ACTA ENDOCRINOLOGICA (BUC)

Background. There have been a number of reports on the relationship between the PPARγ2 Pro12Ala genotype and the development of obesity. Objective. A case-control survey was designed to investigate the potential association between a Pro12Ala polymorphism in the PPARγ2 gene and obesity and/or obesity-related phenotypes in a population from Turkey. Materials and methods. The polymerase chain reaction and restriction enzyme digestion were used to genotype the Pro12Ala polymorphism of the PPARγ2 gene in 149 unrelated obese and 105 non-obese control subjects from Turkey. The data were analyzed statistically. Results. We found that the overall minor allele frequency was 0.12 in cases and 0.095 in controls. In terms of genotype distribution and allele frequencies among the cases versus controls in the population studied, only the genderstratified analysis revealed a significantly higher frequency of Pro/Ala genotype within males. The polymorphism was associated with significantly higher weight, height, waist circumference, central adiposity (waist-to-hip ratio, WHR), lean body weight as well as dry body weight, but not overall adiposity (total body fat percentage, TBF) in cases carrying Ala allele (Pro/Ala or Ala/Ala). However, in the subjects carrying Ala allele of the control group, WHR values were found significantly lower. Conclusion. Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obesity in the studied adult population from Turkey. These data suggest that the Pro12Ala polymorphism in PPARγ2 may be a potential genetic risk factor for central obesity.

Context. Severe hypertriglyceridemia (SH), which calls for a triglyceride (TG) level above 1000 mg/dL, remains an important health issue. While some data exist to offer combination of heparin, insulin and fenofibrate as a reasonable treatment option, safety and benefits of this therapy have not been accurately weighted, largely due to the limited sample size of the relevant studies. Aim. Assess the efficacy and safety of the heparin, insulin and fenofibrate combination in the treatment of patients with SH. Patients - Methods. Patients aged ≥18 years with TG level above 1000 mg/dL and adequate organ function were included. Triglyceride levels were measured immediately before the treatment and on the 3rd and 6th days of the treatment. Treatment dosage, duration, response and side effects were assessed. Patients with hypertriglyceridemia presenting with acute pancreatitis were treated additionally with lipid apheresis. Results. A total of 42 patients were included. Of these, 85.8% came to medical attention with some kind of secondary hypertriglyceridemia causes. The baseline median TG value of the cases was 2141.0 mg/ dL (1026-12250). There were 6 patients (14.3%) with acute pancreatitis at presentation. In patients without pancreatitis, with administration of insulin infusion, unfractionated heparin infusion and fenofibrate capsule, median TG values decreased to 921 mg/ dL (190-6400) on the 3rd day and to 437 mg/ dL (112-1950) on the 6th day of the treatment (p<0.0001, Friedman test). Potential toxicities related to insulin, heparin and fenofibrate combination treatment including hypoglycemia, hemorrhage, rise in creatine kinase levels, hepato - and nephrotoxicity were not observed. Conclusion. In this trial involving patients with SH, our data suggest that insulin, heparin and fenofibrate combination therapy was safe and effective.

Introduction. We aimed to investigate Cardiotrophin-1 (CT-1) levels along with other markers of cardiovascular disease and the association of androgen levels with these parameters in both lean and overweight or obese PCOS patients. Material and Methods. The study included 90 overweight or obese PCOS patients with metabolic syndrome (MS) and 80 lean PCOS patients without MS. The control group consisted of 140 healthy females. Anthropometric measurements, plasma glucose, insulin, lipid and hormone profile, homocysteine, hs-CRP, CT-1 levels and carotid-IMT were evaluated in all study subjects. Results. Fasting insulin, HOMA values were significantly higher in obese PCOS patients. Total testosteron levels were higher in both PCOS groups with respect to both controls. Serum homocysteine, hs-CRP, CT-1 and carotid- IMT values were significantly higher in both PCOS groups compared to controls (p=0.001, pCIMT: 0.005). CT-1 was positively correlated with insulin, HOMA, total testosterone, homocysteine, hs-CRP and carotid IMT. After multiple regression analysis, CT-1 was significantly positively correlated with total testosterone, hs-CRP and carotid IMT. Conclusions. CT-1 was associated with other cardiovascular risk markers and its use as a cardiovascular risk marker might be suggested. Cardiovascular risk was increased even in lean PCOS patients without MS and it might be associated with elevated androgen levels.

