Circulating pro-gastrin releasing peptide (ProGRP) in patients with medullary thyroid carcinoma.

OBJECTIVES: Serum calcitonin (CT) is pivotal in medullary thyroid cancer (MTC) management. Recently, progastrin releasing peptide (ProGRP) has been proposed as a candidate complementary tumor marker of MTC. As current data are sparse our study was undertaken to evaluate the distribution of ProGRP in patients with MTC and its relationship with the tumor burden. Additionally, serial measurement of CT, carcinoembryonic antigen (CEA) and ProGRP was evaluated in three patients undergoing tyrosine kinase inhibitors (TKI). METHODS: Seventy-eight, 125 and 62 sera from patients with MTC, non-medullary malignant and benign thyroid diseases were collected, respectively. ProGRP measurement was performed by Elecsys® assays on Cobas e601 platform (Roche Diagnostics). RESULTS: Significantly higher ProGRP levels were found in MTC compared to non-MTC patients. Among MTC patients ProGRP levels accurately discriminate patients with active from those with cured disease and, respectively, patients with loco-regional active disease from those with distant metastasis. Finally, ProGRP performed better than CT and CEA in monitoring the response to TKI therapy in three patients monitored serially. CONCLUSIONS: Serum ProGRP is promising as a complementary tumor marker in MTC patients. Further studies will be required, mainly focused on monitoring ProGRP during TKI treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and carcinoembryonic antigen.

Clinical performance of calcitonin and procalcitonin Elecsys® immunoassays in patients with medullary thyroid carcinoma.

OBJECTIVES: Medullary thyroid carcinoma (MTC) is caused by a malignant transformation in the parafollicular C-cells of the thyroid, where calcitonin (CT) is released. Nowadays, CT is the main tumor marker used in the diagnosis and follow-up of MTC patients. Nonetheless, procalcitonin (PCT) has recently been proposed as a useful complementary/alternative biomarker in MTC. Our aims were to investigate the diagnostic performance of CT and PCT and their combination in the differential diagnosis between active and inactive MTC and between MTC and non-MTC thyroid diseases, respectively. METHODS: Serum samples were collected from 16 patients with active (i.e. primary tumour before surgery or post-surgical recurrent disease) and 23 with inactive (i.e. complete remission) MTC, 125 patients with non-MTC benign thyroid disease and 62 patients with non-MTC thyroid cancers, respectively. Elecsys® CT and PCT measurements were simultaneously performed on the Cobas e601 platform (Roche Diagnostics, Rotkreutz, Switzerland). RESULTS: Both CT and PCT median values in active MTC (94 pmol/L and 1.17 ng/mL, respectively) were significantly higher compared with inactive MTC (0.28 and 0.06) and either benign (0.37 and 0.06) or malignant (0.28 and 0.06) non-MTC. Undetectable PCT was found in five non-MTC patients with false positive CT results. CONCLUSIONS: Elecsys® PCT assay is a highly sensitive and specific alternative MTC marker. At the very least it appears useful in patients with positive CT results as negative PCT values securely exclude active MTC. The availability of both markers on the same automated platform facilitates reflex or reflective strategies to refine the laboratory diagnosis.

Diagnostic testing for Graves' or non-Graves' hyperthyroidism: A comparison of two thyrotropin receptor antibody immunoassays with thyroid scintigraphy and ultrasonography.

