Decrease In Parathyroid Hormone Research Articles

Orphanic hereditary hypophosphatemic rachit with hypercalciuria, nephrocalcinosis on account of mutation gene SLC34A3(Review and case report)

Orphan Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (OMIM: 241530; ORPHA: 157215) with an autosomal recessive mode of inheritance occurs with an estimated prevalence of 1: 250,000 in the child population. HHRH was first described by M. Tieder, et al. (1985). The syndrome is caused by heterozygous or homozygous mutations in the SLC34A3 gene mapped to chromosome 9q34.3, which encodes a type II sodium phosphate cotransporter (NaPiIIc). Mutations result in loss of NaPi-IIc function and impairment of phosphate reabsorption in the proximal renal nephron. HHRH is characterized by a decrease in phosphate reabsorption in the proximal nephron tubules, manifested by hyperphosphaturia, hypercalciuria, hypophosphatemia, an increase in the concentration of 1,25(OH) 2D3, a decrease in parathyroid hormone (PTH) circulating in the blood, osteomalacia, inhibition of growth, low corrosiveness, low corrosiveness. The article presents the characteristics of the phenotype and genotype of HHRH, diagnostic criteria and treatment strategy. A description of a clinical case of HHRH with hypercalciuria, nephrocalcinosis and urolithiasis due to mutation of the SLC34A3gene is presented.

Influence of hyperbaric oxygen therapy on bone metabolism in patients with neoplasm.

Hyperbaric oxygen therapy (HBOT) is useful in the treatment of complications due to radiotherapy in patients with neoplasm. Its effects on bone metabolism are unclear. In our study, we analyzed the effects of HBOT on bone remodeling in oncological patients with radiotherapy. Prospective clinical study in 23 patients with neoplasms undergoing treatment with HBOT due to complications of radiotherapy (hemorrhagic cystitis, proctitis or radionecrosis) and 25 patients with chronic anal fissure. The average number of HBOT sessions was 20 ± 5 (100% oxygen, 2.3 atmospheres and 90 min per day). Serum levels of aminoterminal propeptide of type I collagen (P1NP), C terminal telopeptide of type I collagen (CTX), alkaline phosphatase (AP), 25hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), were measured at 3 time points: T0 (before beginning HBOT), T1 (at the end of HBOT) and T2 (6 months after HBOT). At baseline, the patients with neoplasm have higher bone turnover than those with anal fissure. These differences were 41% in CTX (0.238 ± 0.202 ng/mL in neoplasm and 0.141 ± 0.116 ng/mL in fissure; p = 0.04), 30% for PTH (46 ± 36 pg/mL in neoplasm and 32 ± 17 pg/mL in fissure; p = 0.04) and 15% for alkaline phosphatase (80 ± 24 U/L in neoplasm and 68 ± 16 U/L in fissure; p = 0.04). In the group with neoplasm, the values of P1NP decreased 6% after HBOT (T0: 49 ± 31 ng/mL, T2: 46 ± 12 ng/mL; p = 0.03). Also, there were non-significant decreases in PTH (-34%) and CTX (-30%). Patients with neoplasm and complications with radiotherapy have an increase in bone remodeling that may be diminished after HBOT.

Relationship between the extent of central node dissection and parathyroid function preservation in thyroid cancer surgery.

The risk and effect of hypocalcemia following surgery of different magnitudes remains unclear. Thus, we assessed whether different extents of central lymph node dissection (CLND) and status of preserved parathyroid glands can influence parathyroid function in differentiated thyroid carcinoma (DTC) patients with initial surgical resection. Participants were categorized into 6 groups based on the extent of the surgical procedures, number of parathyroid glands preserved in situ, and parathyroid autotransplantation. The frequencies of hypocalcemia, serum calcium (Ca) levels, and parathyroid hormone (PTH) levels among the different groups were analyzed. The prevalence of hypocalcemia, number and status of parathyroid glands preserved in situ, and parathyroid autotransplantation were inversely related to extensive CLND (r=-0.18; P<0.05). The decrease of serum Ca and PTH was most severe on postoperative days (POD) 1-7. The incidence of hypocalcemia was higher in Group C than in Group B and A (P<0.05). The average postoperative serum Ca and PTH levels in Group C were significantly lower than group A on POD 1-7 (P<0.05). The incidence of hypocalcemia was obviously increased in Group D compared to Groups E and F (P<0.05). The mean serum Ca and PTH levels in Group D were significantly lower than in Group F (P<0.05), and the same results could be observed between Groups D and E (P<0.05). However, through parathyroid autotransplantation, there was no significant difference that could be found between Groups E and F on POD 1-7 (P>0.05). With the expansion of CLND scope, postoperative parathyroid function will be affected, increasing the risk of postoperative hypocalcemia. When at least 1-2 parathyroid glands were reserved in situ plus at least 1 parathyroid gland autotransplantation, there was little effect on postoperative parathyroid function.