Context. We report the use of subcutaneous somatostatin injection three times a day to decrease hypercortisolism in a patient who had Cushing’s syndrome induced by bronchial carcinoid tumour progressive pneumonia due to immune suppression. Subject and Method. A 46-yearold man with 7-month history of DM type-2, hypertension and cerebrovasculardisease, vertebral compression-fracture was admitted to our clinic. Physical examination was consistent with Cushing’s syndrome. Laboratory results revealed hyperglycemia (143 mg/dL; reference range, <100 mg/dL) and hypokalemia (2.29 mEq/L; reference range, 3.5-5.1 mEq/L). His morning serum cortisol was 40 μg/dL (reference range 6.7- 22.6 μg/dL), urine cortisol-excretion was 2245 μg/24 hours (reference range 58-403 μg/24 hours), after 1 mg dexamethasonesuppression test serum cortisol was 28 μg/dL (6.7-22.6 μg/dL) and ACTH 354 pg/mL (reference range 7.9-66 pg/mL). Adrenal CT and hypophyseal MRI were normal. An ectopic source was searched for Cushing’s syndrome. Chest CT scan of the right lung showed 12x9 mm nodule. High fever cough occurred on the followp. Chest radiograph revealed diffuse pneumonic infiltration. Despite 3-drug antibiotic combination therapy, infection did not improve. Subcutaneous injection of octreotide 3x100 μ/g was initiated to decrease hypercortisolism. The infection improved rapidly after the therapy. The morning serum cortisol, urine cortisol-excretion, ACTH was at the upper normal range (77.1 pg/mL, reference range 7.9-66 pg/mL) on 10th day of treatment. The patient was a consulted for surgery and the nodule was excised. The pathology was consistent carcinoid tumor. Conclusion. Subcutaneous octreotide treatment may be helpful to gain time for exploring the focus in ectopic cushing’s syndrome and to control the serious infections due to hypercortisolism.

Context. Although, many studies have been made on the clinical course of autoimmune thyroiditis, this study focused on women and the factors effecting the natural course such as Selenium. Objective. The study aimed to determine Hashimoto’s thyroiditis (HT) clinical course in adults and the factors that could affect it. Design. The study was in a retrospective manner between 2010-2018. Subjects and Methods. 101 patients with HT were followed for 60.7±32.7 months. Biochemical and ultrasonographic data were collected. We investigated whether the age at diagnosis, family history, smoking habits, levothyroxine replacement therapy, and serum selenium (Se) levels influenced the disease course. Results. No relationship was observed between age and thyroid functions, thyroid volumes (TV), and autoantibody (Ab) levels at diagnosis. Ab levels were irrelevant with TV, echogenicity, and nodularity at diagnosis. However, initial TSH levels were significantly associated with anti-TPO levels (p=0.028, r=0.218). In the untreated group, thyroid functions seemed to be stable. TV decreased significantly in both treated and untreated patients (p<0.001). The decrease in TV was significantly higher in the treatment group (p=0.002). In euthyroid and subclinical hypothyroid patients, levothyroxine therapy did not affect the decrease in TV. Ab levels remained stable in untreated patients, but anti-TPO levels significantly decreased in treated patients (p<0.001). Smoking seemed to increase only anti-Tg levels (p=0.009). Family history was not associated with any of the studied parameters. Serum Se level was negatively correlated only with thyroid echostructure and only in treated patients. TV showed a “Gaussian distribution” in all patients at the diagnosis and at the end, independent of levothyroxine treatment. Conclusions. Most euthyroid patients remained euthyroid during five years of follow-up. The decrease in TV was significantly prominent with LT4 treatment. Importantly, TV followed a normal distribution instead of the bimodal distribution that is classically described.

Aims. In August 2015, FDA published a black box declaring that DPP-4 inhibitors may cause severe joint pains. The impact on autoimmunity marker positivity of these drugs has not been comprehensively evaluated. We compared the incidence of arthritis/arthralgia in patients with T2DM who were using DPP-4 inhibitors and patients who were not using. Methods. A number of 93 DPP-4 inhibitor users and 107 non-users were included into the study. Arthritis/ arthralgia were found in 41 of 93 (44.1%) DPP-4 inhibitor users and in 19 of 107 (17.8%) non-users (p<0.05). Results. No inflammatory rheumatological condition was identified in 27 of 41 (65.9%) patients in DPP-4 inhibitor user group as well as in 13 of 19 (68.4%) patients in non-user group (p>0.05). After adjusting for gender the incidence for arthritis/arthralgia was significantly increased in the DPP-4 inhibitor user group (p value for any DPP-inhibitor <0.05). There was 3.77 times increased risk for arthritis/arthralgia in the DPP-4 inhibitor using group (p value= 0.001) and this risk increases 2.43 times for each year of DPP-4 inhibitor usage. Conclusions. Arthritis/arthralgia were more common among T2DM patients who were using DPP-4 inhibitors compared to non-users, but the seropositivity did not differ between DPP-4 inhibitor users and non-users.

