Parathyroid Adenoma Research Articles

8373 High suspicion for thyroid cancer in patient with thyroid Hemiagenesis

Abstract Disclosure: L. Aoun: None. S. Almardini: None. M. Anise: None. F. Haddadin: None. F. Saliba: None. J. Zaidan: None. Background: Thyroid Hemiagenesis (THA) is a rare condition characterized by congenital absence of one lobe of the thyroid gland. Notably, THA is more prevalent in females and the left lobe is more likely to be absent with or without the isthmus. Most patients are euthyroid, and diagnosis is usually incidental, so the true prevalence of THA is uncertain as there are certainly undiagnosed cases. Studies have shown a link between THA, thyroid cancer, and hyperparathyroidism. We present a case of THA and high suspicion for thyroid cancer. Case Presentation: 54-year-old female with history of Rheumatoid arthritis who presented for evaluation of incidental thyroid nodules, occasional palpitations, tremors, and mild change in her voice. She denied abnormal weight loss or diarrhea. No history of radiation to the neck and no family history of thyroid disease or thyroid cancer. The thyroid exam showed an enlarged left palpable nodule. Labs significant for TSH 1.6 mIU/L (normal: 0.4-4 mIU/L), FT4 0.8 ng/dl (normal 0.7-1.9 ng/dL) and T3 77ng/dL (normal: 60-180 ng/dL). Thyroid U/S showed left hemiagenesis and right sided nodules biggest is 1.1 cm solid, hypoechoic with coarse calcifications, FNA was recommended and showed follicular lesion of undetermined significance, molecular testing was done and Thyroseq came back intermediate to high risk RAS and EIF1AX positive reflecting a 70 % probability of cancer. Based on these results, surgery was recommended, and the patient underwent right thyroidectomy. Surgery was uncomplicated and despite reported higher risk of hyperparathyroidism patient’s calcium and PTH were normal, and no parathyroid adenomas were identified intraoperatively. The pathology from the thyroidectomy showed follicular adenoma of 1 cm and no malignancy. She was started on Synthroid 100mcg daily post op. Discussion: This case demonstrates a case of a benign thyroid nodule and preserved parathyroid levels in the setting of thyroid hemiagenesis. Usually in THA, the contralateral lobe is at an increased risk for pathology of compensatory hypertrophy or hyperplasia. According to available studies, cancer association with THA was more common in left hemiagenesis and parathyroid adenomas more common ipsilateral to hemiagenesis . Despite Our patient’s FNA revealed atypical findings, molecular testing revealed RAS and EIF1AX positive, marking intermediate to high cancer risk. However, the thyroidectomy pathology report unveiled no evidence of malignancy, contraindicating the anticipated high cancer risk in those with left THA. This case highlights the rarity of THA and different possible presentations and cancer risks. Presentation: 6/2/2024

6940 Thrombotic Events in Primary Hyperparathyroidism: Association or Coincidence?

Abstract Disclosure: I.A. Guatemala Funes: None. Z. Zavgorodneva: None. Y. EL-Soufi: None. A. Khan: None. T. Zahedi: None. F. Zhang: None. Introduction: The classical manifestations of primary hyperparathyroidism are nephrolithiasis, osteoporosis, and hypercalcemia-related symptoms, such as abdominal pain, constipation, polydipsia, and polyuria. Parathyroid crisis is a rare and life-threatening presentation of primary hyperparathyroidism characterized by calcium levels above 14-15 mg/dl and marked symptoms of hypercalcemia. Here, we describe a rare case of bilateral pulmonary embolism in a patient with severe hypercalcemia secondary to parathyroid adenoma. Case Report The patient is a 70-year-old female with a past medical history of primary hyperparathyroidism, who presented with profound fatigue, shortness of breath, polyuria and constipation. The patient denied any trauma, immobilization, or long-distance travel. On physical exam patient was confused, dehydrated, and nonhypoxic but with increased work of breathing. Initial labs showed severe hypercalcemia with calcium 19.2 mg/dL, significant elevated PTH 1113.9 pg/mL from her baseline PTH 380.8 pg/mL, normal 25 VitD, and acute kidney injury with creatinine increased from 0.9 mg/dL to 2.8 mg/dL. The calcium level in 24-hour urine collection was 323 mg/24 hours. CT chest angiogram revealed a bilateral lower lobe pulmonary embolism. The lower extremity duplex was negative for venous thrombosis. Thyroid ultrasound demonstrated suspected left parathyroid adenoma 2.1 x 2.1 x 1.4 cm. Renal ultrasound was negative for renal calculi. Following treatment with intravenous fluids, Calcitonin, and Denosumab, her calcium level improved to 10.1 mg/dL. The patient’s symptoms improved and underwent parathyroidectomy. PTH levels decreased significantly after parathyroidectomy. Pathology report confirmed parathyroid adenoma. Discussion The association between hypercalcemia and venous or arterial thrombosis has been rarely reported. Calcium participates directly in the platelet activation, platelet aggregation, and coagulation cascade. However, the true correlation between hypercalcemia and thrombosis is not well understood. It is believed that indirect factors such as vasoconstriction, dehydration, and cytotoxic effects due to hypercalcemia and the direct effects over platelet function and coagulation, may act together to induce thrombosis. Unfortunately, much of the evidence between hypercalcemia and hypercoagulability is based on case reports and our case could be one more evidence that this correlation exists. The patient’s age, absence of other risk factors of hypercoagulability, simultaneous manifestation of hypercalcemic crisis, and acute PE make hypercalcemia as a more likely pathogenetic origin of thrombus formation. Conclusion: Physicians should be cautious of the hypercalcemia-induced thrombotic events caused by dehydration and calcium-triggered vasoconstriction, clotting system activation, or platelet aggregation. Presentation: 6/3/2024

