High Serum Parathyroid Hormone Research Articles

The risk factors for in-stent restenosis following drug-eluting stent implantation in end-stage renal disease patients receiving renal replacement therapy

Abstract Background Chronic renal disease is a recognized risk factor for in-stent restenosis (ISR) following percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). However, the specific risk of ISR among individuals with end-stage renal disease (ESRD) remains unclear or insufficiently studied. Purpose It is imperative to identify the risk factors associated with ISR among patients with ESRD and coronary artery disease following the implantation of DES. This identification is crucial for generating evidence-based strategies aimed at preventing ISR. Methods ESRD patients undergoing renal replacement therapy with concomitant coronary artery disease who underwent PCI with their initial DES implantation at our hospital between January 2013 and December 2022 were included in the study cohort. Clinical data, laboratory test results, and PCI specifics were compared between patients with and without ISR. Univariate and multivariate analyses utilizing Cox proportional hazard regression were employed to identify independent risk factors for DES-ISR. Results Among the 321 patients with ESRD who underwent PCI with DES implantation, totaling 874.5 patient-years of follow-up, 53 cases of ISR occurred during this period, yielding an incidence rate of 6.1 per 100 patient-years. Several baseline characteristics, angiographic findings, and procedural details were found to elevate the risk of ISR significantly. These included underlying diabetes mellitus, peripheral artery disease (PAD), high serum parathyroid hormone levels, LDL-C levels, acute coronary syndrome as the clinical presentation, the presence of triple vessel disease, duration of dual antiplatelet therapy less than 1 year, target lesion involving the left main (LM) or left anterior descending (LAD) artery, target vessel size less than 3 mm, ostial lesion, bifurcation lesion, number of stents implanted equal to or more than 3, and stent size less than 3 mm. In the multivariate Cox proportional hazard model, bifurcation lesion (HR 14.70, 95% CI 4.66-46.38), PCI of LM or LAD (HR 5.29, 95% CI 1.14-24.60), target vessel size less than 3 mm (HR 4.10, 95% CI 1.77-9.50), PAD (HR 3.92, 95% CI 1.52-10.08), and ostial lesion (HR 2.92, 95% CI 1.16-7.38) were identified as independent risk factors for ISR (all p-values < 0.05). Conclusions Among ESRD patients with coronary artery disease, bifurcation lesion, PCI involving the LM or LAD, target vessel size less than 3 mm, PAD, and ostial lesion are identified as independent risk factors for ISR. These findings hold significance in enhancing risk stratification and decision-making concerning treatment planning for this population.Univariate analysis risk factors for ISR

Acute pancreatitis and refractory hypercalcemia in the third trimester caused by parathyroid carcinoma

BackgroundHypercalcemia can be a rare contributor to acute pancreatitis (AP) in pregnancy. This is primarily due to primary hyperparathyroidism (PHPT), resulting from parathyroid carcinoma. We exhibited a case report to analyze the diagnosis and treatment during the onset of hypercalcemia-induced AP.Case presentationA 32-year-old primigravida presented with acute pancreatitis near full-term gestation. Following a cesarean delivery, there was a reduction in serum amylase and peripancreatic exudate, but her serum calcium concentrations persistently elevated over 4.0 mmol/L. Interventions to lower the hypercalcemia were only temporarily effective, until a high serum parathyroid hormone (PTH) concentration of 1404 pg/mL was detected. Ultrasound revealed a 31 mm × 24 mm hypoechoic oval nodule in the left lower lobe of the thyroid gland. She underwent a parathyroidectomy, resulting in a dramatic decrease in serum PTH level, from preoperative levels of 2051 pg/mL to 299 pg/mL just 20 minutes after removal. Similarly, her serum calcium declined from 3.82 mmol/L to 1.73 mmol/L within 24 hours postoperatively. The final histopathology suggested parathyroid carcinoma.ConclusionWhen refractory hypercalcemia is present, serum PTH levels should be measured to determine PHPT. Parathyroidectomy is the optimal strategy for alleviating hypercalcemia and clarifying the underlying pathology.

Clinical characteristics and outcomes of patients operated for primary hyperparathyroidism at Tampere University Hospital in 2017-2018.

