Concordance between radioimmunoassay and fixed cell-based assay in subjects without myasthenia gravis: optimizing the diagnostic approach.

BACKGROUND AND PURPOSE: Acetylcholine receptor antibody (AChR-Ab) detection is crucial in myasthenia gravis (MG) diagnosis and, currently, the radioimmunoassay (RIA) is the gold standard. However, RIA may detect AChR-Ab against nonpathogenic intracellular epitopes. In this study, we performed fixed cell-based assay (F-CBA) in RIA-AChR-Ab positive subjects without MG symptoms, to assess whether F-CBA could show a higher specificity compared to RIA in detecting pathogenic Abs. METHODS: We reviewed medical records of patients referred to our MG outpatient clinic because of RIA-AChR-Ab detection. MG diagnosis was based on clinical examination, electrophysiology and Ab detection. AChR-Abs were tested by RIA in the whole cohort. Serum samples from RIA-positive asymptomatic subjects were retested by F-CBA. RESULTS: Of 605 subjects who tested RIA-AChR-Ab positive, MG diagnosis was confirmed in 599. Six subjects were RIA-AChR-Ab positive although they had never had MG symptoms; in four of these subjects AChR-Abs were not detected by F-CBA, whereas the remaining two (both non-MG thymoma cases) were positive also by F-CBA. CONCLUSIONS: RIA false positivity for AChR-Ab is very rare. Previous literature has demonstrated that F-CBA has higher sensitivity than RIA for MG, especially in ocular cases. Our preliminary results show that, in rare instances, F-CBA may be more specific than RIA for MG diagnosis.

Comparison of Fixed and Live Cell-Based Assay for the Detection of AChR and MuSK Antibodies in Myasthenia Gravis.

BACKGROUND AND OBJECTIVES: Live cell-based assay (CBA) can detect acetylcholine receptors (AChRs) or muscle-specific tyrosine kinase (MuSK) antibodies (Abs) in a proportion of patients with radioimmunoassay (RIA)-double seronegative myasthenia gravis (dSN-MG). A commercial fixed CBA for AChR and MuSK Abs has recently become available; however, comparative studies on fixed and live CBAs are lacking. In this study, we compared the performance of fixed and live CBAs in patients with RIA-dSN MG and assessed their sensitivity in RIA-positive MG samples and their specificity. METHODS: AChR and MuSK Abs were tested in 292 serum samples from 2 Italian MG referral centers by live and fixed CBAs: 192 from patients with MG and 100 from controls. All samples had been previously assessed by RIA: 66 were AChR positive, 40 MuSK positive, and 86 dSN. All controls were negative. Two independent raters assessed the CBA results. Fixed and live CBAs were compared with the McNemar test; interrater and interlaboratory agreement were assessed with Cohen's kappa or interclass correlation coefficient (ICC), as appropriate. RESULTS: In 86 RIA-dSN samples, fixed CBA detected Abs in 10 cases (11.6%, 95% CI 5.7-20.3), whereas live CBA detected Abs in 16 (18.6%, 95% CI 11.0-28.5) (p = 0.0143). Of these sera, those positive by fixed CBA were also positive by live CBA. In addition, live CBA could detect MuSK Abs in 4 and AChR Abs in 2 samples that were negative by fixed CBA, providing an 8% (95% CI 2.9-16.6) further increase in the Ab detection rate. These results were confirmed by flow cytometry. In the RIA-positive cohort, the sensitivity for AChR Abs was 98.5% (95% CI 91.9%-99.9%) for fixed CBA and 100% (95% CI 94.6-100) for live CBA (p = 0.1573). For both assays, the sensitivity for MuSK Abs was 100% (95% CI 91.2-100), and the specificity was 100% (95% CI 96.4-100). Interrater agreement was almost perfect for live and fixed CBAs (Cohen's kappa 0.972 and 0.978, respectively), alike interlaboratory agreement. Interrater agreement for the CBA score ranged from good to excellent (ICC: 0.832-0.973). DISCUSSION: Fixed CBA represents a valuable alternative to RIA for AChR and MuSK Ab detection in patients with MG and could be considered as a first-step diagnostic test. Live CBA can be useful in the serologic evaluation of RIA- and fixed CBA-negative samples.