Decrease in serum calcitriol (but not free 25-hydroxyvitamin D) concentration in hip fracture healing.

To assess the decrease in serum calcitriol concentrations after hip fracture. Serum concentrations of calcitriol, 25(OH)D, parathyroid hormone (PTH), directly measured free 25(OH)D, and indices of bone formation were measured in elderly patients with hip fracture (HF) and patients with elective hip replacement (EHR) at admission and after 7weeks. A total of 45 patients with HF and 17 patients with EHR completed this prospective study. Baseline serum calcitriol levels were ≤ 60pmol/l in 26% of the HF patients. After 7weeks, they significantly decreased (p < 0.001). In patients with EHR, serum calcitriol was within the reference range in all but one patient and did not change during the 7-week recovery phase. Seven weeks after HF, a significant positive relationship was observed between the change in calcitriol and serum 25(OH)D concentration (r = 0.385, p = 0.009) and free 25(OH)D (r = 0.296, p = 0.048), and a decrease in calcitriol during recovery was associated with a decrease in serum PTH (p = 0.038). Seven weeks after HF, changes in both serum PTH and serum 25(OH)D concentrations contributed to the prediction of changes in serum calcitriol (R2 = 0.190, p = 0.012). Unlike patients with EHR, subjects with HF had low serum 25(OH)D and low free 25(OH)D concentrations at admission, while their serum 1,25D levels were relatively elevated. Decreases in circulating calcitriol levels in the 7weeks following hip surgery were associated with a resolution of secondary hyperparathyroidism and low availability of free 25(OH)D.

Surgical treatment of patients with primary hyperparathyroidism with a risk of hypercalcaemic crisis.

The objective of the work was to evaluate the effectiveness of surgical treatment in patients with a high risk of hypercalcaemic crisis due to primary hyperparathyroidism (PHPT) and to determine the best time to undergo surgery. Between 2010 and 2019, 627 patients underwent surgery due to PHPT. Sixty-two patients (9.9%) (47 women and 15 men, aged 28-79 years, average 53.7 years) faced the threat of a parathyroid crisis. In these patients, the average parathyroid hormone (PTH) levels were 774.02 pg/mL (95% CI: 203-1246 pg/mL) and ionised calcium (iCa2+) 1.91 mmol/L (95% CI: 1.70-2.2 mmol/L). The PTH postoperative concentration averaged at 37.86 pg/mL (95% CI: 9.91-42.7 pg/mL) and iCa2 + 1.11 mmol/L (95% CI: 1.07-1.21 mmol/L). Bilateral neck exploration was performed in all patients with the removal of the affected parathyroid gland and biopsies of other parts. Histopathological examination revealed adenoma in 42 cases (67.7%), hyperplasia in 16 (25.7%), and parathyroid cancer in four of the patients (6.6%). Comparison of tests before and after surgery showed a statistically significant decrease in PTH (p < 0.001) and iCa (p < 0.001) in blood serum. A developing hypercalcaemic crisis in the course of hyperparathyroidism is an indication for preoperative intensive medical therapy, along with urgent surgical intervention and removal of diseased parathyroid glands. This type of surgery should be performed as soon as possible, even if there are no imaging tests, only based on an assessment of the general condition of the patient and their serum calcium levels.

Critical analysis of the intraoperative parathyroid hormone decrease during parathyroidectomy for secondary and tertiary hyperparathyroidism

BackgroundThis study aims to determine whether intraoperative parathyroid hormone monitoring helps to predict early surgical outcomes in patients with renal hyperparathyroidism and evaluate the impact on decision making during surgery. MethodsA prospective study was conducted. Serial samples of the intraoperative parathyroid hormone were collected; 2 of these were taken before the excision, and 2 were taken after the planned parathyroid resection (10 minutes and 15 minutes). We tested the criterion of an intraoperative parathyroid hormone percentage decay ≥80% of the highest value of the basal samples as a predictor of success. ResultsOf the 228 patients, parathyroidectomy achieved success in 92.1%. In patients with secondary hyperparathyroidism, the failure group showed a tendency to stabilize or even increase the intraoperative parathyroid hormone values from the 10-minute measure (577 pg/mL) to the 15-minute measure (535 pg/mL) (P = .903). Conversely, intraoperative parathyroid hormone continued to drop in those with a successful outcome: 245 pg/mL (10 minutes) and 206 pg/mL (15 minutes) (P < .001). The failure group had a significantly lower percentage decay (P < .001) from baseline when compared with the success group. The intraoperative parathyroid hormone influenced the surgical management in up to 7% of the cases. The intraoperative parathyroid hormone dosage method showed an accuracy of 86%, a sensitivity of 88%, and specificity of 67%. ConclusionIn patients with renal hyperparathyroidism undergoing parathyroidectomy, the use of intraoperative parathyroid hormone may help to predict an early therapeutic outcome with high sensitivity and accuracy by indicating the operation's success when there is an 80% reduction of baseline intraoperative parathyroid hormone 15 minutes after removal of the enlarged glands, an associated continuous decrease in serum intraoperative parathyroid hormone levels between 10 and 15 minutes, and achievement of plasma target values <500 pg/mL.