OBJECTIVE: Graves' disease (GD) is the most common cause of hyperthyroidism. In many cases, when the aetiological diagnosis of GD is not evident based on the clinical evaluation and thyroid function testing, it may become challenging to distinguish Graves' hyperthyroidism from other forms of thyrotoxicosis. The current study was primarly carried out to compare the diagnostic effectiveness of two TSH receptor antibody immunoassays (IMAs), ultrasonography and thyroid scintigraphy in hyperthyroidism scenario. METHODS: We retrospectively analysed consecutive patients with newly diagnosed and untreated thyrotoxicosis who underwent thyroid functional tests, both TRAb and TSI measurements, thyroid scintigraphy and ultrasonography. TRAb assessment was carried out by Kryptor® compact PLUS, while TSI by Immulite® . Echo pattern 3 corresponded to 'thyroid inferno', and the final diagnosis of GD vs non-Graves' hyperthyroidism was made according to the thyroid scan (qualitative scintigraphy). Receiver operating characteristic (ROC) curves were drawn using the final diagnosis as reference. Clinical sensitivity and specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for all the tests. RESULTS: A total of 124 untreated hyperthyroid patients were included in our study (GD, n = 86 vs non-Graves' hyperthyroidism, n = 38). ROC curves showed that the optimal cut-off values associated with the highest diagnostic sensitivity and specificity was 0.7 IU/L for TRAb Kryptor® (93 [85.4-97.4] and 86.8 [71.9-95.5]) and 0.1 IU/L for TSI Immulite® (94.2 [86.9-98.1] and 84.2 [68.7-93.9]), respectively. For the echo pattern 3, we found a good sensitivity (92.1%) and a high PPV (95.2%) but a quite low specificity value (69.8%) and a relative low NPV (57.5%). For thyroid scintigraphy, the TcTU cut-off value of 1.3% corresponded to the best limit for sensitivity and specificity in our patients (95.3 [88.5-98.7] and 96.4 [81.6-99.4]). The Passing-Bablok regression equation and the Bland-Altman test showed a great degree of correlation and agreement existed between TRAb Kryptor® and Immulite® TSI results. CONCLUSIONS: Thyroid scintigraphy remains the most accurate method to differentiate causes of thyrotoxicosis. However, TRAb assays can be alternatively adopted in this setting, limiting the use of thyroid scintigraphy (TcTU evaluation) to TRAb-negative patients. Thyoid US is less accurate than both TRAb/TSI and thyroid scintigraphy, but the 'thyroid inferno' pattern provides a high PPV for GD.

Measuring thyroglobulin in patients with thyroglobulin autoantibodies: evaluation of the clinical impact of BRAHMS Kryptor® Tg-minirecovery test in a large series of patients with differentiated thyroid carcinoma.

Background The present study was undertaken to evaluate the clinical impact of a thyroglobulin (Tg) minirecovery test (Tg-mRec) in a large series of differentiated thyroid carcinoma (DTC) patients treated and monitored homogeneously in a tertiary referral center. Methods Included were 1120 serum samples from 798 DTC patients. Tg, Tg autoantibodies (TgAb) and Tg-mrec measurements were performed on the automated Kryptor® platform and results compared to the corresponding clinical status. Results Among included samples 228 (20%) were TgAb-positive (TgAb+) and 892 (80%) TgAb-negative (TgAb-), respectively. Tg cutoff points were settled at 0.31 µg/L and 0.15 µg/L for TgAb- and TgAb+ patients, respectively, by ROC curve analysis. The diagnostic performance of serum Tg was reduced in TgAb+ compared to TgAb- patients, however, 87% of TgAb+ patients with recurrent disease and, particularly, all patients with distant metastases were correctly detected by adopting an optimized Tg cutoff for TgAb+ patients. A disturbed recovery was found in only 1% of TgAb- patients and in these cases no clinically relevant information was added by the Tg-mRec. Among TgAb+ patients with undetectable Tg and undisturbed Tg-mRec, no one had recurrent disease. However, a falsely undetectable Tg was demonstrated in two patients with recurrent disease who next to increased TgAb also had a disturbed Tg-mRec test. Conclusions There is no additional clinical benefit from performing Tg-mRec in most patients. It can however be considered in TgAb+ patients with undetectable Tg levels as it may help differentiate between patients with true negative and false negative Tg levels in the presence of such antibodies.

A multi-level strategy for a long lasting reduction in unnecessary laboratory testing: A multicenter before and after study in a teaching hospital network.