The biochemical diagnosis of acromegaly: revising the role of measurement of IGF-I and GH after glucose load in 5 questions.

INTRODUCTION: Acromegaly is a rare disorder characterized by the excessive secretion of growth hormone (GH), mostly caused by pituitary adenomas. While in full-blown cases the diagnosis is easy to establish, milder cases are more challenging. Additionally, establishing whether full cure after surgery is reached may be difficult. AREAS COVERED: In this article, we will review the challenges posed by the variability in measurements of GH and its main effector insulin-like growth factor I (IGF-I) due to both biological changes, co-morbidities, and assays variability. EXPERT OPINION: Interpretation of GH and IGF-I assays is important in establishing an early diagnosis of acromegaly, in avoiding misdiagnosis, and in establishing if cure is achieved by surgery. Physicians should be familiar with the variables that affect measurements of these 2 hormones, and with the performance of the assays available in their practice.

Does mild intrahepatic cholestasis of pregnancy require an aggressive management? Evidence from a prospective observational study focused on adverse perinatal outcomes and pathological placental findings.

OBJECTIVE: To ascertain the most effective approach in pregnancies complicated by mild intrahepatic cholestasis of pregnancy (mICP) by evaluating rates of adverse perinatal outcomes (APOs) and pathological placental findings. METHODS: A total of 89 pregnancies complicated by mICP (defined as total serum bile acids (TSBAs) levels <40 µmol/L) were included. One-drug (ursodeoxycholic acid [UDCA]) (n = 49, 55.1%) and combined (UDCA plus S-adenosyl methionine (SAMe)) (n = 40, 44.9%) therapies were compared. RESULTS: No differences were found in demographic, obstetric, and placental characteristics. In UDCA plus SAMe group, premature delivery was a common clinical decision (14.3 versus 25%, p-value = .201), with increased rates of instrumental vaginal delivery (VD; 28.6 versus 40%, p-value = .522), but similar cesarean section (CS) rates (26.5 versus 25%, p-value = .498). Mean placental weight was comparable (UDCA, mean 595.7 g, SD 213.1 g versus UDCA plus SAMe, mean 586.4 g, SD 102.9 g, p-value = .875). A total of 110 lesions were identified, 64 in 25 placentas of patients assigned to the UDCA and 46 in 15 placentas of patients managed by UDCA plus SAMe. Placental findings attributable to maternal malperfusion were found in 41/25 and 32/15 cases treated by UCDA and UDCA plus SAMe (165 versus 213%, p-value = .774), pathological fetal vascular supply in 17/25 and 8/15 placentas (68 versus 53%, p-value = .777), and inflammatory lesions in 6/25 and 6/15 cases (24 versus 40%, p-value = .757). CONCLUSIONS: Pregnancies complicated by mICP and managed by UDCA alone present similar APO rates and placental histopathology if compared with those treated by UDCA plus SAMe, failing to recognize advantages in the combined therapy. Further prospective studies and data sharing from ongoing RTCs could drive changes in therapeutic plan.

Immunoassay Interference on Thyroid Function Tests During Treatment with Nivolumab.

