PTH Assay Research Articles

Evolution of Endocrine Surgery in India

Evolution of Endocrine Surgery in India

Intraoperative parathyroid hormone monitoring to determine long‐term success of total parathyroidectomy for secondary hyperparathyroidism

Use of intraoperative parathyroid hormone (ioPTH) monitoring during total parathyroidectomy for secondary hyperparathyroidism is common, although its ability to predict long-term normoparathyroid state is not known. Prospective evaluation of 57 consecutive patients undergoing total parathyroidectomy for renal hyperparathyroidism with ioPTH monitoring and follow-up PTH assays were used to categorize the patients into 3 groups: success, adequate biochemical control, and failure. There was no statistically significant difference in percentage reduction of ioPTH between the 3 groups (p = .07), although there was a moderate negative correlation between percentage reduction of ioPTH and percentage reduction of PTH at follow-up (R = 0.57). When used under current guidelines, ioPTH monitoring is of no use in predicting long-term cure for these patients because it does not predict success. Patients that undergo total parathyroidectomy are required to have long-term calcium and PTH assay follow-up because normoparathyroidism cannot be assumed. Using the regression equation calculated, success may be predicted for future patients.

Comparison of three different immunoassay methods for the evaluation of intact parathyroid hormone levels in hemodialysis patients

Background. Intact parathyroid hormone (iPTH) assays react with the non-(1-84) molecular form of PTH. This form behaves as a carboxy-terminal fragment and accumulates during renal failure. We wanted to examine the variation of iPTH levels between the more commonly used different immunoassay methods in hemodialysis patients. Methods. Our study was designed to compare three commercial second-generation immunoassays based on electrochemiluminescent immunoassay (ECLIA), enzyme immunoassay (EIA) and immunoradiometric assay (IRMA) for intact PTH. The serum samples from 88 patients were collected and the iPTH concentrations measured. Results. The median iPTH (IRMA) concentration (99 pg/mL) was lower than both median iPTH (ECLIA) concentration (290.5 pg/ml; p < 0.001) and iPTH (EIA) concentration (369 pg/mL; p < 0.001). The Bland-Altman graphs, which are plots of the percentage differences between the two methods against their mean, suggested that the IRMA methods are not in agreement with the other methods. Conclusion. It would be useful to reduce the variability among the methods with the use of a more standardized calibrator and of the same specific antibodies that only recognize the active PTH molecule.

Hyperparathyroidism, an emerging disease

A retrospective study based on 35 years of personal experience was done. Up to today 2,175 patients were operated, 1,318 for primary hyperparathyroidism (HPT) and 857 for secondary and tertiary HPT. Considering recent years (1999 to July 2010), 918 patients were operated for primary HPT. Preoperatively all the patients performed a cervical ultrasound and/or a sestamibi scan. Open mininvasive procedure was preferred: it is an easily reproducible and costless technique. Using magnifying glasses up to 2.5, an excellent three-dimensional vision was obtained. The operating time is short and if there are any doubts it is possible to extend the exploration to the other side of the neck. Immediate and long-term results were excellent, with a cure rate greater than 99%. Complications in the treatment of a single adenoma are around 0.3%. Patients can be discharged 24-48 h after the operation. Regarding reoperations, a correct diagnostic and therapeutic approach is essential. CT, MRI and SPECT must correlate with the information given by ultrasound and scintigraphy. The intraoperative PTH assay (io-PTH) is required and the approach should be limited to the area where the missed gland probably is. The functionality of the autotransplantation (AT) performed immediately was good. The functionality of the cryopreserved tissue is better for the HPT I in comparison with HPT II. Considering HPT I or HPT II the use of io-PTH is helpful. MIBI scanning is helpful but not essential, except in reoperations. Surgeon experience is another very important factor for good results.

Changing Intraoperative Parathyroid Hormone Collection Sites from Peripheral to Central Does Not Affect Predictive Accuracy during Minimally Invasive Parathyroidectomy

