GA Genotype of the Arg280His Polymorphism on The XRCC1 Gene: Genetic Susceptibility Genotype in Differentiated Thyroid Carcinomas?

Differentiated thyroid carcinomas (DTC) are the most common form of endocrine malignancies. The role of genetic variations in the development of papillary thyroid carcinoma (PTC) is approximately 60.0-70.0%. The X-ray repair cross-complementing group 1 (XRCC1) protein has an important role in DNA repair mechanisms and genomic polymorphisms of XRCC1 gene affect the function of the protein. In the present case-control study, we aimed to compare the genotype frequency distributions of XRCC1 single nucleotide polymorphisms (SNPs) in terms of the presence of other risk factors (Hashimoto's thyroiditis, smoking, obesity, radiation exposure) in patients with thyroid nodules who had fine-needle aspiration biopsy (FNAB) and/or thyroid surgery due to thyroid cancer. The genotype frequency distributions of three common XRCC1 SNPs (Arg194Trp, Arg399Gln, Arg280His) were compared to those with DTC (n = 228), benign thyroid nodules (BTN, n = 100) and healthy controls (n = 93) in terms of certain pre defined risk factors such as the presence of Hashimoto's thyroiditis, smoking, obesity, a family history of thyroid cancer and radiation exposure. The frequency of the GA genotype of Arg280His in DTC cases was found to be higher than in those with BTN and the healthy control group (p <0.001). The DTC group had the lowest frequency of AA genotype of Arg280His (35.5%, p <0.001). Among those with a family history of thyroid cancer, 78.9% had a GA genotype and 21.1% had the AA genotype of Arg280His (p = 0.004). The Arg280His GA genotype was more common in DTC than in cancer-free controls. The GA genotype frequency was also high in DTC cases with a family history of thyroid cancer.

Posttransplant Diabetes Mellitus Incidence and Risk Factors in Adult Liver Transplantation Recipients.

AIM: Posttransplant diabetes mellitus (PTDM) is a metabolic complication that usually occurs after liver transplantation (LT) due to immunosuppression. In this study, our aim was to identify PTDM incidence after LT in our center and the potential risk factors. MATERIALS AND METHODS: In this study, 238 adult LT patients were evaluated in terms of PTDM development. RESULTS: Of 238 patients included in the study, 170 (71.4%) were male, 68 (28.6%) were female and the mean age was 43.5± 13.7 years. Of all patients, PTDM developed in 24 (10.1%). Transient-Hyperglycemia (t-HG) was detected in 31 (13%) patients. PTDM and t-HG patients had a greater body weight than non-PTDM patients (BMI kg/m2: 27.6± 5.3, 25.8± 4.3and 23.9± 3.3, respectively p<0.001 p= 0.028). PTDM and t-HG patients mean age was higher than non-PTDM patients (51.5± 9.68, 48.2± 11.1 and 41.5± 14 years, respectively, p= 0.002 p= 0.023). In the univariate analysis, the only independent risk factor for PTDM was age (OR 1.93, 95% CI 1.31-2.97). CONCLUSION: Age is the most important risk factor for PTDM development after LT. PTDM was found more common in the patient group with greater body weight. Patients with older age and greater body weight should be examined more carefully for PTDM before LT.

ABDOMINAL BIOELECTRIC IMPEDANCE FOR FOLLOW-UP OF DIETERS: A PROSPECTIVE STUDY.

