bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP116 Proton Pump Inhibitor Induced Hypocalcemia - An Overlooked Cause
Authors: Rivera Krystal , Bhat Geetha
Published: November 2022

Hypocalcemia can be caused by hypoparathyroidism, vitamin D deficiency, GI disorders, or hypomagnesemia. Proton-pump inhibitors (PPIs) which are commonly used for acid reflux symptoms can cause hypomagnesemia leading to hypocalcemia. We report an interesting case of acute hypocalcemia caused by a proton pump inhibitor. A 78-year-old female with a past medical history of follicular thyroid cancer diagnosed in 2008, s/p total thyroidectomy in 2008 followed by radioactive iodine ablation in 2009, was sent to the ER in 2019 for acute hypocalcemia with a calcium level of 6.6 mg/dL found on outpatient labs. Notably, she had no previous history of post-surgical hypoparathyroidism or hypocalcemia after her surgery in 2008. Upon initial evaluation in the ER, she presented with mild numbness, tingling, and weakness preceded by a diarrheal illness. She had concomitant hypokalemia of 3.1 mmol/L and hypomagnesemia of 1. 0 mg/dL for which she received IV and oral electrolyte repletion. She was eventually discharged on oral calcium carbonate, calcitriol, and magnesium. During her outpatient follow up, repeat labs showed persistent hypomagnesemia and low intact parathyroid (PTH) levels. Upon further review of her medication list, she reported continued daily use of omeprazole for acid reflux symptoms for the previous two months prior to her hospitalization. Her magnesium levels remained persistently low despite high doses of replacement. Given her persistently low magnesium and PTH levels, omeprazole was discontinued and she remained on calcium, calcitriol, and magnesium supplementation. Her calcium, and intact PTH levels eventually recovered to normal range and magnesium levels improved. Calcitriol was discontinued. She remained on a low dose of magnesium supplementation. In this patient, the development of her acute hypocalcemia was unlikely related to her remote history of the post-surgical thyroidectomy which occurred eleven years prior. Proton pump inhibitor use is often overlooked when evaluating causes of hypocalcemia. PPIs impair gastrointestinal absorption of magnesium through altering the TRPM6/7 channel affinity of magnesium by decreasing intestinal luminal pH. As a downstream effect, the resulting acute hypomagnesemia is thought to decrease PTH secretion as well as cause PTH resistance, which in turn decreases absorption of calcium, both by the renal and gastrointestinal route. There have been published cases that suggest these electrolyte disturbances commonly occur in elderly women with chronic PPI use. Clinicians should be aware of the effects that PPIs may have on electrolyte abnormalities. As a result, it may be reasonable to monitor magnesium and calcium levels while on a proton pump inhibitor.

Presentation: No date and time listed
ODP119 Raloxifene use after denosumab discontinuation partially attenuates bone loss in the lumbar spine in postmenopausal osteoporosis
Authors: Hone Namki , Kim Kyoungjin , Lee Seunghyun , Rhee Yumie , Shin Sungjae
Published: November 2022

Purpose

Discontinuation of denosumab (DMab) is associated with rapid declinein bone density. Sequential antiresorptive drugs are recommended to preserve bone mass after DMab treatment. It remains unclear whether raloxifene exclusively can be used in certain conditions to attenuate bone loss after DMab discontinuation.

Methods

In this retrospective cohort study, data on postmenopausal women with osteoporosis who discontinued DMab treatment after short-term use (at Severance Hospital, Seoul, Korea, between 2017 and 2021) were reviewed. Changes in bone mineral density (BMD) at 12 months after DMab discontinuation was compared between sequential raloxifene users (DR) and control group without any sequential lantiresorptive (DD). Baseline characteristics were matched through 1: 1 propensity score matching (PSM) without replacement.

Results

A total of 66 patients (DR n=33; DD n=33) were studied. In propensity score matched cohort, mean age was 69.3 ± 8.2 years and T-score for lumbar spine and total hip was -2.2 ± 0.7 and -1.6 ± 0.6, respectively, at the time of DMab discontinuation. Common reason for DMab discontinuation or sequential treatment to raloxifene was invasive dental surgery in DR (n=18, 55%) and ineligibility to obtain insurance reimbursement due to improved BMD in DD (n=18, 55%). Raloxifene caused attenuation of BMD loss (-2.78% vs. -5.80%, p=0. 013)of lumbar spine after adjusting for age, BMI, previous fracture history, lumbar spine T-score at the time of DMab discontinuation, prior bisphosphonate exposure, and DMab injection time.

Conclusion

Raloxifene use after short-term DMab treatment (less than 2.5 years) attenuated lumbar spine BMD loss in postmenopausal women.

Presentation: No date and time listed
ODP121 Recurrent atypical parathyroid adenoma: a case report
Authors: Siqueira Hiloma , Lima Cristiane , Furtado Adriana , Ferreira Alana , Canto Marcelo , Cunha Jéssica , Milward Marina , Faria Erika
Published: November 2022

Background

Atypical parathyroid adenoma is a rare cause of hyperparathyroidism, with an incidence ranging from 0.5 to 4.4%. Its recurrence rate is low, around 3%. We describe a young patient with an atypical parathyroid adenoma that recurred twice at the right neck.

