bluuebunny/crossref_metadata_2025 huggingface dataset:
8204 Rare Asymptomatic Presentation Of A Large Pheochromocytoma
Authors: Lorin Arkadiy , Kamini Persaud Christine , Kemm Matthew H
Published: October 2024

Disclosure: A. Lorin: None. C.K. Persaud: None. M.H. Kemm: None.

Background: Pheochromocytoma is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. It is associated with excessive release of catecholamines causing symptoms of hypertension, palpitations, diaphoresis, and headaches. These symptoms are particularly prominent with larger pheochromocytomas. We present the case of a large 13 cm pheochromocytoma (PCC) without the typical associated symptoms. Clinical Case: A 45-year-old male with medical history of osteoarthritis and gastroesophageal reflux presented to his primary care doctor with 2 months of intermittent right upper quadrant abdominal pain associated with nausea. Work up with CT abdomen/pelvis found a 9.3 cm heterogeneous right adrenal mass with mass effect on the right liver lobe, superior pole of the right kidney, duodenum, and pancreatic head. Hormonal testing was notable for plasma metanephrine 257.8 pg/mL (0-88), plasma normetanephrine 12063.7 pg/mL (0.0-218.9), 24 hr urine metanephrine 159 mcg/24 hr (58-276), 24 hr urine normetanephrine 22575 mcg/24 hr (156-729), and chromogranin A 5387 mg/mL (0-101.8). Given lab evaluation, diagnosis was made of pheochromocytoma, and patient was initiated on alpha blockade with doxazosin. Patient’s blood pressure and heart rate were at goal prior to doxazosin initiation and patient needed to be decreased from 1 mg daily to 0.5 mg daily due to side effects of low blood pressure and orthostatic hypotension. Patient had an uncomplicated open right adrenalectomy with pathology showing a 13 cm pheochromocytoma with invasion through the capsule into the periadrenal adipose tissue. Genetic testing revealed no known mutation variants associated with PCC. Labs drawn two weeks postoperatively showed resolution of elevated plasma metanephrine, normetanephrine, and chromogranin A. Conclusion: While the patient had an elevated plasma metanephrine, the normetanephrine was predominantly elevated. Such a hormone profile is more common in extra-adrenal PCCs, consistent with cluster 1 associated genes. This noradrenergic phenotype is likely a reason the patient did not have typical symptoms, despite the size of his pheochromocytoma. A proposed pathophysiologic mechanism for this is the dissociation of renal medulla from the cortex given the large size of the tumor. This would lead to lower local availability of corticosteroid to potentiate the conversion of norepinephrine to epinephrine, thus decreasing likelihood of classical PCC symptoms. Despite lack of expected symptoms and an imaging initially concerning for adrenocortical carcinoma, we should recognize the potential for a large adrenal tumor to represent PCC and evaluate accordingly.

Presentation: 6/1/2024
8275 Recurrent Retroperitoneal Paraganglioma
Authors: Kang Jannat , Gupta Vishaal , Subauste Jose S
Published: October 2024

Disclosure: J. Kang: None. V. Gupta: None. J.S. Subauste: None.

Paragangliomas are rare, highly vascular neuroendocrine neoplasms that may originate from sympathetic or parasympathetic paraganglia and may secrete catecholamines. They are closely related to pheochromocytomas which are considered to be their intra-adrenal counterparts. A 65-year-old African American male with type 2 diabetes and tobacco use presented to his primary care physician with night sweats and unintentional weight loss of about 30 pounds in 3 months. Review of systems and laboratory workup was unremarkable. CT Chest/Abdomen/Pelvis with contrast showed a homogenous, well-circumscribed 4.6cm retroperitoneal mass causing mass effect on portal vein, Inferior vena cava, and right renal artery. Interventional radiology performed fine needle aspiration with intra-procedural blood pressure rising to 201/70 mmHg. Pathology showed paraganglioma, staining positive for synaptophysin, chromogranin A, CD 56 and S-100 protein. Plasma metanephrines were elevated at 2818 pg/mL, plasma normetanephrines at 1247 pg/mL with consistent 24-hour urine results. Workup for other adrenal hormones was negative. No family history of pheochromocytoma/paraganglioma or any clinical manifestations of Von-Hippel-Lindau syndrome or Neurofibromatosis were present. He was started on alpha blockade followed by beta blocker and surgical resection was planned. In the interim, escalating requirements of insulin were noted. Intra-operative course was complicated by systolic blood pressure rising to 290s which resolved after mass was removed. Immunohistochemical studies sent to Mayo, Rochester showed retained cytoplasmic SDHB expression in tumor cells. Hence, no further genetic testing was performed. Post excision, plasma-free metanephrines normalized with significant improvement in blood pressure and diabetes. He was followed with yearly plasma-free metanephrines for surveillance. Although asymptomatic, a three-fold rise of plasma metanephrines was noted five years later. CT Abdomen was concerning for recurrence. Dotate/PET scan showed dotate-avid para-aortic soft tissue lesion measuring 2.3 cm between the celiac artery and the superior mesenteric artery which was surgically excised with pathology consistent with paraganglioma (Ki67<1%). Diagnosis of paragangliomas is often in 3rd - 5th decade. About 30% are hereditary and associated with Von-Hippel-Lindau, Neurofibromatosis-1, MEN2A/B among other syndromes. They are mostly benign but SDHB pathogenic variants are likely to be malignant. Genetic testing should be considered in all paraganglioma patients to screen for germline pathogenic variants in SDH and other genes. Diagnosis of secretory paraganglioma is by urinary and/or plasma fractionated metanephrines and catecholamines. Treatment of choice is surgery when amenable to resection with preoperative medical blockade to prevent perioperative complications.

