bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT499 Amyloid Goiter: A Case Series
Authors: Paz-Ibarra Jose , Concepción-Zavaleta Marcio , Solis Pazmino Andrea Paola , Peralta Jose Somocurcio
Published: October 2023

Disclosure: J. Paz-Ibarra: None. M. Concepción-Zavaleta: None. A.P. Solis Pazmino: None. J. Somocurcio Peralta: None.

Background: Amyloid goiter (AG) is a rare presentation of thyroid swelling, characterized by the presence of deposits of amyloid protein in the thyroid tissue, accompanied by fat deposition or thyrolipomatosis. It may occur in 50% and up to 80% of patients with primary and secondary amyloidosis, respectively. Currently, the treatment is surgical resection of the thyroid gland. The present study reports a case series of primary thyroidal nodular amyloid goiter diagnosed by fine-needle cytology (FNC). Clinical cases:There were 2 female and 1 male patient from Peru. All three patients had comorbidities prior to AG diagnosis. F1: 65 years old, history of Rheumatoid Arthritis, Sjogren’s disease nephron Angio sclerosis, and polycystic kidney disease. F2: 67 years old, history of rheumatoid arthritis, end-stage renal disease (ESRD), arterial hypertension. M1: 28-year-old man with a history of pulmonary tuberculosis, bronchiectasis, and ESRD on HD due to renal amyloidosis of 9 years' evolution. They reported dyspnea, dysphagia, and dysphonia. On their physical examination, they had a bilateral, firm, and diffusely enlarged thyroid gland. Her serum T3, T4, and TSH levels were all normal. The PAAF reported a colloid goiter (Bethesda II). A total thyroidectomy was performed, with no complications. An alcohol-fixed smear was stained with Congo red: the amyloid material appeared cherry red and it also showed apple-green birefringence when observed with a polarizing microscope. Conclusions: Secondary amyloidosis generally has a neoplastic origin or is secondary to chronic inflammatory diseases. The development of a giant goiter with compressive symptoms is the most common form of presentation and represents amyloid infiltration of the gland. Total thyroidectomy is the method of choice for both diagnosis and treatment of amyloid goiter. Histological evaluation of the resected thyroid gland is crucial to make a definitive diagnosis.

Presentation Date: Saturday, June 17, 2023
SAT502 Choristoma: A Very Rare Cause of Thyroid Nodule. Clinical Case and Literature Review
Authors: Rocha José Vicente , da Cruz Rafael Moiteiro , Alexandre Maria Inês , Gomes Ana , López-Presa Dolores , Bugalho Maria Joao
Published: October 2023

Disclosure: J. Rocha: None. R. Moiteiro da Cruz: None. M. Alexandre: None. A. Gomes: None. D. López-Presa: None. M.J. Bugalho: None.

Introduction: A choristoma is a well delimitated benign lesion formed by normal tissue in an unusual location. Choristomas are rare lesions that are mainly reported in the eye, tongue or ears. The etiology of the choristoma is not well established but congenital defects in cell migration and exposure to chronic inflammation are two of the suggested hypothesys. Diagnosis is made after surgical removal of the mass, usually with no other associated abnormalities. To our knowledge, to this day there is only one other case of thyroid choristoma described in literature. Clinical case: A 70-year-old man presented to the emergency department with hyperglycemia, polydipsia and polyuria. Personal history was notable for non-Hodgkin lymphoma in remission after stem cell autologous transplant, currently under high dose prednisolone treatment due to sudden cervical enlargement. Cervical imaging with CT scan showed a 47mm hypodense nodule of the right thyroid lobe. The patient was refered to an Endocrinology appointment.Thyroid function was normal, with normal serum calcitonin and negative anti TPO and antiTG antibodies. Fine-needle aspiration biopsy was notable for folicular lesion of undetermined significance. During the following weeks there was a noticeable thyroid enlargement causing positional dyspnoea and dysphonia. Ultrassound revealed a 73mm nodule of the right lobe, predominantly cystic and isoechoic in the solid regions. At this point the patient underwent total thyroidectomy without complications.Histopathological examination revealed a choristoma composed of cysts lined by squamous epitelium, smooth muscle bundles, mature adipose tissue, areas of calcification and ossification and extramedullary hematopoiesis; there were also signs of old and recent haemorrhage and foreign body granulomas. No cytological atypia or tumoral necrosis were found. Conclusion: Thyroid choristomas are extremely rare entities. Unlike the previously described case our patient had a rapid growth of the cervical mass. This case is specially relevant due to its clinical course, existing comorbidities and rarity of the final diagnosis.

Presentation Date: Saturday, June 17, 2023
FRI218 Von Hippel-Lindau With Pheochromocytoma And Severe Orthostatic Hypotension
Authors: Ebrahimi Neda , Rivas Pajuelo Cynthia G , Habibi Roshanak , Tariq Sarah , Penquite Sara Ashlyn
Published: October 2023

Disclosure: N. Ebrahimi: None. C.G. Rivas Pajuelo: None. R. Habibi: None. S. Tariq: None. S.A. Penquite: None.

Introduction: Von Hippel-Lindau (VHL) syndrome clinically manifests with benign and malignant tumors across multiple organ systems including the cerebellum, retina, kidney, and adrenal glands. Pheochromocytoma occurs in 25-30% of patients with VHL. Up to 50% of patients with pheochromocytoma present with hypertension or paroxysmal hypertension, although patients can be normotensive on presentation. Patients with pheochromocytoma are often severely volume depleted due to chronic vasoconstriction. Here we present a case of VHL with pheochromocytoma complicated by profound orthostatic hypotension after initiation of alpha-blockade.