CONTEXT: Visceral adipose tissue (VAT) is a strong predictor of carbohydrate metabolism disorders. Abdominal bioelectrical impedance analysis (A-BIA) is a simple method for the measurement of VAT and is a promising tool in screening and follow-up of abdominal obesity. However the role of A-BIA in dieting individuals has not been evaluated adequately in longitudinal follow-up studies. OBJECTIVE: The aim of this study is to determine the role of A-BIA in identifying the changes in metabolic predictors after diet and/or exercise therapy. DESIGN: All patients who sought weight loss treatment underwent baseline assessment and were prescribed a program of diet. After a mean follow-up of 3.2 months, data were analyzed. SUBJECTS AND METHODS: Ultimately, 103 participants who reported adhering to the diet, enrolled to the study. We tested associations between changes in body composition measures and changes in laboratory measures using correlations and multivariate linear regression analysis. RESULTS: Mean loss of body weight was 3.4±2.8 kg. All but waist-to-hip ratio, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels changed significantly (p<0.001). Decreases in body weight, body mass index (BMI), and VAT level significantly correlated with decreases in fasting blood glucose, fasting insulin level, and HOMA-IR score (r=0.230-0.371). In multiple linear regression analysis changes in BMI and VAT significantly correlated with change in HOMA-IR score (F(7.93)=2.283, p=0.034, R2=0.147). CONCLUSION: Decreases in BMI and VAT, as determined by A-BIA, were predictors of changes in metabolic laboratory measures. A-BIA is useful for follow-up of patients receiving diet therapy for weight loss.

FAT DISTRIBUTION AND METABOLIC PROFILE IN SUBJECTS WITH HASHIMOTO'S THYROIDITIS.

CONTEXT: Previous studies have associated overt/subclinical hypothyroidism and obesity but have failed to confirm a causative relationship between them. Confusion is even more for subjects with Hashimoto's Thyroiditis (HT). OBJECTIVE: In this study, we aimed to evaluate the fat distribution and metabolic profile of subjects with euthyroid HT as well as to establish an appropriate cut-off level of TSH for the development of metabolic syndrome (Mets) in both groups. PATIENTS AND METHODS: All subjects were euthyroid whether under levothyroxine replacement or not. We recruited 301 volunteers (99 with HT and 202 without thyroid autoimmunity). Together with some metabolic variables, we measured the waist circumference, hip circumference, neck circumference manually; the total body fat with a body composition analyzer; and the visceral fat/trunk fat percentage via abdominal bioelectrical impedance analysis. RESULTS: A significant positive correlation was established between TSH levels and insulin, fasting plasma glucose, HOMA-IR and body mass index (r=0.28; p<0.001; r=0.27; p<0.05: r=0.32; p<0.001: r=0.13; p<0.05 respectively). The prevalence of Metabolic Syndrome (Mets) was comparable in HT and control groups (27.3% vs. 30.7%; p>0.05). The prevalence of Mets was similar when HT subjects using levothyroxine or HT subjects with accompanying thyroid nodules were taken into consideration. Similarly, anthropometric and metabolic parameters were similar in both the HT group and the control group.We were unable to establish the TSH cut-off level by ROC analysis with desired sensitivity and specificity (AUC: 0.563 with 95% C.I. p=0.35; standard error 0.76). CONCLUSIONS: Although weight gain is frequently encountered in subjects with HT, such subjects with thyroid function tests in the euthyroid range have a similar prevalence of Mets and similar metabolic and anthropometric measurements compared to subjects without autoimmunity.

Acromegaly is protective for periodontal tissue - advanced chronic periodontitis is rare in acromegalics.

BACKGROUND: Acromegaly is a complex syndrome which influences the connective tissue and bone metabolism. Although the effects of excess growth hormone on bone tissue are well known, its effect on periodontal tissue is an enigma. METHODS: A total of 23 acromegalic patients (mean age 48.13 ± 9.4 years) were included randomly in to this cross-sectional study. The control group consisted of 60 healthy (mean age 50.3 ± 8.5) individuals. All participants were examined by the same periodontist to evaluate periodontal disease status. RESULTS: We studied a group of 23 acromegalic patients (11 females, 12 males) with estimated duration of disease from minimum of one year to 10 years (mean 4.52 ± 2.9 years). The frequency of advanced chronic periodontitis in acromegalics was significantly lower than in the healthy group (p = 0.002). Advanced periodontitis was 10 times more frequent in healthy population than in the acromegalics. CONCLUSIONS: Advanced chronic periodontitis is 10 times less frequent in acromegalics than in healthy population. Acromegaly is a disease which seems to be protective for periodontal tissue (Tab. 4, Ref. 30).

Newly diagnosed hyperglycemia and stress hyperglycemia in a coronary intensive care unit.