P1425EFFICACY AND SAFETY OF INTRAVENOUS PARICALCITOL TREATMENT IN CHINESE HEMODIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM: A REAL-WORLD DATABASE ANALYSIS

Abstract Background and Aims The aim of this retrospective, real-world data based observational study was to evaluate the efficacy, safety profile of paricalcitol in Chinese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT) under routine clinical practice. Method From the Zemplar Engagement Program (ZEP) database, a total of 668 Chinese hemodialysis patients from 104 dialysis centers between January 2015 and May 2019 were included in the analysis set. Intact parathyroid hormone (iPTH), total serum calcium (Ca), phosphate (P), dosage of intravenous (IV) paricalcitol (Zemplar®) were analyzed and discussed via retrospective analysis of the database during the treatment. The comparison between baseline and end of treatment was made to reveal the fluctuation trend of each biomarker and reflected us with clues of IV paricalcitol’s algorithm in real-world practice. Results Patients were divided into five groups according to the duration of follow-up, which includes Month 0.5-3 (Day 14–90), Month 3-6 (Day 91–180), Month 6-12 (Day 181–360), Month 12-24 (Day 361–720) and Month 24-48 (Day 721–1440). Median iPTH levels decreased from 1183.05 pg/ml at baseline to 676.03 pg/ml at last visit by 30.88% (p &amp;lt; 0.0001). 56.14% of patients had a ≥30% decrease and 29.34% of patients had a ≥50% decrease in iPTH. The proportion of patients achieving the Chinese CKD-MBD Guideline target range (&amp;lt;600 pg/ml) increased from 9.88% at treatment initiation to 40.12% at last observation. Serum Ca levels remained within the normal range throughout the study with only a slight but statistically significant increase in the group of Month 12-24 (P=0.0479). Serum phosphate remained stable in all follow-up groups (P&amp;gt;0.05). Subgroup analyses of 221 patients with hyperphosphatemia at baseline &amp;gt;1.78 mmol/l showed a rapid phosphate reduction from 2.00±0.20 mmol/l to 1.76±0.34mmol/l by 11.64% (P&amp;lt; 0.0001), within the first few weeks, along with the reduction of iPTH. Of all patients, 62.72% experienced a 30% decrease in iPTH within a median time of 16.86 weeks (95% CI, 15.57-17.86), 38.17% experienced a 50% decrease in iPTH within a median time of 21.29 weeks (95% CI, 19.86-23.14). The average weekly dose of paricalcitol was 19.69±8.99ug/week. Total dose of paricalcitol used and baseline iPTH were negatively correlated with the decrease in iPTH. Conclusion This is the first national retrospective real-world observational study since IV paricalcitol is available in China since 2014. It proves that up to 20ug weekly IV paricalcitol treatment is safe and effective in China HD patients with higher iPTH level. Physicians and patients could expect significantly iPTH decrease within 16-21 weeks when IV paricalcitol is initiated. This study also encores the pre-published results of paricalcitol trials and high-quality cohorts, from the real-world perspective. In summary, IV paricalcitol is well tolerated and serves as an effective approach to treat SHPT in Chinese HD patients. Figure.1 Mean iPTH values from baseline to last measurement (pg/ml) Figure.2 iPTH changes compared with baseline stratified by baseline iPTH values (%) Figure.3 Proportion of patients with a &amp;gt;=30% or 50% decrease in parathyroid hormone (%) Figure.4 Changes of iPTH and P from baseline to last measurement in the subgroup of hyperphosphatemia (Mean ± SD); (Hyperphosphatemia, defined as P&amp;gt;1.78 mmol/l)

Intraoperative parathyroid hormone (IOPTH) assay might be better than the second-generation assay in parathyroidectomy for primary hyperparathyroidism

