Decrease In Parathyroid Hormone Research Articles

New calcimimetics for secondary hyperparathyroidism in CKD G5D: do they offer advantages?

Secondary hyperparathyroidism is one of the most frequent metabolic abnormalities found in patients with chronic kidney disease. The calcium-sensing receptor senses extracellular calcium and is the principal regulator of parathyroid hormone secretion. Cloning of the calcium-sensing receptor led to the development of calcimimetics, drugs that decrease parathyroid hormone secretion through the positive allosteric modulation of this receptor. Cinacalcet was the first oral calcimimetic approved by the US Food and Drug Administration (FDA) in 2004 for the treatment of secondary hyperparathyroidism in adult patients on dialysis. Although cinacalcet has demonstrated safety and effectiveness, it has two main problems: gastrointestinal side effects that result in poor adherence, and the inhibitory action on CYP2D6 with the possibility of interactions with commonly used medications. To address the problem of oral compliance, Etelcalcetide, a small synthetic polycationic peptide IV calcimimetic was introduced in 2017. This drug showed a 10% greater decrease in serum parathyroid hormone values compared to cinacalcet but no better gastrointestinal tolerance, with greater risk of hypocalcemia. Several structural modifications were introduced in cinacalcet to produce a new compound called evocalcet. This drug, which was introduced in Japan in 2018, has considerably enhanced bioavailability and decreased both the inhibitory effect on CYP2D6 and half of the gastrointestinal side effects of cinacalcet. Finally, a novel non-peptidic injectable calcimimetic agent, upacicalcet, became available in Japan in 2021. This agent has greater clearance by hemodialysis and shows no effect on gastric emptying. More studies are needed comparing the old calcimimetics to the new ones to establish their future role in the treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) G5D.

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

Predicting cure and hypocalcemia by intraoperative parathyroid hormone decline in normohormonal primary hyperparathyroidism: A multi-institutional validation study

BackgroundNormohormonal primary hyperparathyroidism is characterized by hypercalcemia and inappropriately normal parathyroid hormone levels. We previously reported that intraoperative parathyroid hormone decline of 50–70% for normohormonal and 75–88% for classic primary hyperparathyroidism during parathyroidectomy was predictive of (1) cure and (2) avoidance of hypocalcemia in a single-institution study (derivation cohort). We sought to externally validate these findings. MethodsWe performed a multi-institutional retrospective cohort study of patients undergoing parathyroidectomy for primary hyperparathyroidism from 2002 to 2019 (validation cohort). Primary outcomes were biochemical cure (calcium <10.3 mg/dL) and postoperative hypocalcemia (≤8.8 mg/dL) ≥6 months postoperatively. Test characteristics of the previously derived thresholds were evaluated in this cohort. ResultsA total of 163 (16%) of 1,037 patients had normohormonal primary hyperparathyroidism. Cure rates were similar for normohormonal and classic primary hyperparathyroidism (94% vs 92%, P = .41). In patients who were cured, the median intraoperative parathyroid hormone decrease was lower in normohormonal compared with classic primary hyperparathyroidism (56.8 vs 73.3%, P < .0001). Rates of hypocalcemia were similar for normohormonal and classic primary hyperparathyroidism (14.6% vs 11.9%, P = .44), but increasing percent intraoperative parathyroid hormone decrease beyond 65% disproportionately correlated with hypocalcemia in patients with normohormonal primary hyperparathyroidism. When intraoperative parathyroid hormone thresholds from the derivation cohort were applied, positive predictive values for cure were 97% and 94% for normohormonal and classic primary hyperparathyroidism, respectively; negative predictive values for hypocalcemia were 89% for both groups. For both cohorts combined, a minimal intraoperative parathyroid hormone of 50% provided similar cure rates between groups (95.4% vs 93.8%, P = .42), whereas intraoperative parathyroid hormone exceeding 65% correlated with a greater risk of hypocalcemia in normohormonal compared with classic primary hyperparathyroidism (13.4% vs 6.9%, P = .02). ConclusionThis multi-institutional study externally validated that intraoperative parathyroid hormone decrease of 50–65% predicts cure and hypocalcemia in patients with normohormonal primary hyperparathyroidism.

