High Calcium Research Articles

Sex-Specific Impact of Serum Calcium Levels on Acute Coronary Syndrome Risk: A 19-Year Cohort Study in Korea.

Background: This study aims to investigate the association between serum calcium levels and acute coronary syndrome (ACS) risk, examining whether this relationship differs by sex, given the known differences in calcium metabolism and hormonal influences between males and females. Methods: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were serum calcium level and sex. The incidence of ACS served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction effect of calcium level and sex on ACS incidence. Results: After adjusting for confounding variables, high calcium intake did not significantly increase ACS incidence, with a hazard ratio (HR) of 1.07 (95% CI: 0.90-1.26). There was also no significant difference in ACS risk between females and males (HR: 0.81, 95% CI: 0.61-1.04). However, interaction effect analysis revealed that higher calcium levels were associated with an increased risk of ACS only in females (HR: 1.24, 95% CI: 1.07-1.58), whereas the association in males was not statistically significant (HR: 0.90, 95% CI: 0.71-1.15). Conclusion: Our study results indicate that elevated serum calcium levels alone did not independently increase the risk of ACS; however, high serum calcium levels were associated with an increased risk of ACS in females but not in males, underscoring the importance of sex-specific factors in assessing and managing ACS risk and highlighting the necessity for personalized medical approaches to improve cardiovascular health outcomes for women.

Histone deacetylase 9 promotes osteogenic trans-differentiation of vascular smooth muscle cells via ferroptosis in chronic kidney disease vascular calcification.

Vascular calcification, a common complication of chronic kidney disease (CKD), remains an unmet therapeutic challenge. The trans-differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells is crucial in the pathogenesis of vascular calcification in CKD. Despite ferroptosis promotes vascular calcification in CKD, the upstream or downstream regulatory mechanisms involved remains unclear. In this study, we aimed to investigate the regulatory mechanism involved in ferroptosis in CKD vascular calcification. Transcriptome sequencing revealed a potential relationship between HDAC9 and ferroptosis in CKD vascular calcification. Subsequently, we observed increased expression of HDAC9 in calcified arteries of patients undergoing hemodialysis and in a rat model of CKD. We further demonstrated that knockout of HDAC9 attenuates osteogenic trans-differentiation and ferroptosis in VSMCs stimulated by high calcium and phosphorus. In addition, RSL3 exacerbated ferroptosis and osteogenic trans-differentiation of VSMCs exposed to high levels of calcium and phosphorus, and these effects were suppressed to some extent by HDAC9 knockout. In summary, our findings suggest that HDAC9 promotes VSMCs osteogenic trans-differentiation involving ferroptosis, providing new insights for the therapy of CKD vascular calcification.

Complex Coacervates: From Polyelectrolyte Solutions to Multifunctional Hydrogels for Bioinspired Crystallization

Hydrogels represent multifarious functional materials due to their diverse ranges of applicability and physicochemical properties. The complex coacervation of polyacrylate and calcium ions or polyamines with phosphates has been uncovered to be a fascinating approach to synthesizing of multifunctional physically crosslinked hydrogels. To obtain this wide range of properties, the synthesis pathway is of great importance. For this purpose, we investigated the entire mechanism of calcium/polyacrylate, as well as phosphate/polyamine coacervation, starting from early dynamic ion complexation by the polymers, through the determination of the phase boundary and droplet formation, up to the growth and formation of thermodynamically stable macroscopic coacervate hydrogels. By varying the synthesis procedure, injectable hydrogels, as well as plastic coacervates, are presented, which cover a viscosity range of three orders of magnitude. Furthermore, the high calcium content of the calcium/polyacrylate coacervate (~19 wt.%) enables the usage of those coacervates as an ions reservoir for the formation of amorphous and crystalline calcium-containing salts like calcium carbonates and calcium phosphates. The exceptional properties of the coacervates obtained here, such as thermodynamic stability, viscosity/plasticity, resistance to acids, and adhesive strength, combined with the straightforward synthesis and the character of an ions reservoir, open a promising field of bioinspired composite materials for osteology and dentistry.

The negative electrostatic potential of the coordination between calcium and carboxyl/oxygen group in calcium-peptide complexes contributes to calcium utilization

The coordination electrostatic potential has significantly influenced the binding energy of calcium-peptide coordination complexes. However, its impact on calcium bioavailability is unclear. A calcium-binding peptide (CBP) DEDEQIPSHPPR, purified from soybean yogurt was selected. The study selected tetrapeptide residues of acidic amino acids that play an important role in CBP and designed sixteen tetrapeptides rich in carboxyl oxygen atoms to investigate the influence of electrostatic potential on calcium-peptide binding. The results indicated that DEDE exhibited the strongest binding energy (−375.27 kcal/mol) and binding capacity (464.11 ± 2.14 mg/g) with calcium ions compared to other peptides. Moreover, DEDE also increased intracellular calcium concentration the most, being 2.04 times higher than CaCl2. Calcium ions coordinated with carboxyl oxygen atoms possessing negative electrostatic potential, which correlated positively with the bioavailability of calcium ions. This electrostatic potential analysis provides a theoretical basis for developing and screening bioactive peptides with high calcium bioavailability.

