Serum Intact PTH Levels Research Articles

Upacicalcet, a positive allosteric modulator of the calcium-sensing receptor, prevents vascular calcification and bone disorder in a rat adenine-induced secondary hyperparathyroidism model.

Secondary hyperparathyroidism (SHPT) is a major comorbidity of chronic kidney disease (CKD). Chronic elevation of PTH levels is associated with cortical bone deterioration and increase in the risk of fractures in CKD patients. Here, we evaluated the effect of repeated administration of upacicalcet, a novel positive allosteric modulator of the calcium-sensing receptor, in a rat model of adenine-induced renal failure, by determining serum levels of intact PTH (iPTH), calcium, phosphorus, creatinine, and urea nitrogen. Furthermore, parathyroid hyperplasia (parathyroid gland weight and Ki-67-positive cell density), ectopic calcification (calcium content in the thoracic aorta, kidney and heart and positive von Kossa staining in the thoracic aorta), and bone morphometry parameters (cortical porosity and fibrosis volume) were evaluated. Rats treated with either 0.2mg/kg or 1mg/kg upacicalcet exhibited significantly lower serum iPTH levels than CKD-control rats, as early as 7days after the first dose. Repeated administration of upacicalcet reduced serum iPTH levels and inhibited parathyroid hyperplasia in rats with adenine-induced severe renal failure. Moreover, it suppressed ectopic calcification and cortical pore formation. In contrast, serum calcium and phosphorus levels were not significantly affected, suggesting a low risk of hypocalcemia, which often occurs with SHPT treatment. In conclusion, repeated administration of upacicalcet decreased serum iPTH levels and suppressed parathyroid hyperplasia in the adenine-induced CKD rat model of SHPT. Furthermore, ectopic calcification and cortical pore formation were suppressed without significant changes in blood mineral parameters. Upacicalcet safely inhibited the progression of SHPT in an adenine-induced CKD rat model.

The Relationship between Serum Sclerostin Levels and Bone Mineral Disorders and Vascular Calcification in Hemodialysis Patients

Background and aim of the study: Sclerostin is produced by osteocytes and has been shown to down-regulate the synthesis of many markers of bone formation by osteogenic cells. The aim of this study to investigate the relationship between serum sclerostin levels and bone mineral disorders and vascular calcification in hemodialysis patients (HD).
 Methods:This is a cross-sectional study of 70 patients with ESRD on regular HD for at least six months, Theodor Bilharz Research Institute, Giza, Egypt.Twenty-five subjects who matched the ages, genders, and demographics of the study patients were included as a control group.All patients and control groups included in the study underwent a full through history and clinical examination. Serum calcium, phosphorus, alkaline phosphatase and intact PTH (iPTH) levels were measured. Serum sclerostin was measured by an ELISA. Bone Mineral Densitometry Measurements BMD (g/cm2) was determined by dual-energy X-ray absorptiometry (DXA). CT scan was done to detect the presence or absence of vascular calcification and transthoracic echocardiogram to detect the presence or absence of valvular calcification.
 Results:The mean seumscleostin levels was a statistically significant high in the HD patients when compared with the control group (156.8 ±121.4 Vs.29.38±0.84, p =0.0001 ) and statistically significant high mean ALP in the HD patients when compared with the control group (147.2 ± 94.3 Vs. 38.8 ±23.4, p = 0.0001). The mean BMD was statistically significant low in the HD patients when compared with the controls (0.839±0.086 g/ m2 Vs.1.306 ±0.153 g/ m2, p = 0.0001).The mean seumscleostin levels was statistically significant high in the HD patients with vascular and valvular calcification when compared with HD patients without calcification.Using spearman correlation coefficient analysis, there was statistically significant negative correlations between serum sclerostin levels and iPTH(r=-0.362, p =0.0021), ALP (r=-0.301, p =0.0114), and BMD (r=-0.469, p =0.0278 ), and there was a statistically significant positive correlation between serum sclerostin levels and phosphate(r=0.5829, p =0.0001 ).Independent predictors of BMD in HD patients were determined using multi-variate regression analysis. Sclerostin levels, iPTH, ALP, and age were found to be independent predictors of BMD.
 Conclusion: High sclerostin levels in patients with ESRD on HD were associated with high risk of vascular and valvularcalcification and were independent predictors of low BMD in such population.

