Calcitriol Supplementation Research Articles

12324 Clinical Features And PHEX Variants Of Adults With X-Linked Hypophosphatemia

Abstract Disclosure: L.P. Valadares: None. D.R. Carvalho: None. F.S. Lopes: None. R.S. Oliveira: None. L.G. Castro: None. X-linked hypophosphatemia (XLH), caused by loss-of-function PHEX mutations, is a lifelong renal phosphate-wasting disorder and the main cause of inherited hypophosphatemia. In adults, chronic hypophosphatemia leads to impaired bone mineralization and persistent osteomalacia. Short stature, lower limb deformities and musculoskeletal chronic pain can significantly impact the daily lives of affected individuals. This study aimed to describe the clinical and molecular profiles of 23 adults with genetically proven XLH who are being followed at a tertiary medical center in Brazil. We conducted a retrospective analysis of their medical records. The median age at diagnosis was 3.0 years (IQR 2.0-8.0) and the mean age at first visit at the adult care unit was 30.5 years (±12.7). Their mean final height was 144.2 cm (±10.5), with a mean body mass index (BMI) of 28.1 kg/m2 (±4.9). Nine patients were overweight, and seven were obese. Sixteen patients had a positive family history of rickets, and nine had offspring with XLH. Among the 14 different PHEX mutations that were identified, six had not been previously reported. Hypophosphatemia was observed in 21 patients at presentation at the adult care unit, increased serum alkaline phosphatase levels in 19, and 12 showed increased PTH levels. Chronic bone and muscular pain were reported by sixteen patients, eighteen had lower limb deformities, and six had a history of fractures and/or pseudofractures. Seventeen patients underwent orthopedic surgeries, with an average of 3.8 surgical interventions per patient. Nephrolithiasis and/or nephrocalcinosis were observed in nine patients, but none had glomerular filtration rate below 60 mL/min adjusted to 1.73 m2 of body surface. Three patients were on conventional treatment (phosphate and calcitriol) upon presentation at the adult care unit, five patients had never received XLH-specific treatment, and fifteen discontinued conventional therapy after completing skeletal growth, with a mean therapy duration of 12.1 years (±3.5). Out of the 20 patients without treatment, 16 were initiated on pharmacological therapy based on symptoms and signs of persistent osteomalacia. Eleven started combined phosphate and calcitriol supplementation, while five received calcitriol monotherapy. This cohort underscores that adults with XLH experience significant musculoskeletal morbidity throughout their lives, and require long-term follow-up, including assessment of energy metabolism. Importantly, most of them benefits from maintaining pharmacological treatment in adulthood. Presentation: 6/2/2024

7159 Brown Tumor As Primary Presentation Of Parathyroid Carcinoma In A Young Female

Abstract Disclosure: S.G. Zachariah: None. R. Anand: None. B.Y. Wong: None. H.J. Lee: None. Title Brown Tumor as Primary Presentation of Parathyroid Carcinoma in a Young Female Introduction/Background: Parathyroid carcinoma (PC) is a rare cause of hyperparathyroidism (HPT) accounting for less than 1% of primary HPT cases. The mean age of PC presentation is 62 years. Long-standing HPT can lead to the formation of osteitis fibrosis cystica (brown tumors). In today’s world of advanced screening, they are an increasingly rare presentation of HPT. We present a case of PC presenting as multiple brown tumors in a young woman. Case: A previously healthy 32-year-old woman presented to the emergency department with right shoulder pain after a mechanical fall. MRI revealed multiple osseous lesions of the proximal humerus, glenoid, and scapula, concerning for possible metastatic malignancy. Notable labs: calcium 13.6 mg/dL [8.5 - 10.5 mg/dL], phosphorus 1.7 mg/dL [2.5 - 4.5 mg/dL], alkaline phosphatase 2,369 U/L [< 130 U/L], 25-OH vitamin D 0.8 ng/mL [30 - 60 ng/mL], and parathyroid hormone greater than 2,500 pg/mL [20-80 pg/mL]. Albumin and renal function were normal. CT chest/abdomen/pelvis showed lytic lesions of the left 7th rib, anterior superior iliac spine (with nondisplaced fracture), pelvis, and sacrum. Subsequent pelvic biopsy showed fragmented bony trabeculae with osteoblastic rimming and rare osteoclasts, fragments of fibrous tissue with few plasma cells and hemosiderin laden macrophages, possibly consistent with brown tumor. On parathyroid ultrasound, a 2.2 cm cystic mass was seen along the left common carotid artery. CT neck confirmed the location and also reported C7-T1 spinal lesions. Calcium levels stabilized with IV fluids and 90 mg IV pamidronate. She underwent a left parathyroidectomy and left hemithyroidectomy with central neck dissection. Pathology was consistent with a low-grade parathyroid carcinoma, with a foci of angioinvasion and capsular invasion without lymph node metastases. The Ki-67 index was less than 1%. Post-operatively, the patient was started on calcium and calcitriol supplementation and did not experience hungry bone syndrome. On further discussion, the patient noted that she had a jaw tumor that was previously biopsied and found to be benign. The patient has since been referred for genetic testing. Conclusion/Clinical Lessons: Both PC and its initial presentation with brown tumors are uncommon. Even more rare is the presentation of both in a young, otherwise healthy female. In this context, it is also important to note that brown tumors can mimic osseous metastases and appropriate biochemical, imaging, and histopathological evaluation is needed. The diagnosis of PC under 40 years of age is uncommon and genetic testing is indicated. Syndromes including multiple endocrine neoplasia type 1, familial isolated hyperparathyroidism, and hyperparathyroidism-jaw tumor syndrome are potential causes of inherited PC. Presentation: 6/3/2024

