Gokhan Ozgen

Effect of Weight Loss on Bone Metabolism: Comparison of Vertical Banded Gastroplasty and Medical Intervention

Background: We studied the effects of weight loss on bone metabolism. Methods: 16 consecutive surgically-treated (14 female, 2 male) morbidly obese patients and 65 obese (53 male, 12 female) medically-treated patients were enrolled in an observational study. Surgical treatment for morbidly obese patients was vertical banded gastroplasty (VBG). Studies were performed prior to and 12 months after the start of treatment. Bone mineral density (BMD), bone turnover markers, sex steroids, calcium excretion and parathyroid hormone measurements were done at each visit. Results: Weight loss was more prominent with surgical than with medical treatments. Bone loss was also pronounced in the surgical treatment group, and occurred at the hip level only (P<0.05). Compared to previously reported studies, where the effects of malabsorptive treatments for obesity on bone metabolism were studied, calcium excretion and parathyroid hormone levels did not change after VBG or medical therapy. For both groups, bone markers indicated an increased bone turnover, evidenced by increased urinary excretion of deoxypyridinoline and serum levels of osteocalcin (P<0.05). Sex steroid measurements revealed a decrease in estradiol levels in the surgical treatment group, but not in medical treatment group. This finding was thought to be secondary to less weight loss in the medical group. Conclusion: Our data indicate that weight loss causes bone loss. The bone loss is independent of the method of weight reduction. However, the mechanism of the bone loss is not clear. It may be explained partly by reduced estradiol levels in female patients. Because the mechanisms of bone disease after weight loss remain unclear, it is difficult to determine the most effective treatment. It is important to detect osteopenia early, before fractures occur. Measuring BMD appears to be the only reliable method for screening.

Thyrotoxic autoimmune encephalopathy in a female patient: Only partial response to typical immunosuppressant treatment and remission after thyroidectomy

Hashimotos encephalopathy (HE) is a rare immune-mediated encephalopathy developing in patients with high serum concentrations of anti-thyroid antibodies usually in an euthyroid or hypothyroid state. We report a 31-year-old female patient with thyrotoxic HE whose daughter has been followed up with the same diagnosis. Suboptimal response was observed with intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIG) and plasmapheresis. Reduction of the anti-thyroid auto-antibody concentrations marked the patients improvement in each episode. She relapsed under oral immunosuppressive therapy. After removing the thyroid tissue, full recovery has been achieved for the last 18 months. These data may contribute to clarification of the pathogenetic role of anti-thyroid antibodies in HE. Thyroidectomy can be considered as one of the treatment options especially in thyrotoxic HE patients with uncontrolled relapses. Our patient is the first reported HE case with a family history. Genetic background can underlie the etiopathogenesis of HE as is the case in other autoimmune disorders.

The Interaction of Oxidative Stress Response with Cytokines in the Thyrotoxic Rat: Is There a Link?

Oxidative stress is regarded as a pathogenic factor in hyperthyroidism. Our purpose was to determine the relationship between the oxidative stress and the inflammatory cytokines and to investigate how melatonin affects oxidative damage and cytokine response in thyrotoxic rats. Twenty-one rats were divided into three groups. Group A served as negative controls. Group B had untreated thyrotoxicosis, and Group C received melatonin. Serum malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and nitric oxide derivates (NO•x), and plasma IL-6, IL-10, and TNF-alpha were measured. MDA, GSH, NO•x, IL-10, and TNF-alpha levels increased after L-thyroxine induction. An inhibition of triiodothyronine and thyroxine was detected, as a result of melatonin administration. MDA, GSH, and NO•x levels were also affected by melatonin. Lowest TNF-alpha levels were observed in Group C. This study demonstrates that oxidative stress is related to cytokine response in the thyrotoxic rat. Melatonin treatment suppresses the hyperthyroidism-induced oxidative damage as well as TNF-alpha response.