Case presentation

A 39-year-old woman presented to the ER with low back pain, hyporexia, weight loss, and an oral lesion with purulent discharge. She was diagnosed with nephrolithiasis, severe hypercalcemia (serum calcium concentration: 21,2 mg/dl (Reference range 8,5-10,5) and hyperparathyroidism (serum PTH: 703 pg/mL; reference range 15-45pg/mL). Parathyroid scintigraphy identified an uptake at the site of the lower right parathyroid. A cervical US confirmed the presence of a 3 cm markedly hypoechoic nodule in that location. Fine needle aspiration (FNA) suggested parathyroid adenoma, and PTH washout levels were 1900 pg/ml. Screening for multiple endocrine neoplasia was negative. Biopsy of the mandibular alveolar bone, around the oral lesion, showed giant cell lesion. Lower right parathyroidectomy was performed, and the histopathology showed parathyroid neoplasm with features favoring atypical parathyroid adenoma (lesion measuring 3×2×1.8 cm). Fifteen months after the surgery, the patient presented symptoms of hypercalcemia, with a new elevation of serum PTH levels (738 pg/ml), confirmed with radiotracer uptake at the site of the upper right parathyroid gland. She underwent right parathyroidectomy and hemithyroidectomy. Histopathology revealed an atypical parathyroid adenoma. Immunohistochemistry was positive to galectin 3 in rare cells; Ki 67 positive (2%). After nine months, the patient noticed a subcutaneous nodule in the right anterior cervical region associated with symptomatic hypercalcemia, and a new increase in serum PTH levels (469.5 pg/mL). Parathyroid scintigraphy confirmed radiotracer activity at the nodule described, that was surgically resected. Histopathology was compatible with an atypical parathyroid neoplasm (uncertain malignant potential). The patient remains in regular follow-up, asymptomatic and normocalcemic.

Conclusion

While 96% of patients with atypical parathyroid adenomas are cured with parathyroidectomy, this case shows a very rare description of two recurrences in a short time of follow-up, with an ectopic location in the last one. It should be noted that atypical paratyroid adenomas are already an uncommon presentation of primary hyperparathyroidism. Genetic investigation is warranted in such cases.

Presentation: No date and time listed
ODP568 Success of CME at Improving Knowledge, Competence and Confidence Related to Diagnosing and Treating Hypophosphetemic Bone Disease
Authors: Blatherwick Donald , Larkin Amy
Published: November 2022

Introduction

We sought to determine if an online continuing medical education (CME) activity could improve knowledge and competence of endocrinologists (endos) and rheumatologists (rheums) related to diagnosis and treatment of patients with hypophosphatemic bone disease.

Methods

The effect of an online, 30-minute, CME-certified roundtable discussion among 3 faculty was analyzed to determine efficacy. The activity posted November 4, 2020, and data were collected through February 4, 2021.

Results

Overall, 33% of endo learners and 48% of rheum learners improved their knowledge/competence.

Conclusions

This study demonstrates the success of an online 30-minute roundtable discussion on improving knowledge, competence, and confidence regarding diagnosis and treatment of hypophosphatemic bone disease, with gaps identified for future education.

Presentation: No date and time listed
ODP627 Hypercalcemia in a Patient With Gastrointestinal Stromal Tumor (GIST): Evaluation and Treatment Strategies
Authors: Kalra Kriti , Failor Richard A , Nguyen Tiffany T
Published: November 2022

A 52-year-old African woman was found to have a pelvic mass at the age of 41. Following resection of small bowel tumors at the time, she was diagnosed with GIST and peritoneal metastases were confirmed. Despite treatment with imatinib, her disease progressed and was started on regorafenib. Due to lack of consistent insurance coverage, she took this medication intermittently for several years, and her tumor progressed to develop intra-abdominal peritoneal and pelvic metastases. She underwent debulking surgery, and her disease subsequently remained stable with regorafenib. Unfortunately, she developed hemoptysis which led to discontinuation of regorafenib, and while off treatment, the patient developed altered mentation, extreme lethargy, and poor PO intake. She was found to have a serum calcium of 16 mg/dL and was admitted for treatment of severe hypercalcemia. With intravenous (IV) fluids, calcitonin and zoledronic acid, her calcium improved to 11-12 mg/dL; however, despite additional therapies, including denosumab and repeat zoledronic acid, her calcium did not normalize. Further evaluation revealed: 25-hydroxy-vitamin D3 level 22.2 ng/mL (normal), 1,25-dihydroxy-vitamin D3 107 mcg/mL (elevated), PTH 6. 0 pg/ml (low), and PTHrP 3.3pmol/L (low). She was given a diagnosis of calcitriol-mediated hypercalcemia and started on IV hydrocortisone 100 mg every 12 hours. Her serum calcium started to improve within 48 hours and normalized after eight days to 9.8mg/dL. Her clinical condition improved, and she was discharged with prednisone 20 mg daily. At the time of her post-hospital follow up several days later, her serum calcium remained normal.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
OR01-3 Lack of Bone Mineral Density Testing in Men with Hypogonadism: A Clinical Conundrum
Authors: Pantalone Kevin , Goettemoeller Travis
Published: November 2022

Objective

Hypogonadism is a known risk factor for decreased bone mineral density (BMD) and increased risk of fractures in men. The 2012 Endocrine Society Clinical Practice Guidelines recommend that men ≥ 50 years of age with a diagnosis of hypogonadism undergo BMD testing.1 The objective of this study was to determine the frequency at which men aged ≥ 50 with a diagnosis of hypogonadism underwent BMD testing, and among those that underwent testing, the percentage of men diagnosed with osteopenia or osteoporosis and subsequently treated with an osteoporosis medication.

