Parathyroid Hormone Assay Research Articles

Comparison between intact and bioactive parathyroid hormone assays in patients with severe heart failure

ObjectivesParathyroid hormone (PTH) is a major systemic calcium-regulating hormone. Recent evidence has suggested that measurement of PTH might provide complementary information for the diagnosis and risk stratification of patients with heart failure (HF). The aim of our study was to compare intact and bioactive PTH assays in patients with severe heart failure. Design and methodsThe following measurements were carried out in blood samples from 73 patients with severe heart failure: bioactive PTH (1–84) assay, intact PTH assay, non-PTH (1–84), 25-hydroxyvitamin D, B-type natriuretic peptide (BNP), N-terminal proBNP (Nt-proBNP), Galectin-3 and high sensitive troponin T (hsTnT). ResultsThe correlation between intact and bioactive PTH assays was very high in HF patients. However, the bioactive PTH concentrations were lower than those measured with the intact assay. Intact and bioactive PTH as well as non-PTH (1–84) was significantly and positively correlated to BNP, Nt-proBNP, and galectin-3 but not to hsTnT. The strongest relationships with these cardiac biomarkers and with cardiovascular death were observed with the bioactive PTH assay. ConclusionsThe PTH concentrations obtained with intact and bioactive assays are not comparable in patients with severe HF. The specificity of PTH assays might therefore impact on the potential diagnosis and prognosis values of PTH testing in patients with heart failure.

Switching between parathormone (PTH) assays: the impact on the diagnosis of renal osteodystrophy

Clinical guidelines for decision-making in chronic kidney disease (CKD) consider parathormone (PTH) levels. The measured PTH values differ if novel full length PTH(1-84) assays are used instead of earlier intact iPTH assays. In this study we analyzed how the classification of CKD patients alters when iPTH assays are switched to PTH(1-84) assays. Plasma samples were collected prior to dialysis sessions from 110 consecutive CKD patients on maintenance hemodialysis. PTH levels were determined with iPTH assays (Elecsys, Architect and DiaSorin Liaison N-tact) and PTH(1-84) assays (Elecsys and Liaison). Using KDIGO guidelines patients were classified as being below, above and in the recommended target range (RTR) of PTH. The results of classification with different assays were evaluated and, a novel calculation method of RTR was implemented. The prevalence of patients with PTH in RTR is comparable with each assay, but the individual patients differed. PTH(1-84) Elecsys and Liaison assays classified more patients as being below RTR than iPTH Elecsys and Architect but not Liaison N-tact assay (27.3%, 22.7% vs. 41%, 31.8%, and 36.4%, respectively). In turn, PTH(1-84) Elecsys and Liaison assays identified less CKD patients with PTH above the RTR than iPTH except N-tact assays (6.4%, 10% vs. 16.3%, 19%, and 6.3%, respectively). Using our calculation method, our discrimination values for PTH(1-84) assays to achieve classification identical to that with iPTH Elecsys were lower than those recommended by the manufacturer. Current guidelines for the treatment of secondary hyperparathyroidism in CKD should consider the type of assays used for PTH measurement. Each laboratory should assess its own RTR for PTH tests to achieve comparable classification. The presented calculation is simple, it mimics an everyday situation, switching from one assay to another one, and provides useful RTR values for PTH tests.

Thyroid diseases cause mismatch between MIBI scan and neck ultrasound in the diagnosis of hyperfunctioning parathyroids: usefulness of FNA–PTH assay

To evaluate the efficacy of the main tools in the diagnostic localization of hyperfunctioning parathyroids (HP) in primary hyperparathyroidism (pHPT) with concomitant thyroid diseases. Forty-three patients with pHPT associated with nodular goiter (NG, n=32) and/or autoimmune thyroid diseases (AITDs, n=11) for a total of 63 neck lesions were considered. Sixteen patients displaying HP (16 lesions), unequivocally localized by sestaMIBI scintigraphy (MIBI) and neck ultrasound (US) (group I), were compared with 27 patients (47 neck lesions) displaying equivocal parathyroid localization (group II). In all cases, neck US, MIBI scan, cytology, and parathyroid hormone assay in fine-needle aspiration washout fluid (FNA-PTH) were performed. All patients finally underwent surgery. According to histological examination, high FNA-PTH values (>103 pg/ml) correctly identified all HP in both groups of patients (100% of sensitivity and specificity). Both MIBI and US correctly identified all HP only in group I patients; in contrast, four patterns of mismatch between these techniques were observed in group II patients, leading to low diagnostic performances of neck US (71.4% sensitivity and 78.9% specificity) and of MIBI scan (35.7% sensitivity and 42.1% specificity). The latter was due to both false-negative (mainly in AITD) and false-positive (mainly in NG) scan images. Coexistent thyroid diseases are responsible for mismatch between MIBI and US images resulting in equivocal HP localization. In these cases, FNA-PTH resulted in the most accurate tool to identify HP. However, although safe, it should be advised only to patients with uncertain HP localization.