AIMS: To determine prevalence of newly diagnosed hyperglycemia (NDH) among patients with acute coronary disease, inquire relationship of stress hyperglycemia (SH) with functional outcomes. METHODS: Admission (APG) and first morning fasting plasma glucose (FPG) measurements were obtained, capillary glucose measurements (CGM) every 6-h within first day were performed-Group 1: Normoglycemics. Group 2: NDH cases: No known diabetes, APG>200mg/dl and/or FPG>126 and/or any of CGM>200. Group 2a: unrecognized glycemic disorder, HbA1c>6.0%. Group 2b: stress hyperglycemia, HbA1c<6.0%. Group 3: Recognized diabetes. Duration of ICU stays, APACHE-II scores were recorded. Logistic regression analysis was performed using ICU stay as dependent variable and age, groups, co-morbidities, problems in hospital, APACHE-II scores, CGMs were used as independent risk factors. RESULTS: There were 255 (51.6%) in Group 1, 82 (16.6%) in Group 2; 37 (7.5%) cases in Group 2a, 45 (9.1%) in Group 2b and 157 (31.8%) in Group 3. Group 2b spent longer time in ICU, had higher APACHE-II scores (p=0.0001, p=0.0001). Regression analysis demonstrated SH as an independent risk factor for duration of ICU stay (OR: 2.8, 95% CI: 1.3-6.2). CONCLUSIONS: Hyperglycemia was present in 48.4%; 16.6% had NDH, 9.1% had SH. Poor functional conditions of SH cases pointed that they need to be considered carefully.

Two-year follow-up of thirty-two non-functional benign adrenal incidentalomas.

OBJECTIVE: To evaluate the risk of developing endocrine hyperactivity and carcinoma during a period of up to 5 yr in patients with apparently benign and non-functioning adrenal incidentalomas. PATIENTS AND METHODS: Thirty-two patients (mean age: 57.0+/-8.3 yr) were investigated in a prospective follow-up study for a median time of 24 months. Twenty-eight patients had unilateral and 4 had bilateral masses. Initial average mass diameter was 17.47+/-6.60 mm. All patients were followed up yearly by physical examination, metabolic parameters, hormonal evaluation [morning cortisol after 3-mg dexamethasone suppression, urinary metanephrines, and upright aldosterone/ plasma renin activity (PRA)]. RESULTS: Among the clinical characteristics, 48% of patients were obese, 20% were hypertensive, 13 had Type 2 diabetes and impaired glucose tolerance. During follow-up period no significant change in the functional status was observed and nomalignant transformation occurred. Only 1 patient developed subclinical Cushing's syndrome at the end of the 1st year and referred to surgery. Change in mass size was correlated with homeostasis model assessment of insulin resistance (p=0.002), upright aldosterone/ PRA (p=0.041), cortisol after dexamethasone suppression (p=0.048) and 24-h urinary normetanephrine (p=0.005) levels. Gender, body mass index, glucose metabolism, and blood pressure were not found to be correlated with change in mass size and functional status. CONCLUSIONS: Due to the extremely low risk of developing malignancy during up to 5 yr of follow-up, conservative approach for the management of adrenal incidentalomas is thought to be appropriate. However, possibility of evolution to hormonal hypersecretion makes long-term follow-up of 2-to-5 yr seems to be obligatory.

Systolic pulmonary artery pressure and echocardiographic measurements in patients with euthyroid Hashimoto's thyroiditis.

