Nilgun Guvener

Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity

Aim: Some of our obese patients who were receiving 10u2003mg/day sibutramine reported feeling hunger at night. To address this, we designed a randomized, prospective clinical trial to study the efficacy and safety of 10u2003mg sibutramine twice daily (bid), and compare this treatment with 120u2003mg orlistat three times daily (tid) and 850u2003mg metformin (bid).

Detection of insulin resistance in Turkish adults: a hospital‐based study

Aim: The aim of the present study was to investigate the usefulness of insulin sensitivity check indices in our hospital population.

Ultrasound-guided fine-needle aspiration biopsy and ultrasonographic features of infracentimetric nodules in patients with nodular goiter: Correlation with pathological findings

We evaluated the usefulness of ultrasound-guided fine-needle-aspiration biopsy (US-FNAB) for infracentimetric nodules. In addition, we used sonography to assess the risk of malignancy of thyroid nodules, and we evaluated the extent of disease in infracentimetric cancers. The cytopathological results of 472 US-FNABs from 207 nodular goiter patients (170 women, 37 men; mean age, 51.5±13.1 yr) seen between 1999 and 2004 were categorized into five groups: inadequate, benign, suspicious, follicular neoplasm, and malignant. There were 145 infracentimetric nodules and 327 supracentimetric nodules. All patients underwent surgery. Final histopathological results correlated with cytologic results. The sensitivity, specificity, positive predictive value, negative predictive vallue, and accuracy of US-FNAB for infracentrimetric nodules were 96.3%, 71.2%, 44.8%, 98.8%, and 76.1%; and for supracentimetric nodules, these values were 98.1%, 63.1%, 35.6%, 99.4, and 69.1%, respectively. There were no significant differences between infracentimetric and supracentimetric nodules. More thyroid cancer could be detected in infracentimetric nodules that were hypoechoic or had fine calcification on ultrasonography (which may be helpful in discriminating which nodules are appropriate for FNAB) than in supracentimetric nodules. However, logistic regression analyses showed that no single variable was predictive of malignancy in infracentimetric nodules. The malignancy rate in infracentimetric nodules was 21.4%. In this subgroup, 4 of 31 patients (12.9%) had multifocal tumors at surgery, 3 of 31 had extrathyroidal invasion, and 1 had a metastasis to the lung. In addition, at surgery, 11 of 55 tumors (20%) larger than 1 cm were multifocal. In conclusion, small tumor size does not guarantee a low risk of thyroid cancer, and US-FNAB may be useful tool for diagnosing malignant infracentimetric nodules.

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.

Management of infracentimetric thyroid nodules with respect to ultrasonographic features

An assumed indolent course of thyroid microcarcinomas and concerns about the cost-effectiveness of treatment raise management issues. As various studies have reported controversial results, management remains unclear. The purpose of this study was to examine the use of ultrasonography (US) in detecting malignancies in a series of 589 infracentimetric nodules. Results of fine-needle aspiration biopsies (FNAB) revealed 503 nodules with adequate cytology. Of these, 473 (94%) were benign, 13 (2.6%) were suspicious for malignancy, 13 (2.6%) were malignant, and 4 (0.8%) were follicular neoplasms. Hypoechogenicity and accompanying lymphadenopathy were the independently significant features in detecting malignancies. Certain combinations of US features increase the significance and predictive value for malignant cytology particularly in the presence of lymphadenopathy. When the postoperative histological results of ten patients with a final diagnosis of papillary carcinoma were evaluated for extent of disease, seven (70%) had one or more of the findings of multifocality, metastatic lymph nodes, or extracapsular involvement, thus proving their clinical significance. Our results indicate that thyroid microcarcinomas should be taken seriously if there are possible signs of malignancy on US. With respect to the high benign nature of the micronodules (94%), the number of interventional procedures should be lowered by making assessments based on a combination of US features including lymphadenopathy.

The effect of single-dose orlistat on postprandial serum glucose, insulin and glucagon-like peptide-1 levels in nondiabetic obese patients.

Objectiveu2002 Glucagon‐like peptide‐1 is an insulin secretion‐stimulating gut hormone that is produced in response to food intake. Orlistat (Xenical, F. Hoffman‐La Roche, Basel, Switzerland), which decreases fat absorption and increases intestinal fat content, may therefore affect the secretion of glucagon‐like peptide‐1. In this study we examined the immediate effects of orlistat on postprandial serum glucose, insulin and glucagon‐like peptide‐1 levels prior to a change in body weight.

