bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT210 A Case Of Recurrent Metastatic Parathyroid Cancer Complicated By Multiple Brown Tumors
Authors: Elmaaz Ahmed , Bustamante Eilyn , Batra Manav
Published: October 2023

Disclosure: A. Elmaaz: None. E. Bustamante: None. M. Batra: None.

Introduction: Parathyroid cancer is a rare malignancy with about 25 % incidence of metastasis. Brown tumors are benign bone lesions caused by excessive bone turnover which are rarely associated with parathyroid carcinoma. Here, we present a case of recurrent metastatic parathyroid cancer complicated by multiple brown tumors. Case Presentation: A 63-year-old male presented with back pain, generalized weakness, and significant weight loss. Laboratory findings showed hypercalcemia 14.4 mg/dl, Alkaline phosphatase 253 U/L, and phosphorus 2.3 mg/dl. He was admitted to the hospital for hypercalcemia workup. MRI spine showed a heterogeneous mass arising from the left thyroid lobe and conglomerate lymph node, along with extensive metastatic sclerotic lytic lesions throughout the spine. MRI brain revealed multiple metastatic lesions in the skull base, facial bones, and the right angle of the mandible. Further workup revealed normal PSA, normal serum levels of free lambda and kappa light chains, and normal urine and serum protein electrophoresis. PTH levels, 2435.1 (8.7-77.1) pg/ml, and PTH-rP levels <1.1 pmol/l were noted. Ultrasound-guided FNA of the thyroid mass showed solid growth of malignant parathyroid cells strongly stained for PTH. Biopsy of the body of the T12 vertebra and mandibular lesions showed giant cell lesions of the bone with fibrous dysplasia, consistent with brown tumors. IV hydration, calcitonin, cinacalcet, and IV zoledronic acid started, followed by left hemithyroidectomy and left inferior parathyroidectomy. Surgical pathology was positive for parathyroid carcinoma invading the thyroid gland. His calcium and PTH levels post-surgery significantly improved. A few months later, the patient presented again with hypercalcemia and high levels of PTH. Sestamibi parathyroid scan showed no evidence of parathyroid adenoma. Because of enlarging left neck mass, confirmed by MRI neck, he then underwent excision of the left subcutaneous cervical lesion involving the left sternomastoid muscle. Surgical pathology was consistent with parathyroid carcinoma involving soft tissue. His calcium and PTH levels improved on subsequent follow-up visits. Conclusion: Parathyroid carcinoma is not a common cause of hypercalcemia. Though a rare entity, parathyroid cancer should be considered in the differentials of hypercalcemia and extremely high levels of PTH. Metastasis either locally or remotely should not be overlooked. Brown tumors could mimic bone metastasis and giant cell tumors; therefore, the clinical presentation is important for the diagnosis.

Presentation: Saturday, June 17, 2023
SAT211 PTH-secreting Endometrial Carcinoma: A Rare Cause of Hypercalcemia
Authors: Fanous Ereeny , Park Patricia , Rakhlin Luba
Published: October 2023

Disclosure: E. Fanous: None. P. Park: None. L. Rakhlin: None.

Introduction: Hypercalcemia of malignancy (HCM) is a common occurrence in advanced cancer, but it is rare for gynecological malignancies to be the cause (1). Case Presentation: Our patient is a 48-year-old postmenopausal female with diabetes mellitus and obesity who presented with pelvic pain and vaginal spotting over the course of 2 months. She also reported unintentionally losing approximately 60 lbs over the past year. A CT scan of the pelvis revealed a 6.1 cm uterine mass and thickening of the endometrium up to 2.4 cm. Her electrolyte levels were normal at the time of presentation. A biopsy of the endometrium was performed, and the pathology report indicated endometrial carcinoma. The patient was scheduled for a total hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO). A few weeks prior to her scheduled surgery, the patient reported increased thirst and urination, which she attributed to her diabetes and intake of an SGLT2 inhibitor. On the day of surgery, she was found to have a calcium level of 15.4 mg/dl and an albumin level of 3.6 g/dl. She denied taking calcium supplements or Vitamin D3. The workup for hypercalcemia revealed a PTH level of 338 pg/ml, an undetectable PTH-rp level, and normal levels of Vitamin D1,25 and Vitamin D25. Additional imaging showed numerous pulmonary nodules, which were later confirmed to be metastases from endometrial carcinoma. The thyroid gland and surrounding soft tissue were noted to be unremarkable on available CT images. The patient received a single dose of zolendronic acid and was started on cinacalcet 30 mg twice a day. The calcium gradually normalized. She was initiated on chemotherapy with paclitaxel and carboplatin and underwent a palliative TAH/BSO. Cinacalcet was discontinued after several cycles of chemotherapy. Two months later, the PTH level was checked and found to be 34 pg/ml, with a normal calcium level of 9.5 mg/dl and an albumin level of 4.1 g/dl. Given that the hypercalcemia resolved and the PTH level normalized after chemotherapy and hysterectomy, it is believed that the endometrial carcinoma was the source of ectopic PTH. Conclusion: Approximately 5% of gynecological malignancies are associated with paraneoplastic hypercalcemia [1]. We present a rare case of PTH-secreting endometrial carcinoma, in which surgery and chemotherapy resulted in complete resolution of hypercalcemia and normalization of PTH. Clinicians should consider ectopic PTH production as part of the differential diagnosis in patients who present with malignancy and hypercalcemia.

References: 1. Savvari P, Peitsidis P, Alevizaki M, et al. Paraneoplastic humorally mediated hypercalcemia induced by parathyroid hormone-related protein in gynecologic malignancies: A systematic review. Onkologie. September. 2009;32:517-23.