Presentation: 6/1/2024
12383 Salivary Cortisone Measurement In Mild Autonomous Cortisol Secretion: Retrospective Single-center Cohort Study
Authors: Villavicencio Torres Camila A , Chai Yubo , Grebe Stefan K , Maus Tony D , Bancos Irina
Published: October 2024

Disclosure: C.A. Villavicencio Torres: None. Y. Chai: None. S.K. Grebe: None. T.D. Maus: None. I. Bancos: None.

Background: Mild autonomous cortisol secretion (MACS) is diagnosed based on abnormal post-dexamethasone cortisol >1.8 mcg/dL. Late-night salivary cortisol (SalF) measurements in MACS are usually within normal ranges, and as such are not recommended by the adrenal incidentaloma guidelines. Late-night salivary cortisone (SalE) measurement may have a higher accuracy than SalF in diagnosing MACS. Objectives: To determine associations between SalF and SalE and post-dexamethasone cortisol concentrations in patients with MACS. Methods: We conducted a single-center retrospective cohort study of data between 2020-2023 that included patients with MACS who had concomitant SalF and SalE measurements at the time of diagnosis. Electronic medical records were reviewed for clinical, imaging, biochemical characteristics, and outcome data. Results: In 45 patients with MACS (31, 69% women) evaluated at a median age of 62 years (IQR 54-70), median post-dexamethasone cortisol was 3 mcg/dL (IQR 2.5-5.7), median corticotropin (ACTH) was 11 pg/mL (IQR 5.2-30), and median dehydroepiandrosterone sulfate (DHEAS) was 47.5 mcg/dL (IQR 27.8-98.8). In 36 patients, 24h-urine cortisol was also available, with a median cortisol of 14 mcg/dL (IQR 11.3-18), normal ranges <45 mcg/24h. Median adrenal adenoma size was 2.2 cm (IQR 1.6-3.0), and median unenhanced HU was 10 (IQR -5 to 22).Median SalF was 52 ng/dL (IQR 23.9-97.5), and median SalE was 332 ng/dL (IQR 222.5-607.0), with a median SalE/SalF ratio of 6.6 (IQR 5.7-9.0). SalF was normal (<50 ng/dL) in 22 (49%) patients with MACS, without differences in the post-dexamethasone cortisol concentrations between those with normal and abnormal SalF (median of 3 mcg/dL vs 3 mcg/dL, P=0.94). SalF correlated with SalE (R2=0.83, P<0.0001). However, only SalE was associated with post-dexamethasone cortisol (R2=0.09, P=0.04). Conclusion: SalE is associated with post-dexamethasone cortisol in patients with MACS and, after an appropriate validation, may provide additional value in support of diagnosis of MACS.

Presentation: 6/3/2024
7362 Single-Cell Analysis Of Cortisol-Producing Adrenal Adenomas
Authors: Kono Takashi , Fujimoto Masanori , Taki Yuki , Tanaka Tomoaki
Published: October 2024

Disclosure: T. Kono: None. M. Fujimoto: None. Y. Taki: None. T. Tanaka: None.

Introduction: Cortisol-producing adenoma (CPA) is a common adrenal tumor. Although the contribution of mutations to the pathogenesis of CPA is well-established, mutations alone cannot explain all the diverse clinical manifestations. Therefore, it is important to observe the nature of the tumor from a different perspective, based on the clinical features, and understand the pathogenesis of the disease. Recently, single-cell analysis techniques have been developed to accurately define and analyze diverse cell populations, such as tumor cells, immune cells, and stromal cells, in tumor tissues. It is expected that these techniques will reveal the nature of tumor cells that were not visible in the averaged analysis of the entire tumor. Method: We performed genetic mutation analysis and single-cell RNA sequencing on 58 samples of normal adrenal tissue and 13 cases of CPA. Result: The results showed that both normal adrenal tissue and CPA tumor tissue were composed of various cells, including adrenal cortical cells, immune cells dominated by macrophages and T cells, endothelial cells, and fibroblasts. The genetic mutations of CPA are mainly divided into two groups: (1) mutations in PRKACA and GNAS that contribute to the activation of the cAMP pathway and (2) mutations in CTNNB1 that contribute to the activation of the Wnt pathway. Based on the patterns of genetic mutations, we divided the tumor cells into four groups: PRKACA, GNAS, CTNNB1, and N.D. (Not detected). We then used single-cell analysis of tumor cells to observe the differences in their nature using consensus clustering and module analysis. The results showed that the cluster with the most cells with PRKACA mutations was the largest, and the steroidogenesis gene cluster showed correlated changes. Conclusion: Single-cell analysis revealed that the adrenal tissue is composed of diverse cell populations, and it was possible to identify and analyze specific cell populations. In the future, it is necessary to clarify the relationship between tumor cell origin and zonation, as well as to develop new disease phenotypes and classifications based on the interactions between diverse cells that construct the tissue.

Presentation: 6/1/2024
5179 Uncommon Benign Mimics Of Suspicious Adrenal Nodules
Authors: Zhu L , Loh L M , Gan V , Kek P
Published: October 2024

Disclosure: L. Zhu: None. L. Loh: None. V. Gan: None. P. Kek: None.