Case Report: Hypercalcemia and Acute Kidney Injury Associated with Disseminated Paracoccidioidomycosis

Paracoccidioidomycosis is an acute to chronic systemic mycosis caused by the fungi Paracoccidioides. Hypercalcemia is a rare and not fully understood presentation of this infection. We present a case report of paracoccidioidomycosis associated with hypercalcemia and acute kidney injury (AKI) in an immunocompetent patient. An immunocompetent 30-year-old man from Brazil presented with papular erythematous-violaceous skin lesions, disseminated lymphadenopathy, pain in the left hypochondrium, fever with night sweats, and loss of 25 kilograms in 5 months. The result of a biopsy of the lesions was positive for Paracoccidioides brasiliensis. Laboratory findings were high total calcium and 1,25-dihydroxy vitamin D, with low parathyroid hormone, low albumin, and AKI. Computed tomography scans revealed splenic infarcts without bone lesions. Treatment was performed with methylprednisolone and liposomal amphotericin B. Calcium levels and kidney function normalized within 20 days of hospitalization. The patient was discharged 49 days after admission. A follow-up 6 months later revealed total clinical and serological remission.

Impact of ultra-high-resolution on cardiac CT assessment of coronary artery stenoses, plaque burden/composition, and pericoronary adipose tissue attenuation

Abstract Background Conventional coronary computed tomography angiography (CCTA) overestimates stenoses within stents and calcified arteries due to "blooming" artifacts. Ultra-high-resolution coronary CT (UHR-CT) may overcome this limitation because of higher spatial resolution. Purpose To investigate differences in coronary arterial lumen volume, stenosis severity, and plaque composition, between CCTA and UHRCT in patients with stents and/or high coronary calcium scores. Methods As part of a prospective pilot study, 14 patients referred for invasive coronary angiography for evaluation of obstructive CAD underwent UHRCT (Canon Precision, 160 x 0.25mm slices) prior to catheterization. Images of identical cardiac phases were reconstructed in two badges for comparison: 1) Ultra-high resolution using a 1,024 x 1,024 matrix, 0.25 mm, and 2) conventional resolution with a 524 x 524 matrix, 0.5 mm. All images were reconstructed using iterative reconstruction algorithm (AIDR 3D) and a sharp kernel (FC05). For the left main and three coronary arteries, an automated contour analysis using a dedicated software (QAngioCT RE 3.2, Medis, Netherlands) was performed to compare conventional CCTA vs. UHR-CT resolution images across common vascular and plaque metrics, including lumen and vessel volume, plaque burden/volume, plaque composition based upon predefined fixed intensity cut-off values of CT attenuation, minimal and maximal plaque thickness, pericoronary adipose tissue attenuation (PCAT), minimal lumen area and diameter, and diameter stenosis. All lumen and vessel contours were generated by the software, without manual editing. The segment model proposed by the SCCT was used as reference and the lesions classified as greater than 25% stenosis by visual assessment were recorded. The quality of the images was subjectively assessed using a 5-point Likert scale. Vessel segments with scores 1 (severe artifacts) and 2 (pronounced artifacts) were not included in the analysis. Results The mean patient age was 68.5 years (±6.8), 2 were female (14.3%), 6 patients had stents (11 stented segments) and the mean Agatston score was 947.6 (±449) among the 8 non-stented patients. A total of 56 vessels, 133 segments, and 57 lesions were analyzed. Eight segments (6%) were excluded from the analysis due to poor quality. Results on a per segment and per lesion basis were summarized in the table. The mean PCAT value was significantly lower for the UHRCT images compared to NR reconstruction in both segment (p<0.001) and lesion based (p=0.002) analyses. Plaque differentiation varied by UHRCT resulted in a lower fibrous plaque volumes but higher necrotic (low attenuation) plaque volumes. Conclusions Ultra-high-resolution CT image analysis results in significantly different coronary artery plaque volume and PCAT assessment vs. conventional resolution CCTA. These findings have implications for evaluating high-risk plaque features and perivascular inflammation in patients.Table 1

Assessment of safety, efficacy and learning curve of intravascular lithotripsy in real world practice within a high volume calcium modification centre

