Parathyroid Adenoma Research Articles

Surgeon Review of 4D CT for Identification of Parathyroid Adenomas.

Preoperative localization of parathyroid adenomas aids surgical planning for patients with hyperparathyroidism. This study explores the diagnostic accuracy of surgeon-reviewed 4D computed tomography (4D CT) scans for localization of parathyroid adenomas. A retrospective review of 95 patients with hyperparathyroidism who underwent parathyroidectomy at a tertiary care center was performed. The sensitivity, specificity, positive and negative predictive values, accuracy of identifying abnormal glands by surgeon, and interrater reliability between two head and neck surgeons was assessed. The sensitivity of surgeon localization of all glands was 71% (95% CI, 63%-78%), improving to 76% when combined with radiology reads. The specificity was 98% (95% CI, 95%-99%), the positive predictive value was 95% (95% CI, 90%-99%), and the negative predictive value was 84% (95% CI, 79%-88%) for all abnormal glands. Interrater reliability between surgeons was κ = 0.771. The diagnostic accuracy of surgeon localization of abnormal glands on the 4D CT scan was substantial. Improvement with radiology report integration highlights the benefits of multidisciplinary collaboration. Interrater reliability between two fellowship-trained surgeons was moderate. These findings support the importance of surgeons developing proficiency in reading 4D CT scans to engage in interdisciplinary communication and improve patient outcomes.

Frequency and characteristics of ectopic parathyroid adenomas in a cohort of patients referred for 18F-fluorocholine PET/CT.

This article aimed to study the frequency and characteristics of ectopic/intrathyroidal parathyroid adenomas in patients referred for 18F-fluorocholine PET/computed tomography (CT). From 11 June 2015 to 15 January 2024, 729 patients were studied. Recorded patient variables included hyperparathyroidism type, sex, age, presence of symptoms, renal involvement, bone involvement, parathyroid hormone (PTH), and serum calcium, phosphate, and vitamin D as well as 24-h urine calcium excretion. PET/CT results were also collected. In case of parathyroidectomy, the weight of the adenomas was recorded. Continuous variables were expressed as mean ± SD. Differences were evaluated with Mann-Whitney U-tests or two-sample t-tests, when appropriate. P-values ≤0.05 were considered statistically significant. PET/CT showed no adenoma in 163 (22%), adenoma in 451 (62%), hyperplasia/multiglandular disease in 32 (4%), and equivocal results in 83 (11%) patients. A total of 6/729 (1%) adenomas were located intrathyroidally and 16/729 (2%) had an ectopic location. Patients with ectopic/intrathyroidal adenoma showed significantly higher serum PTH levels than patients with no visualization of adenoma on PET. The mean mass of the adenoma was 1 ± 2.3 g in patients with orthotopic adenomas versus 2.7 ± 3.3 g in patients with ectopic/intrathyroidal adenomas; however, this was not significantly different (P = 0.09). In the presented cohort, the frequency of ectopic/intrathyroidal parathyroid adenomas was 3%. No significant difference in weight was found between orthotopic and ectopic/intrathyroidal parathyroid adenomas.

Adding the fourth dimension to computed tomography neck in the evaluation of parathyroid adenoma

Adding the fourth dimension to computed tomography neck in the evaluation of parathyroid adenoma

Preoperative visualization of parathyroid pathology in patients with primary hyperparathyroidism using PAT/KT: a retrospective study

INTRODUCTION: Topical diagnosis of pathologically altered parathyroid glands in patients with primary hyperparathyroidism is a challenge both for specialists of radial diagnostics and for planning the scope of surgical intervention. The choice of diagnostic modality for localization of parathyroid glands depends on the availability of the method for a particular medical center. PET/CT is a promising method to determine the localization of parathyroid adenomaOBJECTIVE: To analyze the experience of using PET/CT with 11C-methionine and PET/CT with 11C-choline for preoperative diagnosis of parathyroid pathology in patients with primary hyperparathyroidism.MATERIALS AND METHODS: 72 patients diagnosed with PHPT and underwent surgical treatment were included in the study. Before surgical intervention all patients underwent laboratory and instrumental investigations in the scope of: blood tests for PTH, TTH, ionized calcium, calcitonin, 25(OH)D, creatinine, phosphorus, ultrasound of the neck, computer tomography of the neck with intravenous bolus contrasting.RESULTS: PET/CT showed the highest rates of DA in the patient group before primary surgery — 90.9%, compared with ultrasound (89.6%) and CT with IV contrast (84.9%). In the group of solitary adenomas of ectopic MTCS, PET/CT also had a higher DA — 92.8% than the other modalities. In patients with relapsed or persistent disease, the informativity rates of CT with intravenous contrast and PET/CT were similar (Se — 100%, Sp — 94.1%, DT — 96.2%).DISCUSSION: The algorithm for preoperative evaluation of patients to identify the location of pathologic parathyroid glands now includes imaging with two modalities: Neck ultrasound and radionuclide imaging: planar scintigraphy (washout/subtraction), SPECT, SPECT-CT. If the results are questionable, a CT scan of the neck with contrast or PET/CT is performed as a second step. None of the modalities has 100% diagnostic accuracy. Our study demonstrated the superiority of PET/CT over ultrasound and CT w/in contrast in a group of patients scheduled for primary surgical treatment. In a small group of patients, high informative rates of PET/CT and CT with contrast were demonstrated before reoperation, confirming the great potential of these techniques in these patients.CONCLUSION: PET/CT with 11C-methionine and PET/CT with 11C-choline have high diagnostic accuracy in patients with primary hyperparathyroidism before reoperation. PET/CT and CT with contrast showed similarly high diagnostic accuracy for the diagnosis of parathyroid adenoma with persistence or recurrence of the disease in patients with primary hyperparathyroidism.

