Effect of Cabergoline Treatment on Disease Control in Acromegaly Patients.

The aim of this study was to evaluate the efficacy of cabergoline in normalizing plasma IGF-I levels in acromegaly patients with elevated IGF-I levels after surgery and/or SRL therapy. Acromegaly patients (n: 143) were evaluated retrospectively. Patients with elevated IGF-I levels after surgery and/or SRLs therapy and a fixed dose of SRLs treatment for the last six months with no history of radiotherapy in the last three years were included in the study (n: 12). Previous treatment regimens, baseline PRL and IGF-I levels (ULNR), sella MRI, and immunohistochemical findings were evaluated. Cabergoline was used as an add on (n: 11) or single medical treatment (n: 1). The median duration of treatment with SRL alone was 12 months (range 6-48 months). The mean IGF-I value before cabergoline therapy was 1.45±0.4 ULNR. The mean cabergoline dose and duration of treatment were 1.55±0.75 mg/week and 9±6.3 months, respectively. IGF-I normalization was only achieved in patients with serum IGF-I concentration<1.5×ULNR before the onset of cabergoline treatment (n: 9). In some of the patients with IGF-I normalization, baseline prolactin levels were normal (n: 3). Immunopositivity for prolactin in adenoma tissue was found in three patients with IGF-I normalization. Cabergoline therapy is effective in the normalization of IGF-I levels even in normoprolactinemic acromegaly patients when IGF-I levels are mildly or moderately elevated during SRL therapy.

The role of severity and duration of inflammation and hematological parameters on the outcome of subacute thyroiditis.

Background: The role of severity and duration of inflammatory findings on the development of persistent hypothyroidism and anemia has not been clarified in subacute thyroiditis (SAT). Methods: Demographic data and laboratory parameters of patients with SAT were analyzed retrospectively. Results: Permanent hypothyroidism was observed in 28.1% of patients. Baseline elevated erythrocyte sedimentation rate as defined >74.5 mm/h was found to be associated with permanent hypothyroidism, but the duration of inflammation was not different between the recovered and hypothyroid patients. Baseline hemoglobin values improved without specific therapy in 3.5 months. Conclusion: The initial severity but not the duration of inflammation increases the risk for the development of permanent thyroid dysfunction, and anemia improves with the resolution of inflammation.

[Box: see text].

Management and follow-up results of an incidental thyroid carcinoma in a young woman with ovarian teratoma.

Thyroid cancer in ovarian teratoma is reported to be rare and experiences are limited. A 26-year-old woman had undergone bilateral cystectomy and omentectomy for bilateral cystic adnexial masses. Pathological examination showed 1.5 cm follicular variant papillary thyroid carcinoma on the basis of unilateral mature cystic teratoma. Increased CA-125 and CA19-9 levels decreased to normal reference ranges after surgery, but postoperative magnetic resonance imaging indicated multiple abdominal cystic loci. After total thyroidectomy, high dose I-131 was administered to ablate thyroid tissue. Thereafter, levothyroxine was started to achieve subclinical hyperthyroidism. No iodine uptake was detected in post-therapeutic whole body scan (WBS) other than thyroid bed. This finding supported that tumor did not show dissemination to abdomen. No uptake on the first-year evaluation with low-dose I-131 WBS suggested the complete ablation of the thyroid gland. It is recommended that thyroid carcinoma arising from ectopic thyroid tissue in a teratoma should be managed as thyroid carcinoma in thyroid. However, direct dissemination to contiguous regions in abdomen and hematogenous dissemination to distant organs should be in mind. Radical surgery including total abdominal hysterectomy, bilateral salphingo-oopherectomy, pelvic and paraaortic lymph node excision and thyroidectomy is recommended. Fertility preserving surgery may be the surgical procedure as in the present case.

Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

INTRODUCTION: During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain <300 mg/dl. In women with genetic forms of hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. MATERIALS AND METHODS: We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. RESULT AND CONCLUSION: When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

Diagnosis and management of tumor-induced osteomalacia: a single center experience.