An Unusual Presentation of Primary Hyperparathyroidism: Ectopic Parathyroid Gland and Multiglandular Disease

Primary hyperparathyroidism (PHPT) can be associated as a single parathyroid adenoma in approximately 85% of patients, the remaining 15% of them correspond to individuals with hyperplasia. The multiglandular parathyroid disease varies in range 7–33% and contribute a persistent PHPT. We report a case of primary hyperparathyroidism with an unusual presentation of ectopic mediastinal parathyroid. The case was of a 54-year-old female, who started her illness 3 years ago, with frequent headache, regular fatigue and muscle pain, denied losing weight. She was admitted to emergency room for a urinary infection. During the hospitalization showed bilateral nephrocalcinosis, hypercalcemic crisis. She has a background of total thyroidectomy and subtotal parathyroidectomy because a thyroid adenomatous hyperplasia and parathyroid hyperplasia with removal of a total of three parathyroid glands. She had very high PTH level. Laboratory: serum calcium: 16.8mg/dl; ionic calcium: 2.37 mmol/L; P: 1.9 (2.7–4.5g/dL); Hb: 9 g/dL; Platelets: 558 000 per microliter; Leukocytes 9 600 cells/mcL; Albumin: 4g/dl; TSH: 0.06 mU/L; fT4: 1.29 (L-T4 doses were 100 ug). Four months after parathyroid surgery, the intact PTH level dropped from 1602 ng/l to 550 (15–65 ng/L). Computed tomography and Tc-sestamibi scintigraphy - SPECT revealed a residual cervicothoracic mass in retroesophageal region (D1-D2) (Fig1 -2). The patient underwent a new surgery and the intact PTH dropped 39ng/L. Histopathology revealed characteristic features of a parathyroid adenomatous (10 gram weight) (Fig.3); additionally a retroesternal ectopic thyroid tissue. There was not reappearance of high blood calcium and parathormone levels more than 6 months after second surgery for PHPT. An unusual case of PHPT caused by a multiglandular disease parathyroid varies (four glands and a ectopic gland), reliable histopathologic adenomatous and hyperplastic parathyroid disease, and persistent primary hyperparathyroidism with very high serum intact PTH level.Reference: (1) Masi L. Primary Hyperparathyroidism. Brandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs. Front Horm Res. Basel, Karger, 2019, vol 51, pp 1–12. (2) Pecheva M, Mahendran K, Kadlec J, Lofthouse M1, Van Tornout F. Mediastinal giant parathyroid adenoma-a minimally invasive mediastinal surgical approach for an emergency presentation. Ann Cardiothorac Surg. 2016 Jan;5(1):70–3. (3) Cakmak H 1, Tokat AO, Karasu S, Özkan M. Adenoma paratiroideo mediastínico gigante. Tuberk Toraks. 2011; 59 (3): 263–5. (4)Thier M, Daudi S, Bergenfelz A, Almquist M. Predictors of multiglandular disease in primary hyperparathyroidism. Langenbecks Arch Surg. 2018;403(1):103–109.

Poor dietary consumption and limited sun exposure are risk factors for vitamin D deficiency in premenopausal Kuwaiti women: A cross-sectional study

Background: Low serum vitamin D levels are reported constantly among females living in the Arabian Gulf countries, presumably due to their lifestyle, which limits direct sun exposure. Because Vitamin D deficiency has been implicated in a wide range of ailments, healthy females with the deficiency might be at risk for developing many health problems. Thus, the aim was to assess lifestyle risk factors for vitamin D deficiency in healthy women in Kuwait. Methods: A total of 104, disease-free, premenopausal women were recruited for assessment of their serum 25OHD and intact PTH levels. Physical examination, blood withdrawal and interviewer-administered questionnaires were used to collect the relevant data. Associations were detected statistically using nonparametric tests and logistic regression was used to identify risk factors for vitamin D deficiency. Results: Vitamin D deficiency ( < 25 nmol/L) occurred in 84.6%, and hyperparathyroidism ( ≥ 6.9 pmol/L) occurred in 25% of women, among which all were vitamin D deficient. Significant risk factors of vitamin D deficiency were nondaily milk intake (OR:25, CI%:4.2–147), no fish intake (OR:5, CI%:1–22.8), and no weekend sun exposure (OR:8.2, CI%:1.28–52.6). Having PTH ≥ 6 pmol/L was also associated with a higher likelihood of having vitamin D deficiency. Conclusion: Vitamin D deficiency is very common in disease-free, premenopausal Kuwaiti women and can be avoided by improving food consumption and obtaining more sun exposure.

4-Hour postoperative PTH level predicts hypocalcemia after thyroidectomy in children

