Measurement of Calprotectin and PTH in the Amniotic Fluid of Early Second Trimester Pregnancies and Their Impact on Fetuses with Growth Disorders: Are Their Levels Related to Oxidative Stress?

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021-2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415-6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887-13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400-9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51-15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02-16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05-15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.

Evaluation of Vitamin D3 and Calcium Deficiency after Recovery from Extensive Burn.

BACKGROUND: Previous studies in pediatric populations have demonstrated that vitamin D deficiency is common in patients with large burns. The aim of the current comparative study was to investigate the serum level of vitamin D in patients with large burns [>20% total body surface area (TBSA)] after 6 months of therapy. METHODS: This case control study was conducted during 6-month period from 2017 to 2018 in Amiralmomenin Hospital, Shiraz, Iran. Forty two patients with large burns (>20% TBSA) and at least 6 months' post-burn period were enrolled. Also, 42 healthy and age and sex matched controls from those referring for routine check-ups were included for comparison. None of the patients and controls received vitamin D supplements. The serum level of calcium (Ca), parathormone (PTH) and vitamin D were compared between the groups. RESULTS: There was no significant difference between the two study groups regarding the baseline characteristics including the age (p=0.085), gender (p=0.275) and duration of sun exposure (p=0.894). We found that those with major burns had significantly higher serum levels of PTH (50.48±26.49 vs. 33.64±15.80; p=0.001). In addition, the serum levels of vitamin D were significantly lower in burn patients compared to healthy controls (18.15±9.18 vs. 31.43±16.27; p<0.001). CONCLUSION: Major burns (≥20% TBSA) are associated with increased serum levels of PTH and decreased serum levels of vitamin D. However, serum levels of calcium are not affected by major burns.

A randomised controlled trial to examine the effects of cinacalcet on bone and cardiovascular parameters in haemodialysis patients with advanced secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism may lead to increased cardiovascular risk. The use of cinacalcet may improve bone and cardiovascular health with improved parathormone (PTH) and phosphate control. METHODS: This is an open-label prospective randomised controlled trial to compare progression of cardiovascular and chronic kidney disease mineral and bone disorder (CKD-MBD) parameters. Patients were randomised to receive cinacalcet alongside standard therapy or standard therapy alone. Thirty-six haemodialysis patients who had > 90 days on dialysis, iPTH > 300 pg/mL, calcium > 2.1 mmol/L and age 18-75 years were included. Following randomization, all 36 patients underwent an intensive 12-week period of bone disease management aiming for iPTH 150-300 pg/mL. The primary outcome was change in vascular calcification using CT agatston score. Secondary outcomes included pulse wave velocity (PWV), left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), augmentation index (Aix) and bone measurements. The above measurements were obtained at baseline and 12 months. RESULTS: There was no evidence of a group difference in the progression of calcification (median change (IQR) cinacalcet: 488 (0 to1539); standard therapy: 563 (50 to 1214)). In a post hoc analysis combining groups there was a mean (SD) phosphate reduction of 0.3 mmol/L (0.7) and median (IQR) iPTH reduction of 380 pg/mL (- 754, 120). Regression of LVMI and CIMT was seen (P = 0.03 and P = 0.001) and was significantly associated with change of phosphate on multi-factorial analyses. CONCLUSIONS: With a policy of intense CKD-MBD parameter control, no significant benefit in bone and cardiovascular markers was seen with the addition of cinacalcet to standard therapy over one year. Tight control of hyperphosphataemia and secondary hyperparathyroidism may lead to a reduction in LVMI and CIMT but this needs further investigation. Although the sample size was small, meticulous trial supervision resulted in very few protocol deviations with therapy.

Hypocalcemia secondary to hypomagnesemia in a patient on liraglutide.