Multiple fractures due to hungry bone syndrome following parathyroidectomy: a clinical case report and review of literature

BackgroundHungry bone syndrome (HBS) is defined as prolonged hypocalcemia caused by a sudden decrease in parathyroid hormone (PTH) levels after parathyroidectomy (PTX). Multiple fractures after PTX due to HBS in an end-stage renal disease (ESRD) patient on chronic hemodialysis (HD) are challenging and rare medical conditions presented in this study.Case PresentationA 42-year-old ESRD patient on HD 3 times a week presented to Shariati Hospital, Tehran, Iran, complaining of worsening bone pain and loss of appetite. Laboratory data revealed an intact parathyroid hormone (iPTH) concentration of 2500 pg/mL, an alkaline phosphatase (Alp) level of 4340 IU/L, a phosphorus (P) level of 9 mg/dL, and a calcium (Ca) concentration of 7.2 mg/dL. Sestamibi scintigraphy revealed parathyroid adenoma. The findings suggested tertiary hyperparathyroidism (HPT-III), and the patient was scheduled for total PTX. Approximately one month after surgery, the patient was referred due to convulsions, leg mobility problems, and worsening bone pain. There was bilateral femoral ecchymosis. The Ca concentration was 5.8 mg/dL, and radiological evaluations revealed multiple skeletal fractures. HBS after PTX was suggested for this patient. After several days of hospitalization, he suffered subcutaneous emphysema followed by rib fractures and passed away.ConclusionsMultiple fractures after PTX due to HBS following HPT-III in ESRD patients are rare and demanding, highlighting the necessity of timely diagnosis and management of patients with HPT-III. Severe hypocalcemia following PTX can cause skeletal disorders. However, the surgical treatment of parathyroid adenomas may be more important than the risk of complications associated with bone health.

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.

Nanocarbon tracer applied to explore the relationship between the number of exposed parathyroid glands and parathyroid function

After nanocarbon tracer was applied to thyroidectomy, we aimed to investigate the risk factors of hypoparathyroidism and the relationship between the number of exposed parathyroid glands and parathyroid function. This study retrospectively collected clinical data of patients who underwent thyroidectomy at Haining People’s Hospital from January 2019 to December 2022. Levels of parathyroid hormone (PTH) and blood calcium were observed before surgery, 1 day after surgery, and one month after surgery to assess the occurrence of postoperative parathyroid hypofunction. Patients were grouped based on their postoperative PTH levels. Furthermore, basic patient data and surgical data were collected to analyze the risk factors associated with hypoparathyroidism after thyroidectomy using single factor analysis. ANOVA analysis was used to compare the correlation between intraoperative parathyroid exposure and postoperative PTH and blood calcium levels. This study involved 80 patients. On the first day after surgery, the serum PTH and blood calcium levels of patients decreased, and 59 patients (73.75%) had normal serum PTH level after surgery, which was the normal group. Twenty-one patients (26.25%) developed hypoparathyroidism after operation and were divided into hypoparathyroidism group. Single factor analysis showed that the main risk factors of postoperative hypoparathyroidism were lesion location, lymph node dissection, nano carbon, number of lymph node metastasis, intraoperative parathyroid exposure, and inaccurate parathyroidectomy. ANOVA analysis showed that the more parathyroid exposure during operation was accompanied by the more decrease of serum PTH and blood calcium levels after operation. Therefore, the location of thyroid lesions, lymph node dissection, nano-carbon, number of lymph node metastases, intraoperative parathyroid exposure, and parathyroidectomy are risk factors for transient hypoparathyroidism after thyroid surgery. Moreover, intraoperative parathyroid exposure significantly affected serum PTH and blood calcium levels. Performing more accurate thyroidectomy and reducing parathyroid exposure help reduce the occurrence of postoperative hypoparathyroidism and hypocalcemia.