BackgroundHypocalcemia occurs frequently after a total thyroidectomy in pediatric patients. Four hour postoperative PTH monitoring predicts the need for calcium supplementation in the adult thyroidectomy population. We evaluated the role of the 4 h postoperative PTH level in determining the need for calcium supplementation after thyroidectomy in the pediatric population. MethodsThis is a retrospective review of children undergoing total thyroidectomy by a single pediatric surgeon from July 2011 through July 2018. Intact PTH obtained four hours postoperatively determined the need for calcium supplementation for patients beginning in November 2014 onward. Serum total calcium levels were monitored concurrently with serum intact PTH levels. Serum calcium levels were followed in our Multispecialty Pediatric Endocrine Surgery clinic within the month following thyroidectomy. ResultsFrom July 2011 through July 2018, there were a total of 56 total thyroidectomies at our institution. Prior to November 2014, all pediatric total thyroidectomies received calcium supplementation per our institutional protocol. Based on ionized calcium levels, 26.3% (5/19) of children developed hypocalcemia. From November 2014 to July 2018, 37 pediatric patients required total thyroidectomies. 29.7% (11/37) had low 4-h postoperative PTH levels. 72.7% (8/11) patients with low 4-h postoperative PTH levels had corresponding postoperative day 1 total calcium levels less than 8.5 or ionized calcium levels less than 1.12, and five children (45.5%) developed symptomatic hypocalcemia. 70% (26/37) of children had normal 4-h postop PTH levels, with only 5 (19%) ever developing hypocalcemia. No patients with a normal postop PTH level developed symptomatic hypocalcemia or required IV calcium repletion. A single 4-h postoperative PTH <10 pg/dl for identifying hypocalcemia has a sensitivity of 81% and specificity of 91%, with AUC 0.81. ConclusionThe 4-h postoperative serum PTH level can help determine the need for calcium supplementation in pediatric patients undergoing total thyroidectomy, thereby reducing unnecessary calcium supplementation and serial lab draws to monitor for postoperative hypocalcemia. Level of evidenceLevel II.

Low parathyroid hormone level predicts infection-related mortality in incident dialysis patients: a prospective cohort study.

Background/AimsParathyroid hormone (PTH) is an important factor influencing immunologic dysfunction, but the effect of PTH level on infection-related outcomes remains unclear in incident dialysis.MethodsWe evaluated a multicenter prospective cohort study of 1,771 incident dialysis patients (1,260 hemodialysis and 511 peritoneal dialysis) in Korea. Patients were divided into three groups based on serum intact PTH (iPTH) level. The primary outcomes were all-cause and infection-related mortality and multivariate Cox regression analysis was performed to evaluate the role of iPTH in all-cause and infection-related mortality.ResultsDuring the follow-up period of 27.3 months, 175 patients (9.9%) died, and infection-related death represented 20% of all-cause mortality. Both all-cause mortality and infection-related mortality rates (p < 0.001 and p = 0.003, by logrank) were markedly higher in patients with serum iPTH < 150 pg/mL than in the other groups. Multivariate Cox regression analysis revealed that patients with serum iPTH < 150 pg/mL remained at higher risk for infection-related mortality than patients in the target range of 150 ≤ iPTH < 300 pg/mL, after adjusting for confounding variables (hazard ratio [HR], 2.52; 95% confidence interval, 1.06 to 5.99; p = 0.04). The HR of infection-related mortality in patients with serum iPTH < 150 pg/mL was significantly higher in patients with low serum phosphorus, low Ca × P product, low serum alkaline phosphatase and those older than 65 years.ConclusionsLow serum iPTH level is an independent predictor of infection-related mortality in incident dialysis patients.

Effects of milk powder intervention on bone mineral density and indicators related to bone metabolism in Chinese adolescents

SummaryThe study is to determine the effects of milk powder on bone density and metabolism in healthy adolescents. Vitamin D and calcium supplements increased IGF-1 but did not affect bone mineralization or turnover. Higher vitamin D in combination with sufficient calcium supplementation in such populations requires attention.IntroductionBoth calcium and vitamin D play an important role in bone mineralization in adolescents.MethodsIn this one and a half-year randomized controlled trial, 232 participants (aged 12–15 years) were randomly assigned to three intervention groups receiving milk powder fortified with vitamin D 400 IU plus calcium 300, or 600, or 900 mg [Ca3D (n = 54), Ca6D (n = 56), and Ca9D (n = 49)], or one control group maintaining habitual diet [control (n = 73)]. Bone turnover markers, serum intact PTH, 25(OH)D, and IGF-1 levels were measured at baseline and one and a half years, and bone mineral contents and bone areal mineral density were measured by Dual-energy X-ray absorptiometry (DXA) at baseline, one year, and one and a half years.ResultsBaseline average serum 25(OH)D level and calcium intake were 29.4 nmol/L and 363.5 mg/day, respectively. There was a significant increase in bone turnover, total body, hip, lumbar spine bone mineral density (BMD), and total body BMC as well as slight fluctuations in 25(OH)D levels over one and a half years without between-group differences. Significantly decreased serum PTH level was only observed in the Ca6D group (31%, p < 0.0001), in which the intervention effect was also significant (p = 0.0029) compared with the control group. IGF-1 levels increased significantly in all intervention groups (18.5 to 22.8%, p < 0.05) but decreased in the control group (16.5%, p < 0.05), and the group by time interaction was also significant (p = 0.0029).ConclusionsOur study showed that in healthy adolescents with low vitamin D status and calcium intake, mild vitamin D and mild to modest calcium supplements increased IGF-1 but did not affect bone mineralization or turnover. Higher vitamin D in combination with sufficient calcium supplementation in such populations requires attention.

