Zeliha Hekimsoy

Serum Creatine Kinase Levels in Overt and Subclinical Hypothyroidism

The aims of this prospective study were to determine serum levels of creatine kinase (CK) in overt and subclinical hypothyroidism; to investigate the change in CK levels with treatment; and to evaluate the relationship between free triiodsothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) levels and the degree of skeletal muscle involvement, as determined by serum CK levels. Patients with hypothyroidism presenting to our endocrinology clinic were eligible for inclusion in this study. Patients with other causes of CK elevation were excluded. We included 28 patients (25 women and 3 men, ages 41.75 ± 13.65 years) with overt hypothyroidism, 38 patients (37 women, 1 man, ages 40.55 ± 10.48 years) with subclinical hypothyroidism, and 30 age- and gender-matched controls (27 women, 3 men, ages 40.81 ± 11.20 years) in the study. Serum levels of TSH, FT4, FT3, and CK were measured in all subjects. CK elevation was found in 16 patients (57%) with overt hypothyroidism and in 4 patients (10%) with subclinical hypothyroidism. Although a statistically significant elevation of CK levels was found in patients with overt hypothyroidism when compared with patients with subclinical hypothyroidism and controls (p = 0.0001, p = 0.01, respectively), no difference was found between the subclinical hypothyroidism and control groups (p = 0.14). In hypothyroid (overt and subclinical) patients, a positive correlation was found between CK and TSH (r = 0.432; p = 0.04), and a negative correlation between CK and FT3 (r = −0.556; p = 0.002) and between CK and FT4 (r = −0.448; p = 0.04). CK levels decreased to normal levels after thyroid function normalized with treatment. In conclusion, skeletal muscle is affected by hypothyroidism more profoundly in cases of overt hypothyroidism, less so when subclinical hypothyroidism is present.

Vitamin D status among adults in the Aegean region of Turkey

BackgroundVitamin D is a lipid-soluble hormone found in certain foods and synthesized from precursors in the skin when exposed to ultraviolet light. Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes and low levels have been associated with several chronic and infectious diseases. Vitamin D status is assessed by measuring the concentration of serum 25-hydroxyvitamin D [25(OH)D]. Vitamin D deficiency is reported to be common worldwide, but little has been reported about the vitamin D status of adults in Turkey. In this cross-sectional study, we determined the prevalence of 25(OH)D deficiency in adults residing in a city in the Aegean region of Turkey.MethodsA survey was conducted on a representative sample of adults over 20 years old in a non-coastal city at the end of the winter season. Of the 209 households selected by random sampling, 8.6% (n = 18) were unoccupied and 21.5% (n = 45) refused to participate. Blood samples were taken and questions about medical history, vitamin supplementation, sunlight exposure, and dietary calcium and vitamin D intake were asked in face-to-face interviews of 391 adults living in the remaining households.ResultsThe mean serum 25(OH)D concentration was 16.9±13.09 ng/mL, with 74.9% of the subjects having 25(OH)D deficiency (<20 ng/mL), 13.8% having insufficiency (20-29.99 ng/mL), and 11.3% of the subjects having sufficient 25(OH)D (≥30 ng/mL) levels. 25(OH)D deficiency was more common among females (78.7%) than males (66.4%, p < 0.05).ConclusionAdults living in an urban, non-coastal setting in Turkey have a high prevalence of vitamin D deficiency.

Evaluation of markers of inflammation, insulin resistance and endothelial dysfunction in children at risk for overweight.

Objective: Childhood obesity is associated with impaired endothelial function, insulin resistance and inflammation. Being at risk for overweight has been defined as having a body mass index (BMI) between the 85th and 94th percentile for age and sex. In this study, we looked for features linked to cardiovascular risk in children who are at risk for overweight. Design: Twenty-one children who were at risk for overweight (study group) and 20 children with a BMI between the 25th–74th percentiles (controls) were studied. Fasting blood levels of glucose, insulin, total cholesterol, HDL cholesterol, triglycerides, uric acid, fibrinogen and high sensitive C-reactive protein (CRP) were assessed in both groups. LDL-cholesterol, HOMA-IR and QUICKI indices were calculated. Flow-mediated Vasodilatation (FMD) was determined for the evaluation of endothelial function. Results: Increased HOMA-IR was observed in children who were at risk for overweight. Waist circumference was the main predictor of insulin resistance in these children. Higher levels of CRP were found in the study group compared to controls, while plasma fibrinogen did not differ in the two groups. The children who were at risk for overweight had lower FMD values and slightly elevated lipids compared to controls; however, these differences were not statistically significant. Conclusion: Insulin resistance and inflammation indices were higher in children who were at risk for overweight as has been shown for obese children. The data suggest that appropriate treatment strategies for weight control are essential not only for obese children but also for those at risk for overweight.

Down-regulation of the auto-aggressive processes in patients with hypothyroid Hashimoto's thyroiditis following substitutive treatment with L-thyroxine.