Clinical evaluation of two novel biointact PTH(1–84) assays in hemodialysis patients

ObjectivesIn chronic kidney disease–mineral and bone disorder (CKD-MBD), most treatment decisions are guided by parathyroid hormone (PTH) levels. Here, we aimed at assessing the technical and clinical performance of two novel automated biointact PTH(1–84) assays, from Roche Diagnostics (Ro) and DiaSorin (DS), in hemodialysis patients. Design and methodsWe recorded demographics, dialysis treatment characteristics, pharmacotherapy for CKD-MBD and laboratory work-up. Statistical methods included Passing–Bablok, and multiple linear regression. Results121 patients, dialyzing on average for 3.5years (range: 0.1–22.5), with serum phosphate 1.9±0.6mmol/L (mean±SD), participated in the study. Median serum concentration for intact PTH was 223ng/L (range: 5–2844), and for biointact PTH(1–84) was 136ng/L (Ro; range: 1–1644), respectively 138ng/L (DS; range: 4-1580). Both biointact assays were significantly correlated (r=0.98; Ro=0.87×DS+19.60). Bland–Altmann plots revealed an average bias ±2 SD of 10±27ng/L below 200ng/L, and −32±157ng/L above 200ng/L (Ro minus DS). The variably adjusted association between PTH and serum phosphate was very similar, regardless of the PTH assay, but this was not the case for PTH-derived measures (ratios biointact/intact; differences intact minus biointact). (Log)PTH concentrations as well as serum phosphate were significantly associated with serum creatinine, but only in patients with >0mL urine per day. ConclusionsResults from Roche and DiaSorin biointact PTH(1–84) assays were well correlated, but showed increased deviations at higher concentrations. Biointact PTH(1–84) levels are roughly two third of intact PTH. The association between PTH and serum creatinine may depend on residual renal clearance of PTH and/or serum phosphate.

Measuring Parathyroid Hormone (PTH) in Patients with Oxidative Stress – Do We Need a Fourth Generation Parathyroid Hormone Assay?

Oxidation of PTH at methionine residues results in loss of biological activity. PTH may be oxidized in patients with renal disease. The aim of this study was to develop an assay considering oxidation of PTH. Oxidized hPTH was analyzed by high resolution nano-liquid chromatography coupled to ESI-FTT tandem mass spectrometry (nanoLC-ESI-FT-MS/MS) directly and after proteolytic cleavage. The oxidized hPTH(1–84) sample shows TIC-peaks at 18–20 min and several mass peaks due to mass shifts caused by oxidations. No significant signal for oxidized hPTH(1–84) species after removal of oxidized PTH molecules by a specific column with monoclonal antibodies (MAB) raised against the oxidized hPTH was detectable. By using this column in samples from 18 patients on dialysis we could demonstrate that measured PTH concentrations were substantially lower when considering oxidized forms of PTH. The relationship between PTH concentrations determined directly and those concentrations measured after removal of the oxidized PTH forms varies substantially. In some patients only 7% of traditionally measured PTH was free of oxidation, whereas in other patients 34% of the traditionally measured PTH was real intact PTH. In conclusion, a huge but not constant proportion of PTH molecules are oxidized in patients requiring dialysis. Since oxidized PTH is biologically inactive, the currently used methods to detect PTH in daily clinical practice may not adequately reflect PTH-related bone and cardiovascular abnormalities in patients on dialysis.