A 73-year-old man with type 2 diabetes on Liraglutide with a history of coronary artery disease. Admitted to emergency for abdominal pain, severe diarrhea and episodes of tetany attacks. Laboratory workup reveals hypomagnesemia, hypocalcemia and normal parathormone (PTH). After intravenous administration of magnesium and calcium, the blood ionogram quickly normalized. In addition, plasma levels of intact parathyroid hormone increased immediately after magnesium administration. Strongly suggests that hypocalcemia resulted from a disruption of adequate parathyroid hormone secretion caused by hypomagnesemia which in turn was caused by severe diarrhea under treatment with Liraglutide.

Case report: lady with bone pains for 5 years-parathyroid carcinoma.

BACKGROUND: Parathyroid cancer is a rare cause of primary hyperparathyroidism. It presents a diagnostic and therapeutic challenge that may not be recognized preoperatively, and is often not conclusively identified during the operation. We present the case of a lady with backache and hypercalcemia, but with inadequate work-up for her condition for several years. CASE PRESENTATION: A middle aged lady of Asian descent presented with backache. Initial work up revealed mild hypercalcemia, negative work up for multiple myeloma, negative sestamibi scan for parathyroid pathology. A phenomenally elevated parathormone (PTH) level-2105 pg/mL (16-87 pg/mL), and rising serum calcium, 15.1 mg/dL, (8.6-10.5 mg/dL), ordered years later prompted a repeat sestamibi scan and ultrasonography of neck. Based on these investigations, a diagnosis of primary hyperparathyroidism, with high suspicion of parathyroid cancer was made. The patient underwent surgical tumour resection, with subsequent histopathological confirmation of diagnosis. CONCLUSION: In the setting of hypercalcemia, PTH level assessment is a must. This helps to differentiate between the parathyroid dependant and independent causes of high serum calcium, thereby encouraging a comprehensive pathway to the work up of the cause of hypercalcemia. The parathyroid cancer is a very rare cause of hypercalcemia, which needs to be considered in the differentials of primary hyperparathyroidism, particularly in the setting of high PTH levels.

Long-Term Therapy Outcomes When Treating Chronic Kidney Disease Patients with Paricalcitol in German and Austrian Clinical Practice (TOP Study).

Paricalcitol is approved for prevention and therapy of secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), with only short-term data in clinical routine settings. A 12-month observational study was conducted in Germany and Austria (90 centers, 761 patients) from 2008 to 2013. Laboratory values, demographical, and clinical data were documented in 629 dialysis patients and 119 predialysis patients. In predialysis patients, median intact parathormone (iPTH) was 180.0 pg/mL (n = 105) at the start of the study, 115.7 pg/mL (n = 105) at last documentation, and 151.8 pg/mL (n = 50) at month 12, with 32.4% of the last documented iPTH values in the KDOQI (Kidney Disease Outcomes Quality Initiative) target range. In dialysis patients, median iPTH was 425.5 pg/mL (n = 569) at study start, 262.3 pg/mL (n = 569) at last documentation, and 266.1 pg/mL (n = 318) at month 12, with 36.5% of dialysis patients in the KDOQI target range. Intravenous paricalcitol showed more homogenous iPTH control than oral treatment. Combined analysis of all dialysis patients indicated comparable and stable mean serum calcium and phosphate levels throughout the study. Clinical symptoms, such as itching, bone pain, and fatigue, were improved compared with study entry. The spectrum and frequency of adverse events mirrored the known pattern for patients on dialysis. Paricalcitol is efficacious and has a consistent safety profile in sHPT over 12 months.

Epigenetic Alterations in Parathyroid Cancers.

Parathyroid cancers (PCas) are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH); consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile.

