative parathormone determination, laryngeal nerve neuromonitoring, and immunohistochemistry staining, can bring extra benefit to the management of these challenging cases. Full article

Background and Clinical Significance: The concurrent presence of a thyrotropin-secreting hypophyseal adenoma (TSHoma) with a thyroid malignancy, such as papillary thyroid carcinoma (PTC), is exceptionally rare and significantly complicates clinical diagnosis and management. This rare combination raises difficult decisions regarding the treatment sequence and carries the risk of exacerbating either or both conditions. Case report: We present the case of a 59-year-old female patient exhibiting persistent hyperthyroid symptoms with unusually normal TSH levels despite elevated thyroid hormone concentrations. Initial diagnostic imaging revealed a hypophyseal macroadenoma and a diffuse nodular goiter. After the macroadenoma diagnosis, the patient initially refused surgical intervention, and subsequent dopamine agonist therapy proved ineffective. Eight years later, during a routine follow-up, a thyroid ultrasound revealed a diffuse nodular goiter classified as EU-TIRADS 5, and papillary thyroid carcinoma was confirmed through fine needle aspiration biopsy. A total thyroidectomy and subsequent radioactive iodine therapy were performed. However, persistently elevated postoperative TSH levels remained despite high-dose levothyroxine therapy. Due to the increased risk of malignancy recurrence associated with elevated TSH levels, the patient consented to macroadenoma surgery. A successful transsphenoidal macroadenomectomy stabilized the patient’s condition, allowing for the normalization of TSH levels. Conclusions: This case underscores the importance of accurate differential diagnosis and highlights the challenges in managing TSH levels in patients with coexisting thyroid malignancies. With there being no clear guidelines for managing the combination of these conditions, decisions regarding treatment priority should consider the patient’s preferences, the risk of malignancy recurrence or progression, neurological symptoms, and the aggressiveness of the thyroid tumor. Full article

A 49-year-old female presented for nuclear medicine diagnostics of a sonographically suspected parathyroid adenoma dorsal to the cranial pole of the right thyroid lobe. The patient received Tc-99m-pertechnetate and Tc-99m-sestamibi (including SPECT/CT) scans, revealing no sestamibi uptake by the suspected parathyroid adenoma but a ventrally adjacent autonomous thyroid adenoma. Additional F-18-ethylcholine-PET/CT as well as subsequent Tc-99m-sestamibi-SPECT/US and F-18-ethylcholine-PET/US fusion imaging confirmed the suspected diagnosis of simultaneous autonomous thyroid adenoma and parathyroid adenoma. A blood analysis showed additional Graves’ disease. Full article

Background: Oncocytic adenomas (OAs) of the thyroid, previously referred to as Hürthle cell adenomas, are uncommon tumors, particularly in pediatric populations, where they represent a minority of thyroid nodules. Due to their rarity and the potential difficulty in distinguishing benign from malignant forms on cytology, these adenomas present unique diagnostic and management challenges. Here, we report a pediatric case of a large OA of the thyroid, managed with surgical resection following inconclusive fine-needle aspiration (FNA) results. Case Presentation: A 13-year-old girl presented with an enlarging thyroid nodule. An ultrasound examination showed a large (26 × 16 mm), solid, isoechoic nodule with a hypoechoic halo. The FNA findings were inconclusive, indicating a follicular neoplasm with oncocytic features, classified as Bethesda IV. The patient underwent a hemithyroidectomy, and a histopathological examination confirmed an encapsulated OA without evidence of capsular or vascular invasion. The postoperative recovery was uneventful, and follow-up assessments showed no recurrence. Conclusions: OAs in pediatric patients are rare and may pose diagnostic challenges. This case highlights the importance of a comprehensive approach, including surgical resection, for definitive diagnoses in cases where FNA results are inconclusive. Further studies are warranted to establish guidelines for the management of oncocytic thyroid neoplasms in pediatric patients, as well as to understand their clinical behavior in this population. Full article