Case Presentation: A 32-year-old man presented for evaluation of progressive headache and diplopia. Patient was normotensive on initial presentation with BP 129/80mmHg. Brain MRI with contrast subsequently revealed a posterior fossa cystic mass with an avidly enhancing central nodule concerning for hemangioblastoma. Given these findings, a CT chest/abdomen/pelvis was obtained, which demonstrated a 4.6 x 5.0 cm right adrenal mass, several enhancing renal lesions, and multiple cystic lesions throughout the pancreas. This constellation of radiological findings was clinically concerning for VHL. Further endocrinologic work-up revealed plasma metanephrines 663 pg/mL (insert reference range here), plasma catecholamines 770 pg/mL (insert reference range here), which confirmed the diagnosis of pheochromocytoma. Alpha blockade was initiated with doxazosin 4 mg BID, and a high sodium diet (insert g/day). Shortly after initiation of doxazosin, patient developed severe orthostatic hypotension despite salt loading and volume resuscitation. Ultimately doxazosin was discontinued, and surgery was postponed due to severe symptomatic orthostatic hypotension limiting patient’s ability to get out of bed. High sodium diet was continued on hospital discharge and alpha-adrenergic blockade was later re-initiated which patient is tolerating well. Patient is pending adrenalectomy in the coming weeks. Discussion: Orthostatic hypotension in pheochromocytoma is expected due to volume depletion from chronic vasoconstriction. Alpha adrenergic blockade is required to alleviate hypertension, allow for adequate volume expansion, and to prevent a hypertensive crisis intraoperatively. Clinicians should be aware of the commercially available alpha-adrenergic antagonists and when they should be temporarily discontinued. There is no preferred alpha-adrenergic antagonist agent, however doxazosin has shown to cause less orthostatic hypotension and does not have such an antihypertensive effect as of Phenoxybenzamine.

Presentation: Friday, June 16, 2023
THU553 Anti-tumor Effect Of Rosiglitazone Via Upregulating 15-PDGH In Prolactin Secreting Adenoma
Authors: Kang Chan Woo , Hun OH Ju , Wang Eun Kyung , Lee Soohyun , Nam Jung Ho , Hong Jae Won , Lee Eun Jig , Ku Cheol Ryong
Published: October 2023

Disclosure: C. Kang: None. J. Oh: None. E. Wang: None. S. Lee: None. J. Nam: None. J. Hong: None. E. Lee: None. C. Ku: None.

Background: Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPAR γ) ligand, are used to treat type II diabetes. Over the last few years, PPAR γ has received much attention for its ability to exert variable tumors. Objective: The aim of this study is to investigate the anti-tumor effect of rosiglitazone on prolactin secreting pituitary adenomas and its mechanism. Materials & Methods: Lactotroph cell line (GH4, MMQ) were treated with Phosphate-buffered saline (PBS) or rosiglitazone. In vitro analysis such as qPCR, immunoblot, prolactin (PRL) ELISA, Cell proliferation assay, and Fluorescence-activating cell sorting (FACS) analysis were performed to examine the effect of rosiglitazone on Lactotroph cell lines. Result: To investigate the direct effect of rosiglitazone on PRL secretion of the pituitary adenomas, GH4 and MMQ cells were treated with rosiglitazone 1, 5, 10, 50 μM for 72 hr. Both PRL mRNA and secretion levels were significantly decreased by rosiglitazone in a dose-dependent manner. In previous studies, 15-PDGH has been implicated as a tumor suppressor gene with the property that inhibits the tumor growth. Interestingly, 5 μM rosiglitazone upregulated the mRNA and protein levels of 15-PDGH in both GH4 (4.73-fold) and MMQ (4.04-fold) cells. Next, we investigated whether rosiglitazone had any effects on the proliferation of prolactinoma cells. Proliferation of the GH4 and MMQ cells were significantly decreased by rosiglitazone in a dose-dependent manner after treatment. Rosiglitazone potently induced cell cycle arrest in sub-G1inGH4 and MMQ cells. Furthermore, rosiglitazone treatment significantly increased both early (2.31-fold) and late apoptosis (1.9-fold) of GH4 and MMQ cells. Conclusion: These results collectively position 15-PDGH as a potential new therapeutic target for prolactinomas and implicate rosiglitazone as a possible alternative pharmacological approach for prolactinomas.

Presentation: Thursday, June 15, 2023
SAT342 Stress-induced Cardiomyopathy And Pheochromocytoma
Authors: Rivas Pajuelo Cynthia G
Published: October 2023

Disclosure: C.G. Rivas Pajuelo: None.

Introduction Pheochromocytoma (PCC) can be associated with certain genetic syndromes such as Neurofibromatosis type 1(NF1). About 5-7% of patients with NF1 will develop PCC/PGL in their lifetime. Typically, PCC presents with hypertension, and rarely, as stress-induced cardiomyopathy. Herein we present a case of a patient with NF1, and stress-induced cardiomyopathy due to Pheochromocytoma. Case presentation: A 63-year-old woman with medical history of NF1 presented to the hospital for acute hypoxemic respiratory failure and hypertensive emergency. On admission, had troponin level 27 ng/L, pro-BNP 2446 pg/ml; had a transthoracic echocardiogram (TTE) that showed EF of 30%, with global hypokinesis, anteroseptal and inferoseptal akinesis. Given NF1 history and hypertension, a CT chest/abdomen/pelvis was ordered and showed bilateral adrenal adenomas; a 2.6 cm left adrenal adenoma HFU 3, and a right adrenal mass 4.0 x 3.7 cm HFU 45 with indeterminate density. Biochemically, had markedly elevated plasma catecholamines (epinephrine 352 pg/mL, Norepinephrine 1904 pg/mL) and urinary metanephrines (2155 mcg/24 h). She markedly improved after IV diuresis, and prior to discharge was started on alpha-blockade with prazosin. This was titrated as outpatient, with addition of metoprolol 1 week later. MIBG showed intense tracer uptake in the right adrenal gland suggestive of pheochromocytoma, the left adrenal nodule was lipid rich. A repeat TTE 2 months later showed improved EF to 60% and had left heart catheterization revealing normal coronary arteries. She underwent right laparoscopic adrenalectomy, with final pathology report of 4.8 cm pheochromocytoma with negative margins.