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.

Near-infrared autofluorescence pattern in parathyroid gland adenoma.

Parathyroid gland (PG) surgery is often challenging due to the small size and indistinct nature of these glands. The introduction of intraoperative near-infrared autofluorescence (NIRAF) has shown promise in localizing parathyroid tissue. However, the NIRAF features of parathyroid adenomas remain unclear. The aim of this study is to assess the NIRAF pattern of parathyroid adenomas. Patients who underwent surgery for primary hyperparathyroidism at the University Hospital of Pisa, Endocrine Surgery Unit, between December 2021 and February 2022 were enrolled in this study. Intraoperative NIRAF patterns of suspected parathyroid adenomas were evaluated, with particular attention given to the presence of a bright cap. A retrospective study was conducted on 11 patients with primary hyperparathyroidism who underwent parathyroidectomy at our institution. Histopathological examination of the 15 resected specimens confirmed 14 parathyroid adenomas (12 chief cell parathyroid adenomas, 1 oxyphil cell parathyroid adenoma, and 1 mixed cell parathyroid adenoma) and one schwannoma. All adenomas exhibited a heterogeneous NIRAF pattern, distinct from the homogeneous pattern observed in the schwannoma. A bright cap was identified in 9 out of 14 (64.3%) parathyroid adenomas (all chief cell adenomas). On the contrary, all 9 macroscopically normal PGs identified during surgery presented an homogeneous pattern. Our findings support the integration of NIRAF into parathyroid surgical procedures. The heterogeneous NIRAF pattern observed in parathyroid adenomas, often accompanied by a bright cap, offers a promising intraoperative diagnostic tool to differentiate hyperfunctioning from normal parathyroid tissue. Larger-scale randomized trials are warranted to further validate these findings.

Challenges in Managing Insulinomas and Hyperparathyroidism in MEN1: A Clinical Case Study

Pancreatic insulinoma is an uncommon neuroendocrine tumor with an incidence of approximately 1 per million people annually. While the majority of insulinomas are sporadic, a minority are associated with Multiple Endocrine Neoplasia type 1 (MEN1), a rare genetic disorder transmitted in an autosomal dominant pattern. MEN1 is characterized by the presence of hyperplastic or adenomatous parathyroid glands, pancreatic islet cell tumors, and pituitary tumors. The disorder can also involve lesions in the duodenum, adrenal glands, thymus, and bronchi. We report a case of MEN1 presenting with multiple insulinomas in a 37-year-old male, who exhibited symptoms of intermittent hypoglycemia over a decade. Diagnostic workup included biochemical assays , and imaging studies that revealed elevated insulin and C-peptide levels and hypervascular pancreatic lesions, , and pathological findings consistent with MEN1. Surgical intervention involved the enucleation of insulinomas and distal pancreatectomy, followed by removal of parathyroid adenomas. The postoperative evolution was marked by the resolution of hypoglycemic episodes and the persistence of primary hyperparathyroidism. This case underscores the complexity of diagnosing and managing insulinomas within the context of MEN1. It highlights the importance of a multidisciplinary approach to treatment and the need for ongoing surveillance to address both endocrine manifestations and psychological impacts. The findings advocate for comprehensive management strategies and support systems to improve patient outcomes and quality of life.

Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors

The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1, CDC73, GCM2, CASR, VDR, CCND1, and CDKN1B, the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B. The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B, HOXA-AS2, and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1. Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones.