The clinicopathological and molecular features of synchronous parathyroid carcinoma (PC) and thyroid carcinoma in a male patient are presented. At 11, he received mantle field radiotherapy for Hodgkin lymphoma. He had a 26-year adulthood history of recurrent nephrolithiasis treated five times with lithotripsy. At 52, he was referred to our clinic for hypercalcemia. Primary hyperparathyroidism was diagnosed (calcium: 3.46 mmol/L, parathormone: 150 pmol/L, preserved renal function, nephrolithiasis, and osteoporosis). Neck ultrasound revealed a 41 × 31 × 37 mm nodule in the left thyroid and smaller nodules in the right thyroid. Enlarged cervical lymph nodes were not observed. The large nodule was interpreted as parathyroid adenoma on 99Tc-pertechnetate scintigraphy/99Tc-MIBI scintigraphy with SPECT/CT. Total left-sided and subtotal right-sided thyroidectomy were performed. Histopathology confirmed locally invasive, low-grade PC (pT2; positive for parafibromin and E-cadherin, negative for galectin-3 and PGP9.5; wild-type expression for p53 and retinoblastoma protein; Ki-67 index 10%) and incidental papillary thyroid carcinoma (pT1b). Genetic profiling revealed no loss in CDC73, MEN1, CCND1, PIK3CA, CDH1, RB1, and TP53 genes. Deletions in CDKN2A, LATS1, ARID1A, ARID1B, RAD54L, and MUTYH genes and monosomies in nine chromosomes were identified. The tumor mutational burden and genomic instability score were low, and the tumor was microsatellite-stable. The thyroid carcinoma exhibited a TRIM24::BRAF fusion. Following surgery, the parathormone and calcium levels had normalized, and the patient underwent radioiodine treatment for thyroid cancer. The follow-up of 14 months was eventless. In summary, the clinical, laboratory, and imaging features of hyperparathyroidism taken together could have suggested malignancy, then confirmed histologically. The synchronous carcinomas were most likely caused by irradiation treatment diagnosed 41 years after exposure. It seems that the radiation injury initially induced parathyroid adenoma in young adulthood, which underwent a malignant transformation around age fifty. Full article

Thyroid carcinomas are driven by diverse molecular alterations, but the tumor suppressor gene folliculin (FLCN), best known for its role in Birt–Hogg–Dubé (BHD) syndrome, has received limited attention in thyroid tumors. Here, we describe two thyroid tumors with pathogenic FLCN alterations—one germline and one somatic—and analyze the broader prevalence and significance of FLCN in thyroid carcinomas using multiple large sequencing datasets, including ORIEN-AVATAR. Patient 1, with a germline FLCN mutation and a history of BHD syndrome, presented with a well-circumscribed oncocytic adenoma. Molecular testing confirmed biallelic FLCN inactivation, but no additional mutations or aggressive features were observed, and the patient remained disease-free post-thyroidectomy. Patient 2 harbored a somatic FLCN mutation in an oncocytic poorly differentiated thyroid carcinoma, which exhibited extensive angioinvasion, high proliferative activity, and concurrent TP53 and RB1 mutations. The tumor progressed with metastatic disease despite multimodal treatment. Thyroid carcinomas revealed FLCN alterations in 1.1% of cases. Pathogenic mutations were rare but associated with oncocytic morphology, while homozygous deletions occurred more frequently in genomically unstable tumors, including anaplastic thyroid carcinoma. These findings suggest FLCN mutations may act as early oncogenic drivers in oncocytic thyroid neoplasms, while deletions represent secondary events in aggressive tumor evolution. The lack of FLCN coverage in standard thyroid molecular panels likely underestimates its clinical relevance. Including FLCN in genetic testing could improve tumor detection and characterization, particularly in BHD patients who may benefit from routine thyroid screening. Further studies are needed to clarify FLCN’s role in thyroid cancer pathogenesis. Full article

The prevalence of hyperthyroidism in cats has been steadily increasing worldwide since the late 1970s. The main cause of feline hyperthyroidism remains unknown. The underlying cause was studied from the viewpoint of the “One Health” concept, which is an approach integrating environmental, animal and human health. Looking at the dietary difference between cats which are carnivores and dogs which appear to be omnivores like humans, there is a possibility that cats take in a comparatively greater amount of endocrine-disrupting chemicals such as polybrominated diphenyl ethers (PBDEs) than dogs and humans via the fish-based food web. PBDEs have been used worldwide as flame retardants since the 1970s. It is considered that PBDEs mimic thyroid-stimulating hormones to cause a thyroid adenoma, which is often active and produces excessive thyroid hormones, resulting in symptomatic hyperthyroidism. The increasing prevalence of feline hyperthyroidism may be associated with Minamata disease that was caused by methyl-mercury contamination in the 1950s. This environmental contamination firstly wreaked havoc as neurological disorders in local cats, and this occurrence was a sign that severe neurological disorders would next develop in large numbers of local people. The prevalence of feline hyperthyroidism may be a sign of what will next emerge in human beings. Full article