Discussion: Stress-induced cardiomyopathy is a life-threatening complication that can be the initial presentation in patients with PCC. Hypersecretion of catecholamines specifically norepinephrine and epinephrine, are thought to play a role in combination with PCC tumor cells, to act synergistically and induce direct cardiotoxic effect. Treatment with medical management followed by surgical excision of the PCC will reverse cardiomyopathy as in our patient. Ultimately, because patients with NF1 are at increased risk for PCC, it is recommended they undergo screening with plasma metanephrines and catecholamines or urinary metanephrines at least every 1-2 years especially if hypertension or tachycardia are present.

Presentation: Saturday, June 17, 2023
THU407 CRISPR/Cas9-based Knockout Of CFTR Alters Mechano-sensitivity And Proteomic Profile In An Osteocyte Model
Authors: Du Wanting , Chen Junjiang , Ruan Ye Chun
Published: October 2023

Disclosure: W. Du: None. J. Chen: None. Y. Ruan: None.

Osteocytes, the most abundant bone cell type with recognized endocrine functions, play essential roles in mechano-signal transduction in the skeletal system required for bone modelling/remodelling and mineral homeostasis, although the underlying molecular mechanisms are not fully understood. Bone problems are present in cystic fibrosis (CF), a genetic disease resulted from mutations in CF transmembrane conductance regulator (CFTR), which is a Cl− channel gene recently revealed to be expressed in osteocytes with its exact roles largely unexplored. In the present study, CRISPR/Cas9 technology was used to knock out CFTR (CFTR-KO) in MLO-Y4, a commonly used osteocyte model, which resulted in a significant decrease (by 80.7 ± 7.4%) in shear force-induced Ca2+ oscillations (measured by Fura-2 imaging) as compared to wild-type (WT) cells (n = 205 (WT) and 114 (KO) cells, t-test, p < 0.001). However, the CFTR-KO cells did not show, in comparison with WT cells, any reduction in expressing (measured by quantitative PCR, n = 5) Piezo1 or TRPV4, two reported key mechano-sensitive Ca2+ channels in osteocytes, nor change in cell membrane stiffness (measured by atom force microscope, n = 58 (WT) and 64 (KO) cells, t-test, p > 0.05). Moreover, the shear-force-stimulated Ca2+ oscillations in WT cells were observed to be dependent on extracellular Cl−, which together suggested possibly a direct role of CFTR, through its Cl- channel function, in osteocyte mechano-sensitivity. We next performed proteomic analysis by mass spectrometry detection of whole-cell protein extracts from the MLO-Y4 cells, which revealed downregulation of genes related to focal adhesion, gap junction and actin cytoskeleton regulation in CFTR-KO cells. These results, therefore, have suggested a crucial involvement of CFTR in osteocyte function, providing new insights into mechanistic understanding of the mechano-transduction in the skeletal system. This work was supported in part by Health and Medical Research Fund of Hong Kong (No.18191361), Theme-based Research Scheme of Hong Kong (No. T13-402/17N), and Areas of Excellence Scheme of Hong Kong (AoE/M-402/20).

Presentation: Thursday, June 15, 2023
THU417 Associations Between Glucose Metabolism And Trabecular Bone Score In Subjects With Acromegaly
Authors: Kuzma Martin , Payer Juraj , Vanuga Peter , Sagova Ivana , Pavai Dusan , Jackuliak Peter , Killinger Zdenko , Binkley Neil
Published: October 2023

Disclosure: M. Kuzma: None. J. Payer: None. P. Vanuga: None. I. Sagova: None. D. Pavai: None. P. Jackuliak: None. Z. Killinger: None.

Introduction: Previously, it was thought that increased risk of vertebral fractures (VF) in acromegaly is associated with impaired trabecular bone. More recently, cortical bone was proposed as one of the fracture risk determinant. However, trabecular compartment is still decreased. Glucose intolerance is a frequent complication of acromegaly and is directly attributable to the excess circulating growth hormone and IGF-1 concentrations and thus possibly lead to trabecular bone detoriation.Objectives: To assess effect of glucose metabolism on DXA-derived bone parameters, such as bone mineral density (BMD), trabecular bone score (TBS), cortical and trabecular vBMD, surface BMD and cortical thickness of proximal femur among patients with acromegaly. Patients and methods: In total, 70 consecutive patients (24 males/56 female, mean age = 55.6 years) with acromegaly based on current ADA guidelines were divided in two subgroups according to glucose metabolism(GM): abnormal GM (n=35; 14 males/21 females; 15 with active disease) and normal GM (n=35;10 Males /25 Females; 11 with active disease). Subjects were prospectively followed up for two years. At baseline and year 2; all subjects had pituitary hormonal measures, fasting plasma glucose (FPG), HBA1c, C-peptide, insulin resistance index (IRI) and DXA measurement performed. From DXA, BMD, TBS and 3D-Shaper parameters were derived. Results: At baseline; subjects with abnormal GM had lower TBS (1.166±0.15) in comparison to normal GM subjects (1.232±0.12; p<0.05). Insulin like growth factor 1 (IGF-1), FPG, HBA1c, C-peptide, IRI and bone parameters was correlated in simple regression model. FPG, HBA1c, C-peptide and IRI was negatively associated with TBS. No correlation between GM parameters and other bone measures was observed. Multiple regression model of all GM parameters weighted by IGF-1 revealed HBA1c as a significant predictor of TBS value (Estimate =-0,054; p=0.04). At year 2; FPG and HBA1c was negatively associated with TBS. In multiple regression IGF-1-weighted model, no significant predictor of TBS was observed. Conclusion: Acromegaly subjects with abnormal GM have lower TBS in comparison to those with normal GM. The best GM parameter to predict TBS in acromegaly was HBA1c. This study showed that trabecular bone microstructure, as indirectly assessed by TBS, is likely resulting of impaired glucose metabolism.

