Hasan Altunbas

The effect of body weight and weight loss on thyroid volume and function in obese women

objective Thyroid volume and thyroid function may vary in obese and nonobese women. It is not known whether weight loss could affect thyroid volume and function in obese subjects.

Incretins: their physiology and application in the treatment of diabetes mellitus.

Therapies targeting the action of incretin hormones have been under close scrutiny in recent years. The incretin effect has been defined as postprandial enhancement of insulin secretion by gut‐derived factors. Likewise, incretin mimetics and incretin effect amplifiers are the two different incretin‐based treatment strategies developed for the treatment of diabetes. Although, incretin mimetics produce effects very similar to those of natural incretin hormones, incretin effect amplifiers act by inhibiting dipeptidyl peptidase‐4 (DPP‐4) enzyme to increase plasma concentration of incretins and their biologic effects. Because glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone with various anti‐diabetic actions including stimulation of glucose‐induced insulin secretion, inhibition of glucagon secretion, hepatic glucose production and gastric emptying, it has been evaluated as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM). GLP‐1 also manifests trophic effects on pancreas such as pancreatic beta cell growth and differentiation. Because DPP‐4 is the enzyme responsible for the inactivation of GLP‐1, DPP‐4 inhibition represents another potential strategy to increase plasma concentration of GLP‐1 to enhance the incretin effect. Thus, anti‐diabetic properties of these two classes of drugs have stimulated substantial clinical interest in the potential of incretin‐based therapeutic agents as a means to control glucose homeostasis in T2DM patients. Despite this fact, clinical use of GLP‐1 mimetics and DPP‐4 inhibitors have raised substantial concerns owing to possible side effects of the treatments involving increased risk for pancreatitis, and C‐cell adenoma/carcinoma. Thus, controversial issues in incretin‐based therapies under development are reviewed and discussed in this manuscript. Copyright

Insulin resistance in chronic hepatitis C

Aim:  Insulin resistance (IR), glucose intolerance and diabetes mellitus are commonly associated with cirrhosis. The exact pathogenetic mechanisms responsible are still unknown; however, they may be related to both hepatitis C virus itself and to liver injury. IR may be the earliest abnormality, which in the following years may progress to clinical diabetes mellitus. The aim of this study was to investigate the presence of IR by euglycaemic hyperinsulinemic clamp technique, in chronic hepatitis C patients.

Differentiated thyroid carcinoma in children and adolescents. Clinical characteristics, treatment and outcome of 15 patients.

Background: Thyroid carcinoma in childhood and adolescence is uncommon and because of the slow progression of disease the standard treatment is controversial. The aim of this study was to perform a retrospective analysis of treatment results for differentiated thyroid carcinoma in this age group treated in our clinic. Material and Methods: From August 1988 to February 2001, 15 patients between the ages of 8 and 21 years (average 16.8) were treated for differentiated thyroid carcinoma at Akdeniz University Medical School Departments of General and Pediatric Surgery. The patients included 10 (67%) females and 5 (33%) males. None of the patients had a previous positive history of head and neck irradiation. All patients, except 2, were euthyroid at the time of diagnosis. Results: Nine of the patients underwent total thyroidectomy and in 6 cases subtotal thyroidectomy was performed. There were multiple lymph node metastases in 4 (27%) patients and (various forms of) cervical lymph node dissections were performed in these patients. In addition, 2 children (13%) showed pulmonary metastasis. The incidence of surgical complications was 20% (1 permanent, 1 transient hypoparathyroidism and 1 permanent laryngeal nerve injury). Histological examinations revealed the following: papillary carcinoma in 9 (60%), follicular carcinoma in 5 (33%) patients, and Hurthle cell carcinoma in 1 (7%) patient. Postoperative radioiodine ablation was also added to treatment in 10 (67%) of the patients and all patients received L-thyroxine in suppressive doses. After a median follow-up period of 57 months (range 5–149), all patients are alive and disease-free. Conclusion: Our observations suggest that although most children and adolescents with differentiated thyroid carcinoma are seen with more extensive disease than adults, a total or subtotal thyroidectomy with an appropriate lymph node dissection followed by ablative radioiodine treatment carries a more favorable prognosis.