A Miniaturized Endoscopic Device Integrating Raman Spectroscopy and Laser Speckle Technology Via an Image Fusion Algorithm for Intraoperative Identification and Functional Protection of Parathyroid Glands

Abstract The importance of parathyroid glands (PGs) protection is increasingly recognized by thyroid surgeons in the field of minimally invasive video-assisted thyroidectomy (MIVAT). However, current techniques for intra-operative identification and vascularity assessment of the PGs are contentious and complex. This study presents the design and validation of a miniaturized device for fusion near-infrared autofluorescence (NIRAF) based on Raman spectroscopy and laser speckle contrast imaging (LSCI) via an image fusion algorithm for functional protection of PGs in the MIVAT. Our light source components include an integrated light emitting diode (LED) light source fiber, an NIRAF optical fiber, an acquisition optical fiber, and a laser speckle optical fiber in the endoscopic system to achieve identification and vascularity assessment of PGs using a single endoscopic probe. It has been validated in ex vivo tissue experiments that the fluorescence intensity detected by the device was equivalent to that of the marker indocyanine green (ICG) in visual images and superior to that of the thyroid and all other tissues in the neck. Based on clinical studies, MIVAT using functional fluorescence endoscopy, compared with the White light pattern group, the NIRAF combined with LSCI modality group increased the number of intra-operative confirmations of the PGs (P &amp;lt; 0.001), declined the decrease in parathyroid hormone (PTH) (P &amp;lt; 0.05) and calcium levels (P &amp;lt; 0.05) on the first postoperative day, and reduced the incidence of symptomatic hypocalcemia (P &amp;lt; 0.05). Our device may reduce the incidence of postoperative permanent hypoparathyroidism. Application of an miniaturized functional fluorescence endoscope for real-time and label-free PGs identification and vascularity assessment in MIVAT could be realized.

Significant role of 1,25-dihydroxyvitamin D on serum calcium levels after total thyroidectomy: a prospective cohort study.

Although active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of 1,25-dihydroxyvitamin D (1,25(OH)2D) has not been examined. This study comprehensively investigated the effects of 1,25(OH)2D on calcium (Ca) concentrations after total thyroidectomy. Serum Ca, parathyroid hormone (PTH), and 1,25(OH)2D levels were measured in 82 patients with thyroid disease before and after surgery. Serum Ca, PTH, and 1,25(OH)2D levels decreased significantly on the morning of the first postoperative day. Notably, the decrease in 1,25(OH)2D concentration was significantly lower than that of PTH concentration (10.5 ± 33.4% vs. 52.1 ± 30.1%, p<0.0001), with 28% of patients showing increases in 1,25(OH)2D. The only factor predicting a postoperative 1,25(OH)2D decrease was a high preoperative 1,25(OH)2D concentration. Postoperative 1,25(OH)2D concentrations, as well as the magnitude and rate of decrease from preoperative levels, showed strong positive correlations with preoperative 1,25(OH)2D concentrations (p<0.0001 for all three variables) but not with PTH concentrations. These findings suggest that 1,25(OH)2D concentrations after thyroidectomy were more strongly dependent on preoperative concentrations than on the effect of PTH decrease and were relatively preserved, possibly preventing sudden severe postoperative hypocalcemia. A high 1,25(OH)2D level was the most important preoperative factor for hypocalcemia (<2 mmol/L; p<0.05) on the first postoperative day; however, only PTH decrease was statistically significant (p<0.001) when intraoperative factors were added. In the PTH >10 pg/mL group, the decrease in 1,25(OH)2D levels was significantly associated with postoperative hypocalcemia (p<0.05). Similarly, in the PTH levels >15 pg/mL group, a decrease in 1,25(OH)2D concentration was a significant factor, and the amount of PTH decrease was no longer significant. 1,25(OH)2D plays an important role in preventing sudden, severe hypocalcemia due to decreased PTH levels after total thyroidectomy, whereas high preoperative 1,25(OH)2D levels are a significant risk factor for postoperative hypocalcemia. Optimizing preoperative protocols to adjust Ca, PTH, and 1,25(OH)2D levels to improve the management of patients undergoing total thyroidectomy and to prevent extreme intraoperative PTH decreases may reduce the risk of hypocalcemia.

