bluuebunny/crossref_metadata_2025 huggingface dataset:
9288 National Trends in Fragility Hip Fractures Among Community Dwelling Women With Low Femoral Neck Bone Mineral Density
Authors: Atri Avica , Anastasopoulou Catherine
Published: October 2024

Disclosure: A. Atri: None. C. Anastasopoulou: None.

Introduction: Fragility hip fractures are a major public health burden and are considered a good measure of the quality of healthcare. However, contemporary trends in fragility hip fractures in women with low femoral neck bone mineral density (BMD) in the United States are not known. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women aged ≥ 60 years with bone mineral density (BMD) T score ≤ -1 at the femur neck, which was measured by dual energy x-ray absorptiometry (DEXA) on Hologic Discovery Model A Densitometers (Hologic, Inc., Bedford, Massachusetts). Fragility fracture at the hip was defined as self-reported hip fracture resulting from a fall from standing height or less. Participants with missing BMD and fracture data were excluded. ANOVA was used for comparing means. The Cochran-Armitage test was utilized for trend analysis. Results: Overall, in women aged ≥ 60 years with femoral neck T score ≤ -1, the average age of women of low BMD decreased from 71(±7.2) years to 69.6 (±6.7) years, whereas the mean T-score modestly worsened from – 1.96 (±0.62) to -2.04 (±0.77) from 2009-10 to 2017-18. Similarly, the prevalence of women with T score ≤ -2.5 increased from 18.1% to 21.3%. We also found no significant change in proportion of women who reported treatment for osteoporosis (2009-10: 19.8%, 2013-14: 18.5%, 2017-18: 19.7%; p trend = 0.052). However, proportion of women who experienced fragility hip fractures decreased significantly (2009-10: 2.4%, 2013-14: 1.5%, 2017-18: 1.2%; p trend = 0.001). The mean age of index fragility hip fracture was 70.6 years in 2009-10, 68.3 years in 2013-14 and 71.7 years in 2017-18 (p = 0.001). Age stratified analysis showed a decreasing trend in proportion of women ≥ 80 years who experienced their index fragility hip fracture (2009-10: 25.9%, 2013-14: 14.7%, 2017-18: 15%; p trend = 0.001) and 70-79 years (2009-10: 40.9%, 2013-14: 21.1%, 2017-18: 35.8%; p trend = 0.001), while an increasing trend was seen in women 60–69 years (2009-10: 33.2%, 2013-14: 64.2%, 2017-18: 49.2%; p trend = 0.001). Discussion In this nationally representative cohort of community-dwelling US women with a low femoral neck BMD, we found a 50% decrease in burden of fragility hip fractures over a 10-year period from 2009-10 to 2017-18. This trend was observed despite worsening mean femoral neck T-scores, T score ≤ -2.5, and similar rates of osteoporosis treatment. Interestingly, the proportion of women who experienced their index fragility hip fracture showed a declining trend among the 70-79 years and ≥ 80 years age-groups. This change may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education and environment modifications targeted towards the elderly population.

Presentation: 6/2/2024
7660 Navigating Hypercalcemia: MAC Treatment Hurdles and the Unforeseen Impact of Vitamin D Supplementation
Authors: Noguchi Sumire , Lai Sunny , Rajpal Aman
Published: October 2024

Disclosure: S. Noguchi: None. S. Lai: None. A. Rajpal: None.

Introduction: Hypercalcemia is a recognized complication in granulomatous disorders such as sarcoidosis and tuberculosis, resulting from increased 1 alpha-hydroxylase activity in macrophages leading to excessive conversion to 1,25(OH)2 vitamin D (calcitriol). Mycobacterium avium complex (MAC) is an infectious granulomatous disease often suspected in immunocompromised individuals, including those with human immunodeficiency virus (HIV). Additionally, vitamin D deficiency is prevalent in the general population, prompting supplementation. We hereby present a patient with advanced HIV and disseminated MAC who developed severe calcitriol-induced hypercalcemia in the setting of high dose vitamin D supplementation. Case description: A 48-year-old male with advanced HIV (CD4 count <20 cells/mm^3) presented for evaluation of abdominal pain and constipation, and was found to have severe hypercalcemia of 14.8 mg/dL. Five months prior, he had restarted anti-retroviral therapy (ART) after having been out of care for over a year and was diagnosed with disseminated MAC for which he was on azithromycin and ethambutol. Cultures drawn during this admission were negative for MAC. Hypercalcemia was possibly due to paradoxical immune reconstitution inflammatory syndrome (IRIS) and with appropriate management his calcium level rapidly normalized to 9.7 mg/dL and remained stable until the recent admission. He represented one year later with a calcium level of 13.8 mg/dL with suppressed parathyroid hormone levels, which was refractory to bisphosphonate therapy, therefore was empirically initiated on dexamethasone. By day 4, his calcium levels improved significantly and was discharged on a taper regimen. Cultures collected this admission later revealed ongoing MAC infection, which raised concern for treatment failure and calcitriol-induced hypercalcemia. Calcitriol levels were elevated at 105 pg/mL, which further supported this hypothesis. Additionally, prior to admission he had been prescribed ergocalciferol 50,000 units weekly for 8 weeks, after which he was transitioned to 2,000 units daily. This likely exacerbated the calcitriol-induced hypercalcemia by providing sudden availability of substrate, 25-OH vitamin D, for the activated macrophages. Conclusion: ART has reduced the incidence of opportunistic infections such as MAC, however mortality remains high. Vigilant monitoring for complications, particularly life-threatening calcitriol-induced hypercalcemia and timely use of corticosteroids, is crucial. This case also highlights the need for careful oversight in high-dose vitamin D supplementation for individuals with granulomatous disease and vitamin D dysregulation.