Methods

A retrospective chart review was conducted using the enterprise-wide electronic health record system at our institution. Inclusion requirements were an ICD-9 or -10 code for hypogonadism at any time between 7/1/2012 and 9/30/2020, and at least two subsequent visits with providers from primary care, endocrinology, or urology. Patients with a diagnosis of osteoporosis or who had undergone treatment with an osteoporosis medication, prior to the diagnosis of hypogonadism, were excluded. Patients were followed until the date of BMD assessment or censoring (9/30/2021). The testing results and documentation of treatment with an osteoporosis medication were recorded. Categorical variables and continuous variables were summarized using N (%) and median (IQR) or mean (SD), respectively.

Results

A total of 10,169 men with hypogonadism were identified. General characteristics included mean age of 63.4 years (±9.2), 85.2% white, 52.7% with history of smoking, 68.2% with hypertension, 36.9% with type 2 diabetes, and mean BMI of 31.3 kg/m2 (±6.0). Median follow-up time was 6.6 years (3.8, 8.5). Of 728 (7.2%) patients who underwent BMD testing, 352 (48.4%) had osteopenia and 87 (12.0%) had osteoporosis. A total of 5,633 (55.4%) men underwent treatment with testosterone replacement therapy. Of the 87 patients identified as having osteoporosis, 50 (57.5%) were treated with an osteoporosis medication.

Conclusion

Despite a recommendation from the 2012 Endocrine Society for men ≥ 50 years of age with hypogonadism to undergo BMD testing, the rate at which this testing is performed in real-world practice is quite low. The high rate (60.3%) at which low BMD was discovered in hypogonadal men who underwent testing, and further observation of a low rate of treatment with osteoporosis medication when indicated, is alarming and necessitates a call to action for more hypogonadal men to undergo testing and receive appropriate treatment. Further studies are needed to determine the reasons why so few men with hypogonadism undergo BMD assessment and what systems can be put in place to overcome this clinical conundrum.

Reference

1. Watts NB, et al. Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 6, 1 June 2012, Pages 1802–1822, https://doi.org/10.1210/jc.2011-304

Presentation: Saturday, June 11, 2022 12:00 p.m. - 12:15 p.m.
PSAT160 The Dangers of Long-term Aromatase Inhibitor use in an Elderly Hispanic Population
Authors: Acosta Sebastian , Alejandro Angel
Published: November 2022

The most common endocrine therapies for breast cancer are Aromatase Inhibitors (AIs), which can help reduce the recurrence of the disease and its mortality rate. However, because aromatase inhibitors prevent the aromatization of androgens into estrogen, they can have serious effects on bone health. This can lead to accelerated bone loss and an increased risk for fractures, especially among postmenopausal women. In 2017, the Journal of Bone Oncology (JBO) released a joint position statement advising that all patients with breast cancer on endocrine treatment, such as AIs which are known to accelerate bone loss, be placed on bisphosphonate therapy should they present 2 or more risk factors for fracture (1). The purpose of this study was to evaluate patients on AIs at a 5-star Medicare Advantage plan facility and document any discrepancies with regards to whether appropriate treatment is being given to prevent fractures. We hypothesized that we may have a large percentage of patients on AI that have 2 or more risk factors and are not on treatment. An electronic chart review was conducted of 398 patients on AIs between 6/9/2020 and 8/25/2020. Patients were evaluated for the following risk factors: current smoking, personal history of hip/vertebral fracture, current use of glucocorticoids, age > 65, BMD T-score < -1.5, and BMI < 20. Surprisingly, 1 out of every 2 patients treated with an AI was not being treated in accordance with the JBO's recommendations. Of the 398 patients evaluated, 191 presented 2 or more risk factors and were not on antiresorptive treatment. There are a few steps that can be taken to better manage these at-risk patients. First is raising awareness to providers about the dangers of long-term AI use. Additional changes to the EMR system may help as well, such as prompting the ordering provider to consider bisphosphonate therapy if risk factors are present. Lastly, the addition of a fracture reduction clinic can help streamline the referral process to an endocrinologist upon the prescribing of AI therapy. This would allow patients to be fully evaluated for fracture risks and prescribed treatment should they qualify. With the low costs of generic bisphosphonate therapy, if a fracture is prevented, providers can hope to save a significant amount in indirect costs. Through improved awareness of providers of the risks, a more intuitive EMR system, and the creation of a new automatic referral process, we believe that we can vastly improve patient morbidity and quality of life by reducing the chances of fracture in patients on long-term AIs.Reference: (1) Hadji et al., J Bone Oncol. 2017 Mar 23;7: 1-12.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT186 Iatrogenic Calcinosis Cutis in a Patient With Postsurgical Hypoparathyroidism
Authors: Laforteza Alexis Roberto , Ong-Ramos Celeste
Published: November 2022

Clinical Case

A 44-year old woman, diagnosed with post-surgical hypoparathyroidism after total thyroidectomy for papillary thyroid carcinoma, was admitted for symptomatic hypocalcemia. On admission, she had positive Trousseau's and Chvostek's signs, carpopedal spasm and prolonged QT interval on ECG. She had an initial serum ionized calcium of 0.70 mmol/L (RI: 1.09- 1.30). Serum phosphorus was also elevated at 5.8 mg/dL (RI: 2.6-4.7). She was given 2 grams of calcium gluconate via slow IV push and was hooked to calcium gluconate drip, 4 grams in 250 cc D5W to run for 8 hours In less than 24 hours, she developed thrombophlebitis on her right hand, hence the drip was shifted to the left hand. The new IV site also developed phlebitis, necessitating transfer to the right antecubital area. The areas of phlebitis were managed with cold compress, pain relievers, topical antibiotics overlapped with oral antibiotics. She continued receiving calcium gluconate IV drips overlapped with calcium and calcitriol tablets until her serum calcium level normalized. She was discharged stable and improved after 4 days but still with erythema over her previous IV sites. However, 3 weeks after discharge, she developed yellowish erythematous plaques and nodules over her previous IV sites. She consulted with a dermatologist who did a skin punch biopsy showing a granulomatous dermatitis, foreign body type, which confirmed the diagnosis of iatrogenic calcinosis cutis. She was treated with pulse dye laser and intra-lesional triamcinolone, oral antibiotics and pain medications. At present, she still has pain, tenderness, with limitation of movement on both hands. She was referred to a plastic surgeon where she was advised to undergo a total of 3 surgeries over a span of 3-6 months. These would involve the placement of tissue expanders, harvesting of flaps, removal of lesions and reconstruction of scars plus hand rehabilitation after the surgeries.

