Impact of adjuvant chemotherapy in completely resected stage IIIA non-small cell lung cancer.

AIM: Outcome of patients with locally advanced non-small-cell lung cancer (NCSLC) is generally poor, with five-year survival rate of only 23%, when patients are treated with surgery only. The presentation of positive adjuvant therapy trials in NSCLC has changed clinical practice, doubling the number of patients with completely resected NSCLC referred for adjuvant chemotherapy since 2004. Furthermore, few large studies described a large number of stage III patients in non-Asiatic patients and they showed controversial results about survival in completely resected stage IIIA NSCLC. The objective of this study was to evaluate the impact of adjuvant chemotherapy in completely resected stage IIIA NCSLC, administered on a routine basis, outside clinical trials. METHODS: This is a retrospective study of patients with stage IIIA NCSLC treated between 1990 and 2008, and included in a continuous, consecutive database. Inclusion criteria were: age >18 years, complete surgical resection, and pathologically confirmed as stage IIIA. The following clinical data were obtained: age, gender, performance status, histological type, chemotherapy regimens, status at last follow-up and hospital where the treatment occurred. Kaplan-Meier's method was used to determine actuarial survival. Differences in survival were determined by Breslow and log rank analyses. RESULTS: According to these inclusion criteria, 415 patients were considered for the present study. The median follow-up time of all patients was 38.2 months. The adjuvant chemotherapeutic treatment affected survival significantly (P <0.001). Also the type of chemotherapeutic treatment affected survival (P ≤0.001). CONCLUSION: Cisplatin-based adjuvant chemotherapy was beneficial in patients who had a completed resected stage IIIA carcinoma.

Clinical features of patients with type 2 diabetes mellitus and hepatitis C infection

The objective of the present cross-sectional study was to assess the prevalence and the clinical and laboratory features of hepatitis C virus (HCV)-positive patients with type 2 diabetes mellitus (DM) attending either an outpatient clinic or hemodialysis units. Serologic-HCV testing was performed in 489 type 2 DM patients (303 outpatients and 186 on dialysis). A structured assessment of clinical, laboratory and DM-related complications was performed and the patients were then compared according to HCV infection status. Mean patient age was 60 years; HCV positivity (HCV+) was observed in 39 of 303 (12.9 percent) outpatients and in 34 of 186 (18.7 percent) dialysis patients. Among HCV+ patients, 32 were men (43.8 percent). HCV+ patients had higher serum levels of aspartate aminotransferase (0.90 ± 0.83 vs 0.35 ± 0.13 µKat/L), alanine aminotransferase (0.88 ± 0.93 vs 0.38 ± 0.19 µKat/L), gamma-glutamyl transferase (1.57 ± 2.52 vs 0.62 ± 0.87 µKat/L; P < 0.001), and serum iron (17.65 ± 6.68 vs 14.96 ± 4.72 µM; P = 0.011), and lower leukocyte and platelet counts (P = 0.010 and P < 0.001, respectively) than HCV-negative (HCV-) patients. HCV+ dialysis patients had higher diastolic blood pressure than HCV- patients (87.5 ± 6.7 vs 81.5 ± 6.0 mmHg; P = 0.005) and a lower prevalence of diabetic retinopathy (75 vs 92.7 percent; P = 0.007). In conclusion, our study showed that HCV is common among subjects with type 2 DM but is not associated with a higher prevalence of chronic diabetic complications.

Coronary artery calcification is associated with insulin resistance index in patients with type 1 diabetes.

The objective of the present study was to evaluate the risk factors associated with the presence of coronary artery calcification (CAC) in patients with type 1 diabetes (T1D). A cross-sectional study was conducted on 100 consecutive T1D patients without coronary artery disease, with at least 5 years of diabetes and absence of end-stage renal disease. Mean age was 38 ± 10 years and 57% were males. CAC score was measured by multidetector computed tomography (Siemens Sensation 64 Cardiac). The insulin resistance index was measured using the estimated glucose disposal rate (eGDR). The eGDR was lower among CAC-positive patients than among CAC-negative patients, suggesting an increased insulin resistance. In a logistic regression model adjusted for age (at 10-year intervals), eGDR, diabetic nephropathy and gender, CAC was associated with age [OR = 2.73 (95%CI = 1.53-4.86), P = 0.001] and with eGDR [OR = 0.08 (95%CI = 0.02-0.21), P = 0.004]. In T1D subjects, insulin resistance is one of the most important risk factors for subclinical atherosclerosis.