Intraoperative parathyroid hormone (ioPTH) monitoring (IPM) is vital to minimally invasive parathyroidectomy. Techniques vary in assay sampling, potentially affecting predictive accuracy of operative success. Initial guidelines were established using peripheral sites, but central sites may be preferred or necessary when peripheral access is not feasible. We hypothesize that changing collection sites from preexcision peripheral sites to postexcision central sites would not affect IPM accuracy. Analysis of 64 consecutive patients who underwent parathyroidectomy for primary hyperparathyroidism was undertaken. PTH assays were collected simultaneously from a peripheral vein (PV) and central vein (CV) preexcision and at a 10-min interval after initial parathyroid excision. IPM success was defined as PTH decrease ≥50% 10min after initial excision. Predictive accuracy was determined by the need to resect another abnormal gland and biochemical normalization in the postoperative clinic. Receiver operating characteristic (ROC) method with area under the curve (AUC) compared diagnostic accuracy of different assay approaches. Centrally, a statistically higher mean pre- and postexcision ioPTH of 391pg/ml and 58pg/ml was found compared with peripheral means of 156pg/ml and 49pg/ml, respectively (p<0.001). The AUC when changing from a PV preexcision to a CV postexcision ioPTH was 0.89, comparable to AUC for peripheral or central assay collections alone (AUC=0.83 and 0.85, respectively). This study suggests that altering collection sites does not alter assay validity. In cases where peripheral sampling is compromised, changing from a peripheral to central sites will not likely alter the predictive accuracy of IPM significantly.

PTH Assay After Thyroidectomy: A US Surgeon Survey Analysis

PTH Assay After Thyroidectomy: A US Surgeon Survey Analysis

Secondary and Tertiary Hyperparathyroidism: The Utility of ioPTH Monitoring

The aim of the present study was to examine the utility of intraoperative parathyroid hormone (ioPTH) monitoring in patients with secondary (2) and tertiary (3) hyperparathyroidism (HPT). We identified 105 patients with 2HPT (n = 33) and 3HPT (n = 72) who underwent ioPTH monitoring during parathyroidectomy. Data are reported as mean +/- SEM. The 2HPT patients underwent 17 subtotal, 10 total, and 6 re-exploratory parathyroidectomies, whereas the 3HPT patients underwent 54 subtotal, 15 limited, and 3 re-exploratory parathyroidectomies. The percent decrease from the baseline ioPTH level at 5, 10, and 15 min after parathyroid resection, respectively, were 72% +/- 3%, 76% +/- 3%, and 76% +/- 3% in patients with 2HPT, and 52% +/- 6%, 60% +/- 4%, and 69% +/- 4% in patients with 3HPT. IoPTH levels failed to drop >50% from baseline in 5 patients (2HPT: n = 2, 3HPT: n = 3) who were normocalcemic at last follow-up. IoPTH did not alter the surgical approach in any 2HPT patients, but did alter management in 25% of 3HPT patients (15 limited resections and 3 supernumerary glands). Normocalcemia was achieved in 97% of 2HPT patients and 99% of 3HPT patients; 2 patients developed recurrent disease. Intraoperative PTH levels fell by >50% in nearly 95% of patients with 2HPT and 3HPT, and the PTH level reliably predicted postoperative cure. Although the use of ioPTH did not alter surgical management in any patient with 2HPT, this rapid PTH assay affected the surgical care of a quarter of the patients with 3HPT, and it may prove to be a useful adjunct in this group of patients.

The administration of an active vitamin D3 analogue reduced the serum concentrations of 1-84 and truncated parathyroid hormone in pseudohypoparathyroidism type Ib patients

Serum calcium is one of major regulators of PTH amino-terminal (N-terminal) truncation and secretion of full-length (1-84)PTH from parathyroid glands. However, the effect of active vitamin D(3) on PTH truncations remains controversial. To determine whether active vitamin D(3) accelerates the truncation of PTH, the vitamin D(3) analogue alfacalcidol was administered to patients with pseudohypoparathyroidism type Ib (PHP Ib). Both the (1-84)PTH molecule and N-terminally truncated fragments such as (7-84)PTH can be measured by commercially available two-site total PTH (T-PTH) assays. The development of whole PTH (W-PTH) assays specific for full-length (1-84)PTH has enabled us to distinguish between N-terminally truncated PTH and full-length (1-84)PTH. W-PTH/T-PTH ratios were calculated and used as an index of PTH N-terminal truncations. Both serum W-PTH and T-PTH levels were elevated in untreated PHP Ib patients. The administration of alfacalcidol reduced both the W-PTH and T-PTH levels; however, the W-PTH/T-PTH ratios were stable. Serum calcium levels were significantly and negatively correlated with both the W-PTH and T-PTH levels, but not with the W-PTH/T-PTH ratios. Thus, the administration of an active vitamin D(3) analogue did not seem to have a major effect on the rate of PTH N-terminal truncation, even though it did reduce the secretion of both full-length and truncated PTH. Possibly, active vitamin D(3) attenuates the effect of elevated calcium on PTH N-terminal truncation in PHP Ib patients.

