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.

Risk of impulse control disorders in patients with Cushing's disease: do not blame cabergoline but do not give up caution.

PURPOSE: To asses risk of new-onset impulse control disorders (ICDs) in patients with Cushing's disease (CD) who initiated cabergoline (CBG) and to determine frequency of ICDs in CBG-treated patients with CD. METHODS: This naturalistic observational study had prospective and cross-sectional arms which included patients at five referral centers based in Istanbul. Patients who were scheduled for CBG were assigned to prospective arm. These patients underwent neuropsychological tests (Barratt Impulsiveness Scale, Minnesota Impulsive Disorders Interview, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Go/No-Go Task, Iowa Gambling Task, and Short Penn Continuous Performance Test) for assessment of impulsivity and psychiatric evaluations at baseline, 3, 6, and 12 months of CBG treatment. Impulsivity and new-onset ICDs were prospectively assessed. Patients with CD with current CBG treatment for ≥ 3 months and matched CBG-naïve patients with CD were included in cross-sectional arm. These patients underwent the same neuropsychological and psychiatric assessments. The impulsivity and frequency of ICDs were compared between CBG-treated and CBG-naïve patients with CD. RESULTS: The follow-up duration of prospective cohort (n = 14) was 7.3 ± 2.3 months. One patient developed major depressive episode and another patient developed compulsive gambling after CBG. We observed no significant changes in impulsivity scores during follow-up. In cross-sectional arm, CBG-treated (n = 34) and CBG-naïve patients (n = 34) were similar in impulsivity scores and frequency of ICDs [3 patients (8.8%) vs. 2 patients (5.9%) respectively, p = 1.0]. CONCLUSION: CBG-treated patients with CD appeared to have a low risk of ICDs, suggesting that CBG still holds promise as a safe agent in CD.

Transglutaminase 2 expression is associated with increased risk of lymph node metastasis and recurrence in papillary thyroid cancer.

PURPOSE: Transglutaminase 2 (TG2) is associated with mobilization, invasion, and chemoresistance of tumor cells. We aimed to determine whether the immunohistochemical staining with TG2 antibody differs between metastatic and non-metastatic papillary thyroid cancer patients. METHODS: We included 76 patients with papillary thyroid cancer (72% female, median age 52 (24-81) years, follow-up time 107 (60-216) months). Thirty of them with no metastasis, 30 of them with only lymph node metastasis and 16 patients with distant ± lymph node metastasis. Immunohistochemical staining of TG2 antibody was evaluated in the primary tumor and extra-tumoral tissue. We also divided subjects into two groups according to their primary tumor TG2 staining score (group A, high risk group: ≥3, n = 43; group B, low risk group: <3, n = 33). RESULTS: Vascular invasion (p < 0.001), thyroid capsule invasion (p < 0.001), extrathyroidal extension (p < 0.001), intrathyroidal dissemination (p = 0.001), lymph node metastasis (p < 0.001), presence of aggressive histology (p < 0.001) were significantly higher in group A. No significant difference was found between the groups in terms of distant metastasis. Based on ATA risk classification 95.5% of patients with low risk were in group B but 86.8% of intermediate risk and 56.3% of high risk were in group A. In regression analysis, lymph node metastasis increased by 1.9 times with each one point increase in TG2 staining score. CONCLUSION: TG2 staining score of the primary tumor may be a predictive factor for lymph node metastasis. High or low TG2 scores may effect the frequency of follow-up and decision of treatment regimens.

The first successful desensitization protocol in exenatide allergy: a case report.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are important treatment options in obese patients with type 2 diabetes. To date, few immediate allergic reactions due to GLP-1 receptor agonists were reported. One report revealed that a patient with a level 1 anaphylaxis according to Brighton Criteria due to an exendin based GLP-1 receptor agonist was able to tolerate liraglutide (Human GLP-1 analogue), the alternative GLP-1 receptor agonist. Since exenatide is the only available GLP-1 receptor agonist covered by insurance in Turkey, a drug desensitization protocol, the only therapeutic method in hypersensitivity reactions used in case of absence of an alternative drug, was considered. Here, we report a successful desensitization protocol for the first time in two obese diabetic patients with an immediate hypersensitivity to exenatide. CASE PRESENTATION: The first patient was a 47 year-old female. She was referred to our outpatient allergy clinic because of a generalized urticaria developed within minutes after the last dose, following a week of an exenatide BID 5 mcg/20 mcl treatment. Although the reaction was sudden onset, it did not meet the Brighton Criteria of anaphylaxis. The second patient was a 46 year-old female. She had a large local immediate injection site reaction that appeared 15 min following an exenatide BID 5 mcg/20 mcl injection. The injection site reaction was not accompanied by a systemic allergic reaction. We performed desensitization with exenatide to two patients who need GLP-1 receptor agonist treatment. Protocol was completed in 7 steps in approximately 3 h, with the aim of reaching the daily dosage of exenatide. Throughout this process, we observed that both cases tolerated the protocol without any complaints or complications. Following the protocol, the patients safely tolerated the treatment for 3 months. CONCLUSIONS: We present the first successful desensitization protocol to exenatide in both local and/or systemic immediate hypersensitivity reactions and indicate the importance of desensitization in patients who do not have alternative therapies.