Conclusion

Iatrogenic calcinosis cutis is a rare complication from extravasation of calcium-containing solutions during intravenous calcium correction. It appears 2-3 weeks after extravasation and has no definitive treatment. In other case reports, it can be managed conservatively but some may require reconstructive surgery. Prevention of extravasation is the only way to avoid this rare and debilitating condition.Reference: Jiménez-Gallo D, Ossorio-García L, Linares-Barrios M. Calcinosis Cutis and Calciphylaxis. Actas Dermosifiliogr. 2015 Dec;106(10): 785-94.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT196 Monostotic Paget's disease of the bone involving the calcaneus
Authors: Eldin Randa Sharag , Haroon Sarah , Shaker Joseph L
Published: November 2022

Introduction

Paget's disease of bone (PDB) is a chronic bone disorder that is fairly common in older age. It is characterized by an initial increase in osteoclastic activity followed by excessive osteoblastic activity with disorganized bone architecture. PDB may involve any bone and may be monostotic or polyostotic. Herein, we report the rare occurrence of monostotic Paget's involving the calcaneus.

Case Description

A 71-year-old white male with PMH of prostate cancer status post radical prostatectomy presented with acute onset severe left heel and ankle pain. Pain was localized to the retrocalcaneal area and heel pad limiting his physical activity. He denied recent trauma. Physical exam was significant for swelling and tenderness of the left heel. Left foot X-rays showed a slightly enlarged calcaneus with very coarse trabeculae consistent with PDB. A total body bone scan done previously because of the prostate cancer showed intense uptake in the left calcaneus but no significant uptake elsewhere. Laboratory workup showed an elevated total serum alkaline phosphatase of 164 U/L (40-129 U/L) and bone specific alkaline phosphatase 65 ug/L (0.0-20 ug/L). He was treated with a single infusion of Zoledronic acid with good clinical response evidenced by improvement in pain and swelling as well as a significant decrease in bone specific alkaline phosphatase to 10 ug/L six months post-infusion.

Discussion

Monostotic PDB only represents about 20% of PDB cases. The pelvis is the most common location followed by the femur as described by Bachiller-Corral et al (Bone, 2013). In our review of the English literature, we found only nine cases of monostotic PDB involving the calcaneus. The mean age of presentation was 60 years old and most of the cases presented as chronic heel pain not responding to conservative pain alleviating measures. Conventional radiography showed the characteristic features of PDB but the changes observed were difficult to differentiate from that of a malignant process. That led to further imaging in most cases by either CT, MRI scan or SPECT scan. Three out of nine patients were reported to receive bisphosphonate therapy with successful remission with a long duration of disease suppression. Good response to therapy highlights the importance of proper diagnosis.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT209 A Remission of Hypocalcemia in Idiopathic Hypoparathyroidism
Authors: Puzio Helene , Nachawi Noura , Hamaty Marwan , Rao Pratibha
Published: November 2022

Background

Acquired hypoparathyroidism is known to be transient when caused by surgical trauma but unlikely in idiopathic etiology. Herein we describe a unique presentation of idiopathic hypoparathyroidism that was diagnosed in early adolescence and remitted in adulthood.

Clinical Case

A male patient was diagnosed with idiopathic hypoparathyroidism at 13 years old after presenting with severe hypocalcemia resulting in generalized convulsive seizure. At diagnosis, his corrected calcium (cCa) was 6.7 (8.5-10.2 mg/dL) and PTH was 8.5 (15-65 pg/mL). Patient was noted to have oral candidiasis raising concerns for autoimmune regulator mutations associated with autoimmune polyendocrinopathy. Adrenal function was normal. Genetic testing was not done due to cost. Calcium citrate of 500 mg twice daily and calcitriol, gradually increased to 1.5 mcg daily, were initiated with normalization of calcium level. At age 24, he presented with altered mental status and was admitted with hypercalcemia and subarachnoid hemorrhage. He had cCa of 12.6 compared with previous calcium levels ∼ 7 (8.5-10.2 mg/dL), ionized calcium of 1.57 mmol/L, magnesium of 1.8 (1.7-2.3mg/dL), hypophosphatemia of 0.4 (2.7-4.8 mg/dL) and undetectable PTH. Further testing showed AKI with creatinine of 2.1, from baseline of 0.8 (0.7-1.22 mg/dL). Vitamin D 25 OH and 1,25 dihydroxy vitamin D, ACE level and PTHrP were all unremarkable. Workup for multiple myeloma was negative. Adrenal and thyroid function tests were normal. CT brain showed diffuse subarachnoid blood with CTA showing an elongated saccular aneurysm measuring 2.57×1.72×1.85 mm.Hypercalcemia and AKI resolved with hydration. Interestingly, corrected calcium remained in the low-normal range between 8.6 - 8.8 (8.5-10.2 mg/dL), throughout 10 days of hospitalization despite holding all calcium citrate and calcitriol supplements, which were also held on discharge. PTH level prior to discharge was 7 (15-65 pg/mL) with cCa of 9.1 and magnesium of 1.7. At one week follow up, a reduced dose of calcium citrate of 250 mg twice a day and calcitriol 0.5 mcg daily were resumed which resulted in recurrent hypercalcemia and AKI with normalization by holding treatment. Repeated testing after one month showed cCa of 8.6, creatinine of 1.3, PTH of 17, magnesium of 1.7, and 25 OH vitamin D of 27.2 (31-80 ng/mL). Calcium citrate of 250 mg daily along with weekly ergocalciferol of 50,000 units and Magnesium Oxide 400 mg TID were initiated. Testing 8 months after the hospitalization revealed cCa of 8.6, creatinine of 1.2, magnesium of 1.6, and a low-normal PTH of 18 which was the highest value ever recorded for this patient.

