Effects of weight intervention-induced changes in pathological fat mass of patients with extreme obesity and anorexia nervosa on adipokines and visceral adipocyte functions: a prospective, comparative, observational study.

OBJECTIVE: Adipose tissue is the largest endocrine organ in the human body, and as its mass changes, the serum levels of the molecules it secretes also change. Visceral adipose tissue index (VAI) is a simple surrogate marker of visceral adipose tissue dysfunction. This study evaluated the effects of changes in fat mass on adipocytokine behavior and VAI in patients with anorexia nervosa (AN) and extreme obesity (EO). PATIENTS AND METHODS: The study group consisted of three subgroups: Group 1, patients with EO who were candidates for obesity surgery with BMI≥50 kg/m2 (n=20). Group 2, newly diagnosed patients with AN (n=12). Group 3 controls with BMI 20-25 kg/m2 (n=20). The AN and EO groups were followed until at least a 10% weight change before and after the intervention. RESULTS: Prior to the intervention, EO patients exhibited the lowest levels of apelin, omentin, and adiponectin, while AN patients demonstrated the highest levels of these markers. Leptin and IL-6 were elevated in EO and reduced in AN patients. After treatment, all adipokines and VAI increased in AN patients, and omentin, adiponectin, and IL-6 increased in EO patients, while apelin, leptin, and VAI decreased. The change in each adipocytokine (∆) was positively correlated with the other adipocytokines (p<0.050) and negatively correlated with metabolic and VAI changes (p<0.050). The regression analysis determined that the following variables were associated with the change in adipose tissue mass: Δapelin (OR: 1.061; p=0.028) and Δadiponectin (OR: 1.057; p=0.036). CONCLUSIONS: In individuals with pathological adipocyte mass, the change in adipocytokine levels in response to weight change is not as expected. The fact that these changes are not seen in the early period of the weight intervention treatment indicates that these patients have compensatory physiological mechanisms to protect them. In addition, using VAI instead of BMI, whose reliability is increasingly questioned because it does not reflect body fat mass, can be considered an alternative. However, there may be modeling errors in the early stages of weight change and in AN and EO patients where metabolic parameters reach extreme values. Therefore, it should be tested in studies where larger patient groups are followed for a more extended period.

Is the TSHR D727E polymorphism a genetic predisposition for multinodular goiter in the Turkish population?

The D727E germline polymorphism in the thyroid-stimulating hormone receptor gene (TSHR) may cause genetic susceptibility to the development of goiter. Therefore, in this study we investigated allele frequencies and genotype distributions of the TSHR D727E polymorphism, their association with clinical parameters, and the development of goiter in the Turkish population. We investigated the TSHR D727E polymorphism in 123 patients and 97 healthy subjects using the polymerase chain reaction-restriction fragment length polymorphism technique. Peripheral blood was used for DNA extraction. Although no significant difference was found in TSHR D727E polymorphism frequencies between the patients with nodular goiters (26/123 patients, 21.1%) and the controls (12/97 patients, 12.4%) (P = 0.107), the frequency of the TSHR D727E polymorphism in the hyperthyroid+subclinical hyperthyroid patient groups (23%) was significantly higher than in the control subjects (12.4%) (P = 0.024). In this study, nodular goiter presented significantly earlier in GC genotype patients (mean age 35 years) than in CC genotype patients (mean age 42 years) in the hyperthyroid group (P = 0.009). More importantly, TSH levels in the GC variant controls were closely significant lower (1.26 ± 0.49) than in the CC variant controls (1.74 ± 0.84) (P = 0.053). The TSHR D727E polymorphism might be involved in the pathogenesis of toxic multinodular goiter (TMNG). Moreover, this polymorphism might be an indication of early-onset TMNG. However, development of MNG is multifactorial. Therefore, further case-control studies with larger populations are required to verify these observations.

The synergistic effect of ω3 and Vit D3 on glycemia and TNF-α in islet transplantation.

