Benign Parathyroid Research Articles

Evaluation of the relationship between thyroid cancer and the concurrent detection of thyroid nodules on the background of primary hyperparathyroidism

Introduction: Primary Hyperparathyroidism (PHPT) is commonly caused by a benign parathyroid adenoma that results in overactivity of the gland and subsequent hypercalcemia due to elevated parathyroid hormone (PTH). This endocrine pathology is associated with thyroid cancer, specifically Papillary Thyroid Cancer (PTC). However, the explanation for their synchronous presentation is unknown. Moreover, it causes diagnostic and treatment challenges that impact patient outcomes. Aims and Objectives: To critically analyze published research to address the relationship between PHPT and thyroid cancer, the role of ultrasound imaging in detecting sinister thyroid nodules in PHPT patients and the features of PHPT that predispose the risk of thyroid malignancy. Study Design: Literature Review Methodology: Electronic database searches of PubMed and CINAHL Plus through EBSCOhost were conducted using the keywords "primary hyperparathyroidism", "thyroid nodules" and "thyroid cancer". Following application of filters and removal of duplicates, 627 relevant results remained. Articles were screened for eligibility based on predetermined selection criteria. Following a review of titles and abstracts, 10 peer-reviewed articles were chosen for further analysis. The studies included were critically appraised using the EBL Critical Appraisal Checklist. Results: 10 articles were examined, 2 were prospective cohort studies and 8 were retrospective cohort studies. All studies involved exhaustive medical chart reviews of patients with PHPT, to investigate the concomitance of thyroid malignancy. Six studies established cervical ultrasound as the optimal method of recognition and preoperative localization of thyroid and parathyroid lesions. Overall, the incidence of thyroid cancer among PHPT patients ranged between 2.9% to 32.9%. Four studies established age, gender and PTH levels as risk factors. Conclusion: The existing literature is consistent with previous studies and purports that individuals with a background fo PHPT are at an increased risk of thyroid cancer. Furthermore the highest likelihood of identifying thyroid cancer is through preoperative localization of parathyroid adenomas by cervical ultrasound, in female patients over the age of 50. Key Findings: Further research is needed to understand the underlying pathogenesis and genetic mechanisms that encompass the relationship between PHPT and thyroid cancer.

Relationship between serum vitamin D levels and thyroid- and parathyroid-related diseases: a Mendelian randomisation study.

Previous studies have indicated an association between vitamin D and thyroid- and parathyroid-related diseases. However, it remains unclear whether it is a cause of the disease, a side effect of treatment or a consequence of the disease. The Mendelian randomisation (MR) study strengthens the causal inference by controlling for non-heritable environmental confounders and reverse causation. In this study, a two-sample bidirectional MR analysis was conducted to investigate the causal relationship between serum vitamin D levels and thyroid- and parathyroid-related diseases. Inverse variance weighted, weighted median and MR-Egger methods were performed, the Cochran Q test was used to evaluate the heterogeneity and the MR-PRESSO and MR-Egger intercepts were utilised to assess the possibility of pleiotropy. The Bonferroni-corrected significance threshold was 0·0038. At the Bonferroni-corrected significance level, we found that vitamin D levels suggestively decreased the risk of benign parathyroid adenoma (OR = 0·244; 95 % CI 0·074, 0·802; P = 0·0202) in the MR analyses. In the reverse MR study, a genetically predicted risk of thyroid cancer suggestively increased the risk of elevated vitamin D (OR = 1·007; 95 % CI 1·010, 1·013; P = 0·0284), chronic thyroiditis significantly increased the risk of elevated vitamin D (OR = 1·007; 95 % CI 1·002, 1·011; P = 0·0030) and thyroid nodules was significantly decreased the vitamin D levels (OR = 0·991; 95 % CI 0·985, 0·997; P = 0·0034). The findings might be less susceptible to horizontal pleiotropy and heterogeneity (P > 0·05). This study from a gene perspective indicated that chronic thyroiditis and thyroid nodules may impact vitamin D levels, but the underlying mechanisms require further investigation.

Lymphatic and blood vessels in parathyroid tumors: Immunohistochemical study with LYVE-1 and von Willebrand factor.

