Value of parathyroid hormone assay for preoperative sonographically guided parathyroid aspirates for minimally invasive parathyroidectomy

PURPOSE: The key to successful parathyroid surgery is accurate preoperative tumor localization. This study investigates the use of ultrasound (US)-guided parathyroid fine needle aspiration (FNA) as a confirmatory diagnostic method in patients with hyperparathyroidism undergoing minimally invasive parathyroidectomy. METHODS: Patients were selected for minimally invasive parathyroidectomy based on the finding of a single parathyroid adenoma identified with US and/or sestamibi scans and confirmation of the suspected parathyroid lesion via FNA and parathyroid hormone (PTH) assay. The value of aspirate obtained from the thyroid gland intraoperatively served as the negative control. RESULTS: A total of 56 tissue FNAs were performed in 27 patients. US detected masses suggestive of parathyroid lesion in all 27 patients, and 31 US-guided FNAs were performed. No complications related to the procedure were noted. Intraoperatively, FNA was performed in the thyroids of 25 patients undergoing minimally invasive parathyroidectomy. Aspirates from lesions subsequently confirmed as having developed from the parathyroid gland had a mean PTH level of 4,677 +/- 123 pg/ml (range, 3,600-5,000 pg/ml), which was significantly higher than thyroid aspirates, which yielded a mean PTH level of 48 +/- 7 pg/ml (range, 5-57 pg/ml). The sensitivity of US and sestamibi scans in the detection of abnormal parathyroid glands was 88% and 77%, respectively. The sensitivity of US-guided FNA in confirming the parathyroid origin of a lesion was 100%. CONCLUSION: US-guided FNA for PTH assay can be performed safely for the confirmation of lesions identified with preoperative US for the selection of patients eligible for minimally invasive parathyroidectomy.     

Comparison of the performance and clinical utility of a carboxy-terminal assay and an intact assay for parathyroid hormone

A comparison of the performance of a two-site immunochemiluminometric assay for intact parathyroid hormone with that of an in-house radioimmunoassay for carboxy terminal parathyroid hormone has been performed on samples from unselected patients being investigated for hypercalcaemia. The intact parathyroid hormone assay was found to be a simple and robust technique with a broad working assay range (CV less than 10% between 1.8-212 pmol/l) and a detection limit of 0.2 pmol/l. Clinically it is superior to the carboxy terminal assay in its ability to distinguish between patients with hyperparathyroidism from those with other causes of hypercalcaemia especially in the presence of impaired renal function.     

Measurement of parathyroid hormone and application of parathyroid hormone in intraoperative monitoring

There has been a clear progression in assays for the analysis of PTH and its clinical applications. This includes the innovative use of PTH as a point-of-care assay as an intraoperative measure of the success of parathyroid surgery. The rapid PTH assay has served as a model for the development of other rapid hormone assays, such as for adrenocorticotropic hormone,although the clinical usefulness of these other applications is less well established. Knowledge of the circulating forms of PTH continues to progress. Information about the biologic and immunologic activities of these forms will aid in the interpretation and clinical use of current assays and in the development of new assays with improved specificities. The clinical laboratory will continue to play a vital role in providing testing and support for this important mediator of mineral metabolism.     

Technical and clinical characterization of the Bio-PTH (1-84) immunochemiluminometric assay and comparison with a second-generation assay for parathyroid hormone

BACKGROUND: The Bio-Intact parathyroid hormone (1-84) assay (Bio-PTH), a newly developed two-site immunochemiluminometric assay, measures exclusively PTH (1-84) in contrast to second-generation "intact PTH" (I-PTH) assays. We investigated the technical performance and clinical significance of this new assay. METHODS: PTH was measured simultaneously by the Bio-PTH assay and Allegro intact PTH IRMA in sera from Japanese patients with calcium disorders. RESULTS: Measured Bio-PTH in serum was unaffected by six freeze-thaw cycles and was stable at 4 degrees C for 7 days and during storage at -20 or -80 degrees C over 28 days. The calibration curve was linear to 1800 ng/L. The detection limit was 3.9 ng/L. The intra- and interassay imprecision was <2.8% and 3.5%, respectively, for analyte concentrations spanning the range of the calibration curve. Bio-PTH was unaffected by a 1000-fold excess of PTH (7-84), although I-PTH reacted equally with PTH (7-84) and PTH (1-84). Bio-PTH was correlated with I-PTH in healthy individuals (r = 0.953; P <0.0001; n = 26) and in the full population without renal dysfunction (r = 0.994; P <0.0001; n = 62). In 72 volunteers, mean (SD) Bio-PTH was 22.2 (7.1) ng/L, or 62% of the mean I-PTH [36.1 (22.3) ng/L]. This ratio was 51% in hemodialysis patients (n = 177). Mean Bio-PTH was high in patients with primary hyperparathyroidism [121 (85) ng/L; n = 18] and hemodialysis patients [102 (104) ng/L; n = 177], low in idiopathic hypoparathyroidism [5.5 (2.8) ng/L; n = 4], and within 2 SD of the mean for healthy controls in Paget disease of the bone [34 (15) ng/L; n = 9] and bone metastasis [24 (12) ng/L; n = 8]. CONCLUSION: The Bio-PTH assay is sensitive and precise and produces expected results for patients with the studied disorders of calcium metabolism.     