Background: Immune checkpoint inhibitors (ICIs) are associated with several endocrine side effects. In particular, the use of programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors is related to a higher incidence of thyroid dysfunction. Patient Findings: An 85 years-old patient, diagnosed with a metastatic melanoma treated with nivolumab, presented to our hospital with severe ICI-related thyrotoxicosis. Diagnosis was complicated by a biochemical interference on thyroid hormones assay, probably induced by nivolumab. Summary: Baseline laboratory examination conducted before onset of anticancer therapy showed normal thyroid function test (TFTs). A few days after receiving the second nivolumab administration, the patient developed a severe thyrotoxicosis. According to destructive thyroiditis, in a short period thyrotropin (TSH) levels normalized and rapidly increased, but free thyroxine (fT4) levels were inappropriately elevated and did not decrease as expected. The sample was processed by using a Siemens Centaur® immunoassay. We reanalyzed the same sample at another laboratory and with a different immunoassay method (Roche Elecsys®). The results obtained from this assay confirmed severe hypothyroidism with appropriately low fT4 levels. We suspected a possible nivolumab-associated interference on the fT4 assay. Therefore, we subjected the same sample to a polyethylene glycol (PEG) 6000 precipitation, a simple method for the removal of macromolecules, before assaying for fT4 levels. Evaluation of the post-PEG-precipitation sample (Siemens Centaur immunoassay) revealed appropriately low fT4 levels. The patient was started on levothyroxine (LT4) therapy, with monthly TFT monitoring using the Roche immunoassay. Approximately 9 months after starting nivolumab therapy, the patient was advised treatment cessation. A month later, the TFTs were retested on a Siemens Centaur immunoassay, and appropriate fT4 levels were observed in accordance with normal TSH levels on adequate LT4 replacement therapy. Conclusions: We report a possible novel nivolumab-induced biochemical interference on assays of fT4 levels. The hypothesis of a biochemical drug-induced interference is further supported by the disappearance of the interference after the withdrawal of nivolumab. Further studies are needed to prove the biochemical mechanisms of this interference.

Multicenter evaluation of the new immunoassay method for TSH measurement using the automated DxI platform.

AIM OF THE STUDY: Recently, Beckman Coulter Diagnostics set up a new TSH immunoassay for the automated DxI platform. The aim of this study was to evaluate and compare the analytical performance and clinical results of this method with those of previous method. MATERIAL AND METHODS: A multicenter study (named TSH ELAS Study) was organized using 593 serum samples, collected from healthy subjects and patients with thyroid disorders, and 13 control samples, circulated in an External Quality Assessment (EQA) scheme. RESULTS: The values of LoB and LoD, and LoQ at 20% CV were 0.0004mIU/L, 0.001mIU/L and 0.0023mIU/L, respectively. Moreover, TSH concentrations >0.01mIU/L actually show imprecision values lower than 5% CV. This new TSH assay showed a systematic underestimation (on average of 6.25%) compared to old method, which is mainly due to larger differences between methods for samples with low TSH concentrations, related to the better analytical sensitivity of new compared to old method. In a reference population, including 279 apparently healthy adult subjects, Caucasian volunteers (mean age 43.6years, age 20-63years, 138 women and 141 males) the distribution of TSH concentrations was: mean (CI 95%) 1.694mIU/L (1.588-1.779), median 1.495mIU/L (1.412-1.588mIU/L), 97.5th percentile 3.707mIU/L. CONCLUSIONS: The new TSH immunoassay for DxI platform shows some relevant improvements compared to the previous one: use of the most recent WHO 3rd IRP 81/563 standard and monoclonal antibodies (instead of polyclonal antibodies of the old method), and better analytical sensitivities and reproducibility.

Intraoperative high-dose calcium stimulation test in patients with sporadic medullary thyroid carcinoma is highly accurate in predicting lateral neck metastases.

BACKGROUND: Intraoperative measurement of calcitonin is not highly accurate in predicting the completeness of the operative resection after total thyroidectomy combined with central neck dissection (TT-CND) in patients with medullary thyroid carcinoma (MTC). We evaluated whether an intraoperative, high-dose calcium stimulation test (IO-CST) after TT-CND can predict lateral neck involvement. METHODS: Eleven patients who underwent primary operation for sporadic MTC were included. High-dose (25 mg/kg) calcium gluconate was administered after TT-CND with calcitonin measured at 2, 5, and 10 minutes after the calcium gluconate infusion. RESULTS: There were 2 males and 9 females (mean age, 51 years; range, 18-88). Three patients showed lateral neck metastases. At a mean follow-up of 7.0 months (range, 2-10), 1 patient showed distant metastases and 1 a slightly increased calcitonin level. After IO-CST, serum calcitonin increased in all the 3 patients with lateral neck metastases, and it remained unchanged or decreased in the other patients without lateral neck metastases. Percent variation of serum calcitonin after IO-CST was 92% in patients with lateral neck metastases and -3.1 ± 4.9% in patients without lateral neck metastases. CONCLUSION: Calcitonin measurement after IO-CST in patients with sporadic MTC can be highly accurate in predicting lateral neck nodes involvement. These results could represent a stimulus toward the development of a quick calcitonin assay.