Parathyroid tumors exhibit distinct histopathological features that differentiate benign from malignant lesions. This study aimed to study characteristic distribution of lymphatic and blood vessels in normal parathyroid gland and parathyroid tumors to distinguish cancer from benign tumors. Immunohistochemical staining for lymphatic and blood vessels and parathyroid hormone was performed with parathyroid proliferating lesions including adenoma, multiglandular multiple adenomas, atypical tumor, and carcinoma. Lymphatic vessels were immunostained with lymphatic vessel endothelial receptor 1 (LYVE-1) and blood vessels were immunostained with von Willebrand factor (vWf). Normal parathyroid gland contained several round blood vessels with less linear lymphatic vessels. The less parathormone-immunostained adenomas weighing less than 2 g revealed larger blood vessels with perivascular small linear lymphatic vessels, and the larger adenomas contained proportionally larger blood vessels. Smaller multiglandular multiple adenomas were like smaller adenomas with less parathormone staining and contained larger, round blood vessels with perivascular small linear lymphatic vessels. Larger multiglandular multiple adenomas weighing more than 4 g and one atypical tumor contained nodular pattern consisted of alternating strongly parathormone-positive lobes and negative lobes with numerous, dilated blood vessels and perivascular linear lymphatic vessels. Both primary and metastatic carcinomas were strongly and diffusely positive for parathyroid hormone with numerous lymphatic and blood vessels at the invading margin. Thus, normal parathyroid has rich blood vessels which provide accessibility of minced tissues seeding for auto-transplantation. Immunostaining patterns of parathyroid hormone, lymphatic and blood vessels help to distinguish carcinoma from benign parathyroid proliferating lesions. The negative immunohistochemical staining for parafibromin will detect carriers of hyperparathyroidism-jaw tumor (HPT-JT) syndrome and would help in diagnosing parathyroid cancer in both HPT-JT carriers and sporadic patients.

Evaluation of Focused Mini-Incision Parathyroidectomy in Primary Hyperparathyroidism

Abstract Background In the era of effective preoperative localization and availability of intraoperative parathyroid hormone (IOPTH) assay, the trend now in parathyroidectomy is shifting from bilateral neck exploration (BNE) into minimal invasive parathyroidectomy (MIP). The concept of MIP is based on the fact that 85% of cases have single adenoma. This study highlights the outcomes of focused mini- incision parathyroidectomy (FMIP) for the treatment of selected cases of primary hyperparathyroidism. Aim of study: To evaluate and assess the outcome and advantages of focused mini-incision parathyroidectomy in parathyroid adenoma of primary hyperparathyroidism. Patients and Methods This cohort study was conducted at endocrine surgery unit, Ain Shams University Hospital, and Sohag Cancer Institute including 22 patients with benign solitary parathyroid adenoma; 17 retrospective cases & 5 prospective cases. These included patients had been operated with focused mini-incision parathyroidectomy within the time period from January 2018 to December 2020 as retrospective cases and from January 2021 to December 2021 as prospective cases. Results In this study, age ranged from 30 to 70 years with mean age 50.23 ± 10.71 years. The preoperative serum calcium level ranged from 10.8 to 14.2 mg/dl (mean 12.28 ± 1.16 mg/dl). The preoperative parathyroid hormone level was elevated ranging from 256 to 2090 pg/mL (mean 970.68 ± 563.97 pg/mL). In this study, the operative time ranged from 55 to 75 minutes with mean 64.36 ± 6.33 minutes, percentage of IOPTH decrease level ranged from 75-95 % with mean percentage 85.72 ± 6.28 %. There were no cases with intraoperative bleeding or recurrent laryngeal nerve (RLN) injury. Hospital stay ranged from 6-16 days with mean 10.77 ± 3.10 days. There is no wound infection in all cases. All cases reached a success rate up to 100% (decrease the IOPTH level ≥ 75 %, and resolution of preoperative hypercalcemic manifestations). Conclusion Depending to the high successful rate, very low intraoperative morbidity and better postoperative recovery and cosmoses of FMIP technique, it should be the first choice for pHPT cases with solitary parathyroid adenoma, provided by the concordance localization study of U/S and MIBI scan preoperative.

Primary hyperparathyroidism: diagnostic features and surgical outcomes.