Abstract Background There has been a rapid uptake in the use of intravascular lithotripsy (IVL) for calcium modification during percutaneous coronary intervention (PCI) due to its ease of use and excellent safety profile, particularly when compared to atherectomy devices. Purpose To review the adoption and safety of IVL in a high volume centre with established use of alternative calcium modification techniques Methods This was a retrospective analysis of all patients undergoing PCI from the introduction of IVL in January 2019 until December 2023. Patient demographics, comorbidity, procedure details and procedural complications were compared between IVL and non-IVL cases. Line charts were created to demonstrate the uptake and use of IVL per quarter compared with other established calcium modification strategies. A further line chart was created to compare the frequency of IVL use per quarter in more complex cases (left main intervention, ST elevation, treatment of in stent restenosis and in combination with rotational/orbital atherectomy). Results In the analysis timeframe there were 7,843 PCI cases performed, of which there were 301 IVL cases, 263 rotational/orbital atherectomy cases and 77 excimer laser atherectomy. IVL cases were older, more likely to have previous revascularisation (PCI (40.8% vs 57.1 % (p<0.001)) or bypass grafts 4.8% vs 8.0% (p=0.012)), diabetes mellitus (22.7% vs 33.6% (p<0.001)) and hypertension (45.4% vs 56.5% (p<0.001)). From a procedural perspective, treatment of left main and restenosis were more common with IVL compared with the rest of the cohort (7.0% vs 27.6% (p<0.001) and 8.3% vs 28.9% (p<0.001) respectively). IVL cases were more frequently guided by intracoronary imaging (intravascular ultrasound 35.9% vs 70.4% (p<0.001), optical coherence tomography 3.7% vs 18.9% (p<0.001)). Atherectomy was more frequent in IVL cases (excimer laser atherectomy 0.7% vs 7.3% (p<0.001) and rotational/orbital atherectomy 2.6% vs 22.9% (p<0.001)). Figure 1 shows the frequency of IVL use compared with other established calcium modification strategies per quarter and demonstrates the rapid and sustained uptake in IVL usage. Interestingly the use of other atherectomy techniques does not appear to have reduced. Figure 2 shows that IVL was quickly utilised in more complex calcification cases and again this has remained consistent since the introduction. Both figures demonstrate the short learning curve associated with IVL. Finally, there was no significant increase in perforation or slow/no reflow with IVL use (0.5% vs 0.7% (p=0.647) and 1.1% vs 1.3% (p=0.675) respectively) consistent with the published literature. There was an increase in documented coronary dissection with uncertain impact (3.4% vs 6.5% p=0.017). Conclusions IVL has become an essential tool within the calcium modification algorithm as a result of its ease of use, efficacy and excellent safety profile.Calcium modification per quarterFrequency of complex IVL cases

Extremely rare coronary anomaly as cause of palpitations. A case report of single right coronary artery - multimodality imaging and its impact on treatment decisions

Abstract Background We report the case of a white caucasian 63-year-old patient admitted to the clinic because of atypical angina and palpitations. Other comorbidities included hypertension, hyperuricemia and hypercholesterolaemia. He was admitted to a tertiary cardiac centre for deepened diagnostics of his complaints. Case summary Echocardiography revealed no pathology, but due to high Calcium Score (Agatston > 400 units), signs of arrhythmia during exercise and atypical angina complaints further investigations were performed. Invasive coronary angiography revealed stenosis up to 53% in the middle part of the right coronary artery and computed tomography angiography showed no left coronary artery, only malignant-coursed vessel, running from the proximal part of the right coronary artery. Single photon emission tomography findings allowed to come to a decision to not perform invasive treatment (coronary artery bypass grafting), due to acceptable perfusion and viability of the heart muscle. Discussion Single coronary artery is an extremely rare anomaly. This requires highly individualised diagnostic approaches, which include multiple imaging modalities, as each adds different information. While the only coronary vessel was narrowed in 53%, no significant ischemia was detected. Left ventricular function remained preserved.

Improved quantification of coronary stenosis in patients with high calcium scores using spectral reconstructions in coronary CT angiography

Abstract Background Coronary CT angiography has demonstrated reduced accuracy in patients with high calcium scores due to blooming artifacts, often resulting in overestimated stenosis. Purpose This study aimed to assess the impact of spectral reconstructions on coronary stenosis quantification in patients with high calcium scores (>500), utilizing invasive coronary angiography as the gold standard. Methods Twenty consecutive patients referred for coronary artery disease assessment underwent both coronary CT angiography and invasivecoronary angiography. Conventional 120 kV images, 100 keV virtual monoenergetic images, and iodine-no-water images were reconstructed. Two blinded operators independently reviewed the images. Lesions were qualitatively classified in both CCTA and invasive angiography as stenosis of 1-24%, 25-49%, 50-70%, and >70%. Results A total of 87 plaques were evaluated. Mean age was 72 years (SD=7.7) and 79% were male. Pre-test probability were low, medium and high in 15.8, 26.3% and 57.9% of patients respectively. Mean calcium score was 1662, with an average dose of 7.5 mSv (67.9% retrospective studies). Nitrates were administered in 89.5% of patients, and 47.4% received intravenous beta-blockers. Sensitivity, specificity, positive predictive value, and negative predictive value to detect lesions > 50% improved from 94%, 57%, 38%, 97% with conventional images to 94%, 82%, 59%, 98% with 100 keV virtual monoenergetic images. Conclusion Spectral reconstructions significantly enhance diagnostic accuracy in coronary CT angiography of severely calcified coronary arteries.