Studies on the outcomes of parathyroid surgery are scarce. The aim was to report the outcomes and to study the association between pre- and peri-operative information with the outcomes of patients operated for primary hyperparathyroidism. This was a retrospective, descriptive study with unselected patients treated surgically for primary hyperparathyroidism from a catchment population of 704,500 in Finland. Data were acquired from the electronic hospital registers based on parathyroid surgery procedure codes between 1 January 2017 and 31 December 2018. Preoperative data, surgical data, preoperative and postoperative laboratory values, histopathological findings, and postoperative clinical data were recorded. During the 2-year study period, 149 patients with primary hyperparathyroidism were treated surgically with a 97% remission rate. Surgical complications included postoperative bleeding in two patients (1%) and vocal cord paralysis in one patient (0.6%). No postoperative infections were reported. Three patients (2%) developed postoperative hypoparathyroidism necessitating the use of alfacalcidol more than 1 month after surgery. Ionized calcium measured 0-1 days after surgery was not statistically significantly associated with remission or postoperative hypoparathyroidism. Serum parathyroid hormone (PTH) assessed 0-1 days postoperatively was associated with persistent disease, but not with postoperative hypoparathyroidism. The histopathological diagnosis was adenoma or hyperplasia in 112 patients (75%), atypical adenoma in 28 patients (19%), and carcinoma in five patients (3%). Patients with parathyroid carcinoma had higher preoperative ionized calcium and PTH values than those with adenoma or hyperplasia. Most patients who were operated due to primary hyperparathyroidism achieved normocalcemia after surgery, and the frequency of complications was low. Ionized calcium taken 0-1 days after surgery was not associated with remission of hyperparathyroidism or postoperative hypoparathyroidism. High postoperative serum PTH predicted persistent disease.

Parathyroid adenoma in a 33 years female, manifesting as non-traumatic multiple bone fractures

A 33 years old female patient presented to OPD with chief complaints of prolonged fatigue, abnormal gait and difficulty in walking since 7 years. On further evaluation MRI pelvis revealed bilateral non-traumatic pelvic bone fractures, with high Serum parathyroid hormone level (1050 pcg/ml) and hypercalcemia. CECT Neck showed a well-defined soft tissue density lesion involving the posterior-inferior aspect of the right lobe of thyroid gland. Surgical resection was performed and histopathology revealed parathyroid adenoma. Clinical manifestations and PTH and calcium levels gradually decreased to normal after surgery. Patient’s symptoms gradually decreased over a period of 2 month after treatment of the underlying cause. In a young female presenting with bony pains and non-traumatic fractures, a differential diagnosis of parathyroid adenoma must be kept in mind.

Some genetic differences in patients with rheumatoid arthritis

ObjectiveVitamin D is important for bone and cartilage metabolism. Changes in vitamin D blood level may be related to pathological disorders such as rheumatoid arthritis (RA). The main aim of this study is to investigate the association between RA and the vitamin D receptor (VDR) genes FokI and TaqI polymorphisms. One hundred RA patients and fifty healthy matched controls were assessed for VDR FokI and TaqI genotyping. Intact parathyroid hormone (PTH) and calcium (Ca) levels were measured, categorized, and compared between the cases and control groups.ResultsWe found that the FokI genotype frequencies for the RA cases and control groups were FF:Ff:ff = 46%:52%:2% and 50%:50%:0%, respectively (P = 0.76). The TaqI genotype frequencies for the RA cases and control groups were TT:Tt:tt = 45%:44%:11% and 42%:42%:16%, respectively (P = 0.69). A statistically significant high serum PTH level was associated with the ff genotype (p = 0.03), and a significantly low serum Ca level was associated with the TT genotype (p = 0.003). In comparison with controls, no influence of VDR FokI and TaqI genotypes on RA susceptibility or risk was demonstrated.

Current and Emerging Markers and Tools Used in the Diagnosis and Management of Chronic Kidney Disease-Mineral and Bone Disorder in Non-Dialysis Adult Patients.