8106 An Uncommon Cause Of Hyperparathyroidism: A Case Report

Abstract Disclosure: A. Calderon: None. M.C. Aguilera: None. A. Kansara: None. Introduction: Parathyroid adenomas are the most common cause of primary hyperparathyroidism. Imaging techniques to locate parathyroid adenomas and hyperplasia include U/S (Sensitivity: 72%-89%), Sestamibi Tc-99 (Sensitivity of 68-95%), and 4D CT scan (Sensitivity of 80%). Combined imaging modalities increase sensitivity to 95%. We describe a case of symptomatic primary hyperparathyroidism with rapid development of hypercalcemia, and conflicting imaging findings. The final diagnosis was made after surgery and pathology review. Case presentation: A 76-year-old man with a history of hypertension, Parkinson’s disease, and prostate cancer was admitted due to a calcium level of 13 mg/dL (8.0 - 10.2 mg/dl) on routine blood tests. He had complained of progressive fatigue and constipation, attributed to Parkinson’s Disease. Five months prior his calcium was 9.7 mg/dL. Hydrochlorothiazide was discontinued due to hypotension after two months. Blood tests in the hospital showed a corrected calcium of 12.5 mg/dL, phosphorus of 1.7 (2.4 - 4.5 mg/dl), PTH of 195 (15 - 65 pg/ml), with normal vitamin D and undetectable PTHrP. A U/S of the neck showed a 0.4 x 0.5 cm cystic mass in the right-inferior pole of the thyroid. A 4D CT scan of the neck showed a non-enhancing 0.9 x 7 x 1 mm mass in the same location, and a 7 x 4.7 x 4.8 mm mildly enhancing mass in the left lower pole of the thyroid. A parathyroid nuclear scan did not identify a parathyroid adenoma. He underwent minimally invasive parathyroidectomy and was found to have a 3.2 cm enlarged and cystic right inferior parathyroid gland weighing 792 mg. Frozen section showed hypercellular parathyroid with cystic and fibrotic changes. The PTH level dropped 59% after removal of the right cystic mass. The left inferior mass identified on CT scan was identified as normal thyroid tissue. Conclusions: Parathyroid cysts are uncommon neck masses and represent less than 5% of causes of all neck masses. They can be divided into functional and non-functional. Large retrospective studies have shown that about 5% of patients manifest as classic hyperparathyroidism, whereas the most common presentation was neck mass (40%). Identification of parathyroid cysts through imaging can be challenging. In our case, the patient presented with symptomatic and rapidly progressive primary hyperparathyroidism, and imaging findings that were discordant among ultrasound, 4DCT scan and Sestamibi Tc-99 scan. The final surgical and pathology reports identified a large parathyroid cyst. This case emphasizes the variable clinical and imaging behavior of parathyroid cysts, imposing a puzzling medical challenge. Presentation: 6/3/2024

6487 Hypercalcemia In Pregnancy Due To An Ectopic Parathyroid Adenoma: A Diagnostic Dilemma

Abstract Disclosure: S.S. Patel: None. M.B. Sharma: None. Introduction: Hypercalcemia is a rare complication of pregnancy, with the most common cause being primary hyperparathyroidism due to a parathyroid adenoma. Ultrasound is the primary modality used for localization, as sestamibi and computed tomography (CT) carry the risk of potential harm to the fetus. We present the case of hypercalcemia in a pregnant female that failed to resolve after two gland parathyroidectomy, necessitating a sestamibi parathyroid scan to localize an ectopic parathyroid adenoma. Case: A 40-year-old pregnant woman at 12 weeks of gestation presented with hypercalcemia, with a corrected calcium level of 12.5 mg/dL (8.7-10.4 mg/dL). She complained of nausea and vomiting but denied any personal or family history of hypercalcemia. Further evaluation revealed primary hyperparathyroidism as the etiology, with Intact PTH of 429.2 pg/mL (18.5-88.0 pg/mL), ionized calcium of 1.45 mmol/L (1.12-1.32 mmol/L), 25-OH vitamin D of 16.4 ng/mL (30-100 ng/mL), phosphorus of 1.3 mg/dL (2.4-5.1 mg/dL), and creatinine of 0.71 mg/dL (0.5-0.8 mg/dL). Notably, her calcium level had been 19.2 mg/dL two weeks earlier during an episode of hyperemesis gravidarum. Hypercalcemia proved relatively resistant to treatment with intravenous hydration and subcutaneous calcitonin. Ultrasound of the neck failed to reveal a parathyroid adenoma. The patient then underwent surgical neck exploration, during which two parathyroid glands were removed, resulting in an intraoperative PTH drop from 440 to 340 pg/mL. Postoperative calcium levels remained elevated at 12.9 mg/dL, prompting the resumption of treatment. Oral sodium and potassium phosphate was added to bind dietary calcium. After an extensive multidisciplinary discussion, a 99mTc-sestamibi parathyroid scan with a lower dose of sestamibi and without CT was recommended. This revealed an ectopic parathyroid adenoma in the anterior mediastinum. Surgical removal of the ectopic parathyroid adenoma in the second trimester finally led to a significant intraoperative PTH drop from 315 to 28 pg/mL. The postoperative course was complicated by hypocalcemia and hypomagnesemia, requiring calcium, vitamin D, and magnesium supplements. These complications resolved over the following days. The patient remained normocalcemic for the remaining pregnancy and delivered a healthy male infant at 34 weeks. Conclusion: Hypercalcemia in pregnancy is associated with fetal and maternal complications, warranting adequate management and close follow-up. The use of 99mTc-sestamibi parathyroid scan is typically not recommended in pregnancy due to concern for fetal harm; however, there are a few studies showing no association with increased birth defects or adverse pregnancy outcomes at low radiotracer doses. Hence, a sestamibi parathyroid scan can be considered during pregnancy to localize an adenoma after a careful review of the benefits versus risks. Presentation: 6/2/2024