BackgroundIt is unclear whether the third-generation intraoperative parathyroid hormone assay can improve surgical outcomes over second-generation assay in primary hyperparathyroidism. We aimed to compare the rate of decrease and diagnostic accuracy between the two assays after parathyroid adenoma excision. MethodsConsecutive patients undergoing parathyroidectomy with intraoperative parathyroid hormone were analyzed. Blood was drawn before and 10 minutes and 20 minutes after excision of the adenoma. The same blood sample was run simultaneously in the second-generation assays (Elecsys PTH STAT) and third-generation assays (Elecsys 1–84 PTH). Biochemical cure meant >50% intraoperative parathyroid hormone decrease at 10 minutes. Cure meant normocalcemia 6 months after operation. ResultsRelative to the second-generation assay, the value of the intraoperative parathyroid hormone level was less in the third-generation assay before excision (P < .001), at 10 minutes (P < .001), and at 20 minutes (P < .001). The intraoperative parathyroid hormone rate of decrease and the proportion of normalized post-excision intraoperative parathyroid hormone were greater in the third-generation assay (P < .001), but the prediction accuracy appeared similar between the 2 (91.5% vs 91.0%). Patients with worse renal function (estimated glomerular filtration rate <80mL/min/1.73m2) had a slower intraoperative parathyroid hormone decrease in the second-generation but not in the third-generation assay. ConclusionDespite comparable accuracy between the two generations of assay, the third-generation assay might be better than the second-generation assay because of the more rapid decrease in the intraoperative parathyroid hormone and a greater percentage of normalized intraoperative parathyroid hormone, regardless of baseline renal function.

Serum PTH is not a good marker for defining a threshold for vitamin D deficiency.

ObjectiveIn addition to its skeletal effects, vitamin D may also be important for health in general. It is uncertain what level of serum 25-hydroxyvitamin D (25(OH)D), marker of vitamin D status, is sufficient for these effects. With decreasing serum 25(OH)D levels there is an increase in serum PTH. The point at which this occurs has been considered as a threshold for vitamin D sufficiency. The thresholds found have varied widely and have mainly been based on observational studies. However, to truly establish a threshold for vitamin D effects, this has to be based on randomized controlled trials (RCTs).MethodsThe study included 2803 subjects from a general health survey, the Tromsø study, and pooled individual person data from five vitamin D intervention studies (n = 1544). Serum parathyroid hormone (PTH) and change in PTH after vitamin D supplementation were related to serum 25(OH)D levels in steps of 25 nmol/L (<24, 25–49, 50–74, 75–99, and >99 nmol/L).ResultsIn the Tromsø study, in the females there was a gradual decrease in serum PTH with increasing serum 25(OH)D with no apparent plateau, whereas in the males the decrease in PTH in subjects with serum 25(OH)D >74 nmol/l was marginal. In pooled RCTs, there was a significant reduction in serum PTH by vitamin D supplementation regardless of baseline serum 25(OH)D level.ConclusionsThe use of the serum PTH–25(OH)D relation from observational studies to determine a threshold for vitamin D sufficiency is highly questionable.

Vitamin D in chronic kidney disease: is there a role outside of PTH control?

Vitamin D deficiency is common in patients with kidney disease and many patients receive vitamin D supplementation. Several large, well-designed clinical trials have been published in the last few years evaluating the effects of vitamin D supplementation on important outcomes for patients with kidney disease including effects on cardiovascular disease, secondary hyperparathyroidism, and kidney disease progression. Several negative trials have been published showing no effect of cholecalciferol supplementation on cardiovascular events, kidney disease progression, and albuminuria. Long-term supplementation does not appear to be associated with kidney stone disease. Vitamin D supplementation decreases parathyroid hormone (PTH) levels and high levels of 25-hydroxyvitamin D may be required for maximal suppression. There appear to be no effects of vitamin D supplementation on noncalcemic outcomes including progression of kidney disease, albuminuria, or cardiovascular disease. The primary reason to use vitamin D in kidney disease remains to lower PTH levels.