Chronic kidney disease (CKD) is a significant public health concern associated with significant morbidity and has become one of the foremost global causes of death in recent years. A frequent comorbidity of CKD is secondary hyperparathyroidism (SHPT), exemplified by high serum parathyroid hormone (PTH) levels. The mineral metabolism disturbances resulting from CKD and progression to SHPT are currently considered part of the definition of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, CKD-MBD does not only include abnormalities in laboratory-measured parameters; it is a complex condition characterized by dysregulation of bone turnover, mineralization, growth and strength, accompanied by vascular or another soft-tissue calcification. Together, this increases the risk of bone fractures, cardiovascular disease, and overall mortality in CKD-MBD patients. Monitoring serum markers is essential in diagnosing SHPT and CKD-MBD, and there are several recognized indicators for prognosis, optimal clinical management and treatment response in late-stage kidney disease patients receiving dialysis. However, far fewer markers have been established for patients with non-dialysis CKD. This review provides an overview of current and emerging markers and tools used in the diagnosis and management of CKD-MBD in non-dialysis adult patients.

Bone Mineral Density, Trabecular Bone Score and Fractures in Patients Hospitalized for Heart Failure.

This study aimed to evaluate the bone mineral density (BMD), trabecular bone score (TBS), and fracture history of middle-aged patients hospitalized for heart failure (HF), as well as analyze the association of these factors with cardiometabolic parameters and muscle strength. A cross-sectional study with patients aged 40 to 64 years hospitalized for HF was performed. Dual energy X-ray absorptiometry was performed to obtain BMD and TBS. Fracture history, handgrip strength (HGS), and clinical and laboratory cardiometabolic parameters of the patients were evaluated. Altogether, 109 patients were evaluated (female 50.5%). Medians and interquartile ranges for age and length of hospital stay were 58.0 (53.0-61.0) years and 20.0 (11.0-32.0) days, respectively. Osteoporosis was observed in 15.6% of the patients, low TBS was observed in 22.8%, and 6 patients had a history of fragile fracture. No differences between the sexes regarding BMD (p=0.335) or TBS (p=0.736) classifications were observed. No association was observed between low BMD and HF classification (p>0.05) regarding the ejection fraction, ischemic etiology, or New York Heart Association Functional Classification. However, there was a significant association between high serum parathyroid hormone (PTH) and the presence of osteoporosis (62.5 [37.2-119.0] pg/mL vs. 34.2 [25.0-54.1] pg/mL; p=0.016). There was a negative correlation between serum PTH and TBS (r=-0.329, p=0.038) and a higher frequency of reduced HGS in patients with low TBS (92.3% vs. 50.0%; p=0.009). We found relevant frequencies of osteoporosis and bone microarchitecture degradation in middle-aged patients with HF, which were related to high serum PTH concentrations.

Abstract #1373163: A Rare Case of Ectopic Parathyroid Adenoma in the Left Axillary Region

A parathyroid adenoma is a benign neoplasm that arises from parathyroid parenchymal cells. Parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHPT). Ectopic parathyroid adenomas arise within the parathyroid glands located at the four poles of the thyroid [2]. Ectopic parathyroid adenomas result from aberrant migration of the gland during the early stages of development and can be identified in up to 16% of cases of PHPT [3]. They are commonly found in the mediastinum, within the thyroid, and along the path of the vagus or recurrent laryngeal nerves [4]. 45% of ectopic parathyroid adenomas are found in the paraesophageal region, 25% in the cervical thymus, 20% in the cervical mediastinum, 5% in the anterior portion of the mediastinum, and 5% at the level of the thymus [5]. A 64-year-old man with a past medical history of over 20-year history of recurrent nephrolithiasis, type II diabetes mellitus, dyslipidemia, hypertension, and pancreatic cancer presented to our outpatient endocrine clinic for evaluation of hyperparathyroidism. Further investigation of his history revealed that he had struggled with several bouts of urinary calculi throughout his life. These episodes required multiple surgical interventions to treat, including left nephrectomy and ureteral stenting. He had been evaluated for high serum calcium in the past and was diagnosed with PHPT by his urologist, who referred him to our clinic. Also complicating his health was a recent diagnosis of prostate cancer for which, he was undergoing radiation treatment. He had a family history of thyroid disorder in his mother but no family history of parathyroid disorders. Physical examination was unremarkable. Laboratory investigations revealed high serum calcium and high serum parathyroid hormone. Parathyroid scintigraphy with 99mTc-sestamibi revealed a subtle persistent focal region of increased uptake in the left axilla with no other areas of increased uptake, raising the suspicion for parathyroid adenoma in the left axilla. As discussed earlier, ectopic parathyroid adenomas result from aberrant migration of parathyroid tissue during embryological development. Additionally, ectopic parathyroid adenomas are a cause of failed surgery for hyperparathyroidism as well as persistent and recurrent hyperparathyroidism [3, 7-9]. Ectopic parathyroid tissue has a prevalence of 2-43% in anatomic series and has been detected in up to 16% of patients undergoing evaluation for hyperparathyroidism [3, 7, 10]. Ectopic parathyroid adenomas arising within the axilla may present with hypercalcemia and associated skeletal and renal involvement [11, 12]. The case that has been reported had a presentation of PHPT with recurrent nephrolithiasis. As mentioned earlier, 45% of ectopic parathyroid lesions are found in the paraesophageal region with 38% arising within the thymus [7, 10]. However, in this case, the patient presented with a possible ectopic parathyroid adenoma localized to the left axilla and no other areas of increased uptake on tc99m-sestamibi parathyroid scintigraphy.