Presentation: 6/2/2024
8651 Parathyroiditis- An Unusual Autoimmune Mediated-Process Presenting as Primary Hyperparathyroidism
Authors: Abdel-Malek M , Alexiadou K , Chander N , Damji S , Mukhopadhyay S , Palazzo F , Tan T
Published: October 2024

Disclosure: M. Abdel-Malek: None. K. Alexiadou: None. N. Chander: None. S. Damji: None. S. Mukhopadhyay: None. F. Palazzo: None. T. Tan: None.

Background: Inflammatory processes of the parathyroid gland are rare, not widely reported in the literature nor fully understood.Clinical case: A 67-year-old female was referred to the Endocrine team with a diagnosis of primary hyperparathyroidism in the context of severe symptoms related to hypercalcaemia and a background of osteoporosis. There was no known family history of endocrinopathies or autoimmune disease. Despite Cinacalcet treatment, she had a significant hypercalcaemia with an adjusted Calcium level of 2.99 mmol/L (RR 2.20 to 2.60) and a high Parathyroid Hormone (PTH) level of up to 46.1 pmol/L (RR 1.6 to 7.2). Localisation studies in the form of a Sestamibi and ultrasound scan failed to locate a parathyroid adenoma.During a four-gland exploration procedure, she had two pathological glands in the right inferior and left superior positions. She therefore underwent a bilateral inferior parathyroidectomy with no intra or immediate post-operative complications. On removal of the two abnormal parathyroid glands, her PTH level dropped from its peak of 48.1pmol/L to 12.2 pmol/L. However, most remarkably, the outcome of her histology revealed morphological appearances of a chronic parathyroiditis.On post-surgery follow-up, her symptomology of fatigue, nausea, abdominal pain and bowel symptoms resolved in addition to reported improvement in energy level. Her adjusted Calcium remained in the range 1.88mmol/L to 2.32mmol/L with a normalised and appropriately reactive PTH level.Over a year later, she developed sudden onset alopecia as well as oncholysis. Her autoimmune serology was negative with no other endocrine biochemical disturbance observed suggestive of an autoimmune-mediated polyendocrine process.She later developed hypocalcaemia despite high-dose Adcal D3, replete Vitamin D status and detectable PTH level (3.7 to 5.0 pmol/L), requiring admission for intravenous Calcium infusion. She was diagnosed with a functional hypoparathyroidism and subsequently commenced on regular Alfacalcidol with good symptomatic response. Conclusion: This case illustrates how a chronic parathyroiditis can mimic a primary hyperparathyroidism, and the even more unusual late presentation of a functional hypoparathyroidism in this context.

Presentation: 6/2/2024
8031 Pelvic Fracture Related to Brown Tumor in Severe Secondary Hyperparathyroidism
Authors: Bodenstab M , Lieberman-Ulm M , Lagari-Libhaber V S
Published: October 2024

Disclosure: M. Bodenstab: None. M. Lieberman-Ulm: None. V.S. Lagari-Libhaber: None.

Background: Severe hyperparathyroidism can result in end-organ damage to the skeleton, known as osteitis fibrosa cystica (OFC). Histologically, OFC manifests as “Brown tumors”, which are so named due to the hemosiderin deposition that occurs from recurring microtraumas with subsequent hemorrhage. Typical sites of presentation include the mandible, clavicle, ribs, or pelvis, but can occur anywhere in the body. Patients can present with diffuse bone pain, pathological fracture, or bone deformities, though some may be asymptomatic and diagnosed incidentally. While these tumors do not have malignant potential, they can become debilitating in their burden and mimic malignant disease. Treatment focuses on treating the underlying cause of the hyperparathyroidism. Clinical Case: A 52-year-old female with ESRD on thrice weekly hemodialysis secondary to T2DM and HTN presented with right thigh pain and difficulty bearing weight, which began one week after a mechanical fall from standing. X-ray on admission revealed acute nondisplaced pathologic fracture of the right superior pubic ramus related to an underlying 4.7 x 2.2 cm expansile osteolytic lesion. Calcium level corrected for albumin on admission was 9.3 mg/dL, phosphorous 5.6 mg/dL, and PTH 563 pg/mL. Review of our institution’s electronic medical record revealed a maximum PTH level of 1,808 pg/mL three months prior. On CT pelvis, the patient was found to have multiple osteolytic lesions also involving the sacrum, multiple vertebral bodies, and the left pubic ramus, concerning for metastatic disease. Patient underwent pelvic rami bone biopsy resulting as osteoclast type giant cells, hemosiderin deposition and fibrosis in keeping with "brown tumor" of hyperparathyroidism. The patient was started on Cinacalcet 30 mg daily, with plans to titrate as outpatient to target PTH levels. She was also instructed to continue calcium, vitamin D and calcitriol to treat the underlying condition of metabolic bone disease from CKD. Referrals were given for both orthopedic spine and orthopedic oncology for surgical evaluation of her lesions. Discussion: Osteitis fibrosa cystica has become exceedingly rare in the United States and occurs in about 2% of patients with hyperparathyroidism. Due to their low prevalence and radiologic similarity to neoplasm, “Brown tumors” may be mistaken for metastatic disease and can lead to delay in diagnosis. Histology reveals collections of osteoclasts due to excess activity intermixed with fibrous tissue and poorly mineralized woven bone, which will differentiate brown tumor from malignancy. However, further correlation with hypercalcemia and hyperparathyroidism is imperative as brown tumors and other giant cell-containing lesions may be difficult to differentiate histologically. We present this case due to its rarity in clinical practice.

Presentation: 6/2/2024
8312 Predictors of Mortality in Primary Hyperparathyroidism: Long-Term Follow Up
Authors: Gibb F W , Seckl J R , Reid L , Lyall M J
Published: October 2024

Disclosure: F.W. Gibb: None. J.R. Seckl: None. L. Reid: None. M.J. Lyall: None.