Presentation: Saturday, June 17, 2023
SAT214 A Rare Case Of Biopsy-proven Non-uremic Calciphylaxis In A Patient With Secondary Hyperparathyroidism
Authors: Annabel Ogar Ufeh , Gbenga Olafimihan Ayobami , Asemota Iriagbonse , Krishnaraju Ellil , Okafor Akuchi
Published: October 2023

Disclosure: U.A. Ogar: None. A.G. Olafimihan: None. I. Asemota: None. E. Krishnaraju: None. A. Okafor: None.

Introduction: Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare, lethal, metastatic calcification involving cutaneous microvasculature that presents as painful necrotic skin lesions. It typically occurs in patients with end-stage kidney disease (ESKD), renal transplant, or acute kidney injury requiring renal replacement therapy. Calciphylaxis occurring without these comorbidities is termed non-uremic calciphylaxis (NUC), which is rarer. NUC’s etiology is unclear but it has been associated with hyperparathyroidism, malignancies, alcohol liver disease, and connective tissue disorders. There are only a few reported cases of biopsy-proven NUC in patients with secondary hyperparathyroidism, as in our patient. Clinical Case: A 63-year-old female with a history of COPD on home oxygen therapy, smoking, and alcohol use disorder presented with a four-day history of severe, painful, purplish left thigh rash. She had no recent trauma or insect bite. Her physical exam showed a large (6x10 cm), tender, distal anterior left thigh bruise. Laboratory findings were significant for elevated creatine of 4.3 mg/dL from a normal baseline creatinine (0.6 mg/dL), normal serum corrected calcium (10.1 mg/dL) and elevated phosphate (4.7mg/dL). Three days following her admission, the skin lesion had progressed into multiple brown coalescing bullae with central ulceration, collarette, surrounding erythema, warmth, and induration. Due to concern for possible skin and soft tissue infection, empiric vancomycin therapy was started. However, the overall clinical picture was not convincing of an infection, necessitating consultation with the Dermatology team. A skin biopsy was recommended, and this was diagnostic of calciphylaxis. Further testing revealed hyperparathyroidism (202pg/ml), low 25 hydroxy Vitamin D (12ng/ml), and negative autoimmune and thrombophilia workup. Her treatment plan included wound care with debridement, analgesia, and interdisciplinary clinic follow-up. During outpatient follow-up, her wound was seen to be slowly healing with daily wound dressing, and her elevated serum creatinine had resolved. Conclusion: NUC has a high mortality rate (52%) and requires a high index of clinical suspicion to ensure prompt diagnosis and initiation of treatment. Differential diagnoses include atherosclerotic vascular disease, vasculitis, hypercoagulable disorders, and cellulitis as in our patient. Skin biopsy is diagnostic. Aggressive wound care and analgesia are pivotal to treatment, in addition to addressing underlying precipitating conditions. Other treatment options like sodium thiosulphate exist but with uncertain outcomes. Efforts geared at definitive therapeutic modalities are needed.

Presentation: Saturday, June 17, 2023
SAT244 Hypercalcemia Induced By Inconspicuous Histoplasmosis Infection
Authors: Alkhathlan Mujahed , Li Yulong , Siddiqui Ayesha , Goud Sarita
Published: October 2023

Disclosure: M. Alkhathlan: None. Y. Li: None. A. Siddiqui: None. S. Goud: None.

Background: Hypercalcemia is a common condition with a variety of etiologies. In general, it can be categorized as either parathyroid hormone (PTH) dependent or independent. In those with non-PTH mediated hypercalcemia, elevated 1, 25 vitamin D is one of the causes and among pathologies behind it are sarcoidosis, malignancy, and to less extent infectious process. An important determinant in the management of elevated 1,25vitD is to identify the source of 1,25vitD overproduction as the choice of treatment can affect the outcomes and increase the risk of mortality. Clinical Case: Our patient is an 81-year-old man who had been admitted to the hospital for nonspecific fatigue and weakness for two months. He was discharged from another hospital with similar complaints without resolution. At the time of admission, he was noted to have elevated total calcium 12.5 mg/dL (8.4-10.2) with albumin 3.0 g/dL (3.5-5.2), subacute kidney injury with creatinine 3.46 mg/dL (0.7-1.3), suppressed parathyroid hormone (PTH) and markedly elevated 1,25-dihydroxy vitamin D (1,25OH2D) 128 pg/mL (19.9-79.3). His calcium and kidney function were normal 4 months ago. The hypercalcemia was refractory to intravenous fluid, loop diuretic or calcitonin administration. Extensive workup eventually revealed disseminated histoplasmosis infection with blood and urine positive for histoplasmosis antigens. Bone marrow aspiration showed scattered non-necrotizing granulomas. With antifungal treatment, his calcium level returned to the normal range in two weeks (8.9 mg/dL) and was maintained in the normal range. Conclusion: Hypercalcemia is a rare presentation of histoplasmosis. Pubmed keyword search of hypercalcemia and histoplasmosis returned 18 clinical case reports from 1977 to 2021. The case review showed a striking similarity in atypical clinical presentation and diagnosis challenges. Hypercalcemia is most developed in histoplasmosis disseminated cases with elevated 1,25vitD levels and pathology identification of granulomas in some of the cases. With successful antifungal treatment, patients will have prompt recovery of hypercalcemia. Steroid treatment is a well know and effective treatment by suppressing 1-alpha hydroxylation of 25-vitD. However, treatment with steroids before establishing diagnosis due to Inconspicuous presentations or delay in diagnosis may lead to mortality quickly.

Presentation: Saturday, June 17, 2023
SAT252 Homozygous CYP24A1 Gene Mutation Induced Hypercalcemia During Pregnancy
Authors: Ankireddypalli Anvitha Reddy , Alameddine Hind
Published: October 2023

Disclosure: A.R. Ankireddypalli: None. H. Alameddine: None.