BACKGROUND Hashimotos thyroiditis is a chronic, organ-specific autoimmune disease. It is the most common cause of primary hypothyroidism during the adolescent period, via autoimmune thyroid tissue destruction, affecting 2% of the population. The pathogenesis of Hashimotos thyroiditis involves a complex interaction between predisposing genetic and environmental factors. OBJECTIVE In this study, we wanted to investigate the role of cytokines such as IL-2, IL-4, IL-12 and IFN-gamma in the pathogenesis of the disease, and the changes to cytokine levels brought about by treatment with L-thyroxine. METHODS Sixty five female patients, aged 18-73 years with Hashimotos thyroiditis, referred to the Celal Bayar University Medical Faculty Endocrinology out-patients clinic, were included in this study. After a 10-12 week period of L-thyroxine treatment, all patients were restored to the euthyroid state. At the beginning and end of the treatment period, serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), autoantibodies against thyroid peroxidase (anti-TPO), autoantibodies against thyroglobulin (anti-Tg) levels were measured using a chemiluminecent, immunometric method, and cytokine levels were measured using ELISA. RESULTS There was a statistically significant decrease in the serum levels of TSH (p < 0.0001) and a concomitant increase in FT4 serum levels (p < 0.0001). Also, during the post-treatment period, serum levels of anti-Tg (p < 0.01) and anti-TPO (p < 0.001) were significantly lower than during the pre-treatment period. A statistically significant decrease was shown for interleukin (IL)-12 serum levels during the post-treatment period (p < 0.001). However, the decrease in interferon (IFN)-gamma serum levels was not statistically significant (p = 0.276). On the other hand, no change was demonstrated in serum IL-2 and IL-4 levels (p = 0.953 and p = 0.313, respectively) after treatment with L-thyroxine. CONCLUSION Considering that our study involved a 10-12 week period of treatment, the statistically significant decrease in serum IL-12 levels, and the statistically non-significant decrease in IFN-gamma levels, might indicate that a T helper type 1 inflammatory process had been halted or slowed down.

Out-of-Reference Range Thyroid-Stimulating Hormone Levels in Levothyroxine-Treated Primary Hypothyroid Patients: A Multicenter Observational Study

Objective Although levothyroxine (LT4) replacement therapy for hypothyroidism has been established as safe, inexpensive and effective, many studies from different countries reported out-of-reference range thyroid-stimulating hormone (TSH) values for the hypothyroid patients under LT4 treatment. The aim of this study was to determine TSH levels of primary hypothyroid patients under LT4 treatment and to assess self-reported compliance with daily LT4 intake in tertiary care centers in Turkey. Design In this cross-sectional, observational study, adult patients with primary hypothyroidism, receiving LT4 treatment for at least 6 months, were included. The patients were from 12 tertiary care centers in 9 cities of Turkey. TSH and free T4 levels were recorded from patient files and self-reported compliance with daily LT4 intake was assessed by interviewing the subjects at the last visit. Results A total of 1,755 subjects (46 ± 13 years; F/M: 89.9/10.1%) with primary hypothyroidism were enrolled. Of the hypothyroid subjects, 44.8% had out-of-reference range serum TSH levels. TSH values were over the reference range (TSH > 4 mIU/L) in 26.2% and were under the reference range (TSH < 0.5 mIU/L) in 18.6% of the patients. Total duration of LT4 treatment was 5.9 ± 4.7 years and mean dose was 1.2 ± 0.6 μg/kg/day. Non-compliant patients (31.1%) had higher TSH levels (6.9 ± 16 vs 3.8 ± 0.9 mIU/L, P = 0.01) compared to compliant patients. Conclusion The results of this study revealed that nearly half of the hypothyroid patients had out-of-reference range serum TSH values, despite under LT4 treatment. Compliance with LT4 treatment seems to be one of the major determinants to reach the target TSH levels in hypothyroid patients.

impact of telephonic interviews on persistence and daily adherence to insulin treatment in insulin-naïve type 2 diabetes patients: dropout study

Objective The objective of this study is to evaluate the impact of sequential telephonic interviews on treatment persistence and daily adherence to insulin injections among insulin-naïve type 2 diabetes patients initiated on different insulin regimens in a 3-month period. Methods A total of 1,456 insulin-naïve patients with type 2 diabetes (mean [standard deviation, SD] age: 56.0 [12.0] years, 49.1% were females) initiated on insulin therapy and consecutively randomized to sequential (n=733) and single (n=723) telephonic interview groups were included. Data on insulin treatment and self-reported blood glucose values were obtained via telephone interview. Logistic regression analysis was performed for factors predicting increased likelihood of persistence and skipping an injection. Results Overall, 76.8% patients (83.2% in sequential vs 70.3% in single interview group, (P<0.001) remained on insulin treatment at the third month. Significantly higher rate for skipping doses was noted in basal bolus than in other regimens (27.0% vs 15.0% for premixed and 15.8% basal insulin, respectively, P<0.0001). Logistic regression analysis revealed sequential telephonic interview (odds ratio [OR], 1.531; 95% confidence interval [CI], 1.093–2.143; P=0.013), higher hemoglobin A1c levels (OR, 1.090; 95% CI, 0.999–1.189; P=0.049), and less negative appraisal of insulin therapy as significant predictors of higher persistence. Basal bolus regimen (OR, 1.583; 95% CI, 1.011–2.479; P=0.045) and higher hemoglobin A1c levels (OR, 1.114; 95% CI, 1.028–1.207; P=0.008) were the significant predictors of increased likelihood of skipping an injection. Conclusion Our findings revealed positive influence of sequential telephonic interview, although including no intervention in treatment, on achieving better treatment persistence in type 2 diabetes patients initiating insulin.