MON-257 A Case of Primary Hyperparathyroidism Complicated by Vitamin D Deficiency

Background: Primary hyperparathyroidism is a relatively common disorder caused by the inappropriate autonomous secretion of parathyroid hormone which subsequently leads to hypercalcemia. There is increased prevalence of vitamin D deficiency in patients with primary hyperparathyroidism. As these patients are already hypercalcemic, there is reluctance within the medical community to provide vitamin D supplementation due to fear of exacerbating hypercalcemia. Clinical Case: A 17 year old African American male was referred to the pediatric endocrinology clinic for hypercalcemia (total serum calcium level 11.2 mg/dL, 8.6-10.6). His past medical history was significant for a diagnosis of membranoproliferative glomerulonephritis type 2 which was in remission. His most recent blood tests showed normal renal function. A review of his hospital chart showed that his calcium levels had been on the upper end of the reference range or above it for at least a year prior to his presentation to the clinic. He had no signs or symptoms concerning for hypercalcemia. He was not taking any calcium supplements or other medications which are known to be associated with elevated calcium levels. There was no known family history of hypercalcemia. He denied any history of renal stones, adrenal disease, weight loss, or osteoporosis but did report a wrist and knee fracture both of which occurred during competitive wrestling matches. His vital signs and physical exam were unremarkable. On laboratory analysis his serum calcium was 11.0 mg/dL, intact PTH 112 pg/mL (ref range 12-88), 25 hydroxyvitamin D was 10 ng/mL (ref range 20-80), Alk Phos 145 U/L (ref range 100-300), Albumin 4.8 g/dL (3.4-5.0), TSH 1.97 mcIU/mL (0.35-4.0), Free T4 0.8 ng/dL (0.6-1.7), Cr 0.94 mg/dL (0.5-1.3), 24 hour urine calcium excretion was 228 mg and calculated calcium to creatinine ratio was 0.07. Ultrasound of the neck and nuclear parathyroid scan and did not definitively show a parathyroid adenoma but could also not rule out the presence of an adenoma. Given patient’s low 25 OH vitamin D level he was given a 4 week course of supplemental vitamin D (1,000 units daily) with resultant 25 OH vitamin D level of 21 ng/mL. His serum calcium and intact PTH level remained elevated at 10.9 mg/dL and 108 pg/mL respectively. The patient was sent to otolaryngology for evaluation should the need arise in the future for surgical intervention and genetic testing to definitively rule out familial hypocalciuric hypercalcemia was sent. As he is asymptomatic with mild hypercalcemia currently, we will continue to monitor yearly per guideline recommendations. Conclusion: Supplementation with modest doses of vitamin D did not significantly raise our patient’s calcium level and led to an improvement in the 25 hydroxyvitamin D level. Vitamin D repletion should be considered in cases of asymptomatic primary hyperparathyroidism associated with mild hypercalcemia.

Vitamin D, 1,25-Dihydroxyvitamin D, FGF23, and Graft Function after Renal Transplantation.

Vitamin-D has immuno-modulatory properties besides its role in mineral and bone disorder (MBD) and could have a role in allograft outcome. Fifty-two chronic kidney disease patients on dialysis going for transplantation were prospectively studied before and after renal transplantation. FGF23, 25(OH) vitamin D, 1,25-Dihydroxyvitamin D, PTH, serum Ca, serum PO4, and e-GFR status were evaluated. Vitamin D deficiency was seen in 25.0% of recipients before transplant (26.09 ± 12.19 ng/mL) and in 48.1% at 6 months post-transplant (23.36 ± 15.11 ng/mL). 1,25-(OH)2D levels before transplant were 102.37 ± 108.44 pmol/L, which were less than control (143.30 ± 108.0 pmol/L) and decreased further to 46.20 ± 42.11 pmol/mL at 3 months and started increasing to 78.37 ± 60.12 pmol/mL at 6 months post-transplantation without vitamin D supplementation. The prevalence of hypophosphatemia after transplantation was 32.0%, hyperkalemia was 12.0%, elevated intact PTH levels at 3 and 6 months after transplant were seen in 66.7% and 30.8% patients, respectively. FGF-23 levels were high in 72.5% of patients before transplant (495.94 ± 690.68 pg/mL) and decreased to normal levels at 3 months post-transplant (31.63 ± 14.17 pg/m) (control 32.07 ± 9.78 pg/mL). Serum intact PTH levels were 379.54 ± 281.27 pg/mL before transplant and came down to 103.96 ± 68.34 at 3 months and 69.87 ± 116.03 at 6 months post-transplantation. There was trend of higher e-GFR at 1 year post-transplant in patients without vitamin D deficiency (levels ≥30 ng/mL). The dysregulated mineral metabolism continues in post-transplant despite improvement in renal function and normalization of FGF-23.

Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience.

Primary hyperparathyroidism (PHPT) is a common endocrine disease. Although surgical treatment is curative in most cases, there are few alternative therapies for the hypercalcemia caused by PHPT. Cinacalcet is a positive allosteric modulator of the calcium sensing receptor and was conditionally approved in Japan in 2014 to treat PHPT cases. However, there have been few reports on the outcomes. In our present study, we investigated the efficacy and safety of cinacalcet in 61 PHPT patients who were treated with this agent at our hospital between January 2014 and March 2017. The corrected serum Ca and intact PTH levels were significantly reduced by this treatment, whereas the serum phosphorus levels significantly increased. There were no significant differences in the eGFR or urinary Ca to urinary creatinine ratio between baseline and the maintenance phase. In terms of bone mineral density, there were significant increases observed in the 16 cases for whom a baseline value was available, 11 of whom had been treated for osteoporosis. The most common adverse events from cinacalcet treatment were gastrointestinal symptom, such as nausea and appetite loss. Other adverse events included severe dehydration due to hypercalcemia, myalgia, hypocalcemia, and increased urinary calcium excretion. Seven patients were switched to surgical treatment, and the drug was discontinued in 9 other patients, due to adverse effects. Our present study findings demonstrate that cinacalcet is an effective therapeutic option for PHPT from the perspective of hypercalcemia improvement but that adverse gastrointestinal effects of this drug occur at a frequency of about 10%.

FGF 23, PTH and vitamin D status in end stage renal disease patients affected by VDR FokI and BsmI variants

ObjectivesThe aim of this study was to evaluate the association between two VDR SNPs FokI and BsmI and mineral status in ESRD patients. Design and methodsOur case-control study included 100 patients with chronic renal failure in ESRD and 149 healthy subjects. We measured the serum Vitamin D levels and the serum intact PTH level by Electrochemiluminescence Technology (cobas E411 analyzer). We evaluated the serum FGF23 levels by indirect ELISA method. The genotyping of two VDR gene variants FokI and BsmI was carried out by PCR-RFLP technique. ResultsIn our study, the FokI TT genotype was associated with lower risk of ESRD development (OR = 0.176, Padj = 0.039). The difference in PTH and FGF23 levels between cases and controls was statistically significant. The expression of FokI CT genotype in subjects with diabetic nephropathy was associated with a negative correlation between VD and PTH levels (r = −0.620, P = 0.032) and a positive correlation between VD and FGF23 levels (r = 0.967, P = 0.012). A significant differences in VD levels between patients and controls was observed in the presence of FokI TT (P = 0.044) and CT (P = 0.036) genotypes. The expression of FGF23 serum level was significantly elevated in patients than in controls in the presence of the FokI CC and BsmI AG genotypes. ConclusionsIn conclusion, our study shows the existence of an association between VDR FokI, BsmI polymorphisms and mineral status in ESRD patients. The presence of VDR variants affect the protein expression of VD, phosphorus, FGF23 and PTH.

Combined use of a nanocarbon suspension and 99mTc-MIBI for the intra-operative localization of the parathyroid glands

ObjectiveTo investigate the combined use of a nanocarbon (NC) suspension and low-dose 99mTc-MIBI for parathyroid localization during surgery in patients with secondary hyperparathyroidism (sHPT). MethodsBetween March 2010 and September 2015, 40 patients with sHPT were enrolled in this study and were randomized to receive either low-dose 99mTc-MIBI+NC (group I) or low-dose 99mTc-MIBI (group II). Pre- and post-operative serum levels of intact PTH (iPTH), calcium and phosphorus between groups were compared and the intra-operative radioactive counts of the parathyroid glands were measured. ResultsThe post-operative iPTH level was significantly lower in patients of group I (24.2±31ng/L) than in those of group II (106±155ng/L) (P=0.03) while there were no significant differences in intra-operative parathyroid gland radioactive counts between the groups. The duration of the surgical procedure was shorter for patients of group I than patients of group II. There were no serious intra-operative or post-operative complications. ConclusionThe combined use of an NC suspension and 99mTc-MIBI for patients with sHPT is strongly recommended for the localization of parathyroid glands during surgery and is likely to improve clinical outcomes for patients.

Diagnostic Accuracy Study of Intraoperative and Perioperative Serum Intact PTH Level for Successful Parathyroidectomy in 501 Secondary Hyperparathyroidism Patients.