Introduction: The approach and management of hypercalcemia in pregnancy can be challenging. Pregnancy challenges the calcium homeostasis with physiological increase in 1,25 dihydroxy Vitamin D levels by kidneys and placental 1-alpha hydroxylase, however it rarely causes hypercalcemia. In PTH independent hypercalcemia, disorders in vitamin D metabolism should be considered. Here we report a case of PTH independent hypercalcemia due to autosomal recessive homozygous CYP24A1 gene mutation. Case: A 25-year-old primigravid female presented to the clinic at 26 weeks of gestation for management of hypercalcemia. At 25 weeks gestation, laboratory workup revealed calcium: 13.9 mg/dL, albumin: 2.9 g/dL, PTH: < 6 pg/mL, vitamin D: 45.17ng/mL, creatinine: 1.02 mg/dL, alkaline phosphatase (ALP): 117mcg/L. Since getting pregnant she reported nausea and vomiting. She reported excessive thirst, memory loss, fatigue, exertional dyspnea and 10 lbs weight loss. She denied any personal history of kidney stones or family history of calcium or bone disorders. She stopped her prenatal vitamins at the time of hypercalcemia diagnosis. Her work-up was suggestive of PTH independent hypercalcemia. Differential diagnosis included granulomatous disease, malignancy, benign PTHrP secreting tumors, vitamin D metabolism dysfunction and milk-alkali syndrome. Further work-up revealed ionized calcium: 6.2 mg/dL, PTHrP: 5.3 pmol/L, bone specific ALP: 11.8 mcg/L, 25 hydroxy vitamin D: 132 mcg/L, 1, 25 dihydroxy vitamin D: > 200 pg/mL, 24,25 dihydroxy vitamin D: 1.16 ng/mL, 25-hydroxy vitamin D to 24,25 dihydroxy vitamin D ratio: 75.0, which was indicative of CYP24A1 mutation, an enzymatic defect in vitamin D metabolism. Molecular testing confirmed autosomal recessive homozygous CYP24A1 gene mutation. With elevated 24,25 dihydroxy vitamin D levels, it was unlikely that her 1,25 dihydroxy vitamin D was elevated due to malignancy or granulomatous disease. Treatment with prednisone 60 mg daily for 1 month did not improve her calcium levels. She was recommended to limit her calcium intake, avoid vitamin D supplements or sun exposure. At 38 weeks, she delivered a healthy baby without neonatal complication. Postpartum day 2, her labs revealed calcium: 10.7mg/dL with albumin: 2.7mg/dL. Discussion: Diagnosis of CY24A1 gene mutation associated hypercalcemia is based on increased 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D ratio and confirmed by genetic analysis. Recommendations are adequate hydration, limiting calcium intake, avoiding vitamin D supplements and preventing sun exposure. It is important to monitor for neonatal hypocalcemia and worsening of maternal hypercalcemia during breastfeeding. We report this case to raise awareness of this rare cause of hypercalcemia in pregnancy and the importance of checking calcium and vitamin D levels prior to vitamin D supplementation.

Presentation: Saturday, June 17, 2023
OR29-03 Social Isolation Stress Leads To Bone Loss In Adult Male, But Not Female, C57BL/6J Mice
Authors: Mountain Rebecca , Langlais Audrie , Hu Dorothy , Baron Roland E , Lary Christine , Motyl Katherine J
Published: October 2023

Disclosure: R. Mountain: None. A. Langlais: None. D. Hu: None. R.E. Baron: None. C. Lary: None. K.J. Motyl: None.

Social isolation is a potent form of psychosocial stress and is a growing public health concern, particularly among older adults. Even prior to the onset of the COVID-19 pandemic, which has significantly increased the prevalence of isolation and loneliness, researchers have been concerned about a rising “Epidemic of Loneliness”. Social isolation is associated with increased risk for many health conditions, including mental health disorders, as well as higher overall morbidity and mortality. Previous clinical research has demonstrated that psychosocial stressors, and subsequent mental health disorders, are major risk factors for osteoporosis and fracture, which disproportionally affect older adults. The effects of social isolation on bone, however, have not been thoroughly investigated. The aim of this study was to test the hypothesis that social isolation would lead to bone loss in male and female C57BL/6J mice. 16-week-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) for four weeks (N=16/group). Social isolation significantly decreased trabecular bone parameters, including bone volume fraction (BV/TV) by 26% (Grouped: 21.9 ± 3.6%; Isolated: 16.2 ± 2.1%) (p < 0.0001), as well as BMD, Tb. N., and Tb. Th, in the femur of male, but not female, mice. Femoral cortical bone parameters were also significantly decreased in isolated male mice, including a 9% decrease in cortical thickness (Ct.Th.) (Grouped: 0.187 ± 0.011 mm; Isolated: 0.169 ± 0.009 mm) (p < 0.0001), as well as Ct.Ar., Ct.Ar./Tt.Ar., and pMOI. There were no significant differences in cortical measurements in females. Additionally, isolated male mice had signs of reduced bone remodeling represented by reduced osteoblast numbers and osteoblast-related gene expression, and osteoclast-related gene expression. However, isolated females had increased bone resorption-related gene expression, without any change in bone mass. The magnitude of bone loss in isolated males is as high as that seen in previous studies 4 weeks after orchiectomy or ovariectomy. Overall, our data suggest that social isolation has a dramatic negative effect on bone in males, but may operate through different mechanisms or in a different time frame in females. Future studies will focus on investigating potential mechanisms involving changes in endocrine signaling via glucocorticoid, sympathetic nervous system, and estrogen pathways. These results provide critical insight into the effects of isolation on bone and have key clinical implications as we grapple with the long-term health impacts of the rise in social isolation related to the COVID-19 pandemic.