Primary hyperparathyroidism is characterized by elevated plasma calcium levels due to inappropriate secretion of parathyroid hormone (PTH) in most cases by an adenomatous or hyperplastic parathyroid. We present a retrospective analysis of a large cohort of patients operated on of parathyroidectomy in our center analyzing their diagnostic characteristics, intraoperative match and surgical outcomes. We included patients with benign parathyroid disease who underwent parathyroidectomy associated or not with hemi- or total thyroidectomy at the Sant'Anna University Hospital of Ferrara between September 2003 and September 2022. In our study 371 patients fulfilled the inclusion criteria. The most widely used preoperative imaging method was ultrasound, followed by 99mTc-sestamibi scintigraphy. In most cases, preoperative imaging correctly localized the affected parathyroid. Considering the intraoperative site of the pathologically affected parathyroid, the majority of pathological parathyroids were located in the lower districts of the neck and a smaller percentage in the upper, intermediate, and ectopic sites. Postoperative complications were infrequent. The main challenge in parathyroid surgery lies in the difficulty in localizing the pathological parathyroid at the surgical site, which can lengthen the surgical time by increasing comorbidities. Currently, the results on pathological parathyroid localization are good. Technology needs to be developed toward greater diagnostic accuracy and minimally invasive surgical approaches.

Abstract 6265: FLCN variants and their role in parathyroid cancer and atypical parathyroid tumors

Abstract Parathyroid carcinoma (PC) is rare, poses challenges in definitive diagnosis and treatment, and carries a high rate of recurrence and mortality. Atypical parathyroid tumors (APT) have histopathologic features of malignancy but lack unequivocal evidence of invasion and are of uncertain malignant potential. Analysis of genetic alterations that may play a role in PC development, particularly those that might serve as markers of malignant potential, is important for further understanding this disease. FLCN is a gene found on chromosome 17 that encodes folliculin, a ubiquitously expressed protein with roles in multiple cellular processes such as apoptosis and cell signaling. Inactivating FLCN mutations cause Birt-Hogg-Dubé syndrome (BHD), an autosomal dominant condition characterized by benign fibrofolliculomas, pulmonary cysts and spontaneous pneumothorax, and increased risk of renal cancer. Benign parathyroid tumors had previously been reported in a few BHD patients and recently one study has reported a link between FLCN mutations and parathyroid carcinoma. Germline frameshift mutations in FLCN, accompanied by somatic loss of the normal allele, were reported in two unrelated PC patients, both with clinical features suggestive of BHD, but no established diagnosis of BHD. An identical somatic frameshift FLCN mutation was reported in one PC and one APT. Interestingly, the authors noted low coverage of FLCN on whole exome sequencing, resulting in the failure to detect variants identified by Sanger sequencing, thus raising the possibility that prior studies may have missed FLCN variants. To better understand the frequency of germline or somatic FLCN mutations in PC and APT, we performed Sanger sequence analysis of the entire coding region of the FLCN gene on available tumor DNA from 11 PCs and 15 APTs. We identified no inactivating FLCN mutations in any of the PC or APT samples examined. A germline missense variant, resulting in a p.Gly325Val change, predicted to be benign/tolerated by in silico analyses, was seen in one PC and a synonymous variant (c.1233G>A) was seen in one APT. The absence of pathogenic mutations in our series parathyroid carcinoma and atypical parathyroid tumors suggests that FLCN mutations are rare in these parathyroid tumors. Nevertheless, germline FLCN testing and/or additional screening for BHD-related lesions in parathyroid carcinoma patients merits further consideration and study. Citation Format: Callie Burke, Justin Bellizzi, Jessica Costa-Guda, Andrew Arnold. FLCN variants and their role in parathyroid cancer and atypical parathyroid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6265.

Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue

IntroductionCurrent imaging techniques have several limitations in detecting parathyroid glands. We have investigated the calcium-sensing receptor (CaSR) as a potential target for specifically labeling parathyroid glands for radiologic detection. For accurate imaging it is vital that a large differential expression exists between the target tissue and adjacent structures. We sought to investigate the relative abundance of the CaSR in normal and abnormal parathyroid tissue, as well as normal and abnormal thyroid. MethodsExisting clinical specimens were selected that represented a wide variety of pathologically and clinically confirmed malignant and benign thyroid and parathyroid specimens. Sections were stained for the CaSR using immunohistochemistry and scored for intensity and abundance of expression. (H score = intensity scored from 0 to 3 multiplied by the % of cells at each intensity. Range 0-300). ResultsAll parathyroid specimens expressed the CaSR to a high degree. Normal parathyroid had the highest H score (271, s.d. 25.4). Abnormal parathyroid specimens were slightly lower but still much higher than normal thyroid (H score 38.3, s.d. 23.3). Medullary thyroid cancer also expressed the CaSR significantly higher than normal thyroid (H score 182, s.d. 69.1, P < 0.001) but below parathyroid levels. Hürthle cell carcinoma expressed the CaSR to a lesser degree but higher than normal thyroid (H score 101, s.d. 46.4, P = 0.0037). ConclusionsThe CaSR is differentially expressed on parathyroid tissue making it a feasible target for parathyroid imaging. False positives might be anticipated with medullary and Hürthle cell cancers.

SAT212 Collateral Damage A Case Of Refractory Hyperparathyroidism In A Young Woman With End Stage Renal Disease

Abstract Disclosure: E.W. Alvarado: None. V. Alia: None. H. Reinhart: None. R. Giese: None. Background: The Rio Grande Valley (RGV) is a community with the highest incidence of ESRD in the USA. Hyperparathyroidism (HPT), defined as a serum PTH &amp;gt;65 pg/mL, HPT is a secondary complication of ESRD affecting 80% of individuals in this population. Although hyperparathyroidism may be asymptomatic, a severe form, refractory to medication can occur. Refractory HPT is defined as a PTH level 9 times the upper-limit or a serum level &amp;gt;800 pg/mL. This disease causes mutations in parathyroid cells causing parathyroid-gland hyperplasia. Once PTH levels increase to this extent, systemic issues including electrolyte derangements, weight loss, pathologic fractures, osteoporosis, and death can ensue. Due to the high mortality associated with this condition; it is paramount that patients are referred for surgery when medical management is inadequate. Clinical Case: A 31-year-old female with a significant medical history of ESRD on hemodialysis presented for evaluation of a suspected parathyroid carcinoma. Physical examination revealed a frail, short-statured woman who ambulated with a walker. Patient endorsed a 13-year history of uncontrolled HTN on antihypertensives, with a BP of 226/124. The patient presented with a BMI of 16.7, and endorsed a history of multiple fractures, musculoskeletal-pain, fatigue, palpitations, and a 33 pound weight loss over 1.5-years. Labs showed a total calcium of 9.4, phosphorus 6.9, ALP 652, and a PTH of 2423, meeting criteria for refractory HPT. Of note, records received five-months prior to referral showed a PTH of 5343 pg/ml, suggesting earlier surgery could have minimized disease progression. Based on the patient's presentation, MEN was suspected, however workup was negative. The patient was referred to a nearby ER for hemodynamic-stability and further workup of her underlying conditions. Ultrasound revealed two putative inferior parathyroid-glands presumptive for a diagnosis of severe tertiary HPT, but due to PTH&amp;gt;1000 carcinoma could not be excluded. Patient was taken to surgery and intra-operatively 4-gland hypertrophy was noted and a 3.5-gland excision was performed. Intraoperative PTH decreased to 120, and pathology showed benign parathyroid hyperplasia. Post-op day 1 the patient received hemodialysis and lab values revealed severe hypocalcemia prompting close monitoring and aggressive calcium supplementation. The patient’s electrolyte levels stabilized, she was discharged, and follow-up 2-weeks later revealed a PTH of 14.5. Conclusion: This case of a young patient with refractory HPT highlights the region's early onset of ESRD and its subsequent conditions. Noteworthy, the RGV is associated with a multitude of socioeconomic factors that precipitate neglect of chronic illnesses, indicating the substantial need for early identification and intervention to prevent long-term complications to disease in this vulnerable population. Presentation: Saturday, June 17, 2023

Challenges in the Diagnosis of Parathyroid Cancer: Unraveling the Diagnostic Maze