Parathyroidectomy (PTX) is an effective treatment for severe secondary hyperparathyroidism (SHPT); however, persistent SHPT may occur because of supernumerary and ectopic parathyroids. Here a diagnostic accuracy study of intraoperative and perioperative serum intact parathyroid hormone (iPTH) was performed to predict successful surgery in 501 patients, who received total PTX + autotransplantation without thymectomy. Serum iPTH values before incision (io-iPTH0), 10 and 20 min after removing the last parathyroid (io-iPTH10, io-iPTH20), and the first and fourth day after PTX (D1-iPTH, D4-iPTH) were recoded. Patients whose serum iPTH was >50 pg/mL at the first postoperative week were followed up within six months. Successful PTX was defined if iPTH was <300 pg/mL, on the contrary, persistent SHPT was regarded. There were 86.4% patients underwent successful PTX, 9.8% remained as persistent SHPT and 3.8% were undetermined. Intraoperative serum iPTH demonstrated no significant differences in two subgroups with or without chronic hepatitis. Receiver operating characteristic (ROC) curves showed that >88.9% of io-iPTH20% could predict successful PTX (area under the curve [AUC] 0.909, sensitivity 78.6%, specificity 88.5%), thereby avoiding unnecessary exploration to reduce operative complications. D4-iPTH >147.4 pg/mL could predict persistent SHPT (AUC 0.998, sensitivity 100%, specificity 99.5%), so that medical intervention or reoperation start timely.

Hypercalcemia Due to Parathyroid Hormone-Related Protein Induced by Primary Endometrial Clear Cell Adenocarcinoma: Case Report

Humoral Hypercalcemia of Malignancy (HHM) has been reported in association with a number of malignancies. In gynecologic malignancies, ovarian Clear Cell Carcinoma (CCC) is one of the most commonhistologic subtypes, whereas HHM caused by endometrial CCC is very rare. We report a case of endometrial CCC with HHM, with a low serum intact PTH level, elevated serum PTH-related Peptide (PTH-rP), and immunohistochemically demonstrated PTH-rP in the neoplasm.

Clinical Expression of Calcium Sensing Receptor Polymorphism (A986S) in Normocalcemic and Asymptomatic Hyperparathyroidism.

Normocalcemic and asymptomatic hyperparathyroidism diagnosis are becoming more common. However, their pathophysiology is incompletely known. The aim of the present study was to evaluate the clinical effect of calcium-sensing receptor polymorphism (A986S) in normocalcemic and asymtomatic HPT. Prospective study conducted with 61 consecutive normocalcemic and asymptomatic HPT patients was followed up during a minimum period of 1 year. Secondary causes of hyperparathyroidism were ruled out. Calcium and phosphorus metabolism parameters were evaluated in at least 2 determinations during follow-up to classify as normocalcemic or asymptomatic hyperparathyroidism. Bone mineral density and A986S polymorphism genotype were also analyzed. Thiry-eight patients (62.3%) had the genotype A986A, and 23 (36.7%) patients had A986S (20 patients, 32.8%) or S986S (3 patients, 4.9%). Age, sex, and genotype distributions were comparable in both normocalcemic and asymptomatic hyperparathyroidism. In normocalcemic patients, S allele genotype was associated to statistically significant higher level of intact PTH: 92.0 (SD 18.5) vs. 110.6 (SD 24.4) pg/ml, p<0.05; and remained significant after adjustment by multiple linear regression. In asymptomatic hyperparathyroidism, A986A genotype resulted in a statistically significant higher level of intact PTH, alkaline phosphatase and procollagen amino-terminal propeptide; but only serum calcium remained as an independent predictor of serum intact PTH levels after a multiple linear regression. Bone mineral densitometry between genotypes did not show statistically significant differences. A986S polymorphism of CaSR is an independent predictor of PTH level in normocalcemic hyperparathyroidism patients, but not in asymptomatic hyperparathyroidism. More studies are needed to evaluate the effect of other polymorphisms in normocalcemic and asymptomatic hyperparathyroidism.

Impact of Parathyroidectomy on Serum FGF23 and Soluble Klotho in Hemodialysis Patients With Severe Secondary Hyperparathyroidism

Klotho is a transmembrane protein that functions as a coreceptor for fibroblast growth factor 23 (FGF23). Klotho is cleaved and released into the circulation; however, the main site of production, physiological role, and regulation of soluble Klotho in humans are largely unknown. The aim of this study was to determine the impact of parathyroidectomy (PTx) on serum FGF23 and soluble Klotho levels in patients with severe secondary hyperparathyroidism. This was a prospective, single-arm trial conducted at Tokai University School of Medicine. Thirteen hemodialysis patients with severe secondary hyperparathyroidism who were candidates for PTx participated in the study. All patients underwent total PTx with forearm autotransplantation. We evaluated changes in serum FGF23 and soluble Klotho levels for 90 days after PTx. Other biochemical parameters related to mineral and bone metabolism were also assessed. At baseline, serum FGF23 levels were markedly elevated, whereas serum soluble Klotho levels were modestly decreased. PTx resulted in a marked, progressive decline in serum FGF23 levels together with significant reductions in serum calcium, phosphorus, and intact PTH levels. The serum soluble Klotho levels were reduced 13% from baseline on the day after PTx; however, these levels then increased progressively, reaching 34% above the postoperative values. Our results suggest that the parathyroid gland is not the major site of soluble Klotho production in patients with end-stage renal disease, and the production of Klotho by other organ(s) is affected by alterations in mineral metabolism or medications taken after PTx.