A case of familial partial lipodystrophy caused by a novel lamin A/C (LMNA) mutation in exon 1 (D47N)

BACKGROUND Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by selective lack of subcutaneous fat which is associated with insulin resistant diabetes. The Dunnigan variety (FPL2) is caused by several missense mutations in the lamin A/C (LMNA) gene, most of which are typically located in exon 8 at the codon position 482. CASE REPORT Here, we report on a Turkish family with FPL2 which is caused by a novel heterozygous missense LMNA mutation in exon 1 (D47N, c.139G>A), in the rod domain of lamins A/C. Fat distribution and metabolic features of LMNA D47N mutation were similar to typical codon 482 mutation. Metabolic abnormalities were observed as a form of insulin resistant diabetes, hypertriglyceridemia, low HDL cholesterol and hepatic steatosis. There was no evidence for neuromuscular and cardiac involvement. CONCLUSION Although it is previously known that alterations in the rod domain of type A lamins are involved in cardiac and neuromuscular diseases, our current observation shows that exon 1 LMNA mutations may be associated with partial lipodystrophy without any cardiac and neurological abnormalities, at least at the time of the presentation.

Evaluation of Visual Pathways using Visual Evoked Potentials in the Patients with Impaired Fasting Glucose and Impaired Glucose Tolerance

Abstract Purpose: There are many studies on degeneration of the ganglion cells using visual evoked potential (VEP) in Diabetes mellitus (DM). The present study intended to investigate whether the retinopathy findings would be helpful for detecting the degeneration to develop or not in retinal ganglion cells with the VEP test before being detectable in ophthalmoscopic examination on prediabetic patients. Materials and methods: The present study was conducted prospectively after obtaining approval from the Ethics Committee. In our study, the subjects were divided into three groups as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and normal patients. They also underwent physical, ophthalmological and VEP examination. Three main components of VEP obtained from these groups were N75, P100, and N145 latency and N75-P100 amplitude. Results: The study participants consisted of the IFG group (n: 30, female/male ratio: 21/9; mean age: 49.17 ± 10.52 years), the IGT group (n: 30, female/male ratio: 23/7; mean age: 47.00 ± 11.09 years), and the Control Group (n: 40, female/male ratio: 30/10; mean age: 48.03 ± 10.96 years). Difference in sex and age between the study groups (p > 0.05). P100 latency was found to increase significantly in comparison between the IGT and Control Group for both eyes (p right: 0.003, p left: 0.001) whereas it did not increase significantly in the comparison between the IFG and the Control Group (p right: 0.065, p left: 0.116). Conclusion: It was observed that VEP may be a parameter of predictive value that might be used in evaluating prediabetic cases in terms of retinopathies similar to DM.

A subset of patients with acquired partial lipodystrophy developing severe metabolic abnormalities

ABSTRACT Purpose/Aim of the study: Acquired partial lipodystrophy (APL) is a rare disease characterized by selective loss of adipose tissue. In this study, we aimed to present a subset of patients with APL, who developed severe metabolic abnormalities, from our national lipodystrophy registry. Materials and Methods: Severe metabolic abnormalities were defined as: poorly controlled diabetes (HbA1c above 7% despite treatment with insulin more than 1 unit/kg/day combined with oral antidiabetics), severe hypertriglyceridemia (triglycerides above 500 mg/dL despite treatment with lipid-lowering drugs), episodes of acute pancreatitis, or severe hepatic involvement (biopsy-proven non-alcoholic steatohepatitis (NASH)). Results: Among 140 patients with all forms of lipodystrophy (28 with APL), we identified 6 APL patients with severe metabolic abnormalities. The geometric mean for age was 37 years (range: 27–50 years; 4 females and 2 males). Five patients had poorly controlled diabetes despite treatment with high-dose insulin combined with oral antidiabetics. Severe hypertriglyceridemia developed in five patients, of those three experienced episodes of acute pancreatitis. Although all six patients had hepatic steatosis at various levels on imaging studies, NASH was proven in two patients on liver biopsy. Our data suggested that APL patients with severe metabolic abnormalities had a more advanced fat loss and longer disease duration. Conclusions: We suggest that these patients represent a potential subgroup of APL who may benefit from metreleptin or investigational therapies as standard treatment strategies fail to achieve a good metabolic control.