Presentation: Sunday, June 18, 2023
OR02-01 Somatic Mutations In The Zinc Transporter ZnT1 Cause Primary Aldosteronism
Authors: Rege Juilee , Bandulik Sascha , Nanba Kazutaka , Kosmann Carla , Blinder Amy , Plain Allen , Vats Pankaj , Kumar-Sinha Chandan , Marcondes Lerario Antonio , Else Tobias , Yamazaki Yuto , Satoh Fumitoshi , Sasano Hironobu , Giordano Thomas J , Ann Williams Tracy , Reincke Martin , Turcu Adina , Udager Aaron , Warth Richard , Rainey William E
Published: October 2023

Disclosure: J. Rege: None. S. Bandulik: None. K. Nanba: None. C. Kosmann: None. A. Blinder: None. A. Plain: None. P. Vats: None. C. Kumar-Sinha: None. A.M. Lerario: None. T. Else: None. Y. Yamazaki: None. F. Satoh: None. H. Sasano: None. T.J. Giordano: None. T.A. Williams: None. M. Reincke: None. A. Turcu: None. A. Udager: None. R. Warth: None. W.E. Rainey: None.

Primary aldosteronism (PA) is the most common form of endocrine hypertension and affects approximately one in 50 adults. PA is characterized by inappropriately elevated adrenal aldosterone production via renin-independent mechanisms. Aldosterone-driver somatic mutations in a G protein-coupled inwardly rectifying potassium channel (KCNJ5), Na+/K+ and Ca2+ ATPases (ATP1A1 and ATP2B3, respectively), L-type and T-type voltage-gated calcium channels (CACNA1D and CACNA1H, respectively), and chloride voltage-gated channel (CLCN2) have been found in approximately 90% of adrenal aldosterone-producing adenomas (APAs). Other causes of lateralized adrenal PA include aldosterone-producing nodules (APNs). Using next-generation sequencing, we identified recurrent in-frame deletions in SLC30A1 in four APAs and one APN (p.L51_A57del, n=3; p.L49_L55del, n=2). SLC30A1 encodes the ubiquitous zinc efflux transporter ZnT1 (zinc transporter 1). The identified SLC30A1 variants are situated in close proximity to the zinc-binding site (His43 and Asp47) in transmembrane domain II and likely cause abnormal ion transport. PA cases with the unique SLC30A1 mutations showed male dominance and demonstrated increased serum aldosterone and 18-oxo-cortisol concentrations. Functional studies of the mutant SLC30A151_57del variant in a doxycycline-inducible adrenal cell system revealed pathologic Na+ influx caused by the mutant. Aberrant Na+ current led to the depolarization of the resting membrane potential, and thus to the opening of voltage-gated calcium channels. This resulted in an increase in cytosolic Ca2+ activity, which stimulated CYP11B2 mRNA expression and aldosterone production. Collectively, these data implicate the first-in-field zinc transporter mutations as a dominant driver of aldosterone excess in PA.

Presentation: Thursday, June 15, 2023
OR02-06 FGFR2 Mediates Zona Glomerulosa Morphogenesis, Aldosterone Secretion And Β-Catenin-induced Adrenal Hyperplasia
Authors: Chortis Vasileios , Dulanjalee Kariyawasam , Guagliardo Nick A , Shah Manasvi S , Claudio Ribeiro , Barrett Paula Q , Silva Borges Kleiton , Carlone Diana L , Breault David T
Published: October 2023

Disclosure: V. Chortis: None. K. Dulanjalee: None. N.A. Guagliardo: None. M.S. Shah: None. R. Claudio: None. P.Q. Barrett: None. K.S. Borges: None. D.L. Carlone: None. D.T. Breault: None.

Fibroblast Growth Factor Receptors (FGFRs) are tyrosine kinase receptors with critical roles in organogenesis and tissue homeostasis. We have recently shown that Fgfr2 deletion in the outermost zone of the mouse adrenal cortex (zona Glomerulosa, zG) during post-natal development leads to disordered morphology. Interestingly, Fgfr2 is up-regulated in the zG of mice with adrenal hyperplasia due to constitutive activation of Wnt/beta-catenin signaling. Here, we seek to delineate the role of FGFR2 in adrenal morphology and function during postnatal development, adulthood homeostasis, as well as during β-catenin-induced adrenal hyperplasia. To address this, we used i) a mouse model of conditional Fgfr2 loss (Fgfr2-cKO), in which zG-specific Fgfr2 deletion begins during early post-natal development, and ii) an inducible mouse model (Fgfr2-icKO), in which Fgfr2 deletion in the zG during adult life is tamoxifen-dependent. Fgfr2 loss in Fgfr2-cKO mice disrupted zG cell differentiation in steroidogenically mature cells and limited their capacity to proliferate and undergo trans-differentiation into the adjacent zona Fasciculata. zG cell de-differentiation was also evident upon acute loss of Fgfr2 in adult Fgfr2-icKO mice. Furthermore, Fgfr2 loss in a mouse model of beta-catenin-induced zG hyperplasia was sufficient to fully abrogate adrenal hyperplasia. Treatment with pan-FGFR small molecule inhibitors suppressed cellular proliferation in the mouse zG and inhibited aldosterone secretion. Taken together, these results suggest FGFR2 has a critical role in normal adrenal development and tissue homeostasis and is an essential mediator of beta-catenin-induced adrenal hyperplasia. FGFR2 targeting may be meaningful in patients with conditions associated with aldosterone excess.