Post-thyroidectomy hypocalcemia is related to parathyroid dysfunction even in patients with normal parathyroid hormone concentrations early after surgery.

BACKGROUND: Hypocalcemia may develop even in the presence of normal postoperative parathyroid hormone (PTH) concentrations. We aimed to identify risk factors of hypocalcemia in patients with normal PTH concentration early after total thyroidectomy (TT). METHODS: We included 1,504 consecutive patients who underwent TT between January 2012 and December 2013. Significant hypocalcemia was defined as serum calcium concentrations of <8.0 mg/dL. RESULTS: Overall, 333 patients had subnormal PTH 4 hours after surgery (4-hour PTH; <10 pg/mL) and received oral calcium (OC) and calcitriol supplementation. Among the 1,171 patients with normal 4-hour PTH (≥ 10 pg/mL; euparathyroid), 211 experienced hypocalcemia and required OC administration. Among the euparathyroid patients, no difference was found between normocalcemic and hypocalcemic patients in terms of age, hormonal status, preoperative PTH, 25-hydroxy vitamin D (25OH-VD), magnesium, and phosphate concentrations. On univariate analysis, euparathyroid hypocalcemic patients were more frequently females, had significantly lower preoperative serum calcium and 4-hour PTH concentrations, and greater decreases in PTH. Independent risk factors for hypocalcemia with normal 4-hour PTH were preoperative serum calcium concentration and PTH decline of ≥ 50%. CONCLUSION: Female sex, toxic goiter, and 25OH-VD deficiency are not risk factors for post-TT hypocalcemia. Relative parathyroid insufficiency seems to be the principal mechanism of post-thyroidectomy hypocalcemia, even in patients with normal postoperative PTH concentrations.

Is intraoperative calcitonin monitoring useful to modulate the extension of neck dissection in patients with medullary thyroid carcinoma?

BACKGROUND: The extension of the compartment-oriented neck dissection at primary surgery in medullary thyroid carcinoma (MTC) is controversial. Because a <50 % decrease in intraoperative calcitonin levels (IO-CT) after total thyroidectomy plus central neck dissection (TT-CND) has been associated with residual disease, IO-CT monitoring has been proposed to predict the completeness of surgery. The goal of the present prospective study was to verify the accuracy of IO-CT monitoring. METHODS: All patients scheduled for primary surgery for suspected or proven MTC between November 2010 and January 2013 were included. Calcitonin was measured pre-incision (basal level), after tumor manipulation, at the time TT-CND was accomplished (ablation level), 10 and 30 min after ablation. A decrease >50 % with respect to the highest IO-CT level 30 min after ablation was considered predictive of cure. RESULTS: Twenty-six patients were included, and IO-CT monitoring identified 18 of 23 cured patients (true negative results) and 2 of 3 patients with persistent disease (true positive result). In 5 patients with normal basal and stimulated postoperative calcitonin levels, a decrease <50 % was observed (false positive results). In one of three patients with persistent disease a >50 % decrease in IO-CT was observed (false negative results). Specificity, sensitivity, and accuracy of IO-CT were 78.2, 66.6, and 76.9 %, respectively. CONCLUSIONS: Intraoperative calcitonin monitoring is not highly accurate in predicting the completeness of surgical resection. In the present series, relying on IO-CT would result in limited resection in about one third of the patients with residual neck disease and in unnecessary lateral neck dissection in about 20 % of the cured patients.