Recovery of Rare Earth Elements from Coal Fly Ash with High Calcium and Iron Contents Using Alkaline and Acid Leaching

Recovery of Rare Earth Elements from Coal Fly Ash with High Calcium and Iron Contents Using Alkaline and Acid Leaching

Effect of GBFS ratio and recycled steel tire wire on the mechanical and microstructural properties of geopolymer concrete under ambient and oven curing conditions

In this study, the effects of waste steel wire ratios, granulated blast furnace slag (GBFS) ratios, and different curing methods on geopolymer concrete (GPC) were investigated. For this purpose, 12 mixtures were produced and eight of them were cured under ambient conditions and the remaining four were cured in an oven. Steel wire ratios and GBFS ratios were added to GPC as 0–1–2–3 % and 0–10–20 % by volume and weight, respectively. As a result of the mixtures, cubes, cylinders, and beams were obtained and these elements were subjected to compression, tensile, and flexural tests. As a result of the tests, the compressive strengths of the specimens were obtained as 8.5 %, 19.7 %, and 24.9 % for ambient curing and 10.4 %, 23.2 %, and 32.2 % for oven curing, respectively, as the steel wire fiber increased from 0 % to 3 %. The maximum compressive strength of the oven-cured specimen with 3 % steel wire fiber was measured as 42.56 MPa. The tensile strength of GPC also increased as the steel wire increased. The highest tensile strength was obtained with 3 % steel wire. In addition, oven curing conditions increased the tensile strength more than ambient curing. The flexural strength (FS) increased by 21.3 %, 29.4 %, and 33.8 % with increasing steel wire ratios of 1 %, 2 %, and 3 %, respectively. The FS was further increased by oven curing conditions and the maximum FS was achieved with 3 % steel wire. In ambient curing conditions, a successful geopolymerization was achieved due to the high calcium content in the samples containing 20 % GBFS. This allowed to obtain similar strengths between ambient curing and oven curing. Although the oven curing values were higher, similar results were obtained for the samples cured in an ambient containing 20 % GBFS. As a result of the study, mixtures containing 3 % steel wire and 20 % GBFS provided sufficient strength without oven curing and increased the usability of GPC under ambient conditions.

The Pathology and Blood Biochemistry of Juvenile Lates calcarifer on Diets Contaminated With Mycotoxins, Histamines and Rancid Fats-A Case Study.

Mycotoxins, originating from contaminated raw materials or suboptimal feed storage, are a growing concern in tropical aquaculture. Common fungi such as Aspergillus spp. and Fusarium spp. produce mycotoxins including aflatoxin, fumonisin, deoxynivalenol and zearalenone. High doses or prolonged exposure (weeks) to low doses of these mycotoxins (< 20 μg/kg) can depress growth, immunity, and cause mortality. This study investigated poor growth and low survival in juvenile Asian seabass, Lates calcarifer fed two different diets (FM40 and ABS3) for 5 weeks. Analysis of these diets revealed high peroxide values, multiple mycotoxins and high histamine levels. Fish fed the FM40 diet, which was contaminated with aflatoxin B1 (13.2 μg/kg), aflatoxin B2 (1.9 μg/kg), deoxynivalenol (29.5 μg/kg), alternariol (2.2 μg/kg), elevated peroxide value (45.91 mEq/kg), and histamine (129.51 mg/kg) developed mild bile duct hyperplasia, depressed total serum proteins (50.40 ± 10.06 g/L), markedly elevated blood potassium (8.2 ± 0.18 mmol/L), and heavy iron deposits in splenic melanomacrophage centres (Perl's stain) indicative of increased haemolysis. The presence of multiple cytotoxic mycotoxins in FM40 diet could explain the increased haemolysis and elevated blood potassium. In contrast, fish fed the ABS3 diet, which had high histamine levels (210.05 mg/kg), exhibited protein-losing nephropathy with multifocal fibrin plugs (Martius scarlet blue stain) indicating acute renal damage, and elevated blood calcium and phosphorus levels. Histamine is metabolised and excreted through the kidneys and known to induce renal arteriolar constriction, disrupt glomerular filtration barrier and increase permeability resulting in protein loss. This study shows that blood biochemistry and histopathology are useful diagnostic tools for assessing the impact of mycotoxins and histamines on fish health.