Presentation: Thursday, June 15, 2023
THU448 Multiple Non-traumatic Vertebral Fractures After Discontinuation Of Denosumab
Authors: Riahi Shayan , Crawford Andrew Robert , Gruntmanis Ugis
Published: October 2023

Disclosure: S. Riahi: None. A.R. Crawford: None. U. Gruntmanis: None.

Background: In multiple studies, including a post-hoc analysis of the FREEDOM trial1, an increased risk of vertebral fractures has been demonstrated in patients after discontinuation of denosumab. Clinical Case: A 65-year-old female presented to the endocrinology clinic for evaluation of severe osteoporosis. She was diagnosed with osteoporosis in 2017 after a DXA scan demonstrated a lumbar spine T-score of −3.5. She was started on denosumab therapy by her primary care provider to treat her osteoporosis and received a total of 10 injections over 5 years, during which time she experienced no fractures. Her lumbar spine T-score improved to −2.6 in March of 2021. She received her last injection of denosumab in December of 2021 and was told that she no longer needed denosumab therapy. She began to develop severe pain in her back in October of 2022 and noticed a 3-inch height loss. X-rays done in November of 2022 demonstrated a new compression fracture in L2. Due to persistent debilitating pain, patient had repeat X-rays performed 1 week later which demonstrated multiple age indeterminate compression fractures which MRI was able to confirm at T5, T7, and T9-T12. Repeat DXA scan in December of 2022 demonstrated a lumbar spine T-score of −3.1. Serum C-Telopeptide (CTX) was 1060pg/mL. Patient had adequate calcium and vitamin D intake, and secondary causes of osteoporosis were excluded. Conclusion: This case report highlights the rapid reversibility of the beneficial effects of denosumab on bone density and bone remodeling after discontinuation of the drug (evidenced by the significantly elevated CTX), the importance of close follow up, and the use of transition therapy in patients after discontinuation of denosumab to attenuate the risks associated with stopping the medication. It also places import on the use of MRI imaging, especially in the cases of rebound associated vertebral fractures secondary to denosumab discontinuation2 for those patients in whom you have high suspicion to better characterize compression fractures when x-ray findings are not felt to be sufficient.

References: (1) Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Törring O, Valter I, Wang AT, Brown JP. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension. J Bone Miner Res. 2018 Feb;33(2):190-198. doi: 10.1002/jbmr.3337. Epub 2017 Nov 22. PMID: 29105841. (2) Anastasilakis, A.D., Evangelatos, G., Makras, P. et al. Magnetic resonance imaging has an advantage over conventional spine X-rays in the evaluation of rebound-associated vertebral fractures following denosumab discontinuation. Endocrine69, 516–518 (2020). https://doi.org/10.1007/s12020-020-02333-1

Presentation: Thursday, June 15, 2023
THU466 XLH During Pregnancy: A Closer Look Based On Real-World Experience
Authors: Ali Dalal S , Khan Aliya Aziz
Published: October 2023

Disclosure: D.S. Ali: None. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Takeda. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx.

Background: X-linked hypophosphatemia (XLH) is a genetic disorder caused by mutation in the PHEX gene leading to excess serum levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23). High FGF23 causes renal phosphate wasting, decreased production of serum 1,25-dihydroxy vitamin D, and increased metabolism of 1,25-dihydroxy vitamin D, leading to hypophosphatemia. Maintaining normal serum phosphorus levels in pregnant women with XLH is critically important to ensure mineralization of the fetal skeleton. Multiple factors may influence phosphorus homeostasis in pregnancy, including an increase in PTHrP production and a tripling of calcitriol beginning in the first trimester. Case study: 30 years old Gravida 1 Para 0 with XLH, diagnosed at the age of 18 months. She has a pathogenic heterozygous mutation of the PHEX gene (c.1645+1G>A). Treated with phosphate and calcitriol since diagnosis. Had no history of neonatal seizure or respiratory distress, and no dental or renal manifestations. No prior fractures or corrective surgeries and has a normal BMD. No history of enthesopathy, however, has chronic joint pain > 1 year. The pregnancy progressed well with no issues; the patient chose not to undergo amniocentesis for fetal diagnosis. She was monitored closely every 3 weeks, aiming to maintain the serum phosphorus within the normal range to ensure adequate mineralization of the fetal skeleton. The requirements for phosphate increased by 50% in the 2nd trimester and by 125% in the 3rd trimester compared to baseline. While the calcitriol dose increased by 25% in the 3 trimesters compared to baseline. Because further increases in the calcitriol dose were associated with hypercalciuria, the dose was carefully titrated. The mean serum phosphorus level was maintained in the low normal reference range at 0.79 - 0.8 mmol/L (NR: 0.8-1.45), mean TmP/GFR 0.611 (NR: 0.96-1.44). She was induced at 37 weeks due to cholestasis, and delivered with a vaginal delivery. The baby boy weighed 2.690 kg and had slightly low serum phosphorus and calcium levels at birth, which corrected spontaneously. DNA analysis confirmed that the baby also has a pathogenic mutation of the PHEX gene. Conclusion: There was a noticeable variation in the serum phosphorus levels during the 1st and 2nd trimesters and less so in the 3rd trimester and during lactation. The dose of phosphate and active vitamin D required careful upward titration to maintain a normal serum phosphorus level. Therefore, close monitoring is essential. Although the rate of c-sections is higher (76%) amongst the XLH patient population compared to the normal population 27.1%, our patient delivered vaginally with no adverse skeletal outcomes in the mother or neonate.

Presentation: Thursday, June 15, 2023
FRI670 Osteoblast Rna Sequencing In T1d Mice Reveals Genetic Signature Of Maladaptation To Hypoxia And Compromised Collagen Synthesis
Authors: Kim Se Min , Hong Juhyeon , Sultana Farhath , Shelly Eleanor , Korkmaz Funda , Gimenez Judit , Yuen Tony , Daehn Ilse , Choi Jungmin , Zaidi Mone
Published: October 2023

Disclosure: S. Kim: None. J. Hong: None. F. Sultana: None. E. Shelly: None. F. Korkmaz: None. J. Gimenez: None. T. Yuen: None. I. Daehn: None. J. Choi: None. M. Zaidi: None.