Introduction: Adrenal incidentaloma is often detected in imaging studies. In addition to biochemical testing, imaging plays a key role in guiding the management of such lesions. We describe two uncommon cases of benign lesions masquerading as suspicious adrenal nodules. Case 1. A 54-year-old man with hypertension, diabetes, dyslipidaemia, ischaemic heart disease and atrial fibrillation (on warfarin) underwent CT scan to exclude malignancy when he presented with thigh DVT, and was found to have a right 3.2cm adrenal nodule. Adrenal hormone profile was unremarkable. CT contrast characterization showed attenuation of 30, 35, and 32 HU on pre-contrast, venous and 10-minute delayed phase respectively. Given the minimal enhancement in high density areas, possible haemorrhage was considered and he was put on imaging surveillance. CT scans over the following 5 years showed stability of the lesion, resolution of high-density areas, and pre-contrast attenuation of -35HU, suggestive of myelolipoma. Further follow-up over the next 2 years then revealed tumour enlargement to 8.5cm, progressive predominance of dense areas (58 HU), and development of compressive symptoms. In view of mass effect, growing heterogeneity and possibility of a collision tumour, right adrenalectomy was performed. Histopathology revealed myelolipoma with extensive haemorrhage and no evidence of malignancy. Case 2. A 65-year-old woman had hypertension, ischaemic heart disease, dialysis-dependent end-stage renal disease secondary to glomerulonephritis, and oncological history of left renal cell carcinoma (RCC) and low-grade papillary urothelial carcinoma, both surgically resected 10 years ago. A new 1.6cm right adrenal nodule was seen on her surveillance CT scan for RCC. It was not present in a CT scan 7 years ago. The nodule displayed suspicious features such as nodular avid rim enhancement, persistent enhancement on delayed phase of contrast washout and central cystic change. Biochemical screening revealed plasma free metanephrine of 0.33 nmol/L (NR: <0.33) and plasma free normetanephrine of 0.99 nmol/L (NR: <0.71). Other adrenal hormone profiles were unremarkable. Cystic phaeochromocytoma was suspected and she underwent right adrenalectomy and nephrectomy following alpha blockade. Histopathology revealed a well-circumscribed nodule in the supra-renal adipose tissue, with vascular proliferation and features of anastomosing haemangioma. The right kidney was reported to have acquired cystic disease associated RCC. She was well post-operatively and remained on follow-up with the urologist for her RCC. Discussion: Haemorrhagic adrenal myelolipoma and supra-renal anatomosing haemangioma are benign lesions that may have CT characteristics similar to those of sinister lesions. Pre-operative diagnosis can be challenging. Surgical excision may be required to confirm diagnosis and exclude malignancy.

Presentation: 6/3/2024
6485 Unilateral Adrenal Metastasis From Unknown Primary Carcinoma Mimicking Primary Adrenocortical Carcinoma
Authors: Watanabe Suzuka , Suzuki Sawako , Ishiwata Kazuki , Yamazaki Yuto , Sasano Hironobu , Yokote Koutaro
Published: October 2024

Disclosure: S. Watanabe: None. S. Suzuki: None. K. Ishiwata: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None.

Background: Adrenal metastasis from carcinomas of the lung, breast, and melanoma are observed. However, isolated adrenal metastasis with unknown primary carcinoma origin has been rare, and the diagnosis is challenging. We encountered a case of unilateral adrenal tumor clinically diagnosed as non-functional primary adrenocortical carcinoma, but found to be a metastatic tumor on postoperative pathology. Clinical Case: A 68-year-old man was referred to our hospital for examination of an 8mm right adrenal incidentaloma. He underwent hormone therapy for prostate cancer four years ago, and the condition is in remission with no recurrence signs. Follow-up CT revealed that the adrenal tumor rapidly enlarged from 8 mm to 36 mm within six months, and its mean attenuation value was 38 HU. MRI showed that the adrenal tumor had a low signal intensity on T1 and a high signal on T2. At the same time, there is mediastinal lymphadenopathy and a 9-mm nodule in the lower lobe of the right lung, which was considered benign from the stable condition. FDG-PET/CT showed FDG uptake only in the right adrenal tumor (maximum standardized uptake value of 21.39). [1]23I-MIBG scintigraphy did not show any accumulations. The serum and urinary adrenal hormones were all within normal limits. Notably, tumor markers such as prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and cancer antigen 19-9 (CA 19-9) were all within normal ranges. Therefore, we clinically suspected non-functional primary adrenocortical carcinoma, and the laparoscopic right adrenalectomy was performed. The resected right adrenal lesion was encapsulated and measured 79×54×22 mm. On histological analysis, the nodule comprised tumor cells with eosinophilic cytoplasm, and abundant tissue infiltrating lymphocytes. Immunohistochemical studies revealed that the tumor was not of adrenal origin due to negative steroidogenic factor-1 (SF-1) and inhibin alpha staining. From these results, the adrenal tumor was diagnosed as adrenal metastasis from unknown primary carcinoma. The tumor cells were positive for cytokeratin19, CEA, and thyroid transcription factor-1 but negative for PSA, p63, cytokeratin 5/6, insulinoma-associated protein-1, and synaptophysin. Genetically, the adrenal tumor harbored genomic abnormalities in CDKN2A, TP53, NF1, PBRM1, and KEAP1 genes. Conclusion: Isolated adrenal metastasis without a detectable primary tumor is rare but should be considered a differential diagnosis in the case of an enlarged, non-functioning adrenal tumor. Adrenalectomy or tumor biopsy may be actively considered to diagnose and determine the optimal course of treatment.

Presentation: 6/3/2024
6402 Unsuspected Bladder Mass Turns Out To Be A Paraganglioma
Authors: Lamichhane Shristi , Flowers Ashley , Price David T , Kaur Arshpreet
Published: October 2024

Disclosure: S. Lamichhane: None. A. Flowers: None. D.T. Price: None. A. Kaur: None.