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 <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 <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

8400 An Unusual Case of Brittle Bone Disease

Abstract Disclosure: S.M. Middleton: None. M. Mogri: None. Introduction: We present the case of a now 21-month-old F with prenatally suspected skeletal dysplasia; subsequent evaluation revealed concern for a form of brittle bone disease that has not been previously described. Clinical Case: The patient was delivered at 37.0 weeks gestational age via C-section. There had been prior prenatal concerns for a possible skeletal dysplasia. A skeletal survey done on day-of-life 2 noted generalized demineralization of her bones, shortening/bowing of the long bones, an acute right proximal ulnar fracture, and evidence of multiple discontinuous healed rib fractures. A repeat skeletal survey done at day-of-life 19 demonstrated worsening skeletal findings with a very poorly mineralized skull, shortening of the clavicles and extremities, progressive fractures in all extremities and further bowing of the limbs, progressive rib fractures with callus formation, and multiple vertebral bodies with stature loss concerning for compression fractures. Directed genetic testing for osteogenesis imperfecta was negative, so whole exome sequencing was pursued and identified variants of unknown significance in the KAT6B and WDR35 genes not previously described, noting that the patient was heterozygous for both. She was suspected to be a carrier for the WDR35 mutation as it is inherited in an autosomal recessive fashion, and parental genetic testing revealed that the patient’s father carried the same KAT6B mutation and was phenotypically normal. Mutations in these genes have been described in disorders associated with bone abnormalities (such as genitopatellar syndrome and cranioectodermal dysplasia 2), but with different clinical presentations. During the course of her care, she was also identified to have hypophosphatemia shortly after birth and concerns for phosphate wasting; she was noted to have a high fractional excretion of phosphate in the setting of low serum phosphorus despite enteral phosphorus supplementation. She additionally was found to have an elevated FGF23 level at the same time the suspected renal phosphate wasting was identified. Her total calcium has remained normal with normal PTH values; her 25-OH vitamin D has also been normal. She has subsequently been successfully managed on sodium phosphate and calcitriol supplementation, as well as regular zolendronate infusions, without recurrence of fractures, and is clinically doing well with improvements in her respiratory status and overall development. Conclusion: This patient illustrates a severe case of brittle bone disease that presently does not have a clear etiology, though could represent a novel genetic mutation that has not been described and could subsequently be identified with continued review of her genetic testing in the future. Reporting her case could be beneficial to other patients with similar skeletal disease in helping to identify an underlying cause. Presentation: 6/3/2024