Clinical application of carbon nanoparticles suspension in operation of papillary thyroid carcinoma

Objective:The aim of this study is to evaluate the application of carbon nanoparticle lymphatic tracer in total thyroidectomy and bilateral Central District's thyroidectomy for papillary thyroid carcinoma. Method:Sixty-four patients with cN0 papillary thyroid carcinoma that primary treated were random divided into two groups: Trial group and control group. Carbon nanoparticles suspension was injected into the thyroid gland of trial group patients.After ten minutes, total thyroidectomy plus bilateral central neck dissection was performed in the all patients. The black stained tissue in the dissection specimen of trial group was separated. The control group underwent total thyroidectomy plus bilateral central neck dissection. Total lymph node and parathyroid gland in the black stained tissue，and non-black stained tissue in the central compartment dissection specimen of trial group and central compartment dissection specimen of control group were counted respectively.Total lymph node, the mis-cut parathyroid glands in the adipose tissue of central lymph node，post-operative blood calcium and parathyroid hormone（PTH）of two groups were contrasted and analyzed. Result:There are 235 lymph nodes in the black-stained tissue of central compartment dissection specimen of trial group.No parathyroid gland was found in the black-stained tissue.Five lymph nodes and 2 parathyroid glands were found in the non-black stained tissue of central compartment dissection specimen of trial group. There were 164 lymph nodes and 9 parathyroid glands in central compartment dissection specimen of control group. There is statistic difference between the number of lymph nodes in black stain tissue and that of control group（t=8.291, P=0.000）.Rate of staining lymph node were 97.9 percent. No parathyroid glands were found in the black stained tissue. Nine mis-cut parathyroid glands（7.0%） were observed in the control group，while 2（1.6%） in the trial group（P<0.05）.None permanent hypocalcemia and PTH decrease were observed in the two groups.There were 10 patients（31.3%） with temporary hypocalcemia and 9 patients（28.1%）with temporary PTH decrease respectively in the control group，and there was 1 patient（3.1%） and 1 patient（3.1%） respectively in the trial group（P<0.05）. Conclusion:The effect of nano-carbon is ideal, and the parathyroid gland can not be stained black. It can distinguish the thyroid tissue from the surrounding lymphoid adipose tissue and clearly mark the Central District lymph nodes, reduce the risk of parathyroid gland injury during thyroid cancer. Neck dissection in the central region can improve the efficiency of lymph node dissection, protect the parathyroid gland and reduce the risk of postoperative complications.

Evaluation of Serum parathyroid hormone level measurement in total thyroidectomy patients

Background: Postoperative hypoparathyroidism is a common complication after total thyroidectomy. It is necessary to diagnose hypoparathyroidism immediately after total thyroidectomy for minimizing complications.&#x0D; Objective: The objective of this study was to measure and to evaluate the serum parathyroid hormone level in total thyroidectomy patients.&#x0D; Methods: This prospective observational study was carried out in the Department of Clinical Pathology in collaboration with Department of Surgery &amp; Department of Otolaryngology of BSMMU and Department of Otolaryngology of DMCH, Dhaka, during the period of September 2010 to August 2011.&#x0D; Results: Total 65 patients were studied irrespective of age and sex. Decreased serum PTH was found in 9 cases and normal parathyroid hormone was found in 56 cases. Male was 16.0% and female was 84.0%. Females were predominant. The incidence of hypoparathyroidism was 41.5%. Asymptomatic hypoparathyroidism was found in 8 and symptomatic hypoparathyroidism was found in 1 cases. Decreased serum PTH was developed mostly in malignant thyroid diseases. In relation to preoperative PTH values, intraoperative PTH levels were lower from 5.48% to 90.0%, (mean±SD in percentage is 65.3±16.7, p=.001) which is significant in paired t test. The mean difference of intraoperative (20 minutes after total thyroidectomy), parathyroid hormone levels were statistically significant (p&lt;0.05) between patient with decreased parathyroid hormone and patient with normal parathyroid hormone in unpaired t-test.&#x0D; Conclusion: Serum parathyroid hormone level significantly decreased 20 minutes after total thyroidectomy. If clinical sign symptoms of hypoparathyroidism are not developed in postoperative period, patient is safe and can be discharged from hospital.&#x0D; Bangladesh J Otorhinolaryngol; April 2017; 23(1): 5-10

Single Gland, Ectopic Location: Adenomas are Common Causes of Primary Hyperparathyroidism in Children and Adolescents.