Diagnosis and management of parathyroid cancer

Parathyroid cancer is rare, but often fatal, as preoperative identification of malignancy against the backdrop of benign parathyroid disease is challenging. Advanced genetic, laboratory and imaging techniques can help to identify parathyroid cancer. In patients with clinically suspected parathyroid cancer, malignancy of any individual lesion is established by three criteria: demonstration of metastasis, specific ultrasonographic features, and a ratio >1 for the results of third-generation:second-generation parathyroid hormone assays. Positive findings for all three criteria dictate an oncological surgical approach, as appropriate radical surgery can achieve a cure. Mutation screening pinpoints associated conditions and asymptomatic carriers. Molecular profiling of tumour cells can identify high-risk features, such as differential expression of specific micro-RNAs and proteins, and germ line mutations in CDC73, but is unsuitable for preoperative assessment owing to the potential risks associated with biopsy. A validated, histopathology-based prognostic classification can identify patients in need of close follow-up and adjuvant therapy, and should prove valuable to stratify clinical trial cohorts: low-risk patients rarely die from parathyroid cancer, even on long-term follow-up, whereas 5-year mortality in high-risk patients is around 50%. This insight has improved the approach to parathyroid cancer by enabling risk-adapted surgery and follow-up.

Intraoperative parathyroid hormone assay during surgery for secondary hyperparathyroidism: is it time to give up the chase at the hormone?

In the early 1990s, when George Irvin reported his firstresults about the use of a quick intraoperative parathyroidhormone assay (ioPTHa) during surgery for primaryhyperparathyroidism (PHPT), this innovative instrumentappeared to be an extremely promising way to providesurgeons with reliable guidance while performing a para-thyroidectomy for PHPT [1]. In fact, the method had anacceptable certainty of confirming in most patients that allof the hyperfunctioning parathyroid tissue in the neck hadbeen removed, to the extent of defining it as a ‘‘biochem-ical frozen section.’’ Some of the limits of the techniquebecame evident quite soon, because a limited but signifi-cant number of false-positive and false-negative resultsseemed to be unavoidable in every series that was reported,adding some uncertainty about the real effectiveness of thetool [2].The main problem was how to determine the cutoff forthe PTH drop rate and the timing of the blood sample to betested. The choice of these two data can heavily conditionthe balance between a false-positive and a false-negativeresult [3]. These limits can influence even more the out-comes in patients with secondary HPT (SHPT) and tertiaryHPT, where the cutoff seems to be more difficult todetermine, for several reasons [4–6].Correctly, Conzo et al. [7] quoted several proposedcutoff values in their report as a percentage of the initialvalue or as an absolute value. Also, the timing variedgreatly from series to series. The choice by these authors tochoose a 20-min cutoff seems reasonable. Even though thehalf-life of this hormone is limited to very few minutes, itsvalues at the beginning of the operation are much higherthan in PHPT, and because of the manipulation, whichinvolves all of the glands, last much longer. Thus, con-sidering a time consistently longer than 10 min shouldguarantee better results. For the same reason, it is moreimportant to establish a percentage of the PTH drop withrespect to the initial value rather than its absolute value. Infact, if all the parathyroid tissue were removed, PTHshould be, presumably, 0; but this never happens.Nevertheless, a really ‘‘total’’ parathyroidectomy ismandatory, and by then, the use of ioPTHa could signifi-cantly modify the surgical strategy. It is well known,indeed, that removal of four enlarged parathyroid glands isnot sufficient to consider the operation successful: a fifthand even a sixth gland can be present in these patients insignificantly higher percentages than in patients affected byPHPT [4], thus inducing the surgeon to continue the neckexploration. In these patients, an ablation of the upperhorns of the thymus on both sides would be highlyadvisable.However, even if the expected drop does not occur after20 min, this does not necessarily mean that cure has notbeen achieved, because the PTH level might decreasemuch later than 20 min after surgery. Because a supernu-merary gland might be in the mediastinum, an extensiveand time-consuming neck exploration is sometimesunreasonable. For similar reasons, most surgeons do notadvocate the use of sophisticated and costly preoperativeimaging studies, and in any event, these cannot substitutefor the experience of a surgeon with a high volume ofparathyroidectomies [8]. Despite these limits, the use ofioPTHa might help an experienced surgeon in tailoring hisor her operative strategy.The possible prognostic value of ioPTHa to predict apossible hypoparathyroidism after surgery, which comes

Surgical Approach and Outcomes in Patients with Lithium-Associated Hyperparathyroidism

