Atypical Parathyroid Adenoma Research Articles

7254 An Unusual Case Of Hypercalcemia

Abstract Disclosure: S. Shushtarian: None. M. Balogun: None. T. Kaur: None. Hypercalcemia varies depending on severity. Higher serum calcium levels and more severe symptoms may indicate primary hyperparathyroidism or a malignant cancer. This is a case of a 32 year old female who presented with recurrent history of nephrolithiasis, found to have hypercalcemia of 13.4 mg/dL and parathyroid hormone of 1928.9 pg/mL, with phosphorus of 1.5 mg/dL. Ultrasound of her thyroid revealed a complex nodule arising from the right parathyroid gland measuring 2.2 X 2.0 cm. CT chest revealed diffuse osseous sclerosis secondary to metabolic disorder. Sestamibi scan did not localize any parathyroid adenoma. MRI of the thoracic and lumbar spine showed multiple small enhancing lesions throughout the pelvis and in the left rib, likely brown tumors related to hyperparathyroidism. X-ray of bony prominence on the patient’s left knee revealed a large lytic lesion of the proximal tibial diaphysis measuring 5.1 X 1.9 cm, concerning for aggressive neoplasm. Subsequent left tibial bone biopsy revealed giant cell rich lesions consistent with brown tumor of hyperparathyroidism. Due to our patient’s high calcium levels and large nodule size, she was referred to a tertiary center as the concern for parathyroid carcinoma and post-op hungry bone syndrome was high. Pre-op PTH level was 1408 pg/mL and post-op PTH was 96 pg/mL. The tumor removed was 2.1 cm. Post surgical pathology was consistent with atypical parathyroid adenoma. Patient was referred for genetic testing. An atypical parathyroid adenoma (APA) only accounts for 1.2 to 1.3% of cases of primary hyperparathyroidism. 80-85% of primary hyperparathyroidism is due to typical adenoma, and 10 to 15% of cases are due to hyperplasia or multiple gland disease. APA can often be confused with parathyroid carcinoma (PC), as they both have a 1:1 male to female ratio, high serum calcium levels, symptomatic hypercalcemia, high PTH levels, and fragility fractures. There are studies showing that both APA and PC have loss of nuclear parafibromin immunoreactivity. In addition, neither APA nor PC have any correlation with menopause, hormones, or gene deletions, unlike typical adenomas. Biopsy is necessary for diagnosis as the histological and immunohistochemical differences can differentiate APA vs PC. Histological features include pseudo-capsular invasion, bands of fibrosis, pronounced trabecular growth, nuclear atypia, and prominent nucleoli. Also, APA has a strong membranous staining pattern of E-cadherin, whereas PC has a loss of membranous staining. These differences are essential as although APA and PC clinically present similarly, APA lacks the invasive growth and possibility for metastatic disease that PC has. The likelihood for relapse of APA is low. Presence of malignancy criteria are indicative that a mass is actually PC and not APA. Despite this, APA is still considered a tumor of uncertain malignant potential and requires follow up. Presentation: 6/3/2024

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

Severe Hypercalcemia as Presentation of Atypical Cystic Parathyroid Adenoma: A Case Report

Severe Hypercalcemia as Presentation of Atypical Cystic Parathyroid Adenoma: A Case Report

Atypical Parathyroid Adenoma with Multiple Brown Tumors: A Rare Case

Atypical Parathyroid Adenoma with Multiple Brown Tumors: A Rare Case

O-05 A novel mutation of MEN1 gene in familial Multiple Endocrine Neoplasia Type 1 (MEN1): A report of two cases

