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Intact PTH (intact + pth)
Selected AbstractsCalcium supplement necessary to correct hypocalcemia after total parathyroidectomy for renal osteodystrophyINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2000Masayuki Nakagawa Abstract Background: Prediction of the extent of calcium supplement will facilitate safe and efficient management of hypocalcemia in the early postoperative stage of total parathyroidectomy with autotransplantation (PTXa) in patients with renal osteodystrophy. Methods: The correlation between the extent of calcium deficiency, estimated by the amount of calcium supplement over 48 h after PTXa and using various parameters such as carboxy terminal parathyroid hormone (c-PTH), intact PTH (i-PTH), alkaline phosphatase (ALP), serum calcium, serum phosphorus, duration of hemodialysis, total weight of resected parathyroid glands and degree of subperiosteal resorption of the middle phalanx was examined in 49 patients who underwent PTX with subcutaneous autotransplantation. Bone mineral density (BMD) was also determined before, 3 months and 1 year after PTXa with dual energy X-ray absorptiometry (DEXA) in 13 patients. Results: There was a positive correlation between pre-operative i-PTH level (r = 0.56, P < 0.0005) or ALP level (r = 0.50, P < 0.0005) and the amount of calcium supplement over 48 h after PTXa in these patients. Furthermore, the degree of subperiosteal resorption, determined by Jensen's classification, was significantly correlated with the amount of calcium supplement after PTX (P < 0.05). Bone mineral density 3 months after (P < 0.0005) and 1 year after PTXa (P < 0.001) significantly increased compared with BMD before PTXa in all patients examined. Conclusion: These findings suggest that the pre-operative determination of i-PTH, ALP levels and degree of subperiosteal resorption allow the management of hypocalcemia safely and efficiently in renal osteodystrophy patients after PTXa. [source] Familial Hypocalciuric Hypercalcemia Caused by an R648stop Mutation in the Calcium-Sensing Receptor Gene ,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2002Mika Yamauchi Abstract In this study, we report an 84-year-old female proband in a Japanese family with familial hypocalciuric hypercalcemia (FHH) caused by an R648stop mutation in the extracellular calcium-sensing receptor (CaR) gene. At the age of 71 years, she presented with hypercalcemia (11.4 mg/dl), hypocalciuria (Cca/Ccr = 0.003), hypermagnesemia (2.9 mg/dl), and a high-serum parathyroid hormone (PTH) level (midregion PTH, 3225 [160,520] pg/ml). At the age of 74 years, a family screening was carried out and revealed a total of 9 hypercalcemic individuals (all intact PTH values <62 pg/dl) among 17 family members tested, thus, being diagnosed as FHH. Two and one-half of three clearly enlarged parathyroid glands were resected, because persistently high PTH levels (intact PTH, 292 pg/ml; midregion PTH, 5225 pg/ml) and the presence of a markedly enlarged parathyroid gland by several imaging modalities (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], and subtraction scintigraphy) suggested coexistent primary hyperparathyroidism (pHPT); however, hypercalcemia persisted postoperatively. Histological and immunohistochemical examination revealed that the resected parathyroid glands showed lipohyperplasia as well as normally expressed Ki67, vitamin D receptor (VDR), and the CaR. Sequence analysis disclosed that the proband and all affected family members had a heterozygous nonsense (R648stop) mutation in the CaR gene. This mutation is located in the first intracellular loop; thus, it would be predicted to produce a truncated CaR having only one transmembrane domain (TMD) and lacking its remaining TMDs, intracellular loops, and C-terminal tail. Western analysis of biotinylated HEK293 cells transiently transfected with this mutant receptor showed cell surface expression of the truncated protein at a level comparable with that of the wild-type CaR. The mutant receptor, however, exhibited no increase in intracellular free calcium concentration (Ca2+i) when exposed to high extracellular calcium concentrations (Ca2+o). The proband's clinical course was complicated because of associated renal tubular acidosis (RTA) and nephrotic syndrome. However, it was unclear whether their association affected the development of elevated serum PTH and parathyroid gland enlargement. This report is the first to show that an R648stop CaR mutation yields a truncated receptor that is expressed on the cell surface but is devoid of biological activity, resulting in FHH. [source] Development of a Novel Immunoradiometric Assay Exclusively for Biologically Active Whole Parathyroid Hormone 1,84: Implications for Improvement