Patients receiving lithium therapy are at elevated risk of developing hyperparathyroidism. In lithium-associated hyperparathyroidism (LAH), the incidence of multiglandular disease (MGD) is unclear, and the need for routine bilateral cervical exploration remains controversial. Therefore, in LAH patients, surgical approaches, pathologic findings, cure rates, and factors associated with persistent or recurrent disease were investigated. Retrospective analysis of 27 patients with LAH undergoing parathyroidectomy with the intraoperative parathyroid hormone (PTH) assay. The median postoperative follow-up was 7 months; 17 patients had >6 months follow-up. Cervical exploration was unilateral in 9, bilateral in 18 (3 were converted from unilateral). Sixteen patients (62%) had MGD, 12 with four-gland hyperplasia and 4 with double adenomas. Ten patients (38%) had a single adenoma. Twenty-five (93%) of 27 patients had initially successful surgery. Of the 17 patients with >6 months follow-up, two had persistent disease and two experienced recurrent disease. All patients with a single adenoma remain free of disease. Three (75%) of four patients with persistent/recurrent disease had MGD and were receiving lithium at the time of surgery. Patients with persistent/recurrent disease were older (p = 0.01) and had experienced a longer duration of hypercalcemia (p = 0.04). LAH patients have a high incidence of MGD, and bilateral exploration is frequently necessary. With access to the intraoperative PTH assay, it is reasonable to initiate a unilateral approach because many patients will harbor single adenomas and can be reliably rendered normocalcemic. Patients with MGD remain at higher risk of persistent/recurrent disease.

MO‐G‐BRB‐02: Rosalyn S. Yalow, PhD: A Personal and Scientific Memoir

In 1950, Rosalyn S. Yalow, PhD, a medical physicist, was hired to develop The Radioisotope Service at the Bronx VA. She was joined by Sol Berson who had completed his residency in internal medicine. Their initial investigations together were in the application of radionuclides in blood volume determination and the kinetics of iodine metabolism in health and thyroid disease. They were quickly recognized as outstanding clinical investigators. They turned their attention to understanding insulin physiology by labeling insulin and studying the plasma kinetics in a variety of subjects. Radiolabeled insulin was cleared from the blood more slowly in subjects who had received insulin injections. They concluded that the slower clearance was due to insulin antibodies and they quantified the binding phenomenon. They recognized that the quantitative competition of a radiolabeled antigen and an unlabeled antigen molecule for a limited number of binding sites on an antibody provided a basis for the quantitation of an unknown amount of a similar molecule in a sample of plasma or other biological fluid. In 1960, a manuscript entitled “Immunoassay of Endogenous Plasma Insulin in Man” appeared. Using the same principal but identifying unique characteristics of other peptide hormones, the Yalow‐Berson team went on to develop assays for Human Growth Hormone, ACTH, Parathyroid Hormone, Gastrin, Glucagon and other materials of biologic interest. Radioimmunoassay could quantify these substances in less than a drop of plasma. In recognition of these contributions, the Nobel Prize in Medicine and Physiology was awarded in 1977 to Rosalyn S. Yalow, PhD. It is not possible in the limited space and time available to review the impact that the development of radioimmunoassay has had on virtually every field of medical science but the reader is encouraged to review some of the early publications on this subject and to share the excitement and awe that they created at the time of publication and continue to do so for this observer whenever there is an opportunity to review this material. This lecture will provide an overview of the life and principal scientific contributions of a Medical Physicist, Rosalyn S. Yalow, PhD who was awarded the Nobel Prize in Medicine in 1977 in recognition of the development of radioimmunoassay.Learning Objectives:1. Knowledge of key events in the scientific development of Rosalyn S. Yalow, MD.2. Understand the principles of radioimmunoassay.3. Understand the impact of radioimmunoassay methodology on medical science.