Primary hyperparathyroidism (PHPT) in children and adolescents is uncommon. Data-driven guidelines for management in pediatric patients are limited. We performed a retrospective cohort analysis of all patients (1997-2017) with PHPT ≤ 21years of age who underwent parathyroidectomy at three institutions. Clinical and demographic variables were analyzed. Primary operative outcome was cure (normocalcemia > 6months after surgery); secondary outcome was operative success (intraoperative parathyroid hormone decrease of ≥ 50%). We identified 86 patients with a median age of 17years (IQR: 14, 19); 64% (n = 55) were female. The mean preoperative serum calcium was 11.7mg/dL, median parathyroid hormone (PTH) was 110pg/mL, and median urine calcium was 4.1mg/kg/24h. Preoperatively, sestamibi scan localized in 41/71 patients (58%); neck ultrasound localized in 19/44 (43%). The most common pathology at surgery was a single ectopic parathyroid adenoma in 71% (n = 61). A high incidence of ectopic adenomas (25%, n = 22) was observed, most commonly intrathymic (n = 13), followed by tracheoesophageal groove (n = 5), carotid sheath (n = 2), and intrathyroidal (n = 2). Of 56 patients with retrievable data > 6months postoperatively, cure was achieved in 55 of 56 patients (98%). One patient who presented to us with parathyromatosis require subsequent reoperation. In this multi-institutional series of PHPT in children and adolescents, the majority were sporadic PHPT and were due to a single adenoma. We observed a high incidence of ectopic parathyroid adenomas, most commonly intrathymic. Given the high risk for ectopic adenoma in pediatric patients, parathyroid surgery in children and adolescents should be performed by experienced surgeons.

Co-administration of omega-3 fatty acids and metformin showed more desirable effects than the single therapy on indices of bone mineralisation but not gluco-regulatory and antioxidant markers in diabetic rats

Although metformin (Met) is the most recommended anti-diabetogenic drug in type 2 diabetic state, the drug is known to compromise bone integrity. Like metformin, omega-3 fatty acids (ω-3) have gluco-regulatory action; however, it aids bone health. Therefore, the present study investigated the effects of ω-3 and/or metformin in diabetic rats. Fifty rats of ten animals per group were divided into the following: Control; Diabetic untreated; Diabetic + ω-3; Diabetic + metformin (metfm) and Diabetic + ω-3 + metf groups. Diabetes was induced by the administration of streptozotocin (65 mg/kg b.w., i.p.), 15 min after the administration of nicotinamide (110 mg/kg b.w., i.p.). Five days afterwards, treatments started and they lasted for 28 days. ω-3 and metformin were administered at 200 and 180 mg/kg b.w., p.o. respectively. The results showed that the induced diabetes was characterised by significant increases in calcium to phosphorus ratio, tartrate resistant acid phosphatase (TRAP), glucose and insulin resistance; but significant decreases in parathyroid hormone(PTH), phosphorus, TAC and hepatic glycogen. Relative to the diabetic control, treatments with ω-3 or metformin caused significant elevations in hepatic glycogen, total alkaline phosphatase (TALP), osteocalcin, PTH, estradiol, and calcium; however, significant decreases in TRAP and glucose. Co-administration of ω-3 and metformin caused more desirable effects on TALP, c-terminal telopeptide of type 1 collagen, estradiol and calcium to phosphorus ratio compared to the single administration. Relative to ω-3, melatonin showed a more favourable effect on calcium to phosphorus ratio; however, the former proved to have more desirable actions on insulin and TAC. Hence, it was concluded that the combined but not the single administration of ω-3 and metformin could be preferably used in the management of bone health in diabetic state.

Pattern of Intraoperative Parathyroid Hormone and Calcium in the Treatment of Tertiary Hyperparathyroidism.

Tertiary hyperparathyroidism, an autonomous hyperproduction of parathyroid hormone (PTH), has a challenge in its treatment. This study asked whether the intraoperative PTH and calcium drop can confirm the resection of all parathyroid tissues. Case series with planned data collection. Tertiary referral medical center. The study assessed patients with tertiary hyperparathyroidism who were treated at the Hospital of the State University of Campinas from 2007 to 2015. All patients underwent total parathyroidectomy with autotransplantation of parathyroid fragments. PTH and calcium were collected during the preoperative period; at 10, 20, and 240 minutes after resection of the glands; and at 1 year after the procedure. Data were analyzed by analysis of variance and logistic regression analysis with statistical values of P < .05. Thirty-five patients were assessed: 17 women (48.57%) and 18 men (51.43%). The percentage of PTH drop was statistically significant at all times, unlike the calcium analysis, but only PTH collected at 20 minutes was able to confirm the removal of all parathyroid tissues (P = .029). Based on the receiver operating characteristic curve, the 71.2% drop obtained high sensitivity and specificity (P = .028). Treatment success can be predicted by analyzing the decrease of intraoperative PTH and not by calcium. The 71.2% PTH drop at 20 minutes after parathyroidectomy had high sensitivity and specificity to predict surgical cure.

Two cases of spontaneous remission of primary hyperparathyroidism due to auto-infarction: different management and their outcomes.