The current treatment of type 1 diabetes consists of insulin administration. Transplantation of islets of Langerhans is considered very favorable because the full effect of insulin treatment cannot be obtained in severe cases. Although agents such as omega-3 (ω3) and vitamin D3 (Vit D3) are known to contribute to the success of islet allo-transplantation (ITX), in this study we aimed to experimentally determine their effects on glycemia and TNF-α production. Wistar albino rats, which were used as recipients, were given ω3, Vit D3, and islets by gavage, and intraperitoneal- and intraportal injections, respectively. Daclizumab (DAC) was used for immunosuppression. Glycemia levels decreased in rats treated with ω3 and vit D3. TNF-α increased in all groups due to application of STZ. After ITX (day +1), the weakest increase was observed in the ω3 + Vit D3 group. In the ITX+DAC group, compared with that of ITX only, DAC was shown to decrease levels of TNF- α following ITX, only in control group, however, similar levels of TNF-α were observed in other groups. The values in the treated groups were already lower than those of the controls in the ITX group and also remained almost equal in the ITX+DAC group. We suggest that the use of ω3 and Vit D3 together will improve the pro-inflammatory aspect encountered during and after ITXs, and contribute to the reduction of the dose of immunosuppressants in these procedures.

Retrospective comparison of cabergoline and bromocriptine effects in hyperprolactinemia: a single center experience.

INTRODUCTION: Patients with hyperprolactinemia who require medical therapy are typically treated with dopamine agonists (DAs). In most cases, DAs normalize prolactin levels, control symptoms, and substantially decrease tumor size. Here, we aimed to compare the efficacy of cabergoline (CAB) and bromocriptine (BRC) in patients with hyperprolactinemia at a single center. METHODS: Retrospective analysis of the clinical records of 498 patients with hyperprolactinemia [mean age 33.3 ± 10.8 years (range 16-66), 450 women, and 48 men] who had received either CAB (n = 450) or BRC (n = 48) was performed. RESULTS: The mean age, gender distribution, and treatment duration were similar between the CAB and BRC groups (33.2 ± 11 vs. 34.1 ± 9.6 years, male/female 44/406 vs. 4/44, 18.7 ± 12.1 vs. 17.8 ± 6.0 months, respectively; p > 0.05 for all). Mean dosage was 1.5 ± 1.6 mg/week for CAB and 3.8 ± 2.7 mg/day for BRC. Baseline prolactin levels, frequency of galactorrhea, amenorrhea, oligomenorrhea, erectile dysfunction, infertility, and visual impairment were similar between the two groups, whereas the baseline tumor volume was higher in the CAB group. The prolactin normalization rate (87.4 vs. 41.4 %, p = 0.029) and tumor volume shrinkage (79.8 ± 39.1 vs. 54.1 ± 55.3 %, p = 0.015) were significantly higher in the CAB-treated patients than in the BRC-treated patients, while the tumor cure rates were similar. Symptom relief was higher in the CAB group than in the BRC group. More side effects were recorded in patients who took BRC (29.1 vs. 5.3 %, p < 0.001). CONCLUSION: Our data revealed that CAB was more effective than BRC in controlling symptoms associated with hormone excess, normalizing serum prolactin levels, and shrinking prolactinomas.

Comparison of alendronate and raloxifene for the management of primary hyperparathyroidism.

AIM: To evaluate and compare the efficacy of alendronate sodium (ALN) and raloxifene (RLX) for the management of primary hyperparathyroidism (PHPT) in postmenopausal female patients (pts) with osteoporosis. METHODS: Twenty-four postmenopausal women with osteoporosis who were diagnosed with PHPT, but refused the option of surgery, were enrolled. Participants were sequentially randomized into two groups: an ALN-group of 12 pts (70 mg/week) and a RLX-group of 12 pts (60 mg/day). The control group consisted of 10 pts with PHPT who did not have any indications for surgery. RESULTS: The decrease in ionized calcium levels was significantly more pronounced in the ALN group compared to the RLX and control groups (p<0.001). In terms of difference from baseline in bone mineral density (BMD) of the lumbar area in percentages over a period of 12 months, pts in the ALN and RLX groups both showed statistically significant improvements compared to pts in the control group (control vs ALN, p<0.001; control vs RLX, p<0.001). BMD measurements of the femoral and radial areas were comparable in all three groups. CONCLUSIONS: ALN and RLX may improve bone density in the lumbar area of osteoporotic post-menopausal women with PHPT. The more significant decrease in serum calcium levels which was observed in the ALN group compared to both RLX and control groups, suggests that ALN could be used for the short-term control of calcium levels in patients awaiting surgery.

