High PTH Levels Research Articles

7630 Incidental Calvarial Brown Tumor in an ESRD patient with seizures

Abstract Disclosure: K.N. Pereira: None. V. mehta: None. S. Sekaran: None. M. Renzu: None. Brown Tumor [BT], also known as Osteitis fibrosa cystica [OFC], is a rare tertiary manifestation of hyperparathyroidism [HPTH]. BT commonly affects the maxilla/mandible, long bones and spine and presents as lytic bone lesions on imaging. Among the crania-facial bones, the maxilla, palate, temporal bone, nasal cavity, orbital bone and paranasal sinuses are affected. We describe a case of a 37 year old African-American female with extensive medical history including ESRD on hemodialysis who initially presented to the hospital with hypertensive emergency in the setting of 1 week of missed dialysis. During her presentation, she had an unexplained seizure which led to further workup with imaging. CT head revealed findings suspicious of renal osteodystrophy as well as a discrete lucency at the calvarial vertex suggestive of a brown tumor. Endocrinological studies were noted to have very high PTH levels with hypercalcemia, hyperphosphatemia and vitamin D deficiency indicative of tertiary hyperparathyroidism. Based on her clinical presentation, labs and imaging, her bone disease including BT and pathologic fractures, was deemed to be due to tertiary hyperparathyroidism in the setting of ESRD, which were not amenable to surgical intervention. Extensive literature review did not reveal any reported BTs in the calvarial vertex. This case emphasizes on the holistic approach to diagnosis of BTs and underlines that fact that BT can occur in any cortical bone including unusual presentation sites like the calvarial vertex. Presentation: 6/3/2024

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

6463 A Case of Tumour-Induced Osteomalacia Which Remitted After Treatment of Metastatic Prostate Cancer

Abstract Disclosure: J. Chua: None. M. Chuah: None. A case Tumour-induced osteomalacia (TIO) which remitted after treatment of metastatic prostate cancer. Dr Chua Jia Min, Dr Matthew Chuah Bingfeng Abstract Case report: A 69-year-old gentleman with a known history of bladder cancer presented to the emergency department with fatigue, lower back pain and bilateral lower limb weakness worsening over the past one month. MRI and bone scan revealed extensive osteoblastic bone metastases across the skeletal system. This gentleman was referred to the Endocrinology service for the evaluation of high PTH. His corrected calcium was normal at 2.17mmol/L (2.09-2.46mmol/L) and iPTH was raised at 8.74pmol/L (1.60-6.90pmol/L). He was noted to have severe hypophosphatemia 0.34mmol/L (0.94-1.50mmol/L). Bicarbonate levels were normal, there was no glycosuria or proteinuria. There was no history of IV ferrous carboxymaltose use. Further investigations were consistent with urinary phosphate loss - TRP was 0.398 and TMP-GFR was 0.199. ALP was elevated at 282ug/L (39-99ug/L). 25-hydroxyvitamin D was low at 12 ug/L, which accounted for the high PTH levels (secondary hyperparathyroidism). FGF-23 levels returned high at 1293 RU/ml (<180 RU/ml). BMD showed osteoporosis with T-score of -2.6 at the left femoral neck. He was subsequently diagnosed with metastatic prostate adenocarcinoma, based on histology from a bone biopsy of an affected vertebrae. PSA was markedly raised at 606ug/L. A diagnosis of TIO secondary to metastatic prostate cancer was made. The patient was started on PO sodium-phosphate solution 4ml TDS (approximately 3mmol/kg/day of elemental phosphorus), calcitriol 0.25mcg BD and vitamin D was replaced. After phosphate was replete, the patient's weakness and fatigue improved. He was subsequently started on androgen deprivation therapy with leuprorelin acetate injection once every 3 months and apalutamide daily. SC denosumab 60mg Q6monthly was also commenced in view of extensive bone metastases. Repeat imaging showed response to treatment with decrease in the size of the prostate and bone lesions. His PSA levels are now undetectable and TMP-GFR has normalised. His oral phosphate and calcitriol doses were gradually reduced and subsequently stopped. His calcium and phosphate levels remain within normal limits on no supplementation, suggesting remission of his TIO. PTH levels normalised after vitamin D repletion. Learning points TIO is a rare paraneoplastic syndrome usually associated with mesenchymal tumours, and treatment involves resection of the causative tumour. Cases of TIO secondary to prostate cancer (an epithelial cancer) are exceedingly rare. Despite metastatic disease, this patient responded exceedingly well to his cancer therapy. Suppression of the tumour cells with androgen deprivation therapy resulted in the lack of phosphotonin production and remission of his TIO. Presentation: 6/1/2024