12312 A Comparative Genomic Analysis Between Parathyroid Adenomas And Carcinomas With Heterozygous Germline Cdc73 Mutations

Abstract Disclosure: Y. Li: None. W.F. Simonds: None. H. Chen: None. Introduction: Parathyroid cancer is responsible for ∼1% of primary hyperparathyroidism. The hereditary form of this malignancy has been linked to germline mutations of the CDC73 gene. We previously reported that only the germline CDC73 mutations causing a significant impact on the function/expression of its encoded protein are associated with parathyroid carcinomas. On the other hand, these germline mutations may lead to only parathyroid adenomas or no parathyroid disease, suggesting incomplete penetrance. This observation raises the question of what additional genomic events are required for parathyroid tumorigenesis in carriers with germline CDC73 mutations. Methods: Twelve patients harboring heterozygous germline CDC73 mutations were included in this study. Whole exome sequencing was performed in all 12 parathyroid tumors (6 adenomas and 6 carcinomas) and the paired normal tissues. RNA sequencing was successfully performed in three of each parathyroid carcinomas, adenomas, and normal glands. The sequencing raw data were processed using the CCBR-Pipeliner. EnrichR, Gene Set Enrichment Analysis, and CIBERSORT were used for the downstream analyses. Results: All parathyroid carcinomas and adenomas had gained one somatic event predicted to cause a complete inactivation of the second CDC73 allele. Several distinctive genomic features were identified in parathyroid carcinomas compared to adenomas, including more single nucleotide variants bearing the signature of APOBEC deamination, frequent mutations among the genes involved in the PI-3K/mTOR signaling, and substantially more copy number variations and differentially expressed genes. Parathyroid carcinomas also share some genomic features with adenomas. For instance, both tumors have frequent somatic mutations and copy number loss that impact the genes related to T-cell receptor signaling and tumor antigen presentation, suggesting a shared strategy to evade immune surveillance. Consistent with these findings, an in silico estimation of immune cell composition in tumors found an absence of CD8+ T-cells in parathyroid adenomas and carcinomas. Conclusion: Our study provides evidence that biallelic inactivation of CDC73 is essential for parathyroid tumorigenesis in carriers with germline mutations of this gene. Despite sharing some genomic features with adenomas, parathyroid carcinomas have more distinctive alterations in the genome, some of which may be critical for cancer formation. Presentation: 6/2/2024

12312 A Comparative Genomic Analysis Between Parathyroid Adenomas And Carcinomas With Heterozygous Germline Cdc73 Mutations

Abstract Disclosure: Y. Li: None. W.F. Simonds: None. H. Chen: None. Introduction: Parathyroid cancer is responsible for ∼1% of primary hyperparathyroidism. The hereditary form of this malignancy has been linked to germline mutations of the CDC73 gene. We previously reported that only the germline CDC73 mutations causing a significant impact on the function/expression of its encoded protein are associated with parathyroid carcinomas. On the other hand, these germline mutations may lead to only parathyroid adenomas or no parathyroid disease, suggesting incomplete penetrance. This observation raises the question of what additional genomic events are required for parathyroid tumorigenesis in carriers with germline CDC73 mutations. Methods: Twelve patients harboring heterozygous germline CDC73 mutations were included in this study. Whole exome sequencing was performed in all 12 parathyroid tumors (6 adenomas and 6 carcinomas) and the paired normal tissues. RNA sequencing was successfully performed in three of each parathyroid carcinomas, adenomas, and normal glands. The sequencing raw data were processed using the CCBR-Pipeliner. EnrichR, Gene Set Enrichment Analysis, and CIBERSORT were used for the downstream analyses. Results: All parathyroid carcinomas and adenomas had gained one somatic event predicted to cause a complete inactivation of the second CDC73 allele. Several distinctive genomic features were identified in parathyroid carcinomas compared to adenomas, including more single nucleotide variants bearing the signature of APOBEC deamination, frequent mutations among the genes involved in the PI-3K/mTOR signaling, and substantially more copy number variations and differentially expressed genes. Parathyroid carcinomas also share some genomic features with adenomas. For instance, both tumors have frequent somatic mutations and copy number loss that impact the genes related to T-cell receptor signaling and tumor antigen presentation, suggesting a shared strategy to evade immune surveillance. Consistent with these findings, an in silico estimation of immune cell composition in tumors found an absence of CD8+ T-cells in parathyroid adenomas and carcinomas. Conclusion: Our study provides evidence that biallelic inactivation of CDC73 is essential for parathyroid tumorigenesis in carriers with germline mutations of this gene. Despite sharing some genomic features with adenomas, parathyroid carcinomas have more distinctive alterations in the genome, some of which may be critical for cancer formation. Presentation: 6/2/2024