Conclusion

To our knowledge, this is the second reported case of spontaneous remission of idiopathic hypoparathyroidism in adulthood.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT212 Hyperparathyroidism Secondary to Ectopic Parathyroid Adenoma
Authors: Sy Katrina Vina , Gonzales Maria Cecile
Published: November 2022

Background

In the majority of cases, primary hyperparathyroidism is caused by a parathyroid adenoma, most commonly located within the parathyroid glands. However, in some cases, the parathyroid adenoma can be located aberrantly.

Clinical case

A 78 year old female was referred due to hypercalcemia (ionized calcium 1.63mmol/L). Patient has been known to have elevated calcium (both total and ionized) levels for 3 years and osteoporosis. Initial work up on presentation had been unremarkable hence no further investigation was done and treatment was given. Prior to consult, patient had symptoms of bone pains, particularly in her lower extremities. Kidney function was normal. Patient had never had kidney stones but x-ray demonstrated compression fracture of L2 vertebrae. Work up for hypercalcemia was done, revealing the following results: PTH 196.60 pg/mL, TSH 1.810 mIU/mL, FT4 16.46 pmol/L, FT3 3.55 pmol/L, 24 hour urine calcium 88.40 mg/24 hours, and 25 (OH) D 18.32 ng/dL. Neck ultrasound showed findings of normal-sized thyroid gland with mild parenchymal change, benign cystic nodules and no definite evidence of parathyroid nodule. Parathyroid subtraction imaging was done and demonstrated no scintigraphic evidence of parathyroid adenoma or hyperplasia. Patient was prescribed with calcimimetics (Cinacalcet). However, the patient experienced nausea and body pains and opted to discontinue the medication. Further investigation was performed. Radionucleotide parathyroid imaging using Technitium-99m sestamibi was done which revealed slightly increased tracer activity in the lower midline neck on SPECT imaging, an atypical scintigraphic finding of an aberrantly located parathyroid adenoma possibly in the tracheoesophageal or retroesophageal region. There was no definite scintigtaphic evidence of parathyroid adenoma or hyperplasia in the thyroidal beds or ectopic parathyroid in the mediastinum. A second parathyroid scan with SPECT-CT was performed in another institution and showed a 1.2×1.0 cm, sestamibi avid nodule inseparable from the esophagus and left posterior aspect, anterior to the T2 vertebra, consistent with a thoracic retro-esophageal hyperfunctioning parathyroid adenoma. Patient refused surgery at this point and was given medical management with hydration, Vitamin D correction and antiresorptive agent.

Conclusion

Multiple imaging may be needed to reach an accurate diagnosis for persistent hypercalcemia and elevated parathyroid hormone levels with an absence of lesions in the neck. If the criteria for surgery are met, as with parathyroid adenomas within the parathyroid gland, surgical resection is also the gold standard of therapy for ectopic parathyroid adenomas.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF18 | PSAT125 Estimating the relative influence (RI) of genetic risk of 11 glycemic traits on osteoporosis and fractures in 409633 participants in the UK Biobank using Machine learning
Authors: Deshmukh Harshal , Papageorgiou Maria , Sathyapalan Thozhukat
Published: November 2022

Introduction

We used a machine-learning algorithm (gradient boosting) to test the association of genetic risk for 11 glycemic traits with osteoporosis and fractures in the UK Biobank population.

Methods

The study was performed with 409,633 caucasian participants in the UKBIobank. We identified 4626 SNPs associated with 11 glycemic traits from the NGHRI catalogue for GWAS studies. Weighted genetic risk scores (wGRS) were calculated using the effect estimates from the GWAS studies. We used a gradient-boosting machine-learning (GBM) model to identify the relative influence (RI) of baseline variables and wGRS of the glycemic traits on osteoporosis and all-cause fractures in the UK Biobank population. We split the data into training (2/3) and testing set (1/3) and calculated the discriminatory power of the models using the area under the curve (AUC) with the testing model.

Results

The study consisted of 409,633 individuals (53% females) with a median age of 58 (51-63) years and a median BMI of 26.7 (24.1-29.8) kg/m2. The study population had 41954 (10.2%) all-cause fractures and 4995 (1.2%) participants with osteoporosis. In the GBM model, top wGRS associated with all-cause fractures were wGRS for Type 1 diabetes (RI=4.49) and fasting glucose (4.17). In contrast, the top wGRS associated with osteoporosis were wGRS for acute insulin response to glucose (RI=6.74) and Type 1 diabetes (RI=5.62). Both models showed low to moderate discriminatory power with the area under the AUC of 0.57(CI: 0.56-0.57) for fractures and 0.75(CI: 0.74-0.76) for osteoporosis.