Background: Urinary bladder (UB) paragangliomas are extremely rare tumors comprising of less than 0.05% of all bladder neoplasms and 10% of all paragangliomas. The diagnosis is usually suspected based on clinical features of painless hematuria, episodic headaches, hypertension, palpitations associated with micturition or bladder and confirmed biochemically by elevated urinary and/or plasma fractionated metanephrines (MN). Here, we present a case of a UB mass that was initially diagnosed on biopsy and subsequent biochemical workup revealed elevated MN. Case Report: A 64-year-old man with type 2 diabetes and hypertension, admitted for revision surgery of subdural hematoma was incidentally found to have a 3.3 x 3.4 x 3.9 cm polypoid heterogenous hyper enhancing UB mass attached to the anterior wall on CT abdomen done for abdominal pain. Cystoscopy and TURBT were complicated by hypertensive urgency. Pathology turned out to be paraganglioma. Detailed history at this time revealed a long-standing history of frequency, urgency, nocturia 4 times nightly, recurrent urinary tract infections, an episode of gross hematuria 1-2 years ago, and difficulty controlling blood pressure on 4 anti-hypertensives. Subsequently, labs showed plasma free MN of 97 pg/ml (ref range <=57), free normetanephrine (NMN) of 2392 pg/ml (ref range <=148), and total MN of 2489 pg/ml (ref range <=205). Genetic panel was negative for SDHA, SHD, AF2, SDHB, SHDC, SDHD, VHL, RET, TMEM127. He received 6 doses of Lantreotide due to suspicion of metastasis based on abdominal, pelvic, and inguinal lymphadenopathy seen on DOTATATE scan. After preparation with alpha and beta blockers, he underwent uneventful robot-assisted cystectomy with lymph node resection that resulted in a well-differentiated paraganglioma negative for margins, lymph node involvement, and extra bladder extension. A week later, MN reduced, plasma free MN 37 pg/ml, free NMN 178 pg/ml, and total plasma MN 215 pg/ml. His BP improved, and micturition-induced palpitations resolved. Conclusion: Due to the rarity of UB paraganglioma, the diagnosis can be missed and delayed. This has a serious implication due to the risk of hypertensive crisis during the surgery and increased risk of cardiovascular complications. This case highlights the need for awareness among physicians of the clinical presentation associated with UB paraganglioma, its early recognition and management.

Presentation: 6/2/2024
12315 Unveiling A Paraganglioma: Catecholamine-Induced Hyperglycemia Masquerading As Type 2 Diabetes Mellitus
Authors: Salman Shiza , Hussine Mohamed , Tibaldi Joseph
Published: October 2024

Disclosure: S. Salman: None. M. Hussine: None. J. Tibaldi: None.

Background: Excessive catecholamines have been demonstrated to exert adverse effects on insulin homeostasis and carbohydrate metabolism, potentially resulting in the onset of secondary DM. We present a case of a patient who had been previously misdiagnosed with T2DM for an extended period. Clinical Case: A 34-year-old woman with history of T2DM, HTN, and chronic tachycardia on beta blockers, presented with complaints of palpitations, headaches, and abdominal pain for two weeks. Upon admission, she was found to be in DKA, necessitating transient administration of insulin drip. Furthermore, she exhibited persistent tachycardia and intermittent episodes of hypertensive urgency. Notably, thyroid levels revealed euthyroidism. Although DKA resolved, her fasting blood sugar levels remained elevated and refractory to escalating insulin therapy. CT abdomen with contrast revealed a large enhancing mass in the RUQ. MRI abdomen confirmed an 8.1 cm heterogeneously enhancing T2 hyperintense mass located in the RUQ, abutting the right hepatic lobe, right adrenal gland, extrahepatic biliary ducts, and adjacent vessels. Given suspicions of a neuroendocrine tumor, she was transferred to the surgical service for tumor excision. Hormonal analysis revealed elevations in plasma metanephrines (620 pg/mL, n 0-88 pg/mL), plasma normetanephrines (9954 pg/mL, n 0-210.1 pg/mL), 24-hr urine normetanephrines (10,952 μg/24hr, n 110-720 μg/24hr) and 24-hr urine metanephrines (1406 μg/24hr, n 35-278 μg/24hr). Additionally, she exhibited elevated 24-hr urine epinephrine fraction (218 μg/g Cr, 0-20 μg/g Cr) and 24-hr urine norepinephrine fraction (2775 μg/g Cr, 0-45 μg/g Cr). Preoperatively, appropriate alpha and beta blockade were administered, followed by successful retroperitoneal tumor resection. Postoperatively, her glucose levels normalized without the need for further insulin therapy, and no episodes of hypoglycemia were reported. Histopathological examination of the excised mass revealed an 11 cm sympathetic paraganglioma with retention of SDHB staining. Genetic testing for SDHB, SDHD, VHL, and RET mutations is pending. Conclusion: This case underscores the potential oversight of pheochromocytomas and paragangliomas due to their nonspecific symptomatology, often mimicking more prevalent conditions, thereby presenting diagnostic challenges. The catecholamines secreted by these tumors can lead to both impaired insulin secretion and increased insulin resistance, resulting in clinically significant manifestations. The exact mechanism underlying the glycemic dysregulation remains controversial, necessitating further investigation through large-scale multicenter prospective studies to enhance understanding and inform diagnostic and therapeutic strategies for these tumors, which can manifest with severe and potentially fatal glycemic disturbances.

Presentation: 6/1/2024
7686 A Case Of A 66-Year-Old Male With Systemic Macrocytosis Complicated By Osteoporosis
Authors: Michelle Gri Jacqueline , Hillhouse Melodie , Madhavan Parvathy
Published: October 2024

Disclosure: J.M. Gri: None. M. Hillhouse: None. P. madhavan: None.