7214 A Retrospective Cohort Study on Prevalence Of Pituitary Adenomas in MEN2

Abstract Disclosure: R. Ghosh: None. N. Behiri: None. J. Glod: None. S. Gubbi: None. J. Klubo-Gwiezdzinska: None. Background: Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant and present with tumors in at least two or more endocrine organs. MEN2 syndromes that are driven by germline rearranged during transfection (RET) gene pathogenic variants are divided into 2A consisting of medullary thyroid carcinoma (MTC), parathyroid adenomas and pheochromocytoma and 2B presenting with MTC, pheochromocytoma, marfanoid habitus, mucosal neuromas and gastrointestinal ganglioneuromatosis. Pituitary adenomas have been rarely described in MEN2 and hence we conducted a retrospective chart review to determine their prevalence in MEN2. Methods: Retrospective chart screening of MEN2 patients followed at a tertiary referral center between August 1999- August 2022 was done to evaluate the prevalence of pituitary adenomas using biochemical hormonal evaluation and magnetic resonance imaging (MRI) of pituitary based on screening of clinical symptoms. Results: The study consisted of 91 patients (43 MEN2A and 48 MEN2B), aged 35.3±16.9 years (MEN2A) and 18.6±6.4 years (MEN2B), 20/43 (46.5%) women in MEN2A and 24/48 (50%) women in MEN2B. These patients were followed for median duration of 6.5 years (3.3-22) in MEN2A and 8.5 years (5.4-14.6) in MEN2B. RET mutation status was unavailable for 1 MEN2A patient out of 91 patients. Among MEN2A patients, majority (53.5%) were positive for RET C634X mutation followed by RET 804, 609, 631,620 and 666 mutations in the descending order. While in MEN2B cohort all patients were positive for M918T RET mutation. A total of 4/91 (4.4%) patients were found to have pituitary adenomas (3 MEN2B and 1 MEN2A). One patient had clinically symptomatic ACTH producing microadenoma which was surgically resected, and others have asymptomatic non-functioning adenomas. The patient with Cushing’s disease underwent three transsphenoidal resections leading to complete resolution but developed panhypopituitarism. Prevalence of pituitary adenomas in our cohort was significantly higher than the general population screened based on clinical suspicion (p<0.001). Conclusion: Prevalence of clinically symptomatic pituitary adenomas is 1 in 1000 in the general population (1). It is rarely associated with MEN2 syndromes and only few cases are reported in the literature (2). However, screening of all patients with MEN2 for pituitary adenomas, regardless of clinical suspicion, might lead to incidental discovery of asymptomatic pituitary pathology and can provide the actual prevalence. Further studies are needed to evaluate the genetics of these pituitary adenomas in MEN2 syndromes to investigate whether RET protooncogene is indeed the dominant molecular driver of these tumors.

8082 Primary Hyperparathyroidism or Familial Hypocalciuric Hypercalcemia? Why Not Both?

Abstract Disclosure: C.A. Zmijewski: None. P.D. Greenberg: None. S.R. Saul: None. Background: Although considered two separate entities, primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) can present concurrently. Case: A 68-year-old male with hypertension was referred to Endocrinology for hypercalcemia and osteoporosis. The patient reported a long-standing history of intermittent hypercalcemia, first diagnosed at age 30 with a strong family history, both his father and son. He denied symptoms of hypercalcemia, history of nephrolithiasis and fractures, and was not taking calcium supplementations. Labs were notable for intermittent elevations in calcium, the highest being 10.9 mg/dL (8.5-10.5 mg/dL), in addition to phosphorus levels as low as 1.7 mg/dL (2.5-4.5 mg/dL). Vitamin D was replete at 50 ng/mL (32-100 ng/mL) and the highest parathyroid hormone (PTH) was 124 pg/mL (10-66 pg/mL). The 24-hour urine for calcium was 117 mg (100-300 mg) with a Ca/Cr 0.01. DEXA scan showed T scores -2.2 at the right femoral neck and -3.4 at the distal radius (Z score -2.3). Due to the significant osteoporosis, a work-up for secondary causes was completed and was unremarkable. The differential diagnosis for the osteoporosis, elevated parathyroid hormone, and intermittent hypercalcemia included PHPT vs FHH or possibly, a combination. Additional imaging included a renal ultrasound which was negative for nephrolithiasis, Sestamibi and 4D-CT which were both negative for a parathyroid adenoma. Genetic testing confirmed a mutation in the CASR gene. Due to the inability to localize a possible lesion, the decision was made to treat the osteoporosis with zoledronic acid. Conclusion: PHPT is a common endocrine disorder; approximately 100,000 people in the United States develop PHPT annually. Conversely, FHH is a rare endocrine disorder with an incidence rate of 1 in 78,000. PHPT occurs due to the over-secretion of PTH by one or more parathyroid glands. FHH is an inherited autosomal dominant disorder, most commonly due to an inactivating mutation in the calcium-sensing receptor (CASR) gene. Distinguishing PHPT from FHH is important because PHPT is cured with surgery while FHH does not require treatment. Hypercalcemia from FHH, as opposed to PHPT, is suggested by the absence of symptoms, a positive family history, normal or high PTH, and hypocalciuria. However, it can be challenging to separate the two especially in atypical presentations (PTH can be normal in PHPT and elevated in FHH, and Ca/Cr can be < 0.01 in PHPT). But what if these two conditions were to co-exist? Case reports have described patients with concurrent PHPT and FHH (parathyroid adenoma confirmed with pathology and CASR gene mutation confirmed with genetic testing). In these cases, parathyroidectomy can still be considered in co-existing PHPT and FHH to alleviate symptoms and prevent complications of hypercalcemia. Though a rare occurrence, PHPT and FHH have been shown to co-exist in prior case reports. Presentation: 6/1/2024