BACKGROUND: The aim of this study was to investigate systolic pulmonary artery pressure (SPAP) and echocardiographic findings in patients with euthyroid Hashimoto's thyroiditis (HT). METHODS: Thirty (8 male, 22 female, mean age 47.4+/-10.5 yr) consecutive patients with euthyroid HT and 30 (9 male, 21 female, mean age 46.4+/-10.7 yr) healthy controls were included in the study. Transthoracic echocardiography was performed for all patients and levels of thyroid hormones, thyroid autoantibodies, glucose, insulin, urea, and creatinine were compared. RESULTS: There were no significant differences in sex, age, body mass index, serum free T4, serum TSH, lipid profiles between patients and controls. Mean SPAP in patients with euthyroid HT were significantly higher than in controls (31.6+/-5.0 vs 25.6+/-4.5 mmHg, p=0.005). Late diastolic transmitral velocity and isovolumic relaxation time were also significantly higher in patients in comparison to controls. In addition, euthyroid HT patients with tricuspid or mitral regurgitation had a higher grade. Correlation between SPAP and antithyroid antibodies and TSH, however, was not significant in this population. CONCLUSIONS: Pulmonary arterial pressure is higher in patients with euthyroid HT. There may be a relationship between elevated pulmonary arterial pressure and autoimmune thyroid disease independent from thyroid function status. However, further investigations are needed to determine the exact mechanism of association between autoimmune thyroid diseases and pulmonary hypertension.

Unresectable huge sternal and mediastinal metastasis of follicular thyroid carcinoma; radiotherapy as first-line and palliative therapy.

Distant metastases as initial manifestation of follicular thyroid carcinoma is rare. We report a case of an unusual initial presentation of follicular thyroid carcinoma on follow-up. A 52- year-old woman presented with a 12-month history of progressively enlarging mass in the anterior chest wall. The mass was fixed to the chest wall, measuring 12 x 10 cm in diameter. Computed tomography demonstrated a lobulated soft-tissue mass (17 x 11 x 6 cm) destructing sternum and extending into the anterior mediastinum. There was no lung metastasis. Invasion of tumor to the ascending aorta, superior vena cava, and right atrium could not be excluded. Multiple lymph nodes were observed in the supraclavicular regions. Ultrasonography of the thyroid gland showed 46 x 37 mm nodule in the left lobe with milimetric gross calcifications and cystic-necrotic areas. Hyperthyroidism was detected. Biopsy from this nodule and the sternal mass revealed typical histology of follicular carcinoma. She was considered inoperable. Since there was huge tumor burden and iodinated contrast exposure for several times during evaluation, we decided to treat the patient with external beam radiotherapy (EBRT) rather than radioiodine as first-line therapy. After a course of conventional radiation with 50 Gy in 25 fractions over 4 weeks, encompassing the thyroid bed and the gross disease, tumor regressed remarkably in 6 months. In conclusion, when surgical resection is not possible, EBRT may be used for palliative purpose to obtain local control for extensive disease as first-line therapy. The indications of EBRT for differentiated thyroid cancer still remain poorly defined.

Acute effects of orlistat on postprandial serum leptin levels in nondiabetic obese patients.

AIM: Leptin is likely to be involved in the homeostasis of body weight. This study aimed to examine the acute effects of orlistat on postprandial serum glucose, insulin, and leptin levels before any effect on body weight occurred. METHODS: Thirty-four nondiabetic, obese patients were enrolled in this study (body mass index, 35.7+/-3.8 kg/m(2)). Patients were randomly assigned to two groups, one receiving orlistat (120 mg, single dose), and the other received a placebo. A single dose was given before a standard 600-kcal mixed meal containing 60% carbohydrates, 25% lipids, and 15% protein. Blood samples were collected basally before the test meal and then hourly for five hours. Graphic tendencies, peak values, time needed to reach the peak values, and area under the curve values were compared between groups. RESULTS: There were no differences in sex distribution, mean age, anthropometric measurements, and basal glucose, insulin, and leptin levels between the orlistat and placebo groups. Hourly serum glucose and insulin changes were similar between groups, peak levels of insulin occurred in the first hour in control group, although peak levels of insulin did not occur until the second hour in patients in the orlistat group. Also, serum leptin levels had a more horizontal and delayed increase after a mixed meal in patients in the orlistat group than they did in patients in the placebo group. There were no statistically significant differences between the groups. CONCLUSION: One dose of 120 mg orlistat made no changes in postprandial serum glucose, insulin, and leptin levels, although leptin-level increases were smaller in patients receiving orlistat.

High prevalence of neuropathy in patients with impaired 60-minute oral glucose tolerance test but normal fasting and 120-minute glucose levels.