Background: Osteoporosis in men is underestimated and warrants investigation for secondary causes of osteoporosis. Systemic mastocytosis is a rare secondary cause of osteoporosis. Clinical Case: This is a 66-year-old male with a past medical history of severe persistent asthma, eczema, hypertension, GERD with esophagitis, basal cell carcinoma, and systemic mastocytosis (diagnosed in 2010). Family history was significant for lung cancer in both of his parents. Patient was first noted to have hyperpigmented skin lesions on his legs, trunk and upper extremities in the early 1990s. The spots were biopsied and he was diagnosed with urticaria pigmentosa in 1998. Due to persistent symptoms of facial flushing and soft stool, he was referred to Hematology and was started on antihistamines. He later underwent a bone marrow biopsy in 2010 which showed multifocal mast cell aggregates but normal trilineage hematopoiesis. He endorsed back pain shortly after his diagnosis and a DXA scan was completed. The DXA scan showed osteopenia of the spine T score of -1.8, BMD 0.999 mg/mm3 and normal bone density in bilateral hips. He had no history of fractures. He was started on alendronate and remained on the medication from 2012 to 2015. It was stopped due to intolerable symptoms of acid reflux and he required proton pump inhibitors. DXA scan in 2017 showed normal bone density of the hips and osteopenia of the lumbar spine (T score -1.2). DXA scan in 2022 showed a decrease in spine BMD by 6% (T score -1.8) from 2017 to 2022 but unchanged from 2010. Hip bone mineral density was normal but decreased by 10% since 2010 and by 6% since 2017. Labs obtained in May 2022 showed normal serum electrophoresis, normal urine calcium and creatinine ratio, calcium and vitamin D level and urine NTX of 41 nM BCE/mM (21-83) and bone specific alkaline phosphatase level of 31.5 U/L (15-41.3). After discussion with the patient, conservative management with calcium, vitamin D and exercise has been implemented along with close follow up. Should the patient’s bone turnover markers increase or fracture risk increase, additional antiresorptive therapy will be initiated. Conclusion: This case study highlights the importance of screening for osteoporosis in patients with systemic macrocytosis. As this patient was diagnosed with osteopenia at age 53, this case also emphasizes the importance of early screening in both women and men with this rare condition.

Presentation: 6/3/2024
8165 A Case Of Rhabdomyolysis-Induced Hypocalcemia And Hypercalcemia
Authors: Desai Aneree , Lucia Izzi Ana , Flores Chang Bessy Suyin , Sajan Alen
Published: October 2024

Disclosure: A. Desai: None. A.L. Izzi: None. B. Flores Chang: None. A. Sajan: None.

Introduction: Rhabdomyolysis is a syndrome characterized by muscle breakdown and the release of intracellular muscle contents into circulation. It is associated with electrolyte abnormalities and acute renal failure that can lead to prolonged hospitalization. We report a case of persistent hypercalcemia from recovery of acute renal failure and severe rhabdomyolysis. Case Description: A 47-year-old man with past medical history of polysubstance use initially presented with opiate-induced acute encephalopathy and respiratory failure. He developed severe rhabdomyolysis during the hospital course leading to acute renal failure requiring hemodialysis with hypocalcemia. The initial labs showed corrected calcium 6.2 mg/dL [9.2-11.0], ionized calcium 3.48 mg/dL [4.65-5.28], creatinine kinase level was >72,600 U/L [38-174], BUN 110 mg/dL [8-23], creatinine 7.8 mg/dL [0.6-1.2], and GFR 7 ml/min/BSA. His renal function improved over the next several days in the hospital. The serum creatinine improved to 4 mg/dL, BUN 49 mg/dL and GFR 20 ml/min/BSA respectively after couple of intermittent dialysis sessions. Six days after the last hemodialysis session, patient developed severe hypercalcemia with corrected calcium values ranging from 13.5 to 14.7 mg/dL and ionized calcium 7.41 mg/dL. Labs showed PTH 10 pg/mL [15-65], 1,25-dihydroxyvitamin D <10.0 pg/dL [21-65] and 25-OH Vitamin D levels 15.3 ng/ mL [30-96], which is consistent non-PTH medicated hypercalcemia. The 24-hour urine calcium was 696 mg [0-300 mg/24 hrs, 2900 cc]. PTH-related peptide was not collected. He was treated with intermittent doses of calcitonin and a single dose of pamidronate when the calcium levels were >13 mg/dL. Hypercalcemia resolved in eleven days after initially noted to have hypercalcemia. The corrected calcium improved to 10.1 mg/dL on the day of discharge. Discussion:Severe rhabdomyolysis is associated with acute kidney injury. The initial hypocalcemic phase during rhabdomyolysis is due to entry of calcium into damaged myocytes and deposition of calcium salts in damaged muscle. This is seen in the oliguric phase of acute kidney injury. After the recovery of rhabdomyolysis, the polyuric phase persists during renal recovery. During this time, up to one third of patients may have rebound hypercalcemia due to massive muscle calcium release. As per case reports the hypercalcemia phase lasts from 8 days to 3.5 months. In our case, the patient initially developed hypocalcemia in the oliguric phase of acute kidney injury from rhabdomyolysis. He developed hypercalcemia in the polyuric phase of renal recovery. The hypercalcemia resolved with intravenous hydration, calcitonin and pamidronate. Rhabdomyolysis is a rare cause for both hypocalcemia and hypercalcemia. Our case highlights the biphasic calcium response associated with rhabdomyolysis in the setting of renal impairment and recovery.

Presentation: 6/1/2024
8586 A Case Of Vitamin D Toxicity: From Michigan To Hawaii, Vitamin D Is Very High
Authors: Abu Limon Ahmad , Aldasouqi Saleh A , Patel Kunjal , Akanbi Folake , Khan Shaza , Kachhadia Palak
Published: October 2024

Disclosure: A. Abu Limon: None. S.A. Aldasouqi: None. K. Patel: None. F. Akanbi: None. S. Khan: None. P. Kachhadia: None.