Diagnosis of Alterations of Serum Calcium Metabolism

Calcium is essential to homeostasis and functioning of multiple organ systems. Its circulating concentration is maintained within a very tight physiologic range: 2.25 and 2.50 mmol/L. Under physiological conditions, the ionized calcium concentration is regulated by the parathyroid hormone (PTH), and 1,25(OH)(2) vitamin D through interactions on target organs such as kidney, bone and intestine. In mild, moderate, and severe hypercalcemia, laboratory findings are essential in assessing and monitoring disease course and therapy. The main tools are specific standard biochemical tests able to assess calcium balance and renal function, and some specific biochemical tests, such as PTH, 25(OH) vitamin D, and genetic sequencing, used to clarify the cause of hypercalcemia and, subsequently, to determine appropriate therapy. Once hypercalcemia is confirmed by ionized calcium measurement, the intact PTH assay plays a crucial role to differentiate PTH-mediated from non-PTH-mediated hypercalcemia. Mild hypercalcemia is also present in up to 10-20% of patients treated with lithium for bipolar disorders, in 7-8% of those treated with thiazide diuretics, and in patients with prolonged immobilization, while very high (>3.5 mmol/L) serum calcium levels, together with low PTH, and a rapid increase of hypercalcemia, usually suggest a malignancy-associated hypercalcemic syndrome. The measurement of PTH-related protein, a tumor product that mimics certain action of PTH, is useful only in selected cases. The role of biochemical markers of bone turnover for predicting metastatic bone disease, and monitoring bone metabolic changes, and their usefulness as a predictive mean of the likelihood of bone loss or fractures risk is still unclear.

Feasibility of Rapid Parathormone Assay for Enabling Minimally Invasive Parathyroid Excision

There is no doubt that the success of minimally invasive parathyroidectomy (MIP) has changed the whole treatment of patients with primary hyperparathyroidism, especially the approach towards traditional bilateral neck exploration. A single adenoma is the most common cause of primary hyperparathyroidism and its removal results in cure. Hence, it is worth the effort to localise and excise the single adenoma using modern technologies such as high-quality sestamibi scans and to confirm complete excision using rapid intra operative parathormone (IOPTH) assays. The objective of the study was to evaluate the feasibility of rapid IOPTH assay in successfully facilitating minimally invasive parathyroid excision. This research involved the retrospective study of seven patients, who underwent MIP at Sagar Hospital in Bengaluru, India, for parathyroid adenoma. All patients with evidence of unifocal disease on sestamibi scanning and cervical ultrasonography, underwent MIP via 2-3cm lateral incision. Blood samples for measurement of IOPTH were taken at the time of induction of anaesthesia and 10min after the adenoma excision. Reduction of parathormone (PTH) levels of more than 50% in the postexcision sample was taken as evidence for complete extirpation of parathyroid adenoma. A solitary adenoma was identified in all the seven patients. After MIP, IOPTH levels fell in six of the seven patients. Following the surgery, all the cases were followed up for a period of 1month. During this time, except for one patient, six patients remained asymptomatic and blood tests revealed normal serum calcium levels. A histopathological examination confirmed the diagnosis of parathyroid adenoma in six of the seven patients. After accurate preoperative localisation of the adenoma in patients with primary hyperparathyroidism, MIP with IOPTH measurement offers a safe and successful outcome.

Do We Overtreat Post‐Thyroidectomy Hypocalcemia?

Calcium and calcitriol supplements are standard for patients with post-thyroidectomy serum calcium <2.0 mmol/L; however, we wondered whether we overtreat post-thyroidectomy hypocalcemia with intraoperative parathyroid hormone (PTH). We examined quick-intraoperative intact PTH (QiPTH) assay results to find a suitable treatment for post-thyroidectomy hypocalcemia. We studied 197 bilateral thyroidectomy patients. Post-thyroidectomy hypocalcemia was defined as serum calcium <2.0 mmol/L. A QiPTH assay was done 15 min after the thyroidectomy (QiPTH(15)), and hypoparathyroidism was defined as PTH <15 ng/L. The QiPTH(15) assay was used to determine the effects of the thyroidectomy on postoperative PTH levels and serum calcium levels. The natural course and medical response of hypocalcemia was observed in patients with a QiPTH(15) ≥ 15 ng/L. None of the 187 patients with a QiPTH(15) ≥ 15 ng/L developed postoperative hypoparathyroidism. However, 79 patients developed transient hypocalcemia, and those with Graves' disease (47/94) had significantly (p < 0.05) higher hypocalcemia than those with non-Graves' thyroid disease (32/93). The serum calcium of these 79 patients declined to its lowest level within the first postoperative 18 h. Seven patients with serum calcium <1.75 mmol/L were successfully treated using a calcium supplement only, and the others recovered spontaneously without treatment. When post-thyroidectomy QiPTH(15) was ≥ 15 ng/L, postoperative hypoparathyroidism was excluded, but more than one-third of the patients developed post-thyroidectomy hypocalcemia. However, most of them recovered without treatment, and a few recovered after taking only a calcium supplement. We believe that using QiPTH(15) results as a guide will prevent overtreatment of post-thyroidectomy hypocalcemia.