Abstract Introduction Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare (1-9/100000) autosomal dominant disease. It is characterized by primary hyperparathyroidism (90%), enteropancreatic tumor (60-70%), non-functional adrenal adenomas (30%) and pituitary tumors (10-20%). Herein, we present two cases in the same family with MEN1 syndrome caused by a novel mutation. Clinical Case 1: 49-year-old male presented to our clinic with fasting hypoglycemia. Fasting serum glucose (FSG) was 51 mg/dl and serum cortisol was 18 ug/dl. During the hypoglycemia in prolonged fasting test, the serum levels of glucose, insulin and C-peptide were 37 mg/dl, 17.3 mu/l, 7.75 ng/ml respectively (Table 1). Abdominal MRI revealed mass lesions in the pancreas (Figure 1). Ultrasonography of the neck and MIBI scintigraphy performed because of the high levels of calcium and parathyroid hormone (PTH), were consistent with parathyroid adenoma (Table 2). Pituitary MRI showed a 12 mm macroadenoma. He underwent parathyroidectomy and distal pancreatectomy simultaneously. The resected specimens revealed a well-differentiated neuroendocrine tumor (NET) of the pancreas and parathyroid adenoma. The patient had no new hypoglycemic episodes after surgery and serum calcium remained within the normal range (Table 2). Central hypothyroidism and hypogonadotropic hypogonadism which was resulted from the pressure of the adenoma was managed medically. Genetic testing revealed a heterozygous mutation in NM_001370251.1:c.949del(HET). First degree relatives of the patient were screened for MEN. Clinical Case 2: The son of case 1, an 18-year-old male, presented with fasting hypoglycemia. He had a BMI of 37 kg/m2 and underwent gastric botox 3 months prior to his presentation. FPG was 52 mg/dl and serum cortisol was 20 ug/dl. Prolonged fasting test confirmed the diagnosis of insulinoma (Table 1). Abdominal MRI showed a pancreatic tail mass 37×22 mm in size. Gallium 68 PET/CT DOTATATE revealed increased uptake in multiple lesions in the pancreas. Ultrasonography and MIBI scintigraphy showed a parathyroid adenoma. A nonfunctional microadenoma was detected in pituitary MRI. The patient underwent distal pancreatectomy. Following pancreatectomy, right superior and left inferior parathyroidectomies were performed. Since his serum calcium levels started to increase in 48 hours after the operation, the patient has had second operation for left superior parathyroidectomy. After the operation, the serum calcium and parathyroid hormone levels were 9.2 mg/dl, 58 pg/ml respectively. Specimens revealed well-differentiated NET and atypical parathyroid adenoma. The patient was found to have the same genetic mutation with his father and during the follow up the serum glucose and calcium levels remained within the normal range (Table 2). Conclusion In the genetic examination the heterozygous mutation NM_001370251.1:c.949del(HET) in exon 7/11 of the MEN1 gene found in our patients represents a novel mutation.Figure 1.MRI showing pancreatic masses Table 1.Laboratory findings Table 2.Prolonged fasting test

Fine needle aspiration biopsy of parathyroid; is it meaningful? A cytologic study of 81 cases with histological and clinical correlations.

Recognizing the parathyroid gland and distinguishing the parathyroid from thyroid lesions in fine needle aspiration (FNA) is challenging. This study aimed to identify cytomorphologic features suggestive of parathyroid origin and to assess the utility of cytopathology in conjunction with ancillary tests in the identification of parathyroid glands. Ultrasound (US) guided FNA of parathyroid gland and lesions in 81 patients were reviewed concerning clinical history and correlated to histopathologic findings in available cases. FNA smears were evaluated for cellularity, architectural patterns, cellular and nuclear features, and background of the smears. In 78 cases, FNA was supplemented by a measurement of parathormone (PTH) levels in the needle washout fluid (FNA-PTH assay) and/or GATA3/PTH/chromogranin-A immunostainings. Sixty-four cases were diagnosed cytologically as parathyroid lesions in conjunction with FNA-PTH assay and/or immunocytochemical examinations. In an additional nine cases, a diagnosis of parathyroid lesions was rendered after repeated FNA with FNA-PTH assay. The histolopathologic diagnosis of surgically excised cases (n = 75) included parathyroid adenoma (60 cases), atypical parathyroid adenoma (4 cases), parathyroid hyperplasia (10 cases), and parathyroid carcinoma (1 case). Major cytological findings of parathyroid tissue included high cellularity, scattered naked nuclei, cribriform and three-dimensional clusters, stippled chromatin, and oxyphilic cytoplasm while papillary pattern or colloid-like material was identified in three cases respectively. No nuclear grooves or inclusions were seen in any case. High cellularity scattered naked nuclei, cribriform and three-dimensional patterns, stippled chromatin and oxyphilic cytoplasm are cytomorphologic features that favour parathyroid origin. A combination of these features with FNA-PTH assay and/or GATA3, PTH, and chromogranin-A immunostainings on cytologic specimens aid in the identification of parathyroid glands and the distinguishing of parathyroid from thyroid lesions.