7388 Rare Case of Mediastinal Parathyroid Carcinoma

Abstract Disclosure: Y. Esaki: None. J. Moalem: None. A. Israel: None. I. Shafiq: None. Introduction: Parathyroid carcinoma accounts for 1% of primary hyperparathyroidism with an estimated prevalence of 0.005% of all cancers. Ectopic locations of parathyroid tumors have been found in 6-16% of cases, most commonly in the thyroid, the thymus, or behind the esophagus. Parathyroid carcinoma is rarely found in the mediastinum and only 30 cases have been reported in the literature. Clinical Case: A 68-year-old male without significant past medical history was evaluated by his primary care physician for constipation, polyuria and 20 lb weight loss over the past year. He presented to the hospital after blood work revealed serum calcium of 13.5 mg/dl (8.6-10.2 mg/dl). Initial hospital workup demonstrated serum calcium 12.9 mg/dl, phosphorus 2.6 mg/dl (2.7-4.5 mg/dl), 25-OH vitamin D 21 ng/ml (30-60 ng/ml), 1,25-(OH)2 vitamin D 143.0 pg/ml (19.9-79.3 pg/ml), PTH-related protein < 2.0 pmol/L (0.0-2.3 pmol/L) and PTH 1,250.0 pg/ml (15.0-65.0 pg/ml). CT scan revealed a 3.5 cm x 2.6 cm heterogeneous right paratracheal soft tissue mass with areas of calcifications with mass effect on SVC. Thyroid ultrasound showed multinodular thyroid tissues with a left 1.1 cm heterogeneous solid nodule along the mid posterior aspect as well as a 0.5 cm hypoechoic lesion inferior to the left lobe. Sestamibi scan demonstrated a large area of increased uptake corresponding to the mass seen in the superior mediastinum on CT imaging. He underwent neck exploration and left hemithyroidectomy as well as median sternotomy with resection of the paratracheal mass. Intraoperative PTH decreased from the baseline of 1,177.0 pg/ml to 65.6pg/ml following the removal of the paratracheal mass. The final pathology of right anterior mediastinal mass was consistent with a 5 cm parathyroid carcinoma with angioinvasion, intermediate lymphatic invasion, invasion into adjacent structures, and Ki67 proliferative index focally > 5%. His post-operative course was complicated by hypocalcemia, which improved with treatment with calcitriol and calcium supplementation. He declined the genetic testing. His calcium and parathyroid hormone have remained in the normal range after 1 year. Conclusion: This case illustrates a rare case of parathyroid carcinoma found in the mediastinum. It is important to recognize that parathyroid carcinoma can present in ectopic locations including the mediastinum, as this can affect the preoperative investigation and management. Fine needle biopsy (FNA) prior to the initial operation is not recommended as it is difficult to differentiate the parathyroid carcinoma from benign disease based on FNA, and it may cause tumor rupture and seeding. Also, in the mediastinal parathyroid carcinoma, localization of the lesions including the size and invasiveness is critical in order to allow for radical surgery. Presentation: 6/3/2024

6871 Hungry Bone Syndrome After Parathyroidectomy in End-Stage Kidney Disease: A Case Report Analysis

Abstract Disclosure: R. Rani: None. C. Mullarkey-desapio: None. Introduction: Hungry Bone Syndrome (HBS) is a rare yet severe complication following parathyroidectomy, characterized by pronounced hypocalcemia subsequent to a rapid decline in parathyroid hormone (PTH) levels. Renal hyperparathyroidism (RHPT) carries a heightened risk of HBS compared to primary hyperparathyroidism (PHPT), with prevalence varying from 15% to 25% in PHPT to as high as 75-92% in RHPT. This elevated risk in RHPT is attributed to chronically elevated PTH levels, both in terms of duration and intensity as compared to PHPT. Preoperative predictors for HBS occurrence and severity include younger age, larger gland size, lower preoperative calcium levels, elevated bone turnover markers, and the magnitude of PTH elevation. Case Report: We present a case of a 36-year-old female with End-Stage Renal Disease (ESRD) requiring dialysis, complicated by renal osteodystrophy and a radial fracture, unresponsive to medical therapy, who was admitted for parathyroidectomy. Preoperative labs revealed calcium at 8.3 mg/dL, phosphate at 4.1 mg/dL, alkaline phosphatase (ALP) at 797 IU/L, and an extremely elevated parathyroid hormone (PTH) level at 4139 pg/ml. Within 24 hours of parathyroidectomy (three and a half glands were removed, the largest weighing 0.7gm), her PTH levels declined to the 130s, accompanied by symptomatic hypocalcemia (calcium 6.5mg/dL). Initial management involved intravenous calcium gluconate and subsequent high-dose oral calcium (up to 10-16gm daily) with Calcitriol 1 mcg twice daily. Despite repletion, her calcium levels remained low on postoperative day 4 (calcium 6.8mg/dL, phosphate 1.9 mg/dL, magnesium 1.7mg/dL) with PTH at 131 pg/ml, confirming Hungry Bone Syndrome. After seven days of aggressive intravenous and oral calcium supplementation with high-dose Calcitriol, she was discharged with a calcium level of 8.9mg/dL. Discussion: Management of HBS following renal hyperparathyroidism surgery presents significant challenges due to associated comorbidities and other electrolyte abnormalities, with limited literature providing guidance on prevention and management. Our case demonstrated that early suspicion and aggressive management improved patient outcomes. Suspecting HBS in high-risk individuals and initiating interventions pre and post-surgery, including pre-treatment with calcitriol, bisphosphonates, and early aggressive intravenous calcium supplementation post-surgery, could potentially reduce morbidity and length of hospital stay. Presentation: 6/1/2024

The therapeutic potential of 1, 25-dihydroxy vitamin D3 on cisplatin-affected neurological functions is associated with the regulation of oxidative stress and inflammatory markers as well as levels of MMP2/9.