Effects of Religious Fasting on Markers of Oxidative Status in Vitamin D-Deficient and Overweight Orthodox Nuns versus Implementation of Time-Restricted Eating in Lay Women from Central and Northern Greece

Background/Objectives: The Mediterranean diet has been widely suggested to exert significant beneficial effects on endothelial oxidative status and cardiometabolic health. Greek Orthodox monasteries, due to their specific nutritional and sartorial habits, comprise a population thatstrictly adheres to nutritional patterns with restricted eating and a plant-based subset of the Mediterranean diet, often accompanied by profound hypovitaminosis D. Time-restricted eating (TRE) is also adopted bya large part of the general lay Greek population for health-promoting reasons, without restrictions on animal product consumption, as imposed by Orthodox religious fasting. However, the comparative effects of these nutritional patterns on oxidative stress markers remain scarce. Methods: The present study attempted to evaluate the effects of Christian Orthodox fasting (COF) in a group of vitamin D-deficient and overweight Orthodox nuns from Central and Northern Greece compared to the implementation of TRE, a 16:8 dietary regimen (16 h of food abstinence and 8 h of feeding) in a cohort of adult women from the general population from the same region with regard to markers of endothelial oxidative status. A group of 50 women from two Orthodox monasteries in Northern Greece and one group of 50 healthy lay women were included. During the enrollment, a detailed recording of their dietary habits was performed, along with a scientific registry of their demographic and anthropometric characteristics (via bioimpedance). The Orthodox nuns followed a typical Orthodox fasting regimen [daily feeding window (8 a.m.–4 p.m.)], whereas the lay women followed a TRE 16:8 regimen with the same feeding time-window with a recommendation to follow a low-fat diet, without characteristics of the Mediterranean diet. We included a complete biochemical analysis, as well as calciotropic profiles [calcium—Ca, albumin, parathyroid hormone—PTH, and 25-hydroxyvitamin D—25(OH)D] and markers of TAC (total antioxidant capacity), GSH (glutathione),and thiobarbituric acid reactive substances (TBARSs) concentrations as markers of oxidative status. Results: All the groups were compared at the baseline regarding their calcium, PTH, and 25(OH)D concentrations, with no statistically significant differences between the groups apart from higher PTH levels in the nuns due to lower 25(OH)D levels. The Orthodox nuns manifested a lower median GSH compared to the controls (6.0 vs. 7.2, p 0.04) and a higher median TAC (0.92 vs. 0.77, p < 0.001). The TBARS comparisons showed no significant difference between the two groups. No significant associations of oxidative status with 25(OH)D, PTH, and the markers of glucose homeostasis were evident. Conclusions: The results of this small pilot study indicate that both dietary regimens have advantages over the oxidative markers compared to each other, with increased TAC in the group of Orthodox nuns after a 16-week period of COF compared to a 16:8 TRE and increased GSH concentrations in the lay women group. Future randomized trials are required to investigate the superiority or non-inferiority between these dietary patterns in the daily clinical setting.

Influence of serum uric acid on bone and fracture risk in postmenopausal women

AimsUric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture.MethodsAn observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray.ResultsHigher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures.ConclusionsIn the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures.