Intraoperative PTH Assay during Minimally Invasive Parathyroidectomy May Be Helpful in the Detection of Double Adenomas and May Minimise the Risk of Recurrent Surgery

Background. Minimally invasive parathyroidectomy (MIP) is increasingly replacing the traditional bilateral neck exploration in the treatment of primary hyperparathyroidism (PHP). Intraoperative PTH (IOPTH) measurement has recently been introduced as a useful adjunct in confirming successful excision of abnormal parathyroid gland. Aims. We evaluate the safety, efficacy, and clinical usefulness of IOPTH measurement during MIP in a district general hospital. Methods. Retrospective review of eleven consecutive patients with PHP who underwent MIP with IOPTH, following preoperative assessment with ultrasound and sestamibi scans. Results. All patients had successful removal of the abnormal parathyroid gland. The concordance rate between ultrasound and sestamibi scan in localising the parathyroid adenoma was 82%. IOPTH measurement confirmed the removal of adenoma in all cases and, in one case, led to identification of a second adenoma, not localised preoperatively. The median hospital stay was 2 days (range 1–7 days). All patients remained normocalcaemic after a median of 6 months (range 1–10 months). Conclusions. Minimally invasive parathyroidectomy is a feasible, safe, and effective method for treatment of PHP. The use of IOPTH monitoring potentially offers increased sensitivity in detecting multiglandular disease, can minimise the need and risk associated with recurrent operations, and may facilitate cost-effective minimally invasive surgery.

Minimally Invasive Parathyroidectomy: Benefits and Requirements of Localization, Diagnosis, and Intraoperative PTH Monitoring. Long‐Term Results

Surgery is the only curative treatment for primary hyperparathyroidism. Initial parathyroidectomy procedures fail due to ectopic gland location and unappreciated multigland disease. An evidence-based literature review was performed,which surveyed all human studies in PubMed, searching for parathyroidectomy in humans between 1990 and 2009. Between 10 and 30% of patients have multigland disease caused by double adenomas or hyperplasia. Use of preoperative imaging studies and intraoperative PTH monitoring helps parathyroid surgeons overcome these obstacles. Sestamibi nuclear scan and neck ultrasound identify 70-80% of abnormal glands in patients with single adenomas. The sensitivity of ultrasound or sestamibi to identify all abnormal glands in patients with multigland disease is extremely low. Intraoperative PTH monitoring should be utilized in all patients who undergo neck exploration for primary hyperparathyroidism to reduce failures due to multigland disease. Blood samples should be drawn from peripheral veins only and a postresection level 10-15 min after gland removal should have a >50%decrease from baseline preoperative levels, and also must go to the normal range for the PTH assay being used. Contemporary prospective studies (level of evidence III/IV) show that by combining preoperative imaging and IOPTH it is possible to maximize performance of successful outpatient minimally invasive parathyroidectomy.

PROGRESS IN UREMIC TOXIN RESEARCH: Parathyroid Hormone, A Uremic Toxin

Despite the innovations in the treatment of secondary hyperparathyroidism, there are uremic patients with marked elevation in PTH levels. Uremic toxicity is in part attributable to the excess of circulating PTH. It has been known for many years that PTH may induce changes in cell calcium, a key intracellular signal required for normal cell function. The effect of PTH in dialysis patients is not limited to bone; the diversity of biologic effects of PTH is summarized in this review. In addition, the present review addresses other issues: (i) the presence of different circulating PTH fragments in uremic patients, (ii) the PTH assays currently utilized to measure circulating PTH, and (iii) the fact that some of the PTH effects seen in uremic patients may be due to the interaction of C-terminal PTH fragment with putative C-terminal PTH receptors.

Reprint of “Critical issues of PTH assays in CKD” [Bone 44 (2009) 666–670

Reprint of “Critical issues of PTH assays in CKD” [Bone 44 (2009) 666–670

Parathyroid carcinoma. Mini-series of patients successfully treated with minimally invasive surgery using intra-operative PTH assays, and literature review.

Parathyroid cancer is a rare cause of primary hyperparathyroidism, with a surgeon anecdotally expected to see a single case in his/her entire career. In our unit, however, we have treated three patients recently. The accepted optimal treatment of parathyroid cancer is radical resection at the initial surgery, but a low index of suspicion means that most parathyroid cancers are not identified pre- or intra-operatively. This results in the majority of patients having inadequate surgery. All three patients were treated by minimally invasive surgery, with radical en bloc resection based on intra-operative suspicion of malignancy. Pre-operative imaging guides the neck exploration, and intra-operative PTH assays confirm excision of the source of excess PTH. All patients have remained well with no recurrence to date. We review the literature on parathyroid cancer, and suggest features that point to a parathyroid tumour being malignant.