Conclusion

We showed a differential effect of wGRS for various glycemic traits on the risk of fractures and osteoporosis in the UK Biobank population. However, the machine-learning model with wGRS for glycemic traits demonstrated limited capacity to predict fractures and osteoporosis in the general population.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.
RF18 | PSAT162 Male Runners Have Impaired Tibial Cortical Bone Integrity and Strength Compared to Non-athletes
Authors: Haines Melanie , Kaur Snimarjot , Scarff Geetanjali , Lauze Meghan , Gerweck Anu , Slattery Meghan , Miller Karen , Misra Madhusmita
Published: November 2022

Female athletes with low energy availability are at risk for impaired bone microarchitecture and strength associated with hypogonadism. Data are lacking for bone outcomes in male athletes. We studied 31 men 16-30 years (n=15 runners with mean (±SD) mileage 43±4 miles/week, n=16 non-athlete controls). We assessed distal tibia and radius volumetric BMD (vBMD) and microarchitecture by high resolution peripheral quantitative CT (HRpQCT), estimated bone strength by microfinite element analysis and body composition by DXA. Testosterone, estradiol (by LC-MS) and leptin (by electrochemiluminescence) were measured. Groups did not differ for mean age (24.5±3.6y), BMI (22.2±2.6 kg/m2), lean mass, or testosterone or estradiol levels. Mean tibial cortical vBMD was lower and porosity higher in athletes than controls (p<0.01). In contrast, mean tibial trabecular vBMD and number were higher, and separation lower, in athletes (p<0.02). Athletes with BMI ≤ 21 kg/m2 had lower tibial failure load (bone strength estimate) than those with BMI >21 kg/m2 (p=0.007). Lean mass (R=0.85, p<0.0001), serum leptin (R=0.59, p=0.046) and estradiol (R=0.66, p=0.007), but not testosterone, were associated with tibial failure load in athletes. Athlete and control groups did not differ for HRpQCT variables at the radius. Despite weight-bearing activity, male runners have impaired tibial cortical BMD and microarchitecture, which may increase their risk for bone stress injuries. Lower leptin (reflecting lower fat mass) and estradiol (converted from testosterone in adipose tissue), as well as lean mass, are determinants of lower tibial strength in these athletes, suggesting that low energy availability is a risk factor for impaired bone strength in male runners.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m.
RF18 | PSAT165 Effect of Age, Gender, & Ethnicity on the Prevalence of Vertebral fractures in Patients with Primary Hyperparathyroidism
Authors: Al-Bacha Souad , Page Brendan , Lam Han , Singer Michael , Cook Bernard , Sudhaker Rao D , Athimulam Shobana
Published: November 2022

Background

Primary hyperparathyroidism (PHPT) is one of the known causes of secondary osteoporosis. PHPT is associated with increased bone turnover, low bone density and quality; but there have been conflicting results on the risk of fractures. There is limited information on the effects of age, gender, and ethnicity on fracture risk in PHPT.

Objective

To determine the prevalence of vertebral fractures (VFx) and associated risk factors in patients with PHPT

Design: Retrospective cross-sectional study

Setting: Academic medical center in a community setting

Main outcome measured: 1) Bone mineral density (BMD), and T- and Z-scores of the lumbar spine (LS). 2) Vertebral morphometry was assessed using the Genant method to identify asymptomatic vertebral fractures (VFx) on CT spine images. 3) Biochemical measurements included serum PTH, Creatinine (Cr) and Calcium (Ca).

Results

In this retrospective study of consecutive 560 PHPT patients verified by surgery [447 women with a median age of 62y; 362 Caucasians (65%), 142 African Americans (AA, 25%) and 22 unspecified race (10%)] were included. Prevalence of VFx was 13% (n=75), other sites 15% (n=84), wrist fractures 3% (n=16) and hip fractures 1% (n=6). Fracture prevalence at all sites was higher in women, but significant only for VFx (71% vs 29%, p=0.04). In subgroup analysis by age (above or below 50y) and gender, there was no significant difference in LS BMD, T- or Z-score values, serum PTH, Ca and Cr in patients with and without VFx. In subgroup analysis by ethnicity: i) prevalence of all fractures was higher in Caucasians compared to AA and others ii) mean serum PTH (±SD) level was significantly higher in AA vs Caucasian patients with VFx (190 ± 124 vs 121 ± 57 pg/mL, p=0.03) and iii) no significant differences were noted in LS BMD, T-or Z-scores, serum Ca and Cr in patients with VFx.

In multivariate analysis (age, serum Ca, PTH >100, and LS BMD) to predict risk of VFx in all patients, only age [OR 1.07, CI 1.03-1.11) and serum Ca [OR 1.7, CI 1.03–2.79] were significant factors. In women, multivariate analysis identified increasing age to be the only significant risk factor to predict risk of VFx. [OR 1.107, CI 1.03-1.12].

Conclusion

Vertebral fractures (VFx) is more prevalent in comparison to wrist and hip fractures in patients with PHPT. Serum PTH is significantly higher in African American PHPT patients with VFx. Increasing age and serum calcium ≥11.1 mg/dL are significant predictors of VFx in PHPT patients.