A novel murine model of combined insulin-dependent diabetes and chronic kidney disease has greater skeletal detriments than either disease individually.

Diabetes and chronic kidney disease (CKD) consistently rank among the top ten conditions in prevalence and mortality in the United States. Insulin-dependent diabetes (IDD) and CKD each increase the risk of skeletal fractures and fracture-related mortality. However, it remains unknown whether these conditions have interactive end-organ effects on the skeleton. We hypothesized that combining IDD and CKD in mice would cause structural and mechanical bone alterations that are more deleterious compared to the single disease states. Female C57BL6/J mice were divided into four groups: 1) N=12 Control (CTRL), 2) N=10 Streptozotocin-induced IDD (STZ), 3) N=10 Adenine diet-induced CKD (AD), and 4) N=9 Combination (STZ+AD). STZ administration resulted in significantly higher blood glucose, HbA1c (p<0.0001), and glucose intolerance (p<0.0001). AD resulted in higher blood urea nitrogen (p=0.0002) while AD, but not STZ+AD mice, had high serum parathyroid hormone (p<0.0001) and phosphorus (p=0.0005). STZ lowered bone turnover (p=0.001). Trabecular bone volume was lowered by STZ (p<0.0001) and increased by AD (p=0.003). Tissue mineral density was lowered by STZ (p<0.0001) and AD (p=0.02) in trabecular bone but only lowered by STZ in cortical bone (p=0.002). Cortical porosity of the proximal tibia was increased by AD, moment of inertia was lower in both disease groups, and most cortical properties were lower in all groups vs CTRL. Ultimate force, stiffness, toughness, and total displacement/strain were lowered by STZ and AD. Fracture toughness was lower by AD (p=0.003). Importantly, Cohen's D indicated that STZ+AD most strongly lowered bone turnover and mechanical properties. Taken together, structural and material-level bone properties are altered by STZ and AD while their combination resulted in greater detriments, indicating that improving bone health in the combined disease state may require novel interventions.

ODP588 A Rare Case Of Infantile Transient Psuedohypoparathyrodism

Abstract Background Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders in which resistance to parathyroid hormone (PTH) in the proximal renal tubules leads to hypocalcemia, hyperphosphatemia, and impaired 1,25(OH)2 vitamin D production. Clinical Case A 2-month-old child presented with history of recurrent focal seizures since last 10 days. During the first episode, the child was treated with anti- convulsant by paediatrician. Five days later she again developed focal seizures, this time the child was evaluated and serum calcium was 5.6 mg/dl (normal, 8.6-10.2 mg/dl), phosphorus 7.5 mg/dL (normal, 4. 0-7. 0 mg/dL), and magnesium 2. 0 mg/dL (normal 1.8-2.4 mg/dL). In view of symptomatic hypocalcemia, she was treated with I. V. 10% calcium gluconate and oral calcifediol (800 IU/day). The child was seizure free but still had hypocalcemia - serum calcium-6.8 mg/dl, hence the child was evaluated further- serum PTH was 561 pg/mL (normal, 9-91 pg/mL), 25-hydroxyvitamin D was 54.1 ng/mL (normal, 5-60 ng/mL), 1,25 Vit D-6.28 pg/mL (normal, 19.9-79.3pg/mL), TSH-2.69 μUI/mL (normal, 0.35-8. 00 μUI/mL), FT4 was 1.2 ug/dL (normal, 0.9-1.8 ug/dL). Physical examination was unremarkable, and there were no stigmata of AHO, rachitic rosary, or congenital malformations. EEG was normal and CT brain did not show any intraventricular haemorrhage or basal ganglia calcification. Consistent with hypocalcaemia, hyperphosphatemia, high serum PTH levels, and lack of stigmata of AHO, we considered PHP type Ib. Her parents refused further examinations, so PTH infusion and molecular analysis of the GNAS gene could not be performed. The child was discharged in good clinical condition on calcitriol 0.25 ug/day and calcium (elemental calcium 625 mg/day) supplementation. He had no further seizures and normal serum electrolyte levels till 9 months of age. European Pseudohypoparathyroidism Network (EuroPHP Network) has recently proposed a new classification system to cover all disorders of the PTH pathway. Inactivating PTH/PTH-related protein signaling disorder (iPPSD) is the new name proposed for these disorders. iPPSDs can be further divided into subtypes: iPPSD1 to iPPSD6. A minimum of one major criterion is mandatory for the clinical diagnosis of iPPSD. Applying iPPSD criteria to this case, one can observe that they all had persistent hypocalcemia and PTH resistance but no other major or minor criteria. Nevertheless, we speculate whether neonatal transient pseudohypoparathyroidism (ntPHP) could be included among iPPSDs, specifically in the group of unknown molecular defects. Conclusion To the best of our knowledge, this is the second report in which the new classification of iPPSD has been applied and the child has been diagnosed a case of ntPHP. Presentation: No date and time listed