SAT201 A Rare Case Of A Mediastinal Atypical Parathyroid Adenoma Resulting In Severe Hypercalcemia And Brown Tumor

Abstract Disclosure: O.A. Aluko: None. D. Franey: None. R. Quiros: None. W. Burfeind: None. R.E. Amori: None. Introduction: Primary hyperparathyroidism is most often from parathyroid adenomas located usually in close association to the thyroid gland. Ectopic parathyroid glands result in significant variability in the position of the gland, however rarely in the mediastinum. We report a case of a patient with severe hypercalcemia from a large, ectopic mediastinal parathyroid adenoma. Case Report: A 53-year old male with a past medical history of hypercalcemia and nephrolithiasis was sent to the ER for evaluation of hypercalcemia after he was found to have a corrected calcium of 12.5 mg/dl (n8.4 - 10.2 mg/dl) on routine labs. Repeat blood work at presentation confirmed hypercalcemia with a corrected calcium 11.9 mg/dl and elevated ALP of 211 U/l (n 43 - 122 U/L), elevated initial PTH of799 pg/ml (n 18.4 - 80.1 pg/ml), Vit D 32.7 ng/ml (n 30 - 100 ng/ml), and low phosphorus 2.4 mg/dl (n2.7 - 4.5 mg/dl). Calcium slightly improved to 11.7 mg/dl after IV hydration. Chest CT showed a large mediastinal mass compressing trachea and esophagus, suspicious for parathyroid origin, with a smaller left sided lesion suspicious for parathyroid adenoma. CT also showed multiple bone lesions likely brown tumors. He underwent complete robotic resection of the mediastinal mass. Immediately prior to surgery, PTH was 1002.8 pg/ml, and fell to 131.1 pg/ml and 44.1 pg/ml following removal of the mediastinal mass. Adherence of the mass to surrounding structures made resection challenging, resulting in a right vocal cord paralysis. After surgery, he was empirically started on IV calcium and calcitriol for high clinical concern for hungry bone syndrome, both later discontinued as serum calcium remained within normal limits. Pathologic findings reported as highly suspicious, however not definitive for parathyroid carcinoma with no evidence of perineural or lymphovascular invasion. Given rarity, he was referred to a tertiary cancer center where he was diagnosed with Atypical parathyroid Adenoma (APA). He underwent a right pubic biopsy with pathology diagnosis of brown tumor of hyperparathyroidism. He started on cinacalcet 30 mg daily after surgery. There is a future plan for resection of the smaller left sided parathyroid adenoma. Conclusion: This case highlights two rare entities; a mediastinal ectopic parathyroid and atypical parathyroid adenoma. Atypical Parathyroid Adenoma is a not-well defined entity which could mimic a parathyroid carcinoma as seen in our case. The location of the mass in the superior mediastinum is unusual, making it more difficult to diagnose, and could increase risk of complications during resection. Delayed diagnosis of these entities can lead to severe hypercalcemia and skeletal complications infrequently seen in common primary hyperparathyroidism cases. Presentation: Saturday, June 17, 2023

SAT204 Parafibromin: Key To The Diagnosis Of Atypical Parathyroid Adenoma In A Patient With Suspected Carcinoma