Calcitriol as a biologically active form of vitamin D3 has beneficial effects on all body systems. This vitamin has a potent neuroprotective effect via several independent mechanisms against brain insults induced by anticancer drugs. The present study was designed to examine the neuroprotective effects of calcitriol against neurotoxicity induced by cisplatin.Induction of neurotoxicity was done with cisplatin administration (5mg/kg/week) for 5 successive weeks in male Wistar rats. The neuroprotective influence of calcitriol supplementation (100ng/kg/day for 5 weeks) was assessed through behavioral, electrophysiological, and molecular experiments.Cisplatin administration impaired spatial learning and memory and decreased prefrontal brain-derived neurotrophic factor (BDNF). Peripheral sensory neuropathy was induced through cisplatin administration. Cisplatin also reduced the amplitudes of the compound action potential of sensory nerves in electrophysiological studies. Cisplatin treatment elevated MDA levels and reduced anti-oxidant (SOD and GPx) enzymes. Pro-inflammatory cytokines (IL-1β and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were augmented through treatment with cisplatin. Learning and memory impairments along with BDNF changes caused by cisplatin were amended with calcitriol supplementation. Reduced sensory nerve conduction velocity in the cisplatin-treated group was improved by calcitriol. Calcitriol partially improved redox imbalance and diminished the pro-inflammatory cytokines and MMP-2/9 levels.Our findings showed that calcitriol supplementation can relieve cisplatin-induced peripheral neurotoxicity. Calcitriol can be regarded as a promising new neuroprotective agent.

Comparative effects of calcitriol and calcimimetic on bone health in renal insufficiency

AbstractCalcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH‐clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of β‐catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.

Impact of oral administration of calcitriol to prevent symptomatic hypocalcemia after total thyroidectomy: Systematic review and meta-analysis.

One of the most common complications of total thyroidectomy is post-operative transient or persistent hypoparathyroidism that can cause symptomatic hypocalcaemia. To prevent this complication, shorten the period of hospitalization and reduce morbidity, routine supplementation of oral vitamin D and calcium has been suggested. This systematic review and meta-analysis aims to critically assess the association between pre-operative calcitriol supplementation and post-operative hypocalcaemia. Randomized controlled trial studies were identified by searching PubMed, Scopus, and Google Scholar databases up to 30 March 2023. Screening of titles, abstracts, and full texts of articles were performed, and data were extracted for a meta-analysis. This meta-analysis includes data from nine randomized controlled trials with a total of 1259 patients but with significant heterogeneity. The results demonstrate that calcium levels were higher in patients who had pre-operative calcitriol supplementation, with a weighted mean difference (WMD) 0.18 (95% confidence interval (CI) = 0.00, 0.37). Pre-operative calcitriol supplementation did not lead to significant changes in parathyroid hormone (PTH) levels, with WMD -0.49 (95% CI: -1.91, 0.94). Pre-operative calcitriol supplementation leads to higher calcium levels, but the high heterogeneity of the included studies (79% to 98.7%) could affect the results.

Effect of exogenous calcitriol on myopia development and axial length in guinea pigs with form deprivation myopia

The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.

Evaluation of Hypocalcemia Following Total Laryngectomy With and Without Thyroidectomy.