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis.

Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis. The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis. A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed via sensitivity and subgroup analyses. Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.

Vitamin D, parathyroid hormone, glucose metabolism and incident diabetes in the multiethnic study of atherosclerosis

IntroductionHigher concentrations of serum 25-hydroxyvitamin D (25(OH)D) and lower concentrations of parathyroid hormone (PTH) are associated with lower insulin resistance and incident diabetes in non-Hispanic White and Hispanic Americans. Results...

Bone Fragility in Chronic Kidney Disease Stage 3 to 5: The Use of Vitamin D Supplementation.

Frequently silent until advanced stages, bone fragility associated with chronic kidney disease-mineral and bone disease (CKD-MBD) is one of the most devastating complications of CKD. Its pathophysiology includes the reduction of active vitamin D metabolites, phosphate accumulation, decreased intestinal calcium absorption, renal alpha klotho production, and elevated fibroblast growth factor 23 (FGF23) levels. Altogether, these factors contribute firstly to secondary hyperparathyroidism, and ultimately, to micro- and macrostructural bone changes, which lead to low bone mineral density and an increased risk of fracture. A vitamin D deficiency is common in CKD patients, and low circulating 25(OH)D levels are invariably associated with high serum parathyroid hormone (PTH) levels as well as with bone mineralization defects, such as osteomalacia in case of severe forms. It is also associated with a variety of non-skeletal diseases, including cardiovascular disease, diabetes mellitus, multiple sclerosis, cancer, and reduced immunological response. Current international guidelines recommend supplementing CKD patients with nutritional vitamin D as in the general population; however, there is no randomized clinical trial (RCT) evaluating the effect of vitamin D (or vitamin D+calcium) supplementation on the risk of fracture in the setting of CKD. It is also unknown what level of circulating 25(OH)D would be sufficient to prevent bone abnormalities and fractures in these patients. The impact of vitamin D supplementation on other surrogate endpoints, including bone mineral density and bone-related circulating biomarkers (PTH, FGF23, bone-specific alkaline phosphatase, sclerostin) has been evaluated in several RTCs; however, the results were not always translated into an improvement in long-term outcomes, such as reduced fracture risk. This review provides a brief and comprehensive update on CKD-related bone fragility and the use of natural vitamin D supplementation in these patients.

Low muscle mass and early hospital readmission post-kidney transplantation.