7191 When Pain Is Misdiagnosed: A Case of Parathyroid Carcinoma Masked as Fibromyalgia

Abstract Disclosure: H. Pham: None. P.V. Kumar: None. S. Taylor: None. Parathyroid carcinoma is a rare and aggressive cause of hyperparathyroidism, typically associated with <1% of primary hyperparathyroidism cases. Incidence occurs mainly in the 5th decade of life, with less than 4% of all cases presenting in patients under age 30. Here, we highlight a case involving a 28-year-old woman with fibromyalgia who presented for worsening right shoulder pain in the setting of progressive, poorly characterized pain for the past year. Her initial physical exam was unremarkable aside from a non-tender left sided neck enlargement. However, her laboratory results were significant for corrected serum calcium of 15 mg/dL, serum phosphorus of 2.3 mg/dL, parathyroid hormone (PTH) >2500 pg/mL, and alkaline phosphatase 1604 units/L. X-ray of her right shoulder demonstrated mottled bone concerning for degenerative disease. Thyroid ultrasound revealed a complex cystic lesion posterior to the left thyroid lobe measuring 5.3 x 3.9 x 2.9 cm, worrisome for giant parathyroid adenoma. CT abdomen/pelvis showed diffuse osteosclerosis and innumerable lytic lesions, consistent with osteitis fibrosa cystica, as well as bilateral nephrolithiasis, likely medullary nephrocalcinosis. Her hypercalcemia was treated with aggressive hydration with normal saline and IV pamidronate. She underwent surgical resection of her parathyroid adenoma, which was unfortunately complicated by symptomatic hypocalcemia requiring prolonged care in the ICU. Her calcium levels did improve within a few days, and she was subsequently discharged with close outpatient follow-up. Final pathology report showed predominant thickened trabecular growth pattern with focal vascular invasion consistent with parathyroid carcinoma. Our patient’s case represents a rare presentation of parathyroid carcinoma in a young patient without any additional risk factors. Although atypical, her severe symptomatic hypercalcemia, nephrolithiasis, presence of large neck mass, and diffuse skeletal disease warranted immediate concern for malignant hyperparathyroidism instead of benign adenoma. Delayed diagnosis in our patient led to prolonged bone disease and severe complications. While hungry bone syndrome typically manifests post-parathyroidectomy in patients with end-stage renal disease, our patient experienced this complication in the setting of advanced, untreated hyperparathyroidism. We should consider hypercalcemia and hyperparathyroidism in our differential diagnosis for chronic pain, especially if pain remains uncontrolled with conservative measures. The most appropriate initial test for evaluation of hypercalcemia is a PTH level to distinguish between PTH-dependent and PTH-independent etiologies. Parathyroid carcinoma, even in young patients, should be considered when PTH is >3x upper limit of normal, serum calcium is >14, or skeletal and renal involvement is present. Presentation: 6/3/2024