Presentation: Saturday, June 11, 2022 12:42 p.m. - 12:47 p.m., Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
LBODP025 A Novel Drug Discovery For Primary Aldosteronism Targeting Aldosterone Synthase (cyp11b2) And Kcnj5 Mutant
Authors: Otsubo Yuri , Shimada Hiroki , Yokoyama Atsushi , Sugawara Akira
Published: November 2022

Primary aldosteronism (PA) is a common cause of secondary hypertension. PA induces damage to cardiovascular and renal blood vessels. Therefore, PA is regarded as a problem because it increases the risk of stroke, cardiomyopathy, kidney disease, etc. Aldosterone-producing adenomas (APA) are one of the major causes of PA, and gene mutations are often identified in tumor cells. KCNJ5 mutation is well known as a gene mutation that causes the loss of ion selectivity in APA. KCNJ5 is an inwardly rectifying potassium channel. KCNJ5 induces sodium ion influx due to mutations in APA. The sodium ion influx induces depolarization, and which overexpresses CYP11B2. CYP11B2 is the rate-determining enzyme for aldosterone synthesis, overexpression of CYP11B2 induces aldosterone overproduction. Examples of therapeutic drugs for PA and APA include calcium channel blockers, aldosterone antagonist and β-blockers. However, therapeutic drugs for PA and APA targeting cell membrane depolarization have not been developed yet. We aim to find compounds that suppress CYP11B2 expression by membrane depolarization to develop novel therapeutic drugs for PA and APA. By developing a therapeutic drug that targets depolarization, we hope to establish an effective therapeutic method for APA caused by gene mutations such as KCNJ5 mutation. We performed high-throughput screening (HTS) using Tohoku University Compound Library (6080 compounds). First, we generated H295R-CYP11B2 N-Luc cells in which the luciferase gene is inserted downstream of the CYP11B2 locus. The cells H295R-CYP11B2 N-Luc were stimulated with KCl to cause depolarization, after which candidate compounds were added and HTS was performed by Luc assay. As a result, 101 compounds were selected. Furthermore, 25 of 101 compounds were selected by examining the cytotoxicity and dose response. Also, 11 of the 25 compounds suppressed CYP11B2 mRNA expression in KCl stimulated H295R cells. Secondary, we generated KCNJ5 mutant cells that expressed the KCNJ5 mutant (L168R) in a Doxycycline-inducible manner. 3 of 11 compounds that suppressed the expression of CYP11B2 mRNA were selected by examination using KCNJ5 mutant cells. After that, 2 of 3 compounds decreased the aldosterone production. These compounds have a different structure from existing therapeutic drugs such as calcium channel blockers. Since these can be novel therapeutic drugs for PA and APA caused by depolarization such as KCNJ5, we are examining the detailed mechanism of action of the compounds.

Presentation: No date and time listed
LBODP026 Early Atherosclerosis In High-risk Women With Pcos
Authors: Wu Xiaoying , Wilke Michalean , Ghosh Mahua , Becher Harald , Raggi Paolo , Vine Donna
Published: November 2022

Background

Polycystic Ovary Syndrome (PCOS) is associated with increased cardiometabolic risk factors and cardiovascular disease (CVD). Early CVD screening may be an important tool in young high-risk women to effectively prevent premature morbidity from CVD.

Objective

The aim of this study was to provide evidence-based research in the screening and assessment of early atherogenic dyslipidemia, cardiac dysfunction and subclinical atherosclerotic CVD (ACVD) in high-risk women with and without PCOS. Design, Setting, participants: A case-control study in high-risk women aged 25-45 years with (n=45) and without PCOS (n=25), matched for age and body mass index. Main outcome measures: Atherogenic dyslipidemia including a standard lipid panel, total apoB and remnant cholesterol were measured. ACVD was measured using carotid intima-media thickness (cIMT) and presence of carotid plaque, and cardiac function using ultrasound and 2D/3D echocardiography.

Results

Fasting plasma triglycerides (1.9 ± 0.2 vs 1.2 ± 0.2 mM)and remnant cholesterol (0.85 ± 0.1 vs 0.6 ± 0.1 mM) were significantly elevated by 30% and total apoB tended to be elevated by 20% (1. 0 ± 0.1 vs 0.8 ± 0.1 g/L) in PCOS compared to controls. Those with PCOS had a 5-fold higher incidence of carotid plaque compared to controls but no difference in cIMT or cardiac function indices were observed.

Conclusion

Our data shows detection of early ACVD in PCOS compared to controls, and this is associated with atherogenic dyslipidemia. These results suggest early screening and a risk-stratification model may be warranted in high-risk young women with and without PCOS.

Presentation: No date and time listed
ODP139 Association between serum soluble (pro)renin receptor level and worsening of cardiac function in hemodialysis patients: A prospective observational study
Authors: Morimoto Satoshi , Amari Yoshifumi , Suda Chikahito , Bokuda Kanako , Nakajima Fumitaka , Ichihara Atsuhiro
Published: November 2022

A total of 258 maintenance HD patients were recruited and serum s(P)RR concentration was measured.

Background

factors in patients who survived (S group) and patients who died (D group) during the 12-month follow-up period and relationships between serum s(P)RR level and changes in cardiac function during the follow-up period in the S group were investigated. The median serum s(P)RR value at baseline was29.8 ng/ml. Twenty-four patients died during the follow-up period. Cardiothoracic ratio, human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), and E over e-prime were significantly higher in the D group. In the S group, changes in hANP or BNP were significantly greater in the higher serum s(P)RR group than in the lower serum s(P)RR group. High serum s(P)RR level was significantly correlated with changes in BNP, independent of other factors. High serum s(P)RR level was associated with increases in BNP, independent of other risk factors, suggesting that an increased expression of (P)RR may be associated with a progression of heart failure in HD patients and that serum s(P)RR concentration could be used as a biomarker for selecting patients requiring intensive care.