Postoperative hypo parathyroid in patient with total thyroidectomy; a multi-center study

Background: Thyroidectomy complications include nerve damage, hypoparathyroidism, and bleeding. Hypoparathyroidism, marked by reduced parathyroid function, is a common complication, leading to low calcium levels and symptoms like muscle cramps. Incidence rates vary. Surgeons must prioritize parathyroid gland identification and protection during surgery to prevent complications and ensure patient well-being. Aim of the study: The aim of this study has been to evaluate the incidence of hypoparathyroidism and clinical manifestations of hypocalcemia after total thyroidectomy. Methods: This retrospective study, spanning 2020-2022 across four different hospital and teaching institutes in various parts of the world, analyzed 350 patients who underwent thyroid gland surgeries, including 350 total thyroidectomies. Focused on postoperative hypoparathyroidism as an early complication. Inclusion criteria involved age (18-85), complete thyroidectomy, and no prior hypoparathyroidism. Exclusion criteria included coexisting medical conditions and pregnancy. Postoperative hypoparathyroidism diagnosis relied on low serum calcium and parathyroid hormone levels within 24 hours. Result: The study examines the characteristics of a population undergoing thyroid surgeries. Among 144 patients, most are aged 60-65 (41.14%), with 86% females. Total thyroidectomy is standard (87.14%), while 12.86% involve lymphadenectomy. PTH levels below 15.0 pg/ml indicate potential hypoparathyroidism, more prevalent in surgeries with lymphadenectomy. Conclusion: This multicenter study highlights a significant incidence of postoperative hypoparathyroidism after total thyroidectomy and decreased parathyroid hormone (PTH) levels. Early detection and management strategies for postoperative hypoparathyroidism are crucial, with routine monitoring of serum PTH levels within 24 hours post-surgery recommended.

Clinical administration of cinacalcet in parathyroid diseases

Cinacalcet has emerged as an effective therapeutic option for the management of secondary hyperparathyroidism (SHPT) and chronic kidney disease-mineral and bone disorder (CKD-MBD). Through its modulation of the calcium-sensing receptor (CaSR), cinacalcet demonstrates considerable clinical benefits in maintaining parathyroid hormone and serum calcium levels within target ranges. It offers a valuable addition to the available treatment options for patients with these conditions. Cinacalcet binds to the CaSR on parathyroid cells, increasing its sensitivity to extracellular calcium. This results in decreased parathyroid hormone (PTH; parathormone), release through inhibition of intracellular signaling pathways involved in PTH synthesis and secretion. Cinacalcet also indirectly reduces serum calcium and phosphorus levels by suppressing PTH-mediated bone resorption and enhancing renal phosphate excretion.

PTHrP-induced hypercalcemic psychosyndrome under combined anti-PD-L1 and anti-EGFR inhibition in penile squamous cell carcinoma – A case report