Parathyroid carcinoma (PC) is a rare and aggressive cancer affecting the parathyroid glands, presenting diagnostic and therapeutic challenges due to its rarity and overlapping features with benign parathyroid disease. This report describes the case of a 51-year-old patient with significantly elevated serum calcium levels, leading to further investigation. Imaging studies revealed a large nodular mass in the right inferior parathyroid gland. After undergoing right inferior parathyroidectomy, pathology confirmed parathyroid carcinoma. However, the patient experienced a relapse, detected via a neck MRI. This case highlights the importance of specific clinical features, such as rapid calcium increase, elevated parathyroid hormone (PTH) levels, and a large nodular mass, in suspecting malignancy. Differential diagnosis between carcinoma and adenoma can be challenging, and immunohistochemistry aids in diagnosis. Regular follow-up with calcium and PTH monitoring is essential for detecting recurrence. This case underscores the aggressive nature of parathyroid carcinoma and the importance of early diagnosis, surgical intervention, and thorough follow-up care for improved outcomes.

Papillary thyroid carcinoma coexisting with benign thyroid and parathyroid pathology: clinical and pathomorphological features

Background. Papillary thyroid carcinoma (PTC) is the most frequent malignant neoplasm originating from follicular cells of thyroid gland. PTC is often coexisting with other benign thyroid pathology such as chronic lymphocytic thyroiditis, follicular thyroid adenoma, toxic thyroid adenoma, Graves’ disease, non-toxic multinodular goiter. PTC can be diagnosed in patients undergoing surgical treatment for hyperparathyroidism. However, the clinical and pathomorphological features of PTC in the presence of other benign thyroid or parathyroid pathology, as well as possible differences in surgical tactics, remain relevant as evidenced by previously published reports. The purpose of the study is to assess the prevalence and determine the differences in the clinical and pathomorphological parameters of PTC in the presence of benign thyroid and parathyroid pathology. Materials and methods. There were identified 91 patients with PTC, who underwent surgical treatment at the clinical bases of the Department of Surgery of the NSC “Institute of Biology and Medicine” of Taras Shevchenko National University of Kyiv. Results. In the studied PTC cohort, 31 (35 %) patients were without coexisted benign thyroid pathology and 60 (35 %) patients had it (PTC/coexisted). A statistically significantly higher number of mitoses per 10 high power fields in the PTC group were identified in 3 (10 %) patients, as compared to the absence of this pathohistological parameter in the PTC/coexisted (p = 0.037). Further analysis of these 3 cases showed that 4 mitotic figures were found in one PTC, and one mitotic figure in the other two cases per 10 high power fields (400×). Conclusions. Papillary thyroid carcinoma in patients with other benign thyroid pathology is associated with lower biological aggressiveness than PTC without comorbidity as evidenced by a lower frequency of mitotic figures per 10 high power fields. The presence of concomitant benign thyroid pathology can be considered as a favorable prognostic factor for patients with PTC.

Parathyroid Carcinoma: Update on Pathogenesis and Therapy

Parathyroid carcinoma (PC) is a very rare endocrine cancer with aggressive behavior, a high metastatic potential, and a poor prognosis. Surgical resection of affected gland(s) and other involved structures is the elective therapy. Pre-operative and intra-operative differential diagnosis with benign parathyroid adenoma remains a challenge. The lack of a clear pre-operative diagnosis does not allow one, in many cases, to choose the correct surgical approach to malignant PC, increasing persistence, the recurrence rate, and the risk of metastases. An initial wrong diagnosis of parathyroid adenoma, with a minimally invasive parathyroidectomy, is associated with over 50% occurrence of metastases after surgery. Genetic testing could help in identifying patients at risk of congenital PC (i.e., CDC73 gene) and in driving the choice of neck surgery extension. Targeted effective treatments, other than surgery, for advanced and metastatic PC are needed. The pathogenesis of malignant parathyroid carcinogenesis is still largely unknown. In the last few years, advanced molecular techniques allowed researchers to identify various genetic abnormalities and epigenetic features characterizing PC, which could be crucial for selecting molecular targets and developing novel targeted therapeutic agents. We reviewed current findings in PC genetics, epigenetics, and proteomics and state-of-the-art therapies.