Abstract Disclosure: V. Anunobi: None. K. Fernandez-Lopez: None. C. Clement: None. N. Shah: None. L. Belalcazar: None. Introduction: Parathyroid carcinoma (PTCa), although a rare endocrine malignancy, should be considered in the differential diagnosis of severe parathyroid (PTH)-mediated hypercalcemia. We present the case of a patient in whom clinical presentation suggested a PTCa, but histological analysis with the use of a parafibromin (PF) stain helped identify the patient’s parathyroid mass as an atypical parathyroid adenoma (APTa). PF stain is now in the World Health Organization (WHO) guidelines for the differentiation of PTCa and APTa. Case Presentation: A 71-year-old woman was admitted to the hospital for an incidental finding of hypercalcemia and complaints of fatigue, myalgias, constipation and generalized weakness. On exam, the patient was alert and oriented; she had a palpable right neck nodule. Laboratory testing included serum calcium of 13.9 mg/dL (8.6-10.6mg/dL) and phosphorus of 2.4 mg/dL (2.5-5.0 mg/dL). PTH level was 3,547.4 pg/mL (12-88 pg/mL) and eGFR was 67ml/min/1.73m2. Patient had undergone a neck ultrasound prior to admission that described a 2.6 cm right thyroid nodule, however fine needle aspiration revealed that the nodule was a parathyroid mass. Further imaging, including a sestamibi nuclear scan and a neck tomography, confirmed the presence of a large right inferior parathyroid adenoma. After correction of hypercalcemia, the patient underwent a right parathyroidectomy and right hemithyroidectomy. Pathology identified a 7.7 g mass, 3 cm. on its greatest diameter. There was no evidence of lymphovascular or perineural invasion, or extension into the parathyroid capsule or thyroid gland. The mass was strongly positive for PF staining in more than 50 % of tumor cells and was categorized as an APTa. Discussion: Differentiating APTa from PTca is challenging. Preserved PF tumor expression in parathyroid tumors makes PTca unlikely and is linked with a low risk of tumor recurrence. Endocrinologists need to be aware of the utility of the PF stain when evaluating patients suspected to have a PTca. The WHO now recommends that a PF stain be included in the pathological evaluation of these tumors. Presentation: Saturday, June 17, 2023

SAT188 Atypical Parathyroid Adenoma: A Diagnostic Challenge Of Primary Hyperparathyroidism

Abstract Disclosure: S. Bendaram: None. L. Dulipsingh: None. Introduction: Atypical parathyroid adenomas(APA) are parathyroid neoplasms with some atypical histological features and of indeterminate malignant potential. They may occur sporadically or as a part of hereditary syndromes and contribute to 1.2-1.3% cases of Primary Hyperparathyroidism (PHPT). Here, we present an interesting case of hypercalcemia secondary to PHPT due to an underlying APA. Case Presentation: 28 year old white female with no known significant past medical history presented to ED with symptoms of nausea, vomiting and dizziness on standing. Physical examination was unremarkable except for dry mucous membranes and decreased bowel sounds. Initial labs revealed a total calcium of 19.6 mg/dl (8.4-10.2), PTH of 1161pg/ml (10-65), creatinine 1.2mg/dl (0.5-1.0), albumin 5.0 g/dl (3.5-5.0), ionized calcium 2.37 mmol/L (1.19-1.35), phosphorus 3.4 mg/dl (2.5-4.5), magnesium 1.6 mg/dl (1.7-2.8) TSH 0.51 uIU/ml (0.35-5.5), 25-hydroxy Vitamin D 24 ng/ml (30-100),1,25-dihydroxy Vitamin D 68 pg/ml (20-79) and PTHrP 19 pg/ml (11-20). Family history was negative for hypercalcemia, hyperparathyroidism, fragility fractures, pancreatic disease or any genetic syndromes. Inpatient treatment included IV fluids, 2 doses of calcitonin and Pamidronate 60 mg IV. Subsequently, over the hospital course, calcium improved to 11.9 mg/dl with improvement in her symptoms and she was discharged home. 24-hour urine calcium checked on an outpatient visit, after vitamin D replacement, revealed low urine calcium of 31 mg/24 hr. Ultrasound Thyroid demonstrated a 3.7 cm mass inferior to the right hemithyroid, suspicious for parathyroid adenoma versus abnormal lymph node. CT Parathyroid with and without contrast revealed normal thyroid and bilateral inferior parathyroid adenomas, right larger than left. She underwent en-bloc resection of right thyroid and right inferior parathyroid gland with final pathology showing atypical parathyroid adenoma, without evidence for obvious parathyroid carcinoma or metastatic disease. Genetic testing for a total of 53 genes including MEN, BRCA1, BRCA2 were negative. PTH levels normalized post-surgery. Conclusion: Atypical Parathyroid Adenomas have a clinical and biochemical profile more severe that the typical adenomas and, to some extent, similar but less severe to that of patients with parathyroid carcinoma, creating an overall diagnostic challenge. The molecular mechanisms are unclear, with germline CDC73 mutations appearing to be the most common defect. Due to uncertain malignant potential, a close and careful monitoring is recommended for these patients. Presentation: Saturday, June 17, 2023

Differences Between Atypical Parathyroid Tumors and Parathyroid Adenomas in Patients with Primary Hyperparathyroidism

Differences Between Atypical Parathyroid Tumors and Parathyroid Adenomas in Patients with Primary Hyperparathyroidism

Somatic and Germline Mutations in Atypical Parathyroid Tumors

This case series examines somatic and germline mutations in atypical parathyroid adenomas using broad next-generation sequencing of tumor samples obtained from patients who underwent surgical resection from 2020 to 2022.