Coronary artery calcification is associated with insulin resistance index in patients with type 1 diabetes

The objective of the present study was to evaluate the risk factors associated with the presence of coronary artery calcification (CAC) in patients with type 1 diabetes (T1D). A cross-sectional study was conducted on 100 consecutive T1D patients without coronary artery disease, with at least 5 years of diabetes and absence of end-stage renal disease. Mean age was 38 ± 10 years and 57 percent were males. CAC score was measured by multidetector computed tomography (Siemens Sensation 64 Cardiac). The insulin resistance index was measured using the estimated glucose disposal rate (eGDR). The eGDR was lower among CAC-positive patients than among CAC-negative patients, suggesting an increased insulin resistance. In a logistic regression model adjusted for age (at 10-year intervals), eGDR, diabetic nephropathy and gender, CAC was associated with age [OR = 2.73 (95 percentCI = 1.53-4.86), P = 0.001] and with eGDR [OR = 0.08 (95 percentCI = 0.02-0.21), P = 0.004]. In T1D subjects, insulin resistance is one of the most important risk factors for subclinical atherosclerosis.

Effect of metabolic syndrome and of its individual components on renal function of patients with type 2 diabetes mellitus

The objective of this study was to evaluate the effect of metabolic syndrome (MetS) and its individual components on the renal function of patients with type 2 diabetes mellitus (DM). A cross-sectional study was performed in 842 type 2 DM patients. A clinical and laboratory evaluation, including estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease formula, was performed. MetS was defined according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Mean patient age was 57.9 ± 10.1 years and 313 (37.2 percent) patients were males. MetS was detected in 662 (78.6 percent) patients. A progressive reduction in eGFR was observed as the number of individual MetS components increased (one: 98.2 ± 30.8; two: 92.9 ± 28.1; three: 84.0 ± 25.1; four: 83.8 ± 28.5, and five: 79.0 ± 23.0; P < 0.001). MetS increased the risk for low eGFR (<60 mL·min-1·1.73 (m²)-1) 2.82-fold (95 percentCI = 1.55-5.12, P < 0.001). Hypertension (OR = 2.2, 95 percentCI = 1.39-3.49, P = 0.001) and hypertriglyceridemia (OR = 1.62, 95 percentCI = 1.19-2.20, P = 0.002) were the individual components with the strongest associations with low eGFR. In conclusion, there is an association between MetS and the reduction of eGFR in patients with type 2 DM, with hypertension and hypertriglyceridemia being the most important contributors in this sample. Interventional studies should be conducted to determine if treatment of MetS can prevent renal failure in type 2 DM patients.

Degree of catecholamine hypersecretion is the most important determinant of intra-operative hemodynamic outcomes in pheochromocytoma.

Pheochromocytoma resection is often complicated by intra-operative hypertension and post-resection hypotension. Factors associated with these hemodynamic alterations are not well defined. The aim of this study was to analyse the clinical-laboratory features associated with hemodynamic parameters during pheochromocytoma resection. Twenty-seven patients submitted to tumor resection - either open (no.=18) or video laparoscopic - between 1978-2007 were included. Nineteen received pre-operative alpha-blockers. Intra-operative hemodynamic data analysed were: maximum and minimum mean arterial blood pressure (MABP), no. of severe hypertensive (systolic BP >200 mmHg) and hypotensive episodes (MABP <60 mmHg), maximum and minimum heart rate (HR), no. of episodes of tachycardia and bradycardia, need to receive iv intra-operative treatment for hypertension and hypotension and the volume of fluids administered during surgery. Patients were 39.4+/-14.4-yr-old, 66% women. Intra-operative hemodynamic parameters were not different in patients submitted to open or video laparoscopic resection. Maximum intraoperative HR and the percentage of patients with HR>100 beats/min were higher in patients without pre-operative alpha- blocker treatment (no.=8). Pre-operative urinary vanylmandelic acid was positively associated with intra-operative maximum MABP (r=0.535, p=0.047) and with maximum transoperative systolic BP (r=0.805, p=0.016). Pre-operative urinary catecholamine (Pearson correlation r=0.575, p=0.03) and vanylmandelic acid (Pearson correlation r=0.605, p=0.04) levels were associated with maximum intra- operative MABP, adjusted for the presence of pheochromocytoma symptoms, surgical approach and pre-operative alpha-blockers. In conclusion, the degree of pre-operative catecholamine secretion was the most important aspect of transoperative BP control.