Novel PRUNE2 Germline Mutations in Aggressive and Benign Parathyroid Neoplasms

Parathyroid tumors are mostly sporadic but can also occur in familial forms, including different kinds of genetic syndromes with varying phenotypes and penetrance. Recently, somatic mutations of the tumor suppressor gene PRUNE2 were found to be frequent in parathyroid cancer (PC). The germline mutation status of PRUNE2 was investigated in a large cohort of patients with parathyroid tumors from the genetically homogenous Finnish population, 15 of which had PC, 16 atypical parathyroid tumors (APT), and 6 benign parathyroid adenomas (PA). Mutations in previously established hyperparathyroidism-related genes were screened with a targeted gene panel analysis. Nine PRUNE2 germline mutations with a minor allele frequency (MAF) of <0.05 were found in our cohort. Five of these were predicted to be potentially damaging and were identified in two patients with PC, two with APT, and three with PA. The mutational status was not associated with the tumor group nor related to the clinical picture or severity of the disease. Still, the frequent finding of rare germline mutations of PRUNE2 may point to the gene playing a role in the pathogenesis of parathyroid neoplasms.

PS-R03-8: PARATHYROID ADENOMA PRESENTING AS UNEXPLAINED SINUS TACHYCARDIA AND REFRACTORY HYPERTENSION: A CASE REPORT

Introduction: Primary hyperparathyroidism (PHPT) and malignancy account for most cases of hypercalcemia in clinical practice. They commonly occur in relation to a solitary parathyroid adenoma, parathyroid hyperplasia, or carcinoma. Majority of patients are asymptomatic, although some present with vague unusual symptoms. Case: We report a case of a 50-year-old lady presenting with unexplained resting tachycardia, uncontrolled hypertension and generalised ill-health for one year in the background of complicated type 2 diabetes, dyslipidaemia, and hypertension. She had marginally elevated serum ionized calcium with normal serum phosphate levels in the background of early chronic kidney disease. Intact parathyroid hormone level was elevated with concomitant low levels of vitamin D. Clinical evaluation revealed an anterior neck lump which was ultrasonically suspected as a thyroid enlargement with possibility of a deep-seated parathyroid mass. A sestamibi B scan confirmed the presence of a single parathyroid adenoma. The possibility of Multiple Endocrine Neoplasia (MEN) was ruled out. She underwent a successful partial thyroidectomy with removal of the parathyroid mass. Histology revealed a solitary benign parathyroid adenoma. Following surgery, her calcium levels returned to normal range and her unexplained tachycardia had settled, as well as her general wellbeing. Her blood pressure was controlled with 3 antihypertensive drugs. Discussion: Hypercalcemia should be suspected as a rare possibility in the workup of unexplained sinus tachycardia and hypertension, and could be masked with concomitant vitamin D deficiency.

Engineering functional 3-dimensional patient-derived endocrine organoids for broad multiplatform applications

BackgroundRecent advancements in 3-dimensional patient-derived organoid models have revolutionized the field of cancer biology. There is an urgent need for development of endocrine tumor organoid models for medullary thyroid carcinoma, adrenocortical carcinoma, papillary thyroid carcinoma, and a spectrum of benign hyperfunctioning parathyroid and adrenal neoplasms. We aimed to engineer functionally intact 3-dimensional endocrine patient-derived organoids to expand the in vitro and translational applications for the advancement of endocrine research. MethodsUsing our recently developed fine needle aspiration–based methodology, we established patient-derived 3-dimensional endocrine organoid models using prospectively collected human papillary thyroid carcinoma (n = 6), medullary thyroid carcinoma (n = 3), adrenocortical carcinoma (n = 3), and parathyroid (n = 5). and adrenal (n = 5) neoplasms. Multiplatform analyses of endocrine patient-derived organoids and applications in oncoimmunology, near-infrared autofluorescence, and radiosensitization studies under 3-dimensional in vitro conditions were performed. ResultsWe have successfully modeled and analyzed the complex endocrine microenvironment for a spectrum of endocrine neoplasms in 3-dimensional culture. The endocrine patient-derived organoids recapitulated complex tumor microenvironment of endocrine neoplasms morphologically and functionally and maintained cytokine production and near-infrared autofluorescence properties. ConclusionOur novel engineered endocrine patient-derived organoid models of thyroid, parathyroid and adrenal neoplasms represent an exciting and elegant alternative to current limited 2-dimensional systems and afford future broad multiplatform in vitro and translational applications, including in endocrine oncoimmunology.