Monocytes from depressed patients display an altered pattern of response to endotoxin challenge.

It is now well established that major depression is accompanied and characterized by altered responses of the immune-inflammatory system. In this study we investigated the pro-inflammatory activation of monocytes isolated from depressed patients as a parameter not influenced by such confounds as the time of day, the nutritional and exercise status or the age and gender of patients. Monocytes from depressed patients and from healthy controls were isolated in vitro; after 24-h incubation under basal conditions, cells were exposed for 24-h to 100 ng/ml of endotoxin (bacterial lipopolysaccharide, LPS). We found that monocytes from drug-free depressed patients and controls release the same amounts of prostaglandin E2 (PGE2) under basal conditions, whereas monocytes from patients are dramatically less reactive to LPS (8.62-fold increase vs previous 24 hrs) compared to healthy controls (123.3-fold increase vs previous 24 hrs). Such blunted prostanoid production was paralleled by a reduction in COX-2 gene expression, whereas other pro-inflammatory mediators, namely interleukin-1ß (IL-1 ß) and -6 (IL-6) showed a trend to increased gene expression. The above changes were not associated to increased levels of circulating glucocorticoids. After 8 months of antidepressive drug treatment, the increase in PGE2 production after the endotoxin challenge was partially restored, whereas the increase in IL-1 ß and -6 levels observed at baseline was completely abolished. In conclusion, our findings show that the reactivity of monocytes from depressed patients might be considered as a marker of the immune-inflammatory disorders associated to depression, although the lack of paired healthy controls at follow-up does not allow to conclude that monocyte reactivity to endotoxin is also a marker of treatment outcome.

Assessment of salivary free cortisol levels by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in patients treated with mitotane.

OBJECTIVE: Mitotane is an adrenocytolytic agent used in adrenocortical carcinoma, inducing adrenal insufficiency, requiring replacement treatment. Such therapy is not easy to monitor because of mitotane interference. Salivary cortisol reflects a free fraction of plasma cortisol and may be useful in such patients. DESIGN: The aim of our study was to evaluate salivary cortisol by HPLC coupled to tandem-mass spectrometry (LC-MS/MS) and by an electrochemiluminescence immunoassay (ECLIA) in patients treated with mitotane. We enrolled 6 patients receiving mitotane and 2 Addison disease patients as negative controls and determined salivary cortisol rhythm. We also determined the salivary cortisol rhythm in 8 healthy subjects. Salivary samples (n=112) were assayed by ECLIA, using Roche Modular E170, and by LC-MS/MS. RESULTS: The mean values obtained by ECLIA were significantly higher than those obtained by LC-MS/MS in the mitotane group (p<0.001). In fact, in the group measured by LC-MS/MS, we observed several peaks eluting at a retention time different from the cortisol group, presumably due to cortisol-like analogues. In Addison disease, since steroidogenesis is absent, salivary cortisol values measured by the two methods did not show any significant difference (p=0.61). CONCLUSIONS: Salivary cortisol measured by LC-MS/MS is a selective method, excluding cortisol analogues accumulating in treated patients. Therefore, LC-MS/MS offers an effective system to monitor replacement therapy in mitotane treated patients.

Combining early postoperative parathyroid hormone and serum calcium levels allows for an efficacious selective post-thyroidectomy supplementation treatment.