Incidental synchronous intrathyroidal parathyroid carcinomas and papillary thyroid microcarcinoma with compressive neck mass and primary hyperparathyroidism: case report and literature review

BackgroundParathyroid carcinoma (PC) is a rare malignancy, often diagnosed incidentally through postoperative pathological examination. The occurrence of nodular goiter, intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma (PA), and papillary thyroid microcarcinoma (PTMC) is extremely uncommon, which prompted us to report our case experience.Case presentationWe describe a 67-year-old male who presented with a cervical mass causing tracheal compression, which prompted him to seek medical advice. Based on preoperative auxiliary examination results from color Doppler ultrasound, SPECT parathyroid imaging, and blood tests, he was initially diagnosed with a suspected parathyroid adenoma and nodular goiter. Excision of the right lobe and isthmus of the thyroid, and left superior parathyroid gland was conducted, which were sent to intraoperative frozen pathological examination. During intraoperative observation, adhesion around the right thyroid lobe was discovered. Consequently, right central area lymph node dissection was performed due to suspicion of an aggressive malignant tumor. Histology and immunohistochemistry analysis revealed incidental intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma, classical papillary thyroid microcarcinoma, and nodular goiter.ConclusionParathyroid carcinoma should be highly suspected when extremely high levels of PTH and severe hypercalcemia are present, which cannot be simply explained by a preoperatively localized parathyroid adenoma, especially when suspicious malignant adhesion is found during intraoperative exploration. In cases where multifocal thyroid nodules are associated with increased uptake of 99Tc-sestamibi, the possibility of coexisting carcinomas should be considered, not only for thyroid malignancy but also for the potential presence of intrathyroidal parathyroid carcinoma.

Is denosumab an efficient and safe drug for osteoporosis in dialysis patients? Considerations and state of the art about its use in this setting.

In patients with chronic kidney disease (CKD), renal osteodystrophy may be associated with a progressive bone mass loss that increases fracture risk. Denosumab, a monoclonal antibody inhibiting osteoclast activity, is an antiresorptive medication used for the treatment osteoporosis. Its efficacy and safety were initially established in the FREEDOM study, showing a significant reduction in incident fractures in osteoporotic women treated with denosumab. Subsequent post hoc analyses showed its efficacy in patients stratified by kidney function, but these analyses did not include patients with advanced stages of CKD. The capability of denosumab in improving bone mineral density in uremic patients was evaluated in 12 studies including 461 dialysis patients with low bone mineral density. The improvement of bone mineral density was the final end point in these studies assessed during a follow-up of 6-60months. Nine of these studies did not have hyperparathyroidism among criteria for patient inclusion and their participants may have low-turnover bone disease. Despite current recommendations, no patients underwent bone biopsy before denosumab therapy. Overall, findings in these studies suggest that denosumab is a viable option for promoting bone mass recovery in patients with advanced stages of CKD having either high or low serum levels of PTH. However, the increase of bone mineral density was lower in patients with low serum markers of bone turnover at baseline. These studies also highlighted the need for calcium and vitamin D supplementation to prevent hypocalcemia that remains a serious concern. Denosumab emerges as a potentially safe and effective option for enhancing bone health in CKD patients.

#2435 Calciphylaxis: patient demographics, risk factors and outcomes in a single regional centre in New Zealand