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.

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain silent. We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

Creatine kinase elevation in a patient taking rosiglitazone

Rosiglitazone maleate (Avandia) is a member of a new class of oral antidiabetic agents, the thiazolinediones, which enhance sensitivity to insulin in adipose tissue, liver, and skeletal muscle [1]. Pioglitazone, a member of the same class of drugs, has been reported to cause statistically significant increases in muscle creatine kinase (CK) levels [2]. To our knowledge, there have been no reports of the effects of rosiglitazone on muscle enzymes. Here, we report a patient receiving rosiglitazone in whom creatine kinase levels rose. A 31-year-old Turkish man was admitted in January 2001 because of malaise. He was not taking any medication. The patient denied tobacco, alcohol, and illicit drug use. Several members of his family had Type 2 diabetes mellitus. He had no personal history of blood transfusions, viral hepatitis, or autoimmune diseases and no family history of neuromuscular disease. Physical examination revealed no abnormality. Laboratory values at presentation were as follows: fasting plasma glucose 6.99 mmol/ l; alanine aminotransferase 64 IU/l (upper normal limit 41 IU/l); aspartate aminotransferase 41 IU/l (upper normal limit 40 IU/l); fasting plasma insulin 21.6 IU/ml; HOMAIR 5.5; and HbA 1c level 7%. Abdominal ultrasound showed hepatomegaly and increased hepatic echogenicity, with no evidence of biliary obstruction or dilation. The pancreas was normal. Liver biopsy revealed hepatosteatosis. After diet and exercise therapy, the patient was prescribed metformin 1500 mg/day and aspirin 100 mg/day. The patient’s lipid profile was within normal limits without lipid-lowering agents. Two years later, rosiglitazone 4 mg/day was added to the treatment. The dose of rosiglitazone was increased to 8 mg/day after 2 weeks. Two months after the initiation of rosiglitazone, the patient’s CK level was 746 IU/l (normal range 22–240 IU/l), although the patient did not complain of myalgia. The CK-MM isoform was elevated. Thyroid-stimulating hormone (thyrotropin; TSH) level was normal, aspartate aminotransferase was 26 IU/l (normal range 10–40 IU/l), and lactate dehydrogenase was 193 IU/l (upper limit 450 IU/l). Results of serological tests for viral hepatitis (HBsAg, HBsAb, HBcAb, anti-HAV IgM and IgG, and anti-HCV Ab) were negative. Serum creatinine level and results of an electrocardiogram were normal, and there were no signs of hypoglycaemia, hypokalaemia, or hypophosphataemia. Rheumatological screening studies, including erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibody, anti-native DNA, anti-smith, anti-ribonucleoprotein and anti-Ro studies, were all normal or negative. The rosiglitazone was discontinued immediately but metformin was continued. One month after the discontinuation of rosiglitazone, the patient’s CK level returned to normal. Because the patient walked for 45 min each day whilst taking rosiglitazone, we advised him not to exercise, and rosiglitazone (4 mg/day) was restarted. After 15 days, the patient’s CK level was again elevated, but no symptoms were reported by the patient. Rosiglitazone treatment was stopped again, and the patient’s CK level returned to normal. Results of the patient’s liver function tests were normal, and his CK levels remained within the normal range during follow-up (Table 1). Serum CK elevations can be due to a number of factors other than rosiglitazone, including exercise, muscle trauma, metabolic myopathies, muscular dystrophies, acute disease of the brain, medications other than rosiglitazone, alcoholism, hypothyroidism. All have been excluded by history, physical examination and laboratory data. In our patient, after reaching a maximum dose of rosiglitazone, plasma levels of CK were found to be elevated. The CK level returned to normal after discontinuation of the drug and was elevated again when the drug was restarted. Several cases of CK elevation and muscle pain have been reported with the use of pioglitazone [3]. During the period of CK elevation, our patient did not report muscle pain or tenderness. To our knowledge, this is the first report of CK elevation associated with rosiglitazone treatment. It is possible that CK elevation associated with rosiglitazone treatment may be a specific effect of this class of drug or the