Background: Primary hyperparathyroidism has been associated with an increased risk of death and cardiovascular disease in observational studies. We have previously published associations between PTH concentration (and other potential explanatory variables) and mortality risk and now present results based on longer follow up duration. Methods: Retrospective cohort study of individuals (n = 611) presenting with PHPT between 2006 and 2014 to a University teaching hospital. Predictors of mortality were assessed by the Cox proportional hazard model. Results: Median age was 68 years (IQR 58 – 77) and 503/611 (82%) were female. Parathyroid surgery was performed in 274 (45%). Median duration of follow up was 12 years over which time 38% of the cohort died (n = 230). Results are subsequently presented for the total cohort and the subgroup (n = 337, 55%) who did not have parathyroid surgery. Total cohort Higher age at diagnosis (HR 1.09 per year, p <0.001), lower BMI (HR 0.97 per kg/m2, p = 0.037), greater socioeconomic deprivation (HR 0.6 for least deprived quintile, p = 0.01), higher serum creatinine (HR 1.01 per μM, p <0.001) and vitamin D deficiency (HR 1.58, p = 0.005) were all associated with mortality in univariate analysis. Adjusted calcium (HR 1.5 per mM, p = 0.101) and PTH at diagnosis (HR 1.002 per pM, p = 0.415) were not significantly associated with subsequent mortality. However, in a multivariate model, adjusted calcium was independently associated with mortality (HR 9.0 per mM, p < 0.001) whilst higher PTH was associated with a lower risk of death (HR 0.98 per pM, p = 0.012). No surgery cohort Adjusted calcium (HR 13.3 per mM, p < 0.001), PTH (HR 1.04 per pM, p <0.001), higher age at diagnosis (HR 1.07 per year, p <0.001), lower BMI (HR 0.96 per kg/m2, p = 0.012) and vitamin D deficiency (HR 1.4, p = 0.047) were all associated with mortality in univariate analysis. Socioeconomic deprivation (p = 0.218) and creatinine (p = 0.105) were not associated with mortality in the non-surgical subgroup. In multivariate analysis, higher age (p <0.001), higher adjusted calcium (p <0.001), lower BMI (p = 0.025) and socioeconomic deprivation (p = 0.049) were all independently associated with mortality but PTH was not (p = 0.745). Conclusions PTH concentration does not appear to be independently associated with mortality risk in people with PHPT. Plasma calcium concentration appears to be a more important association but can be affected by many factors which are independent of PHPT (e.g. concomitant medications, hydration status, delay in seeking medical attention etc.)

Presentation: 6/2/2024
8298 PrimaryHyperparathyroidism after Initiation of Burosumab in a Patient with X-linked Hypophosphatemic Rickets
Authors: Melhim Abdullah , Samarasinghe Shanika , Camacho Pauline
Published: October 2024

Disclosure: A. Melhim: None. S. Samarasinghe, MD: None. P. Camacho, MD: None.

Title: Primary Hyperparathyroidism after Initiation of Burosumab in a Patient with X-linked Hypophosphatemic Rickets Abdullah Melhim, MD; Shanika P Samarasinghe, MD; Pauline M. Camacho, MD FACE Introduction: X-linked hypophosphatemic rickets is an autosomal dominant disease that is characterized by high phosphate wasting at the proximal tubule resulting in slow growth, rickets and osteomalacia. It is usually associated with low serum phosphate, normal calcium, and either normal or modestly elevated levels of parathyroid hormone (PTH). We present a case of a male patient who developed primary hyperparathyroidism after initiation of Burosumab, a new monoclonal antibody directed against fibroblast growth factor 23 (FGF23). Clinical Case A 47-year-old man with a history of juvenile X-linked hypophosphatemic rickets and confirmed PHEX mutation presented to our clinic. He previously had normal to low-normal PTH levels, normal calcium and vitamin D levels with persistently low phosphorus, despite being on calcitriol and phosphate supplements. Patient was started on Burosumab on 7/2021 and 2 months later was noted to have rising PTH levels up to 104 pg/ml (14 – 67) with high normal calcium of 10.3 mg/dL (8.9 - 10.3), albumin of 4.5 gm/dL, vitamin D, 25- Hydroxy of 34 ng/ml (30 – 80) and low phosphorus of 1.9 mg/dL (2.5 - 4.7) consistent with primary hyperparathyroidism. Initially the patient was normocalcemic with high PTH but eventually developed frank hypercalcemia. After further discussion, the patient reported urinary frequency, constipation, and worsening fatigue, but denied any history of nephrolithiasis. Sestamibi scan completed on 8/2023 revealed increased uptake in a right inferior nodule suggestive of a parathyroid adenoma. He subsequently underwent subtotal parathyroidectomy on 11/2023 confirming enlarged hypercellular right superior and inferior and left inferior parathyroid glands. Few reports have described increasing PTH levels after prolonged anti-FGF23 treatment, however our patient started developing primary hyperparathyroidism only a few months after starting treatment. Some recent studies suggest that FGF23 and PTH could have an interdependent phosphaturic effect, this can explain the development of primary hyperparathyroidism in the setting of suppressed FGF23 levels with Burosumab. Conclusion: Burosumab is a new monoclonal antibody directed against FGF23 recently approved for patients with X-linked Hypophosphatemia (XLH). Burosumab use can result in primary hyperparathyroidism through a poorly understood mechanism, more studies are needed to better understand this relationship. Reference: Erik A Imel, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet 2019 Jun 15;393(10189):2416-2427.

Presentation: 6/1/2024
8690 Severe Hypocalcemia Following Treatment with Venetoclax for AML
Authors: Ruddiman Kathleen , Price Catherine
Published: October 2024

Disclosure: K. Ruddiman: None. C. Price: None.