AIM: The aim of this study was to define the prevalence of neuropathy in patients with impaired 60-min oral glucose tolerance test (OGTT) but normal fasting and 120-min glucose levels and to evaluate risk factors for polyneuropathy and glucose intolerance. METHODS: The hospital files of 320 patients (56.5+/-11.9 years, 73.1% female), who had both electrodiagnostic test for sensory symptoms (nerve conduction studies and needle electromyography) and OGTT in maximum 6 months apart, were studied in this retrospective design study. Serum glucose levels at fasting and 0-, 30-, 60-, 90- and 120-min of OGTT and some biochemical parameters were recorded. RESULTS: Fifteen percent of patients had diabetes mellitus (DM) and 10.9% and 5.6% had impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Twenty-one patients (6.6%) had only impaired 60-min blood glucose levels. Polyneuropathy was found in 44.4%, 28.5%, and 50.0% of patients with IGT, IFG and DM respectively. The prevalence of polyneuropathy was significantly higher in patients with impaired 60-min than OGTT normal subjects (52.4% vs 21.7% p=0.003). Fasting blood glucose, HDL, LDL and TSH levels, age, glucose intolerance low serum folic acid and significantly increased polyneuropathy risk. Age, weight, body mass index, high fasting, 30, 60-, 90-, 120-min serum glucose, insulin and HgA1c levels were risk factors for glucose intolerance. CONCLUSION: Since the prevalence of neuropathy in patients with impaired 60-min glucose levels is high, it would be valuable to look at 60-min glucose levels to detect abnormal glucose metabolism and the neuropathy earlier in the course.

Subclinical hypothyroidism is characterized by increased QT interval dispersion among women.

OBJECTIVE: Increased QT interval dispersion (QTd) is an electrocardiographic parameter shown to be associated with malignant ventricular arrhythmias and sudden death, and QT dispersion corrected for heart rate (QTc) has emerged as a potentially important predictor of cardiac death. Increased QTd has been detected to be directly related to thyroid-stimulating hormone (TSH) levels in overt hypothyroidism, however not much is known about subclinical hypothyroidism (SH). This study was conducted to investigate the QTc in SH and determine the changes following normalization of TSH levels with L-thyroxine. SUBJECTS AND METHODS: Fifty-eight women with naive SH due to Hashimoto's thyroiditis, mean age 39.37 +/- 10.43 years, and 54 age-, sex- and weight-matched controls with normal TSH were included after exclusion of any factor that might interfere with cardiac conductibility. Electrocardiographic measurements were performed with a magnifier and Bazett's formula was used to calculate QTc. The patients were separated into two groups regarding basal TSH levels (subgroup A: 5 > TSH > 10 mIU/l, n = 36; subgroup B: TSH > 10 mIU/l, n = 22). L-Thyroxine 1-2 microg/kg/day was administered to subgroup B. RESULTS: Mean QTc interval of the study group was significantly longer than that of the control group (100 +/- 30 vs. 76 +/- 30 ms, p = 0.000). It was also longer in subgroup A (5 > TSH > 10 mIU/l, n = 36) and subgroup B (p = 0.001, p = 0.000, respectively). In subgroup B, following normalization of serum TSH, mean post-treatment QTc measurement was similar to that of the control group (75 +/- 40 vs. 76 +/- 30 ms, p > 0.05). CONCLUSION: We detected prolonged QTc among SH cases. Prolongation remained significant for the whole group as well as the two subgroups. The differences in QTc were corrected when TSH levels of >10 mIU/l returned to normal.

Prevalence and prediction of malignancy in cytologically indeterminate thyroid nodules.