The prevalence of chronic diabetic complications and metabolic syndrome is not associated with maternal type 2 diabetes

The maternal history of type 2 diabetes mellitus (DM) has been reported more frequently in patients with type 2 DM than paternal history. The aim of the present study was to determine if there was an association between maternal history of DM and the presence of chronic complications or metabolic syndrome (MetS) in patients with type 2 DM. A cross-sectional study was conducted with 1455 patients with type 2 DM. All outpatients with type 2 diabetes attending the endocrine clinics who fulfilled the eligibility criteria were included. Familial history of DM was determined with a questionnaire. Diabetic complications were assessed using standard procedures. The definition of MetS used was that of the World Health Organization and the National Cholesterol Education Program's Adult Treatment Panel III report criteria. Maternal history of DM was present in 469 (32.3 percent), absent in 713 (49.1 percent) and unknown in 273 patients (18.7 percent). Paternal history of DM was positive in 255 (17.6 percent), negative in 927 (63.8 percent) and unknown in 235 patients (16.1 percent). The frequency of microvascular chronic complications in patients with and without a positive maternal history of DM was similar: diabetic nephropathy (51.5 vs 52.5 percent), diabetic retinopathy (46.0 vs 41.7 percent), and diabetic sensory neuropathy (31.0 vs 37.1 percent). The prevalence of macrovascular chronic complications and MetS was also similar. Patients with type 2 DM were more likely to have a maternal than a paternal history of DM, although maternal history of DM was not associated with an increased prevalence of chronic complications or MetS.

Diabetic retinopathy is associated with early autonomic dysfunction assessed by exercise-related heart rate changes

Diabetic retinopathy has been associated with cardiac autonomic dysfunction in both type 1 and type 2 diabetes mellitus (DM) patients. Heart rate (HR) changes during exercise testing indicate early alterations in autonomous tonus. The aim of the present study was to investigate the association of diabetic retinopathy with exercise-related HR changes. A cross-sectional study was performed on 72 type 2 and 40 type 1 DM patients. Autonomic dysfunction was assessed by exercise-related HR changes (Bruce protocol). The maximum HR increase, defined as the difference between the peak exercise rate and the resting rate at baseline, and HR recovery, defined as the reduction in HR from the peak exercise to the HR at 1, 2, and 4 min after the cessation of the exercise, were determined. In type 2 DM patients, lower maximum HR increase (OR = 1.62, 95 percentCI = 1.03-2.54; P = 0.036), lower HR recovery at 2 (OR = 2.04, 95 percentCI = 1.16-3.57; P = 0.012) and 4 min (OR = 2.67, 95 percentCI = 1.37-5.20; P = 0.004) were associated with diabetic retinopathy, adjusted for confounding factors. In type 1 DM, the absence of an increase in HR at intervals of 10 bpm each during exercise added 100 percent to the odds for diabetic retinopathy (OR = 2.01, 95 percentCI = 1.1-3.69; P = 0.02) when adjusted for DM duration, A1c test and diastolic blood pressure. In conclusion, early autonomic dysfunction was associated with diabetic retinopathy. The recognition of HR changes during exercise can be used to identify a high-risk group for diabetic retinopathy.

Vascular complications of black patients with type 2 diabetes mellitus in Southern Brazil.