PURPOSE: The aim of this study is to review the clinical and laboratory characteristics, diagnostic and treatment modalities of tumor-induced osteomalacia (TIO) cases managed in a single center. MATERIAL METHODS: Demographic and clinical features, biochemical findings, diagnostic procedures, treatment modalities, and outcomes of nine patients who had the diagnosis of TIO were reviewed retrospectively. RESULTS: Mean age of the study group (F/M: 4/5) was 45.8 ± 10.8 years, and mean time from the onset of symptoms to diagnosis was 4.7 ± 2.8 years. The clinical manifestations were muscle weakness and difficulty in walking (8/9), hip pain (3/9), multiple fractures (2/9), stress fracture (2/9). Mean plasma phosphorus concentration was 1.28 ± 0.4 mg/dl at presentation. We performed radionuclide imaging modalities (18F-FDG PET/CT, Ga68-DOTATATE PET/CT, octreotide scintigraphy) in seven of nine patients, and tumor was detected in all. Lower extremity (n = 6; %67), head region (n = 2; %22) and thorax (n = 1; %11) were the tumor locations of our cases. Eight patients underwent surgery and remission was achieved postoperatively in all of the operated patients and plasma phosphorus level normalized in 4 ± 2 days. Pathological examination revealed mesenchymal tumors with different subtypes. Recurrence occurred in three patients at 13 ± 10.5 months after the first surgery. Two patients were reoperated and radiotherapy was also performed in one of them. CONCLUSION: Hypophosphatemia necessitates careful evaluation for the etiology. TIO is one of the important causes of adult-onset hypophosphatemic osteomalacia. Diagnosis of TIO is essential because the laboratory and clinical findings resolve after appropriate treatment.

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

CONTEXT: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.

Serum adipokines and low density lipoprotein subfraction profile in hypopituitary patients with growth hormone deficiency.

The aim was to evaluate the concentrations of lipid subfractions in relation to adipokines and metabolic parameters in adult growth hormone (GH)-deficient hypopituitary patients on conventional replacement therapy. The study included 21 GH deficient-hypopituitary patients (age: 36.0 ± 15.1 years, male/female: 7/14) on conventional replacement therapy other than GH and 20 comparable controls (age: 37.3 ± 14.0 years, male/female: 6/14). Lipid subfractions (Lipoprint system), serum adipokine (leptin, adiponectin, resistin) concentrations, body composition, a surrogate marker for insulin resistance (HOMA) and conventional lipid profile were evaluated. No statistically significant difference was found with respect to HOMA, adipokine concentrations and anthropometric parameters between patients and controls except for significantly increased waist-to-hip ratio in hypopituitary group. Total and LDL cholesterol concentrations were significantly higher in the patients. LDL particle size (268.88 ± 3.16 vs. 271.31 ± 3.11 Å, P = 0.151) and small-dense LDL subfraction did not differ significantly. According to logistic regression analysis, triglyceride concentrations ≥1.69 mmol/L was the sole parameter significantly and independently predicted small (<268 Å) LDL particle size (P = 0.019) in the whole group. Increased triglyceride concentrations affect LDL particle size in GH-deficient hypopituitary patients. Small dense LDL seems not directly contribute to atherogenic potential in hypopituitarism.

A rare cause of dilated cardiomyopathy: hypocalcemia.

Dilated cardiomyopathy (DCM) is characterized by systolic dysfunction and is usually idiopathic. A rare cause of reversible DCM is hypocalcemia. Calcium plays a key role in myocardial contraction. Hypocalcemia can lead to a decrease in contraction, left ventricular systolic dysfunction, and heart failure with reduced ejection fraction (EF). Hypocalcemia-related reversible DCM reports are rare. Herein, we present two cases with heart failure caused by hypocalcemia developed due to hypoparathyroidism. The first case presented with severe heart failure and an extremely low serum calcium level (4.4 mg/dL) due to idiopathic hypoparathyroidism. The second case, which was also admitted with heart failure due to hypocalcemia, had iatrogenic hypoparathyroidism due to a subtotal thyroidectomy. In both cases, patients had reduced left ventricular systolic functions (EF was 33% and 42%, respectively). After calcium replacement and heart failure treatment, calcium levels were normalized. A significant and rapid improvement in heart failure was achieved in both cases (EF 60% and 50%, respectively). Serum calcium levels should always be measured in patients with heart failure, and the etiology of hypocalcemia should be sought. In addition to the standard pharmacotherapy of heart failure with reduced EF, calcium supplementation is essential for treating these patients.

Evaluation of the effect of L-thyroxin therapy on cardiac functions by using novel tissue Doppler-derived indices in patients with subclinical hypothyroidism.