Hypoparathyroidism and associated hypocalcemia are well-established complications following laryngectomy. This study further characterizes the rates of hypocalcemia in patients undergoing total laryngectomy (TL) with and without thyroidectomy and hemithyroidectomy. Retrospective cohort study. TriNetX. We queried TriNetX, a deidentified patient database, to identify patients who underwent TL with and without thyroidectomy and hemithyroidectomy. Rates of hypocalcemia, low parathyroid hormone (PTH), calcium, and calcitriol supplementation were compared between groups with multivariable repeated measures logistic regression. We identified 870 patients in the TL without thyroidectomy cohort, 158 patients in the hemithyroidectomy cohort, and 123 in the total thyroidectomy cohort. Rates of hypocalcemia differed between patients receiving total thyroidectomy versus TL alone for 0 to 1 month (odds ratio [OR]: 2.88 [1.95-4.26]) 1 to 6 months (OR: 5.08 [2.29-11.3]), and 6 to 12 months (OR: 2.63 [1.003-6.88]) postoperatively, with adjustment for age at laryngectomy, race, ethnicity, and gender. Results were similar among those who received calcium supplementation. The rate of low PTH levels differed in these groups for 0 to 1 month (OR: 5.13 [3.10-8.51]), 1 to 6 months (OR: 3.47 [1.46-8.22]), and 6 to 12 months (OR: 3.63 [1.40-9.38]) following surgery. Rates of postoperative calcium supplementation were increased for patients receiving total thyroidectomy versus TL for 1 to 6 months (OR: 2.44 [1.62-3.68]), and 6 to 12 months following surgery (OR: 1.79 [1.18-2.72]). Patients undergoing TL with total thyroidectomy have a higher risk of postoperative hypocalcemia compared to patients receiving TL alone. Risk of parathyroid injury in these patients may warrant further emphasis on PTH measurement after surgery and a multidisciplinary approach to management.

Dietary supplementation with calcitriol or quercetin improved eggshell and bone quality by modulating calcium metabolism

This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens. In trial 1, 72 Hy-Line Brown layers (80-week-old) with weak-shelled strength (25 to 30 N) were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet (4% calcium level) or basal diets supplemented with 0.5% calcium, 5 μg/kg calcitriol or 500 mg/kg quercetin for 4 weeks. In trial 2, 360 Hy-Line Brown layers (60-week-old) were divided into 3 groups with 8 replicates of 15 birds: control group (basal diet), calcitriol group (basal diet + 5 μg/kg calcitriol), and quercetin group (basal diet + 500 mg/kg quercetin). This trial lasted for 12 weeks. The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials (P < 0.05). In trial 2, compared with the control group, both calcitriol and quercetin supplementations improved femoral bone quality, calcium retention of hens and calcium content in uterine fluid at 18.5 h post-oviposition (PO) (P < 0.05), along with enhancing uterine morphology. Compared to the control group, supplemental calcitriol or quercetin up-regulated the relative mRNA expression levels of uterine transient receptor potential cation channel, subfamily V, member 6 (TRPV6) at 8.5 h PO and plasma membrane calcium-ATPase (PMCA), vitamin D receptor (VDR), estrogen receptor alpha (ERα) at 18.5 h PO (P < 0.05), but down-regulated the uterine caspase 3 (CASP3) relative mRNA expression level at 8.5 h PO (P < 0.05). Meanwhile, the femoral relative mRNA expression levels of tartrate-resistant acid phosphatase (TRAP) (up-regulated at 8.5 and 18.5 h PO) and alkaline phosphatase (ALP) (up-regulated at 8.5 h PO but down-regulated at 18.5 h PO) were also affected by calcitriol or quercetin supplementation (P < 0.05). Compared to the calcitriol, quercetin increased hen-day egg production and femoral medullary bone volume/bone tissue volume but reduced femoral stiffness (P < 0.05), which were accompanied by increased relative mRNA expression levels of uterine TRPV6, estrogen receptor beta (ERβ) at 18.5 h PO (P < 0.05). Overall, both dietary calcitriol and quercetin could improve eggshell and bone quality by modulating calcium metabolism of aged layers. Compared to calcitriol, dietary quercetin up-regulated the expression of uterine calcium transporters, without affecting eggshell quality.

Estimation of IL-8, IL-38, Vitamin D, TPO Ab, and CRP Levels in Iraqi Hashimoto Thyroiditis Patients