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

7200 A Unique Case Of Hypercalcemia From Primary Hyperparathyroidism With Thymoma And Concurrent Pulmonary Tuberculosis

Abstract Disclosure: S. Jing Hang Randy: None. L. Huiling: None. Background: Several case reports have reported the rare association of thymoma with primary hyperparathyroidism. We describe a unique case of hypercalcemia with such association but was also found to have concurrent pulmonary tuberculosis. Clinical Case: A 50-year-old Indian female with a significant history of anterior mediastinal mass underwent median sternotomy with mass resection and was found to have peri-operative hypercalcemia. Her only complaint was chronic cough. Initial investigations showed high adjusted calcium 2.78 mmol/L (2.15– 2.50 mmol/L), normal phosphate 1.1 mmol/L (0.8– 1.4 mmol/L) and high PTH 24.7 pmol/L (1.6– 6.9 pmol/L). Apart from the mediastinal mass, a whole-body CT scan showed multiple prominent mediastinal lymph nodes with non-specific subcentimetre lung nodules. The post-operative finding was a Type AB thymoma with necrotizing granulomatous inflammation in adjacent station I lymph node. Differentials for patient’s hypercalcemia included primary hyperparathyroidism, malignancies such as lymphomas and infectious causes in particular tuberculosis. Her 25-OH Vitamin D was low at 9 ug/L (30 - 100 ug/L), 1,25-dihydroxyvitamin D was elevated at 205 pg/mL (18-64 pg/mL) while creatinine, ALP, serum ACE and PTHrP were unremarkable. She was subsequently admitted for worsening hypercalcemia, fever and left pleural effusion with generalized lymphadenopathy where she underwent an Endobronchial Ultrasound-guided Transbronchial Needle Aspirate of station IV lymph nodes before being started on tuberculosis treatment. The AFB culture showed Mycobacterium Tuberculosis Complex thereafter. Parathyroid sonography revealed a 2.2cm x 0.9cm x 0.8cm lobulated hypoechoic lesion posterior to the inferior pole of left thyroid lobe. However, a confirmatory sestamibi scan could only be done 6 weeks post-thymectomy given the raw surgical bed, with a possibility of false-negative result for cervical parathyroid adenoma given a recent thymectomy. It subsequently showed a hyperfunctioning left inferior parathyroid nodule with no other suspicious focal uptake in the neck or mediastinum. Patient underwent a focused left parathyroidectomy. Histology showed features consistent with parathyroid adenoma. A stepwise trajectory of her calcium normalization was observed with hydration, intravenous zoledronic acid for her osteoporosis, tuberculosis treatment, adjuvant radiation therapy for her thymoma with margins involvement, and parathyroidectomy. Conclusion: This case illustrates the challenges faced while considering localizing scans for primary hyperparathyroidism with recent thymectomy given the common embryological origin of inferior parathyroid and thymus. It also demonstrates the possible co-existence of separate pathologies in hypercalcemia and the need to exercise prudent clinical judgement to further evaluate for these various etiologies. Presentation: 6/2/2024

6634 Dual-Mediated PTH And Osteolytic Hypercalcemia In Metastatic Endometrial Carcinoma

Abstract Disclosure: C.K. Persaud: None. D.J. Beckman: None. Background: Hypercalcemia of malignancy occurs in 20-30% of advanced stage cancer patients. Etiologies include parathyroid hormone-related peptides (PTHrP)-mediated, osteolytic metastases-mediated, overproduction of 1,25-dihydroxycholecalciferol, and rarely parathyroid hormone (PTH)-mediated. PTH-mediated hypercalcemia of malignancy is rare and occurs through ectopic PTH production or primary hyperparathyroidism. We report a rare case of both PTH-mediated and osteolytic-mediated hypercalcemia in the setting of malignancy. Clinical Case: A 57-year-old female with history of endometrial cancer and multiple solid organ metastasis, presented with two weeks of progressive poor oral intake, nausea, emesis, and right flank pain. On hospital admission, she had a serum calcium of >20.1 mg/dL (8.6-10.2), PTH of 203 pg/mL (15.0-65.0), and creatinine of 1.7 mg/dL (0.7-1.2, baseline 1.3). Non-contrasted CT chest/abdomen/pelvis noted increased size of known right adrenal metastasis, new left adrenal metastasis, periaortic lymphadenopathy, and scattered nodules in the subcutaneous tissues of the abdomen and chest, however bone metastasis were not noted. Patient’s hypercalcemia was treated with zoledronic acid, calcitonin, cinacalcet, and eventually denosumab due to difficulty controlling hypercalcemia. Additional labs obtained during evaluation included ionized calcium >2.5 nmol/L (1.12-1.32), PTHrP <2.0 pmol/L (<2.0), 1,25-dihydroxycholecalciferol <10 pg/mL (21-65). Patient’s right adrenal metastasis biopsy one month prior to admission was subsequently stained for PTH and was negative. Technetium-99m sestamibi scan was obtained for localization of parathyroid adenoma or carcinoma. The scan did not localize, however did show numerous new lytic lesions in the skull, spine, sternum, rib cage, and right humerus. Patient’s hospital course was complicated by progressively worsening renal function, anemia, and thrombocytopenia. Patient was discharged to a long-term acute rehab facility off hypercalcemia treatment with a corrected calcium of 10.0 mg/dL. Conclusion: PTH-mediated hypercalcemia is a rare cause of hypercalcemia of malignancy. PTH levels are typically low or low-normal in osteolytic mediated hypercalcemia. Generally, if PTH is elevated in hypercalcemia, an alternate etiology is not evaluated. This case highlights a rare dual-mediated hypercalcemia of malignancy. The patient’s PTH level elevation was discordant with her high degree of hypercalcemia and prolonged treatment course. She was subsequently found to have widespread bone metastases contributing to hypercalcemia. While multiple etiologies of hypercalcemia can be rare, it is important to evaluate for all contributing causes, especially with additional clinical conditions, such as malignancy. Presentation: 6/3/2024