Atypical parathyroid adenomas, a challenging diagnosis and management - Case Report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Atypical parathyroid adenomas and parathyroid carcinomas: Are there any differences?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Severe PTH-dependent Hypercalcemia Secondary to Atypical Parathyroid Adenoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1406955: Two Parathyroidectomies in the Third Trimester for Severe Primary Hyperparathyroidism (PHPT) Resulting in Distinct Maternal and Fetal Outcomes

Parathyroidectomy (PTX) is well-tolerated in the second trimester of pregnancy in women with severe PHPT. We present two women requiring PTX in the third trimester of pregnancy due to the severity of the disease. Case 1: 30 y.o female presented at 33 weeks’ gestation with leg pain and severe PTH-mediated hypercalcemia; serum corrected calcium 4.2mmol/L (NR: 2.15-2.6), PTH 147.9 pmol/L (NR:1.6-6.9). She was symptomatic for 2 yrs prior and had a history of nephrolithiasis; the renal US showed 10-20 non-obstructing renal calculi. Femur X-ray demonstrated an aggressive lesion, identified as a brown tumor, on histopathology with additional bone lesions on skeletal survey. Severe hypercalcemia was managed with IV fluids, calcitonin and cinacalcet 30 mg BID. Neck-CT showed a 4cm parathyroid adenoma with no overt malignant features. Subtotal PTX was performed at 33w2d, and PTH dropped to 4.7pmol/L postop. Histopathology reported atypical parathyroid adenoma. Post PTX patient went into premature rupture of membranes, c-section done at 34 weeks’ gestation. Day 8 post PTX, the patient developed hungry bone syndrome, she also had a mechanical fall and sustained a pathological fracture of the femur, the site of brown tumor. Baby was admitted to NICU with hypoparathyroidism, resolved at 3 months of age. Case 2: 32 y.o female presented at 27 weeks’ gestation with incidental hypercalcemia and high PTH. Nausea and vomiting worsened from the 18th week of gestation. No end-organ involvement. Corrected calcium 3.04 mmol/L, PTH 17.1 pmol/L. Managed with IV fluids, and remained symptomatic with no improvement in hypercalcemia. PTX for parathyroid adenoma was performed at 30 weeks’ gestation with excellent maternal and fetal outcomes. PTH dropped to 2.0 pmol/L postop. Had spontaneous vaginal delivery at 39 weeks’ gestation, no neonatal hypocalcemia. Baby has normal milestones. Biochemical workup for Multiple Endocrine Neoplasia type1 (MEN1) was unremarkable for both patients, DNA testing is outstanding. The duration of PHPT, the severity of hypercalcemia, and the involvement of end-organ damage are critical factors that may influence both maternal and fetal outcomes in women with PHPT who undergo PTX in the third trimester.

Clinical and genetic analysis of atypical parathyroid adenoma compared with parathyroid carcinoma and benign lesions in a Chinese cohort.