Cinacalcet Monotherapy in Neonatal Severe Hyperparathyroidism: A Case Study and Review

Neonatal severe hyperparathyroidism (NSHPT) is a severe form of familial hypocalciuric hypercalcemia characterized by severe hypercalcemia and skeletal demineralization. In most cases, NSHPT is due to biallelic loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR), but some patients have heterozygous mutations. Conventional treatment consists of iv saline, bisphosphonates, and parathyroidectomy. The aim of this project was to characterize the molecular basis for NSHPT in an affected newborn and to describe the response to monotherapy with cinacalcet. Clinical and biochemical features were monitored as cinacalcet therapy was initiated and maintained. Genomic DNA was obtained from the proband and parents. The CASR gene was amplified by PCR and sequenced directly. The patient was a full-term male who developed hypotonia and respiratory failure soon after birth. He was found to have multiple fractures and diffuse bone demineralization, with a marked elevation in serum ionized calcium (1.99 mmol/L) and elevated serum levels of intact PTH (1154 pg/mL); serum 25-hydroxyvitamin D was low, and fractional excretion of calcium was reduced. The serum calcium level was not reduced by iv saline infusion. Based on an extensive family history of autosomal dominant hypercalcemia, a diagnosis of NSHPT was made, and cinacalcet therapy was initiated with a robust and durable effect. Molecular studies revealed a heterozygous R185Q missense mutation in the CASR in the patient and his father, whereas normal sequences for the CASR gene were present in the patient's mother. We describe the first use of cinacalcet as monotherapy for severe hypercalcemia in a newborn with NSHPT. The rapid and durable response to cinacalcet suggests that a trial of calcimimetic therapy should be considered early in the course of NSHPT.

Postoperative PTH Measurement Is Not a Reliable Predictor for Hypocalcemia After Total Thyroidectomy in Vitamin D Deficiency: Prospective Study of 203 Cases

Several factors have been used to predict post total thyroidectomy (TT) hypocalcemia. Serum intact PTH (PTH) levels <10 pg/mL after TT is considered to be the most accurate predictor. The aim of the present study was to evaluate the accuracy of PTH as a predictor of post-TT hypocalcemia in patients with vitamin D deficiency. The present prospective study was conducted from 2009 to 2011 and included patients undergoing TT for benign goiter. The PTH levels 8h after TT in patients who were vitamin D sufficient (group A; S Vit D >20ng/mL) versus those who were vitamin D deficient (group B) were compared. Comparison was also performed between patients belonging to group A and group B who developed hypocalcemia. Appropriate statistical tests were applied. A total of 203 patients (19 males, 184 females) underwent TT; 58.6% (n = 119) belonged to group A and 41.4% (n = 84) to group B. Their mean age was 36.81 ± 12.9years, and the mean duration of goiter was 45.35 ± 54.6months. Hypocalcemia occurred in 41 patients (20.2%). Among them 15 belonged to group A and 26 to group B (p = 0.002). The mean PTH in patients who developed hypocalcemia was 12.75 ± 8.91 versus 22.58 ± 15.38 in those who did not develop hypocalcemia (p = 0.00). Furthermore it was seen that the mean PTH in vitamin D sufficient hypocalcemic patients (n = 15) was 7.12 ± 1.79 and that in vitamin D deficient hypocalcemic patients (n = 26) was 16 ± 9.77 (p = 0.001) CONCLUSIONS: Our findings suggest that the fall in PTH after TT in vitamin D deficient patients is unreliable in predicting hypocalcemia and should not be relied on to plan early postoperative discharge.

Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism

BackgroundSecondary hyperparathyroidism (SHPT) is one of the common complications in dialysis patients, and is associated with increased risk of vascular calcification. The effects of cinacalcet hydrochloride treatment on bone and mineral metabolism have been previously reported, but the benefit of cinacalcet on vascular calcification remains uncertain. The aim of this study was to evaluate the impact of cinacalcet on abdominal aortic calcification in dialysis patients.Subjects and methodsPatients were on maintenance hemodialysis with insufficiently controlled SHPT (intact parathyroid hormone [PTH] >180 pg/mL) by conventional therapies. All subjects were initially administered 25 mg cinacalcet daily, with concomitant use of calcitriol analogs. Abdominal aortic calcification was annually evaluated by calculating aortic calcification area index (ACAI) using multidetector computed tomography (MDCT), from 12 months before to 36 months after the initiation of cinacalcet therapy.ResultsTwenty-three patients were analyzed in this study. The mean age was 59.0±8.7 years, 34.8% were women, and the mean dialysis duration was 163.0±76.0 months. After administration of cinacalcet, serum levels of intact PTH, phosphorus, and calcium significantly decreased, and mean Ca × P values significantly decreased from 67.4±7.9 mg2/dL2 to 52±7.7 mg2/dL2. Although the ACAI value did not decrease during the observation period, the increase in ACAI between 24 months and 36 months after cinacalcet administration was significantly suppressed.ConclusionLong-term administration of cinacalcet was associated with reduced progression of abdominal aortic calcification, and achieving appropriate calcium and phosphorus levels may reduce the rates of cardiovascular events and mortality in patients on hemodialysis.

Renal Bone Disease Among Patients With ESRD

Dear Editor, With interest, we read the article by Sidy Secket et al. on the mineral and bone disease in black African hemodialysis patients: A report from Senegal. The authors evaluated 118 end-stage renal disease (ESRD) patients under hemodialysis and showed that chronic kidney disease related mineral and bone disease (CKD-MBD) are frequent in Senegalese hemodialysis patients with prevalence of 66.9 % and hyperparathyroidism is the most commonplace disorder followed by adynamic bone disease and osteomalacia (1). Unfortunately CKD-MBD is also common in other developed and developing countries and this will cause an enormous financial burden for health-care systems (2, 3). There appears to be an increased risk of all-cause and cardiovascular mortality among ESRD patients with disorders of mineral metabolism (4). Although, renal bone and mineral disease are progressive lesions among patients with CKD, symptoms and/or signs due to the various CKD-MBD, such as fractures, bone and muscle pain, generally do not occur until the patient is undergoing maintenance dialysis (2). Five main types of renal bone and mineral disease can be seen among patients with CKD. These are 1) osteitis fibrosa cystic, in which bone turnover is increased due to secondary hyperparathyroidism, 2) adynamic or aplastic bone disease, in which bone turnover is low due primarily to excessive suppression of the parathyroid glands and in some cases due to aluminum deposition, 3) osteomalacia, in which bone turnover is also low in combination with a marked increase in the volume of unmineralized bone, most current cases result from aluminum deposition in bone among patients who used aluminum-containing antacids as phosphate binders, 4) mixed renal osteodystrophy, a mixture of the first and three type, in which elements of both high and low bone turnover may be observed and presented as marrow fibrosis and increased unmineralized osteoid, and 5- beta 2-microglobulin-associated amyloid deposit’s bone disease in which occur in patients on long-term dialysis and characterized by bone cysts (5-8). It appears that the prevalence of the different types of bone disease is considerably different between developed and developing countries (1, 9). For example in the result of Sidy Secket et al. study in Senegal a developing country, osteitis fibrosa cystica due to secondary hyperparathyroidism is the most common type of renal osteodystrophy which occurred in 55 patients with ESRD followed by adynamic bone disease in which occurred in 21 patients and osteomalacia in which occurred in 1 patient (1). However in developed countries, the prevalence of secondary hyperparathyroidism among dialysis patients has markedly decreased compared to last few decades and at present, the most common disorder is non-aluminum-induced adynamic bone disease, with osteitis fibrosa due to secondary hyperparathyroidism, osteomalacia, and mixed disease less frequently observed (10-13). High frequency of non-aluminum-induced adynamic bone disease in developed countries can be explained by multiple factors, including changes in therapeutic strategies such as the increased and earlier use of vitamin D analogs and calcium-containing phosphate binders (14, 15). Patients' demographics (older and increased number of diabetic patients) may also be implicated in the increasing number of patients with adynamic bone disease among these countries. For example in a bone biopsy study in 84 patients with stage 5 CKD not yet on maintenance dialysis, adynamic bone disease was the most common type of renal bone disease among patients with diabetes mellitus (14). We have a methodological comment on the study by Sidy Secket et al. The authors did not perform bone biopsy for diagnosing the type of renal bone disease and it is a limited factor for the study (1). Bone biopsy is the gold standard for establishing the various types of renal osteodystrophy and there is some new evidence that biochemical parameters such as is serum intact PTH level is not sufficiently accurate for establishing the type of renal bone disease among patients with CKD (16). The discrepancy between biochemical parameters and the type of renal bone disease was shown in retrospective study of Gal-Moscovici A et al. They compared serum intact PTH levels with results from bone biopsy and showed no correlation between bone biopsy results and PTH levels in 150 to 500 pg/mL and 500 to 1,200 pg/mL. However a significant correlation is observed in this study between adynamic bone disease and PTH levels less than 150 pg/mL (16).