Evaluation of the ‘putative’ role of intraoperative intact parathyroid hormone assay during parathyroidectomy for secondary hyperparathyroidism. A retrospective study on 35 consecutive patients

In the surgical treatment of secondary hyperparathyroidism (2HPT) of chronic kidney disease (CKD), a parathyroidectomy (PTx) of 4 glands can only be presumed as 'total', and indications for autoimplantation are complex. Intraoperative rapid parathyroid hormone assay could be useful to predict a radical resection. We evaluated iPTH levels 20 min and 24 h after a 4-gland PTx in 35 patients to determine the predictive value of intraoperative iPTH assay. We analysed retrospectively 35 patients affected by 2HPT of CKD, 13 undergoing total parathyroidectomy (TP) and 22 TP + autoimplantation (TPai), after removing 4 glands in 33 cases and 5 glands in 2. Intact PTH assays were acquired after 40 min before induction of anaesthesia, after removing both ipselateral glands, at 20 min after surgery and on postoperative day 1. 20 min after 4-gland PTx, a decrease of iPTH levels >80 % of the preoperative value was observed in 27 of 35 cases (77.1 %) and <80 % in 8 of 35 cases (22.8 %). In 6 of these 8 patients, iPTH levels were within the normal range 24 h after surgery. Although the intraoperative iPTH assays are of interest in the treatment of 2HPT, the predictive value of this method is not entirely satisfactory. In fact, a 4-gland PTx ensures euparathyroidism in most cases, even when intraoperative iPTH assays are not trustworthy; however, intraoperative iPTH assay, although not a perfect 'tool', is a proved aid for the surgeon in making his decision.

A Prospective Evaluation of Quick Intraoperative Parathyroid Hormone Assay at the Time of Skin Closure in Predicting Clinically Relevant Hypocalcemia after Thyroidectomy

BackgroundPost-thyroidectomy hypocalcemia is a major contributing factor in delayed hospital discharge and dissuading surgeons from ambulatory thyroidectomy. We prospectively evaluated the accuracy and reliability of quick parathyroid hormone level measurement at skin closure (PTH-SC) in predicting clinically relevant hypocalcemia (i.e., patients requiring calcium ± calcitriol supplements on hospital discharge).MethodsOf the 117 patients who underwent a total or completion total thyroidectomy and PTH-SC, 17 (14.5 %) had hypocalcemic symptoms or adjusted calcium <1.90 mmol/L requiring calcium and/or calcitriol supplements on discharge. Serum calcium was checked regularly in the perioperative period until stabilization and an additional quick PTH was checked on the following morning (PTH-D1). Univariate and multivariate analyses were performed to evaluate potential preoperative clinicopathologic factors and postoperative day 0 biochemical indicators. Youden’s index and the area under the ROC curve (AUC) were used to determine the best cutoff value and predictability of significant variables or criteria, respectively.ResultsIn the multivariate analysis, low preoperative adjusted calcium (p = 0.041) and low PTH-SC (p = 0.001) were the two independent variables associated with hypocalcemia. PTH-SC (≤1 or >1 pmol/L) had a higher specificity (95.0 %) and AUC (0.887) than serial calcium monitoring or PTH-D1 alone. Although 3/98 of patients with PTH-SC >1 pmol/L required calcium supplements on discharge, they required only the minimum amount to maintain normocalcemia.ConclusionPTH-SC is an accurate and reliable means of predicting clinically relevant hypocalcemia. It would be reasonable to discharge those with PTH-SC >1 pmol/L on the same operative day as the risk of life-threatening hypocalcemia would seem unlikely.

PTH Assays: Understanding What We Have and Forecasting What We Will Have

Parathyroid hormone (PTH) assays have evolved continuously for the last 50 years. Since the first radioimmunoassay was described in 1963, several assays based on immunological identification have been published (first generation assays). The routine assays used nowadays are immunometric “sandwich-type”. They are based on two different monoclonal antibodies, one amino-terminal and the other carboxyl terminal specific. These second generation assays are widely available and adapted to most of the automation platforms. The specificity of the amino terminal antibody defines if the immunometric assay measures only the bioactive PTH circulating form (including the first amino terminal amino acids) or the “intact” PTH, which includes, besides bioactive PTH, other “long” carboxyl-terminal forms, for example, 7–84-PTH. Assays for “intact” PTH are the most commonly available and the potential advantage of the bioactive PTH assays is still debatable. Next generation of assays will be based on different principles, mainly mass spectrometry in samples submitted to a prior purification and fragmentation steps. These assays will provide information about the whole spectra of PTH peptides in circulation, with a significant increase of the information regarding this biologically important peptide hormone.