Association of Medicaid expansion of the Affordable Care Act with operations for benign endocrine surgical disease

•Background: The Affordable Care Act's Medicaid expansion increased insurance coverage and access to care for endocrine cancers, though impact on benign endocrine disease is unknown.•Methods: Patients undergoing operations for benign thyroid, parathyroid, and adrenal disease were collected from the Vizient® Clinical Data Base from 2009 to 2016 and grouped by state Medicaid expansion status in January 2014. Insurance coverage was analyzed by difference-in-differences analysis, and logistic regression evaluated odds of operation by insurance status.•Results: 134,242 patients were included. Medicaid coverage in expansion states increased for all operations (Adj-DD 5.78%, p < 0.001) with decreases in uninsured and private insurance. Medicaid patients had increased odds of undergoing thyroid operations (OR 1.56, p < 0.001) and decreased odds of parathyroid (OR 0.68, p < 0.001) or adrenal operations (OR 0.70, p < 0.001) versus private insurance.•Conclusion: Medicaid expansion increased insurance coverage for benign endocrine disease, however, barriers remain for Medicaid patients with parathyroid and adrenal disease.

Immunohistochemical Profile of Parathyroid Tumours: A Comprehensive Review

Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022). Loss of parafibromin indicates a greater probability of malignant course and should trigger the search for inherited or somatic CDC73 mutations. Aberrant immunophenotype is characterised by a set of markers that are lost (parafibromin), down-regulated (e.g., APC protein, p27 protein, calcium-sensing receptor) or up-regulated (e.g., proliferation activity by Ki-67 exceeding 5%) in parathyroid carcinoma compared to benign parathyroid disease. Aberrant immunophenotype is not the final proof of malignancy but should prompt the search for the definitive criteria for carcinoma. Histogenetic studies can be necessary for differential diagnosis between thyroid vs. parathyroid origin of cervical or intrathyroidal mass; detection of parathyroid hormone (PTH), chromogranin A, TTF-1, calcitonin or CD56 can be helpful. Finally, immunohistochemistry is useful in pathogenetic studies due to its ability to highlight both the presence and the tissue location of certain proteins. The main markers and challenges (technological variations, heterogeneity) are discussed here in the light of the current WHO classification (2022) of parathyroid tumours.

Diagnostic significance of parafibromin expression in parathyroid carcinoma

Parathyroid carcinomas are difficult to distinguish from adenomas according to the current diagnostic criteria. The judgment of local infiltration is subjective and inconsistent. Existing studies have found that the CDC73 gene encoding parafibromin is related to the occurrence of parathyroid carcinomas. This study is aimed at investigating whether the immunohistochemistry of parafibromin is helpful in distinguishing malignant from benign parathyroid tumors. A total of 53 patients with parathyroid carcinoma from Peking Union Medical College Hospital were included. Metastasis was found in 17 of 53 patients. In addition, another 53 patients with parathyroid adenomas were included as controls. Appropriate sections were stained with an immunohistochemical autostainer. Three senior pathologists evaluated the sections and analyzed their clinicopathological features independently. The loss of parafibromin expression only occurred in malignant tumors, including all carcinomas with metastasis (17/17) and 14 of 36 carcinomas with only local infiltration. All staining results of adenomas (53/53) were positive. Considering invasion as the gold standard of malignancy, the sensitivity of parafibromin staining is 58%, and the specificity is 100%. If the gold standard is changed to metastasis, the sensitivity becomes 100%, and the specificity becomes 84%. By analyzing clinicopathological features with metastasis and parafibromin staining, it is found that local-infiltrative carcinomas with positive staining results have better biological behaviors than carcinomas that lack parafibromin expression. Parafibromin staining is highly recommended as an auxiliary method in the diagnosis of parathyroid carcinoma.