Calcitonin assay in wash-out fluid after fine-needle aspiration biopsy in patients with a thyroid nodule and border-line value of the hormone

Assaying calcitonin (CT) in the wash-out fluid from fine-needle aspiration biopsies (CT-FNAB) could be useful in the diagnosis of medullary thyroid carcinoma (MTC). The aim of this study was to correlate serum CT with cytology and CT-FNAB. Twenty-seven subjects (age range 27-75 yr) were studied. FNAB was performed in a thyroid nodule (no.=16) or lymph-node (no.=1 previously operated on for MTC) or in the prevalent nodule of multinodular goiters (no.=10). CT-FNAB values obtained in 37 subjects with normal serum CT (<10 ng/l) who underwent FNAB for thyroid nodules served as a negative control. In these subjects, CTFNAB values were 8.2+/-6.4 ng/l (range 2-30 ng/l). In patients with a thyroid nodule under evaluation for MTC, serum CT and CT-FNAB values were 14.5+/-3.9 ng/l (range 10-24 ng/l) and 16.4+/-29.8 ng/l (range 2-144 ng/l), respectively. In 4 patients, CT-FNAB values were higher than the highest values found in our negative controls (30 ng/l), but cytology results were compatible with a benign thyroid lesion and pentagastrin testing was negative. In 3 cases with CT-FNAB <30 ng/l, cytology was indicative of an indeterminate or probably follicular malignant lesion and histology was negative for MTC. None of the other subjects in whom pentagastrin testing was conducted showed serum CT values >100 ng/l. Our data do not show any correlation between CT-FNAB and serum CT. In conclusion, borderline CT values in patients with thyroid nodules are not rare. Our experience suggests that CT-FNAB does not have the same importance as that reported in the literature for thyroglobulin and PTH assay in wash-out fluid after FNAB in malignant thyroid and hyperfunctioning parathyroid lesions.

False low parathyroid hormone values secondary to sample contamination with the tissue plasminogen activator

Fluctuating parathyroid hormone values (PTH) are common in patients undergoing haemodialysis. Widely varying PTH results in an 82-year-old haemodialysis (HD) patient could not be explained. When PTH in the same blood sample was no longer detectable 24 h after blood draw, it was hypothesized that contamination with the catheter lock solution containing tissue plasminogen activator (tPA, alteplase) caused degradation of PTH in vitro. Leftover samples from 21 patients on maintenance HD as well as control samples from healthy volunteers (n = 3) were incubated at 4 degrees C with small amounts of tPA (25 and 50 microL). In addition, pooled samples from HD patients with various PTH levels were incubated with 6.5, 12.5 and 25 microL of tPA and analysed with two different PTH assays with incubation times up to 48 h. A rapid decline of PTH values to 2.5-33.5% of the original baseline was observed after 24 h with a further decrease to <1-15% after 48 h. The two different assays gave very similar results when the samples were incubated with tPA. Minimal contamination of a blood sample with tPA results in degradation of PTH in a time-dependent manner. The tPA is therefore unique as a contaminant since its enzymatic activity means that even tiny amounts of contamination will lead to major errors in PTH results by digestion of the protein. This phenomenon was independent of the assay used. Strict attention to the technique when drawing a blood sample from a catheter is mandatory to prevent contamination and avoid spurious test results.

Chirurgie de l’hyperparathyroïdie primaire en 2008

In recent years, different minimally invasive techniques of parathyroidectomy have been described. The concept of these limited explorations is based on the fact that 85% of patients will have a single-gland disease. Minimally invasive techniques are targeted on one specific parathyroid gland and in most cases the exploration of other glands is not performed. These interventions are today possible for three main reasons: the available imaging techniques permit to localize the diseased gland, the use of rapid intraoperative PTH assay can confirm the successful extirpation, new instrumentation and miniaturized cameras have been adapted for this kind of surgery. Not all patients presenting with primary hyperparathyroidism are candidate for this surgery. Contraindications are mainly due to a large goiter, previous surgery in the parathyroid vicinity, suspicious multiglandular disease and equivocal preoperative localization studies. Currently 60% of patients with primary hyperparathyroidism can benefit of these techniques. Studies comparing conventional parathyroid surgery to minimally-invasive techniques have shown a diminution of postoperative pain and better cosmetic results with minimally-invasive techniques. If early results are similar to those obtained with conventional parathyroidectomies, it is still too soon to evaluate what will be the recurrence rate of these new techniques. One can expect that minimally invasive and conventional parathyroid surgery will probably turn out to be complementary in the near future.