A 10-Year Experience in Intraoperative Parathyroid Hormone Measurements for Primary Hyperparathyroidism: A Prospective Study of 91 Previous Unexplored Patients

Introduction. Primary hyperparathyroidism (PHP) is characteristically determined by high levels of calcium and high or inappropriate levels of parathyroid hormone (PTH). Technological advances have dramatically changed the surgical technique over the years once intraoperative parathyroid hormone (IOPTH) assay had allowed for focused approaches. Objective. To evaluate our 10-year experience in employing a rapid intraoperative PTH assay for PHP. Methods. A prospective cohort of 91 PHP-operated patients in a tertiary institution in São Paulo, Brazil, from June 2000 to April 2011. Results. We had 85 (93.4%) successful parathyroidectomies, 6 (6.6%) failed parathyroidectomies in 91 previous unexplored patients, and 5 (100%) successful remedial surgeries. The IOPTH was true-positive in 88.5%, true-negative in 7.3%, false-positive in 2.1%, and false-negative in 2.1% of the procedures. IOPTH was able to obviate additional exploration or to ask for additional exploration in 92 (95.8%) procedures. Conclusion. The IOPTH revealed to be an important technological adjunct in the current parathyroid surgery for PHP.

Lanthanum carbonate: a postmarketing observational study of efficacy and safety

Hyperphosphatemia is associated with morbidity and mortality in hemodialysis patients. The use of calcium chelators is restricted by the risk of hypercalcemia and vascular calcifications. Sevelamer, a non-calcium chelator, is associated with risks of metabolic acidosis and poor compliance. Lanthanum carbonate is a non-calcium chelator not associated with these issues. However, accumulation in liver and bone has been a reason for concern. Adult patients (n=112) from 9 hemodialysis centers, with serum phosphorus >5.5 mg/dL and on hemodialysis for >1 year, were selected to switch to lanthanum carbonate (mean dosage: 2,189 ± 491 mg/day); 103 completed the study. Laboratory assays for serum phosphate, calcium, parathyroid hormone, alkaline phosphatase, gamma-glutamyl transpeptidase (gammaGT), aspartate transaminase, alanine transaminase and plasma bicarbonate were performed monthly. Seven patients underwent a bone biopsy for evaluation of lanthanum bone content. Switching to lanthanum carbonate led to a reduction in mean serum phosphate levels (-18.2%; p<0.001) and calcium × phosphorus product (-17.6%; p<0.0001). There were no important changes in other variables, except for an increase in transaminases in 2 patients with preexisting liver disease, who discontinued therapy. An increase in plasma bicarbonate concentration was observed (p=0.001). Although some lanthanum was detected in bone, its distribution did not follow the mineralization front. Lanthanum carbonate is effective and well tolerated, provided that recipients do not have preexisting liver disease. After 8 months of treatment, lanthanum was not detected in the mineralization front of bone. In hemodialysis patients, lanthanum carbonate does not seem to be involved in metabolic bone disease.

Serum Intact Parathyroid Hormone Level After Total Thyroidectomy or Total Thyroidectomy Plus Lymph Node Dissection for Thyroid Nodules: Report From 296 Surgical Cases