7633 Novel CASR Gene Mutation in a patient with Familial Hypocalciuric Hypercalcemia and Papillary Thyroid Cancer

Abstract Disclosure: A. Parihar: None. E.S. Nylen: None. S.M. Gandhi: None. Familial Hypocalciuric Hypercalcemia (FHH) is predominantly caused by loss-of-function mutations in the calcium-sensing receptor (CaSR) characterized by a benign elevation in calcium and PTH which can be mistaken for primary hyperparathyroidism (PHPT). Missense mutations in the CaSR gene causing FHH have been documented but not much is known regarding their clinical significance. We describe a patient with FHH found to have a novel variant mutation. A 37-year-old male with hypogonadism and fatty liver was incidentally found to have hypercalcemia suggestive of PHPT with elevated PTH (102-114 pg/ml), normal vitamin D, and Fractional Excretion of Calcium (FECa) of 0.014. His father also had hypercalcemia and had undergone parathyroid surgery. The patient denied kidney stones and had a normal bone density. Subsequent Sestamibi and 4D CT scan suggested parathyroid adenoma on the left mid-lower pole of the thyroid. Neck ultrasound also showed a left 1.2 x 1 x 1 cm thyroid nodule as well as a left neck mass with calcifications. Fine needle aspiration was positive for metastatic Papillary thyroid cancer(PTC) in the left neck mass and patient underwent total thyroidectomy along with subtotal parathyroidectomy and lateral neck dissection. Thyroid pathology confirmed multifocal PTC with lymph node involvement that were BRAF V600 positive. Parathyroid pathology was benign hyperplasia. The PTH level decreased appropriately intraoperatively (69%), but postoperatively a rise was noted with levels remaining 70-90 pg/ml with normal calcium levels. Repeat FECa was 0.007, supporting the diagnosis of FHH. Given patient’s father also had hypercalcemia, genetic testing was pursued. This revealed CaSR gene missense mutation (c.1382T>C p.Leu461Pro, heterozygous). This variation is not present in population databases and has been classified as a variant of uncertain significance. It can be difficult to distinguish PHPT from FHH based on FECa as in this case. The patient also had PTC which is not known to be associated with FHH. Due to uncertain significance of this novel CaSR missense mutation, long term follow-up and further familial genetic testing will help better understand clinical implications. Presentation: 6/2/2024

7752 Navigating Hypercalcemia in Pregnancy: A Case Report

Abstract Disclosure: J. Gabbay: None. S. Steinmetz-Wood: None. Introduction: Primary hyperparathyroidism (PHPT) in pregnancy is rare but presents many diagnostic and therapeutic challenges. Prompt diagnosis and treatment are important due to associated maternal and fetal risks, however evaluation of urine calcium to differentiate from Familial Hypocalciuric Hypercalcemia (FHH) becomes less reliable due to physiologic changes in pregnancy, sestamibi scans. CT scans require radiation, parathyroidectomy introduces surgical risk, and medical alternatives like bisphosphonates can interfere with fetal skeletal development. Clinical Case: A 24-year-old woman who presented to the emergency room for progressive nausea and abdominal pain was found to be pregnant with elevated serum calculated calcium to 11.4 mg/dL (2.84 mmol/L). She had a history of renal stones, longstanding hypercalcemia of unknown etiology and a remote family history of parathyroid “issues”. Follow up laboratory work showed a PTH of 75.8 pg/ml (8.04 pmol/L) with an elevated 24-hour urine calcium and a low 25OH vitamin D. Given her history of kidney stones and overt symptoms it was our clinical judgement that this was not a case of FHH. She was started on IV fluids twice weekly. After an unrevealing neck ultrasound, an MRI neck showed a 7 mm lesion along the posterior aspect of the left thyroid suggestive of a parathyroid adenoma. Sestamibi scan was avoided due to the risks of radiation to the developing fetus. Given the presumptive diagnosis of parathyroid adenoma, the lack of response to aggressive hydration, and the maternal and fetal risks of hypercalcemia during pregnancy, parathyroidectomy was pursued in her second trimester. Intra-operative inspection and biopsy showed the lesion to be only a lymph node. She underwent 4-gland exploration and the left inferior parathyroid gland, which appeared abnormal and enlarged, was removed. The intra-operative PTH dropped only from 98 to 80 (10.4 to 8.5 pmol/L). She otherwise had an unremarkable hospital course and at discharge her calcium was normal with an undetectable PTH, which can be an expected finding in pregnancy. On follow up she was feeling well with sustained normocalcemia and low PTH levels. Given the age at which her hyperparathyroidism started, she was referred to genetics for further evaluation. Clinical Lessons/Conclusion: There were significant biochemical and radiological limitations in the management of this case. Normally an inappropriately normal PTH with elevated serum calcium and normal urine calcium/creatinine clearance ratio confirms the diagnosis of PHPT, however in pregnancy it should be noted that FHH could also present with normal or elevated urine calcium due to absorptive hypercalciuria in pregnancy. Additional clinical history and reasoning was needed for management as well as a skilled surgeon, where preoperative localization was limited and was not ultimately helpful. Presentation: 6/2/2024