A comparative study of pre-operative imaging methods in patients with primary hyperparathyroidism: ultrasonography, 99mTc sestamibi, single photon emission computed tomography, and magnetic resonance imaging.

AIM: This study compares the accuracy rates achieved in ultrasonography (US), 99mTc-sestamibi (MIBI), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) as imaging methods used in the pre-operative localization of the enlarged parathyroid glands. SUBJECTS AND METHODS: For the purposes of this study, US, MIBI, SPECT, and MRI were performed on 98 patients with primary hyperparathyroidism (pHPT). All patients underwent parathyroidectomy. RESULTS: Pre-operative localization of an abnormal parathyroid gland was successfully performed in 82 of the cases scanned with US (83.7%), while the result was 66 in the cases scanned with MIBI (67.3%), 71 of the cases were successfully localized with SPECT (72.4%), while MRI revealed the diseased gland in only 60 of the total cases (61.2%). In MIBI-positive and -negative patients there was a statistically significant difference among cases in terms of adenoma volume (1.30±1.51 vs 0.58±0.91, p<0.05). Sensitivity, specificity and diagnostic accuracy values were 87.2%, 25.0%, and 83.0%; 70.2%, 50.0%, and 69.4%; 75.5%, 50.0%, and 74.5%; 63.8%, 50.0%, and 63.3% for US, MIBI, SPECT, and MRI, respectively. The respective values for sensitivity, specificity, and diagnostic accuracy were 94.9%, 25.0%, and 91.1% when US was combined with MIBI. CONCLUSIONS: Combining US and MIBI as imaging methods for pre-operative imaging of pHPT often produces more satisfactory results. While the accuracy of US is relatively low in the ectopic localizations, the size of the lesion can be an important factor in the accuracy achieved with MIBI.

Alkaline phosphatase: can it be considered as an indicator of liver fibrosis in non-alcoholic steatohepatitis with type 2 diabetes?

OBJECTIVE: While isolated hepatosteatosis is a benign disease, in minority of cases non-alcoholic steatohepatitis (NASH) may even lead to cirrhosis in long-term. In order to find the stage of the disease and determine the prognosis, a liver biopsy is indicated. In this study, we studied the relationship of liver histopathological findings with serum levels of hepatic enzymes. METHODS: We recruited 52 cases of NASH with Type 2 diabetes mellitus. Diagnosis of NASH was made based on biochemical tests, ultrasound images and liver biopsy. RESULTS: Steatosis was mild in 57.7%, moderate in 30.8%, and severe in 11.6% of patients. While no infiltration was found in 78.8% of cases, there was a grade-1 infiltration in 15.4% and a grade-2 infiltration in 5.8% of cases. Similarly, no fibrosis was found in 42.3% of patients, but there was a stage-1 fibrosis in 50%, and a stage-2 fibrosis in 7.7% of cases. In patients with severe steatosis, serum levels of AST were higher than mild or moderate stage steatosis. Accordingly, in patients with no inflammation, serum levels of ALT were higher than in patients with inflammation. However, in patients with fibrosis, triglycerides levels were significantly lower and ALP was significantly higher than in patients without fibrosis. The correlation analysis indicated a positive association between serum levels of ALP and C-peptide. CONCLUSION: In addition to conventional risk factors such as age, presence of diabetes, female sex; higher levels of ALP may be considered as a risk factor linked to hepatic fibrosis in patients with NASH and type 2 diabetes (Tab. 6, Ref. 8).

