Repeat endoscopic endonasal transsphenoidal surgery for residual or recurrent Cushing's disease: safety, feasibility, and success.

PURPOSE: The success and outcomes of repeat endoscopic transsphenoidal surgery (ETS) for residual or recurrent Cushing's disease (CD) are underreported in the literature. This study aims to address this gap by assessing the safety, feasibility, and efficacy of repeat ETS in these patients. METHODS: A retrospective analysis was conducted on 56 patients who underwent a total of 65 repeat ETS performed by a single neurosurgeon between January 2006 and December 2020. Data including demographic, clinical, laboratory, radiological, and operative details were collected from electronic medical records. Logistic regression was utilized to identify potential predictors associated with sustained remission. RESULTS: Among the cases, 40 (61.5%) had previously undergone microscopic surgery, while 25 (38.5%) had prior endoscopic procedures. Remission was achieved in 47 (83.9%) patients after the first repeat ETS, with an additional 9 (16.1%) achieving remission after the second repeat procedure. During an average follow-up period of 97.25 months, the recurrence rate post repeat surgery was 6.38%. Sustained remission was achieved in 48 patients (85.7%), with 44 after the first repeat ETS and 4 following the second repeat ETS. Complications included transient diabetes insipidus (DI) in 5 (7.6%) patients, permanent (DI) in 2 (3%) patients, and one case (1.5%) of panhypopituitarism. Three patients (4.6%) experienced rhinorrhea necessitating reoperation. A serum cortisol level > 5 µg/dL on postoperative day 1 was associated with a reduced likelihood of sustained remission. CONCLUSION: Repeat ETS is a safe and effective treatment option for residual or recurrent CD with satisfactory remission rates and low rates of complications.

Association of Human Leukocyte Antigen Genotypes with Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine-Induced Subacute Thyroiditis.

Background: Despite mass vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) is rarely seen as a complication. The reason why some individuals are susceptible to developing vaccine-induced SAT is not known. SAT develops in genetically predisposed individuals who carry specific human leukocyte antigen (HLA) haplotypes. It is unknown whether specific HLA alleles are associated with SARS-CoV-2 vaccine-induced SAT. Objective: This study compared the HLA profiles of patients with SARS-CoV-2 vaccine-induced SAT to controls, to assess whether there is an association between specific HLA genotypes and development of SAT. The relationship between HLA genotypes and the clinical course of SARS-CoV-2 vaccine-induced SAT was also evaluated. Methods: A case-control study was conducted in a Turkish tertiary care center. Fourteen patients with SARS-CoV-2 vaccine-induced SAT and 100 healthy controls were included. HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 frequencies were analyzed by next-generation sequencing. Results: The frequencies of HLA-B*35 and HLA-C*04 alleles were significantly higher in SARS-CoV-2 vaccine-induced SAT cohort when compared with controls (HLA-B*35: 13 [93%] vs. 40 [40%], p < 0.001; HLA-C*04: 13 [93%] vs. 43 [43%], p < 0.001, respectively). More severe thyrotoxicosis was seen in patients having HLA-B*35 and HLA-C*04 homozygous alleles (free thyroxine: 4.47 ng/dL [3.77-5.18] vs. 1.41 ng/dL [1.22-2.63], p = 0.048). Inflammation tended to be more severe in homozygous patients (C-reactive protein: 28.2 mg/dL [13.6-42.9] vs. 4.8 [1.2-10.5], p = 0.07). Conclusions: The frequencies of HLA-B*35 and HLA-C*04 alleles were higher in SARS-CoV-2 vaccine-induced SAT compared with controls. Homozygosity for HLA-B*35 and HLA-C*04 was associated with thyrotoxicosis and a greater inflammatory reaction. Our findings should be confirmed in studies of other populations.

SARS-CoV-2 Vaccine-induced Thyroiditis: Safety of Revaccinations and Clinical Follow-up.