OBJECTIVES: Subclinical hypothyroidism (SH) is characterized by normal serum free T4 (fT4), free T3 (fT3) levels and increased serum thyroid stimulating hormone (TSH) levels.The aim of this study was to assess the validity of tissue Doppler imaging (TDI) in evaluating cardiac effects of SH and to demonstrate the improving effects of L-thyroxin(L-T4) on TDI parameters. METHODS: Twenty-seven patients with SH and 22 healthy controls were evaluated by standard echocardiography and TDI. TDI-derived systolic velocities [isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IW), peak systolic velocity during ejection period (Sa)] and diastolic indices (peak early (Ea) and late diastolic (Aa) velocities, Ea/Aa, E/Ea ratios and Tei index) were measured. After restoring euthyroidism, all measurements were repeated. RESULTS: At baseline, left ventricular (LV) systolic velocities (IW and IVA) and diastolic indices were significantly impaired in the SH group. After L-T4 therapy, left ventricular systolic and diastolic functions were improved. Right ventricular (RV) systolic velocities were similar between the study group and the healthy controls but diastolic functions were impaired in the SH group, at baseline. Tei index of the RV was improved after L-T4 therapy. RV IVA remained unchanged after hormone replacement therapy. CONCLUSIONS: SH is associated with biventricular systolic and diastolic dysfunction. IVA which is an accurate estimate of subclinical systolic dysfunction, was significantly impaired in the left ventricle and had improved after L-T4 therapy. We found that IVA is able to detect early effects of subclinical hypothyroidism on LV systolic functions and L-T4 therapy can improve ventricular functions.

The Metabolic Effects of Pre-probiotic Supplementation After Roux-en-Y Gastric Bypass (RYGB) Surgery: a Prospective, Randomized Controlled Study.

PURPOSE: Following Roux-en-Y gastric bypass (RYGB), positive alterations are observed in gut microbiota and intestinal peptides. Previous studies demonstrated similar alterations observed in cases when pre-probiotics are used without surgery. The aim of this trial was to evaluate the effectiveness of early use of pre-probiotics after RYGB. MATERIAL AND METHODS: The operation and follow-up of the patients were performed at Istanbul University Medical Faculty. Thirty-two patients who had undergone RYGB were randomized to pre-probiotic group (PreProBG, n = 16; 200 g/day yogurt plus 10 g/day inulin+oligofructose) and probiotic group (ProBG, n = 16; 200 g/day yogurt only) for 6 months. Blood samples (glucose, insulin, A1c, GLP-1, PYY), anthropometric measurements, and appetite ratings have been evaluated at baseline and 3 (m3) and 6 (m6) months after RYGB. RESULTS: Initial anthropometric measurements and appetite ratings decreased significantly after surgery and there were no significant differences between the groups. The decrease of area under the curve(insulin) was less and has a positive correlation with the changes in anthropometric measurements in PreProBG. GLP-1 and PYY which increased dramatically after surgery in all patients were higher in PreProBG. But this increase had a negative correlation with the changes in anthropometric measurements during the study. CONCLUSION: Increased insulin, GLP-1, and PYY secretion was more enhanced by pre-probiotic use in early postoperative period. But this increase not only in anthropometric measurements but also in appetite ratings affects negatively, contrary to expectations. In summary, it should be investigated with new studies that use of pre-probiotics in the late postoperative period may be more effective in patients with weak insulin and incretin response and therefore insufficient weight loss. Trial Registration clinicaltrials.gov Identifier: NCT03517345.

Gastroesophageal Reflux in Asymptomatic Patients with Diabetes: An Impedance Study Diabetes, Obesity and Gastroesophageal Reflux.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is more frequent in patients with diabetes mellitus (DM).The aim of the present study was to evaluate gastroesophageal reflux (GER) in asymptomatic patients with DM using 24-h pH impedance. MATERIALS AND METHODS: 19 healthy controls and 35 patients with DM without typical GERD symptoms were enrolled in the study. A 24-h pH-impedance study, esophageal manometry and gastroscopy were performed on all patients with DM. In the control group, an impedance study was performed on all subjects, and gastroscopy and esophageal manometry were performed on those who consented to the procedures. Patients with diabetes were categorized as obese [body mass index (BMI)>30 kg/m2] or non-obese (BMI<30 kg/m2) and both groups were compared with healthy controls. RESULTS: The mean BMI was similar in the control group (27.3±2.6 kg/m2) and the diabetic group (28.7±5 kg/m2) (p>0.05).Erosive esophagitis was found in 7.5% of the DM group. Esophageal dysmotility was higher in diabetics compared to the control group (45.5 vs. 11%, p=0.04). Neuropathy was found to be an independent risk factor for dysmotility. The mean DeMeester score (DMS) (25.6±32.5 vs. 11.2±17, p=0.01) and bolus exposure time (2.1±1.3 vs.1.3±1.3 min, p=0.009) were higher in the DM group compared with the control group.The difference was mainly observed between obese diabetics and the control group (p<0.05). The mean DMS, pathologic acid reflux, and esophageal dysmotility rate were higher in patients without complications of DM (p<0.05). BMI was higher in these patients than in patients with complications. CONCLUSION: Acid reflux is common in patients with diabetes.GER is associated with the existence of obesity rather than hyperglycemia.