6699 Primary Hyperparathyroidism With Severe Hypercalcemia Secondary to Giant Parathyroid Adenoma

Abstract Disclosure: M.P. Lieberman-Ulm: None. M.A. Yanez-Bello: None. V.S. Lagari-Libhaber: None. Background: Parathyroid adenomas are often detected in asymptomatic patients without palpable neck mass and are responsible for 80 to 85% of cases of primary hyperparathyroidism. Oversized or “Giant” parathyroid adenomas (GPAs) are defined as parathyroid adenomas that weigh more than 3.5 g. These are rare, representing less than 1.5% of parathyroid adenomas. The majority of reported cases of GPAs are associated with elevation of PTH and calcium levels, though usually not as high as is seen in patients with parathyroid carcinoma, where PTH levels typically reach greater than three times the upper limit of normal and serum calcium greater than 14 mg/dL. Clinical Case: A 73-year-old man presented with altered mental status and was found to have severe hypercalcemia (serum calcium 20.5 mg/dL, albumin 4.4 g/dL) and AKI stage III (eGFR 16 mL/min/1.73m2). Physical exam showed palpable, mobile, left-sided fullness, and further lab evaluation revealed intact PTH of 2,934 pg/mL, vitamin D, 25-OH of 24.8 ng/mL, and PTHrP of 14 ng/mL. Phosphorous level was not collected prior to treatment. Neck ultrasound was unremarkable. CT revealed a 9 cm hypodense lesion inseparable from the posterior aspect of the left thyroid lobe extending inferiorly to the posterior mediastinum at the level of the carina. Sestamibi scan showed scintigraphic evidence of parathyroid adenoma in the left tracheoesophageal groove. Patient was treated with IV fluids, zoledronic acid, calcitonin, cinacalcet and furosemide in addition to receiving hemodialysis on arrival. He then underwent resection of the mediastinal parathyroid gland. Pathology revealed parathyroid adenoma (16.6 g) without evidence of gross or microscopic invasion into adjacent structures, vascular or perineural invasion. Size greater than 3.5 g classified this mass as a giant parathyroid adenoma. Post-operatively, the patient’s PTH and corrected calcium normalized (17 pg/mL and 9.4 mg/dL, respectively). Conclusion: Giant parathyroid adenomas are a rare cause of primary hyperparathyroidism. Generally, parathyroid adenomas present with less severe clinical and biochemical characteristics than those of parathyroid carcinomas. However, the characteristics of GPA can be similar to parathyroid carcinoma, and differentiating between the two can be challenging. Parathyroid masses are differentiated with histologic diagnosis along with haematoxylin and eosin stain findings. In the case of our patient, his clinical picture was suggestive of parathyroid carcinoma given the severity of his disease, but pathology revealed parathyroid adenoma. Additionally, his calcium and PTH levels normalized after parathyroidectomy. This case may be representative of rare, aggressive giant parathyroid adenoma, however close follow up is imperative to ensure patient does not develop metastatic disease in the future, which would suggest underlying malignancy all along. Presentation: 6/2/2024

12492 Clinical Resolution Of Parkinsonism And Dementia Following Radio Frequency Ablation Of A Parathyroid Adenoma

Abstract Disclosure: P. Finny: None. T. George: None. A.K. Francis: None. Background: Parkinsonism is a rare neurological manifestation of primary hyperparathyroidism. Radiofrequency ablation (RFA) of parathyroid adenomas is a novel treatment modality. Clinical Case: A 78 year old lady presented to our Emergency department with hypercalcemic encephalopathy. She had long standing Diabetes mellitus, Bronchial asthma and Parkinsonism with dementia for the past 14 years. She was bed bound with dependence on carers for activities of daily living (ADL). She had been diagnosed elsewhere in 2018 to have primary hyperparathyroidism due to a right inferior parathyroid adenoma and had a right hemithyroidectomy with a failed parathyroidectomy. She was being managed with Cinacalcet 60 mg daily for the past 4 years. Prior to this admission she had discontinued Cinacalcet for a few days. Her initial serum calcium was 15.3 mg/dl (8.7-10.7), phosphorus 1.80 mg/dl (2.5-4.5) and PTH 451 pg/ml (15- 88). She was aggressively treated with intravenous normal saline hydration followed by Furosemide injection. Then she was given Calcitonin injections subcutaneously and IV Zoledronic acid infusion. Her calcium dropped to 11.8 mg/dl within 48 hours of admission, and her sensorium improved. Imaging studies showed no visible parathyroid adenoma on ultrasound, but the 4D CT scan of the neck revealed a left inferior parathyroid adenoma of size 1.1 x 1.2 cm. This was concordant on the Technetium 99m Sestamibi scan. Her MRI Brain showed bilateral globus pallidus calcification. In view of her multiple comorbidities making her a poor candidate for general anaesthesia, non-surgical options were considered. A percutaneous ultrasound guided RFA of the left parathyroid adenoma was successfully performed. Post procedure the PTH dropped from 321 pg/ml to 54.9 pg/ml within 24 hours. The calcium, phosphorus and PTH remained normal. Her Parkinsonism and dementia significantly improved and we could wean her off the anti- parkinsonian and anti-psychotic medication. She became ambulant and regained her cognitive functions. This clinical and biochemical remission was maintained over the next 22 months of follow up. Conclusion: RFA is a novel therapeutic option in treating parathyroid adenomas among surgically unfit patients. Reversal of advanced Parkinsonism following correction of chronic hypercalcemia led to this patient regaining a good quality of life. 4D CT scan of the neck is useful in localizing the parathyroid adenoma when there is discordance between the ultrasound and Sestamibi scan.