IntroductionParaneoplastic hypercalcemia is a life-threatening complication and is usually caused by tumoral secretion of parathyroid hormone-related peptide (PTHrP). Endocrinopathies are common adverse events of immune checkpoint inhibitor (ICI) therapy, but only few reports describe ICI-induced hypercalcemia. Case descriptionWe report the case of a 56-year-old patient with penile cutaneous squamous cell carcinoma (cuSCC) who experienced progression after adjuvant radiochemotherapy. Within the AliCe trial, a multicenter, single-arm phase-II study for stage III/IV non-resectable/metastatic cuSCC, he received avelumab (anti-programmed cell death-ligand 1 antibody) in combination with cetuximab (anti-epidermal growth factor receptor antibody). Two hours after the initial treatment, the patient developed severe delirium, initially unresponsive to symptomatic treatment. Paraneoplastic hypercalcemia was diagnosed on the basis of decreased parathyroid hormone, normal calcitriol, and elevated PTHrP levels. Although ICI-related hypercalcemia could not be fully ruled out, study treatment was continued without further neurological symptoms, but had to be discontinued due to disease progression. The patient showed a good response to palliative chemotherapy lasting 10 months before he died due to progressive disease. ConclusionThis case demonstrates the potential risk of severe hypercalcemia. While hypercalcemia of malignancy is associated with an unfavorable prognosis, immune-mediated hypercalcemia should be considered in patients receiving ICI.

An individual approach to intraoperative parathyroid hormone measurement during total thyroidectomy

PurposeHypocalcemia is a common complication of thyroidectomy. Measurement of the intraoperative serum parathyroid hormone (PTH) levels became an established technique but it requires further improvements. We aimed to assess intraoperative PTH level testing results against the hypothesis that the PTH assay may be performed almost immediately after thyroid gland removal. MethodsA retrospective cohort study. During total thyroidectomy surgery, the patients had PTH levels measured at the cutting time and again immediately after the thyroid gland is removed. Post-operatively, serial total blood calcium levels were obtained twice daily and recorded. ResultsAmong 63 enrolled patients, 39 had multinodular goiter, 15 thyroid carcinoma, and nine had Graves' disease. The mean age was 59.8 ± 15.3 years, 43 females. The mean PTH level before surgery was 45.8 ± 22.0 pg/mL. Post-operatively, 11/63 patients developed hypocalcemia with serum calcium levels <8 mg/dL. Four patients with ≥50 % decrease in PTH concentration were normocalcemic a day after surgery and were discharged early. Four patients with ≥70 % PTH decrease were treated accordingly during prolonged hospitalization and did not suffer from permanent hypocalcemia. The cut-off value of 70 % decrease after the gland removal was able to predict postoperative hypocalcemia with a sensitivity of 100 %, specificity 82.9 %, PPV 60.0 % and NPV 100 %. ConclusionMeasurements of intraoperative PTH may not be performed at fixed time intervals but after 1–2 min after removal of the thyroid gland. Defining those not at risk would allow the majority of patients to be waived from post-operative blood calcium testing and safely discharged early after surgery.

Parathyroid Hormone Decrease During Sepsis Predicts Re-Hospitalization in Hemodialysis Patients

Parathyroid Hormone Decrease During Sepsis Predicts Re-Hospitalization in Hemodialysis Patients

Quality of life in patients with hyperparathyroidism before and after surgical treatment

BACKGROUND: Hyperparathyroidism (HPT) is a syndrome characterized by excessive synthesis of parathyroid hormone (PTH), an imbalance of phosphorus-calcium metabolism, and damage to target organs. Radical treatment of any clinical variant of HPT is surgical. In this regard, the assessment of the quality of life (QoL) of patients before and after surgery is an indicator that reflects the impact of the disease on the patient’s health and the effectiveness of the treatment.AIM: To study QoL of patients with various clinical variants of HPT before and after surgical treatment.MATERIALS AND METHODS: The single-center prospective study included patients operated on for primary (PHPT), secondary (SHPT) and tertiary HPT in 2019–2021. A comparison was made of preand postoperative QoL indicators with a sample comparable in sex and age from residents of the Irkutsk region.RESULTS: The study included 100 patients, of which 13 had multiple lesions of the parathyroid glands (PTG) and 51 with solitary lesions in PHPT, 34 with SHPT and 2 with SHPT. Indicators QoL of patients with HPT before surgery is statistically significantly lower than in the region. The greatest decrease in QoL was found in the group of patients with multiple PTG lesions in PHPT. Improvement in QoL was achieved in 90% of the studied patients. Despite the identified complications, there was an improvement in QoL after surgery in case of achieving remission of the disease. Persistence of the disease is an outcome that does not allow for a statistically significant improvement in QoL after surgery for any type of HPT. Deterioration of QoL according to some indicators was found in 10% of patients. In patients with solitary PTG lesions in PHPT, deterioration in QoL is associated with postoperative hypocalcemia against the background of the «hungry bones» syndrome, and in patients with SHPT with a decrease in parathyroid hormone below population indicators.CONCLUSION: The study demonstrates QoL of patients with various clinical variants of hyperparathyroidism before and after surgical treatment. The dynamics of QoL indicators depending on the nosology, volume, duration, outcome and complications of operations is shown.