Leptin concentration indexed to fat mass is increased in untreated anorexia nervosa (AN) patients.

CONTEXT: Data regarding serum adipocytokine and ghrelin concentrations in different stages of anorexia nervosa (AN) is conflicting. OBJECTIVE: Our aim is to determine serum concentrations of adiponectin (ApN), leptin and ghrelin in different stages of AN and to evaluate their relationships with study parameters. DESIGN SETTING AND PARTICIPANTS: Study group was composed of four subgroups: Group 1: patients with a recent diagnosis of AN (n = 19); group 2: weight recovered (10% increase in body weight compared with baseline) subgroup of group 1 during follow-up (n = 10); group 3: recovered patients with a previous history of AN but normal menstrual cycles and body weight currently (n = 10); group 4: control group (n = 10). Venous blood was obtained for measurements of biochemical/hormonal parameters, ApN, leptin and ghrelin. Body composition was determined by bioimpedance analysis. MAIN OUTCOME MEASURES: Changes in adipocytokine and ghrelin concentrations and relationships with anthropometric/biochemical parameters. RESULTS: Leptin: fat mass (kg) ratio was significantly higher in group 1 patients compared with group 4 (4.3 +/- 4.6 vs. 1.1 +/- 0.5 microg/l kg, P < 0.01). No significant difference was observed among ghrelin concentrations. Leptin showed significant positive correlation with body fat mass in all groups. ApN showed significant positive association with body mass index in Group 1. CONCLUSIONS: Leptin concentrations indexed to fat mass may indicate a nonphysiological higher set point of leptin per unit fat mass in treatment-naive AN patients. Correlation pattern between ApN and fat mass is modified also. Altered adipocytokine profile in AN may contribute to anorectic behaviour.

Calcitriol treatment in patients with low vitamin D levels.

The aim of the the study is to compare the effects of cholecalciferol and calcitriol on bone mineral metabolism in women with vitamin D deficiency. Calcitriol was associated with a significant increase in bone mineral density at the lumbar spine in patients with low vitamin D levels. PURPOSE/INTRODUCTION: Active vitamin D analogs may have larger impact in decreasing bone loss and fracture rate compared to cholecalciferol in osteoporosis. However, their effects in the treatment of vitamin D deficiency compared to cholecalciferol are not clear. The aim of the present study is to compare the effects of cholecalciferol and calcitriol on bone mineral metabolism and bone mineral density in pre- and postmenopausal women with vitamin D deficiency. METHODS: This was a 6-month prospective, open-label, controlled clinical trial. Eligible 120 participants were pre- and postmenopausal women diagnosed with vitamin D deficiency. Forty-three subjects (group 1) received 1000 IU of cholecalciferol and 1 g of calcium daily. The other 77 subjects (group 2) received 0.5 µg calcitriol in addition to 400 IU of cholecalciferol and 1 g of calcium daily. RESULTS: Oral vitamin D supplementation did not increase bone mineral density after 6 months of intervention in group 1. On the other hand, bone mineral density at the lumbar spine increased from 0.809 ± 0.172 to 0.848 ± 0.161 g/cm2 in group 2 patients (p < 0.017 vs baseline). CONCLUSIONS: Oral daily calcitriol was associated with a significant increase in bone mineral density at the lumbar spine in patients with low vitamin D, elevated PTH, and osteoporosis.

Prevalence of papillary thyroid cancer in subacute thyroiditis patients may be higher than it is presumed: retrospective analysis of 137 patients.