OBJECTIVE: Controversy surrounds the evaluation of nodules with indeterminate cytology results. Malignancy rates in these nodules are not low. We examined the malignancy rates in nodules that showed follicular neoplasm or atypical cells on cytology and attempted to predict malignancy based on ultrasonographic features. DESIGN AND PATIENTS: We retrospectively analysed 5 years' cytopathology results of fine-needle aspiration biopsy (FNAB) specimens of indeterminate follicular thyroid lesions prior to thyroidectomy. The prevalence of malignancy on final histology was determined. The sonographic features of the thyroid nodules with respect to size, echogenicity, echo structure, border shape and presence of calcification were analysed. RESULTS: A total of 86 patients (15 men, 61 women; mean age 52.1 +/- 12.5 years) with indeterminate cytology underwent thyroidectomy and had histopathological diagnoses. The average nodule was 18.9 +/- 12.3 mm. The prevalence of malignancy in patients with atypical cell cytology was 51.7% (30 of 59), and the prevalence of malignancy in patients with follicular neoplasm cytology was 15% (4 of 27). Malignancy prevalence was higher in patients who had follicular neoplasm cytology with atypical cells than in those without atypical cells (2 of 7 and 2 of 20, respectively). We found no significant correlations between sonographic or clinical features and malignancy in this patient group. Sonographic features and nodule size are not useful predictors of malignancy. CONCLUSION: Until better molecular markers for malignancy are developed, surgical consultation remains necessary after examination of cytologically indeterminate FNAB specimens in patients with follicular thyroid lesions. But in follicular lesions without atypical cells the malignancy rate is low and reassessment later on could be an alternative approach.

Thyroid cancer in hyperthyroidism: incidence rates and value of ultrasound-guided fine-needle aspiration biopsy in this patient group.

Three hundred and thirty-three hyperthyroidism cases were retrospectively investigated to provide information about the association between hyperthyroidism and thyroid cancer. There were 112 cases of toxic multinodular goiter (TMNG), 77 cases of toxic nodular goiter (TNG) and 144 cases of Graves' disease (GD). All nodules detected in GD patients, all nodules greater than 1 cm diameter in nodular goiter patients, nodules 5-10 mm size diameter if they had calcification were fine-needle biopsied (FNAB) under ultrasound guidance (US-guided), and a total of 612 such biopsies were performed. The biopsy samples were cytologically assessed as benign (no.=552; 90.2%), suspicious (no.=6; 1.1%), malignant (no.=13; 2.1%), or inadequate for diagnosis (no.=41; 6.7%). All patients with a biopsy diagnosis of malignant or suspicious nodules underwent surgery. Histological examination confirmed the diagnosis of thyroid cancer in all 13 (2.1%) patients with malignant FNAB findings. Papillary thyroid carcinoma (PTC) was identified in 2 patients with TMNG (%1.8), 5 with TNG (%6.5) and 5 with GD (%3.5). Metastatic follicular thyroid carcinoma (FTC) was identified in a patient with TNG. Thyroid malignancy (micro- or macrocarcinoma) was diagnosed pre-operatively in all 13 cases by US-guided FNAB. Thyroid cancer was diagnosed in 6 (5.5%) of the 109 nodules detected in the TNG group, 2 (0.44%) of the 452 nodules detected in the TMNG group, and 5 (9.8%) of the 51 nodules detected in the GD group. Two (2.6%) of the 77 functioning nodules in the TNG patients were malignant, but none of the 402 functioning nodules in the TMNG patients was malignant. In patients with hyperthyroidism, US-guided FNAB is useful for detecting thyroid cancer in nodules greater than 5 mm diameter before radioiodine therapy or surgery.

Thermolabile methylenetetrahydrofolate reductase enzyme genotype is frequent in type 2 diabetic patients with normal fasting homocysteine levels.