of Accurate Assessment of Parathyroid FunctionJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2001Ping Gao Abstract We developed a novel immunoradiometric assay (IRMA; whole parathyroid hormone [PTH] IRMA) for PTH, which specifically measures biologically active whole PTH(1,84). The assay is based on a solid phase coated with anti-PTH(39,84) antibody, a tracer of125I-labeled antibody with a unique specificity to the first N-terminal amino acid of PTH(1,84), and calibrators of diluted synthetic PTH(1,84). In contrast to the Nichols intact PTH IRMA, this new assay does not detect PTH(7,84) fragments and only detects one immunoreactive peak in chromatographically fractionated patient samples. The assay was shown to have an analytical sensitivity of 1.0 pg/ml with a linear measurement range up to 2300 pg/ml. With this assay, we further identified that the previously described non-(1,84)PTH fragments are aminoterminally truncated with similar hydrophobicity as PTH(7,84), and these PTH fragments are present not only in patients with secondary hyperparathyroidism (2° -HPT) of uremia, but also in patients with primary hyperparathyroidism (1° -HPT) and normal persons. The plasma normal range of the whole PTH(1,84) was 7,36 pg/ml (mean ± SD: 22.7 ± 7.2 pg/ml, n = 135), whereas over 93.9% (155/165) of patients with 1° -HPT had whole PTH(1,84) values above the normal cut-off. The percentage of biologically active whole PTH(1,84) (pB%) in the pool of total immunoreactive "intact" PTH is higher in the normal population (median: 67.3%; SD: 15.8%; n = 56) than in uremic patients (median:53.8%; SD: 15.5%; n = 318; p < 0.001), although the whole PTH(1,84) values from uremic patients displayed a more significant heterogeneous distribution when compared with that of 1° -HPT patients and normals. Moreover, the pB% displayed a nearly Gaussian distribution pattern from 20% to over 90% in patients with either 1° -HPT or uremia. The specificity of this newly developed whole PTH(1,84) IRMA is the assurance, for the first time, of being able to measure only the biologically active whole PTH(1,84) without cross-reaction to the high concentrations of the aminoterminally truncated PTH fragments found in both normal subjects and patients. Because of the significant variations of pB% in patients, it is necessary to use the whole PTH assay to determine biologically active PTH levels clinically and, thus, to avoid overestimating the concentration of the true biologically active hormone. This new assay could provide a more meaningful standardization of future PTH measurements with improved accuracy in the clinical assessment of parathyroid function. [source] A high prevalence of hypovitaminosis D in Finnish medical in- and outpatientsJOURNAL OF INTERNAL MEDICINE, Issue 6 2001R. Kauppinen-Mäkelin Abstract.,Kauppinen-Mäkelin R, Tähtelä R, Löyttyniemi E, Kärkkäinen J, Välimäki MJ (Peijas Hospital, Vantaa; United Laboratories, Leiras Research, and Division of Endocrinology; Helsinki University Central Hospital, Helsinki, Finland). A high prevalence of hypovitaminosis D in Finnish medical in- and outpatients. J Intern Med 2001; 249: 559,563. Objective.,To study the prevalence of hypovitaminosis D [serum 25(OH)D , 37 nmol L,1)] in Finnish medical in- and outpatients in a cross-sectional study. Methods.,The subjects were 106 consecutive medical inpatients (57 females, 49 males with mean ages of 65 and 58 years) from the Peijas Hospital, Vantaa, Finland, and 99 ambulatory patients (48 females, 51 males with mean ages of 42 and 46 years) contacting a private outpatient centre in Helsinki, Finland. Serum 25(OH)D, vitamin D binding protein (DBP), free vitamin D index (FDI), intact PTH (iPTH), and albumin-corrected calcium were measured. Results.,Serum 25-hydroxyvitamin D [25(OH)D] was 37 nmol L,1 or less in 70% of female and in 61% of male inpatients and in 44% of female and in 37% of male outpatients. In the whole population, a statistically significant inverse association (P < 0.0001) was detected between iPTH and 25(OH)D levels; the iPTH concentration appeared to start increasing when 25(OH)D concentration was 50 nmol L,1 or less. The association remained the same (P < 0.0001) when FDI was used instead of 25(OH)D in the calculations. When the sexes were analysed separately, the statistically significant association was found only in females (P < 0.0001 for iPTH versus 25(OH)D; P < 0.0001 for iPTH versus FDI) but not in males. Conclusion.,Hypovitaminosis D is very common amongst Finnish in- and outpatients in both sexes, causing secondary hyperparathyroidism in females. More extensive studies are warranted to elucidate the vitamin D status of the Finnish population. [source] Structure,function relationship studies of PTH(1,11) analogues containing sterically