Ethnicity has been shown to be associated with micro- and macrovascular complications of diabetes in European and North American populations. We analyzed the contribution of ethnicity to the prevalence of micro- and macrovascular complications in Brazilian subjects with type 2 diabetes attending the national public health system. Data from 1810 subjects with type 2 diabetes (1512 whites and 298 blacks) were analyzed cross-sectionally. The rates of ischemic heart disease, peripheral vascular disease, stroke, distal sensory neuropathy, and diabetic retinopathy were assessed according to self-reported ethnicity using multiple logistic regression models. Compared to whites, black subjects [odds ratio = 1.72 (95%CI = 1.14-2.6)] were more likely to have ischemic heart disease when data were adjusted for age, sex, fasting plasma glucose, HDL cholesterol, hypertension, smoking habit, and serum creatinine. Blacks were also more likely to have end-stage renal disease [3.2 (1.7-6.0)] and proliferative diabetic retinopathy [1.9 (1.1-3.2)] compared to whites when data were adjusted for age, sex, fasting plasma glucose, HDL cholesterol, hypertension, and smoking habit. The rates of peripheral vascular disease, stroke and distal sensory neuropathy did not differ between groups. The higher rates of ischemic heart disease, end-stage renal disease and proliferative diabetic retinopathy in black rather than in white Brazilians were not explained by differences in conventional risk factors. Identifying which aspects of ethnicity confer a higher risk for these complications in black patients is crucial in order to understand why such differences exist and to develop more effective strategies to reduce the onset and progression of these complications.

Vascular complications of black patients with type 2 diabetes mellitus in Southern Brazil

Ethnicity has been shown to be associated with micro- and macrovascular complications of diabetes in European and North American populations. We analyzed the contribution of ethnicity to the prevalence of micro- and macrovascular complications in Brazilian subjects with type 2 diabetes attending the national public health system. Data from 1810 subjects with type 2 diabetes (1512 whites and 298 blacks) were analyzed cross-sectionally. The rates of ischemic heart disease, peripheral vascular disease, stroke, distal sensory neuropathy, and diabetic retinopathy were assessed according to self-reported ethnicity using multiple logistic regression models. Compared to whites, black subjects [odds ratio = 1.72 (95 percentCI = 1.14-2.6)] were more likely to have ischemic heart disease when data were adjusted for age, sex, fasting plasma glucose, HDL cholesterol, hypertension, smoking habit, and serum creatinine. Blacks were also more likely to have end-stage renal disease [3.2 (1.7-6.0)] and proliferative diabetic retinopathy [1.9 (1.1-3.2)] compared to whites when data were adjusted for age, sex, fasting plasma glucose, HDL cholesterol, hypertension, and smoking habit. The rates of peripheral vascular disease, stroke and distal sensory neuropathy did not differ between groups. The higher rates of ischemic heart disease, end-stage renal disease and proliferative diabetic retinopathy in black rather than in white Brazilians were not explained by differences in conventional risk factors. Identifying which aspects of ethnicity confer a higher risk for these complications in black patients is crucial in order to understand why such differences exist and to develop more effective strategies to reduce the onset and progression of these complications.

The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications

The aim of the present study was to analyze the frequency of K121Q polymorphism in the ENPP1 gene of Brazilian subjects according to ethnic origin and to determine its possible association with diabetes mellitus (DM) and/or diabetic complications. A cross-sectional study was conducted on 1027 type 2 DM patients and 240 anonymous blood donors (BD). Ethnicity was classified based on self-report of European and African descent. The Q allele frequency was increased in African descendant type 2 DM patients (KK = 25.9 percent, KQ = 48.2 percent, and QQ = 25.9 percent) and BD (KK = 22.0 percent, KQ = 53.8 percent, and QQ = 24.2 percent) compared to European descendant type 2 DM patients (KK = 62.7 percent, KQ = 33.3 percent, and QQ = 4.1 percent) and BD (KK = 61.0 percent, KQ = 35.6 percent, and QQ = 3.4 percent). However, there was no difference in genotype distribution or Q allele frequency between diabetic and non-diabetic subjects (European descendants: DM = 0.21 vs BD = 0.21, P = 0.966, and African descendants: DM = 0.50 vs BD = 0.51, P = 0.899). In addition, there were no differences in clinical, laboratory or insulin resistance indices among the three genotypes. The prevalence of DM complications was also similar. In conclusion, K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample.

High frequency of immature dendritic cells and altered in situ production of interleukin-4 and tumor necrosis factor-alpha in lung cancer.