Abstract Background and Aims Calciphylaxis, a condition associated with microvascular calcification and subsequent formation of non-healing tender skin lesions, has previously been estimated to affect only approximately 1% of patients with ESRD each year. However, clinicians practicing in a regional renal unit in the North Island of New Zealand have noted an increase in the frequency of clinical diagnoses of this condition over recent years. The aim of this review was to analyze patient demographics and risk factors and attempt to identify any correlation with subsequent outcomes. Method A cross sectional retrospective review of dialysis patients from Palmerston North Hospital's Renal Unit who were found to have diagnoses of calciphylaxis, was performed. The following factors were assessed: gender, ethnicity, smoking status, diabetes, obesity, hypertension, dialysis modality, prescription of phosphate binders, vitamin D analogues, and sodium thiosulphate (STS). We included patients with both histologically proven calciphylaxis and clinical diagnosis only. Levels of serum PTH, calcium and phosphate at the time of diagnosis were reviewed, though only PTH levels were included in the final analysis. Results A total of nineteen patients were identified having calciphylaxis as a diagnosis in the period studied. Findings were limited due to the small patient cohort size, but of those identified and reviewed some commonalities were found. Included were 9 NZ European people and 8 NZ Māori people. There were 8 females. One patient was a current smoker at time of diagnosis and five were documented as ex-smokers. Fourteen patients (74%) had type 2 diabetes mellitus and hypertension. Twelve patients (63%) were obese. Eighteen patients (95%) had hyperparathyroidism. Warfarin use was seen in 10 of the patients studied (52%) and twelve (63%) had used phosphate binders. Nine patients (47%) were diagnosed in the period between 2011 and 2021, with the remaining ten (53%) diagnoses occurring in 2022 or 2023. The majority (90%) were treated with STS, however 84% died. Dialysis modality at time of diagnosis and throughout disease span was also reviewed. Eight patients (42%) used only haemodialysis (HD), six patients (32%) used both modalities and five patients (26%) used only peritoneal dialysis. The majority (63%) of patients were on haemodialysis at time of diagnosis. Conclusion Calciphylaxis appears to be increasing dramatically in the single center studied in this review. Positive correlations were identified between high levels of PTH, obesity, hypertension, type 2 diabetes, and use of warfarin. Unfortunately, due to small case numbers, and poor historical documentation, further conclusions could not be drawn easily. A further RCT would be required to investigate the efficacy of STS as a treatment for calciphylaxis.

#1451 Calcimimetics reduce the progression of high-phosphate diet-induced tubular damage

Abstract Background and Aims During chronic kidney disease (CKD) progresses, there is an increased phosphate load and the concentration of the phosphaturic hormones PTH and FGF23 rises. In patients, phosphate and FGF23 are discussed as risk factors for CKD progression. We have recently shown that mice with high phosphate, PTH and FGF23 levels develop Stat3/Kim-1-mediated proximal tubule damage and tubulointerstitial fibrosis associated with increased MCP-1 expression and accumulation of macrophages. Calcimimetics lower PTH and FGF23 levels in hemodialysis patients and are thought to have both cardio- and nephroprotective effects. In a preclinical study, cinacalcet was shown to stabilize podocyte function in proteinuric mice. Therefore, we postulate that calcimimetics also have a positive effect on the progression of tubular damage in mice with high phosphate, PTH and FGF23 levels. Method For the induction of phosphaturic hormones with concomitant tubule damage, male C57BL/6 mice were fed a 2.0% high phosphate diet (HPD) and compared to animals on a 0.8% control phosphate diet (CPD). After four months, one HPD group was additionally treated with 1 mg/kg body weight/day etelcalcetide (KP-2326). Six months after the start of the trial, blood and urine samples as well as kidneys were taken for biochemical, histological and molecular biological examinations. Results KP-2326 treatment reduced HPD-induced PTH and FGF23 levels, but had no effect on increased phosphate excretion or elevated serum phosphate levels. Histologically, tubular damage was not as pronounced in the KP-2326-treated HPD animals as in the HPD group without therapy. The increased BUN levels caused by HPD and the albuminuria were significantly reduced by KP-2326. KP-2326 reduced HPD-mediated activation of Stat3 in proximal tubule cells and decreased Kim-1 synthesis at both mRNA and protein levels. Moreover, KP-2326 significantly reduced the mRNA expression of Ccl2 and the macrophage-specific marker Adgre1 compared to the untreated HPD group, which was histologically reflected in a lower accumulation of F4/80+ macrophages around the damaged tubules. Conclusion Treatment with KP-2326 was able to reduce the progression of HPD-induced tubule damage, at least in part due to the reduction in PTH and FGF23 levels.

#3065 Factors associated with recurrence or persistently high parathormone levels after parathyroidectomy in patients with CKD