SummarySpontaneous remission of primary hyperparathyroidism (PHPT) due to necrosis and haemorrhage of parathyroid adenoma, the so-called ‘parathyroid auto-infarction’ is a very rare, but previously described phenomenon. Patients usually undergo parathyroidectomy or remain under close clinical and biochemical surveillance. We report two cases of parathyroid auto-infarction diagnosed in the same tertiary centre; one managed surgically and the other conservatively up to the present time. Case #1 was a 51-year old man with PHPT (adjusted (adj.) calcium: 3.11 mmol/L (reference range (RR): 2.20–2.60 mmol/L), parathyroid hormone (PTH) 26.9 pmol/L (RR: 1.6–6.9 pmol/L) and urine calcium excretion consistent with PHPT) referred for parathyroidectomy. Repeat biochemistry 4 weeks later at the surgical clinic showed normal adj. calcium (2.43 mmol/L) and reduced PTH. Serial ultrasound imaging demonstrated reduction in size of the parathyroid lesion from 33 to 17 mm. Twenty months later, following recurrence of hypercalcaemia, he underwent neck exploration and resection of an enlarged right inferior parathyroid gland. Histology revealed increased fibrosis and haemosiderin deposits in the parathyroid lesion in keeping with auto-infarction. Case #2 was a 54-year-old lady admitted with severe hypercalcaemia (adj. calcium: 4.58 mmol/L, PTH 51.6 pmol/L (RR: 1.6–6.9 pmol/L)) and severe vitamin D deficiency. She was treated with intravenous fluids and pamidronate and 8 days later developed symptomatic hypocalcaemia (1.88 mmol/L) with dramatic decrease of PTH (17.6 pmol/L). MRI of the neck showed a 44 mm large cystic parathyroid lesion. To date, (18 months later), she has remained normocalcaemic.Learning points:Primary hyperparathyroidism (PHPT) is characterised by excess parathyroid hormone (PTH) secretion arising mostly from one or more autonomously functioning parathyroid adenomas (up to 85%), diffuse parathyroid hyperplasia (<15%) and in 1–2% of cases from parathyroid carcinoma.PHPT and hypercalcaemia of malignancy, account for the majority of clinical presentations of hypercalcaemia.Spontaneous remission of PHPT due to necrosis, haemorrhage and infarction of parathyroid adenoma, the so-called ‘parathyroid auto-infarction’, ‘auto-parathyroidectomy’ or ‘parathyroid apoplexy’ is a very rare in clinical practice but has been previously reported in the literature.In most cases, patients with parathyroid auto-infarction undergo parathyroidectomy. Those who are managed conservatively need to remain under close clinical and biochemical surveillance long-term as in most cases PHPT recurs, sometimes several years after auto-infarction.

The Effect of Ketoanalogues on Chronic Kidney Disease Deterioration: A Meta-Analysis.

The effects of ketoanalogues (KA) on chronic kidney disease (CKD) deterioration have not yet been fully confirmed. To strengthen the evidence of the role of KA in CKD, PubMed and Embase were searched for studies published through February 2019. Effect sizes from ten randomized control trials (RCTs) and two non-RCTs comprising a total of 951 patients were pooled and analyzed. A restricted protein diet supplemented with ketoanalogues (RPKA) was found to significantly delay the progression of CKD (p = 0.008), particularly in patients with an estimated glomerular filtration rate (eGFR) > 18 mL/min/1.73 m2 (p < 0.0001). No significant change in eGFR was found when comparing a very-low-protein diet and a low-protein diet (p = 0.10). In addition, compared with the placebo, RPKA did not cause malnutrition (albumin: p = 0.56; cholesterol: p = 0.50). Moreover, RPKA significantly decreased phosphorous levels (p = 0.001), increased calcium levels (p = 0.04), and decreased parathyroid hormone (PTH) levels (p = 0.05) in patients with eGFR < 18 mL/min/1.73 m2. In conclusion, RPKA could slow down the progression of CKD in patients with eGFR > 18 mL/min/1.73 m2 without causing malnutrition and reverse CKD-MBD in patients with eGFR < 18 mL/min/1.73 m2.

Effects of vitamin D supplementation on bone turnover markers and other bone-related substances in subjects with vitamin D deficiency.