Abstract Background: Hashimoto’s disorder is an autoimmune disease affecting cells of the thyroid gland via the diffusion of the lymphocytes into thyroid cells. Calcitriol is the active form of Vit.D3; there were a strong correlation between low Vit-D levels and development of autoimmune diseases exists and calcitriol supplementation might play a protective role in the pathophysiology of autoimmune diseases. Objectives: This study aimed to estimate the levels of interlukin-8 (IL-8), interlukin-38 (IL-38), Vitamin D, thyroid peroxidase (TPO) Ab, and c-reactive protein (CRP) in Iraqi patients suffering from Hashimoto disease. Materials and Methods: In this study, 90 individuals (males and females) were enrolled, and divided into two groups: Hashimoto’s disorder group (60) patients and the healthy control group (30) persons were checked by the physician with the aid of medical history. The levels of TSH, Vit.D3, anti-TPO Ab, T4, IL-8, and IL-38 were measured for all the study groups. Results: A highly significant reduction (P &lt; 0.001) was shown in mean levels of Vit D, T4, and IL-38 among the patient’s group in comparison with the controls, whereas a significant reduction (P &lt; 0.05) was revealed in mean levels of CRP among patients in comparison with the controls. Also, the results showed a highly significant elevation (P &lt; 0.001) in mean levels of TSH, IL-8, and anti-TPO antibodies among the Hashimoto disease group in comparison with the controls. Conclusion: Hashimoto disease caused highly significant decreases in mean levels of Vit. D, T4, IL-38, and CRP, whereas there was a highly significant increase in the levels of TSH, IL-8, and anti-TPO antibodies.

Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients.

Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT. We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy. One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13mg2/dL2 (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients. Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.

The Effect of Vitamin D Supplementation on Autoimmune Bullous Skin Disorder Intensity Score on Bullous Pemphigoid and Acute Kidney Injury: A Case Report

Introduction: Bullous pemphigoid is the most common bullous-type autoimmune disease. Hypovitaminosis D is often associated with autoimmune disease and found in 86,7% bullous pemphigoid patients. Vitamin D supplementation in bullous pemphigoid patients ought to ameliorate its clinical symptoms.&#x0D; Case presentation: A-58 years old male patient with bullous pemphigoid and acute kidney injury admitted with a chief complaint of infected blisters all over the body. The patient had been treated for 1 week with worsening swallowing pain and low intake. On the 12th day of hospitalization, the patient was given calcitriol supplementation of 0,25 mcg per day. There was an improvement in clinical symptoms shown on autoimmune bullous skin disorder intensity score (ABSIS) from 57 on inpatient day 7 to 17.5 on inpatient day 20. Patient discharged on the 20th day of hospitalization with no emerging blisters and the ability to swallow minced food by mouth.&#x0D; Conclusion: Calcitriol supplementation of 0,25 mcg per day for 10 days helps to improve the ABSIS score in bullous pemphigoid patient with acute kidney injury. Administration of calcitriol is considered safe and well tolerated.

Effect of calcitriol supplementation on infectious biomarkers in patients with positive systemic inflammatory response: A Randomized Controlled Trial

Background: Sepsis is one of the common causes of hospitalization of patients in intensive care units. A significant role for vitamin D in sepsis has been proposed, which is due to its active metabolite, calcitriol. Aims: Evaluate the effect of calcitriol supplementation on infectious biomarkers, including procalcitonin and presepsin. Methods: Patients with sepsis were divided into intervention and control group. Patients in the intervention group received intravenous calcitriol daily for 3 days. The serum levels of procalcitonin and presepsin were evaluated on days 0, 3, and 5 after administration. Results: Fifty-two SIRS-positive patients were evaluated. Baseline characteristics, changes in Sequential Organ Failure Assessment (SOFA) score and blood levels of vitamin D were not significantly different between the two groups. Procalcitonin levels on day 5 and the differences between day 5 and 0 were significantly lower in the intervention group (P = 0.02). Presepsin on the third and fifth days in the intervention group was reduced, but in the control group, there was an ascending trend. However, there was no significant difference between the two groups on days 3 and 5 (P = 0.17 and P = 0.06, respectively) or between days 3 as well as 5 and the baseline presepsin level (P = 0.93 and P = 0.92, respectively). The ICU length of stay and 28-day mortality did not differ significantly either between the two arms of the study. Conclusions: Finally, the results of this study showed that the administration of intravenous calcitriol could reduce the levels of procalcitonin but did not have a significant effect on presepsin.

Calcitriol restrains microglial M1 polarization and alleviates dopaminergic degeneration in hemiparkinsonian mice by boosting regulatory T-cell expansion.

Vitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg. Hemiparkinsonian mice model was established through the injection of 6-OHDA into the striatum. Mice were pretreated with calcitriol before 6-OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro-inflammatory cytokines levels, T-cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo. We show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6-OHDA-induced PD model. Mechanistically, calcitriol promoted anti-inflammatory/neuroprotective Treg and inhibited pro-inflammatory/neurodestructive effector T-cell generation in this model. This process significantly inhibited T-cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro-inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti-inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody-mediated Treg depletion assay. As predicted, the anti-inflammatory effects of calcitriol in the PD model were diminished following Treg depletion. These findings suggest that calcitriol's anti-inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.