BACKGROUND: Reducing unnecessary laboratory blood testing in the hospital setting represents a challenge to improve the adequacy of healthcare and a tricky task for teaching hospitals. Our hospital network actively participates in the Choosing Wisely Campaign and is engaged in avoiding unnecessary low value interventions and investigations. We aimed to study whether a multi-level approach combining educational and web-system based interventions, could be effective in reducing laboratory testing and related costs. METHODS: Multicenter, proof of concept, prospective, observational, before and after study, in a network of public hospitals in Switzerland. All patients admitted between 1 January 2015 and 31 December 2017 were analyzed. A multi-level strategy based on online continuous monitor benchmarking and educational support was applied in the internal medicine services. The primary outcome was a significant reduction in the number of laboratory tests per patient and per day during the hospital stay. Secondary outcomes were reduction in the blood sample volume taken per patient and per day in laboratory costs. RESULTS: Over the 36 months of the study, 33 309 admissions were analyzed. A significant reduction of laboratory tests per patient and per day of hospitalisation was found:-11%, P-value<0.001; -6%, P-value <0.001. The mean monthly blood volume, per patient and per day of hospital stay and laboratory costs per patient was also significantly reduced: -7%, P-value<0.05; -3%, P-value<0.01, and -17%, P-value<0.01, respectively. CONCLUSIONS: The obtained reduction in the number of laboratory tests, blood volume withdrawn and related costs, support the idea that an open web-based system, involving all health care providers, coupled with educational interventions, can be helpful in generating awareness of prescriber habits and to catalyze changes in their behaviour. The peer pressure related to the unmasked benchmarking process did probably play a determinant role.

Body Mass Index and skin reactivity to histamine and Dermatophagoides pteronyssinus in children and adolescents followed in a pediatric allergy service.

SUMMARY: Rationale. Recent data suggest that the nutritional status assessed by body mass index (BMI) is positively associated with skin reactivity to histamine in children. Objective. To study the relation between BMI and skin reactivity to histamine and Dermatophagoides pteronyssinus in allergic children and adolescents. Methods. The medical charts of patients attended in our outpatient clinic between 2013 and 2014 (n = 972) were evaluated. Only patients with asthma, allergic rhinitis or wheezing infants sensitized to at least one aeroallergen were selected: a total of 626 patients (6 months to 19 year-olds; 60.1% male) were enrolled. Weight (kg), height (m), BMI (weight/height2), and the mean diameter of the wheals induced by histamine (10 mg/ml) and Dermatophagoides pteronyssinus in skin prick tests (SPT) were obtained. Skin index (SI; ratio of allergen-induced wheal diameter and corresponding histamine diameter) was also analyzed. Results. All patients had shown a mean wheal diameter of histamine greater than 1 mm. There was no increased skin reactivity to histamine with increasing BMI Z score (ZBMI). However, a significant correlation between BMI and the mean wheal of histamine was observed in patients < -1 ZBMI. Similar results were observed with Dermatophagoides pteronyssinus, (even considering the SI). Conclusions. We did not document interference of nutritional status (ZBMI) on the skin reactivity to histamine or Dermatophagoiodes pteronyssinus in atopic patients. Further investigation is required.

Macro-TSH: An Uncommon Explanation for Persistent TSH Elevation That Thyroidologists Have to Keep in Mind.

A macro-thyroid-stimulating hormone (macro-TSH) is an infrequent yet noteworthy phenomenon in the thyroid field. A 69-year-old patient presented with persistently elevated thyroid-stimulating hormone (TSH) levels ranging from 30 to 50 mIU/L, paradoxically accompanied by normal thyroid hormone levels and normal thyroid ultrasound, with no findings on pituitary magnetic resonance. Laboratory studies were conducted to investigate potential interferences impacting the accuracy of TSH measurements. After excluding other potential causes, polyethylene glycol (PEG) precipitation technique was used, which led us to the diagnosis of macro-TSH. This result was confirmed through chromatography. Macro-TSH, although rare, emerged as the key contributor to the patient's unexplained increase in TSH levels. This case highlights the importance of considering macro-TSH as a potential etiology in cases characterized by unexplained TSH elevation, offering insights into diagnostic protocols and expanding our understanding of thyroid function anomalies.