7506 Rare Case of Hyperparathyroidism in Third Trimester Pregnancy Requiring Urgent Parathyroidectomy

Abstract Disclosure: A. Rothstein Costris: None. E. Davydov: None. S. Levy: None. Introduction: Primary hyperparathyroidism (PHPT) during pregnancy has risks to both the mother and her fetus. Complications include maternal pre-eclampsia, miscarriage, hyperemesis gravidarum, nephrolithiasis and pancreatitis. Fetal complications encompass hypocalcemia, tetany, intrauterine growth retardation and fetal demise. Though medical treatment is available, parathyroidectomy is the only definitive treatment. Traditionally, surgery is done in the second trimester of pregnancy. We report a case of a third trimester parathyroidectomy in a 29 yo female with PHPT. Case representation: A 29-year-old G1P0 woman at 28 weeks gestation presented with persistent nausea and vomiting, constipation, joint pain, and increased forgetfulness. She has moved to USA from Saudi Arabia and had not received prenatal care in the USA. She was found to have a PTH of 224 (15-65 pg/mL), Calcium of 13.5 (8.2-10.2 mg/dL), Ionized Calcium of 1.63 (1.00-1.35 mmol/L), and a corrected Calcium of 14.2 (8.7-10.1 mg/dL). Electrolyte abnormalities were also noticed, with a Potassium of 2.8 (3.5-5 mmol/L), Phosphorus of 1.7 (2.5-4.5 mg/dL) and Magnesium of 1.2 (1.8-2.3 mg/dL). Vit. D levels were found to be extremely low <7 (20-40 ng/mL). Due to severe dehydration, persistent nausea, vomiting, and hypercalcemia, the patient received fluid resuscitation and Vit. D supplementation. A neck CT scan identified an 11 x 6 x 14 mm arterially hyperenhancing soft tissue structure at T1-T2, suggesting a probable parathyroid adenoma in the right paratracheal region. Management options included surgery or conservative therapy with fluids and Cinacalcet. A joint decision was made between Maternal Fetal Medicine, ENT and Endocrinology to proceed with parathyroidectomy. Surgical excision revealed an enlarged, hypercellular right inferior parathyroid gland (0.51g). Postoperative laboratory studies at 2 weeks showed normal PTH, Ca, Ionized Ca. Conclusion: It is preferable to conduct surgery for PHPT during the second trimester of pregnancy. However, when PHPT leads to severe symptoms, surgery might be considered in the third trimester. The severity of our patient’s symptoms led to inability to tolerate oral intake, deeming surgery necessary. The multidisciplinary team agreed that surgery in the third trimester would be the best course of treatment as it will result in normocalcemia immediately. Second trimester parathyroidectomy is viewed as safer due to the completion of organogenesis and lower teratogenicity risks. Performance of surgery during the third trimester may lead to an increase in the risk of premature birth. However, untreated hypercalcemia may increase fetal loss and thus third trimester parathyroidectomy can be considered as a treatment option for PHPT in pregnancy. It is also imperative to discuss all options with the patient. In our case, the patient had opted for surgery which was successful. Presentation: 6/3/2024

8737 Primary Hyperparathyroidism (PHPT) “Phenotypes” and the Results of Parathyroid [99mTc]Tc-Sestamibi SPECT/CT Scintigraphy: Minimizing the Risk of Negative Imaging Results

Abstract Disclosure: K. Kucharczyk: None. A. Drynda: None. J. Podlewski: None. M. Trofimiuk-Muldner: None. A. Hubalewska-Dydejczyk: None. Introduction. Primary hyperparathyroidism (PHPT) is a prevalent endocrinopathy typically identified through biochemical testing. PHPT is characterized by hypercalcemia accompanied by increased or inappropriately normal plasma parathyroid hormone (PTH) concentrations. Preoperative imaging is conducted when surgery is indicated to pinpoint parathyroid adenomas. [99mTc]Tc-Sestamibi scintigraphy is highly specific and sensitive in diagnosing PHPT, with a higher adenoma detection rate demonstrated for patients with larger lesions or higher blood calcium concentrations. The study aimed to investigate the relationship between the results of biochemical tests and clinical manifestations (PHPT “phenotype”) and the rate of positive results of parathyroid [99mTc]Tc-Sestamibi scintigraphy. Materials and methods. This was a retrospective study of patients suspected of PHPT who underwent parathyroid [99mTc]Tc-Sestamibi SPECT/CT scintigraphy between 2010 and 2022. Patients’ cluster analysis was conducted based on PTH, serum calcium (Ca), and phosphate (Pi) concentrations to find distinct patterns in these parameters. Furthermore, we compared the distributions of additional patients’ attributes, including gender, lesion size, serum vitamin D, ALP concentrations, urinary calcium, urolithiasis prevalence, as well as parathyroid scintigraphy results. Results. 513 patients were divided into 5 clusters using different algorithms. Finally, clusters from K-means methods were selected based on statistical metrics and expert interpretation. Those were organized in ascending order of positive scintigraphy results, with Cluster 5 reaching a 79.5% positivity rate and median values of PTH - 315.5 pmol/L, Ca - 2.96 mmol/L, and Pi - 0.7 mmol/L. As the proportion of positive imaging outcomes declined, median PTH and calcium concentrations decreased while phosphate concentrations increased. In Cluster 1, with 30% of positive imaging results, medians were as follows: PTH - 79.06 pmol/L, Ca - 2.55 mmol/L and Pi - 1.1 mmol/L. A comparative analysis of various clinical and biochemical parameters revealed statistically significant differences between clusters. Patients from Clusters with a higher frequency of positive scintigraphy were significantly more likely to be males, vitamin D deficient, with higher ALP concentrations, diagnosed with urolithiasis, and harbouring larger lesions. Conclusions. PHPT “phenotypes” correlated with disease severity are evidently linked to parathyroid scintigraphy detection rate. Therefore, it is crucial to know that false-negative imaging is more likely in PHPT patients with minor deviations in laboratory tests. Judicious assessment of biochemical and clinical features may limit the number of redundant parathyroid scintigraphies and, in consequence, reduce healthcare costs and unnecessary radiation exposure. Presentation: 6/2/2024

Postoperative pancytopenia in a patient with giant parathyroid adenoma and brown tumor: a case report

BackgroundParathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies.Case presentationWe present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal.ConclusionsPancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

Insulinoma-associated protein 1 (INSM1) immunohistochemical expression in normal, hyperplastic, and neoplastic canine neuroendocrine tissues.