Patients exhibiting features of frailty and sarcopenia increasingly are presenting for kidney transplantation (KT) assessment. Sarcopenia, when ascertained by radiological measures, is associated with a higher transplant waiting list mortality; but studies on post-operative outcomes are lacking. We aimed to determine the clinical significance of low muscle mass in chronic kidney disease (CKD) patients subsequently receiving KT. We retrospectively analyzed 63 patients with Stage 4-5 CKD who, between 2012 and 2020, had undergone abdominal computed tomography (CT) scanning up to 2years before KT. The degree of skeletal muscle loss was assessed using the total cross-sectional skeletal muscle area at the third lumbar vertebral level (L3). Cox proportional-hazards regression and Frailty models were used to identify risk factors for early hospital readmission post KT. Thirty-four patients (54%) displayed low muscle mass, which was independently associated with a lower serum creatinine and phosphate, lower body mass index, lower mean muscle attenuation of the L3 cross-sectional area, and higher serum parathyroid hormone (for all p < 0.05). Deceased donor transplant recipients (n = 45) with low muscle mass demonstrated greater hospital readmissions within 30days of KT [adjusted hazard ratio (HR) = 4.24, 95% CI 1.40-12.90, p = 0.01]. Low muscle mass is highly prevalent in the pre-transplant CKD population and is associated with increased hospital readmission in the early post-transplant period.

Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells.

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.

Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men

Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator. This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men. A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported. Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group. High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.

Osteitis Fibrosa Cystica and pathological fractures\u2014the classic but neglected skeletal manifestation of primary hyperparathyroidism: a case report

BackgroundOsteitis fibrosa cystica is the classic manifestation of primary hyperparathyroidism (PHPT), occurs after prolonged exposure of bone to high serum parathyroid hormone (PTH) level. It has become increasingly rare due to early detection of PHPT.Case presentationA 37-year-old woman was referred to our institution for fixation of multiple fractures of upper and lower extremities that had been reoccurring in the past 5 years. Her medical history showed right-shoulder, left-elbow, and right-femur fractures after a fall 5 years previously. One month ago, she sustained fractures of the right distal humerus, left tibia, and left femur without history of trauma. Upon arrival to our hospital, a thorough review of her plain radiographs demonstrated brown tumors at multiple sites, along with a salt-and-pepper appearance of the skull and a rugger-jersey spine, compatible with osteitis fibrosa cystica. Patient was diagnosed with PHPT, confirmed by high-corrected serum calcium (13.6 [8.6–10.0] mg/dl), low serum phosphate (2.2 [2.5–4.5] mg/dL), high serum alkaline phosphatase (1482 [35–105] U/L), and significantly elevated parathyroid hormone (PTH 3850 [15–65] pg/mL). A histologically confirmed, 2.5-cm parathyroid adenoma was removed by parathyroidectomy. Ten days later, closed reduction and internal fixation of the left proximal femoral shaft was performed. Pain and ambulation were significantly improved 6 months postoperatively. At the 1.5-year follow-up, fracture unions and complete mineralization of brown tumors were noted; the patient could ambulate with neither pain nor an assistive device.ConclusionsPHPT has become more asymptomatic in countries where routine calcium screening is performed. Nevertheless, the classic skeletal involvement, osteitis fibrosa cystica, should not be overlooked, particularly in young patients who present with a low-energy fracture.

Comparative Transcriptomic Profiling Revealed Distinctive Patterns in Differentially Expressed Genes Related to Clinicopathologic Features of Parathyroid Carcinoma and Adenoma

Parathyroid carcinoma is a rare malignancy which remains as a clinical unmet need lacking effective therapeutic intervention. (1) In this study, we compared mutational profile of parathyroid carcinoma, adenoma, and normal parathyroid tissue using RNA-Seq based transcriptomics analysis and whole exome sequencing. A total of 40 parathyroid specimens [parathyroid carcinoma (n=8), adenoma (n=24), and normal tissue incidentally obtained from thyroidectomy for various reasons (n=8)] from 39 individuals (women n=34, 87%; mean age 51 year) were analyzed. Compared to adenoma and normal parathyroid groups, parathyroid carcinoma group had younger age (carcinoma 35 ± 12 vs. other 56 ± 16 year, p=0.001) and higher serum parathyroid hormone (PTH; 231 [145–474] vs. 114 [88–196] vs. 34 [29–41] pg/mL, p=0.001) prior to surgery. CDC73 mutation was found in 7 of 8 carcinoma specimens, which harbored germline mutation in 6 of them. Among top feature gene mutations for classifying adenoma and carcinoma, carcinoma-specific genes showed high specificity, whereas adenoma-related key features were largely overlapped with normal tissues. Transcriptional profiling revealed 546 carcinoma-specific differentially expressed genes (DEGs), 135 adenoma-specific DEGs, and 323 common DEGs. Hierarchical clustering with 546 carcinoma-specific DEGs detected four clusters with distinctive clinicopathologic characteristics (cluster 1 [n=12]: 7 normal tissues and 5 adenomas; cluster 2 and 3 [n=22]: all adenomas except one normal tissue; cluster 4 [n=9]: all parathyroid carcinomas except one adenoma). Carcinoma-specific DEGs include upregulation of GRIN2A, LYPD1, and SOX2 and downregulation of ENTPPL, MYO3B, and PIK3C2G. Gene ontology enrichment revealed that these DEGs were mainly involved in the binding of cell adhesion molecule, actin, and Rho GTPase, and extracellular matrix structural constituent. Two adenoma clusters significantly differed in urinary calcium excretion level (403 [312–488] vs. 205 [150–327], p=0.037) without significant differences in median PTH (102 [86–138] vs. 125 [92–229] pg/mL) and calcium level (11.1 ± 1.0 vs. 11.0 ± 0.9 mg/dL; P>0.05 for all). In summary, parathyroid carcinoma had distinctive transcriptional profiles which might improve the early detection of parathyroid carcinoma. Parathyroid adenomas were clustered into two groups with regard to urinary calcium excretion level based on transcriptional profiles, which merits further investigation. Reference: (1) Pandya C et al., JCI Insight. 2017 Mar 23; 2(6): e92061. Sources of Research Support: This study was supported by Severance Hospital Research Fund for Clinical Excellence (SHRC C-2019-0032; C-2020-0035).