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.

Cytokine Profile in Patients With Maturity-onset Diabetes of the Young (MODY).

BACKGROUND/AIM: High-sensitivity C-reactive protein (hs-CRP) is used in the differential diagnosis of maturity-onset diabetes of the young (MODY)-3, but other inflammatory markers have not been investigated in MODY patients. We aimed to compare the serum levels of anti-inflammatory and proinflammatory cytokines between MODY patients and healthy subjects and show the inflammatory features in MODY subtypes. PATIENTS AND METHODS: Thirty patients with clinically suspected MODY and 34 healthy controls were included in this study. Next-generation sequencing (NGS) was used for the molecular diagnosis of MODY subtypes. Serum levels of cytokines were measured using a multiplexed cytokine assay and hs-CRP concentration was determined by the immunoturbidimetric assay. RESULTS: The hs-CRP levels were higher in both NGS-confirmed (MODY, n=17) (p=0.009) and NGS-unconfirmed (non-MODY, n=13) patients (p<0.001) than those in controls. However, IL-1ß (p=0.001), IL-6 (p=0.018), IL-31 (p=0.003), TNF-α (p<0.001), and sCD40L (p=0.007) levels of MODY patients and IL-1ß (p=0.002), IL-31 (p<0.001), IL-22 (p=0.018), and sCD40L (p=0.039) levels of non-MODY patients were lower than those of controls. While hs-CRP levels were lower in MODY3 patients than non-MODY3 patients (p=0.009), IL-17A (p=0.006) and IL-23 (p=0.016) levels for the first time in this study were found to be higher in patients with MODY3 than in patients with other MODY subtypes (p<0.05). CONCLUSION: MODY patients had lower serum levels of the proinflammatory cytokines IL-1ß, IL-6, TNF-α, IL-31, and sCD40L compared to healthy controls. High IL-17A and IL-23 levels along with low hs-CRP levels may be potential markers to distinguish MODY3 from other MODY subtypes.

Precision Diagnosis of Maturity-Onset Diabetes of the Young with Next-Generation Sequencing: Findings from the MODY-IST Study in Adult Patients.

Maturity-onset diabetes of the young (MODY) is a highly heterogeneous group of monogenic and nonautoimmune diseases. Misdiagnosis of MODY is a widespread problem and about 5% of patients with type 2 diabetes mellitus and nearly 10% with type 1 diabetes mellitus may actually have MODY. Using next-generation DNA sequencing (NGS) to facilitate accurate diagnosis of MODY, this study investigated mutations in 13 MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, and KCNJ11). In addition, we comprehensively investigated the clinical phenotypic effects of the genetic variations identified. Fifty-one adult patients with suspected MODY and 64 healthy controls participated in the study. We identified 7 novel and 10 known missense mutations localized in PDX1, HNF1B, KLF11, CEL, BLK, and ABCC8 genes in 29.4% of the patient sample. Importantly, we report several mutations that were classified as "deleterious" as well as those predicted as "benign." Notably, the ABCC8 p.R1103Q, ABCC8 p.V421I, CEL I336T, CEL p.N493H, BLK p.L503P, HNF1B p.S362P, and PDX1 p.E69A mutations were identified for the first time as causative variants for MODY. More aggressive clinical features were observed in three patients with double- and triple-heterozygosity of PDX1-KLF11 (p.E69A/p.S182R), CEL-ABCC8-KCNJ11 (p.I336, p.G157R/p.R1103Q/p.A157A), and HNF1B-KLF11 (p.S362P/p.P261L). Interestingly, the clinical effects of the BLK mutations appear to be exacerbated in the presence of obesity. In conclusion, NGS analyses of the adult patients with suspected MODY appear to be informative in a clinical context. These findings warrant further clinical diagnostic research and development in different world populations suffering from diabetes with genetic underpinnings.