Presentation: No date and time listed
ODP152 Impact of Dietary Cholesterol on LDL: Lessons in Absorption and Overconsumption
Authors: Porter Michael , Wellons Melissa
Published: November 2022

Background

The impact of dietary cholesterol on lipid profiles have remained controversial, highlighted by alterations in the 2015-2020 American Heart Association dietary guidelines abolishing the prior dietary cholesterol limit of 300mg/day. Eggs often are the example cited in this debate as they are a rich source of dietary cholesterol without comparative high levels of saturated fat, 1 of which the effects on LDL cholesterol are well established. To date, evidence has been mixed although most studies show only modest increases in LDL with dietary cholesterol. 1 However, recent research supports significant variation in these findings among predisposed individuals. 2 Heterogeneity in dietary cholesterol absorption can potentially account for these variations and has important clinical implications.

Clinical Case

A 58 year old woman with PMH ulcerative colitis, hyperlipidemia, and radiological evidence of CAD without prior CVD, presented for management of hyperlipidemia. At baseline, her lipid panel in 2015 noted an LDL-C of 125 mg/dL. In 2017, LDL-C was 255 mg/dL, prompting treatment with Atorvastatin. Following initiation of Atorvastatin, LDL-C improved to 137 mg/dL. However, on Atorvastatin, she experienced dermatitis and underwent Dermatology evaluation/biopsy. Medication reaction was favored as the etiology and Atorvastatin was discontinued. In Jan. 2019, off of Atorvastatin, LDL-C was 162 mg/dL. From around 2015-2018, the patient consumed a vegan diet. In 2019, she incorporated nine eggs per day (1600mg dietary cholesterol) into her diet. She denied additional changes to diet or consumption of other animal products. In Aug. 2019, LDL-C was 378 mg/dL. In Aug. 2020, LDL-C was 420 mg/dL. In Aug. 2020, she was advised that her goal LDL was 100 mg/dL or less. She was advised to limit her egg yolk consumption to four per week (∼100 mg/day of cholesterol). She continued to avoid all other animal products. In Oct. 2020, without addition of medication or other notable lifestyle changes her LDL-C decreased to 204 mg/dL. In Jan. 2021, her LDL-C was 130 mg/dL. From 2015-2021, her weight ranged 93-103lbs (BMI ∼16). In Aug. 2021, her LDL-C was 142 mg/dL. Ezetimibe 10mg daily was then added with reduction in LDL-C to a near-target of 103 mg/dL (27% reduction) within four months.

Conclusion

For the average American, current guidelines do not recommend egg restriction as an effective tool for LDL-C lowering. However, as shown in this case, certain individuals may be more prone to high LDL-C when consuming high cholesterol diets. Further study on how to better identify these susceptible individuals could help personalize nutritional and medication treatment plans for patients with dyslipidemia. References: Blesso CN, Fernandez ML. Dietary Cholesterol, Serum Lipids, and Heart Disease: Are Eggs Working for or Against You? Nutrients. 2018 Mar 29;10(4): 426. Grundy SM. Does Dietary Cholesterol Matter? Curr Atheroscler Rep. 2016 Nov;18(11): 68.

Presentation: No date and time listed
LBODP047 Correlation Of Insulin Resistance And Short-term Outcome In Non-diabetic Patients With St Segment Elevation Myocardial Infarction
Authors: Al-Ali Saja , Alidrisi Haider Ayad , Abdulhameed Abdulameer
Published: November 2022

Background

Obviously, hyperglycemia and insulin resistance (IR) are common in patients with ST-segment elevation myocardial infarction (STEMI) in the hospital, and they are connected to poor clinical outcomes. Additionally, insulin resistance is a substantial risk factor for cardiovascular diseases. The case of acute myocardial infarction likewise has a bleak prognosis. The study aimed to evaluate the association between IR and short-term outcomes of acute STEMI patients without diabetes mellitus in the form of reperfusion success, the occurrence of heart failure, development of arrhythmias, and mortality. Method: A cross-sectional study was done from August 2021 to December 2021 in two cardiology centers in Al-Sadr teaching hospital and Basrah oil hospital in Basrah, southern Iraq. Sixty-one nondiabetic hospitalized patients with acute STEMI were included in the study. Clinical data were collected by direct interview with the patients, 25(41%) of them received thrombolytics and 36 (59%) were managed with percutaneous transluminal coronary angioplasty. From each patient, a fasting blood sample was taken for glucose, triglyceride, and insulin to measure IR in the form of the homeostasis model assessment for IR (HOMA-IR) and triglyceride glucose index (TyG index). Both measures were grouped into three tertiles, for HOMA-IR (tertile 1 < 2.5, tertile 2 2.5 - <5, and tertile 3 ≥5) and for TyG index (tertile 1 <4.73, tertile 2 4.73 - <4.87, and tertile 3 ≥4.87). The patients were evaluated within 1-week for (reperfusion success, echocardiography for calculation of the ejection fraction (EF), arrhythmias, and mortality), and within 4-weeks for mortality.

Results

Within the tertile 3 of HOMA-IR, the patients were significantly more likely to have EF < 55% (35%), and higher 4-weeks mortality (35%). Also for the TyG index and within the tertile 3 (≥ 4.87), there was a significantly higher 4-weeks mortality (30%). Pearson correlation also showed significant and negative correlations between both HOMA-IR and TyG index values and EF. While reperfusion success, arrhythmias, and 1-week mortality did not correlate significantly with both HOMA-IR and TyG index.

Conclusion

Insulin resistance as defined by HOMA-IR and TyG index was significantly associated with poor outcomes in patients with acute STEMI in the form of EF<55 and 4-weeks mortality.

Presentation: No date and time listed