Background: Hyperthyroidism, characterized by excessive thyroid hormone production, presents in diverse clinical forms, including overt and subclinical disease. Accurate and timely diagnosis is critical to prevent complications such as cardiac dysfunction, osteoporosis, and thyroid storm. Objective: To provide a comprehensive review of the clinical presentation, diagnostic methods, and management strategies for hyperthyroidism, focusing on current practices, advancements, and challenges in treatment. Methods: This review synthesizes findings from peer-reviewed literature on the diagnosis and management of hyperthyroidism. Results: Thyroid function tests (TFTs) are the cornerstone of hyperthyroidism diagnosis, with suppressed TSH levels and elevated T3 and/or T4 levels confirming overt disease. Thyroid receptor antibodies (TRAb) are critical for diagnosing autoimmune hyperthyroidism and predicting relapse risk. Iodine scintigraphy is utilized in specific cases, such as suspected toxic adenoma or multinodular goiter. Management strategies include beta-blockers for symptomatic relief, though side effects such as bradycardia and fatigue may occur. Antithyroid medications, including methimazole and propylthiouracil, inhibit hormone synthesis, with remission more likely in patients with low TRAb levels and small goiters. Definitive treatments include radioactive iodine therapy (RAI), which effectively reduces thyroid activity but often results in hypothyroidism, and thyroidectomy, a surgical option for large goiters or malignancy, with potential complications like hypocalcemia and recurrent laryngeal nerve injury. Conclusions: The management of hyperthyroidism necessitates a personalized approach integrating diagnostic precision, emerging innovations, and patient-centered care. Full article

Background/Objectives: Carcinoembryonic antigen (CEA) is a cell-surface glycoprotein serving as a drug target, diagnostic marker, and serum marker for cancer monitoring. However, prevalence data on CEA expression in cancer tissues vary considerably. This study was designed to determine CEA expression in normal and neoplastic tissues. Methods: A tissue microarray containing 13,725 samples from 120 different tumor types, as well as 76 different normal tissue types, was analyzed by immunohistochemistry (IHC). Results: CEA was detectable in 65 (54.2%) of 120 tumor categories, including 49 (40.8%) tumor types with at least one strongly positive case. CEA positivity was most common in colorectal adenomas (100%) and carcinomas (98.7%), other gastrointestinal adenocarcinomas (61.1–80.3%), medullary carcinomas of the thyroid (96.3%), pulmonary adenocarcinoma (73.7%), mucinous carcinomas of the ovary (79.8%) and the breast (43.2%), small-cell carcinomas of the lung (64.3%), and urinary bladder (38.9%). CEA overexpression was linked to high tumor grade and invasive growth (p < 0.0001 each) in urinary bladder cancer, and estrogen and HER2 receptor positivity (p ≤ 0.0158) in invasive breast cancer of no special type. In colorectal adenocarcinomas, reduced CEA expression was associated with mismatch repair deficiency (p < 0.0001). Conclusions: The comprehensive list of CEA-positive human tumor types demonstrates that CEA is expressed in a broad range of epithelial neoplasms, many of which might benefit from CEA serum monitoring and anti-CEA therapies. Full article

Thyroid cancer is the most common type of endocrine malignancy. Papillary thyroid carcinoma (PTC) is its predominant subtype, which is responsible for the vast majority of cases. It is true that PTC is a malignant tumor with a very good prognosis due to effective primary therapeutic approaches such as thyroidectomy and radioiodine (RAI) therapy. However, we are often required to indicate second-line treatments to eradicate the tumor properly. In these scenarios, molecular therapies are promising alternatives, especially if specifically targetable mutations are present. Many of these targetable gene alterations originate from gene fusions, which can be found using molecular diagnostics like next-generation sequencing (NGS). Nonetheless, molecular profiling is far from being a routine procedure in the initial phase of PTC diagnostics. As a result, the mutation status, except for BRAF V600E mutation, is not included in risk classification algorithms either. This study aims to provide a comprehensive analysis of fusion mutations in PTC and their associations with clinicopathological variables in order to underscore certain clinical settings when molecular diagnostics should be considered earlier, and to demonstrate yet unknown molecular–clinicopathological connections. We conducted a retrospective fusion mutation screening in formalin-fixed paraffin-embedded (FFPE) PTC tissue samples of 100 patients. After quality evaluation by an expert pathologist, RNA isolation was performed, and then NGS was applied to detect 23 relevant gene fusions in the tumor samples. Clinicopathological data were collected from medical and histological records. To obtain the most associations from the multivariate dataset, we used the d-correlation method for our principal component analysis (PCA). Further statistical analyses, including Chi-square tests and logistic regressions, were performed to identify additional significant correlations within certain subsets of the data. Fusion mutations were identified in 27% of the PTC samples, involving nine distinct genes: RET, NTRK3, CCDC6, ETV6, MET, ALK, NCOA4, EML4, and SQSTM1. RET and CCDC6 fusions were associated with type of thyroidectomy, RAI therapy, smaller tumor size, and history of Hashimoto’s disease. NCOA4 fusion correlated with sex, multifocality, microcarcinoma character, history of goiter, and obstructive pulmonary disease. EML4 fusion was also linked with surgical procedure type and smaller tumor size, as well as the history of hypothyroidism. SQSTM1 fusion was associated with multifocality and a medical history of thyroid/parathyroid adenoma. NTRK3 and ETV6 fusions showed significant associations with Hashimoto’s disease, and ETV6, also with endometriosis. Moreover, fusion mutations were linked to younger age at the time of diagnosis, particularly the fusion of ETV6. The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes. Full article

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. Full article