We report a patient case who is a 46-year-old male, managed for Type 2 diabetes and Vitamin D deficiency (Defined by 25-hydroxy vitamin D levels less than 20ng/ml) at Michigan State University Endocrinology specialty clinic.He started taking 5000 IU daily Vitamin D supplements and on subsequent follow up his levels corrected to 88 ng/ml. His supplements were held.On a routine repeat lab check, his 25-hydroxy vitamin D level is reported to be higher than 200 ng/ml. Which meets the biochemical diagnosis of Vitamin D toxicity. His Calcium level was 9.7 mg/dL (N 8.7-10.3 mg/dL) and PTH-intact level was 38.3 pg/mL (N 14.0-72.0 pg/mL).On questioning the patient, he assured us he is still not on any Vitamin D supplements and that he just got back from a two-weeks long trip from Hawaii and spent hours daily on the beach without using sunblock.He is sure he didn't get tanning, sunburns, or any burns during that period.He was feeling fine without any symptoms or complications.While in Michigan during the winter, with limited number of sunny days, His 25-hydroxy vitamin D levels trended down slowly over the following few months, while Vitamin D supplements kept on hold.The most common cause of Vitamin D toxicity is excessive supplemental Vitamin D use. Other reasons can be related to excessive tanning or burns, that our patient didn't have. Excessive sun exposure or dietary intake is not a known reason to raise Vitamin D levels to a toxic range.Our patient lives in Mid-Michigan, an area known for low number of sunny days (150-180 sunny/ partly sunny days per year ), Which is a reason for high prevalence of vitamin D deficiency in the population. This is Compared to mostly sunny days on the Hawaiian Islands.Coming Back home for the winter season did help his Vitamin D levels to continue trending down back to a safe, non-toxic range.

Presentation: 6/2/2024
8184 A Case With Primary Hyperparathyroidism Caries A New Variant Of Uncertain Significance (VUS) Of The Multiple Endocrine Neoplasia Type 1 (MEN1) Gene
Authors: Guzelce E Caliskan , Fieg E , Pallias C
Published: October 2024

Disclosure: E. Caliskan Guzelce: None. E. Fieg: None. C. Pallias: None.

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal dominant disorder caused by mutations in the MEN1 tumor suppressor gene. MEN1 syndrome is classically characterized by a predisposition to tumors of the parathyroid glands, anterior pituitary, and pancreatic islet cells. However, the clinical spectrum of this disorder has been expanded: carcinoid tumors,adrenal adenomas and lipomas are more common than in the general population.We report a case whose personal and family history is highly suggestive of and consistent with a monogenic disorder such as MEN1, also found to be a carrier of a new variant of uncertain significance (VUS) of the MEN1 gene. A study performed with the French Universal Mutation Database (UMD) for the MEN1 gene showed that one-third of the missense MEN1 variants were VUSs, mainly due to the lack of clinical and segregation data. Therefore, it is very important to identify and report the subjects with VUS of the MEN1 gene. Case report: 68-year-old female with a past medical history significant for hypertension, type 2 diabetes mellitus, hyperlipidemia, CKD stage 4, and nephrolithiasis, GERD who presented with chief complaints of nausea and upper abdominal/epigastric pain and dark stools and found to have moderate hypercalcemia c/w primary hyperparathyroidism, several pancreatic cystic lesions most likely branch duct intraductal papillary mucinous neoplasms, and multinodular goiter and adrenal adenoma. Family history significant for recurrent hyperparathyroidism and nephrolithiasis; her daughter and brother had nephrolithiasis; her daughter has undergone parathyroidectomy twice. The patient's mother died at a young age because of gastric ulcer-related complications. Hyperparathyroidism-related genes were analyzed; AP2S1, CASR, CDC73, CDKN1B, GNA11, RET, MEN1, and only a Variant of Uncertain Significance, c.247_249dup (p.Leu83dup), was identified in MEN1 gene. The patient’s daughter and granddaughter are found to have the same mutation. Conclusion: This variant, c.247_249dup, results in the insertion of 1 amino acid(s) of the MEN1 protein (p. Leu83dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). The literature has not reported this variant in individuals affected with MEN1-related conditions.

Presentation: 6/3/2024
8472 A Little Too Much Of Tums: A Unique Presentation Of Milk Alkali Syndrome
Authors: Al-Hiti Zena , Misbah Afrah
Published: October 2024

Disclosure: Z. Al-Hiti: None. A. Misbah: None.

Milk-Alkali Syndrome is characterized by a triad of hypercalcemia, metabolic alkalosis, and renal dysfunction. Historically associated with the excessive consumption of milk and alkali-containing antacids, it has re-emerged in recent years due to the widespread use of calcium and vitamin D supplements. It primarily results from an imbalance between calcium intake and renal excretion, leading to elevated calcium levels in the bloodstream. We present a case of milk-alkali syndrome with persistent renal dysfunction after normalizing calcium levels. We present the case of a 65-year-old male who presented to the emergency department with generalized weakness, poor oral intake, and confusion for 3 days. He was noted to have been more adherent with taking his prescribed medications over the last 2 weeks, which include calcitriol 0.5 mcg BID, calcium acetate 667 mg TID, and calcium carbonate 800 mg TID. On admission, he was afebrile and hemodynamically stable. . On examination, he had dry mucous membranes. He had no focal neurological deficits but he was confused and lethargic, and was only oriented to self. Other examination was noncontributory. Complete blood count and urinalysis were largely unremarkable. Chemistry demonstrated an elevated calcium level of 16.0 (8.3-10.6 mg/dL), ionized calcium of 7.3 (4.6-5.3 mg/dL), sodium of 134 (135-145 mmol/L), potassium of 5.4 (3.5-5.1 mmol/L), high phosphorus of 5.3 (2.4-5.1 mg/dL), and bicarbonate of 36 (20-31 mEq/L). Creatinine was elevated at 2.9 (0.6-1.1 mg/dL) from baseline of 1.3 to 1.4 mg/dL, and he had a BUN of 40(9-23 mg/dL). Venous blood gas showed a pH of 7.54( 7.32-7.42), pCO2 of 56 (40-52 mm Hg), and bicarbonate of 38 (23-28 mEq/L), indicating metabolic alkalosis. TSH was elevated at 36.15 (0.55- 4.78 uIU/mL) with a level of 140 two weeks back. Chest X-ray, renal ultrasound and CT head all showed no acute disease. Further work-up revealed a low PTH level of 6.3 (18.4-80 pg/mL), normal PTHrP level and 25-OH Vitamin D. There was no monoclonal gammopathy. Management included aggressive IV fluid resuscitation and IV calcitonin. However, no zoledronic acid was given due to a history of parathyroidectomy and risk of hypocalcemia. His serum calcium improved and eventually normalized. His confusion resolved. However, his creatinine and BUN increased to 3.4 mg/dL and 77, respectively, and did not improve to his baseline. This case highlights the importance of recognizing Milk-Alkali Syndrome as a potential consequence of over-the-counter calcium supplementation and highlights the potential for acute kidney injury which could be irreversible. Healthcare providers should be vigilant in identifying patients at risk, which includes older patients and patients with chronic kidney disease. Early recognition and appropriate management are crucial to prevent further renal deterioration and improve outcomes in individuals with Milk-Alkali Syndrome.