Initial evaluation of waste phosphogypsum for its use as a precursor for bioceramic materials

In this study, the phosphogypsum waste taken from various places in the factory dump located in Kėdainiai (Lithuania) was reinspected and characterised by different physico-chemical characterisation methods. The results of X-ray diffraction analysis, thermogravimetric analysis and differential scanning calorimetry, Fourier transform infrared spectroscopy, energy-dispersive X-ray analysis, elemental analysis using inductively coupled plasma optical emission and X-ray fluorescence spectroscopy confirmed that the main crystalline phase of the phosphogypsum waste is gypsum (CaSO4·2H2O). The surface morphology of the investigated materials was analysed using scanning electron microscopy. The specific surface area was determined by the Brunauer–Emmet–Teller method. The pore size distribution of the material produced was obtained using the Barrett–Joyner–Halenda method. This study also demonstrated that the phosphogypsum waste could be successfully used as a precursor for the dissolution-precipitation synthesis of high quality bioceramic calcium hydroxyapatite.

Strength, durability, and heat development characteristics of high-performance concrete containing ground coal bottom ash with low and high calcium

Currently, the availability of fly ash has reduced continuously due to the shutdowns of coal-fired power generating plant as climate change concerns have increased. Therefore, the aim of this paper is to find an alternative pozzolan by examining the employment of low- and high-calcium oxide (CaO) ground bottom ash which has been abandoned rather using in concrete production. The bottom ashes were blended with fly ash as a partial substitution of cement (OPC) by observing their generic effects on the compressive strength, cumulative heat generation, chloride ion penetration, and water sorptivity of high-performance concrete. The samples of bottom ash were prepared by oven drying, particle size cutting, and grinding to enhance the reactivity and consistency. High-performance concretes were made at a water-to-binder (W/B) ratio of 0.27 and partial replacement of OPC up to 50 % by weight of the binder. The results indicated that the concretes with 28-day compressive strengths of 101.0 and 109.0 MPa (21.6 % and 28.2 % stronger than OPC concrete) were produced with 50 wt% OPC replacement with high- and low-calcium ground coal bottom ashes (HCBA and LCBA), respectively. These findings suggest that HCBA and LCBA have high pozzolanic reactivity and high possibility for utilization as pozzolan or supplementary cementitious materials in concrete. In addition, the binary blended binders (OPC-HCBA and OPC-LCBA) and ternary blended binders (OPC-HCBA-FA and OPC-LCBA-FA) produced had better chloride ion penetration resistance, less cumulative heat evolution, and lower water sorptivity than 100 % OPC as a cementitious material. Partial OPC replacement by HCBA and LCBA improved the chloride ion penetrability class of OPC concrete from “very low” to “negligible.” The cumulative heat generation due to the pozzolanic reaction of HCBA and LCBA from the partial replacement of OPC up to 50 % reduced 30–44 % relative to the OPC-based mixture throughout during 72 hours after mixing. The CaO content strongly influenced early compressive strength development and cumulative heat evolution but had less impact on chloride ion penetration resistance and water sorptivity.

Risk factors of early death in heat stroke and the challenges of emergency care in Hungary - a case series study

Background and aimThe increasing frequency of heat waves worldwide is a major challenge for emergency care providers worldwide. The aim of this study was to analyze the clinical features, treatment options, and early outcomes of heat stroke patients presenting to a large academic emergency department (ED) in Hungary and to provide guidance in management for other emergency professionals.MethodsPatients presenting to the ED between June 1, 2024, and July 31, 2024, with a body temperature above 40 °C were analyzed in a retrospective cohort study. Data collection included demographic, clinical and laboratory parameters. Predictors of mortality were analyzed with Mann-Whitney U test.ResultsEight patients were included in our analysis. Three patients died in the ED (37.5%). Patients who died had significantly lower pH (7.07 vs. 7.4, p = 0.036), higher potassium (7.3 vs. 3.2 mmol/L, p = 0.036), higher calcium (1.19 vs. 0.97 mmol/L, p = 0.036), higher lactate (10.9 vs. 3.5 mmol/L, p = 0.036) and higher PaCO2 (57.2 vs. 28 mmHg, p = 0.036) at admission compared to those who did not die.ConclusionsThe risk of heat stroke due to climate change-induced heat stress and the consequent thermoregulatory disruption may now be significant in temperate climate zones where it was not previously present. Standardization of differential diagnostic and therapeutic procedures could reduce mortality. pH, potassium, lactate and calcium levels may play an important role in predicting the outcome of heat stroke.