Presentation: Thursday, June 15, 2023
THU405 A Delicate Balance
Authors: Mohan Nikita , Sanjiv SHAH Manasi
Published: October 2023

Disclosure: N. Mohan: None. M.S. Shah: None.

Introduction: Primary hyperparathyroidism is a disorder of excessive parathyroid hormone production causing increased calcium levels, usually due to a parathyroid adenoma. Commonly these cases are asymptomatic and detected incidentally on routine labs. They can be managed conservatively with sufficient fluid intake and avoiding dehydration. Congestive heart failure patients on diuretics with primary hyperparathyroidism require a delicate balance of their volume status to prevent exacerbation of either condition. We present a case of a woman with repeated hospitalizations due to poor volume status control. Clinical Case: An 82-year-old female with congestive heart failure (CHF), primary hyperparathyroidism (diagnosed 17 years ago), sick sinus syndrome with a pacemaker, and persistent atrial fibrillation presented to the emergency room with worsening b/l lower limb swelling for a few months. The remaining review of systems was largely negative. At home, she was on Losartan, Furosemide, and Carvedilol. Vitals were stable and physical exam revealed b/l lower extremity pitting edema. Chest x-ray showed cardiomegaly with mild pulmonary vascular congestion. Pertinent labs were NT pro-BNP 2190, Calcium 11.3 mg/dL, PTH 143 pg/mL, and Vit D, 25-hydroxy 48.6 ng/mL. The patient was started on IV diuretics and her home medications for CHF exacerbation. ECHO showed EF 39%, grade III diastolic dysfunction, severe pulmonary hypertension, mitral and tricuspid regurgitation. She was managed conservatively for her hypercalcemia and advised to maintain hydration at home. Spironolactone and Dapagliflozin were added to her regimen, and Furosemide was increased at discharge. The patient was re-admitted three weeks later with fatigue and decreased fluid intake. Vitals were stable and physical exam revealed dehydration. Pertinent labs were Calcium 13.4 mg/dL, Potassium 5.7 mmol/L, Creatinine 1.7 mg/dL (baseline 1.0), PTH 204 pg/mL, and Vit D 54.1 ng/mL. Repeat ECHO showed EF 15%. She was started on gentle 0.9% NS IV fluid to correct the hypercalcemia while preventing volume overload. Hypercalcemia and acute kidney injury improved with hydration. She was put on Cinacalcet 30 mg and home medications were modified for better volume control at discharge. Conclusion: This case highlights the complications of balancing the volume status with primary hyperparathyroidism and CHF. This patient’s primary hyperparathyroidism was well-controlled for more than fifteen years on adequate hydration. However, worsening CHF resulted in a higher requirement for diuretics, thereby worsening her hypercalcemia. Even though parathyroidectomy is an established treatment modality, she was not a suitable candidate due to age and comorbidities. Hence, to prevent such complications, parathyroidectomy must be considered early in patients with heart disease and even in asymptomatic hyperparathyroidism.

Presentation: Thursday, June 15, 2023
THU588 Sparing Confirmatory Testing In Primary Aldosteronism: The Combination Of Renin, Aldosterone And Potassium Levels
Authors: Chua Ong Lopez Albert Macaire , Mandocdoc Dimayuga Diana Colleen , Leo Estabillo Tiu , Castillo Dampil Oliver Allan , Mendoza Erick , Lim Villa Michael , Macabuag-Oliva Andrea Marie
Published: October 2023

Disclosure: A.C. Ong Lopez: None. D.M. Dimayuga: None. L.E. Tiu: None. O.C. Dampil: None. E. Mendoza: None. M.L. Villa: None. A.M. Macabuag-Oliva: None.

Background and Objective: The diagnosis of primary aldosteronism (PA) is comprehensive which includes case-detecting testing, case confirmation followed by subtype classification. In certain instances, one may not proceed with further confirmatory testing in the setting of spontaneous hypokalemia, suppressed renin, and PAC > 15 ng/dL. However, this quality of evidence is very low. This study sought to determine the optimal laboratory combination patterns that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various combination settings and correlating to the recent evidence and clinical practice guidelines. Methodology: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study with a sampling total of 116 participants aged 18 years and above who underwent saline infusion test between January 2010 to March 2023. The main outcome measures comprise the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia) which include the sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.0.0 & MedCalc 20.218. Results: Of the 116 patients who underwent saline infusion test, 76 (65.52%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 89.11%, 100.00%) and positive predictive value at 100% (95% CI 82.35, 100.00%). The optimal combination criteria with the best balance of the diagnostic performance indices were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has a sensitivity of 34.72% (95% CI 23.88% , 46.86%), specificity of 93.75% (95% CI 79.19%, 99.23%), positive predictive value (PPV) of 92.59% (95% CI 75.71%, 99.09%), negative predictive value (NPV) of 38.96% (95% CI 28.05%, 50.75%), positive likelihood ratio (LR+) of 5.56 (95% CI 1.40, 22.06), negative likelihood ratio (LR-) of 0.70 (95% CI 0.58, 0.84), and a diagnostic accuracy of 52.88% (95% CI 42.85%, 62.75%). Conclusion: Hypertensive patients with spontaneous hypokalemia who had initial screening test results of PAC > 20 ng/dL and PRA < 0.6 ng/ml/hr can be diagnosed as overt primary aldosteronism and may not proceed with dynamic confirmatory testing. This is in line with the 2016 Endocrine Society Clinical Practice Guideline recommendation.

Presentation: Thursday, June 15, 2023
FRI089 Massive Hypertriglyceridemia? Think Oral Contraceptive Pills!
Authors: Ali Israa , Hamdi Mohammed
Published: October 2023

Disclosure: I. Ali: None. M. Hamdi: None.