Abstract Factors associated with recurrence or persistently high parathormone levels after parathyroidectomy in patients with secondary hyperparathyroidism receiving renal replacement therapy Background and Aims Resistant hyperparathyroidism that indicates surgery usually occurs in patients with CKD who receive renal replacement therapy (RRT). This study aims to evaluate the factors associated with persistent or recurrent high levels of PTH after parathyroidectomy due to SHPT in patients receiving RRT. Method In this retrospective study, we included 66 adult patients (mean age: 46.86 ± 13.79) with parathyroidectomy for SHPT receiving renal replacement therapy. Clinicopathological features, laboratory parameters (preoperatively, at the first hour of surgery, at least every three months for at least two years after surgery), type of surgery and pathologic diagnosis were recorded from the medical records. Persistence was defined as failure to achieve a decrease in PTH level of more than fifty percent of preoperative PTH level. Recurrence was defined as elevated PTH levels after six months post-operation (>600 pg/mL). Results The demographics and clinical characteristics of the study population are described in Table 1. High PTH levels were observed in nineteen patients, while recurrence was observed in nine. Persistence was associated with lower preoperative ALP levels (455.27 ± 296.23, 619.72 ± 593.18, p = 0.017). Recurrence was associated with higher preoperative CRP levels (22.89 ± 6.82, 6.82 ± 5.35, p:0,046) and postoperative high phosphorus levels (4.93 ± 0.99, 4.16 ± 1.09, p = .049). Conclusion In our study persistence of high parathormone levels were more common in patients with lower preoperative ALP levels and recurrence was associated with higher preoperative CRP levels and postoperative inadequate phosphorus control. In conclusion, patients with lower ALP and higher CRP levels can be suitable for total parathyroidectomy, which is associated with a lower recurrence rate in SHPT. Also, postoperative phosphorus control can be a key point for preventing the patients' recurrence of high PTH level.

Biochemical Clusters as Substitutes of Bone Biopsies in Kidney Transplant Patients.

Bone and mineral metabolism abnormalities are frequent in kidney transplant recipients and have been associated with cardiovascular morbidity. The primary aim of this study was to analyse the association between routine clinically available biochemical evaluation, non-routine histomorphometric bone evaluation, and vascular disease in kidney transplanted patients. A cross-sectional analysis was performed on 69 patients, 1-year after kidney transplantation. Laboratory analysis, radiography of hands and pelvis, bone biopsy, bone densitometry, and coronary CT were performed. One-year post-transplantation, nearly one-third of the patients presented with hypercalcemia, 16% had hypophosphatemia, 39.3% had iPTH levels > 150pg/mL, 20.3% had BALP levels > 40 U/L, and 26.1% had hypovitaminosis D. Evaluation of extraosseous calcifications revealed low Adragão and Agatston scores. We divided patients into three clusters, according to laboratory results routinely used in clinical practice: hypercalcemia and hyperparathyroidism (Cluster1); hypercalcemia and high BALP levels (Cluster2); hypophosphatemia and vitamin D deficiency (Cluster 3). Patients in clusters 1 and 2 had higher cortical porosity (p = 0.001) and osteoid measurements, although there was no difference in the presence of abnormal mineralization, or low volume. Patients in cluster 2 had a higher BFR/BS (half of the patients in cluster 2 had high bone turnover), and most patients in cluster 1 had low or normal bone turnover. Cluster 3 has no differences in volume, or turnover, but 60% of the patients presented with pre-osteomalacia. All three clusters were associated with high vascular calcifications scores. Vascular calcifications scores were not related to higher bone mineral density. Instead, an association was found between a higher Adragão score and the presence of osteoporosis at the femoral neck (p = 0.008). In conclusion, inferring bone TMV by daily clinical biochemical analysis can be misleading, and bone biopsy is important for assessing both bone turnover and mineralization after kidney transplantation, although hypophosphatemia combined with vitamin D deficiency is associated with abnormal mineralization. The presence of hypercalcemia with high levels of PTH or high levels of BALP, or hypophosphatemia and vitamin D deficiency should remind us to screen vascular calcification status of patients.Clinical Research: ClinicalTrials.gov ID NCT02751099.

Patellar and quadriceps tendon rupture are associated with hip fracture in hemodialysis patients with severe hyperparathyroidism.