The main feature of skeletal abnormality in type 1 diabetes (T1D) is low bone turnover with decreased osteoblastic bone formation [1, 2]. However, the mechanism of osteoblast dysfunction remains unclear. We generated T1D mice using low dose streptozotocin (STZ). T1D mice showed lower bone mass (g/cm2) at the femur (0.07 vs. 0.09*) and trends at lumbar spine (0.05 vs. 0.06, p=0.08) compared with control group at 8 weeks after inducing T1D. Osteoblasts were differentiated using bone marrow mesenchymal stem cells, and RNAseq was performed to analyze the transcriptome of osteoblasts. In gene set enrichment analysis, several pathways including immune, hypoxia, and glycolytic pathway were enriched. The osteogenic genes panel showed decreased Bglap and Col1a1 expression, together with lower expression of Bmp2 and Wnt5a, suggesting decreased bone formation might be related to the suppression of BMP and WNT signaling. Particularly, P4ha2, encoding prolyl 4-hydroxylase subunit alpha–2, which are responsible for posttranslational modification of collagen were downregulated in T1D osteoblasts (log2FC = – 1.7**). Among genes in hypoxia pathway, Egln3 encoding prolyl hydroxylase domain-containing protein 2 and Vhl encoding von Hippel-Lindau tumor suppressor, both of which stabilize HIF–α were downregulated (log2FC = – 2.8** and – 0.31*, respectively) likely for promoting HIF–α dependent gene expression in hypoxia. However, genes of the growth signaling pathway namely Pgf, Vegfa, and Igf1r were downregulated (log2FC = – 3.1**, – 0.4* and – 0.5**, respectively). Altogether, our findings suggest that maladaptation to hypoxic condition in T1D with compromised growth signaling pathway and impaired collagen synthesis might be related to osteoblasts dysfunction in T1D bone. (* p < 0.05 and ** p < 0.001)

[1] Shanbhogue VV et al, JBMR. 2015[2] Rubin MR et al, JCEM. 2022

Presentation: Friday, June 16, 2023
FRI678 Baseline Characteristics Of Fracture Liaison Service In Ajou University Hospital
Authors: Chung Yoon-Sok , Kim Jung-Hyun , Lee Soo-Ryeon , Choi Yong Jun
Published: October 2023

Disclosure: Y. Chung: None. J. Kim: None. S. Lee: None. Y. Choi: None.

Introduction: Fracture Liaison Service (FLS) had been set-up in many countries and regions. The Ajou University Hospital (tertiary care academic medical center in South Korea) has launched FLS program mainly composed of femoral fragility fractures. Methods: The baseline characteristics of study subjects were recorded on their initial admission. Data were derived from Ajou University Hospital from April 2019 to August 2022 for hip fracture patients aged 50 or older. Results: The average age was 78.4 years old (range 55 ∼ 98), with 68 male patients and 203 female patients (total 271 subjects). Area of fractures are intertrochanter 120, neck 102, subtrochanter 16, diaphysis 16, and unknown 13 subjects. Fracture type are fragility (osteoporosis) 209, atypical (antiresoprtive drug associated) 15, periprosthetic 17, cancer-related 10, osteomalacia 1, high-energy trauma 6, and unknown 13 subjects. Location of fall were 153 indoor, 73 outdoor, and 45 unknown. Bathrooms and bedrooms accounted for the largest portion of indoor falls. The bone mineral density (BMD) were tested in 215 subjects before discharge. Among them 132 were osteoporosis, 77 were osteopenia or normal, and 6 were undetermined in BMD. Of the 245 subjects who measured the serum 25-OH-Vitamin D, 206 were lower than the normal reference range. Among 244 subjects who measured serum PTH, 64 were higher than the normal reference range. The serum CTX and P1NP were also measured in 240 and 234 subjects, respectively. Among them, 52 subjects and 68 subjects revealed higher than the normal reference range of CTX and P1NP, respectively. Conclusion: Baseline characteristics of study subjects were evaluated in the Ajou University Hospital FLS Program. A significant number of patients included in the FLS were confirmed to have osteopenia or normal BMD. The majority of fracture patients had vitamin D deficiency, and a significant number of fracture patients had elevated serum CTX and P1NP levels.

Presentation: Friday, June 16, 2023
FRI690 Should Treatment For Osteoporosis Be Started In Patients With Primary Hyperparathyroidism Within The First Year After Parathyroidectomy?
Authors: Swe Khine Mon , Chiu Alexander , Pelley Elaine
Published: October 2023

Disclosure: K. Swe: None. A. Chiu: None. E. Pelley: None.

Osteoporosis is one of the indications for parathyroidectomy in patients with primary hyperparathyroidism. Studies show the improvement of bone mineral density (BMD) in the lumbar spine and hip within the first year after parathyroidectomy. Therefore, the decision to treat osteoporosis has usually been delayed until a follow-up bone densitometry scan (DXA) at least one year after parathyroidectomy. To study the BMD changes with or without osteoporosis treatment till first follow-up DXA after parathyroidectomy, we retrospectively reviewed a prospective database of patients undergoing parathyroidectomy for primary hyperparathyroidism between 2010 to 2017 at our institution. We included both male and female patients between the ages 50 to 80, with a history of fragility fracture and/ or T score less than -2.4, and normal renal function. We excluded patients with persistent hyperparathyroidism post-surgery, osteoporosis medication within 3 years before surgery, and DXA performed outside of our facility. Patients who received osteoporosis medication between surgery and the first follow-up DXA were compared to those who underwent surgery alone. We compared the changes in BMD at the total hip and lumbar spine (L1-L4) between baseline and the first follow-up DXA for the two groups. Data was evaluated using a student’s t-test. A total of 386 patients underwent parathyroidectomy during the study period of which 92 patients met the inclusion criteria. Among them, 28 patients were treated after surgery and 64 patients had parathyroidectomy alone. The mean duration to treatment initiation after surgery was approximately 4 months (SD +/- 3 months), and the mean duration until the first follow-up DXA after the surgery was 17 months (SD +/- 8 months). There was no difference in the change of BMD at the total hip between two groups. Both increased by 0.01 g/cm2 (p=0.74). However, there was a greater increase in BMD at the lumber spine for those treated (0.047 g/cm2 increase) compared to surgery alone (0.019 g/cm2 increase) (p=0.02). We concluded that initiation of osteoporosis treatment within the first year after parathyroidectomy led to similar BMD outcomes at the total hip, but the treatment group experienced greater gains in BMD at the lumbar spine compared to parathyroidectomy alone, in patients with primary hyperparathyroidism and osteoporosis.