Background: Venetoclax is a chemotherapeutic agent which has known side effects of tumor lysis syndrome, but few reports of isolated hypocalcemia. Clinical case: A 73 year old male with medical history pertinent for myeloproliferative and myelodysplastic disease was admitted for evaluation of failure to thrive. Workup revealed progression to acute myeloid leukemia. Following treatment with decitabine 34mg/day for 5 doses and initiation of venetoclax 100mg daily, he developed progressive, severe, symptomatic hypocalcemia with positive Trousseau and Chvostek sign. The patient was normocalcemic prior to admission with serum calcium ranging between 8.6-9.7mg/dL. Corrected calcium at admission was 8.8mg/dL. Serum calcium decreased steadily following venetoclax, requiring repletion with 3 doses of calcium chloride and gluconate 1gm IV and initiation of oral calcium carbonate 1900mg TID. At its nadir, corrected calcium was 6.1mg/dL on day 19 of treatment with venetoclax despite oral and IV repletion. Further workup showed undetectable 25 hydroxy vitamin D, PTH 62pg/mL, normal range uric acid, low phosphorus (lowest 2.2mg/dL), mild hypokalemia (lowest 3.2mg/dL), and mild hypomagnesemia of 1.8mg/dL. GFR was >90mL/min. Hypocalcemia improved after 3 infusions of calcium gluconate 10gm IV in 1 L normal saline to 7.2mg/dL. Oral repletion with calcium carbonate was transitioned to calcium citrate due to concomitant PPI use. PO calcium citrate titrated to 2850 mg TID to target corrected calcium 7.5 - 8.5 and limit further need for diuresis following calcium gluconate infusions. Ergocalciferol 50,000 IU was given thrice weekly in addition to daily cholecalciferol 5,000 IU with improvement in 25 hydroxy vitamin D to 17ng/mL. This patient was suspected to have multifactorial etiology for hypocalcemia, secondary to undetectable 25 hydroxy vitamin D as well as diuresis with furosemide during the admission, but the most strongly attributed factor was initiation of venetoclax prior to development of progressive hypocalcemia. FDA prescribing information reports hypocalcemia as a side effect of venetoclax when used in treatment for CML, but in phase 2 and 3 studies of venetoclax used alone and in combination with low dose cytarabine to treat AML, no significant episodes of hypocalcemia were reported. Tumor lysis syndrome (TLS) is a known adverse effect of venetoclax in which hypocalcemia is an expected feature, however, this patient did not have laboratory to support this diagnosis. His other electrolyte deficiencies were mild and transient. Conclusion: While electrolyte abnormalities associated with TLS are an expected side effect of venetoclax, isolated severe hypocalcemia is a rarely reported side effect. Calcium should be closely monitored during treatment.

Presentation: 6/1/2024
7073 Treasure or Terror: Dilemmas in the Management of a Giant Parathyroid Adenoma
Authors: Galia A d , De Guzman R , Suib - Salvilla S
Published: October 2024

Disclosure: A.D. Galia: None. R. De Guzman: None. S. Suib - Salvilla: None.

Background: Primary hyperparathyroidism is a common endocrine disorder with an incidence of 25 per 100,000 people in the general population. More commonly caused by parathyroid adenomas in 80-85%, giant parathyroid adenomas weighing more than 3.5 g or measuring more than 2 cm may rarely occur. There have been no reported prevalence data of parathyroid adenoma among ASEAN countries, especially in the Philippines. Clinical Case: A 43-year-old, female, Filipino, initially asymptomatic with anterior neck mass for 8 years then presented with generalized body malaise, easy fatigability, lower extremities pain and numbness. Six years ago, neck ultrasound showed left thyroid nodule; abdominal sonogram showed bilateral medullary nephrocalcinosis, with hypercalcemia, elevated intact PTH, and elevated creatinine. She was unable to undergo further workup and management until she presented a few months ago because of generalized body malaise, abdominal pain, nausea, and vomiting because of hypercalcemia and non-oliguric renal failure. Serum ionized calcium was 1.90 mmol/L (NV 1.15 - 1.30), intact PTH 2000 pg/mL, and serum creatinine 6.08 mg/dL. With unavailability of calcitonin and pamidronate, medical management of hypercalcemia included cautious hydration followed by diuresis, zoledronic acid, and cinacalcet. Sestamibi scan showed a large parathyroid adenoma. Bone densitometry showed osteoporosis (T score = below -2.5). After medical evaluation, she underwent parathyroidectomy under general anesthesia. Intact PTH level perioperatively were as follows: pre-op = 2,078.2 pg/mL; 30 mins = 477.1 pg/mL; 1 hour = 335.7 pg/mL, 1 day = 67.2 pg/mL. The resected mass was 4.2 x 2.4 x 1.6 cm and weighed 4 g; histopathology report was consistent with Parathyroid Adenoma. Post-operatively, patient did not develop hungry bone syndrome. Conclusion: Giant parathyroid adenoma is a rare condition that is usually asymptomatic but can lead to serious complications. In the Philippines, limited availability of laboratory techniques (PTH and sestamibi scan) and availability of medications for hypercalcemia may contribute to underdiagnosis and management. Early detection and treatment can help prevent further complications and improve the overall quality of life.

Presentation: 6/3/2024
5117 Unusual Sarcoid Presentation as a Case of Hypercalcemia
Authors: Salim Michael , Chauhan Aditya , Avula Sreekant , Ahmed Ammar , Zekarias Kidmealem
Published: October 2024

Disclosure: M. Salim: None. A. Chauhan: None. S. Avula: None. A. Ahmed: None. K. Zekarias: None.