Cinacalcet Reverses Short QT Interval in Familial Hypocalciuric Hypercalcemia Type 1.

Familial hypocalciuric hypercalcemia type 1 (FHH-1) defines an autosomal dominant disease, related to mutations in the CASR gene, with mild hypercalcemia in most cases. Cases of FHH-1 with a short QT interval have not been reported to date. Three family members presented with FHH-1 and short QT interval (<360 ms), a condition that could lead to cardiac arrhythmias, and the effects of cinacalcet, an allosteric modulator of the CaSR, in rectifying the abnormal sensitivity of the mutant CaSR and in correcting the short QT interval were determined. CASR mutational analysis was performed by next-generation sequencing and functional consequences of the identified CaSR variant (p.Ile555Thr), and effects of cinacalcet were assessed in HEK293 cells expressing wild-type and variant CaSRs. A cinacalcet test consisting of administration of 30 mg cinacalcet (8 Am) followed by hourly measurement of serum calcium, phosphate, and parathyroid hormone during 8 hours and an electrocardiogram was performed. The CaSR variant (p.Ile555Thr) was confirmed in all 3 FHH-1 patients and was shown to be associated with a loss of function that was ameliorated by cinacalcet. Cinacalcet decreased parathyroid hormone by >50% within two hours, and decreases in serum calcium and increases in serum phosphate occurred within 8 hours, with rectification of the QT interval, which remained normal after 3 months of cinacalcet treatment. Our results indicate that FHH-1 patients should be assessed for a short QT interval and a cinacalcet test used to select patients who are likely to benefit from this treatment.

Incidence of hypoparathyroidism after total thyroidectomy using conventional versus harmonic scalpel

Background As complete thyroidectomies are common procedures, we examine the effects on parathyroid hormone (PTH) levels of using a harmonic scalpel in conjunction with standard techniques. Patients and methods Eighty participants of this prospective, randomized research who had total thyroidectomies in the General Surgery Department were divided into two equal groups at random: complete thyroidectomy was performed with a harmonic scalpel in group I and a standard approach in group II. Results There is a significant correlation between the surgical technique used and the decrease in PTH after surgery. Conclusion If the conventional method was applied following thyroidectomy, there was noticeable decrease in the postoperative serum PTH. When harmonic scalpel is used throughout a thyroidectomy, there is minimal risk of hypoparathyroidism, excellent dissection, and safety.