Presentation: Friday, June 16, 2023
FRI694 Hypercalcemia And Renal Failure As Initial Presentation Of A Rare Case Of Primary Splenic Large B Cell Lymphoma
Authors: Ding Ning , Majumdar Sachin K
Published: October 2023

Disclosure: N. Ding: None. S.K. Majumdar: None.

Background: Hypercalcemia can be seen in patients with malignancy. However, primary splenic large B cell lymphoma presenting with hypercalcemia and renal failure is rare. Clinical Case: A 75-year-old male with PMH of migraine headaches and hearing loss was sent to the hospital by his primary care doctor due to lab abnormalities, including hypercalcemia and renal failure. He also had abdominal pain, weakness, polyuria, and weight loss for several weeks. He took calcium 1000 mg and vitamin D 5000 units daily. Laboratory tests showed creatinine 2.8 (0.4-1.3) mg/dL, calcium 13.8 (8.8-10.2) mg/dL, ionized calcium 6.75 (4.6-5.08) mg/dL, phosphorus 3.6 (2.2-4.5) mg/dL, PTH 12.6 (15-65) pg/mL, PTHrP 23 (14-27) pg/mL, 25-hydroxy vitamin D 53 (30-100) ng/mL, 1,25-dihydroxy vitamin D 171 (18-72) ng/L, CTX collagen C-telopeptide 1137 pg/ml, SPEP without significant abnormality, UPEP with Bence-Jones proteinuria. Skeletal series showed no suspicious lesions, but MRI abdomen revealed an 11 cm splenic mass. Patient underwent splenectomy and pathology revealed diffuse large B-cell lymphoma. Following surgery, his hypercalcemia resolved without additional interventions. 1,25-dihydroxy vitamin D reduced to 25 ng/l and CTX reduced to 451 pg/ml. Further workup, including bone marrow biopsy and imaging, were negative. Patient was subsequently diagnosed with primary splenic large B cell lymphoma. He completed R-CHOP therapy and had no hypercalcemia in follow-up labs. Conclusion: Calcitriol-mediated hypercalcemia occurs in less than 1% of lymphomas, and primary splenic lymphoma constitutes less than 1% of non-Hodgkin lymphomas. The case represents an extremely rare etiology for hypercalcemia. Interestingly, elevated 1,25-dihydroxy vitamin D and hypercalcemia resolved after splenectomy. Clinicians should consider lymphoma as a potential cause of hypercalcemia and renal failure in elderly patients.

Presentation: Friday, June 16, 2023
FRI696 Endocrine Shades Of Silicone Fillers: A Case Of Calcitriol-mediated Hypercalcemia
Authors: Martinez Cruz Maria S , Lozovoy Madsen-Barbosa Thaesy G , Haas Christopher J
Published: October 2023

Disclosure: M.S. Martinez Cruz: None. T.G. Lozovoy Madsen-Barbosa: None. C.J. Haas: None.

Introduction: In rare cases, foreign body granuloma (FBG) reaction is so vast that it leads to severe systemic disease, including increased granuloma-mediated production of calcitriol. Case Description: A 42-year-old woman was referred to the ED due to elevated serum calcium and worsening GFR on routine blood work. She endorsed a two-week of generalized weakness, myalgias, polyuria, polydipsia, and intermittent constipation with prior episodes of such symptomatology. On her first presentation, severe hypercalcemia (13.8 mg/dL), acute-on-chronic renal disease, a normal TSH, an appropriately low PTH, elevated PTHrP, a low 25-hydroxy vitamin D, and a normal 1,25 dihydroxy-vitamin D were noted. She was treated with IV fluids and zoledronic acid 4mg IV one time with subsequent normalization of calcium levels. Six months later, she was re-admitted with similar complaints. Additional blood workup was unremarkable, including urine and serum protein electrophoresis and kappa/lambda ratio. She once again presented with similar complaints; additional workup revealed a normal 25-hydroxy vitamin D, mildly elevated serum angiotensin-converting enzyme, and a negative QuantiFERON-TB gold, but a marked elevation of 1,25 dihydroxy-vitamin D (138 pg/mL). She admitted to subcutaneous silicone filler injections in the lips, cheeks, and hips applied by a non-healthcare provider six years ago. She described that one year after the injections, she had noted intermittently indurated erythematous areas in the skin of the hips and upper lateral thighs that were notably tender to palpation. Diagnostic imaging included a whole-body PET-CT that demonstrated moderate FDG uptake within the subcutaneous adipose tissue of the lateral aspect of bilateral gluteal regions extending from the iliac crests to the upper thighs. She was diagnosed with silicone filler injection-induced hypercalcemia secondary to granulomatous inflammation and initiated on prednisone 20 mg PO daily with progressive normalization in her hypercalcemia (9.7 mg/dl) a month after initiation of treatment. Unique features/Teaching points: FBG reactions occur more commonly against permanent fillers like silicone, especially if injected in larger volumes and highly vasculature areas like hips or buttocks. These reactions may occur years after the initial injection. In rare cases, significant granulomatous immune response leads to the overactivity of 1-alpha-hydroxylase in activated macrophages, resulting in uncontrolled overproduction of calcitriol and, subsequently, hypercalcemia. FBG reactions may also cause increased levels of PTHrP, further contributing to hypercalcemia. Treatment focuses on general hypercalcemia management and FBG remission, most effectively achieved with anti-inflammatory corticosteroid doses. Further studies are needed to evaluate long-term treatment efficacy.