Background The association of subacute thyroiditis (SAT) and papillary thyroid carcinoma is a rare finding. In this study, we aimed to investigate the prevalence of differentiated thyroid cancer in a cohort of patients followed with the diagnosis of SAT. Patients and methods We retrospectively screened medical records of Endocrinology and Metabolism outpatient clinic in the past 20 years for patients with SAT. Patients with nodules and suspicious ultrasonography findings who underwent fine needle aspiration biopsy (FNAB) and operated due to malignancy risk were identified. Results We identified 137 (100 females, 37 males) patients with reliable records to confirm the diagnosis of SAT. The mean age of female patients was 41.1 ± 9.1 (range, 20-64) and of male patients was 43.0 ± 9.3 (range, 20-65). One or more FNAB was performed in 23 of the patients (16.8%) at the beginning and/or during the follow-up period when needed. Seven patients with suspicious FNAB findings were operated, and histopathological examination of the nodules confirmed the diagnosis of papillary thyroid carcinoma in 6 patients (4.4%). Conclusions Our observations suggesting a relatively higher prevalence of thyroid cancer in a small series of SAT patients warrant further studies to identify the real frequency of differentiated thyroid cancer and its association with inflammatory pathogenesis of SAT. This finding is compatible with the trend of increased thyroid cancer incidence all over the world. A repeat ultrasonography after resolution of clinical and inflammatory findings, and FNAB should be recommended to all patients with suspicious nodules.

Hypovitaminosis D is Associated with Endothelial Dysfunction in Patients with Metabolic Syndrome.

OBJECTIVES: Recent research has shown that hypovitaminosis D may increase the risk of hypertension, vascular disease, diabetes mellitus, obesity and Metabolic Syndrome (MetS). Endothelial Dysfunction (ED) is one of the key components of MetS which is associated with an imbalance between vasoactive substances such as Nitric Oxide (NO) and Endothelins (ET). In this study, we assessed the association of 25(OH) D3 level with endothelial dysfunction and subclinical atherosclerosis in MetS patients. DESIGN AND METHODS: 105 MetS patients and 48 controls were included. 25(OH) D3 levels were measured using Ultra-High Performance Liquid Chromatography (UHPLC). NOx (NO2 plus NO3) and Endothelin- 1(ET-1) concentrations were determined along with routine biochemical tests. Flow-Mediated Dilatation (FMD) and carotid Intima-Media Thickness (cIMT) were measured by ultrasonography. RESULTS: In MetS patients, vitamin D and NOx levels were significantly lower (p<0.001), while ET-1 levels were higher than controls (p<0.005). MetS patients with ED exhibited significantly lower vitamin D levels than their counterparts free of ED. Vitamin D levels were correlated positively with FMD and NOx, and negatively with systolic blood pressure and body mass index. Subclinical atherosclerosis as assessed by the cIMT did not associate with low vitamin D levels. CONCLUSION: Vitamin D deficiency seen in MetS patients is more prominent in the presence of ED. Hypovitaminosis D may affect endothelial cells, and participate in the development of hypertension.

A rare cause of dilated cardiomyopathy: hypocalcemia

SUMMARY Dilated cardiomyopathy (DCM) is characterized by systolic dysfunction and is usually idiopathic. A rare cause of reversible DCM is hypocalcemia. Calcium plays a key role in myocardial contraction. Hypocalcemia can lead to a decrease in contraction, left ventricular systolic dysfunction, and heart failure with reduced ejection fraction (EF). Hypocalcemia-related reversible DCM reports are rare. Herein, we present two cases with heart failure caused by hypocalcemia developed due to hypoparathyroidism. The first case presented with severe heart failure and an extremely low serum calcium level (4.4 mg/dL) due to idiopathic hypoparathyroidism. The second case, which was also admitted with heart failure due to hypocalcemia, had iatrogenic hypoparathyroidism due to a subtotal thyroidectomy. In both cases, patients had reduced left ventricular systolic functions (EF was 33% and 42%, respectively). After calcium replacement and heart failure treatment, calcium levels were normalized. A significant and rapid improvement in heart failure was achieved in both cases (EF 60% and 50%, respectively). Serum calcium levels should always be measured in patients with heart failure, and the etiology of hypocalcemia should be sought. In addition to the standard pharmacotherapy of heart failure with reduced EF, calcium supplementation is essential for treating these patients.

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS: This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS: Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. CONCLUSION: We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Comparison of 68Ga-DOTATATE PET-CT, ¹8F-FDG PET-CT and 99mTc-(V)DMSA scintigraphy in the detection of recurrent or metastatic medullary thyroid carcinoma.