Evaluation of nutrient composition of selected small indigenous fish species in Bangladesh and potential contribution to nutrient intakes

Small indigenous fish (SIF) are recognized as easily available, and abundant source of macronutrients and micronutrients in Bangladesh. The current investigation was undertaken to assess the existing heavy metal, mineral, vitamin, and others nutrient content of small indigenous freshwater fish in Bangladesh. Eight indigenous fish (Mola, Tengra, Baim, Punti, Chanda, Guchi, Koi, and Taki) were selected for this study. The AAS (Atomic Absorption Spectrophotometer), ICP-MS (Inductively Coupled Plasma-Mass Spectrometry), and the Association of Official Analytical Chemists methods outlined were used to determine the proximate compositional analysis of fish. The highest fat content was found in koi fish. Protein was highest in both baim and taki fish. Iron, zinc, vitamin A, and vitamin B12 content were highest in mola fish. Highest calcium and phosphorus were found in the chanda and taki fish. The study concludes that small indigenous fish are valuable sources of fat, protein, ash, iron, zinc, calcium, phosphorus, potassium, vitamin A, and vitamin B12, which are important for maintaining good health. Our findings suggest that small indigenous fish could serve as a viable option for addressing the nutritional needs for the children (6–23 m age), and Pregnant and lactating women in Bangladesh as a tool to fight malnutrition.

Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) in a One-Year-Old Child: A Case Report and Literature Review

Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is a rare autosomal recessive metabolic disorder characterized by abnormal phosphate regulation and soft tissue calcifications. Early diagnosis is crucial for optimal management to prevent complications. Case Presentation: A one-year-old child presented with intermittent fevers and a gluteal mass. Ultrasound revealed a calcified abscess, and biopsy confirmed a pseudocyst. Further workup identified elevated blood calcium, phosphorus, and neutropenia. The patient was ultimately diagnosed with HFTC. Discussion: Early diagnosis of HFTC is challenging due to the rarity of the disease and the potential for non-specific initial symptoms. This case highlights the importance of considering HFTC in the differential diagnosis for a young child with unexplained soft tissue masses or skeletal abnormalities, even outside the usual age range. Conclusions: This case report emphasizes the need for a high index of suspicion for HFTC in pediatric patients with suggestive clinical features, regardless of age. Early diagnosis and prompt intervention are essential to improve long-term outcomes and prevent complications.

12520 Preliminary Findings From An Ongoing Open-label Phase 2 Study Demonstrate That The Calcilytic Encaleret Can Improve The Relationship Between Blood And Urinary Calcium In Individuals With Post-surgical Hypoparathyroidism

Abstract Disclosure: I.R. Hartley: Research Investigator; Self; Calcilytix Therapeutics, Inc. R.I. Gafni: Research Investigator; Self; Calcilytix Therapeutics, Inc. K.L. Roszko: Research Investigator; Self; Calcilytix Therapeutics, Inc. X. Li: None. E.A. Ferguson: Research Investigator; Self; Calcilytix Therapeutics, Inc. C.A. Moore: Research Investigator; Self; Calcilytix Therapeutics, Inc. K.A. Pozo: Research Investigator; Self; Calcilytix Therapeutics, Inc. K.T. Ampuero: Research Investigator; Self; Calcilytix Therapeutics, Inc. A.V. Sridhar: Employee; Self; Calcilytix Therapeutics, Inc. A.S. Mathew: Employee; Self; Calcilytix Therapeutics, Inc. M. Roberts: Employee; Self; Calcilytix Therapeutics, Inc. S.H. Adler: Employee; Self; Calcilytix Therapeutics, Inc. E.F. Nemeth: Consulting Fee; Self; Calcilytix Therapeutics, Inc. M.T. Collins: Research Investigator; Self; Calcilytix Therapeutics, Inc. Parathyroid hormone (PTH) and the calcium-sensing receptor (CaSR) are the primary regulators of blood and urinary calcium. The independent contributions of PTH and the CaSR on renal calcium handling are not well understood, largely due to their intertwined physiology. In individuals with functioning parathyroid tissue, calcilytics (negative modulators of the CaSR) increase PTH secretion and decrease urinary calcium excretion, leading to increased blood calcium levels. We hypothesized that calcilytic administration to individuals with post-surgical hypoparathyroidism (PSH) may reveal the PTH-independent effects of CaSR modulation on renal calcium handling and clarify the potential therapeutic role of calcilytics in PSH. Four women (26-69y) with PSH enrolled in an ongoing, open-label, phase 2, proof-of-principle study of encaleret, an oral investigational calcilytic (NCT05735015). Encaleret 162 mg was administered every 12 hours for up to 10 doses. Calcitriol was discontinued one day prior to the first dose of encaleret. All participants received calcium supplementation initially. To maintain eucalcemia, 1 participant discontinued calcium supplementation and 3 required re-initiation of low-dose calcitriol (0.25 mcg daily). Results are presented as mean (range) of fasting baseline pre-dose levels compared to fasting levels 12 hours after the last dose of encaleret. Fractional excretion of calcium (FECa), a measure of renal calcium handling that quantifies the relationship between blood and urinary calcium, decreased by 52% (34-78). Albumin-corrected blood calcium increased from 8.4 mg/dL (range 8.1-8.6; nl 8.4-10.2) to 9.3 (8.6-10.7). Urinary calcium excretion decreased from 348 mg/day (range 204-501; nl &amp;lt;250) to 169 (76-350), with normalization in 3 participants and a 30% decrease in the fourth. Baseline PTH of 7.4 pg/mL (range 4.6-10.1; nl 15-65) transiently increased 30 minutes after the first dose to 13.0 (4.5-18.1), then returned to near baseline levels. Bone turnover markers were normal and did not change on encaleret. There were no serious adverse events reported. The only treatment-related adverse events (AEs) were mild hypercalcemia causing headache in 1 participant. Her blood calcium levels continued to be mildly elevated for 60 hours after the last dose of encaleret even after calcium and calcitriol supplementation was discontinued. Despite elevated blood calcium, her 24-hour urine calcium remained &amp;lt;200 mg/day. Encaleret reduced FECa in the first four participants with PSH, improving the relationship between blood and urinary calcium. These preliminary results from this Phase 2 study support continued evaluation of encaleret as an orally administered therapy for the treatment of patients with PSH. Presentation: 6/1/2024