Improved intraoperative verification of parathyroid glands by determining their autofluorescence in the infrared spectrum

Background. Detection of parathyroid glands by spectroscopy of their autofluorescence in the near-infrared spectrum (NIRAF) is considered a promising intraoperative tool in addition to their verification with visual identification. The study was aimed to evaluate the role of NIRAF by using two different imaging systems to confirm parathyroid glands during operations for benign and malignant thyroid and parathyroid tumors. Materials and methods. The study included 62 patients who underwent verification of NIRAF by using two different imaging systems equipped with a near-infrared (NIR) camera during surgery. Intravenous fluorophore of indocyanine green was applied to amplify the NIRAF signal. Results. Normal parathyroid glands were identified and mobilized after a visual inspection in 50 patients (80 %), which was subsequently confirmed by evaluation with NIRAF spectroscopy. Determination of NIRAF in the parathyroid glands and their differentiation from lymph nodes was achieved in 8 (13 %) patients with papillary thyroid carcinoma. In 3 (5 %) patients, the parathyroid gland was identified in the area of the postoperative scar, using NIRAF but not by the visual identification. In 2 (3 %) cases, the appearance of the signal was determined but with a decrease in the intensity of the NIRAF from the parathyroid glands during their unintentional removal. The strong NIRAF signal intensity was observed from the parathyroid gland after changing the position of the NIR camera when using the Fluobeam 800 device at an angle of approximately 45–65° to the area of the parathyroid gland location. The Fluobeam LX demonstrated a satisfactory NIRAF signal without any specific changes in camera position. NIRAF signal was determined in the tissue of toxic thyroid adenomas. NIRAF signal of the low intensity was detected in the invasion of thyroid carcinoma in a capsule of a thyroid gland. No NIRAF signal was observed from metastatic and normal lymph nodes. Conclusions. The use of NIRAF parathyroid spectroscopy technology allows impro-ving their imaging and verification as an additional method during surgery of the neck. The practical value of NIRAF spectroscopy of the parathyroid gland is increased in the case of reoperations due to the risk of accidental removal of the parathyroid gland as well as for differential diagnosis between the parathyroid gland and metastatic lymph nodes.

Parathyroid Tumors: Molecular Signatures.

Parathyroid tumors are rare endocrine neoplasms affecting 0.1–0.3% of the general population, including benign parathyroid adenomas (PAs; about 98% of cases), intermediate atypical parathyroid adenomas (aPAs; 1.2–1.3% of cases) and malignant metastatic parathyroid carcinomas (PCs; less than 1% of cases). These tumors are characterized by a variable spectrum of clinical phenotypes and an elevated cellular, histological and molecular heterogeneity that make it difficult to pre-operatively distinguish PAs, aPAs and PCs. Thorough knowledge of genetic, epigenetic, and molecular signatures, which characterize different parathyroid tumor subtypes and drive different tumorigeneses, is a key step to identify potential diagnostic biomarkers able to distinguish among different parathyroid neoplastic types, as well as provide novel therapeutic targets and strategies for these rare neoplasms, which are still a clinical and therapeutic challenge. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of different clinical types of parathyroid tumors, both in familial and sporadic forms of these endocrine neoplasms.

439 Managing Parathyroid Carcinoma in the Age of COVID 19

AimParathyroid carcinoma is a rare malignancy accounting for 1% of cases of primary hyperparathyroidism. Pre-operative diagnosis is difficult because in the absence of metastatic disease, the presentation is similar to benign parathyroid disease. In patients with hyperparathyroidism and severe hypercalcaemia or a significantly raised parathyroid hormone (PTH) level clinicians should consider parathyroid carcinoma and expediting surgical management. During the current pandemic, a high index of suspicion should be maintained to ensure that care is not compromised. A review of the management of patients with suspected parathyroid carcinoma during the COVID-19 pandemic is presented.MethodIn our tertiary referral centre for Endocrine surgery, 4 presentations of parathyroid cancer were reviewed. Their investigations, surgical management and post-operative outcomes are described with a brief literature review of parathyroid cancer.ResultsOf the four cases of parathyroid carcinoma described, all presented with severe hypercalcaemia and significantly raised PTH levels. Pre-operative mean calcium was 3.36mmol/L and mean PTH was 80pmol/L (52-99.8). Patients were imaged with a combination of cross-sectional imaging and ultrasound. Two patients had evidence of distant disease at presentation. 1 patient was transferred as an inpatient to our centre and the other three patients were seen within 2 weeks of referral; the mean time from referral to surgery was 14days (1-23). Post-operatively, all patients achieved normocalcaemia, with PTH levels normal in all but one.ConclusionsDespite limitations on face-to-face clinic consultations and reduced capacity for elective surgery during the COVID-19 pandemic, all patients were investigated and managed promptly to ensure superior outcomes.