BACKGROUND: Optimal treatment protocol to prevent symptomatic hypocalcemia following total thyroidectomy is still matter of debate. We prospectively evaluated the efficacy of a selective supplementation protocol based on both early postoperative intact parathyroid hormone (iPTH) and serum calcium levels. METHODS: Two hundred thirty consecutive patients were divided in three different groups of treatment according to iPTH levels 4 h after total thyroidectomy (4 h-iPTH) and serum calcium levels in the first postoperative day (1PO-Ca): group A (4 h-iPTH > 10 pg/ml, 1PO-Ca ≥ 8.5 mg/dl), no treatment; group B (4 h-iPTH > 10 pg/ml, 1PO-Ca < 8.5 mg/dl), oral calcium (OC) 3 g per day; and group C (4 h-iPTH ≤ 10 pg/ml), OC 3 g + calcitriol (VD) 1 µg per day. Development of biochemical and/or symptomatic hypocalcemia was evaluated. RESULTS: Fifty-nine patients (25.6%) had subnormal 4 h-iPTH levels (≤10 pg/ml) (group C). Among patients with normal 4 h-iPTH levels, 25 (10.9%) had subnormal 1PO-Ca (<8.5 mg/dl) (group B). The remaining 146 patients (63.5%) had normal 4 h-iPTH and 1PO-Ca levels (group A). One patient in group A, 2 in group B, and 18 in group C developed biochemical hypocalcemia. Only one patient in group C experienced major symptoms. Treatment was discontinued within 1 month in all the patients in group B. At a mean follow-up of 303 days, five patients in group C were still under supplementation treatment. CONCLUSION: The proposed supplementation protocol seems efficacious in preventing symptomatic hypocalcemia. It could allow a safe and early discharge of most patients, thus avoiding the constraints and the costs of routine supplementation.

Intraoperative PTH monitoring during parathyroidectomy: the need for stricter criteria to detect multiglandular disease.

PURPOSE: Usefulness of rapid intraoperative parathyroid hormone assay (RI-PTH) for diagnosis of multiglandular disease during parathyroidectomy is still debated. MATERIALS AND METHODS: Two hundred seven patients were selected for focused parathyroidectomy for a suspicious single adenoma. RI-PTH results were interpreted on the basis of our criteria for prediction of multiglandular disease (a < 50% drop from the highest pre-excision level and/or a T20 concentration higher than reference range and/or >7.5 ng/L higher than the T10). The results of these criteria were compared with the Miami Criterion (MC). RESULTS: One hundred ninety-seven uniglandular disease and ten multiglandular disease were found. Our criteria identified all but one patient with multiglandular disease (false positive (FP) rate 0.5%; specificity 90%). On the basis of MC, RI-PTH monitoring would have resulted in five FP results, with a specificity of 50%. CONCLUSIONS: Despite the higher rate of unnecessary bilateral exploration, our criteria results in a lower FP, markedly reducing the risk of missing multiglandular disease.

A novel MEN1 frameshift germline mutation in two Italian monozygotic twins.

BACKGROUND: This report describes clinical, biochemical and molecular findings regarding two Italian monozygotic twins carrying a novel multiple endocrine neoplasia type 1 (MEN1) mutation inherited from their mother. METHODS: Clinical, biochemical and genetic evaluations of the above-mentioned family members were performed. RESULTS: All three members were heterozygous for a deletion involving the first nucleotide at codon 98 in exon 2 of the MEN1 gene, which results in early termination of the protein. The clinical phenotypes were as follows: one out of the two twins suffered from insulinoma and hyperparathyroidism, while the second one was asymptomatic. Furthermore, the mother suffered from hyperparathyroidism, as well as from hypergastrinemia for several years before the daughter was diagnosed of MEN-1. CONCLUSIONS: We describe a family with a new heterozygous mutation (g.292delC) in the MEN1 gene not described previously. The mutation leads to a truncated protein without activity, explaining the clinical picture of this family.

Parathyroidectomy monitored by intra-operative PTH: the relevance of the 20 min end-point.