Spontaneous rupture of the patellar (PTR) and quadriceps (QTR) tendon is infrequent. Systemic diseases such as diabetes mellitus, CKD, and secondary hyperparathyroidism (SHPT) are risk factors. The present cohort study aimed to evaluate risk factors associated with tendon rupture in hemodialysis (HD) patients with SHPT, as well as outcomes including surgical complications, re-ruptures, and fracture. Baseline clinical, laboratorial data, and radiographs were analyzed. Patients were followed up from March 2012 to March 2020. One-hundred thirty-one patients (≥18yr of age, on HD ≥ 6mo, with SHPT) were included. Incidence rates of PTR and QTR were 2.3 and 1.7/10000 HD patients/yr, respectively. The mean age of patients with tendon rupture was 44.0 ± 11.2yr. These patients exhibited higher serum levels of phosphorus (6.3 ± 1.5mg/dL vs 5.6 ± 1.1mg/dL; P = .005), PTH (2025.7 ± 667.6pg/mL vs 1728.4 ± 684.8pg/mL; P = .035), and C-reactive-protein (35.4 ± 32.9mg/dL vs 17 ± 24.5mg/dL; P = .002) compared to the group without tendon rupture. The mean follow-up was 56.7 ± 27.1mo. No patient required a new surgical approach or experienced re-rupture. Of all patients, 31% experienced hip fracture: 50% in the group with rupture (29.5 ± 17.4mo after the tendon rupture) vs 26% without tendon rupture (P = .015). After adjustment, the hazard ratio for hip fracture was 2.87 (95% CI, 1.27-6.49; P = .012). Patients with SHPT and high levels of phosphorus, PTH, and inflammatory markers were at greater risk for tendon rupture. Surgical complication rates were low. However, results suggest that tendon rupture of knee extensor mechanism in HD patient with SHPT should be regarded as a "red flag" for future hip fracture.

Evaluation of Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio in primary hyperparathyroidism before and after parathyroidectomy

Aims: This study aimed to evaluate Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratios, which are new ventricular repolarization (VR) parameters in primary hyperparathyroidism (PHPT) patients, and also investigate the potential effect of parathyroidectomy (PTx) on these parameters. Methods: In total, 27 patients with PHPT who underwent PTx and 25 control subjects were selected for our study. Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratios of patients planned for PTx were compared to healthy matched controls. Electrocardiographic parameters measured 6 months after the surgery were also compared with preoperative values for each patient. Results: Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were significantly higher in PHPT patients compared to the control group (p<0.001, for all).It was observed that the parameters mentioned after surgery decreased significantly, and there was no statistical difference when compared to the control group.The correlation analysis revealed a significant and positive correlation between corrected calcium (CCa) and PTH levels with Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio (for Ca; r=0.515, p=0.006; r=0.398, p=0.040; r=0.797, p<0.001 respectively vs. for PTH; r=538, p=0.04; r=0.422, p=0.028; r=0.812, p<0.001 respectively). Conclusions: This study showed that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were prolonged in PHPT.These values, which are accepted as an indicator of sudden cardiac death after PTx, decreased significantly. In addition, both high PTH and high calcium(Ca) levels appear to have the potential to cause arrhythmogenic effects separately.

Parathyroid hormone level predicts mortality in hemodialysis; an old problem remains still

Several studies have found a clear association between higher PTH levels and increased mortality risk in hemodialysis patients. The studies indicate that higher levels of PTH are linked to a higher risk of cardiovascular events, such as heart attacks and strokes, as well as an increased risk of bone fractures.

SAT210 A Case Of Recurrent Metastatic Parathyroid Cancer Complicated By Multiple Brown Tumors