Pancreatic MR imaging and endocrine complications in patients with beta-thalassemia: a single-center experience.

Iron deposition in various organs can cause endocrine complications in patients with transfusion-dependent beta-thalassemia. The aim was to investigate the relationship between endocrine complications and pancreatic iron overload using magnetic resonance imaging (MRI). Forty patients with transfusion-dependent thalassemia (TDT) were enrolled in the study. The magnetic resonance imagings of the patients were performed using a 1.5 Tesla Philips MRI scanner. Two out of three patients had at least one clinical endocrine complication. The rate of iron deposition was 62.5% in liver, and 45% in pancreas tissue, and was 12.5% in heart tissue. Pancreatic T2* and hepatic T2* values were significantly positively correlated (p = 0.006). Pancreatic T2* and ferritin were significantly negatively correlated (p = 0.03). Cardiac T2* values were negatively correlated with fasting blood glucose (p = 0.03). Patients with short stature had significantly higher cardiac iron burden (22.3 vs. 36.6 T2*ms; p 0.01), and patients with hypothyroidism had higher liver iron concentrations (9.9 vs. 6.4 LIC mg/g; p = 0.05). The ferritin level of 841 ng/mL and liver iron concentration (LIC) value of 8.7 mg/g were detected as the threshold level for severe pancreatic iron burden (AUC 70%, p:0.04, AUC 80%, p = 0.002, respectively). Moreover, males were found to have decreased pancreas T2* values compared with the values in females (T2* 19.3 vs. 29.9, p = 0.05). Patients with higher ferritin levels over than 840 ng/mL should be closely monitored for pancreatic iron deposition, and patients with endocrine complications should be assessed in terms of cardiac iron burden.

A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission.

BACKGROUND: Transsphenoidal endoscopic surgery is the first-line treatment for growth hormone-secreting adenomas. OBJECTIVE: To analyse the results of the transsphenoidal endoscopic approach for acromegaly and to determine the predictive factors of remission. METHODS: A single-centre retrospective review was performed in patients who underwent endoscopic transsphenoidal surgery for acromegaly between January 2009 and January 2019. Demographic features, clinical presentation, histopathology records, complications and pre- and postoperative radiologic and endocrinological assessments were evaluated. The factors that influenced the remission rates were investigated. RESULTS: A total of 73 patients underwent surgery via the transsphenoidal endoscopic approach. Cavernous sinus invasion was detected in 32 patients (43.8%); and macroadenoma, in 57 (78%). The pathology specimens of the 27 patients (36.9%) showed dual-staining adenomas with prolactin. A total of 51 patients (69.8%) attained biochemical remission 1 year after surgery. A second operation was performed in 10 patients (13.6%) with residual tumours without biochemical remission in the first year. Six (60%) of the patients attained remission at the last follow-up. Transient diabetes insipidus was observed in 18 patients (24.6%); and rhinorrhoea, which was resolved with conservative treatment, in 4 (5.4%). None of the patients developed panhypopituitarism. The presence of cavernous sinus invasion and preoperative IGF-1, immediate postoperative GH and third-month IGF-1 levels were predictive of remission. CONCLUSION: Transsphenoidal endoscopic surgery is a safe and effective treatment for acromegaly. Reoperation should be considered in patients with residual tumours without remission.

Monogenic Childhood Diabetes: Dissecting Clinical Heterogeneity by Next-Generation Sequencing in Maturity-Onset Diabetes of the Young.