Accuracy of PTH assay and corrected calcium in early prediction of hypoparathyroidism after thyroid surgery

To evaluate the accuracy of the intraoperative parathyroid hormone (ioPTH) and 6-hour PTH (6hPTH) assay in predicting transient hypoparathyroidism after thyroidectomy. A nonrandomized prospective study was conducted on patients undergoing thyroid surgery. Of 138 patients undergoing thyroid surgery, intraoperative PTH was measured 10 minutes after gland removal. Serum calcium, magnesium, inorganic phosphorus, albumin, and PTH levels were assayed 6 and 16 hours after surgery and daily until patient discharge. The development of postoperative hypocalcemia was associated with low ioPTH (P < 0.0001) and 6hPTH (P < 0.0001) values, and the decline of PTH from baseline (P < 0.0001). The cutoff for percentage decline of ioPTH and 6hPTH (55.7% and 379%, respectively) was more accurate than an absolute value. Accuracy, and positive and negative predictive values were 88 percent, 63 percent, and 100 percent for ioPTH and 75 percent, 46 percent, and 100 percent for 6hPTH, respectively. With the use of ioPTH decline in association with 16-hour corrected calcium, it is possible to distinguish early normocalcemic patients from hypocalcemic ones in most cases.

Spontaneous remission of severe hyperparathyroidism with normalization of the reversed whole PTH/intact PTH ratio in a haemodialysis patient

Secondary hyperparathyroidism is one of the most common and serious abnormalities in patients with chronic kidney disease. Despite recent progress in the treatment of hyperparathyroidism, advanced uraemic nodular hyperplasia, or rarely, sporadic primary adenoma accompanied by chronic renal failure is usually resistant to medical treatment and requires parathyroidectomy [1,2]. Spontaneous remission of hyperparathyroidism is a very rare complication, either primary or secondary, especially in patients on dialysis. The aetiology of spontaneous infarction has not been elucidated, but excessive tissue growth may well be one of the most clinically relevant factors, because a large parathyroid gland is susceptible to ischaemic insult [3]. For the management of hyperparathyroidism in chronic kidney disease, second-generation PTH assays, such as intact PTH assay, have been widely used [4]. However, these assays react not only with full-length PTH (1–84), but also with large C-terminal fragments, mostly PTH (7–84). The newly developed third-generation PTH assays, such as whole PTH assay, are more sensitive and specific when measuring bioactive PTH (1–84) [5]; therefore, PTH values obtained with second-generation assay are generally higher than those obtained with third-generation PTH assay [6]. Rare exceptions to this rule, however, have been reported in severe primary or secondary hyperparathyroidism and parathyroid carcinoma [7–10]. We present here a case of a haemodialysis patient with severe hyperparathyroidism, in whom abnormally higher whole PTH levels than intact PTH levels normalized after

Association of increased active PTH(1–84) fraction with decreased GFR and serum Ca in predialysis CRF patients: modulation by serum 25-OH-D

As the serum calcium and glomerular filtration rate decreased, the proportion of active PTH(1-84) molecules in PTH immunoreactivity increased in serum from predialysis uremic patients, particularly those with vitamin D insufficiency. The PTH(1-84) fraction was altered in predialysis patients with chronic renal failure (CRF). Serum PTH in predialysis CRF patients without any medication was measured by PTH(1-84)-specific whole PTH assay and intact PTH assay cross-reacting with N-truncated PTH. In CRF patients, the glomerular filtration rate (GFR) correlated positively with serum Ca and 1,25-dihydroxyvitamin D (1,25(OH)(2)D), and inversely with serum Pi, log intact PTH, and log whole PTH. In multiple regression analysis, including age, gender, body mass index, GFR, Ca, and Pi and 1,25(OH)(2)D as independent variables, serum Ca and GFR associated significantly with serum log whole PTH and intact PTH. Serum log whole PTH/intact PTH ratio, which increased as serum Ca and GFR decreased, retained a negative correlation in those with serum 25-hydroxyvitamin D levels below 20 ng/ml, but not in those above 20 ng/ml. The ratio also correlated positively with serum log tartrate-resistant acid-phosphatase-5b, log cross-linked N-telopeptide of type-I collagen, and log bone alkaline-phosphatase. As GFR declined with suppression of serum Ca, the proportion of active PTH molecules increased in predialysis CRF patients, particularly those with vitamin D insufficiency.

Accuracy of PTH assay and corrected calcium in early prediction of hypoparathyroidism after thyroid surgery

Accuracy of PTH assay and corrected calcium in early prediction of hypoparathyroidism after thyroid surgery