hindered dipeptide mimeticsJOURNAL OF PEPTIDE SCIENCE, Issue 8 2007Nereo Fiori Abstract The N -terminal 1,34 fragment of parathyroid hormone (PTH) is fully active in vitro and in vivo and reproduces all biological responses characteristic of the native intact PTH. In order to develop safer and non-parenteral PTH-like bone anabolic agents, we have studied the effect of introducing conformationally constrained dipeptide mimetics into the N -terminal portion of PTH in an effort to generate miniaturized PTH-mimetics. To this end, we have synthesized and conformationally and biologically characterized PTH(1,11) analogues containing 3R -carboxy-6S -amino-7,5-bicyclic thiazolidinlactam (7,5-bTL), a rigidified dipeptide mimetic unit. The wild type sequence of PTH(1,11) is H-Ser-Val-Ser-Glu-Ile-Gln-Leu-Met-His-Asn-Leu-NH2. The following pseudo-undecapeptides were prepared: [Ala1, 7,5-bTL3, 4, Nle8, Arg11]hPTH(1,11)NH2 (I); [Ala1, 7,5-bTL6, 7, Nle8, Arg11]hPTH(1,11)NH2 (II); [Ala1, Nle8, 7,5-bTL9, 10, Arg11]hPTH(1,11)NH2 (III). In aqueous solution containing 20% TFE, only analogue I exhibited the typical CD pattern of the ,-helical conformation. NMR experiments and molecular dynamics calculations located the ,-helical stretch in the sequence Ile5 -His9. The dipeptide mimetic unit 7,5-bTL induces a type III ,-turn, occupying the positions i , 1 and i of the turn. Analogue II exhibited an equilibrium between a type I ,-turn and an ,-helix, and analogue III did not show any ordered structure. Biological tests revealed poor activity for all analogues (EC50 > 0.1 mM). Apparently, the relative side-chain orientation of Val2, Ile5 and Met8 can be critical for effective analogue-receptor interaction. Considering helicity as an essential property to obtain active PTH agonists, one must decorate the correctly positioned dipeptide mimetic azabicycloalkane scaffold with substitutions corresponding to the displaced amino acids. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] PTHrP-independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19-negative precursor B acute lymphoblastic leukemiaPEDIATRIC BLOOD & CANCER, Issue 7 2007Hidetaka Niizuma MD Abstract Hypercalcemia in childhood acute lymphoblastic leukemia (ALL) is rare and occasionally associated with parathyroid hormone-related protein (PTHrP). However, the pathogenesis of PTHrP-independent hypercalcemia remains unclear. We report two children with precursor B ALL who had marked hypercalcemia (15.8 and 16.6 mg/dl, respectively) and disseminated osteolysis. Serum tumor necrosis factor-, (TNF-,) and IL-6 were markedly elevated, whereas 1,25(OH)2 vitamin D3, intact PTH and PTHrP were decreased or undetected. Analysis of urinary deoxypyridinoline (DPY) or bone biopsy of the osteolytic lesion showed an increased bone resorption, and administration of bisphosphonate improved the hypercalcemia. Patients had ALL with immunophenotype positive for CD10, CD34, and HLA-DR but negative for CD19 and obtained remission with chemotherapy. These findings suggest that increased osteoclastic bone resorption via stimulation with TNF-, and IL-6 may be mechanism causing PTHrP-independent hypercalcemia in some patients with precursor B ALL lacking CD19 expression. Pediatr Blood Cancer 2007;49:990,993. © 2006 Wiley-Liss, Inc. [source] Serum intact parathyroid hormone as a predictor of hypocalcaemia after total thyroidectomyANZ JOURNAL OF SURGERY, Issue 11 2005Patsy S. H. Soon Background: Hypocalcaemia from hypoparathyroidism is a complication of total thyroidectomy. The aim of the present study was to determine whether an early postoperative level of serum parathyroid hormone (PTH) after total thyroidectomy predicts the development of significant hypocalcaemia and the need for treatment. Methods: Patients undergoing total thyroidectomy had their serum level of intact PTH checked 1 h after removal of the thyroid gland. Serum calcium level was checked on the following morning. Oral calcium and/or calcitriol was commenced if the patient developed hypocalcaemic symptoms, or if the corrected serum calcium level was <2.0 mmol/L. Results: Seventy-nine patients were included in the present study. Thirteen patients had symptoms of hypocalcaemia on postoperative days 1 or 2 and 66 patients remained asymptomatic. The postoperative intact PTH, day 1 calcium and day 2 calcium was 0.32 ± 0.60 pmol/L, 2.01 ± 0.11 mmol/L, and 2.02 ± 0.16 mmol/L, respectively, for the symptomatic group and 1.98 ± 1.25, 2.21 ± 0.13, and 2.19 ± 0.14, respectively, for the asymptomatic group. Calcium support was given to 25 patients, of whom 14 also required calcitriol. Conclusion: Serum PTH 1-h after total thyroidectomy is a reliable predictor of hypocalcaemia and can allow safe early discharge of patients from hospital. [source] | ||||||||||