#3579 AN INITIAL LOW-DOSE ETELCALCETIDE APPROACH IS EFFECTIVE AND COST-SAVING IN HEMODIALYSIS PATIENTS WITH MODERATE SECONDARY HYPERPARATHYROIDISM

Abstract Background and Aims Etelcalcetide (ETC) is an intravenous calcimimetic approved for the management of secondary hyperparathyroidism (sHPT) in hemodialysis (HD) patients, with benefits in terms of reduction of FGF23 levels and prevention of progression of left ventricular hypertrophy. The label recommendation is a starting dose of 5 mg after HD, to be titrated every 4 weeks according to parathyroid hormone (PTH) and calcium levels. However, it remains unclear what dosage is best to start with and, thus, how this treatment can be implemented in a real-life setting. The aim of this study was to assess the efficacy and cost-effectiveness of ETC started at lower doses than those suggested by the manufacturer in patients with moderate sHPT. Methods This is a retrospective observational study comparing two different initial ETC dosing strategies, a “Low-dose approach” (LD, ETC starting dose&amp;lt;10 mg/week) and a “Classic approach” (CL, ETC starting dose≥10 mg/week), in terms of effects on CKD-MBD related biomarkers and costs during the first year of prescription. The study was conducted on HD patients with basal PTH between 500 and 1500 ng/l, treated with ETC for at least 3 months between 2018 and 2022 at ASST Spedali Civili di Brescia. Monthly monitoring of serum calcium, phosphorus and PTH was performed in both groups for dose adjustment. Results Overall, 53 patients were identified, 24 in the LD and 29 in the CL group. Both groups showed similar baseline characteristics (Table 1). Median follow-up was 52 weeks, during which 4 patients (one in the LD and three in the CL group) discontinued ETC (Table 1). At the end of follow-up, 92% of patients in the LD and 90% in the CL group achieved a decrease in PTH ≥30% compared to baseline, with median PTH levels of 282 (207 - 332) and 294 (151 – 382) ng/l, respectively (p = 0.825). Other CKD-MBD biochemical parameters were comparable between the two groups at all timepoints (Figure 1). The median of average ETC weekly doses per patient was 7.6 (6.2 – 10.2) mg in the LD and 10.6 (9.7 – 15) mg in the CL group (p&amp;lt;0.001). During follow-up, the median ETC dose remained stable in the LD group, while partially decreasing in the CL group (Figure 1). Use of paricalcitol was comparable in both groups. At cost analysis, the median of average ETC weekly costs per patient was €36.6 (29.6 – 50.0) in the LD and €50.5 (46.4 – 71.7) in the CL group (p&amp;lt;0.001). This translates into an average yearly cost per patient of €1909 and €2635 using the LD and CL approach, respectively, with a saving of €726 per patient-year in favour of the LD strategy. Conclusion In this retrospective study in HD patients with moderate sHPT, we showed that starting ETC at a lower dose than the one suggested by the manufacturer is as effective as the classic approach in terms of control of CKD-MBD parameters, with a significant reduction in treatment costs. Future prospective studies will be needed to validate the results in bigger cohorts, test whether these benefits can extend beyond the first year of treatment and assess the effects on FGF23 levels and other relevant clinical outcomes.