Introduction: Oral contraceptive pills (OCPs) are common cause of Hypertriglyceridemia (TG) that should be recognized early by clinicians. Concern is raised regarding pursing further genetic test for Familial hypertriglyceridemia for female who developed massive hyper triglyceridemic after starting hormonal therapy. Case: A 37-year-old female patient with history of prediabetes with A1c of 5.7% and one attack of pancreatitis. Normal BMI, No regular medications, negative family history for lipid disorder. Rare social intake of alcohol. Routine annual lab showed triglycerides level of 164 in 2016, otherwise normal biochemical evaluation. No treatment pursued. Later She was started on OCPs (Kariva 0.15-0.02 mg) for contraception. Late 2019, blood work-up showed cholesterol level of 979, TG of 3170 and HDL level of 22. She was started on a statin therapy and fenofibrates beside stopping OCP, she maintained normal lipid profile while being off OCPs, until 2022 when she restarted an OCPs (Lo Loestrin 1mg-10 mcg) for 2 months that resulted in elevated cholesterol level of 1222, triglycerides of 5177 and HDL of 10.OCP was stopped, lipids level trended down with cholesterol of 961, triglycerides of 2005 and HDL of 22 then normalized after 2 months. Patient did not have any clinical symptom or complain. Discussion: High triglyceride concentration is an independent predictor of coronary heart disease and ischemic stroke. Many patients with triglycerides >1000 mg/dl have familial hypertriglyceridemia with superimposed additional exogenous factors which further raise triglyceride concentrations like exogenous estrogens, SERMs, hyperestrogenemia of pregnancy, poorly controlled diabetes mellitus, hypothyroidism, alcohol excess, exogenous corticosteroids, and drugs including isotretinoin and protease inhibitors. OCP induced hypertriglyceridemia occurs due to estrogen’s action in decreasing hepatic triglyceride lipase and lipoprotein lipase activity. This causes an overall increase in low and intermediate-density triglycerides and cholesterol that can increase free fatty acids to toxic level. The marked increase of TG and cholesterol in this patient while being on OCP is unusual and strongly indicate underlying familial hypertriglyceridemia exacerbated by starting OCP. Further genetic work up is being done. As OCP or other estrogen therapy are frequently given unwittingly to women with preexisting hypertriglyceridemia that lead to severe clinical consequences. Estrogen containing medication should not be considered if fasting triglyceride is above 500 mg/dl. In women on hormonal treatment with treatment-resistant hypertriglyceridemia, the likelihood that the hormonal treatment is nullifying drug efficacy is high so it should be stopped for a short trial while continuing modifying triglyceride-lowering medications.

Presentation: Friday, June 16, 2023
FRI093 Severe Hypertriglyceridemia Post Liver Transplant- A Multifactorial Disorder
Authors: Saand Aisha R , Drinnon Alexsandra R , Mubeen Faiza , Shakil Jawairia
Published: October 2023

Disclosure: A.R. Saand: None. A.R. Drinnon: None. F. Mubeen: None. J. Shakil: None.

Introduction: Hypertriglyceridemia (HTG) is a known complication in solid organ transplant patients. In addition to increasing cardiovascular complications and mortality risk, these metabolic abnormalities also increase the risk of allograft atherosclerosis and vasculopathy. Although medications used in post-transplant management have a well-documented effect of worsening lipid profile, multiple factors may be contributing in the development of severe HTG. Case Description: We describe a 68-year-old male with elevated triglycerides (TG) of 3957 mg/dL on hospital admission for pneumomediastinum. He received liver transplant 2 years prior due to alcohol-related liver cirrhosis. He had normal TGs prior to the transplant. Immunosuppressant regimen included tacrolimus (TAC) and methylprednisone. Lipoprotein electrophoresis was normal. Intravenous insulin infusion was initiated with moderate improvement however, upon transition to oral medications: fenofibrate, omega-3 fatty acids, niacin and rosuvastatin, TGs continued to increase. Reinitiating insulin infusion showed no improvement. TAC was switched to cyclosporin with transient decrease in TGs. Upon discharge amylase and lipase levels remained normal despite TG elevation. When readmitted for an unrelated reason, his TGs were elevated at 2218 mg/dl. Plasmapheresis was initiated but was complicated by anaphylaxis with angioedema requiring intubation. After partial plasmapheresis, TGs significantly decreased and soon returned to normal. Post-discharge, the patient was changed back to previous TAC dosage due to cyclosporin related renal injury. His steroid dose was reduced and icosapent was added, resulting in no further recurrence of HTG. Discussion: Following liver transplant, about 15-40% recipients have increased cholesterol levels and about 40% have HTG. Although, immunosuppressant-induced dyslipidemia is seen frequently, additional risk factors have been identified. A retrospective study of 85 patients post liver transplant showed HTG developed early within the first month in about 67% patients and persisted throughout the first year. Some common factors predictive of HTG post liver transplant include pre-liver transplant hepatocellular disease and post-transplant renal dysfunction. A study in pediatric patients post liver transplant observed that changes in lipoprotein and HDL subfraction post-transplant may lead to hypertriglyceridemia. Our case suggests that HTG may be multifactorial given the persistent elevation of TGs despite the change in immunosuppressant regimen. Patient factors as well as genetic characteristics of the donor liver may be potential causes. Recognizing this variation in patient populations may be extremely important due to high risk for pancreatitis and cardiovascular events. Early identification and management may prevent complications.