8402 The Usefulness of the Contrast-Enhanced Ultrasound (CEUS) in Preoperative Localization of Parathyroid Gland Adenomas

Abstract Disclosure: A. Żyłka: None. K. Dobruch-Sobczak: None. H. Piotrzkowska-Wróblewska: None. P. Góralski: None. J. Gałczyński: None. E. Bakuła-Zalewska: None. M. Dedecjus: None. Objectives: Preoperative localization of parathyroid gland adenomas in patients diagnosed with primary hyperparathyroidism (pHPT) is challenging process. The aim of the study was to assessed the usefulness of contrast-enhanced ultrasound (CEUS) as complimentary diagnostic modality to conventional ultrasonography for detection of hyperfunctioning parathyroid gland lesions. Methods: Between the years 2021 and 2022, 36 adult patients (33 women and 3 men, aged 37-76) diagnosed with pHPT, underwent high-resolution ultrasound (US) and CEUS of parathyroid gland adenomas, suspected after fine-needle aspiration biopsy with positive parathormone (PTH) wash-out results and/or avid in 99mTechnetium -sestamibi scintigraphy. During CEUS examination 1.5 ml of SonoVue contrast has been injected and followed by analysing of qualitative CEUS enhancement features. All patients were qualified to surgical treatment according to clinical symptoms, laboratory and imaging findings and underwent parathyroidectomy with histopathologic results confirming parathyroid gland adenomas. Analysis of the B-mode features and visual CEUS enhancement patterns was performed retrospectively. Ten CEUS qualitative parameters of lesions were assessed including: homo- or heterogenous enhancement; hyper- or hypoenhancement; distribution of contrast in wash-in phase as: centripetal, centrifugal or combined and in wash-out phase as: centrally, peripherally or combined. Then the model was extended using the results based on US B-mode imaging which involved size, echogenicity, calcifications, cystic components and vascularity patterns assessed in Color Doppler (CD) and superb microvascular imaging (SMI). Results: Histopathologic results included 36 parathyroid adenomas (in 33 women and 3 men), the medium size 18.8mm (±11.1) and volume 3.7mm3 (±8.2). In B-mode US examination the majority of lesions were assessed as hypoechoic (n=36; 100%) with dominant inhomogenous echostructure (n=20; 55.5%), mixed vascularity (n=24; 66.6%) and polar vessel observed in 14 lesions (38.8%). There were no adenomas with calcifications, cystic components were observed only in 4 nodules (11.1%). In the CEUS study, dominated qualitative features were homogenous (n=22; 61,1%) and hyperenhancement (n=27; 75%), with centripetal distribution of contrast in wash-in phase (n=24; 66,6%) and dominant centrally wash-out of the contrast (n=20; 55,5%). Conclusions: Preliminary results indicate ultrasonographic patterns characteristic for parathyroid gland adenomas in multiparametric ultrasound involved CEUS examination, which seemed to be valuable tool for localization hyperfunctional parathyroid glands. Further multicenter studies should be performed to standardize qualitative CEUS features in order to diagnose primary hyperparathyroidism preoperatively. Presentation: 6/1/2024

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

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

8402 The Usefulness Of The Contrast-Enhanced Ultrasound (CEUS) In Preoperative Localization Of Parathyroid Gland Adenomas

Abstract Disclosure: A. Żyłka: None. K. Dobruch-Sobczak: None. H. Piotrzkowska-Wróblewska: None. P. Góralski: None. J. Gałczyński: None. E. Bakuła-Zalewska: None. M. Dedecjus: None. Objectives: Preoperative localization of parathyroid gland adenomas in patients diagnosed with primary hyperparathyroidism (pHPT) is challenging process. The aim of the study was to assessed the usefulness of contrast-enhanced ultrasound (CEUS) as complimentary diagnostic modality to conventional ultrasonography for detection of hyperfunctioning parathyroid gland lesions. Methods: Between the years 2021 and 2022, 36 adult patients (33 women and 3 men, aged 37-76) diagnosed with pHPT, underwent high-resolution ultrasound (US) and CEUS of parathyroid gland adenomas, suspected after fine-needle aspiration biopsy with positive parathormone (PTH) wash-out results and/or avid in 99mTechnetium -sestamibi scintigraphy. During CEUS examination 1.5 ml of SonoVue contrast has been injected and followed by analysing of qualitative CEUS enhancement features. All patients were qualified to surgical treatment according to clinical symptoms, laboratory and imaging findings and underwent parathyroidectomy with histopathologic results confirming parathyroid gland adenomas. Analysis of the B-mode features and visual CEUS enhancement patterns was performed retrospectively. Ten CEUS qualitative parameters of lesions were assessed including: homo- or heterogenous enhancement; hyper- or hypoenhancement; distribution of contrast in wash-in phase as: centripetal, centrifugal or combined and in wash-out phase as: centrally, peripherally or combined. Then the model was extended using the results based on US B-mode imaging which involved size, echogenicity, calcifications, cystic components and vascularity patterns assessed in Color Doppler (CD) and superb microvascular imaging (SMI). Results: Histopathologic results included 36 parathyroid adenomas (in 33 women and 3 men), the medium size 18.8mm (±11.1) and volume 3.7mm3 (±8.2). In B-mode US examination the majority of lesions were assessed as hypoechoic (n=36; 100%) with dominant inhomogenous echostructure (n=20; 55.5%), mixed vascularity (n=24; 66.6%) and polar vessel observed in 14 lesions (38.8%). There were no adenomas with calcifications, cystic components were observed only in 4 nodules (11.1%). In the CEUS study, dominated qualitative features were homogenous (n=22; 61,1%) and hyperenhancement (n=27; 75%), with centripetal distribution of contrast in wash-in phase (n=24; 66,6%) and dominant centrally wash-out of the contrast (n=20; 55,5%). Conclusions: Preliminary results indicate ultrasonographic patterns characteristic for parathyroid gland adenomas in multiparametric ultrasound involved CEUS examination, which seemed to be valuable tool for localization hyperfunctional parathyroid glands. Further multicenter studies should be performed to standardize qualitative CEUS features in order to diagnose primary hyperparathyroidism preoperatively. Presentation: 6/1/2024