Introduction. Bartter’s Syndrome is a renal tubular defect characterized with low or normal blood pressure, hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism due to renal sodium loss. Herein we reported a case who presented with growth retardation, growth hormone deficiency previously treated with growth hormone for a period of 6 months in mind and with hypopituitarism similar findings such as primary amenorrhea, fatigue, weakness and just diagnosed as Bartter’s syndrome. Case report. A 18 year-old female patient was referred to our hospital for amenorrhea, growth retardation and fatigue. Her history revealed that she was diagnosed with growth hormone deficiency two years ago and given growth hormone treatment for 6 months. Physical examination showed growth retardation. Laboratory tests revealed that serum potassium was 2,3 mmol/L. Further investigations demonstrated metabolic alkalosis, increased urinary potassium excretion and hyperreninemic hyperaldosteronism. The patient was considered as Bartter syndrome and spironolactone, indomethacin and potassium chloride were initiated. While she had growth retardation and primary amenorrhea, we searched basal hormone levels and performed stimulation tests for evaluating pituitary reserve. Insulin tolerance test showed that serum growth hormone and cortisol levels were 10 mcg/dL and 19 mcg/dL respectively during hypoglycemic period. It demonstrated that both of the axes were intact. Luteinizing hormone releasing hormone test showed that hypothalamo pituitary gonadal axis was also intact. Conclusions. Bartter syndrome can lead to growth retardation that mimicking hypopituitarism in case of delay in diagnosis.

Background. Thyroid nodules are a common pathology worldwide. Fine needle aspiration biopsy (FNAB) is an important diagnostic method for the investigation of malignancy in thyroid nodules. However, according to the Bethesda System used to classify the results, patients with atypia of undetermined significance/follicular lesion of undetermined significance (AUS / FLUS) may not be classified as benign or malignant. Therefore, it may be necessary to determine some clinical risk factors to apply the best treatment in these patients. Aim. To determine the factors that increase the risk of malignancy in this patient group. Methods. A retrospective study including 138 patients with an FNAB categorized as AUS/FLUS and operated between June 2015–September 2018. Demographical, Laboratory (TSH) and Ultrasound variables (number, size and characteristics of nodules) of the patients were compared among postoperative histopathological results. Results. Hypo-echoic structure, microcalcification and irregular margin of the nodules were detected to be associated with malignancy in patients with FNAB results of AUS/FLUS (p <0.001). Conclusion. We suggest that surgical treatment should be considered if the patients have nodules with the hypo-echoic structure, microcalcification and irregular margin with an FNAB histopathological result of AUS / FLUS.

A 54 years old man, who had undergone a cystectomy and urinary diversion surgery 31 years previously, complained of progressive generalized bone pain, muscle weakness and walking abnormality for six months. Laboratory investigations revealed elevated alkaline phosphatase, high serum chloride level and metabolic acidosis. Osteomalacia was suspected due to clinical and laboratory findings. Osteomalacia due to hyperchloremic metabolic acidosis is a complication of urinary diversion. Regular monitoring of pH, chloride, bicarbonate, and calcium-phosphorus metabolism is therefore essential for early diagnosis and treatment.

Background. Idiopathic hypoparathyroidism is a rarely seen disease which progresses with the hypocalcaemia, hyperphosphatemia and low level of parathyroid hormones. The main symptoms such as leg cramps and generalized muscle weakness result from neuromuscular irritability due to hypocalcaemia, and skeletal abnormalities as well as ectopic calcifications are among the well known features. Case Report. A 32 year-old male patient was referred to our clinic with four years of progressive inflammatory low back and hip pain, prolonged morning stiffness. Upon physical examination limited movements and posture resembling that seen in patients with ankylosing spondylitis (AS) were observed. In laboratory investigation revealed hypocalcaemia (4.6 mg/dL), hyperphosphatemia (7.0 mg/dL) and hypoparathyroidism (7.2 pg/mL). Serum C reactive protein and erythrocyte sedimentation rate were normal. The direct graphic and sacroiliac magnetic resonance image were identified sacroiliitis. A rise in bone density in dual-energy x-ray absorptiometry was recorded. According to the Modified New York criteria, AS includes the whole diagnostic criterias completely. Conclusion. Idiopathic hypoparathyroidism, when undiagnosed for a long period, may result in extreme calcification of soft and bony tissues. The vertebral calcification may be so intense that it may result in an AS like clinical picture. Therefore, idiopathic hypoparathyroidism should also be considered in the differential diagnosis of AS .