PURPOSE: We aimed to compare the efficacies of gallium-68 (68Ga) DOTATATE PET-computed tomography (CT), fluorine-18 fluorodeoxyglucose (18F-FDG) PET-CT and technetium-99m (99mTc)-(V)DMSA scintigraphy in the detection of residual/metastatic medullary thyroid carcinoma (MTC). MATERIALS AND METHOD: We retrospectively evaluated DOTATATE PET-CT, 18F-FDG PET-CT and (V)DMSA scintigraphy of 22 MTC patients, all taken within a 6-month period in each patient, because of high levels of calcitonin (Ct) and carcinoembryonic antigen (CEA). We investigated the relationships between the results of the imaging modalities and tumour marker levels and the sporadic versus hereditary nature of the disease, as well as the effect of imaging results on patient management. RESULTS: The ages of the patients at diagnosis were between 20 and 69 years. The median levels of Ct and CEA were 871.5 pg/ml and 11.2 ng/ml, respectively. In the patient-based analysis, we observed at least one focus of abnormal uptake in 15 of 22 DOTATATE PET-CT (68.2% sensitivity), eight of 18 18F-FDG PET-CT (44.4% sensitivity) and five of 15 (V)DMSA scans (33.3% sensitivity). These data showed a significant difference between DOTATATE PET-CT and (V)DMSA scintigraphy (P=0.016), whereas the relationships between DOTATATE PET-CT and 18F-FDG PET-CT and between 18F-FDG PET-CT and (V)DMSA scintigraphy showed no significant differences (P>0.05). In the lesion-based analysis, 134 lesions were detected with DOTATATE PET-CT, 76 lesions with 18F-FDG PET-CT and nine lesions with (V)DMSA scintigraphy. CONCLUSION: DOTATATE PET-CT is an efficient imaging modality in MTC patients with increased Ct and CEA (especially >1000 pg/ml and 50 ng/ml, respectively) for localizing recurrent or metastatic disease. 18F-FDG PET-CT can be performed if DOTATATE PET-CT is not available, but (V)DMSA scintigraphy is not recommended.

Serum ghrelin and adiponectin levels are increased but serum leptin level is unchanged in low weight Chronic Obstructive Pulmonary Disease patients.

BACKGROUND: Weight loss and muscle wasting are common features reported in COPD patients and they are all related with systemic inflammation. In this study, the relationship between pulmonary functions and inflammatory and metabolic parameters in low weight COPD patients were investigated. METHODS: Fifty male COPD patients were grouped according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Group 1: Mild-moderate COPD patients (n=18; with a mean age of 66.4 ± 9.2 yrs; body mass index (BMI):19.7 ± 1.5 kg/m(2)), group 2: Severe-very severe COPD patients (n=32; with a mean age of 65.9 ± 10.0 yrs; BMI:19.3 ± 1.6 kg/m(2)), group 3: Control group composed of healthy nonsmoking males (n=17; with a mean age of 50.2 ± 8.4 yrs; BMI:21.85 ± 1.5 kg/m(2)). Anthropometric parameters, serum levels of adiponectin (ApN), ghrelin, leptin, hsCRP, IL-6, IL-1ß, IL-8, TNF-α and pulmonary functions were compared. RESULTS: Adiponectin concentration was higher in group 1 (43.3 ± 28.6 ng/mL; p<0.05) and group 2 (59.9 ± 31.8 ng/mL; p<0.001) when compared with the control group (23.5 ± 13.6 ng/mL). Ghrelin concentrations were higher in COPD groups (1281.0 ± 1173.7 and 1840.0 ± 403.6 pg/mL; p<0.05) compared to the control subjects (554.0 ± 281.9 pg/mL). When the groups were compared, no significant difference was found for leptin, IL-1ß, TNF-α, and IL-8. Interleukin-6 and hsCRP levels were higher in group 1 than in the control group. ApN was negatively correlated with BMI and FEV1. In all groups, FEV1 showed positive correlation with BMI, skinfold thicknesses, insulin and triglyceride; negative correlation with age, pack/years, HDL-Chol and ApN. Increased SHBG with decreased insulin level and HOMA-IR may indicate increased insulin sensitivity in COPD groups. CONCLUSION: The anti-inflammatory effect of ApN and ghrelin is more evident in severe-very severe COPD patients.