8385 Coexistence of Parathyroid Adenoma & Papillary Thyroid Cancer: A Rare Case Report

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. M. Roy: None. S. Rathore: None. Prevalence of primary hyperparathyroidism (pHPT) ranges from 0.1- 0.4% in general population. Nodular thyroid disease is an increasingly common incidental diagnosis due to widespread use of ultrasound. Papillary thyroid cancer (PTC) is the most common cancer of thyroid gland. Here we report a 53 year old post-menopausal woman presented with weight loss, generalised body aches, arthralgia, myalgia, and proximal muscle weakness. She was hypertensive and clinically euthyroid. Physical examination revealed generalized tenderness all over the body but no thyroid or parathyroid nodules on palpation. Biochemical evaluation showed hypercalcemia 12.1mg/dl (8.4-10.2mg/dl), PTH>2000pg/ml (14-72pg/ml), ALP-1855 U/L (40–125 U/L), decreased phosphorous of 2.4mg/dl (25-4.6 mg/dl), and vitamin-D of 46 nmol/L ( 75-250 nmol/L). USG neck revealed a heterogeneous lesion at the lower pole of right lobe of thyroid gland & two small hypoechoic nodules seen in the right lobe of thyroid gland. FNAC from nodules was inconclusive. USG abdomen revealed nephrocalcinosis. DEXA scan showed severe osteoporosis. Tc99mSestamibi SPECT-CT showed uptake at lower pole of right lobe of thyroid. On exploration, two nodules were palpated in the right lobe of the thyroid and simultaneous right hemi-thyroidectomy was performed. Histopathologic report confirmed parathyroid adenoma (figure 1) as well as presence of carcinoma in the two nodules: one was a papillary thyroid cancer (Classic variant) and the other a follicular variant of papillary thyroid carcinoma (figure 2). Margins were negative for malignancy. She was treated with levothyroxine to maintain TSH <0.1U/L and followed up with annual ultrasound screening. At 2 year follow up, patient was symptom free with improved T score on DEXA scan and no nodule over residual thyroid gland. Discussion: Co-existence of pHPT and PTC ranges from 2.3-4.3%. The use of ultrasound neck as a routine imaging modality for localisation of parathyroid adenoma allows detection of thyroid nodules. Benign and/or malignant thyroid nodules are commonly seen in patients with pHPT and this can range from 2-15%. Women have higher risk for co-existence. The relationship between the two diseases is thought to be incidental. Some authors have suggested possible role of shared genes, embryological factors, transcription factors, vitamin-D deficiency and hyperparathyroidism that could lead to activation of angiogenic factors and carcinogenesis. Fig. 1. Parathyroid adenoma. (a)Tc99m sestamibi scan showing right inferior parathyroid adenoma (b) Parathyroid adenoma (400x high power) comprising predominantly of Chief cells with mild pleomorphism. Fig. 2. Histopathology of PTC. (a)Papillary Carcinoma thyroid. 10xPhotomicrograph showing areas of calcification. (b) Papillary Carcinoma thyroid. Photomicrograph showing thyroid with papillary pattern with areas of infiltration. Presentation: 6/1/2024