Diabetes is a common disorder with a heterogeneous clinical presentation and an enormous burden on health care worldwide. About 1-6% of patients with diabetes suffer from maturity-onset diabetes of the young (MODY), the most common form of monogenic diabetes with autosomal dominant inheritance. MODY is genetically and clinically heterogeneous and caused by genetic variations in pancreatic ß-cell development and insulin secretion. We report here new findings from targeted next-generation sequencing (NGS) of 13 MODY-related genes. A sample of 22 unrelated pediatric patients with MODY and 13 unrelated healthy controls were recruited from a Turkish population. Targeted NGS was performed with Miseq 4000 (Illumina) to identify genetic variations in 13 MODY-related genes: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, and KCNJ11. The NGS data were analyzed adhering to the Genome Analysis ToolKit (GATK) best practices pipeline, and variant filtering and annotation were performed. In the patient sample, we identified 43 MODY-specific genetic variations that were not present in the control group, including 11 missense mutations and 4 synonymous mutations. Importantly, and to the best of our knowledge, the missense mutations NEUROD1 p.D202E, KFL11 p.R461Q, BLK p.G248R, and KCNJ11 p.S385F were first associated with MODY in the present study. These findings contribute to the worldwide knowledge base on MODY and molecular correlates of clinical heterogeneity in monogenic childhood diabetes. Further comparative population genetics and functional genomics studies are called for, with an eye to discovery of novel diagnostics and personalized medicine in MODY. Because MODY is often misdiagnosed as type 1 or type 2 diabetes mellitus, advances in MODY diagnostics with NGS stand to benefit diabetes overall clinical care as well.

Pituitary Iron Deposition and Endocrine Complications in Patients with ß-Thalassemia: From Childhood to Adulthood.

The endocrinological complications are a great concern in transfusion-dependent ß-thalassemia (ß-thal) patients. The pituitary iron deposition is regarded as the main cause of hormonal changes in thalassemic patients. In this study, our aim was to explore the association between endocrinological complications and pituitary iron overload by magnetic resonance imaging (MRI). Fifty transfusion-dependent thalassemia (TDT) patients were recruited for the study. Pituitary MRIs of patients were taken using a 1.5 Tesla Philips MRI machine. There was at least one clinical endocrine complication in two of three patients. The iron accumulation was moderate in the liver (60.0%) and was mild in hypophysis (16.0%) and in heart (8.0%). The hypogonadism and diabetes mellitus (DM) were not seen with a significantly increased pituitary iron burden. The hypogonadism was related to cardiac iron deposition (p = 0.04). The short stature was associated with a hepatic iron overload (p = 0.05). The conventional follow-up of patients with TDT might be inadequate and screening of patients with MRI of hypophysis along with heart and liver leads to better results.

Determination of genetic changes of Rev-erb beta and Rev-erb alpha genes in Type 2 diabetes mellitus by next-generation sequencing.

BACKGROUND: The nuclear receptors Rev-erb alpha and Rev-erb beta are transcription factors that regulate the function of genes in glucose and lipid metabolism, and they also form a link between circadian rhythm and metabolism. We evaluated the variations in Rev-erb alpha and Rev-erb beta genes together with biochemical parameters as risk factors in type 2 diabetic (T2DM) patients. METHODS: Molecular analyses of Rev-erb alpha and Rev-erb beta genes were performed on genomic DNA by using next-generation sequencing in 42 T2DM patients (21 obese and 21 non-obese) and 66 healthy controls. RESULTS: We found 26 rare mutations in the study groups, including 13 missense mutations, 9 silent mutations, 3 5'UTR variations, and a 3'UTR variation, of which 9 were novel variations (5 missense and 3 silent and 1 5'UTR). Six common variations were also found in the Rev-erb genes; Rev-erb beta Chr3:24003765 A > G, Rev-erb beta rs924403442 (Chr3:24006717) G > T, Rev-erb alpha Chr17:38253751 T > C, Rev-erb alpha rs72836608 C > A, Rev-erb alpha rs2314339 C > T and Rev-erb alpha rs2102928 C > T. Of these, Rev-erb beta Chr3:24003765 A > G was a novel missense mutation (p.Q197R), while others were identified as intronic variants. T2DM patients with Rev-erb beta rs924403442 T allele had lower body surface area (BSA) than noncarriers (GG genotype) (p = 0.039). Rev-erb alpha rs72836608 A allele and Rev-erb alpha rs2314339 CC genotype were associated with decreased serum HDL-cholesterol levels in T2DM patients (p = 0.025 and p = 0.027, respectively). In our study, different effects of Rev-erbs polymorphisms were found according to gender and presence of obesity. Rev-erb alpha rs72836608 (C > A) and rs2314339 (C > T) and Rev-erb alpha rs2102928 (C > T) were associated with low HDL-C levels in male T2DM patients. In female patients, Rev-erb alpha rs2102928 (C > T) was associated with high microalbuminuria and Rev-erb beta rs9244403442 G > T was associated with low HDL and high BSA values. In addition, Rev-erb alpha Chr17: 38,253,751 (T > C), rs72836608 (C > A), and rs2314339 (C > T) and Rev-erb beta Chr3:24003765 (A > G) were associated with increased serum GGT levels in obese T2DM patients. In non-obese patients, Rev-erbs SNPs had no effect on serum GGT levels. CONCLUSION: Our findings indicate that variations in the Rev-erb alpha and Rev-erb beta genes can affect metabolic changes in T2DM and these effects may vary depending on gender and obesity.