INTRODUCTION: Antigen-presenting cells, like dendritic cells (DCs) and macrophages, play a significant role in the induction of an immune response and an imbalance in the proportion of macrophages, immature and mature DCs within the tumor could affect significantly the immune response to cancer. DCs and macrophages can differentiate from monocytes, depending on the milieu, where cytokines, like interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce DC differentiation and tumor necrosis factor (TNF)-alpha induce DC maturation. Thus, the aim of this work was to analyze by immunohistochemistry the presence of DCs (S100+ or CD1a+), macrophages (CD68+), IL-4 and TNF-alpha within the microenvironment of primary lung carcinomas. RESULTS: Higher frequencies of both immature DCs and macrophages were detected in the tumor-affected lung, when compared to the non-affected lung. Also, TNF-alpha-positive cells were more frequent, while IL-4-positive cells were less frequent in neoplastic tissues. This decreased frequency of mature DCs within the tumor was further confirmed by the lower frequency of CD14-CD80+ cells in cell suspensions obtained from the same lung tissues analyzed by flow cytometry. CONCLUSION: These data are discussed and interpreted as the result of an environment that does not oppose monocyte differentiation into DCs, but that could impair DC maturation, thus affecting the induction of effective immune responses against the tumor.

Expression of a dendritic cell maturation marker CD83 on tumor cells from lung cancer patients and several human tumor cell lines: is there a biological meaning behind it?

The present paper shows, for the first time, the membrane expression of the dendritic cell maturation marker CD83 on tumor cells from lung cancer patients. CD83 was also detected on freshly cultured fibroblast-like cells from these tissues and on several adherent human tumor cell lines (lung adenocarcinomas P9, A459 and A549, melanomas A375 and C81-61, breast adenocarcinomas SKBR-3 and MCF-7 and colon carcinoma AR42-J), but not in the non-adherent MOT leukemia cell line. CD83 may have immunosuppressive properties and its expression by cancer cells could have a role in facilitating tumor growth.

High-normal levels of albuminuria predict the development of micro- and macroalbuminuria and increased mortality in Brazilian Type 2 diabetic patients: an 8-year follow-up study.

AIM: To analyse the risk factors for the development of micro- and macroalbuminuria and mortality rates in a cohort of normoalbuminuric Type 2 diabetes mellitus (DM) patients. METHODS: In this prospective study, 193 Type 2 DM patients with urinary albumin excretion (UAE) < 20 microg/min, 96 men (50%), aged 56.5 +/- 9 years, were followed for a mean period of 8 +/- 3 years. UAE and estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) were measured. The outcomes were development of persistent micro- and macroalbuminuria and mortality. RESULTS: Twenty patients were lost to follow-up. Of the 173 remaining patients, 33 (19%) died. The Cox analysis [hazard ratio (HR), 95% confidence interval] revealed that the baseline significant predictors of mortality were higher UAE [above median (5 microg/min); HR 2.7, 1.2-6.1; P = 0.02], male sex (HR 3.9, 1.7-9.2; P = 0.002), age (HR 1.6, 1.3-1.9; P = 0.0001), and fasting plasma glucose (HR 1.2, 1.1-1.3; P = 0.004). Smoking and eGFR were not significant in this model. Follow-up renal data were available for 158 patients: 34 (22%) progressed to microalbuminuria and seven (4%) to macroalbuminuria, and the baseline predictors were a higher UAE (> 5 microg/min, HR 2.5, 1.2-5.1; P = 0.02), presence of diabetic retinopathy (HR 2.5, 1.3-5.0; P = 0.009), fasting glucose (HR 1.1, 1.0-1.2; P = 0.015), and male sex (HR 2.2, 1.1-4.7; P = 0.04), independently of smoking and hypertension. Lower GFR (HR 0.98, 0.97-1.00; P = 0.07) was of borderline significance. CONCLUSIONS: In normoalbuminuric Type 2 DM patients, the development of micro- or macroalbuminuria and mortality rates was independently and positively associated with higher levels of albuminuria, although still in the traditionally established normal range.

Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes.