7508 Primary Hyperparathyroidism Caused By A CDC73-related Atypical Parathyroid Tumor

Abstract Disclosure: R. Cardenas: None. S. Tariq: None. R. Habibi: None. N. Ebrahimi: None. E. Astiazaran-Symonds: None. Background: Primary hyperparathyroidism (PHPT) is a common endocrine disease, causes include: parathyroid adenomas (80-85%), parathyroid hyperplasia (10-15%), atypical parathyroid adenomas (APA) (1.2 %) and parathyroid carcinomas (PC) (1%). APA share many anatomic and histopathologic features with PC making the distinction between the two challenging. Although most are sporadic, some APA are caused by germline mutations in the CDC73 gene, which is associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome PC and familial isolated PHPT with APA. Clinical Case: A 42-year-old female presented to the clinic for evaluation of recurrent PHPT. She was diagnosed at age 22 when she experienced fatigue, polydipsia with hypercalcemia (12.9mg/dl). She underwent superior bilateral parathyroidectomy with pathology consistent with parathyroid adenoma. Twenty years later, symptoms recurred and tests showed hypercalcemia (13.0 mg/dl), elevated PTH (252 pg/dl), kidney function preserved (GFR: 82.5 ml/min), normal vitamin D 25 OH (31 ng/dl). Patient denied history of nephrolithiasis or fractures. Family history was positive for kidney stones in father and siblings, also history of a jaw tumor in niece. Sestamibi scan showed a left inferior parathyroid adenoma. Patient underwent resection of the adenoma; pathology revealed a left parathyroid adenoma with atypical parathyroid tumor, >95% cellularity with cytologic features concerning for malignancy, prominent macronucleoli, necrosis, elevated mitotic activity and Ki67 with 15% tumor cells without vascular invasion. Post-op Calcium and PTH normalized (9.6 mg/dl and 10.8 pg/ml, respectively). Genetic testing via multi-gene panel identified a whole gene deletion of CDC73, consistent with hyperparathyroidism-jaw tumor syndrome. Panoramic jaw x-rays did not show jaw tumors. Genetic testing for family members is underway. Conclusion: Although somatic mutations in CDC73 are frequently found in sporadic APA and PC, germline mutations are a rare cause of PHPT associated with these tumors. Histopathological examination is necessary to confirm the diagnosis of APA and to differentiate it from PC, which has a recurrence rate >50%. APA should be treated as a “tumor of uncertain malignant potential” and needs to be carefully and periodically followed up with measurement of Ca, PTH and vitamin D. Confirmation of a CDC73 mutation by genetic testing helped identify the increased risk for other associated tumors in jaw, kidneys and uterus prompting initiation of surveillance with panoramic jaw x-rays with neck shielding, renal US and pelvis US. Genetic testing of family members will allow timely detection and treatment of individuals at risk. Presentation: 6/3/2024

7073 Treasure or Terror: Dilemmas in the Management of a Giant Parathyroid Adenoma

Abstract Disclosure: A.D. Galia: None. R. De Guzman: None. S. Suib - Salvilla: None. Background: Primary hyperparathyroidism is a common endocrine disorder with an incidence of 25 per 100,000 people in the general population. More commonly caused by parathyroid adenomas in 80-85%, giant parathyroid adenomas weighing more than 3.5 g or measuring more than 2 cm may rarely occur. There have been no reported prevalence data of parathyroid adenoma among ASEAN countries, especially in the Philippines. Clinical Case: A 43-year-old, female, Filipino, initially asymptomatic with anterior neck mass for 8 years then presented with generalized body malaise, easy fatigability, lower extremities pain and numbness. Six years ago, neck ultrasound showed left thyroid nodule; abdominal sonogram showed bilateral medullary nephrocalcinosis, with hypercalcemia, elevated intact PTH, and elevated creatinine. She was unable to undergo further workup and management until she presented a few months ago because of generalized body malaise, abdominal pain, nausea, and vomiting because of hypercalcemia and non-oliguric renal failure. Serum ionized calcium was 1.90 mmol/L (NV 1.15 - 1.30), intact PTH 2000 pg/mL, and serum creatinine 6.08 mg/dL. With unavailability of calcitonin and pamidronate, medical management of hypercalcemia included cautious hydration followed by diuresis, zoledronic acid, and cinacalcet. Sestamibi scan showed a large parathyroid adenoma. Bone densitometry showed osteoporosis (T score = below -2.5). After medical evaluation, she underwent parathyroidectomy under general anesthesia. Intact PTH level perioperatively were as follows: pre-op = 2,078.2 pg/mL; 30 mins = 477.1 pg/mL; 1 hour = 335.7 pg/mL, 1 day = 67.2 pg/mL. The resected mass was 4.2 x 2.4 x 1.6 cm and weighed 4 g; histopathology report was consistent with Parathyroid Adenoma. Post-operatively, patient did not develop hungry bone syndrome. Conclusion: Giant parathyroid adenoma is a rare condition that is usually asymptomatic but can lead to serious complications. In the Philippines, limited availability of laboratory techniques (PTH and sestamibi scan) and availability of medications for hypercalcemia may contribute to underdiagnosis and management. Early detection and treatment can help prevent further complications and improve the overall quality of life. Presentation: 6/3/2024