The malignant potential and molecular signature of atypical parathyroid adenoma (APA) remain elusive. Data from Asia are still lacking. This was a retrospective study on a large APA cohort in a single center from mainland China. A total of 320 patients with primary hyperparathyroidism (PHPT), containing 79 APA, 79 Parathyroid cancer (PC) and 162 benign lesions cases, were enrolled after surgery for collection of clinical data and genetic analysis. APA patients showed earlier mean onset age than benign group (46.9 ± 17.1 vs. 52.0 ± 14.3 yrs). Less bone involvement and gastrointestinal symptoms were presented in APA compared to PC (35.4% vs. 62.0%, and 17.7% vs. 41.8%), while more urolithiasis was seen in APA than in benign lesions (57.0% vs. 29.6%). The APA group had moderate hypercalcemia (mean 3.02 ± 0.44mmol/L) with elevated serum PTH (median 593.0pg/ml) and proportion of hypercalcemic crisis as 22.8%, all higher than those of benign lesions but lower than those of PC group. The recurrence/no remission rate of the APA group was significantly lower than that of the PC and similar to the benign group (5.1% vs. 31.6% vs. 3.1%). Germline CDC73 mutation was the most common molecular abnormality in both PC and APA subjects. APA patients with nonsynonymous germline variants showed earlier onset age (28.5 ± 16.9 vs. 48.1 ± 17.7 yrs) and more cases developing no remission/recurrence (25.0% vs. 0.0%). Patients with APA presented clinical and biochemical characteristics much less severe than PC and resembling the benign neoplasms, with a relatively good prognosis. Germline gene variations were associated with earlier onset and probably more recurrence of PHPT in APA.

Shear wave elastography for differentiating parathyroid neoplasms with malignant diagnosis or uncertain malignant potential from parathyroid adenomas: initial experience

ObjectiveParathyroid carcinoma (PC) and atypical parathyroid tumor (APT) are rare parathyroid disorders carrying the risk of recurrence of varying degrees. This study aims to explore the value of 2D-shear wave elastography (SWE) in the discrimination of PC/APT among suspicious parathyroid lesions.Methods and materialsIn this prospective study, patients with primary hyperparathyroidism and suspicious parathyroid lesions on ultrasonography (US) were recruited. All the lesions were assessed by SWE before surgery. The velocity (m/s), Young’s modulus (Kpa), and elastogram of SWE were compared between pathologically proven parathyroid carcinoma or atypical parathyroid tumor (Group1) and parathyroid adenoma (Group2). All the SWE parameters were displayed at the setting of 50 or 70 kPa. Correlations between SWE and the lesion size as well as biochemical parameters were analyzed.Results36 target lesions were enrolled for analysis. The mean shear wave velocity (SWV) between the two groups was 2.4 m/s vs 1.9 m/s, respectively, while the mean Young’s modulus was 11.1 kPa vs 18.2 kPa, respectively. The cut-off values are 2.35 m/s and 17.05 kPa correspondingly. The sensitivity and specificity of the selecting cut-off values were 0.56 vs 0.63 and 0.95 vs 1.0 (area under the curve [AUC]: 0.813 vs 0.852 [95% confidence interval (CI): 0.669–0.956 vs 0.720–0.983]; p < 0.001, p < 0.001; respectively). In contrast, the max SWV and Young’s modulus showed a better sensitivity of 0.75 and 0.81, respectively. The “colored lesion” and “stiff rim” patterns on the elastogram are more indicated in parathyroid carcinoma and atypical parathyroid tumor, whereas the negative elastogram prevails in parathyroid adenoma. The SWV and Young’s modulus of the parathyroid lesions were independent of the tumor size, but the max SWV and Young’s modulus slightly correlated with serum parathyroid hormone concentration (PTH) (r = 0.398, p = 0.016; r = 0.396, p = 0.017).Conclusions2D-shear wave elastography plays a useful role in the preoperative assessment of parathyroid lesions with suspicious malignancy. The mean SWV and Young’s modulus are advised as the favored diagnostic parameter with the best AUC and excellent specificities, while the max SWV and Young’s modulus are more sensitive to distinguish the PC and APT compared with other parameters.

Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism

PurposeCDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT).MethodsDuring genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples.ResultsDNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3.ConclusionGermline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge.