Assessment of Insulin Resistance in the Idiopathic Hirsutism

Background: Idiopathic hirsutism (IH) is the second most common cause of hirsutism, after polycystic ovary syndrome and occurs in about 15% of hirsute women. There are not many studies showing whether patients with IH also have insulin resistance. In the present study, we aimed to investigate the insulin sensivity in IH with non-obese and changing hormone levels during the hyperinsulinemic-euglycemic clamp. Methods: Twenty (20) non-obese women with IH (Group I) ranging in age from 20 to 30 (mean 25 ± 5) years were studied. Hirsutism in women with normal testosterone (T) levels and regular menstrual cycles is as defined IH. Twenty (20) healthy women (mean age 23 ± 2 years) (Group II) were included in this study as the control group. Insulin sensitivity was assessed with modified euglycemic insulin clamp technique. Samples of prolactin, luteinizing hormone (LH), follicle-stimulating hormone, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, cortisol, estradiol, progesterone, 17-OH progesterone (17-OHP), total T, and free T (FT) were obtained at baseline and at 2nd hour during clamp. Results: Steady-state (120 min) glucose disposal rates were higher in Group II than Group I (7.51 ± 0.83 vs. 5.76 ± 1.89 mg/kg/min). Mean FT, ACTH, cortisol, LH, prolactin and 17-OHP levels were found to have decreased statistically significantly (p < 0.05) in Group I. Mean FT, ACTH, and prolactin levels were found to have decreased statistically significantly (p < 0.05) in Group II during the clamp. Mean baseline levels of FT, LH and prolactin were greater in women with hirsutism than in the control subjects (p < 0.05). Insulin mediated glucose disposal was lower in the normal weight women with IH than in those without hirsutism. Conclusions: Mean FT, 17-OHP and dehydroepiandrosterone sulfate levels decreased during euglcemic-hyperinsulinemic clamp in IH.

Ret proto-oncogene mutations in apparently sporadic Turkish medullary thyroid carcinoma patients: Turkmen study.

Objective: Medullary thyroid carcinoma (MTC) frequently occurs in a sporadic form, but a substantial number of cases are hereditary and appear as part of the multiple endocrine neoplasia type 2 (MEN2) syndromes. Germline mutations in ret proto-oncogene have been shown to be the underlying cause of MEN2 syndromes. Design: We carried out a multi-center study that aimed to perform mutational analysis of so called sporadic MTC patients. Methods: Fifty-six MTC patients verified by histopathologic examination were subjected to genetic analysis. Exon 10, 11, 13, 14, 15 and 16 of the ret gene were analyzed by DNA sequencing and restriction enzyme digestion method. Results: Among 56 apparently sporadic MTC patients, we identified 6 (10.7%) ret germline mutation carriers. Three individuals carried mutations at codon 634 in exon 11, one at codon 618 in exon 10, and two at codon 804 in exon 14. Identification of the predisposition gene mutation has allowed DNA-based strategy for direct mutation detection in patients with apparently sporadic MTCs. A substantial number of patients with apparently sporadic MTC carried germline mutations and 50% of their first degree relatives are expected to have or to develop MTC and/or other endocrine tumors. Conclusions: These results indicate the importance of careful genetic surveillance of any patient with apparently sporadic MTCs.

The role of allopurinol on oxidative stress in experimental hyperthyroidism

Aim: During hyperthyroidism, production of free oxygen radicals derives, where xanthine oxidase may also play an important role. Allopurinol, a xanthine oxidase inhibitor, has a significant effect on thyrotoxicosis-related oxidative stress. However, the relationship between thyroid hormones, oxidative stress parameters and allopurinol remains to be explored. Methods: Forty-two Wistar albino rats were divided into three groups. Rats in group A served as negative controls, while group B had untreated thyrotoxicosis and group C received allopurinol. Hyperthyroidism was induced by daily 0.2 mg/kg L-thyroxine intraperitoneally in groups B and C; 40 mg/kg allopurinol were given daily intraperitoneally. Efficacy of the treatment was assessed after 72 h and 21 days, by measuring serum xanthine oxidase (XO), malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and nitric oxide derivates (NO·x). Results: In both time periods, serum XO, MDA, GSH and NO·x levels were significantly increased after thyroid hormone induction (p<0.05). Levels of XO, MDA and NO·x decreased with allopurinol treatment (p<0.05). There was a remarkable decrease in triiodothyronine levels in group C after 72 h (p<0.05), and in both triiodothyronine and thyroxine levels in group C after 21 days (p<0.05). There was no difference between groups B and C in means of serum GSH, GR and GPx levels (p>0.05). Conclusions: This study suggests an association between allopurinol and the biosynthesis of thyroid hormones. Allopurinol prevents the hyperthyroid state, which is mediated predominantly by triiodothyronine and not by XO. This issue has to be questioned in further studies where allopurinol is administered in control subjects.