磁共振功能性成像用于胶质瘤术前术中的研究进展

脑胶质瘤是最常见原发脑内肿瘤,起源于神经胶质细胞,以局部侵袭性生长为特征。MRI是诊断脑胶质瘤的主要影像手段。随着MR波谱成像(MR spectroscopy,MRS)、扩散张量成像(diffusion tensor imaging,DTI)和血氧水平依赖性功能磁共振成像(blood oxygen level-dependent functional magnetic resonance imaging,BOLD-f MRI)等功能MRI的发展,对于以手术为主的胶质瘤,能进行个性化的术前规划和术中监测,从而降低术后损伤,改善预后。作者就MRI及MRS、DTI、BOLD-f MRI这三种功能成像对胶质瘤术前规划和术中监测及存在的问题进行综述。     

Intraoperative blood sampling for parathyroid hormone measurement during total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism

Normalisation of intact parathyroid hormone serum level confirms sufficient resection of parathyroid tissue after total parathyroidectomy in patients with secondary hyperparathyroidism. The short half-life of the intact parathyroid hormone is such that complete resection may even be confirmed by intraoperative monitoring of the hormone, and operative exploration thus reduced. We tested intact parathyroid hormone serum levels in 9 patients during total parathyroidectomy, preoperatively, after the removal of each gland, after autotransplantation and 1 month postoperatively. The serum levels of the intact parathyroid hormone were significantly reduced after removal of each gland. The total percentage decrement after parathyroidectomy with autotransplantation was 77%. However intact parathyroid hormone levels had normalised in all patients one month after the operation. The absence of perioperative normalisation of intact parathyroid hormone serum levels in our patients cannot be defined as a predictor of incomplete resection in total parathyroidectomy. The definition of an intraoperative cut-off-level concerning the decrement of intact parathyroid hormone levels remains to be proven in further studies.     

术前及术中超声、CT及术中触诊诊断肝肿瘤的一致性评价

目的 评价术前超声、CT及术中超声、术中触诊诊断肝肿瘤良恶性的一致性.方法 分析70例肝肿瘤患者的术前超声、术前CT检查、术中超声以及术中触诊结果,对四种检查结果与病理及随访结果诊断肝肿瘤良恶性的一致性进行评价.结果 术前超声与病理及随访结果诊断肝肿瘤良恶性的一致性为中等(Kappa值0.63),术中触诊与病理及随访结果的诊断一致性较低(Kappa值0.38),CT以及术中超声检查与病理及随访结果诊断一致性较高(Kappa值分别为0.71及0.89),而术中超声与CT检查之间诊断一致性也较高(Kappa值为0.53).而术前超声与术中超声以及术前超声与术中触诊之间诊断一致性均较低(Kappa值均为0.23).结论 在肝肿瘤诊断评价中,CT与术中超声具有较高的诊断一致性,虽然术前超声与术中触诊诊断结果一致性较低,但在临床工作中依然不可或缺,而若能将四者结合应用,将有助于肝肿瘤的诊断与治疗.     

Potential clinical utility of a new IRMA for parathyroid hormone in postmenopausal patients with primary hyperparathyroidism