Abstract Disclosure: A. Elmaaz: None. E. Bustamante: None. M. Batra: None. Introduction: Parathyroid cancer is a rare malignancy with about 25 % incidence of metastasis. Brown tumors are benign bone lesions caused by excessive bone turnover which are rarely associated with parathyroid carcinoma. Here, we present a case of recurrent metastatic parathyroid cancer complicated by multiple brown tumors. Case Presentation: A 63-year-old male presented with back pain, generalized weakness, and significant weight loss. Laboratory findings showed hypercalcemia 14.4 mg/dl, Alkaline phosphatase 253 U/L, and phosphorus 2.3 mg/dl. He was admitted to the hospital for hypercalcemia workup. MRI spine showed a heterogeneous mass arising from the left thyroid lobe and conglomerate lymph node, along with extensive metastatic sclerotic lytic lesions throughout the spine. MRI brain revealed multiple metastatic lesions in the skull base, facial bones, and the right angle of the mandible. Further workup revealed normal PSA, normal serum levels of free lambda and kappa light chains, and normal urine and serum protein electrophoresis. PTH levels, 2435.1 (8.7-77.1) pg/ml, and PTH-rP levels <1.1 pmol/l were noted. Ultrasound-guided FNA of the thyroid mass showed solid growth of malignant parathyroid cells strongly stained for PTH. Biopsy of the body of the T12 vertebra and mandibular lesions showed giant cell lesions of the bone with fibrous dysplasia, consistent with brown tumors. IV hydration, calcitonin, cinacalcet, and IV zoledronic acid started, followed by left hemithyroidectomy and left inferior parathyroidectomy. Surgical pathology was positive for parathyroid carcinoma invading the thyroid gland. His calcium and PTH levels post-surgery significantly improved. A few months later, the patient presented again with hypercalcemia and high levels of PTH. Sestamibi parathyroid scan showed no evidence of parathyroid adenoma. Because of enlarging left neck mass, confirmed by MRI neck, he then underwent excision of the left subcutaneous cervical lesion involving the left sternomastoid muscle. Surgical pathology was consistent with parathyroid carcinoma involving soft tissue. His calcium and PTH levels improved on subsequent follow-up visits. Conclusion: Parathyroid carcinoma is not a common cause of hypercalcemia. Though a rare entity, parathyroid cancer should be considered in the differentials of hypercalcemia and extremely high levels of PTH. Metastasis either locally or remotely should not be overlooked. Brown tumors could mimic bone metastasis and giant cell tumors; therefore, the clinical presentation is important for the diagnosis. Presentation: Saturday, June 17, 2023

SAT203 Parathyroid Adenoma Masquerading As Parathyroid Carcinoma

Abstract Disclosure: M. Fariduddin: None. A. Lupieri: None. H.L. Calero: None. A. Rubenfeld: None. Y. Eisenberg: None. Case: 22 y/o pregnant female (5 weeks gestation) presented to the endocrinology clinic after a hospital admission for nausea, vomiting, constipation, fatigue and joint pain with labs showing calcium (corrected) of 14 mg/dL and PTH of 1200 pg/ml. Labs in the clinic showed calcium at 16 mg/dL and PTH 1500 pg/ml. She was re-admitted for IV fluids, calcitonin and zoledronic acid. Severe hypercalcemia, young age, and extremely high PTH levels were highly suggestive of parathyroid cancer. CT of neck showed a 2 cm right inferior parathyroid mass abutting the esophagus with concern for esophageal invasion with no evident plane between the mass and the esophagus. No cervical adenopathy was noted. Patient in conjunction with her obstetrician made an informed decision to terminate the pregnancy as this was an undesired pregnancy. She underwent an urgent right inferior gland parathyroidectomy. The mass was not fixed to underlying structures and was resected in-toto. Pathology showed chief cells with clear cytoplasm, and homogeneously round nuclei. There were no atypical mitoses, lymphovascular invasion, perineural invasion, or other invasive features concluding the final pathology as parathyroid adenoma. Discussion: Primary hyperparathyroidism predominantly affects postmenopausal women. Most common cause is parathyroid adenoma (80-85%). Parathyroid carcinoma is a rare cause of primary hyperparathyroidism (1-2%).80% people with parathyroid adenoma and primary hyperparathyroidism are diagnosed incidentally with mildly elevated calcium. PTH elevation is around 1.5-2 times the upper limit of normal. Symptoms are mild sequelae of hypercalcemia. PTH levels 5-10 times upper limit of normal, severe hypercalcemia (Ca > 14 mg/dl) or a hypercalcemia crisis are highly suspicious for parathyroid cancer. Surgical resection is the mainstay of treatment. Clinical criteria play a key role in early identification of parathyroid carcinoma in order to get these patients to surgery before tumor spread and improve long term survival. Our patient with significantly elevated calcium and parathyroid hormone had an atypical presentation of a parathyroid adenoma thus uncovering the limitations of clinical criteria in identifying a parathyroid carcinoma. Most of the patients with a parathyroid adenoma will eventually require surgery, however the technique, extent and urgency of surgery is affected based on clinical situations like these. The timing of the surgery could be detrimental when coupled with a scenario like our patient’s pregnancy wherein you could delay the surgery until the second trimester had the patient wanted to continue the pregnancy. This case highlights the importance of awareness of atypical presentations of parathyroid adenomas and to have a cautious approach in patients with clinical concern for parathyroid carcinoma especially if there is a potential benefit to delay surgery. Presentation: Saturday, June 17, 2023