Presentation: Friday, June 16, 2023
FRI141 Dietary Salt Regulates mTORC1 Signaling In Humans And Mice With Hypertension
Authors: Aljaibeji Hayat , Brooks Daniele L , Garza Amanda E , Gerges Peter , Heydarpour Mahyar , Luminita Pojoga , Williams Jonathan S , Williams Gordon , Romero Jose R
Published: October 2023

Disclosure: H. Aljaibeji: None. D.L. Brooks: None. A.E. Garza: None. P. Gerges: None. M. Heydarpour: None. P. Luminita: None. J.S. Williams: None. G. Williams: None. J.R. Romero: None.

Raptor and the mammalian target of rapamycin (mTOR) form a complex (mTORC1) that has been proposed to play a role in aldosterone (ALDO) production. Pharmacological inhibition of mTORC1 reduces blood pressure (BP) and ALDO levels. However, the effects of environmental factors such as dietary salt on mTORC1 in humans are unclear. We studied the impact of one-week liberal Na+ (LIB, 200 mmol/day) and restricted (RES, 10 mmol/day) Na+ diets on Raptor and mTOR expression in human peripheral blood mononuclear cells (PBMC) from hypertensive subjects. Raptor and mTOR expression were higher on PBMCs from subjects on a LIB than on RES Na+ diet (n=13; P=0.036 and P=0.0008, respectively). We also studied Caucasian subjects (n=792) from the Hypertensive Pathotype (HyperPATH) cohort using the Multi-Ethnic Genotyping Array on the Illumina platform. Candidate gene association analyses showed that the single nucleotide polymorphic (SNP) Raptor gene variant, rs99001846, was associated with BP and ALDO levels. Multivariate linear regression analyses performed on hypertensive and normotensive participants showed that in hypertensives, rs99001846 risk allele carriers (AA/GA), as compared to non-risk carriers (GG), were associated with increased systolic BP levels on bothLIB and RES Na+ diets (P=0.02, P=0.01 respectively). In addition, risk allele carriers, as compared to non-risk carriers, showed increased ALDO and reduced Na+ excretion on a LIB Na+ diet (P=0.009, P=0.025, respectively). We also studied a mouse model of low nitric oxide and high AngII-mediated hypertension and observed increased cardiac Raptor and mTOR expression (n=4, P=0.0008 and P=0.03 respectively). We then performed in silico bioinformatic analyses of rat zona glomerulosa cells following 2 hr treatment with 100 nM angiotensin II (AngII) using the Gene Expression Omnibus (GEO). AngII treatment led to the activation of mTOR signaling pathways as shown by increased expression of insulin receptor substrate type 2 (P=0.00001) and Low-density lipoprotein-related receptor 5 (P=0.03). Also, AngII reduced the expression of Eukaryotic Translation Initiation Factor 4E Binding Protein 1 by 43% (P= 0.001) and increased expression of CAP-Gly Domain Containing Linker Protein 1 by 70% (P= 0.00003) - important signaling molecules that are downstream of mTOR activation. Our results suggest that in hypertension, Na+ intake and Raptor gene variants modify mTORC1. Thus, mTOR/Raptor expression are a potential biomarker of ALDO-mediated cardiovascular injury.

Presentation: Friday, June 16, 2023
FRI142 The Pathophysiologic Spectrum Of Primary Aldosteronism Determined Via Saline Suppression Testing In Overweight Hypertensive And Pre-hypertensive People
Authors: Warachit Parksook Wasita , Michelle Brown Jenifer , Milks Julia , Moore Anna , Niebuhr Yvonne , Honzel Brooke , Vaidya Anand
Published: October 2023

Disclosure: W.W. Parksook: None. J.M. Brown: Consulting Fee; Self; Bayer, Inc. J. Milks: None. A. Moore: None. Y. Niebuhr: None. B. Honzel: None. A. Vaidya: Consulting Fee; Self; Corcept, HRA Pharmaceuticals, Mineralys.

Background: Emerging evidence shows that primary aldosteronism is not a categorical condition, but rather a pathophysiologic continuum that manifests across a broad range of severity. Saline suppression testing has long been used to “confirm” primary aldosteronism while employing relatively arbitrary and categorical thresholds. Methods: Overweight to obese participants with metabolic risk factors and pre-hypertension or stage 1 hypertension with suppressed renin activity (<1.0 ng/mL/h) (n=42) underwent deep phenotyping protocols to assess the pathophysiologic continuum of the primary aldosteronism phenotype. Participants completed a seated saline suppression test (SSST), to maximally suppress Angiotensin II-mediated aldosterone production, and dexamethasone suppression and cosyntropin stimulation testing, to maximally suppress and stimulate ACTH-mediated aldosterone production. The association of each parameter with the continuum of aldosterone levels was assessed using linear regression. Results: Following SSST, there was a continuum of non-suppressible and renin-independent aldosterone production. Categorically, 29% of participants had post-SSST plasma aldosterone levels ≥10 ng/dL, and another 45% had levels 6-10 ng/dL; however, there was a continuous spectrum of aldosterone values above and below these arbitrary thresholds. Across the continuum of post-SSST aldosterone levels, greater non-suppressibility of aldosterone was associated with greater non-suppressibility of aldosterone post-dexamethasone (β= 1.05, P<0.001), greater stimulation of aldosterone post-cosyntropin administration (β= 1.42, P<0.001), and greater aldosterone-to-renin ratio (β= 3.44, P=0.01). Conclusion: Despite existing categorical thresholds for SSST, dynamic phenotyping studies in overweight/obese stage I hypertensive and pre-hypertensive individuals demonstrate a continuum of non-suppressible and renin-independent aldosterone production following SSST that parallels higher levels of ACTH-dependent aldosterone production. These findings underscore the fallibility of currently recommended diagnostic limits for SSST and suggest that primary aldosteronism pathophysiology transcends these relatively arbitrary thresholds.