CONTEXT: The number of reported cases with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) and Graves' disease (GD) is growing. However, active debate continues about managing such side effects and the safety of repeat or booster doses of the vaccines in such cases. OBJECTIVES: This study aims to present long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT or GD cases and provide data regarding the safety of revaccinations. METHODS: Patients diagnosed with SARS-CoV-2 vaccine-induced SAT or GD were included. Data regarding the long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT and GD cases and outcomes of repeat or booster SARS-CoV-2 vaccinations were documented. The literature, including cases of SARS-CoV-2 vaccine-induced SAT or GD, was reviewed. RESULTS: Fifteen patients with SARS-CoV-2 vaccine-induced SAT and 4 with GD were included. Pfizer/BioNTech COVID-19 vaccine (BNT162b2) was associated with symptoms in a majority of cases with SAT and all with GD. Median time from vaccination to symptom onset was 7 and 11.5 days, respectively, while 7 and 2 patients required medical treatment in SAT and GD groups, respectively. Remission was documented in 10 SAT patients, with a median time to remission of 11.5 weeks. No exacerbation/recurrence of SAT occurred in 7 of 9 patients who received a repeat vaccination dose, while symptoms of SAT worsened following the second vaccination in 2 cases. None of the patients experienced severe side effects that could be associated with revaccinations. CONCLUSIONS: Revaccinations appear to be safe in patients with SARS-CoV-2 vaccine-induced SAT cases, while more evidence is needed regarding SARS-CoV-2 vaccine-induced GD.

Oxysterol species generated by auto-oxidation in subclinical hypothyroidism.

BACKGROUND: Auto-oxidized oxysterols are implicated in the pathogenesis of various chronic diseases. Their concentrations are indicators of oxidative stress in vivo and associated with atherosclerosis. Subclinical hypothyroidism is related with cardiac diseases and oxidative stress, but the exact mechanisms underlying these associations are not clear yet. OBJECTIVE: To investigate the auto-oxidized oxysterols, 7-ketocholesterol (7-KC) and cholestane-3ß,5α,6ß-triol (chol-triol), in patients with subclinical hypothyroidism, as well as to evaluate the impact of restoring euthyroidism on oxysterol concentrations. METHODS: In this prospective observational study, 64 patients with newly diagnosed autoimmune thyroiditis (41 with subclinical hypothyroidism and 23 euthyroidism), and 45 healthy controls were enrolled. Age, gender, and body mass index were matched among patient groups and healthy controls. Anthropometric measurements were obtained and fasting plasma 7-ketocholesterol and cholestane-3ß,5α,6ß-triol concentrations were measured by using liquid chromatography coupled with tandem mass spectrometry. Levothyroxine was then administered to all patients with subclinical-hypothyroidism. After three months, measurements of the oxysterols and serum cholesterols from the patients who have become euthyroid were repeated. RESULTS: Concentrations of 7-ketocholesterol and cholestane-3ß,5α,6ß-triol were significantly higher in patients with subclinical-hypothyroidism when compared to both euthyroid patients and healthy controls (p < 0.001 for both oxysterols). After restoration of euthyroidism, concentrations of 7-ketocholesterol and cholestane-3ß,5α,6ß-triol decreased significantly and reached similar concentrations observed in healthy controls (p < 0.001 for both oxysterols). CONCLUSIONS: Auto-oxidized oxysterol species are higher in patients with mild thyroid dysfunction, and supported the rationale for treating subclinical-hypothyroidism.

Clinical and demographic aspects of Paget disease of bone: A multicentric study from Turkey.

OBJECTIVE: Paget disease of bone (PDB) is a metabolic bone disease that has been rarely reported in the Eastern countries. This study aimed to evaluate the clinical and demographic characteristics of patients with PDB followed up at endocrinology clinics in Turkey. METHODS: An invitation was sent to tertiary endocrinology clinics to complete a survey on the demographic, clinical, radiological, and laboratory parameters, as well as treatment modalities of patients with PDB. This study enrolled clinically and radiologically proven 185 patients with PDB from 18 endocrinology centers based in 10 cities of Turkey. RESULTS: This cohort of PDB had female preponderance (women/men: 105/80) with a mean age, during diagnosis, of 57±10 years. Most of the patients (59.6%) were symptomatic at diagnosis. Bone pain and headache were the predominant clinical symptoms. Polyostotic disease was observed in 67.5% (n=125) of patients. Frequently affected bones were skull (41.6%), pelvis (53.5%), spine (41%), and femur (25.4%). Moreover, 17 patients with skull involvement had hearing loss. Mean serum alkaline phosphatase (ALP) level (552±652 IU/L; range: 280-5762 IU/L) was over the normal reference cutoff with normal serum calcium levels. Intravenous bisphosphonates (zoledronic acid, 5 mg; pamidronate, 60-90 mg) were the most used drugs (75%) for the treatment of PDB. Most of the patients (87.1%) treated with intravenous bisphosphonates responded well, with a decrease in serum ALP level (117±114 IU/L) in the 12th month of therapy. Furthermore, 16 patients relapsed after the second year of therapy; 3 patients did not respond to the initial intravenous bisphosphonate treatment. CONCLUSION: The patients with PDB followed up by endocrinology clinics of Turkey exhibited polyostotic disease with classical clinical, radiological, and biochemical features and women's predominance with good response to intravenous bisphosphonate therapy.