Comparison of Efficacy of Sibutramine or Orlistat Versus Their Combination in Obese Women

Objective: Sibutramine and orlistat are currently used for weight loss. We aimed to investigate the effect of orlistat and sibutramine combination therapy in treatment of obese women. Subjects and Design: Study population consisted of 89 obese women who had a body mass index ≥ 30 kg/m2, were normotensive, and had normal glucose tolerance. All patients were placed on a diet which contained fat approximately 30% of total calorie intake and the diet was designed to cause an energy deficit of approximately 2.51–3.56 megajoule/day. At the first month of diet (baseline), all patients were randomly divided into three therapy groups: Diet + Orlistat (group 1; n = 30 patients), Diet + Sibutramine (group 2; n = 29 patients), Diet + Orlistat + Sibutramine (group 3; n = 30 patients). Body weight, body fat distribution and serum lipid levels were evaluated baseline and after six months in all subjects. Results: Mean weight loss was 5.5 ± 4.9 kg (p = 0.024) in group 1, 10.1 ± 3.6 kg (p < 0.001) in group 2, 10.8 ± 6.6 kg (p < 0.001) in group 3 after the six months. Weight loss was significantly greater in group 2 (p = 0.003) and group 3 (p = 0.002) when compared with group 1. Percentage of mean weight loss was 5.5 ± 3.1% in group 1, 10.2 ± 4.8% in group 2, 10.6 ± 5.7% in group 3. Percentage of weight loss was higher in group 2 (p = 0.01) and group 3 (p = 0.009) when compared with group 1. Weight loss and percentage of weight loss were not different between group 2 and group 3. Conclusion: These three regimens had different results on weight loss in obese women. Combination drug therapy and sibutramine therapy were both more effective than orlistat therapy alone. However, no significant difference was noted between combination drug therapy and sibutramine treatment groups.

Incidental Thyroid Carcinoma in Thyrotoxic Patients Treated by Surgery

Background and Aims: Thyroid malignancy detected incidentally in patients who are operated for thyrotoxicosis has been reported at different rates. The aim of this study was to investigate the rate of incidental thyroid carcinoma in thyrotoxic patients managed with surgery in our institution. Methods: Of the 375 thyrotoxic patients who had thyroid surgery between the years of 1997–2004, 70.7% were females and 29.3% were males. Among thyrotoxic patients 65.3% (n = 245) had toxic multinodular goiter (TMG), 16.8% (n = 63) had toxic adenoma (TA) and 17.9% (n = 67) had Graves’ disease. Results: Twenty-six (6.9%) of all thyrotoxic patients had thyroid carcinoma. Eighteen (7.3%) of TMG, 4 (6.3%) of TA and 4 (6%) of Graves’ disease patients had thyroid carcinoma. Histologic examination revealed 18 papillary (9 microscopic), 5 follicular, 2 hurthle cell and 1 anaplastic carcinoma. Conclusion: In our study, incidental thyroid carcinoma was found in 6.9% of subjects with thyrotoxicosis. Papillary thyroid microcarcinomas constituted 34.6% (26/9) of these newly diagnosed thyroid carcinomas. The incidence of thyroid carcinoma was not higher in subjects with Graves’ disease compared to TMG and TA. The rate of incidental thyroid carcinoma in subjects with thyrotoxicosis treated with surgery was similar to previous studies reported from different countries.

Hypocalcemic Cardiomyopathy due to Untreated Hypoparathyroidism

Hypocalcemic cardiomyopathy due to hypoparathyroidism is a very rare condition which is usually refractory to conventional treatment for cardiac failure but which responds favorably to restoration of normocalcemia. A 55-year-old man and a 46-year-old woman with a history of postoperative hypoparathyroidism presented with symptoms of cardiac failure and hypocalcemia. A presumptive diagnosis of dilated cardiomyopathy was considered by echocardiography and endomyocardial biopsies were consistent with cardiomyopathy. The coronary angiograms were normal and there was no apparent cause for dilated cardiomyopathy in these patients. The history of the patients and partial recovery of cardiac function after restoration of normocalcemia suggest that hypocalcemia was the cause of dilated cardiomyopathy.