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.

Disease Activity May Not Affect the Prognosis of Coexisting Thyroid Cancer in Acromegalic Patients.

Acromegaly is known to be associated with high incidence of malignancies probably due to the mitogenic effects of IGF-1. Differentiated thyroid cancer (DTC) is reported to be one of the most frequent malignancies associated with acromegaly. But there is no data about the clinical course of DTC in acromegalic patients. In this study, we evaluated the course of DTC in 14 acromegalic patients retrospectively. Fourteen papillary thyroid cancer patients without acromegaly, who were matched with the acromegalic patient group for age, gender and properties of thyroid cancer, were investigated as the control group. We identified no change in the course and treatment responses of DTC in association with the acromegaly activity, gender, age and disease duration, and all patients were found to be in remission for DTC at the time of investigation. Retrospective analysis of this cohort suggests that the activity of acromegaly may not affect the treatment responses and prognosis of coexisting DTC.

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.

Association of Pro-apoptotic Bad Gene Expression Changes with Benign Thyroid Nodules.

BACKGROUND/AIM: This study aimed to investigate the role of the mitochondrial apoptotic pathway in benign thyroid nodules. MATERIALS AND METHODS: Paired samples of nodular and normal tissues were collected from 26 patients with nodular goiters undergoing thyroidectomy. Variable expression of Bcl-2, Bax and Bad genes were evaluated by quantitative PCR. RESULTS: Expression level of Bad gene in nodules was found to be significantly decreased compared to normal tissues (p=0.049). A positive correlation was observed between nodule size and Bad expression levels (correlation coefficient=0.563, p=0.004); and this correlation was stronger in hot nodules (n=18, correlation coefficient=0.689, p=0.003). No significant difference was observed between nodular and normal tissue expressions of Bax and Bcl-2. CONCLUSION: These results suggest that Bad expression correlates with the size of benign thyroid nodules and also its relatively lower expression in nodules, warrant further investigation.

Evaluation of Glutathione Peroxidase and KCNJ11 Gene Polymorphisms in Patients with New Onset Diabetes Mellitus After Renal Transplantation.

Introduction Genetic mutations such as C599T polymorphism in glutathione peroxidase [GPX1] gene and polymorphisms in potassium channel (KCNJ11) genes have recently been proposed in the etiopathogenesis of new onset diabetes mellitus after renal transplantation (NODAT). We aimed to examine the association of GPX1 and KCNJ11 polymorphisms in NODAT. Materials and Methods This is a monocenter case-control study with a total of 118 renal transplant recipients who were divided into 2 groups; NODAT and normal glucose tolerance. Relation of GPX1 and KCNJ11 polymorphisms were investigated between these groups. PCR-RFLP method was used for genotyping of polymorphisms in the GPX1 (rs1050450) and KCNJ11 (rs1805127) genes. Two alleles were visualized for each gene (C/T for GPX1 and A/G for KCNJ11). Results NODAT was correlated with age at transplantation (p<0.001, r=0.380), post-transplant systolic blood pressure (BP) (p=0.02, r=0.211), post-transplant non-HDL cholesterol levels (p=0.01, r=0.803), degree of weight change at the end of the first year (p=0.01, r=0.471), presence of pre-transplant hypertension (HT) (p=0.02, r=0.201), family history of diabetes (p=0.01, r=0.29) and dyslipidemia (p=0.012, r=0.362). GPX1 polymorphism of TT (mutant) allele was significantly more frequent in patients with NODAT (p<0.001, r=0.396) independent from other diabetogenic risk factors. KCNJ11 polymorphisms were similar in both groups and did not show any significant association with NODAT (p=0.10). Conclusions In addition to several diabetogenic risk factors, C599T polymorphisms in GPX1 gene might also contribute to the development of NODAT. Further studies on larger patient series are necessary in order to reach definitive suggestions.