Presentation: 6/2/2024
12478 A Pilot Evaluation Of Automated Morphometry Performance On Vertebral Fracture Assessment (vfa) And Its Impact On Interpretation
Authors: Syed S , Binkley N
Published: October 2024

Disclosure: S. Syed: None. N. Binkley: None.

Introduction: Prevalent vertebral fractures convey increased fracture risk but are often clinically silent; thus, imaging is required for their detection. Vertebral fracture assessment (VFA) can be performed at the time of DXA. We hypothesized that VFA automated morphometry does not accurately identify the number of vertebrae visualized nor the number of fractures present and sought to begin exploring if morphometry impacted the formal interpretation. Methods: Patients seen by an Orthopedic bone health provider were studied. Their VFA images were independently assessed by two physicians, after which a consensus “gold standard” (GS) reading was reached. The number of vertebral bodies able to be assessed and the number of fractures identified by morphometry (M), the formal interpretation (I) and the GS result were compared by one way ANOVA. Results: The study cohort included 100 patients with mean (SD) age 77.6 (8.6) years, 81% female with BMI 26.7 (5.0) kg/m2, 91 of whom had prior clinical fracture. M reported visualizing more vertebral bodies than I and GS; 1243, 1168 and 1063 respectively. I identified numerically more (13) fractures than did M (150 vs. 137) but was lower than GS (167). The automated and formal reports were identical in 52 patients; in this subgroup, 8 patients (15%) had vertebral fractures that were not identified on the formal interpretation. In this same group of 52 patients, an additional 7 (13%) with vertebral fractures had 9 vertebral fractures missed. Conclusion: In this pilot study assessing VFA, automated vertebral morphometry reports identifying more vertebrae than are actually able to be evaluated while missing almost 18% of vertebral fractures that were actually present. That the formal interpretation is identical to that of morphometry in over 50% of patients, while missing vertebral fractures over 12% of the time, implies that morphometry is adversely impacting the formal interpretation and thereby potentially patient care. Further study with larger datasets is indicated.

Presentation: 6/3/2024
7027 A Rare And Multifactorial Etiology Of Severe Parathyroid Hormone Independent Hypercalcemia In An Adult Female With Rett Syndrome
Authors: Foo Madeline I , Thompson Michael
Published: October 2024

Disclosure: M.I. Foo: None. M. Thompson: None.

Background: Symptomatic hypercalcemia is a rare, but potentially life-threatening disorder. Although dehydration is an unusual cause of severe hypercalcemia, in the appropriate clinical setting dehydration may amplify underlying mild or moderate hypercalcemia to dangerous levels.Case: A 46-year-old non-verbal, non-mobile Caucasian female with Rett Syndrome (RS) with Stage III Chronic Kidney Disease (CKD3) who is dependent on percutaneous endoscopic gastrostomy (PEG) tube for nutrition and known PTH independent hypercalcemia of unknown etiology presented to the hospital with intractable vomiting and constipation, an outpatient serum calcium level of 16.0 mg/dL, and serum creatinine 4.03 mg/dL (baseline 1.2 mg/dL). Initial laboratory assessment revealed elevated corrected serum calcium levels (15.7 mg/dL), with appropriately suppressed PTH levels (12.5 pg/mL) and hypernatremia (146 mmol/L). Thyroid function tests, both Vitamin D 1,25(OH)2D and D 25(OH)D levels and PTH-RP were normal. Computed tomography of the abdomen and pelvis revealed bilateral nephrolithiasis and moderate stool burden, but no evidence of malignancy or granulomatous disease. Skeletal scintigraphy was also without evidence of osseous metastatic disease or Paget’s disease of bone. An in-depth interview with the patient’s caregiver uncovered that the patient had a relative intolerance to enteral hydration and had been receiving minimal water flushes prior to admission, contributing to severe dehydration. Hypercalcemia was ultimately ascribed to prolonged immobilization due to RS compounded by inadequate fluid intake and auto-diuresis secondary to hypercalciuria in the setting of CKD (prior baseline eGFR 45 mL/min/1.73m2).Outcome: The patient's hypercalcemia improved after a multidisciplinary and multi-directed approach involving intravenous and enteral fluid resuscitation, calcitonin, furosemide, and ultimately zoledronic acid following improvement in creatinine with fluid resuscitation. The dietary service employed a strategy of 24-hour enteral feeding, increasing both the frequency and amount of enteral water, which the patient tolerated well, and provided her with a new pump for home use. Education on monitoring tube feed tolerance and providing adequate enteral hydration was provided to both the caregiver and group home. On discharge, eGFR stabilized at 33 mL/min/1.73m2 and corrected calcium stabilized at 10.0–10.4 mg/dl. She was provided with an endocrinology follow-up to continue bisphosphonate therapy.Discussion: Hypercalcemia of immobility should remain a differential diagnosis in severe hypercalcemia, especially PEG tube dependent patients with underlying kidney disease. This case highlights the importance of thorough history taking and a multidisciplinary strategy to guarantee optimal care and mitigate potential adverse outcomes in medically complex patients.

Presentation: 6/2/2024
7331 A Rare Case Of Familial Hypoparathyroidism
Authors: Sekhon Navharsh , Zin Win Kyaw
Published: October 2024

Disclosure: N. Sekhon: None. K.Z. Win: None.