OBJECTIVE: To investigate the plasma homocysteine concentrations with regard to nutritional, metabolic and genetic factors and to find out the frequency and impact of thermolabile methylenetetrahydrofolate reductase (T-MTHFR) polymorphism in patients with type 2 diabetes mellitus. DESIGN: A cross-sectional study. SUBJECTS: A total of 94 subjects with type 2 diabetes mellitus and 91 healthy age- and sex-matched nonsmoking volunteers were recruited. MAIN OUTCOME MEASURES: Age, sex, duration and complications of diabetes mellitus, metabolic variables, fasting plasma homocysteine levels, and presence of T-MTHFR polymorphism were evaluated for all participants. Presence of T-MTHFR polymorphism was analysed to define any possible role in diabetes progress, complications and metabolic milieu. RESULTS: Fasting homocysteine levels were similar in diabetic patients and controls. Prevalence of homozygous polymorphism of thermolabile MTHFR gene (TT) was encountered more frequently in patients with diabetes mellitus than the healthy controls (P = 0.004). Subgrouping of the patients with respect to MTHFR genotype revealed similar metabolic variables and frequency of chronic complications of diabetes mellitus in groups. Patients with TT genotype revealed longer diabetes duration when compared with the patients having heterozygous mutation of thermolabile MTHFR or normal homozygous MTHFR genotypes (P = 0.046). CONCLUSIONS: Type 2 diabetic patients have similar fasting plasma homocysteine levels with that of age- and sex-matched healthy people. There is no correlation between diabetic complications and this amino acid metabolite. On the contrary, thermolabile variant of MTHFR genotype is found to be more frequent in diabetic patients especially in those who have experienced a longer duration of disease.

Factors associated with bone metabolism in acromegalic patients: hypogonadism and female gender.

The purpose of the study was to determine the factors associated with bone metabolism in acromegalic patients. Thirty three patients with acromegaly who had been followed on a regular basis in the endocrinology clinic were enrolled for the study. Among the factors acting upon bone metabolism, age, gender, body mass index (BMI), duration and activity of the disease, length of remission, treatment modalities and functional status of the pituitary were evaluated. Their influences on the determinants of bone remodelling and bone mineral density (BMD) were tried to be elucidated. The median age of the 33 acromegalics (19 females, 14 males) was 39.73 +/- 10.1 years. Twenty-three patients (9 males and 14 females) were eugonadal. Ten patients had been diagnosed with history of at least one year of untreated hypogonadism (5 males and 5 females; for 1 - 10 years). The BMD values of the lumbar vertebrae, the femur and the radius were correlated with each other. Patients were grouped according to their T-scores as decreased, normal, and increased BMD. Groups were similar with regard to age, BMI, gender, duration of disease, and remission, GH, IGF-1, IGFBP-3 levels, markers of bone turnover. Presence of hypogonadism and duration of hypogonadism revealed statistically significant difference among the 3 groups (p = 0.005 and p = 0.035, respectively). Hypogonadal acromegalic patients had decreased BMD compared to eugonadal acromegalics and healthy population while the eugonadal female acromegalic patients revealed increased BMD of lumbar vertebrae, femur, and distal radius compared to the sex-matched healthy population.

Influence of 1,25-dihydroxyvitamin D3 as an immunomodulator in renal transplant recipients: a retrospective cohort study.

Many studies suggest that 1,25-dihydroxyvitamin D3 (1,25-[OH](2) D3) and its analogues are potent dose-reducing drugs for other immunomodulators, helping to prevent graft rejection. In this study, we retrospectively grouped renal transplant recipients into two cohorts based on 1,25-[OH](2) D3 use to analyze the immunomodulatory effects. Ninety-two subjects were initially enrolled: group A (n = 43) recipients who had osteoporosis and were treated with 1,25-[OH](2) D3, and group B (n = 49) was a control group. We evaluated the effects on the number of acute rejection episodes, the immunosuppressive drug doses, serum calcium levels, and overall graft survival. Although before treatment the number of acute rejection episodes was statistically higher among group A than group B patients, after introduction of 1,25-[OH](2) D3, the difference became nonsignificant. This study showed that osteoporotic renal transplant recipients experienced fewer acute rejection episodes after 1,25-[OH](2) D3 treatment.

Effects of sibutramine in obese female subjects with type 2 diabetes and poor blood glucose control.

