Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study.

OBJECTIVE: Only few studies analysed the capability of cytology in detecting medullary thyroid cancer (MTC), and they reported a low accuracy of this diagnostic technique. Recently, calcitonin (CT) measurement in aspiration needle washout (FNA-CT) of thyroid and neck lesions has been reported as a sensitive tool for MTC. The aim of this study is to compare the sensitivity of FNA-CT and cytology in detecting MTC and to assess a cut-off value of FNA-CT for clinical practice. PATIENTS: Thirty-eight MTC lesions from 36 patients were retrospectively studied, diagnosed and treated in four different centres. Furthermore, 52 nonmedullary lesions from subjects undergone biopsy following increased serum CT were collected as a control group. RESULTS: Cytology detected MTC in 21/37 lesions with 56·8% sensitivity. The median FNA-CT value was 2000 pg/ml (range 58-10 000 pg/ml) in MTC and 2·7 pg/ml (range <2-13 pg/ml) in controls (P < 0·001). Using a cut-off of 39·6 pg/ml, MTC lesions could be identified with 100% sensitivity and specificity. As the most important finding, 14 histologically proved MTC lesions could be detected by FNA-CT, despite they were cytologically diagnosed as benign or nonconclusive. CONCLUSIONS: This study shows, as the first in a multicentre series, that FNA-CT sensitivity is higher than that of cytology in diagnosing MTC. To avoid false-negative MTC by cytology, CT measurement in aspiration needle washout is to be performed in all patients undergoing biopsy following high serum CT.

One in five subjects with normal thyroid ultrasonography has altered thyroid tests.

The relation between thyroid ultrasonography and laboratory, and the relationship of thyroid volume with clinical and anthropometric parameters, are not well clarified. Aim of the study was to investigate normal and hypoechoic-inhomogeneous not nodular thyroid gland in predicting thyroid tests, and to assess the correlation of thyroid volume with several clinical parameters. The series included 434 subjects (244 with normal thyroid ultrasonography, and 190 with hypoechoic-inhomogeneous thyroid) at their first evaluation. Subjects with normal ultrasonography and skewed tests were re-evaluated after one year. All subjects with normal ultrasound showed normal free-T4, while TSH was elevated in 9.8% of cases and thyroid antibodies were positive in another 9.8%. In patients with hypoechoic-inhomogeneous thyroid, free-T4 was low in 33.2%, TSH was elevated in 78.4% and thyroid antibodies were positive in 76.3%. Normal ultrasonography matched with normal tests in 81.1% of cases while hypoechoic-inhomogeneous thyroid in 9.5% (p<0.001). The re-evaluation of tests showed no significant difference. In subjects with both normal ultrasonography and tests, thyroid volume was correlated with age (p=0.001), weight (p=0.003), BMI (p=0.04), body surface area (p=0.002). Thyroid laboratory assessment was different between subjects with ultrasonographically normal or hypoechoic-inhomogeneous thyroid. Thyroid volume of thyroid diseases-free subjects was correlated with age, weight, BMI and body surface area, and this should be of interest to investigate the references of normality of thyroid size.

Should we use ultrasound features associated with papillary thyroid cancer in diagnosing medullary thyroid cancer?

In thyroid nodule management, ultrasound (US) features, such as hypoechogenicity of the lesion, irregular margins, microcalcifications, and intralesional vascular signal, alone or combined, have to be considered as suggestive for malignancy. Because of the low prevalence of medullary thyroid cancer (MTC), a few papers analyzed US characteristics associated with this cancer in small series, with controversial results. Aim of this study was to evaluate in MTC the US risk factors of thyroid nodule. In this order, a series of nodules histologically proven as MTC and a group of nodules with histology of papillary cancer (PTC) were retrospectively compared with a control group of benign nodule. Fifty percent MTC were solid hypoechoic and 16% showed microcalcifications with significant difference with respect to the benign group (p<0.05 for both parameters), while no significant difference was recorded regarding margins nor nodular vascularization. The presence of at least one US risk feature was almost equal in MTC (58.3%) and controls (55.5%). On the contrary, at least one US risk factor was significantly (p<0.001) more frequent in PTC than in benign group or MTC series. This study showed low frequency of ultrasound features associated to PTC when analyzed in medullary cancer. Because of the poor literature focusing on this topic, and the herein used design, these data contribute to the knowledge about presentation of MTC at US. We advice for further prospective studies on larger series to define the US presentation of this cancer type.

Insulin decreases intracellular oxidative stress in patients with type 2 diabetes mellitus.