7254 An Unusual Case Of Hypercalcemia

Abstract Disclosure: S. Shushtarian: None. M. Balogun: None. T. Kaur: None. Hypercalcemia varies depending on severity. Higher serum calcium levels and more severe symptoms may indicate primary hyperparathyroidism or a malignant cancer. This is a case of a 32 year old female who presented with recurrent history of nephrolithiasis, found to have hypercalcemia of 13.4 mg/dL and parathyroid hormone of 1928.9 pg/mL, with phosphorus of 1.5 mg/dL. Ultrasound of her thyroid revealed a complex nodule arising from the right parathyroid gland measuring 2.2 X 2.0 cm. CT chest revealed diffuse osseous sclerosis secondary to metabolic disorder. Sestamibi scan did not localize any parathyroid adenoma. MRI of the thoracic and lumbar spine showed multiple small enhancing lesions throughout the pelvis and in the left rib, likely brown tumors related to hyperparathyroidism. X-ray of bony prominence on the patient’s left knee revealed a large lytic lesion of the proximal tibial diaphysis measuring 5.1 X 1.9 cm, concerning for aggressive neoplasm. Subsequent left tibial bone biopsy revealed giant cell rich lesions consistent with brown tumor of hyperparathyroidism. Due to our patient’s high calcium levels and large nodule size, she was referred to a tertiary center as the concern for parathyroid carcinoma and post-op hungry bone syndrome was high. Pre-op PTH level was 1408 pg/mL and post-op PTH was 96 pg/mL. The tumor removed was 2.1 cm. Post surgical pathology was consistent with atypical parathyroid adenoma. Patient was referred for genetic testing. An atypical parathyroid adenoma (APA) only accounts for 1.2 to 1.3% of cases of primary hyperparathyroidism. 80-85% of primary hyperparathyroidism is due to typical adenoma, and 10 to 15% of cases are due to hyperplasia or multiple gland disease. APA can often be confused with parathyroid carcinoma (PC), as they both have a 1:1 male to female ratio, high serum calcium levels, symptomatic hypercalcemia, high PTH levels, and fragility fractures. There are studies showing that both APA and PC have loss of nuclear parafibromin immunoreactivity. In addition, neither APA nor PC have any correlation with menopause, hormones, or gene deletions, unlike typical adenomas. Biopsy is necessary for diagnosis as the histological and immunohistochemical differences can differentiate APA vs PC. Histological features include pseudo-capsular invasion, bands of fibrosis, pronounced trabecular growth, nuclear atypia, and prominent nucleoli. Also, APA has a strong membranous staining pattern of E-cadherin, whereas PC has a loss of membranous staining. These differences are essential as although APA and PC clinically present similarly, APA lacks the invasive growth and possibility for metastatic disease that PC has. The likelihood for relapse of APA is low. Presence of malignancy criteria are indicative that a mass is actually PC and not APA. Despite this, APA is still considered a tumor of uncertain malignant potential and requires follow up. Presentation: 6/3/2024

9295 Characteristics Of Adults with Autosomal Dominant Hypocalcemia Type 1 (ADH1) Enrolled In The CLARIFY Disease Monitoring Study