OBJECTIVE: In this study, we evaluated the efficacy of sibutramine in combination with hypoglycemic drugs in obese type 2 diabetic women whose glucose levels were poorly regulated. RESEARCH DESIGN AND METHODS: Female patients with type 2 diabetes, poorly controlled glucose levels, and HbA(1c) >8% were randomly assigned to one of two groups. In addition to their prescribed hypoglycemic agents (maximum doses of sulfonylureas and metformin), one group (n = 30) received a placebo twice daily for 6 months and the other (n = 30) received sibutramine 10 mg b.i.d. for the same period. RESULTS: One patient in the sibutramine group was excluded during the study period because of hypertension; thus, a total of 29 data sets were analyzed for this group. In the placebo group, five patients had to be excluded because of low treatment efficacy, leaving a total of 25 who completed the study. Comparing the changes that occurred over 6 months in the sibutramine and placebo groups, the former showed significantly greater reductions in fasting blood glucose (P < 0.0001), second-hour postprandial blood glucose (P < 0.0001), insulin resistance (P < 0.0001), waist circumference (P < 0.0001), BMI (P < 0.0001), HbA(1c) (P < 0.0001), diastolic blood pressure, pulse rate, uric acid levels, and all elements of the lipid profile except HDL cholesterol and apolipoprotein A1. CONCLUSIONS: The addition of sibutramine to oral hypoglycemic therapy resulted in significant weight loss and improvement in metabolic parameters in this patient group. Sibutramine is an effective adjunct to oral hypoglycemic therapy in obese women with type 2 diabetes.

Unusual case of metastatic thyroid nodule: nonpalpable breast mass as origin.

OBJECTIVE: To document a case of thyroid cancer metastatic from the breast. METHODS: We present the clinical, laboratory, radiologic, and biopsy findings in our patient and review the related literature. RESULTS: A 47-year-old female patient was referred to our clinic because of dyspnea and generalized bone pain. Physical examination revealed a diffusely enlarged nodular goiter, and fine-needle aspiration biopsy demonstrated intrathyroidal anaplastic cells. Total thyroidectomy was done, and the histopathologic diagnosis was anaplastic carcinoma. Unexpected rapid progression of the disease with cervical and intrathoracic lymphadenopathies and osteoblastic metastatic lesions without radioiodine uptake prompted us to attempt to rule out a primary nonthyroidal malignant lesion metastatic to the thyroid gland. The plasma level of CA 15-3 was profoundly increased (388 U/mL). Detailed reassessment of the patient disclosed a small mass in the right mammary gland with histopathologic features similar to those of the thyroidectomy material. Reevaluation of the thyroid specimens resulted in a final diagnosis of primary breast carcinoma in conjunction with metastatic carcinoma of the thyroid. CONCLUSION: Thorough systemic clinical assessment of a patient with a thyroid nodule and careful study of biopsy specimens should be done to ascertain whether the nodule is a primary or a metastatic lesion.

Chlamydia pneumonia seropositivity correlates with serum fibrinogen and lipoprotein a levels: any role in atherosclerosis?

The aim of the study is to determine the impact of Chlamydial seropositivity on atherosclerosis in a group of patient requiring coronary and/or carotid revascularization. A population of 30 diabetic patients (group 3) and 26 nondiabetic patients (group 2) with angiographically documented coronary and/or carotid artery disease were enrolled for the study. Volunteers from the relatives of hospital staff with no known disease (n=29; group 1) were included as the control group. Serum samples from the participants were assayed for cardiovascular risk factors including total serum cholesterol, triglyceride and lipoprotein levels, fibrinogen, Hb A1c levels and IgG titers for Chlamydia pneumonia (C. pneumonia). Chlamydial seropositivity was analysed further to determine a possible impact on atherogenesis. Serum LDL cholesterol levels revealed statistically significant difference between groups 1 and 2 (p=0.001). There was no difference between groups 2 and 3 regarding LDL cholesterol levels. There was no significant difference among the groups with respect to C. pneumonia seropositivity and the other atherosclerotic risk factors. Chlamydial seropositivity was found to be more frequent in males than in females (p=0.008). In the C. pneumonia seropositive group, serum fibrinogen and lipoprotein a levels were found to be significantly higher than the seronegative group (p=0.0001 and p=0.001, respectively). Other atherogenic risk factors were similar in the seropositive and negative groups. The causal role of Chlamydial infections in atherosclerotic plaque formation might be due to their influence on the serum fibrinogen and lipoprotein a levels.