Presentation: Friday, June 16, 2023
FRI699 Hyperphosphatemia In The Setting Of Sodium Hypochlorite Use
Authors: Champagne Kareen , Mooradian Arshag D , Gupta Nidhi , Haas Michael J , Gandhi Gunjan Y , Jurado-Flores Marilu M
Published: October 2023

Disclosure: K. Champagne: None. A.D. Mooradian: None. N. Gupta: None. M.J. Haas: None. G.Y. Gandhi: None. M.M. Jurado-Flores: None.

Introduction: Acute elevation of serum phosphorous occurs for various reasons, including cellular injury (hemolysis, rhabdomyolysis, tumor lysis syndrome), decreased excretion (acute renal injury), or increased absorption/intake. Case Description: A 20-year-old woman presented as a pedestrian struck by a car after a motor vehicle accident. She sustained significant injury to the left leg, including degloving injury, femur, and tibia fracture requiring intramedullary nailing, skin graft, and multiple debridements. A review of systems was positive for chronic constipation. Physical exam was remarkable for several large, deep wounds on the left leg with a wound vac. Her wound was treated with sodium hypochlorite 0.25% solution. Laboratory results revealed that serum CK was 2,903 U/L on admission, and serum phosphorous level was normal and only started to rise one month after admission. She was transfused for blood loss and received IV fluids intermittently. Serum ionized calcium was low on admission at 0.90 mmol/L, calcium supplement was started, and hypocalcemia resolved. GFR dropped twice (at 46 and 62 mL/min/1.73M2) during admission but recovered to normal within a day. Serum phosphorous was elevated and ranged from 4.7-8.0 mg/dL, magnesium level fluctuated between 1.5-2.5 mg/dL, the parathyroid hormone was low at 7.0 pg/ml, 25-hydroxy vitamin D was low at <5.0 ng/ml, 1,25-dihydroxy vitamin D was low at <5.0pg/ml, FGF-23 was high at 616 RU/ml. Sevelamer was given for 9 days and discontinued. Sodium hypochlorite 0.25% solution and calcium supplement were discontinued, and vitamin D supplementation was initiated. The fractional excretion of phosphorous calculated from spot urine phosphorous and creatinine was low at 3.03%. Seven days later, plasma phosphorous levels normalized. Discussion: Sodium hypochlorite is a strong alkali (pH ∼11) and is the active ingredient of bleach. When exposed to water, it forms hypochlorous acid that generates superoxide radicals, leading to oxidative injury and cell death. This solution is bactericidal and may cause some tissue injury as well. It is used in healthcare settings to disinfect dialysis machines and tunneled catheters, surgical equipment, wound cleaning, hand hygiene, and root canal sterilization. It may increase the risk of hyperphosphatemia when used in a patient with immobilization, bone fractures, hypoparathyroidism, low vitamin D, multiple blood transfusions, and wound debridements. There have been rare reports of acute kidney injury with an intravenous bleach injection.

Presentation: Friday, June 16, 2023
SAT190 The Effect Of Mechanical Loading On Bone Growth Ex Vivo
Authors: Aeppli Tim , Zhang Zhengpei , Zaman Farasat , Savendahl Lars S
Published: October 2023

Disclosure: T. Aeppli: None. Z. Zhang: None. F. Zaman: None. L.S. Savendahl: None.

Background: Bone growth is a multi-step process that involves proliferation and differentiation of chondrocytes within the growth plate. Apart from local regulation by various signaling pathways, chondrocytes respond also to external cues such as nutrition, inflammation and mechanical load that may increase or stunt growth. The Hueuter and Volkmann law describes the effect of mechanical loading on bone growth stating that bone growth is inhibited by increased mechanical compression and is promoted by reduced loading. To this date, no data is available investigating the local effects of mechanical loading on bone growth in the absence of systemic growth factors in small embryonic bones. Aim: The aim was to study the effects of mechanical loading on bone growth in an ex vivo bone culture model. Methods: Cultured femur and metatarsal bones from rats (E19.5) were studied and local/direct effects of mechanical loading on bone growth were investigated. A range of different mechanical forces was applied to femur and metatarsal bones every 2-3 days. To monitor bone growth, digital pictures were taken and bone length was measured every 2-3 days. The loaded bones were compared to control bones (sham-loaded). Results: When applying different mechanical load to metatarsal bones, bone growth was suppressed in a dose-dependent manner. On day 5, after applying mechanical loading (0.4 N) twice on day 0 and 2, metatarsal bone growth was significantly suppressed when compared to unloaded control bones (p<0.05). In contrast, when mechanical loading was applied repetitively to femur bones, bone growth was significantly stimulated (p<0.001) when compared to unloaded control bones. Conclusion: In conclusion, depending on the type of bone (embryonic rat metatarsal bone and the larger rat femur bone) mechanical loading exerts opposite effects on bone growth in an ex vivo culture model. The effect of mechanical loading on bone growth requires further in vivo investigations to increase our understanding on the role of mechanical loading in different bones and bone growth disorders.

Presentation: Saturday, June 17, 2023
SAT217 Chronic Asymptomatic Hypoparathyroidism Due To Two Separate Single Nucleotide Heterozygous Mutations In The CaSR Gene
Authors: Anto Antony Mc , Gundlapally Sindhusha , Storm Shelby , Russell Peyton , Verma Vipin , Kant Ravi
Published: October 2023

Disclosure: M. Antony: None. S. Gundlapally: None. S. Storm: None. P. Russell: None. V. Verma: None. R. Kant: None.