Background: Hypercalcemia may arise from a variety of causes and can pose challenging diagnostic dilemma. Clinical Case: An 89-year-old male presented with worsening malaise related to persistent hypercalcemia. He reported productive cough, polyuria, polydipsia, generalized muscle weakness and weight loss. Physical exam was remarkable for upper and lower extremities weakness. Laboratory tests showed calcium 11.6 (8.8-10.2 mg/dL), phosphorus 2.8 mg/dL (2.5-4.5 mg/dL), albumin 4.2 g/dL (3.5-5.2 g/dL), parathyroid hormone (PTH) 10 pg/mL (15-65 pg/mL), parathyroid hormone-related protein (PTH-rp) 4.5 pmol/L (0.0-2.3 pmol/L), TSH 6.24 (0.30 - 4.20 uIU/mL), free T4 1.10 ng/dL (0.90-1.70 ng/dL), GFR 61 mL/min/1.73m2, 25 OH Vit D 31 ng/mL (20-75 ng/mL), vit D 1,25-dihydroxy 134 pg/mL (19.9-79.3 pg/mL), calcium urine/creatinine 0.54. Hypercalcemia was first noted 11 months before the visit with a level of 14.0 mg/dL (8.8-10.2 mg/dL), phosphorus 3.5 mg/dL, PTH 11, PTH-rp 1.4 pmol/L, 25 OH Vit D 62 ng/mL, Vit D 1,25-dihydroxy 90 pg/mL, angiotensin-1-converting enzyme 12 U/L (16-85 U/L), serum and urine electrophoresis showed no monoclonal gammopathy present, and tuberculosis interferon-gamma test negative. Autoimmune workup was unremarkable, except for weak positive anti-signal recognition particle (SRP) antibodies and anti-Mi-2 antibodies. CT chest/pelvis/abdomen demonstrated peripheral predominant reticular opacities suggestive of interstitial lung disease and no malignant findings. Treatment history included zoledronic acid 11 months before the visit. The patient was referred for a granulomatous disease workup.Upon one month follow-up, the hypercalcemia symptoms were worsening. Repeat calcium was 12.3 mg/dL and fungal serologies were negative. The patient was started on prednisone empirically. PET CT was ordered and revealed patchy inflamed musculature of extremities suspicious of dermatomyositis/polymyositis. Further labs showed unremarkable myomarker panel, u3-Hydroxy-3-Methylglutaryl Coenzyme A reductase (HMGCR) antibody, Anti-cN-1A antibody, ACE 53 U/L, creatine kinase 32 U/L (39-309 U/L), aldolase 5.4 U/L (1.2-7.6 U/L), soluble IL-2R 1,021 U/mL (137-838 U/mL), and lysozyme 3.89 ug/mL (<2.75 ug/mL). A muscle biopsy was done, which showed benign skeletal muscle with patchy myofiber atrophy, patchy interstitial fibrosis, and focal interstitial mild chronic inflammation with no evidence of sarcoid granulomas in the sample. One week lab follow-up post initiation of steroid showed calcium of 10.1 mg/dL and subsequently improvement in his overall labs. Working diagnosis of sarcoid myositis was made. Conclusion: This case report highlights the approach of diagnosing a rare case of hypercalcemia due to sarcoid myositis. In a highly clinical suspicious patient, PET CT scan might be a necessary modality for diagnosis.

Presentation: 6/2/2024
8216 When calcium makes you breathless, exploring hypocalcemia-induced bronchospasm
Authors: Nikita Pereira Kristal , Sundaram Vignesh , Sai Sreemantula Harsha
Published: October 2024

Disclosure: K.N. Pereira: None. V. Sundaram: None. H.S. Sreemantula: None.

When calcium makes you breathless, exploring hypocalcemia-induced bronchospasm Hypocalcemia, characterized by low levels of serum calcium, is an uncommon yet potentially life-threatening condition with various clinical manifestations. This case report delves into an unusual manifestation of hypocalcemia-induced bronchospasm in a 54-year-old male with an extensive medical history, including chronic kidney disease, insulin-dependent type 2 diabetes mellitus, hypertension, hyperlipidemia, ascending aortic aneurysm and hyperthyroidism. Despite multiple interventions in the emergency department like nebulized bronchodilators and intravenous steroids, his 4 day misery of respiratory distress persisted. Physical exam was notable for tachypnea, audible wheezing, and accessory muscle use for respiration. Work up was negative for infectious and pulmonary causes including asthma or chronic obstructive pulmonary disease. However, his laboratory results unveiled severe hypocalcemia (calcium: 5.7 mg/dL), elevated creatinine (Cr: 5.90), and blood urea nitrogen (BUN: 64), profound vitamin D deficiency with a 25-OH vitamin D level below 7 and elevated parathyroid hormone (PTH- 375.7). He was ultimately diagnosed with hypocalcemia-induced bronchospasm as intravenous calcium gluconate administration led to gradual respiratory improvement. This case highlights the necessity of considering hypocalcemia-induced bronchospasm in respiratory distress differentials, even in patients with concurrent asthma or COPD histories. The rarity of this presentation, coupled with the patient's complex medical history, underscores diagnostic challenges, necessitating a high index of suspicion. Timely hypocalcemia assessment and calcium replenishment are vital in averting mortality linked to this unusual manifestation. Clinicians must exercise caution to prevent misinterpreting symptoms as asthma or COPD exacerbation, as this could lead to potentially fatal outcomes.

Presentation: 6/1/2024
9324 X-Linked Hypophosphatemic Rickets (XLH): Experience Argentina
Authors: Giacoia E , Cantó A C , Balonga M C
Published: October 2024

Disclosure: E. Giacoia: Research Investigator; Self; Ultragenyx. A.C. Cantó: Research Investigator; Self; Ultragenyx. M.C. Balonga: Research Investigator; Self; Ultragenyx.

Introduction: XLH is a genetic disease characterized by rickets and osteomalacia caused by pathogenic variants in PHEX with disruptions in bone mineral homeostasis. In adults, the deformities described in childhood persist, in addition to osteomalacia, pain, stiffness, enthesopathies, arthrosis, delayed fracture consolidation and hypoacusia1,2.Objective: To describe the clinical, biochemical characteristics and complications such as kidney stones, hypoacusia, enthesopathy and type of mutation (isolated or familiar).Materials and methods: Descriptive and analytical study. 10 patients diagnosed with XLH were analyzed and evaluated from January to December 2023. Laboratory samples and complementary studies were carried out. The PHEX gene mutation was searched. Informed consents were obtained. Results: P: Phosphate, Ca: Calcium, 25OHD: Vitamin D3/10 patients had kidney stones, 4/10 hypoacusia, 4/10 enthesopathies.3/10 were de novo mutations and rest were familial.Conclusions: We observed a tendency towards hypophosphatemia and slightly increased PTH values. We consider that the experience acquired through follow-up consultations is the best tool to advance medical knowledge and thus achieve early diagnosis, access to medical treatment and multidisciplinary teamwork for improving the quality and survival of life of patients with this rare disease. Reference: (1) Juan Guillermo Cardenas-Aguilera et al. Expert Consensus on evidence-based recommedations for the diagnosis, treatment, and follow-up of X-linked hypophosfatemic rickets (XLH). Revista colombiana de nefrología, vol 11, number 1, marzo 20242. Andrea Trombetti et al. Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia. Nat Rev Endocrinol. 2022 Jun;18(6):366-384.