Research about the changes of calcium regulation hormone and bone mineral density in patients with type 2 diabetes mellitus / 中国糖尿病杂志

Objective To research the changes of calcium regulation hormone and bone mineral density (BMD) in type 2 diabetes mellitus (T2DM ) patients and analyze the main impact factors. Methods 117 T2DM patients (T2DM group ,M/F=52/65 ,age 40~79 years) and 63 age‐ and gender‐matched healthy people (NC group) were selected in this study. According to the course of diabetes ,blood glucose control and the value of BMD ,T2DM patients were divided into subgroups :course≤10 years ,and>10 years ;HbA1 c≤8% ,and>8% ;normal BMD ,osteopenia ,and osteoporosis (OP). Serum 25‐hydroxy vitamin D3 [25(OH)D3 ]and Parathormone (PTH) were measured and BMDs of lumbar spine (L1 ~L4 ) , femoral neck ,total hip ,and whole body were evaluated for all the subjects. Result (1)Compared with NC group ,the level of serum 25(OH)D3 and BMDs of femoral neck and total hip decreased significantly in T2DM group[ (35.57 ± 12.30)nmol/L ,(0.848 ± 0.136)g/cm2 ,(0.873 ± 0.150)g/cm2 vs(44.94 ± 17.40) nmol/L ,(0.927 ± 0.173)g/cm2 ,(0.934 ± 0.140)g/cm2 ,respectively ,P10 years[ (0.814 ± 0.148) ,(0.840 ± 0.157) vs (0.882 ± 0.111) ,(0.908 ± 0.139) g/cm2 ,respectively ,P0.05). (3)Compared with HbA1c≤8% group ,BMD of femoral neck and total hip in HbA1c> 8% group decreased [(0.830 ± 0.131) ,(0.832 ± 0.161) vs (0.891 ± 0.130) ,(0.949 ± 0.130)g/cm2 ,respectively ,P 0.05). (4)The rates of OP and osteopenia (41.03% ,47.86% ) in T2DM were higher than those in NC group (26.98% ,33.33% ) (χ2 =4.367 ,4.669 ,P<0.05). The duration of diabetes and the levels of HbA1c and PTH were longer or higher in OP group than those with normal BMD or osteopenia (P<0.05). (5)Logistic regression analysis showed that BMD negatively correlated with the duration of diabetes ,HbA1c ,and PTH (β= 0.076 ,0.213 ,0.112 ,respectively ,P< 0.05) ,and positively correlated with 25(OH)D3 (β= -0.043 ,P<0.05). Conclusion The values of BMD decreased and the incidence of OP is higher in T2DM patients ,particularly in patients with longer diabetic duration and poor glycemic control.

Osteomalacia inducida por tumor / Tumor-induced osteomalacia

La osteomalacia inducida por tumor es un síndrome paraneoplásico secundario en la mayoría de los casos a tumores de origen mesenquimal. Se caracteriza por pérdida aumentada de fosfato a nivel urinario por el efecto inhibidor que ejerce el factor de crecimiento fibroblástico 23 sobre el transporte de fósforo en el túbulo renal proximal. Debe sospecharse en un paciente con debilidad y dolor osteomuscular generalizado que se presente con hipofosfatemia, normocalcemia, fosfatasa alcalina elevada y niveles de 25 hidroxivitamina D y PTH normales. El tratamiento definitivo de la enfermedad es la resección quirúrgica del tumor. Cuando se desconozca la neoplasia primaria o no sea posible el tratamiento quirúrgico debe iniciarse reposición de fósforo y calcitriol. En este artículo se presenta el primer caso de una paciente con osteomalacia inducida por tumor asociada a un carcinoma lobulillar infiltrante de seno.

The tumor-induced osteomalacia is a paraneoplastic syndrome secondary in most cases to tumors of mesenchymal origin. It is characterized by increased lost of urinary phosphate by the inhibitory effect exerted by the fibroblast growth factor 23 on phosphorus transport in the proximal renal tubule. Should be suspected in a patient with weakness and generalized muscle in addition to hypophosphatemia, normocalcemia, elevated alkaline phosphatase and normal serum 25-hydroxyvitamin D and PTH. The definitive treatment of the disease is surgical resection of the tumor. When the primary tumor is unknown or is not possible the surgical treatment should be initiated replacement of phosphorus and calcitriol. This paper presents the first case of a patient with tumor-induced osteomalacia associated with lobular breast cancer.