Patients affected by diabetes mellitus have oxidative stress with an impaired glutathione (GSH) redox state. The objective of this study was to determine the influence of insulin on oxidative stress, defined as a reduced intracellular GSH/GSH disulfide (GSSG) ratio and lipid peroxidation by plasma thiobarbituric acid reactive substances (TBARSs) in patients with type 2 diabetes. Two experimental interventions were used: (1) measurement of GSH/GSSG ratio after insulin incubation in erythrocytes from 10 type 2 diabetic patients, and (2) measurement of intraerythrocytic GSH/GSSG ratio and plasma TBARS in 14 type 2 diabetic patients during an in vivo hyperinsulinemic condition obtained from a euglycemic hyperinsulinemic clamp study. We confirmed that our patients underwent oxidative stress as shown by the significant difference in intracellular GSH/GSSG ratio in diabetic patients as compared to controls (13.56+/-3.84 vs 27.89+/-8.37, P<.0001). We found a significant elevation in the GSH/GSSG ratio after 2 hours of incubation with insulin in erythrocytes from diabetic patients (11.56+/-1.98 to 15.61+/-2.62, P<.001). During the clamp studies, GSH/GSSG ratio had already increased after 60 minutes and even more after 120 minutes (baseline, 15.04+/-4.19; at 60 minutes, 19.74+/-6.33; at 120 minutes, 25.33+/-11.15; P<.0001). On the contrary, no significant changes were observed in plasma TBARS (3.59+/-0.77 to 3.56+/-0.83, NS). We conclude that insulin in patients with type 2 diabetes mellitus can reduce intracellular oxidative stress through increased GSH/GSSG ratio.

Endothelial dysfunction and oxidative stress in type 1 and type 2 diabetic patients without clinical macrovascular complications.

AIMS: To evaluate the relationship between oxidative stress and endothelial dysfunction (ED) in diabetic patients without clinical macrovascular complications. METHODS: In 27 type 1, 56 type 2 diabetic patients and 35 healthy controls the redox state (GSH, GSSG; enzymatic method), endothelin-1 (ET-1; ELISA) and von Willebrand factor (vWF; ELISA) plasma levels, urinary vascular endothelial growth factor (VEGF; ELISA) were measured. RESULTS: Decreased GSH levels (p<0.05, type 1 and type 2), GSH/GSSG ratio (p<0.05 type 1, p<0.001 type 2) and elevated vWF levels (p<0.001, type 1 and type 2) were observed in diabetic patients in comparison with controls. A negative correlation between GSH and vWF (p<0.02 and p<0.001, in type 1 and type 2, respectively) and GSH and BMI (p<0.02 in type 1 and type 2) was observed. ET-1 was positively correlated to age (p<0.05) and diabetes duration (p<0.03) in type 1, while vWF was correlated to systolic blood pressure (p<0.05) in type 2 diabetic patients. Urinary VEGF was higher in type 2 (p<0.05) in comparison with type 1 diabetic patients and was correlated to glycemia (p<0.05) and systolic blood pressure (p<0.05). CONCLUSIONS: These data might indicate that markers of oxidative stress and ED are altered in diabetic patients without clinical macrovascular complications.

Impairment of cell and plasma redox state in subjects professionally exposed to chromium.

BACKGROUND: Chromium (Cr) is widely used in chemical, tannery, building, and metal industries. More recently, it has been demonstrated that Cr induces oxidative stress in mouse brain. Nevertheless very few data exist on in vivo oxidative damage in humans exposed to Cr. METHODS: Changes in antioxidant parameters both in plasma (acid ascorbic redox state and total antioxidant capacity) and in red blood cells (glutathione (GSH) redox state) of 40 subjects (age 37.65 +/- 7.46; M/F 20/20) professionally exposed to Cr who were recruited from metal, chemistry, and building industries were evaluated. We also evaluated the levels of lipoperoxidation (thiobarbituric acid-reactive material, TBA-RM) and thiol levels in plasma to assess the extent of oxidative stress state. To evaluate Cr exposure rate, we measured urinary-chromium (U-Cr) by an electrothermic atomization-atomic absorption spectrometry (ETA-AAS) method. RESULTS: In this study, we found that Cr exposure induced a decrease both in GSH (P < 0.0005) and GSH/oxidized glutathione (GSSG) ratio (P < 0.0001) in red blood cells from workers with respect to control subjects. Furthermore, we also demonstrated a significant decrease of plasma acid ascorbic levels (45.7 +/- 14.9 vs. 53.5 +/- 16.5 micromol/L; P < 0.05) and in total plasma antioxidant capacity (1,126.3 +/- 212.2 vs. 1,266.9 +/- 207.8 micromol/L; P < 0.05) in subjects exposed to Cr. No difference was found with regard to TBA-RM and thiol levels. CONCLUSIONS: This study demonstrated that in humans, an oxidative stress occurs for Cr exposures as low as those considered safe. This oxidative stress appears to be able to affect intracellular and plasmatic antioxidant defense.