FRI698 Hypoparathyroidism Secondary To Covid-19

Abstract Disclosure: M. Hussain: None. T.K. Reddy: None. A. Mohiuddin: None. D. Lovre: None. R. Galagan: None. Introduction: New onset adult hypoparathyroidism is most often caused by thyroid surgery or autoimmune illness. To date, little is known about the effect of the novel coronavirus (SARS-CoV-2) on parathyroid glands. Most recent hypotheses are that Covid-19 might affect the parathyroid glands directly through invasion of parathyroid gland tissues by SARS-CoV-2 virus or indirectly secondary to respiratory failure and chronic respiratory alkalosis. Case Report: We report the case of a 32-year-old male with post-viral hypoparathyroidism secondary to COVID-19.Only a few cases of COVID-19 induced hypoparathyroidism have been reported in the literature. Our patient was admitted to the hospital for severe and symptomatic hypocalcemia three weeks after a viral-like upper respiratory tract infection and diarrhea. He complained of paresthesias, muscle cramps and muscle weakness. He had no autoimmune or neck surgical history. Initial lab test results revealed a corrected calcium of 4.5 mg/dL (8.4-10.3 mg/dL), ionized calcium 2.4 mg/dL (4.5-5.3 mg/dL), PTH &amp;lt; 1.0 pg/mL (12-65 pg/mL), phosphorus 6.2 mg/dL (2.5-4.7 mg/dL), magnesium 1.6 mg/dL (1.5-2.6 mg/dL), Vit D, 25-hydroxy 17.3 ng/mL (30-100 ng/mL), and creatinine 1.13 mg/dL (0.7-1.4 mg/dL), consistent with hypoparathyroidism. An ECG showed QTc prolongation to 506 msec. SARS-coV-2/flu/RSV cepheid multiplex was negative, SARS-CoV-2 Spike Ab was positive. He had never received a COVID vaccine. The patient was admitted to ICU for IV calcium drip, oral calcium and calcitriol supplementation. He was transitioned to a medical ward when his severe hypocalcemia was corrected and he was ultimately discharged on oral calcitriol 1 mcg BID and calcium carbonate 1000 mg po TID. A thorough workup for a cause of the hypoparathyroidism was performed, including anti-PTH antibody, 21-hydroxylase antibody, TSI, and TPO antibody, all of which were negative. Genetic testing was performed, including CASR gene sequencing analysis and AIRE DNA sequencing, both of which were negative. After other causes of hypoparathyroidism were excluded, COVID-19 was reasoned to be the etiology of this patient’s hypoparathyroidism. Our case highlights a post-viral hypoparathyroidism secondary to COVID-19. Further studies are needed to elucidate the mechanistic relationship between COVID-19 and hypoparathyroidism. Presentation: Friday, June 16, 2023

SAT213 Post-parathyroidectomy Acute Pseudogout Flare-up; A Case Report

Abstract Disclosure: S. Rabiei: None. V. Kantorovich: None. Introduction: Acute post-parathyroidectomy pseudogout has been reported in the early post-operative. Although the exact mechanism is unknown, accepted theories include decreased solubility of calcium pyrophosphate and unbalanced equilibrium between production and hydrolysis of inorganic phosphate. We present a patient who developed an acute pseudogout attack after parathyroidectomy. The Case: Patient is a 45-year-old male with a history of nephrolithiasis who presented to outpatient clinic with a right-sided neck mass that has been present for several years with recent increase in size. He reported unintentional weight loss (25 pounds) and night sweats. On physical examination, a right lateral neck mass measuring 6 x 4 cm was noted. CT scan of the neck demonstrated a complex mass with calcification. Serum calcium (Ca), phosphorus (P), potassium (K), and alkaline phosphatase levels were 17.2 mg/dL, 1.8 mg/dL, 2.6 mmol/L, and 1,782 U/L, respectively. Serum intact parathyroid hormone (iPTH) was 3,341 pg/mL. The patient was then admitted. He received intravenous fluid, zolindronic acid, and started on vitamin D supplementation in preparation for surgery. Pre-operative CT scan of the chest, abdomen, and pelvis was concerning for metastatic disease (retroperitoneal lymphadenopathy, multiple bilateral lung solid nodules, liver, kidney and bone lesions). The patient underwent complete resection of the tumor. Intra-operative frozen section confirmed parathyroid tumor with atypia. Twenty-minute post-excision iPTH was 476 pg/mL. In the early post-operative period, serum Ca level was reduced to 7.5-8.5 mg/dL and oral Ca and calcitriol supplementation were administered. However, serum PTH reached levels as high as 900 pg/mL. Post-operative MRI demonstrated benign liver and kidney lesion with non-visualization of the previously reported retroperitoneal lymph nodes and pulmonary nodules on the CT.A few days later, the patient complained of bilateral knee pain. Serum Ca, P, and PTH levels were 7.9 mg/dL, 3.0 mg/dL, and 861 pg/mL, respectively. The skeletal survey revealed diffuse osseous metabolic process with scattered lucent osseous lesions compatible with osteitis fibrosa cystica/brown tumors as well as chondrocalcinosis of knees and hand joints. Prednisone was started for treatment of presumed acute CPPD attack with subsequent significant resolution of patient’s joint pain. Discussion: This case demonstrated the importance of thorough evaluation of musculoskeletal complaints in patients with hyperparathyroidism. Bone and joint pain in patients with hyperparathyroidism is common and is most often the result of high bone turnover. However, other etiologies including acute pseudogout should be contemplated in order to provide the appropriate treatment. Post-parathyroidectomy acute pseudogout attack should generally be treated in the same way as in the general population. Presentation: Saturday, June 17, 2023