Adenine-induced chronic kidney disease induces a similar skeletal phenotype in male and female C57BL/6 mice with more severe deficits in cortical bone properties of male mice.

Chronic kidney disease (CKD) causes bone loss, particularly in cortical bone, through formation of cortical pores which lead to skeletal fragility. Animal models of CKD have shown variability in the skeletal response to CKD between males and females suggesting sex may play a role in this variation. Our aim was to compare the impact of adenine-induced CKD on cortical parameters in skeletally mature male and female C57Bl/6 mice. After 10-weeks of adenine-induced CKD, both male and female adenine mice had high serum parathyroid hormone (PTH), high bone turnover, and cortical porosity compared to non-CKD controls. Both sexes had lower cortical thickness, but only male mice had lower cortical bone area. CKD imparted greater deficits in mechanical properties of male mice compared to female mice. These data demonstrate that both male and female mice develop high PTH/high bone turnover in response to adenine-induced CKD and that cortical bone phenotypes are slightly more severe in males, particularly in mechanical properties deficits.

Reduced Kidney Function and Relative Hypocalciuria-Observational, Cross-Sectional, Population-Based Data.

This observational, cross-sectional, epidemiological analysis investigated relationships of kidney function to urine calcium and other variables. The analyses targeted two population-based samples of adults (Gubbio study and Moli-sani study: n = 3508 and 955, respectively). Kidney function was assessed as estimated glomerular filtration rate (eGFR). Calcium/creatinine ratio (Ca/Cr) was used as index of urinary calcium in timed overnight urine under fed condition (Gubbio study), morning urine after overnight fast (Gubbio study), and first-void morning urine (Moli-sani study). Moli-sani study included also data for glomerular filtered calcium load, tubular calcium handling, and serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, calcium, and 25-hydroxyvitamin D. eGFR positively and independently related to Ca/Cr (p < 0.001). In multivariate analyses, eGFR lower by 10 mL/min × 1.73 m2 related to overnight urine Ca/Cr lower by 14.0 mg/g in men and 17.8 mg/g in women, to morning urine Ca/Cr lower by 9.3 mg/g in men and 11.2 mg/g in women, and to first-void urine Ca/Cr lower by 7.7 mg/g in men and 9.6 mg/g in women (p < 0.001). eGFR independently related to glomerular filtered calcium load (p < 0.001) and did not relate to tubular calcium handling (p ≥ 0.35). In reduced eGFR only (<90 mL/min × 1.73 m2), low urine Ca/Cr independently related to low serum 1,25-dihydroxyvitamin D (p = 0.002) and did not relate to hyperphosphatemia, high serum parathyroid hormone, or hypocalcemia (p ≥ 0.14). Population-based data indicated consistent associations of lower kidney function with lower urine calcium due to reduction in glomerular filtered calcium. In reduced kidney function, relative hypocalciuria associated with higher prevalence of low serum 1,25-dihydroxyvitamin D.