Somatotropin adenoma and resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is a rare disease characterized by non-suppressed TSH in spite of high free thyroid hormone levels. Up to date, in the literature, there are more than 600 RTH cases, but co-incidental hypophyseal adenoma was reported in only 1 case. In the literature, despite reported cases with thyrotropinoma accompanying RTH, we could not find a case with somatotropinoma accompanying RTH. Here, we report a 34-yr-old male patient, who was admitted to the hospital with complaints of dyspnea, chest pain, and palpitation in 2003. His alpha- subunit value was normal and the alpha-subunit/TSH molar ratio was <1. His response to TRH stimulation test was normal. His TSH level was suppressed in the T3 suppression test. Hypophyseal magnetic resonance imaging showed a 6-mm hypophyseal microadenoma. Levels of all anterior hypophyseal hormones, including GH and IGF-I, were normal. Oral glucose tolerance test (OGTT)-GH suppression test was normal. The patient was followed with the diagnosis of RTH and incidental hypophyseal adenoma. After 3 yr, because of high levels of IGF-I: 901 ng/ml (68-324), the OGTT-GH suppression test was reported and no suppression was detected. Thus, the patient was referred to surgery with the pre-diagnosis of RTH and acromegaly. Immunohistochemistry was showed as strong GH staining with low Ki 67 index while TSH and other anterior hypophyseal hormones stainings were negative. Post-operative thyroid hormones were still high.

Molecular analysis and long-term clinical evaluation of three siblings with Alström syndrome.

Alström syndrome is a rare, autosomal recessive disorder characterized by a wide spectrum of clinical features including early-onset retinal degeneration leading to blindness, sensorineural hearing loss, short stature, obesity, type 2 diabetes, hyperlipidemia and dilated cardiomyopathy. Renal, hepatic and pulmonary dysfunction may occur in the later phases of the disease. The three affected sisters, from a consanguineous Turkish family, with the characteristic features of Alström syndrome, were clinically diagnosed in 1987 and followed for 20 years. DNA sequence analysis of ALMS1, the causative gene in Alström syndrome, identified a novel homozygous disease-causing mutation, c.8164C>T, resulting in a premature termination codon in exon 10 in each of the three affected sisters. Furthermore, we describe the longitudinal disease progression in this family and report new clinical findings likely associated with Alström syndrome, such as pes planus and hyperthyroidism.

Natural killer cell activity in multidrug-resistant pulmonary tuberculosis.

BACKGROUND: Multidrug-resistant pulmonary tuberculosis (MDRTB), a major problem in developing countries, may result from either insufficiency of host cellular immune response or mycobacterial mechanisms which has been more intensively investigated so far. OBJECTIVES: The aim of the study was to investigate natural killer cell activity (NKA) and T lymphocyte subsets in HIV- patients with secondary MDRTB. METHODS: 20 male patients with MDRTB (mean age 38 +/- 8 years), 15 nonresistant tuberculosis male patients (NRTB) (mean age 36 +/- 11 years) and 12 healthy male controls (mean age 35 +/- 8 years) were included. The percentages of CD3+, CD4+, CD8+, CD25+, CD11b+ and CD16+56+ cells were measured by flow-cytometric analysis of peripheral blood lymphocytes (PBL). NKA was evaluated using the anticandidal index method. RESULTS: The mean tuberculin response was higher in MDRTB and NRTB patients compared to controls (15.4 +/- 3.8, 15.1 +/- 3.3 and 10.9 +/- 2.8 mm, respectively; p < 0.001). There was no significant correlation between PPD response and PBL subsets or NKA. The percentages of both CD3+ and CD3+CD4+ T lymphocytes were significantly lower in MDRTB (62.4 +/- 12.1 and 33.9 +/- 9.0%) compared to NRTB (70.8 +/- 7.5 and 42.9 +/- 8.6%; p < 0.05). Patients with MDRTB had significantly lower NKA compared to NRTB and controls (30.9 +/- 11.3, 49.7 +/- 15.5 and 40.0 +/- 8.5%, respectively; p < 0.01). CONCLUSION: This reduction in NKA may suggest a role for impaired NK function in the pathogenesis of MDRTB in HIV- patients.