BACKGROUND: A new commercially available (so-called second-generation) IRMA for parathyroid hormone (PTH) separately detects intact PTH and its N-truncated fragments; however, no studies have compared the first- and second-generation IRMAs for PTH in patients with primary hyperparathyroidism (PHPT) to assess their respective diagnostic accuracies. METHODS: We concomitantly investigated 39 postmenopausal patients with PHPT and a control group of 70 healthy postmenopausal women matched for age, renal function, and vitamin D status. In all individuals, PTH was measured with a classic IRMA (PTH-S; DiaSorin Inc.), which uses antibodies directed against epitopes 1-34 and 39-84, and a new method (Scantibodies Laboratory. Inc.), which uses antibodies against epitopes 1-4 and 39-84 (PTH-W) and epitopes 7-34 and 39-84 (PTH-T). We also assayed serum PTH in 10 PHPT patients every 24 h for 5 days after successful surgery. RESULTS: The different assays gave serum PTH values that were >2 SD higher than values for the control population in 59% (PTH-S), 77% (PTH-W), and 82% (PTH-T) of patients with PHPT. However, ROC curve analysis showed no significant differences among the three PTH assays, demonstrating overlapping diagnostic sensitivities. In PHPT patients, the correlation among the assays was highly significant (r = 0.91-0.92; P <0.001). The ratio PTH-W:PTH-T x 100 showed a gaussian distribution in both PHPT patients and controls, whose mean (SD) values [63.4 (13.3)% vs 64.5 (9.5)%, respectively] did not differ significantly. After parathyroidectomy, the mean percentages of variation in PTH detected with all of the assays were quite similar. CONCLUSIONS: The distribution of the PTH-W:PTH-T ratio in patients and controls suggests that PHPT does not markedly influence the rate at which biologically inactive fragments are generated by central or peripheral cleavage of PTH. The similar postoperative curves seem to contradict the hypothesized effect of acute hypocalcemia in modulating the central secretion of hormonal fragments. Our results indicate that the three investigated assays have similar diagnostic sensitivities in PHPT.     

Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma.

Parathyroid adenomas are common benign neoplasms for which no chromosomal defects have been described. We recently found two parathyroid adenomas bearing clonal restriction fragment abnormalities involving the PTH locus, and now show that in one of these tumors: (a) a DNA rearrangement occurred at the PTH locus; (b) the rearrangement separated the PTH gene's 5' flanking region from its coding exons, conceivably placing a newly adjacent gene under the influence of PTH regulatory elements; (c) the DNA that recombined with PTH normally maps to 11q13, the known chromosomal location of several oncogenes and the gene for multiple endocrine neoplasia type I; and (d) the rearrangement was a reciprocal, conservative recombination of the locus on 11q13 (Human Gene Mapping Library assignment D11S287) with PTH (on 11p15). These data provide molecular cytogenetic evidence for the clonal occurrence of a major chromosome 11 aberrancy in this benign parathyroid tumor. The D11S287 clone could prove useful in genetic linkage analyses, in determining precise 11q13 breakpoints in other neoplasms, and in identifying a gene on chromosome 11 that may participate in parathyroid tumor development.     

Evaluation of an immunochromatographic assay for rapid identification of Mycobacterium tuberculosis complex in clinical isolates

Identification of Mycobacterium tuberculosis complex (MTC) remains slow. Over the years, several new technologies have been proposed to accelerate and simplify the detection of MTC. In this context, we evaluated an immunochromatographic assay (ICA) (BIO-LINE SD Ag MPT64 TB) for rapid identification of MTC, based on detection of a specific MPT64 antigen of MTC. We have tested it on i) mycobacterial cultures: 210 MTC strains and 28 nontuberculous mycobacteria; ii) M. bovis bacille Calmette-Guérin strain SSI (Statens Serum Institut, Denmark); and iii) 22 microorganisms other than mycobacteria, isolated from cultures. We concluded that this kit has an excellent specificity (100%) and sensitivity (99%) from isolated cultures. The ICA (BIO-LINE SD Ag MPT64 TB) allows excellent MTC identification from clinical isolates. It is a rapid, simple, and inexpensive test, and has a definite contribution in the rapid laboratory diagnosis of tuberculosis.     

Evaluation of the specificity of a luteinizing hormone beta and alpha subunit assay.

A non-specific antihuman FSH antiserum which is able to bind 125I-labelled FSH, LH, LHbeta and LHalpha subunits, has been shown to contain at least three different antibody populations directed against different parts of the LH and FSH molecule. This antiserum has been used to develop a rather specific radio-immunoassay for determination of the common alpha subunit. Further, by gel filtration it is shown that the LH IRC2/69 preparation contains about 30% of intact LH and about 10% of alpha and LHbeta subunit, respectively. In contrast, the LH 68/40 preparation contains about 96% of intact LH and only small amounts of alpha and LHbeta subunit. Also, a considerable difference in the content of the alpha sub-unit was found between two different FSH preparations. The contamination of the preparations of the intact hormones is shown to have a marked influence on the cross-reactivity of the substances in an LHbeta and alpha subunit radioimmuno-assay.     