Longitudinal Postvaccine SARS-CoV-2 Immunoglobulin G Titers, Memory B-Cell Responses, and Risk of COVID-19 in Multiple Sclerosis Over 1 Year.

BACKGROUND AND OBJECTIVES: Some disease-modifying treatments impair response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in multiple sclerosis (MS), potentially increasing the risk of breakthrough infections. We aimed to investigate longitudinal SARS-CoV-2 antibody dynamics and memory B cells after 2 and 3 messenger RNA (mRNA) vaccine doses and their association with the risk of COVID-19 in patients with MS on different treatments over 1 year. METHODS: Prospective observational cohort study in patients with MS undergoing SARS-CoV-2 mRNA vaccinations. Antispike (anti-S) immunoglobulin G (IgG) titers were measured by chemiluminescence microparticle immunoassay. Frequencies of spike-specific memory B cells were measured on polyclonal stimulation of peripheral blood mononuclear cells and screening of secreted antibodies by ELISA. RESULTS: We recruited 120 patients with MS (58 on anti-CD20 antibodies, 9 on sphingosine 1-phosphate (S1P) receptor modulators, 15 on cladribine, 24 on teriflunomide (TFL), and 14 untreated) and collected 392 samples up to 10.8 months after 2 vaccine doses. When compared with untreated patients, anti-CD20 antibodies (ß = -2.07, p < 0.001) and S1P modulators (ß = -2.02, p < 0.001) were associated with lower anti-S IgG, while TFL and cladribine were not. Anti-S IgG decreased with months since vaccine (ß = -0.14, p < 0.001), independently of treatments. Within anti-CD20 patients, anti-S IgG remained higher in those with greater baseline B-cell counts and were not influenced by postvaccine anti-CD20 infusions. Anti-S IgG increase after a 3rd vaccine was mild on anti-CD20 and S1P modulators. Spike-specific memory B-cell responses were weaker on S1P modulators and anti-CD20 than on TFL and influenced by postvaccine anti-CD20 infusions. The frequency of breakthrough infections was comparable between DMTs, but the risk of COVID-19 was predicted by the last measured anti-S IgG titer before infection (OR = 0.56, 95% CI = 0.37-0.86, p = 0.008). DISCUSSION: Postvaccine anti-S IgG titers decrease over time regardless of MS treatment and are associated with breakthrough COVID-19. Both humoral and specific memory B-cell responses are diminished on S1P modulators. Within anti-CD20-treated patients, B-cell count at first vaccine determines anti-S IgG production, whereas postvaccine anti-CD20 infusions negatively affect spike-specific memory B cells.

Evaluation of serum parathyroid hormone-related peptide in hyperthyroid patients.

BACKGROUND: Hypercalcemia occurs in 10-20% of patients with hyperthyroidism, but its pathogenesis is still unclear. AIM: To evaluate changes in parathyroid hormone-related peptide (PTH-rP) concentration in hyperthyroid patients compared with healthy controls. METHODS: We studied PTH-rP, parathormone (PTH) and ionized calcium levels in 153 hyperthyroid patients, and 89 control subjects. These variables were revaluated after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months in a subgroup of 47 patients. RESULTS: Pretreatment PTH-rP and ionized calcium level were significantly higher in hyperthyroid patients than in controls, whereas an opposite trend occurred for PTH. All parameters normalized after carbimazole therapy. CONCLUSION: Untreated hyperthyroid patients exhibited a significant elevation in serum ionized calcium and PTH-rP and a significant reduction in serum PTH levels when compared with healthy controls. Our data favoured the hypothesis of a direct involvement of PTH-rP in the pathogenesis of hypercalcemia in hyperthyroid patients.

Interference in thyroid-stimulating hormone determination.