Background: Autosomal dominant hypoparathyroidism disorders are very rare and mostly asymptomatic. We present an interesting case of autosomal hypoparathyroidism with a new variant of gene defect on genetic analysis. Case: A 66-year-old female was referred to the endocrinology clinic for familial hypoparathyroidism and calcium oxalate nephrolithiasis. She had onset of seizures at age 16. She was diagnosed with hypocalcemia and hypoparathyroidism at age 30 when she had her first episode of nephrolithiasis. She had recurrent nephrolithiasis and lithotripsies, ultimately developing chronic kidney impairment that was at stage 3b at the time of evaluation. Renal Ultrasound revealed bilateral nephrolithiasis, and nephrocalcinosis. There was a history of hypoparathyroidism in her father, paternal uncle, and son. Her medications included calcium carbonate-vitamin D3 600-400 mg-unit oral 2 tablets daily and calcitriol 0.5 mcg daily. The pertinent physical examination finding was a short stature with height 4’11” and calluses in fingers. Her recent serum chemistry showed calcium 8.8 mg/dL (reference range 8.3 - 10.6 mg/dL), PTH < 6.3 pg/mL (reference range 18.4 - 80.1 pg/ mL), and phosphorus 3.3 mg/dL (reference range 2.4 - 5.5 mg/dL). 24 hr urine calcium was 96 mg (reference range 50-300 mg/24h). She was treated with hydrochlorothiazide for nephrolithiasis but was discontinued due to hypokalemia. We performed genetic testing that resulted positive for CASR NM_001178065.1 with heterozygosity and damaging missense predictions inherited as autosomal dominant or recessive. Discussion: The calcium-sensing receptor (CaSR) has an important role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion and urinary calcium excretion. Familial hypoparathyroidism disorders are divided into Autosomal dominant hypocalcemia (ADH) type 1 and Autosomal dominant hypocalcemia (ADH) type 2. ADH1 is caused by an activating mutation of calcium-sensing receptor (CASR). The estimated prevalence of ADH1 ranges from 1 per 70,000 to 3.9 per 100,000. It is characterized by mild to moderate hypocalcemia, hyperphosphatemia, hypercalciuria, and inappropriately low but detectable PTH levels. It can be associated with Bartter syndrome Type 5. ADH2 is due to mutations in the alpha subunit of the G protein G11 (Gα11). Our patient had classic symptoms of hypocalcemia including short stature, seizures, kidney stones and its sequelae. Her 24-hour urine analysis showed inappropriately normal urine calcium with low normal serum calcium, undetectable serum PTH, and normal phosphorus. Our patient’s genetic analysis revealed a heterozygous defect in gene CASR with DNA variants c.2564G>A with damaging missense predictions. There is no such variant reported or listed in the ClinVar database. To our knowledge, this is the first such case of an autosomal dominant hypoparathyroidism with this gene defect.

Presentation: 6/1/2024
6874 A Rare Case Of Hereditary 1,25 (OH)2D Resistant Rickets
Authors: Umarji G , Thelmo F , Jabbour S A
Published: October 2024

Disclosure: G. Umarji: None. F. Thelmo: None. S.A. Jabbour: None.

Vitamin D-dependent rickets type 2A (VDDR2A) also known as hereditary 1,25 (OH)2D resistant rickets is due to biallelic loss-of-function mutations in the gene encoding vitamin D receptor on chromosome 12q13.11, thus, it represents a true form of tissue resistance to vitamin D. It is a scarce form of rickets with approximately only 120 cases reported. A 37-year-old male was referred to endocrinology by neurosurgery for evaluation of metabolic bone disease. Seven years ago, he was in a car accident which resulted in a lumbar spine injury causing radiculopathy and severe low back pain leading to lumbar spine decompression/fusion. However, he suffered from nonunion of bones and had to undergo another surgery a year later with recurrent postoperative nonunion of bones. During the operation, the surgeon noticed that his spine seemed demineralized. He had a history of multiple minor fractures in childhood, decreased hearing in left ear for two years, fragile teeth for many years, and some hair loss since age 30. Physical exam showed a height of 1.82 m, weight 89.3 kg with body mass index of 26 kg/m2, broken teeth, no leg bowing and normal stance. Laboratory results showed normal renal function, thyroid function tests and testosterone level, corrected calcium 8.3 mg/dL (8.7-10.2), 25-OH-vitamin D 54 ng/mL (30-100), phosphorus 2.8 mg/dL (2.8-4.1), intact parathyroid hormone 65 pg/mL (15-65), bone-specific alkaline phosphatase 21 mcg/L (4-27), 24-hour urine calcium 156 mg/day (100-300), 24-hour urine phosphorus 1,752 mg/day (390-1,425), FGF-23: 93 RU/mL (44-215) and 1,25 (OH)2D 92 pg/mL (24-81.5). Dual absorptiometry of the lumbar spine and hip showed osteopenia with Z scores of -2.2 and -1.2 respectively. Genetic testing for metabolic bone disease panel showed heterozygous mutation in VDR gene at nucleotide position c.146+9dup associated with autosomal recessive VDDR2A. We present a very rare form of vitamin D resistant rickets. As many patients with VDDR2A are unable to respond to any form of vitamin D, it is suggested that VDDR2 be more appropriately described as hereditary 1,25 (OH)2D resistant rickets (HVDRR), hereditary resistance to 1,25 (OH)2D, or even pseudovitamin D-deficiency type IIA (PDDR IIA). Clinical features include severe rickets, bone pain, hypotonia, dental caries and alopecia. Biochemical features include hypocalcemia, hypophosphatemia, normal to elevated alkaline phosphatase, normal 25(OH)D and importantly, elevated 1,25-(OH)2D levels. Management is with high doses of calcium and vitamin D therapy. While rare, this disease highlights the need for a comprehensive evaluation of metabolic bone diseases and a thorough understanding of calcium and vitamin D metabolism.

Presentation: 6/2/2024