ODP121 Recurrent atypical parathyroid adenoma: a case report

Abstract Background Atypical parathyroid adenoma is a rare cause of hyperparathyroidism, with an incidence ranging from 0.5 to 4.4%. Its recurrence rate is low, around 3%. We describe a young patient with an atypical parathyroid adenoma that recurred twice at the right neck. Case presentation A 39-year-old woman presented to the ER with low back pain, hyporexia, weight loss, and an oral lesion with purulent discharge. She was diagnosed with nephrolithiasis, severe hypercalcemia (serum calcium concentration: 21,2 mg/dl (Reference range 8,5-10,5) and hyperparathyroidism (serum PTH: 703 pg/mL; reference range 15-45pg/mL). Parathyroid scintigraphy identified an uptake at the site of the lower right parathyroid. A cervical US confirmed the presence of a 3 cm markedly hypoechoic nodule in that location. Fine needle aspiration (FNA) suggested parathyroid adenoma, and PTH washout levels were 1900 pg/ml. Screening for multiple endocrine neoplasia was negative. Biopsy of the mandibular alveolar bone, around the oral lesion, showed giant cell lesion. Lower right parathyroidectomy was performed, and the histopathology showed parathyroid neoplasm with features favoring atypical parathyroid adenoma (lesion measuring 3×2×1.8 cm). Fifteen months after the surgery, the patient presented symptoms of hypercalcemia, with a new elevation of serum PTH levels (738 pg/ml), confirmed with radiotracer uptake at the site of the upper right parathyroid gland. She underwent right parathyroidectomy and hemithyroidectomy. Histopathology revealed an atypical parathyroid adenoma. Immunohistochemistry was positive to galectin 3 in rare cells; Ki 67 positive (2%). After nine months, the patient noticed a subcutaneous nodule in the right anterior cervical region associated with symptomatic hypercalcemia, and a new increase in serum PTH levels (469.5 pg/mL). Parathyroid scintigraphy confirmed radiotracer activity at the nodule described, that was surgically resected. Histopathology was compatible with an atypical parathyroid neoplasm (uncertain malignant potential). The patient remains in regular follow-up, asymptomatic and normocalcemic. Conclusion While 96% of patients with atypical parathyroid adenomas are cured with parathyroidectomy, this case shows a very rare description of two recurrences in a short time of follow-up, with an ectopic location in the last one. It should be noted that atypical paratyroid adenomas are already an uncommon presentation of primary hyperparathyroidism. Genetic investigation is warranted in such cases. Presentation: No date and time listed

ODP099 Hyperparathyroidism Causing life Threatening Hypercalcaemia in Pregnancy

Abstract 31 year old woman (G2P0) 14 weeks pregnant was admitted for investigation of acute renal failure. Her creatinine was 171umol/L (normal: 45-84umol/L). Prior to her admission, patient was under investigation for a small for gestational age (SGA) baby, and had amniocentesis for suspected triplody. However, the result was normal. On admission, the patient gave a history of severe nausea and vomiting that started at 6 weeks gestation. There was also a history of constipation, lethargy and weakness. Admission blood tests showed a severe primary hyperparathyroidisim with corrected calcium level of 4.1mmol/L (normal: 2.2-2.6mmol/L), PTH=36.9 (1.6-6.9pmol/L), and thyrotoxicosis (TSH&amp;lt;0. 01, FT4=32.2 (12-22pmol/L). Her 24hour Urinary calcium was raised at 19.1mmol (normal: 2.5-7.5mmol/24hours) and 25 OH Vitamin D3 was 64nmol/L (Vitamin D &amp;gt;50 considered replete). On examination, there was a palpable nodule in the region of the left thyroid lobe. The patient was treated with 6 hourly IV fluids and carbimazole 20mg OD. Ultrasound of the neck showed a heterogenous vascularised lesion along the inferior aspect of the left thyroid lobe, 21×22×26mm in size. The lesion was thought to be a large atypical parathyroid adenoma (APA), although a parathyroid carcinoma could not be ruled out on ultrasound. Meanwhile, the patient remained hypercalcaemic with corrected calcium of 3.2mmol/L, despite aggressive IV fluids and cinacalcet 60mg BD. Her renal function improved, creatinine=110umol/L. The patient was also noted to be hypertensive, with BP ranging between 150/80 to 160/110mmHg. She was still having GI symptoms, namely retching and vomiting. In light of biochemical and clinical findings, parathyroidectomy was done in the second trimester of pregnancy. The surgery was uneventful. Cinacalcet was stopped and Ad Calcium was normal within 48hours of surgery. Ad cal=2.58, PTH low at 0.7. Patient was discharged after parathyroidectomy. The histology report was in keeping with atypical parathyroid adenoma (APA). Ultimately, our patient had a spontaneous vertex delivery of a male infant at 35+2. The baby was SGA and spent time in SCBU with fits and hypocalcaemia (Ad Cal=1.8). Baby was seen by neonatologist post discharge, and has normal development at the time of writing. Presentation: No date and time listed