In observational studies, vitamin D deficiency is a risk factor for low bone density and future fractures, whereas a causal relation has been difficult to show in randomized controlled trials (RCTs). Similarly, vitamin D deficiency has been associated with increased bone turnover, but RCTs with vitamin D have not shown conclusive effects. This could be due to inclusion of vitamin D sufficient subjects and low vitamin D doses. In the present study 399 subjects with mean baseline serum 25-hydroxyvitamin D (25(OH)D) 34.0 nmol/L completed a four months intervention with vitamin D3 20,000 IU per week versus placebo. Mean serum 25(OH)D increased to 89.0 nmol/L in the vitamin D group and decreased slightly in the placebo group. A small, but significant, decrease in the bone formation marker procollagen of type 1 amino-terminal propeptide (P1NP) was seen in the vitamin D group as compared to the placebo group (mean delta P1NP -1.2 pg/mL and 1.5 ng/mL, respectively, P < 0.01). No significant effects were seen on serum carboxyl-terminal telopeptide of type 1 collagen (CTX-1), Dickkopf-1, sclerostin, tumor necrosis factor-alpha, osteoprotegerin, receptor activator of nuclear factor ĸB ligand, or leptin. Subgroup analyses on subjects with low baseline serum 25(OH)D did not yield additional, significant results. In subjects with high baseline serum parathyroid hormone (PTH) > 6.5 pmol/L and post-intervention decrease in PTH, the decrease in P1NP was more pronounced, they also exhibited significantly reduced serum CTX-1 and increased serum sclerostin. In conclusion, supplementation with vitamin D appears to suppress bone turnover, possibly mediated by PTH reduction. Our findings need to be confirmed in even larger cohorts with vitamin D insufficient subjects.

Factors associated with parathyroid hormone control in haemodialysis patients with secondary hyperparathyroidism treated with cinacalcet in real-world clinical practice: Mimosa study.

BackgroundSecondary hyperparathyroidism (SHPT) is frequent in haemodialysis (HD) patients. Oral cinacalcet-hydrochloride (HCl) decreases parathyroid hormone (PTH); however, real-life PTH data, according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, are still lacking. Our goal is to assess the percentage of cinacalcet-HCl-treated HD patients with controlled SHPT (PTH <9× upper limit of the normal range) after 12 months (M12) of treatment.MethodsThis is a retrospective observational study in HD patients with SHPT treated by cinacalcet-HCl between 2005 and 2015 and dialysed in seven French HD centres using the same database (Hemodial™).ResultsThe study included 1268 patients with a mean (standard deviation) follow-up of 21 ± 12 months. Their mean dialysis vintage was 4.3 ± 5.6 years. PTH values were available and exploitable at M12 in 50% of them (645 patients). Among these patients, 58.9% had controlled (mean PTH of 304 ± 158 pg/mL) and 41.1% uncontrolled SHPT (mean PTH of 1084 ± 543) at M12. At the baseline, patients with controlled SHPT were older (66 ± 15 versus 61 ± 17 years), and had lower PTH (831 ± 346 versus 1057 ± 480 pg/mL) and calcaemia (2.18 ± 0.2 versus 2.22 ± 0.19 mmol/L) than uncontrolled patients. In multivariate analysis, these three factors still remained significantly associated with controlled SHPT.ConclusionIn this real-life study, 41.1% of HD patients with SHPT treated with cinacalcet-HCl remained with a PTH above the KDIGO recommended target after 12 months of treatment. Apart from the possibility of non-compliance, the severity of SHPT appears to be a major factor determining the response to cinacalcet-HCl treatment, reinforcing the importance of treating SHPT at earlier stages.

Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration

Calcimimetics decrease parathyroid hormone (PTH) secretion in patients with secondary hyperparathyroidism. The decrease in PTH should cause a reduction in bone turnover; however, the direct effect of calcimimetics on bone cells, which express the calcium-sensing receptor (CaSR), has not been defined. In this study, we evaluated the direct bone effects of CaSR activation by a calcimimetic (AMG 641) invitro and invivo. To create a PTH "clamp," total parathyroidectomy was performed in rats with and without uremia induced by 5/6 nephrectomy, followed by a continuous subcutaneous infusion of PTH. Animals were then treated with either the calcimimetic or vehicle. Calcimimetic administration increased osteoblast number and osteoid volume in normal rats under a PTH clamp. In uremic rats, the elevated PTH concentration led to reduced bone volume and increased bone turnover, and calcimimetic administration decreased plasma PTH. In uremic rats exposed to PTH at 6-fold the usual replacement dose, calcimimetic administration increased osteoblast number, osteoid surface, and bone formation. A 9-fold higher dose of PTH caused an increase in bone turnover that was not altered by the administration of calcimimetic. In an osteosarcoma cell line, the calcimimetic induced Erk1/2 phosphorylation and the expression of osteoblast genes. The addition of a calcilytic resulted in the opposite effect. Moreover, the calcimimetic promoted the osteogenic differentiation and mineralization of human bone marrow mesenchymal stem cells invitro. Thus, calcimimetic administration has a direct anabolic effect on bone that counteracts the decrease in PTH levels.