Insulinoma-associated protein 1 (INSM1), a recently identified neuroendocrine marker, is a transcriptional regulator with highly conserved INSM1 homologues in various species. This study investigated the immunohistochemical reactivity of the INSM1 antibody in 20 normal canine neuroendocrine tissues from various anatomical locations, 87 hyperplastic or neoplastic tissues of neuroendocrine origin, and 62 non-neuroendocrine neoplasms and compared the results with those of chromogranin A and synaptophysin in neuroendocrine neoplasms. Western blot was performed on fresh canine pituitary glands and canine parathyroid glands to confirm the specificity of the anti-INSM1 antibody. The results showed that the anti-INSM1 antibody could detect nuclear expression in normal canine neuroendocrine tissues, except for the parathyroid glands. INSM1 was detectable in 79/87 (91%) of the hyperplastic and neoplastic neuroendocrine lesions, but all parathyroid carcinomas and parathyroid adenomas (three samples each) were negative for INSM1. In contrast, INSM1 was detected in only one of 62 (2%) non-neuroendocrine neoplasms. The overall percentage of neuroendocrine neoplasms that immunolabeled positively for all three markers was 89%. In addition, the nuclear expression of INSM1 was easier to interpret than that of chromogranin A or synaptophysin. These findings confirm that INSM1 is a useful immunohistochemical marker for diagnosing canine neuroendocrine neoplasms, except for parathyroid neoplasms, and should be considered as part of immunohistochemistry panels to improve diagnostic capability.

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.

Acute Pancreatitis Revealing Primary Hyperparathyroidism Due to Unilateral Parathyroid Hyperplasia Associated with Parathyroid Adenoma

Primary hyperparathyroidism is a common endocrine pathology characterized by elevated levels of parathyroid hormone, the most common clinical manifestations being renal or skeletal damage accompanied by moderate or severe hypercalcemia. Around 80-85% of primary hyperparathyroidism cases are caused by a single parathyroid adenoma, 4-5% by multiple adenomas, 10-15% by parathyroid hyperplasia and less than 1% by parathyroid carcinoma. We report the case of a patient with primary hyperparathyroidism presenting with acute pancreatitis. After cooling of the pancreatitis, the patient underwent surgery. Post-operative follow-up showed definitive hypocalcemia, and pathological examination revealed the association of parathyroid hyperplasia and a unilateral parathyroid adenoma.

Characterisation of Kürsteiner canals of parathyroid: imparting relevance to a one-and-a-quarter-century-old concept.

Kürsteiner canals (KC) were described at least 125 years ago as pharyngeal pouch embryological remnants of parathyroid and thymic development. While considered precursors for a subset of parathyroid cysts and salivary heterotopias (SH), they remain enigmatic. We now define a comprehensive phenotype of KC remnants and investigate their role in a spectrum of parathyroid lesions. `Sixty-two cystic and 22 non-cystic parathyroid lesions (73 patients) were retrieved from our institutional archive (2011-23) and evaluated for the presence of KC and prevalence of KC phenotype in parathyroid hormone (PTH)-positive and PTH-negative cysts. KC phenotype was defined as: cysts and tubules with surrounding sclerosis; bland, unilayered lining with frequent nuclear indentation of lumina; vesicular chromatin relative to chief cells; attenuated eosinophilic to 'hyper-cleared' cytoplasm; and staining pattern PTH-negative, SOX-10-positive, CK7-positive, GATA-3-positive and PAX-9 dim, a subset with oestrogen/progesterone receptor (ER/PR) positivity. Thirty PTH-negative cysts were identified in the neck/mediastinum; 14 of this group also showed SH. Thirty-two PTH-positive cysts included: 11 cystic parathyroid adenomas, 17 hyperplastic parathyroids, and four carcinomas. KC showed two distinct subtypes and were often found near PTH-negative cysts. PTH-negative cysts were associated with inferior parathyroids, SOX-10 positivity, fibrosclerosis, vesicular nuclei indenting cyst lumina and hyper-cleared or attenuated eosinophilic cytoplasm. KC are common in parathyroids and show a distinct histological and immunohistochemical profile, with an inferior predilection favouring branchial cleft III distribution. Diagnostically, the high prevalence of this phenotype in PTH-negative cysts and salivary heterotopia supports derivation of non-functioning cysts from KC. Conversely, PTH-positive cysts are more compatible with cystic change within hyperfunctioning glands.

Postoperative hungry bone syndrome in primary hyperparathyroidism: A case report.

Hungry bone syndrome (HBS) is a forgotten and underdiagnosed cause. Postoperative HBS refers to patients with high bone turnover before surgery, but after surgery, the inhibition of osteoclast resorption by intact parathyroid hormone suddenly decreases, resulting in a sudden increase in the amount of calcium resorbed by the bone, and a rapid, severe and persistent hypocalcemia, which may be accompanied by hypophosphatemia and hypomagnesemia. We present a case with information about HBS and related complications after parathyroidectomy (PTX). The patient was a 57-year-old woman who presented to the hospital with "pain in both ankles for more than 3 years and in both knees for more than 2 years." A parathyroid mass was found preoperative. Unilateral resection of the lesion was performed under general anesthesia. On gross examination, the mass was reddish brown in color, about 2.9 × 2.5 × 2.3 cm, with abundant blood supply. Postoperative pathology diagnosed parathyroid adenoma. The patient was diagnosed with HBS on day 3 post-PTX, which lasted for 9 days. After active calcium supplementation and other pharmacological interventions, her test parameters gradually returned to normal and she was discharged on the 13th day after surgery. Using the case of a patient with primary hyperparathyroidism with HBS lasting 9 days after PTX for diagnosis and management, we aimed to summarize possible predictors and perioperative management strategies to reduce the incidence, severity, and duration of postoperative HBS.