SERUM PROLACTIN LEVELS IN BEHCET'S SYNDROME

Abstract: Since prolactin (PRL) has been implicated as playing a role in the pathogenesis of certain autoimmune diseases and since Behçet’s Syndrome (BS) is a unique systemic vasculitis, we investigated serum PRL levels in patients with BS. We found that mean PRL levels in patients with clinically active BS, were not significantly higher than patients with clinically inactive BS and healthy controls. This finding may be regarded as evidence that a contribution of hyperprolactinemia to the aetiopathogenesis of BS seems unlikely.

The relationship of the apolipoprotein E gene polymorphism in Turkish Type 2 diabetic patients with and without nephropathy.

Objective: Apolipoprotein E (ApoE) genetic variation which is a major constituent of plasma lipoproteins causes diabetic nephropathy progress. Chronic kidney disease is associated with increased E2 allele and the decreased E4 allele risk. The aim of this study was to investigate the association between ApoE gene polymorphism in the development of diabetic nephropathy in Type 2 diabetes Turkish patients. Research design and methods: The objective of the study is to investigate the influence of ApoE gene polymorphism in the development of diabetic nephropathy in Turkish Type 2 diabetes. The ApoE genotypes were determined retrospectively in 46 patients with nephropathy and 56 without nephropathy and a control group of 35 healthy individuals. Genomic DNA was extracted from peripheral leukocytes of the subjects using the High Pure PCR Template Preparation Kit. For the detection of the presence of the three ApoE E alleles ε2, ε3, and ε4 (codon 112 and 158) were analyzed by the commercial LightCycler ApoE Mutation Detection Kit. Results: No differences in ApoE genotype or the allelic frequencies of ε2, ε3 or ε4 were found between the Type 2 diabetic patient group (with and without nephropathy) and a control group. Conclusions: We conclude that the ApoE gene polymorphism is not associated with the development of diabetic nephropathy in Turkish Type 2 diabetic patients. Lack of association between ApoE gene polymorphism and Type 2 diabetic nephropathy might be due to ethnic differences.

Dehydroepiandrosterone and human adipose tissue

Objective: The aim of this study was to investigate whether DHEA alters the proliferation and differentiation of human sc and visceral adipose cells in primary cultures. Method: Sc and omental adipose tissue was obtained from 10 female donors aged 36±3.6 yr with a body mass index (BMI) of 33±3.21 kg/m2. Stromal vascular cells were isolated and cultured using modified procedures described by Entenmann and Hauner. For the proliferation assay, stromal-vascular cells from sc and visceral adipose tissue cultures were fed with proliferation media containing 0, 25 or 100 μM DHEA for 3 days. At the end of this treatment period, two type cultures were prepared for determining their metabolic activity using the sulforhodamine B staining procedure. Results: The metabolic activity of proliferating human visceral adipose tissue was higher than sc adipose tissue. The activity of proliferating human visceral tissue cultures decreased more than the sc tissue as the level of DHEA in the cultures was increased. Conclusions: These data suggest that DHEA predominantly influences the proliferation and differentiation of human omental adipose tissue.

A novel CYP11B1 mutation in a Turkish patient with 11β-hydroxylase deficiency: An association with the severe hypokalemia leading to rhabdomyolysis

ABSTRACT Congenital adrenal hyperplasia is an autosomal recessive disorder caused by the loss of one of five steroidogenic enzymes affecting cortisol synthesis. In deficiency of 11 β- hydroxylase, 11-Deoxycortisol cannot be converted to cortisol and deoxycorticosterone cannot be converted to corticosterone. We present our 11β-hydroxylase deficiency case with hypokalemia and with a novel mutation. A 20-year-old male patient who’d been on steroid replacement treatment for adrenal insufficiency for 18 years was admitted with spasm, dyspnea and syncope attacks. On laboratory examination his potassium level was 1.4 meq/L and creatinine kinase and myoglobin levels were increased indicating rhabdomyolysis. Potassium infusion was started. 11 β- hydroxylase deficiency related congenital adrenal hyperplasia was diagnosed as the patient had adrenal insufficiency, hypertension and hypokalemia. Spironolactone treatment was started in addition to potassium infusion. Potassium levels were back to normal in the follow-up. Hypokalemia-related rhabdomyolysis regressed. In CYP11B1 whole genome sequencing analysis, p.A199P and p.R448H compound heterozygous mutation was detected. Thus, these two compound heterozygous mutations may be associated with the severity of the disease.