Presentation: 6/1/2024
8449 A Chronic Treatment of Interleukin-12 Restores Diet-Induced Hepatic Insulin Resistance and Liver Fibrosis in Mice with Interferon-gamma Signaling Deficient Macrophages
Authors: Devarakonda Rao Suryateja , Kim Boyeon , Kyung Kim Bu , Kasina Kaushal , Narouz Emily , Tauer Lauren A , Hu Xiaodi , Kim Jason K
Published: October 2024

Disclosure: S.D. Rao: None. B. Kim: None. B. Kim: None. K. Kasina: None. E. Narouz: None. L.A. Tauer: None. X. Hu: None. J.K. Kim: Advisory Board Member; Self; Elevian.

Inflammation and insulin resistance play a major role in metabolic dysfunction-associated steatotic liver disease, and macrophages and their release of cytokines modulate the underlying pathogenesis. We have recently found that mice with interferon-γ (IFNγ) signaling-deficient macrophages (Lyz-IFNγR2 KO) are protected from diet-induced insulin resistance in the liver and further rescued from developing liver fibrosis following NASH diets. Here, we examined the role of interleukin-12 (IL-12) as a macrophage-derived pro-inflammatory cytokine mediating the effects of macrophage IFNγ signaling on liver pathology. Mouse recombinant IL-12 (0.05 ng/hour/g body weight) was chronically administered via subcutaneously implanted osmotic pumps for 2 weeks in male Lyz-IFNγR2 KO and wild-type (WT) mice after 10 weeks of a high-fat diet (HFD) (n=3∼4/group). A 2-hour hyperinsulinemic-euglycemic clamp with 3H-glucose and [1]4C-2-deoxyglucose was performed to measure insulin action and glucose metabolism in mice. A chronic IL-12 treatment caused hyperglycemia (179±15 mg/dl) and insulin resistance in the liver with 30.6±15.7% suppression of hepatic glucose production (HGP) during insulin clamps in HFD-fed WT mice. IL-12 treatment also restored hyperglycemia and hepatic insulin resistance in HFD-fed Lyz-IFNγR2 KO mice with 45.3±21.2% suppression of HGP during insulin clamps. This is in stark contrast to euglycemia (145±5 mg/dl) and 77.3±9.7% suppression of HGP during insulin clamps in HFD-fed Lyz-IFNγR2 KO mice that were protected from diet-induced insulin resistance in the liver. Next, mouse recombinant IL-12 was chronically administered for 2 weeks in male Lyz-IFNγR2 KO and WT mice after 8 weeks of a Gubra Amylin NASH (GAN) diet (n=4∼6/group). Using a 3D-ultrasound imaging system, we found that IL12-treated WT mice developed fatty liver (54.3±3.9 counts in brightness) and fibrosis (4.8±0.4 kPa in Young’s Modulus) after the GAN diet. Similarly, IL12-treated Lyz-IFNγR2 KO mice developed fatty liver (53.8±7.7 counts) and fibrosis (4.9±0.7 kPa) after the GAN diet. Histological analysis of liver samples from both groups of mice further confirmed fibrosis and lipid droplets after IL-12 treatment. Overall, these results showed that a chronic IL-12 treatment restored diet-induced hepatic insulin resistance and liver fibrosis after GAN diet in Lyz-IFNγR2 KO mice, indicating a critical role for IL-12 as a macrophage-derived cytokine and downstream effector of IFNγ signaling in mediating metabolic liver disease.

Presentation: 6/1/2024
6568 A Novel Case of Liddle Syndrome in Siblings: Insights into a Rare Genetic Mutation
Authors: Humrickhouse Ashley B , Peltsverger Maya
Published: October 2024

Disclosure: A.B. Humrickhouse: None. M. Peltsverger: None.

Introduction: Liddle syndrome (LS) is an inherited form of hypertension caused by a mutation in the epithelialsodium channel (ENaC). This condition is characterized by hypertension (HTN), hypokalemia,hyporeninemia, and metabolic alkalosis, although clinical presentation can vary. Asymptomaticearly-onset HTN is common, and if left undiagnosed, it can lead to advanced renal disease,cardiovascular complications, stroke, and even sudden death. Treatment typically involves theadministration of ENaC blockers such as amiloride and triamterene. We present a novel case ofLS in two siblings resulting from a missense mutation in the SCNN1B gene. Case Presentation: The patient is a 24-year-old Hispanic female who presented for evaluation of poorly controlledHTN and severe hypokalemia of 2.9 mmol/L during the first trimester of pregnancy. She wasdiagnosed with HTN at age eighteen. The family history was notable for resistant HTN in herfather and younger brother. Biochemical evaluation revealed normal plasma-free metanephrinesand 24-hour urine-free cortisol. Low plasma renin activity (0.530 ng/mL/hr) and aldosterone(<1.0 ng/dL) were detected on multiple tests. The urine-free cortisol-to-cortisone ratio was <0.5,excluding the diagnosis of apparent mineralocorticoid excess syndrome. The diagnosis of LS wasconfirmed by genetic analysis, which identified a novel heterozygous mutation, c.1859 A>G(Tyr620Cys), in the SCNN1B gene, which had not been reported in the literature to date. Thesame mutation was identified in her brother. The patient was treated with a high dose ofamiloride (15 mg daily), which controlled her HTN and hypokalemia throughout her pregnancy. Discussion: LS is an autosomal dominant disorder with genetic heterogeneity. It is characterized by HTN,low plasma aldosterone and renin activity, and increased potassium excretion. This leads tohypokalemia and metabolic alkalosis. LS is caused by germline mutations found in theSCNN1A, SCNN1B, and SCNN1G genes, which encode the alpha, beta, and gamma subunits ofthe ENaC channel. These mutations lead to enhanced sodium reabsorption in the kidneys,independent of aldosterone. Our patient was diagnosed with hypertension at the age of 18.However, the diagnosis of LS was not made until six years later when she presented during herfirst trimester of pregnancy. Treatment with amiloride effectively controlled her hypertension andhypokalemia, which allowed her to deliver a healthy child. Amiloride was also prescribed for thepatient's brother. A combination of biochemical analysis and genetic testing enables a betterunderstanding of the various clinical presentations, ensuring appropriate treatment andprevention of end-organ damage. Genetic counseling is essential for families affected by LS.