BACKGROUND: Thyroid-stimulating hormone (TSH) measurement plays a major role in the diagnosis of thyroid disorders. Despite the good quality of immunochemical tests measuring TSH levels, the presence of interfering substances can sometimes alter the TSH results. DESIGN: We reported the case of a 79-year-old man affected by primary autoimmune hypothyroidism hospitalized for pneumonia. A TSH value > 100 mIU L(-1) (reference: 0.44 mIU L(-1)) was found at admission. No signs and symptoms of hypothyroidism were found upon clinical examination and serum concentration of the free thyroxine (FT4) was normal. RESULTS: Serum treatment in heterophile antibody blocking tubes did not change the TSH result in our assay, while normal levels were found in a different immunoassay method. An abnormal pattern was found in protein electrophoresis at admission, with IgG / j and IgM / k monoclonal bands proved in immunofixation. Interestingly, the disappearance of monoclonal bands was paralleled with a normalization of the TSH value. CONCLUSIONS: We suggest in this study that the TSH determination might be influenced by the presence of transient paraproteins.

Vasculitides associated with IgG antineutrophil cytoplasmic autoantibodies in childhood.

Immunoglobulin (Ig)G antineutrophil cytoplasmic autoantibodies are causally associated with necrotizing vasculitides that are characterized immunopathologically by little or no deposition of immunoreactants, such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss angiitis, "renal-limited" vasculitis and a number of drug-induced vasculitides. Clinical routine testing targets the antigens myeloperoxidase and proteinase 3. However, in all of the conditions mentioned, the renal histopathologic findings are indistinguishable. Churg-Strauss angiitis (characterized by necrotizing vasculitis, granulomatous inflammation and tissue eosinophilia), Wegener granulomatosis (characterized by necrotizing vasculitis and granulomatous inflammation) and microscopic polyangiitis (characterized by necrotizing vasculitis) often present with fever, weight loss and a multisystem involvement (ear, nose, throat, lung, eyes, peripheral nerve and heart). Fifty years ago these conditions were very often fatal within 6 months of diagnosis. The introduction of corticosteroids and cyclophosphamide has resulted in a dramatic clinical benefit. Patients who develop treatment-related morbidity can be switched from cyclophosphamide to azathioprine after achieving remission. In patients with less severe disease, methotrexate achieves remission with a success rate similar to that of cyclophosphamide. Plasma exchange, in association with immunosuppression, is likely to be a beneficial therapy for patients with severe kidney disease or pulmonary hemorrhage.

25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.

Lack of concordance between EMIT assay and LC-MS/MS for Therapeutic Drug Monitoring of Mycophenolic Acid: Potential increased risk for graft rejection?

Therapeutic drug monitoring (TDM) of immunosuppressive drugs is crucial in organ-transplanted patients to prevent rejection or toxic effects due to inadequate dosage. Mycophenolic acid (MPA) is a commonly used immunosuppressant in this setting. Nowadays, MPA concentrations are monitored by Enzyme Multiplied Immunoassay Technology (EMIT), and Liquid Chromatography (LC)-based techniques, particularly coupled to Tandem Mass Spectrometry (LC-MS/MS). This study evaluates the concordance between TDM results for MPA obtained through CE-IVD EMIT and LC-MS/MS assays in plasma samples. LC-MS/MS quantification was based on a commercial kit and the analytical performance in terms of accuracy was tested through external proficiency tests and inter-laboratory comparison with a home-made HPLC-UV method. Both these evaluations confirmed the reliability of the LC-MS/MS method (1.6 % and 9.0 % of bias, respectively). Conversely, the comparison between EMIT and LC-MS/MS showed overestimation by EMIT of 33.5 %. This bias resulted concentration-dependent, ranging from 46.4 % in the concentration range of 1-2 mg/L, to 21.4 % over 4 mg/L. Considering the theoretical clinical impact of this overestimation, a fraction comprised between 12.4 % and 31.4 % of samples which resulted over three different minimum effective concentration values by EMIT (no indication for dose adjustment) had discordant indications by LC-MS/MS (dose adjustment needed). Concluding, this study highlights a clinically relevant systematic overestimation of MPA concentration by EMIT, supporting the switch to LC-MS/MS techniques for TDM purpose. However, further prospective studies are needed in order to evaluate the clinical impact of switching the TDM activity from EMIT to LC-MS/MS in a larger cohort in a long period.

Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma.

BACKGROUND: To examine the prevalence of significant interference from heterophile antibodies (HAb) in the measurement of serum thyroglobulin (Tg), we evaluated a large cohort of samples from patients with differentiated thyroid carcinoma (DTC). METHODS: Serum Tg measurements were performed in 406 serum samples before and after incubation of each serum sample in heterophile-blocking tubes (HBT) at room temperature for 1 h. We calculated the difference between the original Tg value and the value obtained after HBT treatment. We considered any sample showing an absolute percent difference >3 SD from the mean percent difference as being affected by HAb interference. RESULTS: We identified five patients (1%) as showing interference from HAb. Of these, three (60%) showed a false positive or falsely increased Tg concentration without any recurrence following clinical work-up; two (40%) showed a false negative or falsely reduced Tg levels, and metastases were detected in both cases by imaging procedures. CONCLUSIONS: HAb may increase as well as reduce the measured Tg in a significant number of patients. A positive HAb interference should be suspected if Tg elevation does not fit the clinical pictures. A negative interference is a more challenging problem because increases in Tg generally occur as the first sign of recurrence of DTC. Therefore, treatment using HBT tubes of all sera referred for Tg measurement should be considered in order to prevent both unwarranted investigations or therapy, and delayed diagnosis of recurrence in patients affected by DTC.

[Detection of hereditary hemochromatosis]. / Dépistage de l'hémochromatose génétique.

Hereditary hemochromatosis is one of the most common genetic disorders. The prognosis of hemochromatosis is normal when phlebotomy therapy is started prior to manifestation of cirrhosis or diabetes. High ferritin is not always a marker of iron overload and ferritin must thus be coupled with transferrin saturation. Only high transferrin saturation entails a genetic research (HFE or type 1). The identification of rare types of hemochromatosis (types 2-4) is only required in particular cases. The evaluation of the iron overload is now based on hepatic MRI determination rather than liver biopsy.

The favorable effect of regional citrate anticoagulation on interleukin-1beta release is dissociated from both coagulation and complement activation.

BACKGROUND: It has been claimed that regional citrate anticoagulation (RCA) improves unfavorable calcium and magnesium dependent cellular and humoral events due to blood/dialyzer membrane interactions during hemodialysis (HD). This study aimed to verify whether the favorable effect of RCA on biocompatibility is independent from coagulation pathway modulation. METHODS: A randomized controlled cross-over single blind trial comparing the activity of the coagulation pathway (thrombinantithrombin complexes (TAT), fibrinopeptide A (FPA), prothrombin fragments 1+2 (F 1+2) and D-dimer (DD)), complement activation (C3a) and interleukin-1 beta secretion (IL-1beta) in nine chronic HD patients treated with RCA or heparin. Blood samples were obtained from the arterial (C3a, IL-1beta, TAT, F 1+2, FPA and DD) and venous (TAT, F 1+2, FPA) lines 2 min after starting treatment and repeatedly during the procedure after 15 min (C3a and IL-1beta), 30 min (C3a), 45 (C3a) and 180 min (TAT, F 1+2, FPA and DD). RESULTS: In both treatment protocols significant enhancement was observed in the coagulation activity during the dialysis session, documented by an increase in TAT (p<0.001), F 1+2 (p<0.001) and FPA (p=0.001). Comparing the two anticoagulation modalities, no differences were noticed in the activity of the coagulation pathway, but a significantly higher complement activity (C3a=886 (832-908) vs. 770 (645-857) ng/mL, p<0.05) and lower IL-1beta secretion (235 (206-285) vs. 538 (346-974) pg/mL, p<0.05) was observed in RCA. CONCLUSIONS: Due to an RCA protocol guaranteeing the same extent of anticoagulation activation as standard heparin, we demonstrated that the significantly lower IL-1beta secretion obtained with RCA is independent from the anticoagulation modulation and dissociated from the complement activity.

Estimation of glomerular filtration rate in hospitalised patients: are we overestimating renal function?