#6814 A NEW SORBENT DEVICE FOR MULTIPLE CLINICAL PURPOSES: CURRENT EVIDENCE AT A PRIVATE HOSPITAL IN MEXICO

Abstract Background and Aims Adsorption is an extracorporeal technique utilized for blood purification, it also complements convection and diffusion for solute removal. Since 1991 we had used blood purification techniques, over the years, new adsorption cartridges had been developed, the new ones involving treatment for inflammatory conditions, chronic uremic symptoms and autoimmune diseases. HA130, HA230, and HA330 (Jafron, Zhuhai City, China) are among the widely used adsorption cartridges in China. We report highlights of the use of hemoperfusion using HA130 cartridges in the Mexican population cohorts in the context of multiple chronic inflammatory conditions in order to support evidence of effectiveness and safety. Method We retrospectively analyzed the medical records of 14 critically ill patients in the context of chronic inflammatory conditions such as acute kidney injury in chronic kidney disease, acute lung injury due to SARS-COV-2 infection and sepsis. Hemoperfusion in addition to standard therapy (fluid resuscitation, vasopressors, antimicrobial therapy and ventilatory support) resulted in the improvement of inflammatory substances levels when compared to standard therapy alone. Out of the 14 patients, 7 patients used HA130 cartridges and 7 patients with standard therapy alone. Results There were no significant side effects associated with HA130 cartridge use. HA 130 cartridges were found to be effective in reducing uremic symptoms in chronic hemodialysis patients, improvement of pruritus score and decreased parathyroid hormone and phosphate product (p&amp;lt;0.5) when compared to HD alone, creatinine (MARS: −24 μmol/L, −19.5 to −10.46, p &amp;lt; 0.001; SPAD: −2 μmol/L, −9.0 to +7.0/L, p = 0.314) and urea (MARS: −0.9 mmol/L, −318 to −0.189, p = 0.024; SPAD: −0.1 mmol/L, −1.0 to +0.68, p = 0.523). 66.6% of cost-effectiveness when compared to standard therapy. Conclusion In the group of patients that used HA130 cartridges we found statistically significant (p &amp;lt;0.05) reduction of pruritus score, PTH, phosphate product, creatine and urea when compared to the group of patients with standard therapy alone. The development in new cartridges technology allows more wide applications for renal patients. As we expand to involve other indications for this therapy there is cost-effectiveness improvement for the patients.More studies in different clinical settings are needed in order to achieve adsorption therapy national recommendations. We also found that the HA130 cartridges are effective in reducing uremic symptoms and microinflammatory status in acute kidney injury in chronic kidney disease patients due to the elimination of middle and small molecule uremic toxins and inflammatory mediators and endotoxins. This may translate as an improvement of quality of life and survive rates in patients with chronic hemodialysis, even though more studies are needed in order to prove this assumption.

Vitamin D Deficiency and its Relation to Lipid Profile

Background Vitamin D deficiency is considered as a major public health problem all over the world. Vitamin D acts as a hormone with multi-functions. The main source of vitamin D is solar UV radiation, which converts 7-dehydrocholesterol to pro-vitamin D which is modified to vitamin D given normal skin temperature. Vitamin D deficiency is a common disorder presents in all ages and in both genders. Vitamin D plays an important role in modulating the immune response to infections and reduction inflammatory response. Vitamin D deficiency has a genetic predisposition. There is a correlation between low 25-hydroxyvitamin D levels and dyslipidemia, so correction of vitamin D deficiency is important for treating disturbance in lipid profile. Repletion of 25-hydroxy vitamin D levels raised serum calcium level and decrease parathyroid hormone levels.

Evaluation of the Consequences of Targeted or Focused Mini-Incision Parathyroidectomy in Patients With Primary Hyperparathyroidism

Surgical approaches to primary hyperparathyroidism (PHPT) have been associated with a change from invasive to non-invasive methods in the last 20 years. In this cross-sectional descriptive study, 55 patients with primary adenoma-induced HPT underwent surgery. The parathyroid gland in patients with primary hyperparathyroidism caused by parathyroid adenoma was removed by open surgery with an incision of about 2 cm in the neck in a targeted manner in a site localized by ultrasound or Sestamibi scan. The patients' personal information, including age, sex, length of hospital stay, serum calcium and parathyroid hormone (PTH) levels, success rate, and problems and unwanted adverse consequences of surgery (e.g. infection and bleeding) were recorded for each patient and collected information was analyzed in SPSS software. Most patients were women (80%) and individuals in the age range of 41-60 years (47.3%). The hospital stay length ranged from 2 to 5 days with an average of 3.25±0.9 days. Success was considered as a decrease in PTH and calcium levels during the first 24 h after the intervention, and success rates of 100, 98.2, and 69.1%, respectively, were evaluated for a reduction of at least 50% in PTH levels and less than 40 ng/ml of PTH levels. No major complications were reported in the studied patients. Wilcoxon test revealed significant decreases in patients' postoperative serum calcium and PTH levels (P=0.000). Mini-incision Parathyroidectomy with limited incision was associated with significant reductions in serum calcium and PTD without complications.