Evaluation of a chemiluminescence immunoassay for the determination of intact parathyroid hormone using the ADVIA Centaur

We tested a new chemiluminescence immunoassay for intact parathyroid hormone (PTH) (ADVIA Centaur intact PTH-serum assay). It is a two-site sandwich immunoassay using direct chemiluminescence technology. We investigated precision with serum pools at three levels of the analyte, analyzed in duplicate for 12 days. Total coefficients of variation (CVs) were between 4.6 and 14.4%. The intra-assay precision was between 4.4 and 6.1%. Day-to-day reproducibility was between 1.5 and 13.1% for pools with a PTH concentration between 10 pg/ml and 70 pg/ml (about 1 to 7 pmol/l). The analytical sensitivity was 3.1 pg/ml. The functional sensitivity did not differ from 3 SD minimal detectable concentration (MDC). The linearity was good in the range from 3.1-1930 pg/ml. Comparison with the IRMA used in our laboratory was analyzed by Passing-Bablok and Bland-Altman plots and revealed a proportional bias of +/-60% (slope: 1.58; IC: 1.53 to 1.63) and a systematic bias of -3.3 pg/ml which should not have any clinical consequence in the interpretation of the results. We established a reference range based on our hospital population. We evaluated 87 subjects without abnormality of calcium metabolism and with normal vitamin D supply. Three groups of patients were also analyzed: 57 patients with vitamin D insufficiency, 17 with renal failure and 15 with hypercalcemia (7 due to primary hyperparathyroidism and 8 due to another etiology). Reference ranges were from 10.2 to 93 pg/ml for CLIA measurement and from 6.4 to 68 pg/ml for IRMA measurement. PTH values measured by CLIA varied from 6 to 142 pg/ml in patients with vitamin D insufficiency. By CLIA measurement, intact PTH was between 26 and 892 pg/ml in renal failure, between 54 and 201 pg/ml in primary hyperparathyroidism and between 0 and 29 pg/ml in patients with another etiology of hypercalcemia. The results of PTH measurements in EDTA plasma did not differ significantly from those performed in serum (Passing Bablock).     

Section 1. Parathyroid: Intraoperative quick parathyroid hormone assay in the surgical management of hyperparathyroidism

Intraoperative quick parathyroid hormone (QPTH) assay is claimed to prevent failure during parathyroidectomy for hyperparathyroidism. The causes of operative failure have included multiglandular disease, ectopic parathyroid glands, supernumerary parathyroid glands, errors in frozen section evaluations, and missed diagnosis. A QPTH assay has been recognized as a useful method of determining whether hyperfunctioning tissues have been completely excised. However, an intraoperative QPTH assay may fail to detect the presence of double parathyroid adenomas. Use of this assay in conjunction with preoperative and intraoperative localization studies has led to the advocacy of more directed cervical procedures, such as limited, video-assisted, and endoscopic parathyroidectomy.     

Experiences with total parathyroidectomy and autotransplantation of intraoperatively selected parathyroid tissue in reactive renal hyperparathyroidism]

Surgery is indicated in cases of therapy-resistant reactive renal hyperparathyroidism with clinical symptoms and signs. The method of choice is total parathyroidectomy, with autotransplantation of parathyroid tissue into the forearm musculature. Twenty-two patients were parathyroidectomized. In 19 cases the intraoperative selection of tissue for autotransplantation was made by means of a stereoscopic magnifying glass. With one exception, only fragments of type 1a glands and type 1a-like areas obtained from type 2 glands were transplanted. In 18 of the 22 cases parathyroid hormone levels decreased from 1131 +/- 657 preoperatively to 87 +/- 53 pg/ml postoperatively. In 4 patients with postoperative values over 200 pg/ml a transplant-related recurrence of hyperparathyroidism or a remaining 5th gland in the cervical region was suspected. In all 22 patients serum calcium, as well as alkaline phosphatase levels returned to normal and the clinical signs of hyperparathyroidism disappeared.     

Serum amyloid A (SAA): a concise review of biology, assay methods and clinical usefulness.

Serum amyloid A (SAA) is a family of proteins encoded in a multigene complex. Acute phase isotypes SAA1 and SAA2 are synthesized in response to inflammatory cytokines. SAA and C-reactive protein (CRP) are now the most sensitive indicators for assessing inflammatory activity. In viral infection and kidney allograft rejection, SAA proved more useful than CRP. Development of convenient assay methods for SAA will facilitate its use in clinical laboratories.