UNLABELLED: QUESTIONS UNDER STUDY AND PRINCIPLES: Estimating glomerular filtration rate (GFR) in hospitalised patients with chronic kidney disease (CKD) is important for drug prescription but it remains a difficult task. The purpose of this study was to investigate the reliability of selected algorithms based on serum creatinine, cystatin C and beta-trace protein to estimate GFR and the potential added advantage of measuring muscle mass by bioimpedance. METHODS: In a prospective unselected group of patients hospitalised in a general internal medicine ward with CKD, GFR was evaluated using inulin clearance as the gold standard and the algorithms of Cockcroft, MDRD, Larsson (cystatin C), White (beta-trace) and MacDonald (creatinine and muscle mass by bioimpedance). RESULTS: 69 patients were included in the study. Median age (interquartile range) was 80 years (73-83); weight 74.7 kg (67.0-85.6), appendicular lean mass 19.1 kg (14.9-22.3), serum creatinine 126 µmol/l (100-149), cystatin C 1.45 mg/l (1.19-1.90), beta-trace protein 1.17 mg/l (0.99-1.53) and GFR measured by inulin 30.9 ml/min (22.0-43.3). The errors in the estimation of GFR and the area under the ROC curves (95% confidence interval) relative to inulin were respectively: Cockcroft 14.3 ml/min (5.55-23.2) and 0.68 (0.55-0.81), MDRD 16.3 ml/min (6.4-27.5) and 0.76 (0.64-0.87), Larsson 12.8 ml/min (4.50-25.3) and 0.82 (0.72-0.92), White 17.6 ml/min (11.5-31.5) and 0.75 (0.63-0.87), MacDonald 32.2 ml/min (13.9-45.4) and 0.65 (0.52-0.78). CONCLUSIONS: Currently used algorithms overestimate GFR in hospitalised patients with CKD. As a consequence eGFR targeted prescriptions of renal-cleared drugs, might expose patients to overdosing. The best results were obtained with the Larsson algorithm. The determination of muscle mass by bioimpedance did not provide significant contributions.

Preoperative undetectable serum thyroglobulin in differentiated thyroid carcinoma: incidence, causes and management strategy.

BACKGROUND: In recent years serum thyroglobulin (Tg) measurement during thyroxine (T4) treatment and/or after stimulation by endogenous TSH or recombinant human TSH (rhTSH) has eclipsed other diagnostic procedures in managing patients with differentiated thyroid cancer (DTC). However, preoperative undetectable Tg was reported in up to 12% of patients affected by DTC and recurrences of DTC with no increase in serum Tg have also been described. Clearly, a negative Tg measurement may falsely reassure both the patient and the clinician in these cases. AIM: We retrospectively evaluated the incidence of undetectable or reduced preoperative serum Tg in a group of 436 patients affected by DTC. Additionally, we evaluated the role of Tg retesting by two different immunoassays in patients with low Tg at first measurement. METHODS: We retrospectively selected 17 patients with undetectable (i.e. less than functional sensitivity of assay method) or reduced Tg (i.e. between functional sensitivity and minimum normal value) among 436 patients with histologically proved DTC. The remaining 419 patients were used as control cases. Frozen sera from all patients were retested by two different Tg immunoassays. RESULTS: Globally, 17 out of 436 (3.8%) patients showed undetectable (n = 5, 1.1%) or reduced (n = 12, 2.7%) preoperative Tg. The Tg level was above the minimum normal value in 3 and 4 out of 5, and 8 and 9 out of 12 of these patients, respectively, when two different immunoassays were employed. On the other hand, undetectable or reduced Tg levels were found in 3.0%-5.1% of control cases when different immunoassays were used. CONCLUSIONS: Regardless of the method employed, 3.0-5.1% of patients with DTC showed undetectable or reduced preoperative Tg. This fact must be recognized, as Tg cannot be used as a benchmark for DTC follow-up in these cases. However, Tg retesting with different immunoassays seems to be useful in ruling out these pitfalls in a large majority of patients, and also indicates the most effective assay to be employed in these cases.