SAT224 Nonsurgical Hypoparathyroidism: 40 Years After Diagnosis

Abstract Disclosure: L.I. Kaplan: None. A. Yuen: None. P.D. Greenberg: None. Background: The majority of cases of hypoparathyroidism occur after neck surgery. The most common nonsurgical cause is autoimmune, either in isolation or part of Autoimmune Polyglandular Syndrome Type 1. Hypomagnesemia is a functional cause. Hypoparathyroidism can occur as part of genetic syndromes that include congenital anomalies, short stature and developmental delay. Non-syndromic genetic etiologies including Autosomal Dominant Hypocalcemia type 1 (ADH1), a gain of function mutation in the calcium sensing receptor (CaSR) that can present in infancy, childhood or adulthood with hypocalcemia (50% symptomatic), hypercalcuria (10%) and basal ganglia calcification (35%). For ADH1, targeted therapies are being developed. Clinical Case: A 90-year-old male was diagnosed with hypoparathyroidism at age 50 when he presented with hand cramping and was found to have hypocalcemia with low PTH. He was started on calcitriol and calcium supplementation. Many years later he started following at our endocrine clinic. Past medical history includes prostate cancer treated with radiation and androgen deprivation therapy, HTN, and pre-diabetes. He has no history of neck surgery, other endocrinopathies, candidiasis, vitiligo or congenital anomalies. He has no family history of hypocalcemia and has two children without calcium abnormalities. His DEXA shows stable +T scores in LS spine and bilateral hips. He has not had brain imaging. Nephrocalcinosis was not reported on renal ultrasound. More than 10 years ago, he presented with severe hypercalcemia, acute renal failure (Ca 13.5 mg/dl, Cr 6.0mg/dl, Phos 5.5mg/dl) and ureteral stones after taking over the counter calcium supplements in excess. He underwent stone removal with return to baseline renal function. Subsequently, he underwent knee replacement surgeries and required IV calcium until he was able to swallow pills. Since this time, he has been managed on calcitriol, calcium carbonate, vitamin D3, and chlorthalidone with close follow up for adjustment of regimen to target Ca 8.0-8.5 mg/dl. He has not had a recurrence of severe hypercalcemia, hyperphosphatemia or nephrolithiasis. He feels well and lives at home with his wife. Lab values over the past 10 years are as follows: Ca 8.1-10.6 mg/dl (8.5-10.5), Alb 4.0-4.6 g/dl (3.5-5.4), Phos 4.3-5.5 mg/dl (2.8-4.5), Mg 1.7-1.9 mg/dl (1.3-2.1), K 3.7-4.4 mEq/L (3.6-5.2), Cr 1.0-1.5 mg/dl (0.5-1.3), PTH 0.00-1.4 pg/ml (10-55), 25 OH Vit D 18-58 ng/ml (32-100), 1,25 OH Vit D3 25.5-37.2 pg/ml (19.9-79.3), 24hr Urine Ca 162- 384 mg/24 hrs (50-400). Clinical lessons: Chronic hypoparathyroidism can be well managed with close follow up and frequent lab monitoring. This patient should be referred for genetic testing, particularly to look for ADH1 mutation in the CaSR gene as targeted treatments are being developed. His children should be tested for any mutations found in him. Presentation: Saturday, June 17, 2023