Abstract Disclosure: S.W. Ing: Advisory Board Member; Self; Ultragenyx, Amolyt. Grant Recipient; Self; Alexion Pharmaceuticals, Inc.. Research Investigator; Self; BridgeBio Pharma, Takeda, Amolyt, Radius Health, Inc, Ultragenyx. P. Harmatz: Research Investigator; Self; BridgeBio Pharma. S. Mora: Research Investigator; Self; BridgeBio Pharma. E.A. Imel: Research Investigator; Self; BridgeBio Pharma. P.J. Tebben: Research Investigator; Self; BridgeBio Pharma. M.L. Warren: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt. Speaker; Self; Ascendis. N. Ma: Research Investigator; Self; Calcilytix Therapeutics, Ultragenyx, Inozyme. Other; Self; Up To Date. A.A. Khan: Research Investigator; Self; BridgeBio Pharma, Ascendis. A. Palermo: Research Investigator; Self; BridgeBio Pharma. B. Decallonne: Research Investigator; Self; BridgeBio Pharma. S. Lemoine: Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. G. Mantovani: Research Investigator; Self; BridgeBio Pharma. A. Linglart: Consulting Fee; Self; Alexion, Novo Nordisk, Merck, Pfizer, Inc.. Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. H. Wasserman: Research Investigator; Self; BridgeBio Pharma. A.P. Barbosa: Research Investigator; Self; BridgeBio Pharma. C. Cardot-bauters: Research Investigator; Self; BridgeBio Pharma. M. Roberts: Employee; Self; BridgeBio Pharma. A. Mathew: Employee; Self; BridgeBio Pharma. S. Adler: Employee; Self; BridgeBio Pharma. M.C. Zillikens: Research Investigator; Self; BridgeBio Pharma. R.J. Clifton-Bligh: Consulting Fee; Self; Ipsen, Kyowa Kirin, Amgen Inc, Eisai. Research Investigator; Self; BridgeBio Pharma. L. Rejnmark: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt, Takeda, Kyowa Kirin. Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) concentrations, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. While a rare disease, ADH1 is one of the more frequently identified causes of genetic hypoparathyroidism. Conventional therapy includes calcium (Ca) and/or active vitamin D, but this regimen incompletely corrects the hypocalcemia and is associated with persistent hypercalciuria, which may result in renal complications including nephrocalcinosis (NC), nephrolithiasis (NL), and chronic kidney disease (CKD). The CLARIFY disease monitoring study [NCT05227287] is a global, multicenter, longitudinal study to understand disease burden, management, and progression in children and adults with ADH1 over a 5-year period. Here we report data on the characteristics of adult participants at study entry. As of November 2023, 45 adults (≥18 years) with ADH1 were enrolled, with a mean±SD age of 42.1±16.5 years (range 18-80). The mean±SD age of a hypocalcemia diagnosis was 19.1±19.1 years, while the mean±SD age for a diagnosis of ADH1 was 28.2±20.6 years. As reported on medical history, in decreasing order of prevalence, 36% (16) had NC, 22% (10) had intracranial calcifications, 11% (5) had history of seizures, 11% (5) had CKD, 9% (4) had cataracts, 7% (3) had NL, and 4% (2) had undergone renal transplant. Treatment data were available for 43 participants and included the following: 74% (32) Ca and active vitamin D, 9% (4) Ca alone, 9% (4) active vitamin D alone, 37% (16) magnesium, 33% (14) thiazide diuretics, 26% (11) potassium, 7% (3) phosphate binder, 7% (3) PTH, and 5% (2) no treatment. Mean±SD fasting values collected prior to conventional therapy dose are presented. PTH concentrations (10.1±8.2 pg/mL [nl 15-65]) and albumin-corrected calcium ([cCa]=7.5±1.0 mg/dL [nl 8.5-10.5]) were low. Despite the low mean cCa, the mean 24-hr urine calcium was elevated (268±183 mg/d, [nl &amp;lt;250 women, &amp;lt;300 men]). Blood phosphate was 4.8±0.8 mg/dL [nl 2.5-4.8] while blood magnesium was 1.8±0.2 mg/dL [nl 1.8-2.4]. 25-OH vitamin D was 35.0±13.5 ng/mL [nl 30-80]. Renal function as assessed by CKD-EPIcr_R showed eGFR of 86±23 mL/min/1.73m² (range 36-123). This study represents the largest cohort of adults with ADH1 described to date. These data highlight variability in therapeutic approaches in a real-world setting with some participants receiving up to 6 different medications/supplements. Despite being followed in expert centers, and treated with available therapies, patients on average have low cCa with relatively high 24-hr urine calcium excretion. The CLARIFY study provides an opportunity to better understand the progression and burden of disease in participants with ADH1. Presentation: 6/3/2024