Molecular Mechanisms of Death Ligand-Mediated Immune Modulation : A Gene Therapy Model to Prolong Islet Survival in Type 1 Diabetes

Type 1 diabetes results from the T cell‐mediated destruction of pancreatic beta cells. Islet transplantation has recently become a potential therapeutic approach for patients with type 1 diabetes. However, islet‐graft failure appears to be a challenging issue to overcome. Thus, complementary gene therapy strategies are needed to improve the islet‐graft survival following transplantation. Immune modulation through gene therapy represents a novel way of attacking cytotoxic T cells targeting pancreatic islets. Various death ligands of the TNF family such as FasL, TNF, and TNF‐Related Apoptosis‐Inducing Ligand (TRAIL) have been studied for this purpose. The over‐expression of TNF or FasL in pancreatic islets exacerbates the onset of type 1 diabetes generating lymphocyte infiltrates responsible for the inflammation. Conversely, the lack of TRAIL expression results in higher degree of islet inflammation in the pancreas. In addition, blocking of TRAIL function using soluble TRAIL receptors facilitates the onset of diabetes. These results suggested that contrary to what was observed with TNF or FasL, adenovirus mediated TRAIL gene delivery into pancreatic islets is expected to be therapeutically beneficial in the setting of experimental models of type 1 diabetes. In conclusion; this study mainly reveals the fundamental principles of death ligand‐mediated immune evasion in diabetes mellitus. J. Cell. Biochem. 104: 710–720, 2008.

No effect of simvastatin treatment on insulin sensitivity in patients with primary hypercholesterolemia.

Objective. Statins, in addition to cholesterol lowering, have nonlipid effects on formation and progression of atheromatous plaque. Insulin resistance and hyperinsulinemia may have detrimental influences on the arterial wall. Statins (may also) inhibit insulin signal transferring in vascular smooth cell cultures. However, their effect on insulin sensitivity remains controversial. Therefore, we decided to investigate the effect of simvastatin on insulin sensitivity in hypercholesterolemic patients. Patients and Methods. Eighteen patients with primary hypercholesterolemia were divided into simvastatin group (n = 9; 4 females, 5 males; BMI 30.6 ± 4 kg/m2; mean ages 57 ± 6 years) and placebo group (n = 9; 4 females, 5 males; BMI 28 ± 2.9 kg/m2; mean ages 49 ± 10 years). Simvastatin (20 mg/day) or placebo were given for 2 months. Total and HDL cholesterol were measured and LDL cholesterol was calculated by Friedewald formula. Insulin sensitivity was determined by using euglycemic hyperinsulinemic clamp technique [40 µU/m2/min insulin infusion rate; glucose disposal rate (M) = mg/kg/min] before and after treatment. Results. Plasma levels of total, LDL and HDL cholesterol decreased significantly in simvastatin group after treatment (p = 0.000, p = 0.000, and p = 0.048, respectively). Plasma levels of total cholesterol decreased significantly (p = 0.032), whereas LDL and HDL levels remained unchanged in placebo group. M value (mg/kg/min) decreased insignificantly in simvastatin group (4.32 ± 1.57 vs. 3.71 ± 1.91) and increased in placebo group (3.55 ± 1.91 vs. 3.95 ± 0.95). Conclusion. Short‐term simvastatin treatment did not affect insulin sensitivity determined by “gold standard” euglycemic hyperinsulinemic clamp method in hypercholesterolemic patients in this research. Further studies with simvastatin using higher doses and longer duration should be performed.

EGFR and p53 expression and proliferative activity in parathyroid adenomas; an immunohistochemical study

EGFR (epidermal growth factor receptor), p53, and proliferative markers provide some clues as to the formation of several tumours. In this study the mechanism of the genesis of parathyroid adenomas was investigated using immunohistochemistry. Sections of parathyroid adenomas from 12 cases were stained using PCNA (proliferating cell nuclear antigen), EGFR, and p53 immunohistochemistry. Correlations between PCNA LI (labelling index), EGFR expression, p53 expression, age, serum parathormone, Ca and P levels, and tumour diameter were investigated. PCNA LI was 45.8±33.1 (mean±standard deviation) and all the cases were somewhat positive. Five cases (41.67 %) were EGFR positive. Maximum 10 % of the cells were positive in these cases. All the cases were p53 negative. There was a correlation between PCNA LI and serum parathormone level (r=0.607, p=0.036). According to these results, parathormone synthesis is high when the proliferative activity of parathyroid adenoma is high. Four of the five EGFR‐positive patients were below 35 years of age. These data may indicate that formation of parathyroid adenoma in young patients is related to a mechanism involving EGFR. Absence of p53 expression suggests that p53 mutation is not a common component of parathyroid adenomas.