Introduction: The most common cause for acquired hypoparathyroidism is either post-surgical or autoimmune destruction of the parathyroid glands. The clinical presentation can range from an asymptomatic state to severe life-threatening symptoms that require intensive therapeutic management with intravenous and/or oral calcium, calcitriol and in some cases, recombinant parathyroid hormone therapy. Hypoparathyroidism secondary to CASR (calcium sensing gene receptor) gene mutation is an uncommon etiology that can also have a varied clinical presentation as above. Clinical Case: A 60-year-old Caucasian male with no significant past medical history was found to have chronic hypocalcemia. He denied experiencing symptoms such as numbness, tingling or cramping sensation around face, lips, or upper extremities. He denied a history of movement disorder or dental problems. He denied a history of neck surgeries or neck radiation exposure. He denied a family history of calcium disorders. He was on calcium carbonate/Vitamin D3 600 mg/400 I.U once daily. The first documented low corrected serum calcium was 6.9 mg/dl (8.6-10.0 mg/dl) in November of 2017. Since then, there have been multiple low corrected serum calcium levels ranging between 7 to 7.6 mg/dl. Patient underwent endocrinology work-up after withholding the above calcium/Vitamin D3 supplementation and it revealed a low corrected serum calcium of 7.6 mg/dl with an inappropriately normal serum PTH level of 37 pg/ml (15-65 pg/ml), normal vitamin D level of 45.1 ng/ml (> 30.0 ng/ml), normal serum phosphorus 3.8 mg/dl (2.5-4.5 mg/dl), and normal serum magnesium 1.8 mg/dl (1.6-2.6 mg/dl). The 24-hour urine calcium was 93 mg/24 hour with a corresponding 24-hour urine creatinine of 1836 mg (1040-2350 mg/24hour) and urine volume of 1625 ml. CASR gene analysis revealed two separate single nucleotide heterozygous mutations. The first mutation was at Exon 4/7, nucleotide position was c.614G>A and Amino Acid position was p.Arg205His. The second mutation was at Exon 7/7, nucleotide position was c.2546T>C and Amino Acid Position is p.lle849Thr. Due to lack of specific symptoms, patient was not initiated on specific therapies such as calcitriol or Natpara (recombinant PTH) and was advised to continue taking the daily calcium/vitamin D3 supplementation. He is being currently monitored every 4 to 6 months to assess for any clinical symptoms along with pertinent laboratory work-up. Conclusion: Hypoparathyroidism due to CASR gene mutation has a varied clinical presentation. One-third of cases do not develop any clinical symptoms, such as our patient and hence do not warrant any specific treatment other than periodic clinical and biochemical assessment.

Presentation: Saturday, June 17, 2023
SAT242 Unusual Case Of Sarcoidosis Presenting With Severe Hypercalcemia: Case Report
Authors: Bhullar Guriqbal , Vora Mehul
Published: October 2023

Disclosure: G. Bhullar: None. M. Vora: None.

Background: This case study discusses an unusual case of hypercalcemia found on routine labs. Clinical Case: A middle-aged Caucasian female with history of MVP, HTN, and anxiety was found to have normal-high calcium of 10.4 mg/dL (nml 8.7-10.4mg/dL) during routine labs offered by her employer. She considered herself relatively asymptomatic and underwent repeat lab testing at her PCP’s office 2 months later which showed calcium of 13.9 mg/dL, ionized calcium of 1.70 mmol/L (nml 1.12-1.32 mmol/L), and intact PTH of 12.4 pg/mL (nml 14.0-72.0 pg/mL). 1 day later, patient presented for an urgent outpatient endocrinology visit. Further questioning revealed polydipsia, polyuria, fatigue, and history of nephrolithiasis more than 10 years ago. Medications included vitamin D, metoprolol, spironolactone, and sertraline. She denied bone pain, weight loss, or GI issues. Physical exam, including heart, chest, and abdomen, was unremarkable. The patient was admitted to a local hospital for hydration and further workup. During her hospital stay, XRAY of chest revealed consolidation in right upper lobe with suspicion of bilateral hilar adenopathy. Contrast CT of chest, abdomen, and pelvis revealed extensive adenopathy, pulmonary nodules, and alveolar consolidation in right upper lobe. Calcified granulomas were found in the spleen. Lab studies showed elevated ACE levels at 87 U/L (nml 14-80 U/L), and elevated activated vitamin D at 108 ng/ml (nml 24.8-81.5 ng/ml). Biopsy results were positive for nonnecrotizing granuloma and negative for malignancy. No suspicious osseous lesions or thyroid gland abnormalities were found. PTHrP and serum protein electrophoresis were found to be in normal range. Hypercalcemia was corrected and patient was treated with glucocorticoids before discharge. Clinical Lesson: Patients with sarcoidosis usually endorse nonspecific symptoms and complaints of pulmonary manifestation may be absent at presentation. 6-13% of sarcoidosis cases involve hypercalcemia (1,2), furthermore, hypercalcemia is more frequently found in white patients (3), who more often present as asymptomatic (4). Thus, clinicians must maintain a high level of suspicion for granulomatous diseases in patients presenting with hypercalcemia regardless of the patient’s symptomology and physical exam findings. References: (1) Baughman RP, Janovcik J, Ray M, Sweiss N, Lower EE. ﻿﻿Calcium and vitamin D metabolism in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2013;30(2):113-120.(2) Studdy PR, Bird R, Neville E, James DG. Biochemical findings in sarcoidosis. J Clin Pathol. 1980;33(6):528-533.(3) Burke RR, Rybicki BA, Rao DS. Calcium and vitamin D in sarcoidosis: how to assess and manage. Semin Respir Crit Care Med. 2010;31(4):474-484.(4) Newman LS, Rose CS, Maier LA. Sarcoidosis [published correction appears in N Engl J Med 1997 Jul 10;337(2):139]. N Engl J Med. 1997;336(17):1224-1234.

Presentation: Saturday, June 17, 2023