12350 A Rare Case Of Giant Parathyroid Adenoma Managed Medically For 8 Months: A Case Report

Abstract Disclosure: S. Labram: None. L. Bilandzic: None. Background: Single parathyroid adenoma is the most common cause of primary hyperparathyroidism, and is attributed to approximately 85% of cases[1]. However, those classified as giant (weighing over 3.5 g and having a size greater than 2cm2) are exceedingly rare. This reports a rare case of primary hyperparathyroidism caused by giant parathyroid adenoma and details biochemical response following medical and surgical management. Case Report: A 64 year old black female presented with severe abdominal pain, confusion and constipation. Investigations revealed severe hypercalcemia of 17.3 mg/dl with massively elevated parathyroid hormone of 1255 pg/mL. Ultrasound showed a large hypoechogenic lobulated mass inferior to the left thyroid lobe representing a giant parathyroid adenoma. Due to delayed surgery the patient was initially treated medically over the course of 8 months. Over these months she was admitted to hospital 3 times for symptomatic hypercalcemia and received a total of 3 zolendronic acid infusions. Despite this she was unable to achieve long term remission of hypercalcemia. Cinacalcet was added and tolerated at the dose of 30 mg daily. Hypercalcemia improved, but remained elevated at a range of 11-13 mg/dL and the symptoms of brain fog and constipation did not subside entirely. She was eventually able to undergo surgical resection, and a giant parathyroid adenoma weighing 8.9 g was excised. Intraoperative intact parathyroid hormone (IOiPTH) sampling showed > 50% reduction (prior to removal 878pg/mL, 10 minutes after removal 132 pg/ml, 20 minutes after removal 96pg/mL). Pathological review showed an atypical parathyroid tumor. As the tumor lacked invasive growth it did not meet criteria for carcinoma. Conclusions: This is a rare case of primary hyperparathyroidism caused by a giant solitary parathyroid adenoma. The gold standard for management of primary hyperparathyroidism secondary to parathyroid adenoma is minimally invasive parathyroidectomy. However in our case, due to inability to access immediate surgery, challenging and prolonged medical treatment of severe hypercalcemia followed for 8 months. Ultimately, normalization of calcium level was achieved only by surgical intervention. IOiPTH measurements showed appropriate decrease confirmatory for the complete removal of the adenoma.

8063 Cystic Parathyroid Adenoma: A Rare Cause Of Severe Hypercalcemia

Abstract Disclosure: M. Owrangi: None. F. Hasan: None. Introduction: Parathyroid adenomas are the most common cause of primary hyperparathyroidism, but within this category, a rare subtype exists - cystic parathyroid adenomas (CPAs). Comprising only 0.5-1% of all parathyroid lesions, CPAs present unique diagnostic and therapeutic challenges. We report a case of a female patient presenting with severe hypercalcemia caused by a CPA. Case presentation: A 44-year-old African American female with a history of nephrolithiasis presented with abdominal pain and signs of dehydration. Labs were remarkable for serum calcium 13.2 mg/dL, albumin 4.0 g/dL, phosphorus 1.8 mg/dL, iPTH 617.7 pg/mL, 25-OH vit D 12.1 ng/mL, creatinine 0.85 mg/dL. She was initially resuscitated aggressively with IV fluids resulting in an improvement in serum calcium level to 10.3 mg/dL. Thyroid US showed a cystic nodule deep to the left thyroid lobe. Sestamibi parathyroid scan was consistent with a left superior parathyroid adenoma. She underwent 2 gland parathyroidectomy 3 months after the initial presentation. Intraoperatively serum PTH decreased by 91% after resection of the 2 parathyroid adenomas. Pathology confirmed the presence of 2 parathyroid adenomas, the larger one measuring 2.8 cm and weighing 3.8 g. Discussion: We describe a case of a middle-aged female presenting with severe hypercalcemia due to CPA. Her initial presentation was concerning for parathyroid carcinoma given the severity of hypercalcemia. However, the radiologic findings, coupled with surgical pathology, indicated that she had CPA. CPAs can be either functional, causing primary hyperparathyroidism (PHPT) with elevated serum calcium levels, or non-functional, remaining asymptomatic. Clinical features of PHPT associated with CPAs are similar to those with solid adenomas and include fatigue, GI symptoms, nephrolithiasis, bone pain, and neuropsychiatric manifestations. However, CPAs may exhibit certain distinct presentations: i) higher pre-operative serum calcium levels; and ii) increased risk of symptomatic hypercalcemia. Despite their rarity, CPAs deserve special attention due to their unique presentation, challenging diagnosis, and potential for severe hypercalcemia. Surgical parathyroidectomy is the definitive treatment for functional CPAs. Accurate localization and complete excision of the adenoma are crucial to avoid recurrence. Most CPAs occur in the fourth and fifth decade of life and are more common in women (female to male ratio of 2.5:1). 65-85% of cases are located in the neck and the majority arise from the inferior parathyroid glands and are left-sided, and may very rarely be intrathyroidal. Presentation: 6/2/2024