Presentation: Friday, June 16, 2023
OR24-06 The Role Of Oxidative Stress In The Association Of Smoking And Alcohol Consumption With Hepatic Steatosis
Authors: Shaheen Magda , Schrode Katrina , Pan Deyu , Michael Najjar Sonia , Friedman Theodore C
Published: October 2023

Disclosure: M. Shaheen: None. K. Schrode: None. D. Pan: None. S.M. Najjar: None. T.C. Friedman: None.

Hepatic steatosis (HS) is the most prevalent chronic liver disease in the United States. While heavy alcohol consumption is known to be a risk factor for HS, the effect of moderate consumption is still debated. Similarly, while smoking is a known risk factor for many chronic conditions, its contribution to HS is still in question. A potential mechanism by which these factors could increase risk for HS is through oxidative stress. Oxidative stress is an imbalance between free radicals and antioxidants in the body that causes inflammation and cellular damage. Behaviors such as smoking and alcohol consumption are thought to increase oxidative stress. This study aims to determine the role of oxidative stress in the relationship between smoking and moderate alcohol consumption with HS among the adult population of the United States. We analyzed data for 3444 participants from the National Health and Nutrition Examination Survey 2017-2018. Hepatic steatosis was measured by FibroScan® using controlled attenuation parameter (CAP) values, and we used levels of γ-glutamyltransferase (GGT) as a biomarker for oxidative stress. We categorized alcohol consumption and smoking as none, former (for smoking), light, and moderate-heavy following the National Center for Health Statistics. We used bivariate chi square analysis and multivariable logistic regression adjusting for the demographics, laboratory, and co-morbidity and consider the design and weight. We developed two models with and without oxidative stress. In bivariate analyses, oxidative stress was significantly associated with heavier smoking and alcohol consumption, and with HS (all p<0.05). A multivariable model without oxidative stress showed that light drinking alone, light smoking alone, and combination of light smoking and light drinking were not associated with HS (p>0.05), but moderate-heavy smoking combined with light drinking or moderate-heavy drinking increased the odds of HS compared to abstinence from both smoking and drinking (Adjusted Odds Ratio [AOR]=3.9, 95% Confidence Interval [95% CI]= 1.5 - 10.2, p=0.006; AOR=6.2, 95% CI= 1.4 - 26.9, p= 0.014, respectively). When we included oxidative stress in the model, oxidative stress was independently associated with HS (AOR=1.1, 95% Ci=1.0-1.1, p=0.011) and the odds ratios for the interaction of smoking and alcohol did not change, indicating that oxidative stress was not a mediator of these relationships. Our findings indicated that smoking and alcohol consumption can interact to increase the odds of HS in the US population independent of oxidative stress. Further research is needed to identify the underlying mechanisms.Grants: R01MD012579, R24DA017298, U54MD007598, S21MD000103, UL1TR001881

Presentation: Saturday, June 17, 2023
THU244 Clinical Factors Affecting Dapagliflozin Response For Glycemic Control And Body Weight Reduction: Post-hoc Analysis Of BEYOND Study
Authors: Jeung Ahn Kyu , Ji Eun Jun , In-Kyung Jeong
Published: October 2023

Disclosure: K. Ahn: None. J. Ji Eun: None. J. In-Kyung: None.

Background: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, ameliorates hyperglycemia and obesity by inhibiting renal glucose reabsorption. However, significant heterogeneity exists in glucose-lowering efficacy and the magnitude of the weight loss among patients with type 2 diabetes. Herein, we aimed to evaluate the clinical factors affecting response to dapagliflozin treatment. Methods: We performed a post-hoc analysis of the BEYOND (Effects of Dapagliflozin Compared with Glimepiride on Body Composition in Patients with Type 2 Diabetes Inadequately Controlled with Metformin) randomized, double-blind, parallel-group trial. Patients were randomly assigned (1:1) to receive the addition of either dapagliflozin 10 mg per day or glimepiride 1∼2 mg per day to background metformin therapy for 52 weeks. Changes in HbA1c and body weight from baseline during the observation period were assessed for all patients. Responder to dapagliflozin was defined by >1% reduction in A1c and >3% reduction in body weight at week 52. Then, we classified the total subjects into 4 groups: non-responder of both A1c reduction and body weight reduction, responders of A1c reduction but non-responder of body weight reduction, non-responder of A1c reduction but responders of body weight reduction, and responders of both A1c reduction and body weight reduction.

Results: Among 56 patients in a dapagliflozin arm, 55.4% (N = 31) and 57.1% (N = 32) experienced clinical responses as indicated by reductions in HbA1c and in body weight reduction, respectively. Younger age and higher HbA1c level at baseline were significantly associated with a greater HbA1c reduction, and a higher estimated glomerular filtration rate (eGFR) was significantly associated with a greater body weight reduction. However, there was no association between the change in HbA1c and the change in body weight (r = −0.133, P = 0.328). Responders of both A1c reduction and body weight reduction were most common (32.1%), non-responders of A1c reduction but responders of body weight reduction were second-most (25.0%), responders of A1c reduction but non-responders of body weight reduction were 23.2%, and non-responders of both A1c reduction and body weight reduction were 19.6%. Subjects with higher fasting plasma glucose (FPG) and HbA1c in addition to lower eGFR at baseline had a greater reduction in HbA1c, but less reduction in body weight. Conversely, those with lower FPG and HbA1c in addition to higher eGFR at baseline had a greater reduction in body weight, but less reduction in HbA1c level. Conclusion: Patients with type 2 diabetes actually exhibit a heterogeneous response to dapagliflozin treatment. Glucose-lowering efficacy of dapagliflozin was associated with worse baseline glycemic status, and body weight reduction was associated with baseline higher eGFR.

Presentation: Thursday, June 15, 2023