BackgroundTransient hypocalcemia is one of the postoperative complications of thyroidectomy for thyroid nodules, and intraoperative and postoperative intact parathyroid hormone (iPTH) assays are used to predict postoperative hypocalcemia.ObjectivesThe current study was conducted to evaluate a single serum iPTH measurement on postoperative day 1 (POD 1) as a means to predict hypocalcemia occurrence after total thyroidectomy (TT).Patients and MethodsThe subjects consisted of 36 patients who underwent TT and 260 patients who underwent TT plus lymph node (LN) dissection for thyroid nodules treatment. The TT performance procedure to prevent postoperative hypoparathyroidism combines parathyroid gland preservation in situ with autotransplantation of resected or devascularized parathyroid glands. The patients’ serum iPTH level was measured on POD 1, and their serum calcium level was measured on POD 1 and on POD 3 while they were still inpatients. The serum iPTH level was subequently measured at each outpatient clinic visit until it recovered to the normal range.ResultsHypoparathyroidism after TT and TT plus LN dissection was ultimately diagnosed in a total of 229 patients, and in 69 of them hypocalcemia was diagnosed on POD 1. All of the 69 patients diagnosed with hypocalcemia received calcium and vitamin D supplementation therapy. The serum iPTH level of 67 of 229 patients was within normal range on POD 1, and four of them developed hypocalcemia on POD 1. Permanent hypoparathyroidism developed in 37 of 296 patients after undergoing TT or TT plus LN dissection for thyroid nodules in the hospital.ConclusionsA single serum iPTH measurement on POD 1 is useful to determine whether or not to start calcium and vitamin D supplementation in order to maintain normocalcemia after surgery.

Imaging techniques in parathyroid surgery for primary hyperparathyroidism

As more patients present with the incidental diagnosis of primary hyperparathyroidism due to biochemical screening, treatment guidelines have been developed for the treatment of hyperparathyroidism. Management of primary hyperparathyroidism has evolved in recent years, with considerable interest in minimally invasive approaches. Successful localization of the diseased gland(s) by nuclear imaging and anatomical studies, along with rapid intraoperative parathyroid hormone assay, has allowed for focused and minimally invasive surgical approaches. Patients in whom the localization studies have identified single-gland adenoma or unilateral disease are candidates for such focused approaches instead of the traditional approach of bilateral exploration. These imaging techniques have also been critical in the successful management of patients with persistent or recurrent disease.

Intraoperative parathyroid hormone as an indicator for parathyroid gland preservation in thyroid surgery

Intra-operative parathyroid hormone (PTH) levels have successfully been used to assess surgical ablation of parathyroid adenomas, the use of this same test to predict preservation of viable gland has not been widely used. to test the sensitivity and specificity of intraoperative rapid PTH assay test in predicting permanent postoperative hypoparathyroidism, and applicability to guide the search for inadvertently removed parathyroid glands for possible auto transplantation. 52 patients undergoing total thyroidectomy for non-malignant thyroid diseases were included. Intraoperative rapid PTH assay test was performed. If levels were reduced, or less than 3 parathyroid glands were detected, removed thyroid gland was examined for unintentionally removed parathyroid tissue for possible auto transplantation. There was a strong correlation between intraoperative rapid PTH assays and those taken 24 hours after surgery, 16 out of 52 patients had reduction of the PTH intraoperatively to levels below 25 pg/ml, of them, 11 patients (who had values between 15-24 pg/ml) recovered to normal PTH levels within 4 weeks, while the 5 patients with intraoperative PTH levels below 15 pg/ml failed to regain normal PTH levels up to 12 weeks postoperatively, even in those patients where parathyroid tissue was auto transplantated. The 4 patients who had parathyroid tissue reimplanted intraoperatively restored some of their parathyroid function as indicated by relative rise of their PTH levels, but did not reach even the low normal levels. (ROC) curve for prediction of early hypoparathyroidism using intraoperative rapid PTH assay was statistically highly significant with optimal cutoff value for predicting early hypocalcaemia level <27 pg/ml, (sensitivity 100%, specificity 68.2%). (ROC) curves for predicting permanent hypoparathyroidism using intraoperative rapid PTH assay or standard PTH assay taken 24 hours after surgery were statistically significant with optimal cutoff value PTH level <12 pg/ml on the intraoperative PTH curve or <15 pg/ml on the postoperative PTH curve (sensitivity 100%, specificity 100%). Intraoperative PTH assay may allow intraoperative monitoring of parathyroid function, predicting postoperative outcomes, may identify patients at risk of developing postoperative hypoparathyroidism, guiding surgeons to re-examine removed specimens for inadvertently removed parathyroid tissue with possible auto transplantation, or more practically a guide to early replacement therapy to prevent hypocalcaemia, leading to safe and early hospital discharge. Limitations in our study to be reconsidered in further studies, are relative small sample size, inability for randomisation, and the variable values reported for the cut off value of PTH causing hypocalcaemic symptoms needing intervention.