Presentation: 6/1/2024
12355 An Adolescent Female With Congenital Lipodystrophy Presenting With Repeated Acute Metabolic Decompensations Rescued By A Novel Leptin Receptor Agonist
Authors: Chambers D M , Chan Y M , Crocker M K
Published: October 2024

Disclosure: D.M. Chambers: None. Y. Chan: None. M.K. Crocker: None.

Patient SH is a now 17-year-old female treated for generalized congenital lipodystrophy with a course complicated by severe hypertriglyceridemia, type 2 diabetes mellitus, hypertension, hepatosteatosis, and intermittent menstrual irregularity. She had been managed successfully with metreleptin for 2 years, but in 2022-2023, she developed repeated episodes of pancreatitis (4 times over a 14-month period) secondary to severe hypertriglyceridemia (serum triglycerides >8000 mg/dL). During her admissions, she had markedly increased insulin requirements (up to 12 units/kg/day) with refractory hyperglycemia despite maximal treatment with metreleptin, empagliflozin, and oral semaglutide. In the clinical context of her acute metabolic worsening, she was suspected of having a neutralizing antibody against metreleptin. Serum leptin was undetectable 1 hour after observed metreleptin doses; direct measurement of neutralizing antibodies is pending. She was transitioned from metreleptin to mibavademab, an investigational leptin receptor agonist, on an expanded use IND. She subsequently experienced significant improvements in her fasting triglyceride levels (<300 mg/dL) with no subsequent episodes of pancreatitis since starting therapy in August 2023. She has also had improvements in other aspects of her metabolic health including decreased insulin requirements with decreasing hemoglobin A1c, decreased need for adjunctive lipid and hypertension therapy, and improving menstrual regularity. Her clinical course demonstrates: 1) clinical indicators of a rare but serious loss of efficacy of metreleptin therapy; 2) adjunctive options for management of generalized lipodystrophy; and, 3) an individual experience with a novel leptin agonist therapy in the treatment of generalized lipodystrophy.

Presentation: 6/3/2024
7454 Angiotensin AT1 Receptor Type 1 (AT1) Autoantibodies In Patients with Primary Aldosteronism
Authors: Waraich Jotinder K , Kline Gregory , Choi May Y , Jeremy Sigal Ronald , Caughlin Cori , Przybojewski Stefan J , Leung Alexander
Published: October 2024

Disclosure: J.K. Waraich: None. G. Kline: None. M.Y. Choi: None. R.J. Sigal: None. C. Caughlin: None. S.J. Przybojewski: None. A. Leung: None.

Background: Primary aldosteronism (PA) is a condition characterized by excessive aldosterone secretion, and accounts for at least 10% - 20% of all cases of hypertension. Determination of PA subtype (i.e., unilateral vs. bilateral aldosterone hypersecretion) is clinically important to inform targeted treatment. We hypothesized that pathogenesis of PA is immune-mediated and autoantibodies to angiotensin receptor type 1 (AT1) may determine PA subtype. Aims: The aim of this study was to examine whether AT1 autoantibodies predict PA subtype. Methods: We conducted a cross-sectional study of patients with PA who were referred for adrenal vein sampling (AVS) for subtyping. AT1 autoantibody titres were measured using an enzyme-linked immunosorbent assay. AT1 antibodies were defined as present when the titre was >17 U/mL, negative if <10 U/mL, and indeterminate if between 10-17 U/mL. AVS was used as a gold standard to determine lateralization and PA . The frequency of positive AT1 autoantibodies was determined according to PA subtype and clinical predictors of lateralization. Baseline patient characteristics were reported as means (and standard deviations) for normally distributed variables, and medians (and interquartile ranges) for non-normally distributed variables. Fisher’s exact test was performed for categorical variables and Kruskal-Wallis test for continuous variables. Results: 54 patients had successful cannulation of both adrenal veins (mean age, 52.7 years; 46.3% male; mean body mass index, 31.2 kg/m2). AT1 antibodies were detected in 14 (25.9%) of the patients, absent in 32 (59.3%), and indeterminate in 8 (14.8%). Among the 25 patients with unilateral PA, 8 (32.0%) had positive AT1 antibodies, 15 (60.0%) negative, and 2 (8.0%) indeterminate. Similarly, among the 29 patients with bilateral PA, 6 (20.7%) had positive AT1 antibodies, 17 (58.6%) negative, and 6 (20.7%) indeterminate. There was no significant association detected between AT1 antibody status and lateralization (p=0.39). There were no associations between AT1 autoantibody status and any of the clinical factors traditionally predictive of PA, including sex (p=0.94), older age (p=0.76), hypokalemia (p=0.91), higher estimated glomerular filtration rate (p=0.46), or magnitude of aldosterone-to-renin ratio elevation (p=0.58). There was also no association between AT1 titres and these factors. Conclusion: AT1 autoantibodies are common in patients with PA; over a quarter of patients who underwent AVS in our study. Although they were not predictive of PA subtype, these results may still suggest that PA is immune-mediated. Future studies comparing AT1 autoantibodies in PA to other controls are underway.