OBJECTIVES: RI-PTH measurements are a prerequisite for minimally invasive parathyroidectomy, providing guidance regarding the removal of hyper-functioning tissue. Different criteria of PTH decrease, concentration and clearance were analyzed in order to predict surgical treatment. DESIGN AND METHODS: Blood samples at pre-incision, manipulation, 5, 10 and 20 min after resection, were collected from 145 patients presenting unambiguous, pre-surgical "single adenoma" diagnosis. RESULTS: The meeting of Irvin criterion would have permitted the identification of 28% uncured cases leading to 4% unnecessary neck exploration. On the contrary, we would have identified all of the uncured patients, to the detriment of 7% unnecessarily prolonged procedure by taking into account PTH drop, concentration and clearance shape at 20 min. CONCLUSIONS: The 20' end-point plays a key role in the correct determination of surgical outcome, strongly improving the possibility of adequate patient treatment. However, since the high success rate of traditional parathyroidectomy, yet not provided by RI-PTH, the utmost improvement to hyper-parathyroidism surgical treatment by RI-PTH could be achieved in pre-operative equivocal glands localization or multiglandular disease selected population to quickly guide and confirm the complete removal of all hyper-secreting tissue.

Parathyroid hormone levels 4 hours after surgery do not accurately predict post-thyroidectomy hypocalcemia.

BACKGROUND: We evaluated the reliability of intact parathyroid hormone (iPTH) levels 4 hours after thyroidectomy (4h-iPTH) as a predictor of hypocalcemia in a large series of patients. METHODS: A prospective experimental design involving 523 consecutive patients between September 1, 2004, and June 30, 2005, was employed. The specificity, sensitivity, and overall accuracy of 4h-iPTH in predicting post-thyroidectomy hypocalcemia and symptoms were determined. RESULTS: A total of 199 patients developed hypocalcemia (serum calcium concentrations <8.0 mg/dl). Five patients still were receiving vitamin D/oral calcium at 6 months after the operation. Seventy-three patients experienced mild symptoms. The 4h-iPTH levels were reduced in hypocalcemic patients (28.8 +/- 15.3 vs 11.2 +/- 11.6 pg/ml) (P < .001). The 4h-iPTH levels were within the normal range (10 to 65 pg/ml) in 360 patients (290 normocalcemic) and subnormal in 163 patients (129 hypocalcemic, of whom 62 were symptomatic). The accuracy of 4h-iPTH levels <10 pg/ml in predicting post-thyroidectomy hypocalcemia and symptoms was 80.1% and 78.6%, respectively. False-negative results were observed in 70 hypocalcemic patients (13.4%), 11 of whom were symptomatic (2.1%). CONCLUSIONS: Subnormal 4h-iPTH levels alone did not accurately predict clinically relevant postoperative hypocalcemia. The optimal cut-off level and its integration with preoperative and postoperative serum calcium concentrations should be reconsidered.

Early prediction of postthyroidectomy hypocalcemia by one single iPTH measurement.

BACKGROUND: We prospectively evaluated the possibility to make an early prediction of postthyroidectomy hypocalcemia by postoperative intact parathyroid hormone (iPTH) measurements. METHODS: Fifty-three consecutive patients who underwent bilateral thyroid resection were included; iPTH was measured preoperatively, at the end of the surgical procedure, and at 2, 4, 6, 24, and 48 hours after the operation. Patients who had hypocalcemia (serum total calcium, <8.0 mg/dL) were compared with normocalcemic patients. RESULTS: Sixteen patients experienced hypocalcemia. Six patients experienced symptoms. No significant difference was found between hypocalcemic and normocalcemic patients concerning demographic, pathologic, and preoperative laboratory data, surgical procedure, and intraoperative findings. Postoperative iPTH levels were reduced in hypocalcemic patients at the end of the procedure and at 2, 4, 6, 24, and 48 hours after the operation ( P < .001). IPTH levels below the normal range (<10 pg/mL) at 4 and 6 hours after the operation correctly predicted postoperative hypocalcemia and symptoms in all but 1 patient with a self-limiting, asymptomatic hypocalcemia (serum calcium concentration, 7.8 mg/dL) (specificity, 100%; sensitivity, 94%; overall accuracy, 98%). CONCLUSIONS: One single iPTH measurement reliably can predict, early after thyroidectomy, which patients are prone to clinically relevant postoperative hypocalcemia and necessitate supplementation treatment and which patients are eligible for a safe early discharge.