Diabetic retinopathy is one of the leading causes of blindness in working-age individuals. Diabetic patients with proteinuria or those on dialysis usually present severe forms of diabetic retinopathy, but the association of diabetic retinopathy with early stages of diabetic nephropathy has not been entirely established. A cross-sectional study was conducted on 1214 type 2 diabetic patients to determine whether microalbuminuria is associated with proliferative diabetic retinopathy in these patients. Patients were evaluated by direct and indirect ophthalmoscopy and grouped according to the presence or absence of proliferative diabetic retinopathy. The agreement of diabetic retinopathy classification performed by ophthalmoscopy and by stereoscopic color fundus photographs was 95.1% (kappa = 0.735; P < 0.001). Demographic information, smoking history, anthropometric and blood pressure measurements, glycemic and lipid profile, and urinary albumin were evaluated. On multiple regression analysis, diabetic nephropathy (OR = 5.18, 95% CI = 2.91-9.22, P < 0.001), insulin use (OR = 2.52, 95% CI = 1.47-4.31, P = 0.001) and diabetes duration (OR = 1.04, 95% CI = 1.01-1.07, P = 0.011) were positively associated with proliferative diabetic retinopathy, and body mass index (OR = 0.90, 95% CI = 0.86-0.96, P < 0.001) was negatively associated with it. When patients with macroalbuminuria and on dialysis were excluded, microalbuminuria (OR = 3.3, 95% CI = 1.56-6.98, P = 0.002) remained associated with proliferative diabetic retinopathy. Therefore, type 2 diabetic patients with proliferative diabetic retinopathy more often presented renal involvement, including urinary albumin excretion within the microalbuminuria range. Therefore, all patients with proliferative diabetic retinopathy should undergo an evaluation of renal function including urinary albumin measurements.

Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes

Diabetic retinopathy is one of the leading causes of blindness in working-age individuals. Diabetic patients with proteinuria or those on dialysis usually present severe forms of diabetic retinopathy, but the association of diabetic retinopathy with early stages of diabetic nephropathy has not been entirely established. A cross-sectional study was conducted on 1214 type 2 diabetic patients to determine whether microalbuminuria is associated with proliferative diabetic retinopathy in these patients. Patients were evaluated by direct and indirect ophthalmoscopy and grouped according to the presence or absence of proliferative diabetic retinopathy. The agreement of diabetic retinopathy classification performed by ophthalmoscopy and by stereoscopic color fundus photographs was 95.1 percent (kappa = 0.735; P < 0.001). Demographic information, smoking history, anthropometric and blood pressure measurements, glycemic and lipid profile, and urinary albumin were evaluated. On multiple regression analysis, diabetic nephropathy (OR = 5.18, 95 percent CI = 2.91-9.22, P < 0.001), insulin use (OR = 2.52, 95 percent CI = 1.47-4.31, P = 0.001) and diabetes duration (OR = 1.04, 95 percent CI = 1.01-1.07, P = 0.011) were positively associated with proliferative diabetic retinopathy, and body mass index (OR = 0.90, 95 percent CI = 0.86-0.96, P < 0.001) was negatively associated with it. When patients with macroalbuminuria and on dialysis were excluded, microalbuminuria (OR = 3.3, 95 percent CI = 1.56-6.98, P = 0.002) remained associated with proliferative diabetic retinopathy. Therefore, type 2 diabetic patients with proliferative diabetic retinopathy more often presented renal involvement, including urinary albumin excretion within the microalbuminuria range. Therefore, all patients with proliferative diabetic retinopathy should undergo an evaluation of renal function including urinary albumin measurements.

Conditions associated with very low values of glycohaemoglobin measured by an HPLC method.

AIMS: To identify the causes of very low glycohaemoglobin (GHb) values in a sample of patients with diabetes in southern Brazil using high performance liquid chromatography. METHODS: Between August 1996 and December 2001 all samples from patients with diabetes at a university hospital with GHb values below the reference range (4.7-6.0% HbA(1c)) were submitted to cellulose acetate electrophoresis. Medical records were reviewed to identify conditions that might be associated with these low values. RESULTS: Among 29 657 samples analysed, 130 patients had GHb < 4.7%. Seventy three patients (56%) were heterozygous for HbS, HbC, or HbD (19 black, two mulatto, and 52 white patients). The other 57 patients (44%) without Hb variants had low haematocrit and haemoglobin values (42 patients) or other conditions such as pregnancy, lipaemia, malignancy, cirrhosis, acetylsalicylic acid use, and absence of diabetes (15 patients). CONCLUSIONS: The presence of an Hb variant may falsely lower GHb measurements. However, anaemia is also a source of negative interference. The haematological status should be considered for the correct interpretation of GHb results.

Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing's disease.

Transsphenoidal pituitary surgery is the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure, there is no agreement regarding the definition of successful treatment. We prospectively studied postoperative serum cortisol dynamics in 41 patients with CD (including a total of 45 surgeries). The mean postoperative follow-up period was 4.8 yr. Remission was defined as clinical and laboratory signs of adrenal insufficiency, glucocorticoid dependence, and serum cortisol suppression on overnight oral 1-mg dexamethasone suppression test. Serum cortisol was measured preoperatively and postoperatively at 6, 12, and 24 h (28 surgeries) and at 10-12 d (45 surgeries). No statistical difference was detected in mean preoperative and 6-h postoperative cortisol levels between surgically induced remission patients [22.1 +/- 7.73 microg/dl (610 +/- 213.3 nmol/liter) and 25.2 +/- 19 microg/dl (695.2 +/- 524.4 nmol/liter)] and surgical failure patients [23.6 +/- 6.95 micro g/dl (651.4 +/- 161.8 nmol/liter) and 37.5 +/- 18.1 microg/dl (1035 +/- 499.6 nmol/liter); P = 0.50 and P = 0.17]. At 12 and 24 h after surgery, the difference was significant (P = 0.009 and P < 0.0001). Mean cortisol levels were 12.44 +/- 13.3 microg/dl (343.3 +/- 367.1 nmol/liter) and 4.72 +/- 6.72 microg/dl (130.3 +/- 185.5 nmol/liter) in the remission group and 26.3 +/- 7.06 microg/dl (725.9 +/- 194.8 nmol/liter) and 23.5 +/- 6.86 microg/dl (648.6 +/- 189.3 nmol/liter) in the failure group (P = 0.009; P < 0.0001). At 10-12 d after the procedure, the difference was also significant (P < 0.0001): cortisol levels were 2.52 +/- 3.32 microg/dl (69.5 +/- 91.6 nmol/liter) in the remission group and 24.9 +/- 13.3 microg/dl (687.2 +/- 367.1 nmol/liter) in the failure group. In conclusion, in the immediate postoperative period of transsphenoidal surgery, remission of CD is not necessarily defined by undetectable serum cortisol. During the first 10-12 d after surgery, cortisol nadir correctly classified the remission [cortisol, 7.0 microg/dl (193.2 nmol/liter) or less] and the failure groups [cortisol, 8.0 microg/dl (220.8 nmol/liter) or more]. Glucocorticoid should be administered only after laboratory and/or clinical evidence of adrenal insufficiency.

Accuracy of ultrasonography to establish the diagnosis and aetiology of permanent primary congenital hypothyroidism.

OBJECTIVE: To compare ultrasonography and 99mTc thyroid scintigraphy for the aetiologic diagnosis of permanent congenital hypothyroidism (CH). STUDY DESIGN: Eighty-eight consecutive patients with CH were recruited at an endocrinology outpatient clinic and submitted to high-frequency ultrasonography and to 99mTc scintigraphy. RESULTS: Seventy-six patients were diagnosed with permanent CH and 12 with transitory CH. The agreement between ultrasound and scintigraphy was very high (kappa coefficient = 0.866; P < 0.001) for the entire group. In permanent CH patients, ultrasonography identified 67 cases of dysgenesis (absence of thyroid gland in the usual anatomical location in 66 and hemiagenesis in one), and this diagnosis was confirmed by scintigraphy (absence of functional thyroid tissue in 43 and ectopia in 24). In the other nine permanent CH patients, the thyroid was in the usual anatomical location on ultrasonography but scintigraphy did not identify functional tissue in one patient. In the 12 transitory CH patients, a normally shaped thyroid was detected by ultrasound in the usual location, whereas scintigraphy showed absence of functional tissue in two identical twins and scarce concentration of isotope in a third patient. CONCLUSION: Ultrasonography is an accurate method to establish the presence of dysgenesis and might be used as the first imaging tool in patients with CH, whereas scintigraphy should be used mainly to distinguish agenesis from ectopia. Further examination is required to differentiate permanent CH with a normally located and shaped gland from transitory hypothyroidism.