Cardiac effects of parathyroid hormone excess; an updated mini-review

Hyperparathyroidism causes high levels of PTH, which can lead to a variety of cardiovascular problems that can pose a significant risk to an individual’s overall health. In more severe cases, such as high blood calcium levels due to primary hyperparathyroidism, the individual may also experience increased risks of kidney stones, bone fractures, and osteoporosis.

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

BackgroundSevere secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery.MethodsWe aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage.ResultsFrom 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002).ConclusionsOur data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.Graphical abstract

Mineral and Bone Metabolism Markers and Mortality in Diabetic Patients on Haemodialysis.

Diabetic patients on haemodialysis have a higher risk of mortality than non-diabetic patients. The aim of this COSMOS analysis was to assess whether bone and mineral laboratory values (calcium, phosphorus, and PTH) contribute to such risk. COSMOS is a multicentre, open-cohort, 3-year prospective study, which includes 6797 patients from 227 randomly selected dialysis centres from 20 European countries. The association between mortality and calcium, phosphate or PTH was assessed using Cox proportional hazard regression models using both penalized splines smoothing and categorization according to KDIGO guidelines. The effect modification of the association between the relative risk of mortality and serum calcium, phosphate or PTH by diabetes was assessed. There was a statistically significant effect modification of the association between the relative risk of mortality and serum PTH by diabetes (p = 0.011). The slope of the curve of the association between increasing values of PTH and relative risk of mortality was steeper for diabetic compared with non-diabetic patients, mainly for high levels of PTH. In addition, high serum PTH (> 9 times the normal values) was significantly associated with a higher relative risk of mortality in diabetic patients but not in non-diabetic patients (1.53[95%CI:1.07-2.19] and 1.17[95%CI:0.91-1.52]). No significant effect modification of the association between the relative risk of mortality and serum calcium or phosphate by diabetes was found (p = 0.2 and p = 0.059, respectively). The results show a different association of PTH with the relative risk of mortality in diabetic and non-diabetic patients. These findings could have relevant implications for the diagnosis and treatment of CKD-MBD.

The Influence of Hyperparathyroidism Patient Profile on Quality of Life After Parathyroidectomy.

Improvements in quality of life (QoL) after parathyroidectomy in patients with primary hyperparathyroidism (PHPT) is discussed. It has not been analyzed whether these improvements can be influenced by a specific socio-personal or clinical patient profile. to analyze QoL differences after parathyroidectomy and to determine a socio-personal and clinical profile that influences improvement after parathyroidectomy. A longitudinal prospective cohort study in patients with PHPT. SF-36 and PHPQOL questionnaires were completed by the patients. A comparative preoperatory analysis was carried out, at three and twelve months after surgery. Student's t test was used for the correlations. The size of the effect was assessed using G*Power software. A multivariate analysis was performed to evaluate the socio-personal and clinical variables affecting the improvement in QoL after surgery. Forty-eight patients were analyzed. Three months after surgery an improvement was found in physical function, general health, vitality, social function, emotional role, mental health and in the patient's declared health assessment. One year after the intervention a general improvement was observed, with a greater effect on mental health and declared health evolution. Patients with bone pain presented with a higher probability of improvement after surgery. Patients with prior psychological disease had a lower associated probability of an improvement and high levels of PTH related to a greater probability of improvement after surgery. There is an improvement in the QoL of PHPT patients after parathyroidectomy. Patients with bone pain and high PTH levels prior to the parathyroidectomy present with a greater probability of having a greater improvement in QoL after surgery.