Presentation: 6/1/2024
6649 Associations of Fibroscan Results with Body Composition and Laboratory Measures in Patients with Obesity and Inflammation
Authors: Lyman Alexa , Nwosu Ejike , Gopalakrishna Harish K , Rotman Yaron , Abdul Majeed Nehna , Lazareva Julia , Brady Sheila M , Paul Demidowich Andrew , Adam Yanovski Jack
Published: October 2024

Disclosure: A. Lyman: None. E. Nwosu: None. H.K. Gopalakrishna: None. Y. Rotman: None. N. Abdul Majeed: None. J. Lazareva: None. S.M. Brady: None. A.P. Demidowich: Grant Recipient; Self; Dexcom, Inc. J.A. Yanovski: Grant Recipient; Self; Soleno Therapeutics (DCCR), Rhythm Pharmaceuticals (setmelanotide), Hikma Pharmaceuticals (colchicine), Versanis Bio (bimagrumab.

Background: Obesity and inflammation are believed to contribute to hepatic dysfunction and risk for metabolic dysfunction-associated steatohepatitis (MASH). Fibroscan (Echosens) can non-invasively quantify liver fat content (LFC) by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by transient elastography as a surrogate for fibrosis. Other surrogate markers for liver fibrosis include Fibrosis-4 (FIB-4) and the AST-to-Platelet Ratio Index (APRI) indices. Central obesity is a stronger predictor of MASH than appendicular fat. It is unknown whether the associations between these measures hold in a population with obesity and inflammation. Hypotheses: We hypothesized that LFC and LSM would be positively associated with Body Mass Index (BMI), central obesity (trunk), but not appendicular fat percentage, as well as with HOMA-IR, hs-CRP, and both FIB-4 and APRI indices in patients with obesity and inflammation. Methods: A convenience sample of adult participants with BMI ≥30 kg/m2 and hs-CRP ≥2.0 mg/L in a clinical trial (n=38) underwent body composition by DXA, Fibroscan, and fasting blood sampling for glucose, insulin, hs-CRP, AST, ALT, and platelets, all on the same day. LSM results were considered valid if the interquartile range for > 10 measurements was ≤30%. ANCOVA analysis was used to examine associations between these parameters. Results: The cohort had a mean age=48 years (SD=12.5 years), BMI=39.3 kg/m2 (SD=6.0 kg/m2,), CAP=296.0 dB/m (SD=54.0 dB/m), LSM=5.9 kPa (SD=2.4 kPa), hs-CRP=7.2 mg/L (SD=6.1 mg/L), HOMA-IR=5.9 (SD=4.5), FIB-4=0.80 (SD=0.33), and APRI=0.24 (SD=0.11). Using univariate linear regression analysis, we found CAP to be positively associated with increased trunk body fat % (p=0.009, partial η2=0.202) and BMI (p=0.006, partial η2=0.195) independent of sex. Similarly, LSM was positively correlated with increased trunk body fat % (p=0.047, partial η2=0.125), APRI (p=0.025, partial η2=0.156), and log-transformed HOMA-IR (p=0.018, partial η2=0.150). We did not observe significant associations between hs-CRP, FIB-4 or appendicular body fat % with CAP or LSM in our population. Conclusion: As hypothesized, measures of liver fat content and fibrosis by Fibroscan CAP and LSM were positively associated with body composition (predominantly trunkal fat), measures of insulin resistance, and laboratory indices of hepatic fibrosis and steatosis in people with obesity and inflammation.

Presentation: 6/3/2024
7834 Case Series using intravenous insulin to treat Severe Hypertriglyceridemia
Authors: Khan Farooq , Eltayeb Musab , Ryan James , Murphy Matthew
Published: October 2024

Disclosure: F. Khan: None. M. Eltayeb: None. J. Ryan: None. M. Murphy: None.

Background: Very severe hypertriglyceridemia (>22.4 mmol/L) is associated with high risk of acute pancreatitis and atherosclerotic cardiac events. Conventional treatments tend not to yield immediate results. There is a lack of clinical guidelines for acute very severe HTG; and potential therapeutic options such as insulin, heparin, plasmapheresis, and octreotide have been tested and shown to be effective. We present a series of four cases where intravenous insulin was useful as an emergency treatment for severe HTG. Clinical Cases: Case 1: 48-year-old male was admitted with very severe hypertriglyceridemia with triglycerides levels of 45.3mmol/L (reference range: 0-1.7 mmol/L), new diagnosis Diabetes Mellitus with ketosis and was started on intravenous insulin. After three days of intravenous insulin, triglyceride levels reduced by 47.93%. Case 2: 28-year-old male, admitted with acute pancreatitis secondary to very severe hypertriglyceridemia (66.9mmol/L), a new diagnosis of Diabetes Mellitus with ketosis, was commenced on intravenous insulin. There was a reduction in triglycerides by 77.5% in 3 days and 96.6% in 9 days with intravenous insulin treatment. Case 3: 29-year-old female, admitted with new diagnosis Diabetes Mellitus with ketosis and very severe hypertriglyceridemia (50.67mmol/L) was treated with intravenous insulin. Total triglyceride reduction was 65.8% in 48 hours. Case 4: 27-year-old female, admitted Diabetic Ketoacidosis (DKA), new diagnosis Diabetes Mellitus, very severe hypertriglyceridemia (24.3mmol/L) was treated with intravenous insulin. 65.8% reduction in triglycerides was seen in after 72 hours. Conclusion: These cases show the efficacy of insulin infusion with encouraging results, especially when plasmapheresis is not readily available however larger studies including a randomized controlled trials is needed to confirm the efficacy and safety for the use of intravenous insulin to establish a universal and effective treatment for this severe life-threatening metabolic disorder. Reference: Simha V. Management of hypertriglyceridemia BMJ 2020; 371 :m3109 doi:10.1136/bmj.m3109

Presentation: 6/3/2024