Apoptosis Inhibitor of Macrophage, Monocyte Chemotactic Protein-1, and C-Reactive Protein Levels Are Increased in Patients with Metabolic Syndrome: A Pilot Study.

Background: Apoptosis inhibitor of macrophage (AIM) and monocyte chemotactic protein-1 (MCP-1) are molecules that cause migration of M1 macrophages to visceral adipocytes, which is the first step in development of metabolic syndrome. The aim of this study is to evaluate the status of AIM and MCP-1 in metabolic syndrome and to investigate their use as biomarkers. Methods: Forty metabolic syndrome patients and 40 healthy individuals were enrolled in the study. Serum AIM, MCP-1, and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay. Results: AIM, MCP-1, and CRP levels were significantly higher in the metabolic syndrome group (P < 0.01, P < 0.01, and P < 0.05, respectively). There was a positive correlation of serum AIM, MCP-1, and CRP levels with waist circumference (r = 0.480, r = 0.663, and r = 0.418, respectively; P < 0.01). Receiver operating characteristic (ROC) curve analyses revealed AIM, MCP-1, and CRP cutoff points as 2383.7 ng/mL, 172.8 pg/mL, and 0.366 mg/dL, which could be used in the diagnosis of metabolic syndrome with highest sensitivity and specificity. In the logistic regression model, including age, AIM, CRP, and MCP-1 as covariates, having serum AIM and CRP levels above cutoffs were significant independent predictors for metabolic syndrome (odds ratios 13.8 and 21.3), whereas the serum MCP-1 level was not a significant independent predictor, although the odds ratio was 2.6 (P = 0.193). Conclusions: These results suggest that AIM and MCP-1 may play a role in the pathogenesis of metabolic syndrome. AIM and CRP levels may be used as biomarkers in the diagnosis of metabolic syndrome. Although MCP-1 is not an independent predictor, its elevation in metabolic syndrome is noteworthy, which warrants further analyses in larger groups.

Clock gene PERIOD3 polymorphism is associated with susceptibility to Graves' disease but not to Hashimoto's thyroiditis.

Circadian disruption has been linked with immune-related morbidities including autoimmune diseases. PERIOD3 (PER3) clock gene is a key player in the mammalian circadian system. This study evaluated the possible association of PER3 rs2797685 (G/A) polymorphism and susceptibility of autoimmune thyroid diseases (AITD) and assessed if this SNP contributes to disease characteristics and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The PER3 rs2797685 (G/A) polymorphism was assessed in 125 patients with AITD [Graves' disease (GD), 69; Hashimoto's thyroiditis (HT), 56] and 115 unrelated healthy controls. Subjects carrying at least one variant allele of PER3 rs2797685 (GA+AA) had increased risk for GD (OR 1.9, 95% CI 1-3.61, p= .05). There were no differences in the frequencies of genotypes and alleles of the PER3 rs2797685 polymorphism between HT patients and control subjects. No association was observed between genotypes of the studied SNP and any of the disease characteristics in GD and HT patients. The GA+AA genotype of PER3 rs2797685 was associated with lower levels of IL-6 in patients with Graves' disease. There were no differences between genotypes of the studied SNP regarding TNF-α levels in GD, HT or control groups. In conclusion, this study provides the first evidence for a genetic association between GD and the PER3 gene, highlighting the possible relevance of polymorphisms in clock genes in the etiopathogenesis of AITD. However, functional studies to identify the underlying molecular mechanisms of this association are needed to translate these findings to clinical applications.

Thyroid volumes and serum VEGF levels in dyslipidemic patients: effects of statin treatment

Background/aim: Defective vascularization may be important in thyroid nodular disease. In this study, we aimed to investigate serum vascular endothelial growth factor (VEGF) levels in dyslipidemic patients with thyroid nodules, as well as the effects of statin therapy Materials and methods: The study included 37 dyslipidemic patients with thyroid nodules and 32 dyslipidemic patients without thyroid nodules. Anthropometry, serum VEGF levels, biochemical parameters, thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) levels, and thyroid sonography were determined before and after 6 months of statin therapy. Results: Patients with and without thyroid nodules had similar metabolic parameters. Serum VEGF levels did not differ between the groups. In patients with nodules, VEGF levels remained unchanged (P = 0.931) after statin therapy. However, serum VEGF levels were lowered by statin treatment in patients without nodules (P = 0.030). Statin therapy resulted in a decrease in the dominant thyroid nodule volume. The changes in thyroid volume and dominant thyroid nodule volume were not correlated with changes in VEGF, body mass index, total cholesterol, low-density lipoprotein cholesterol, or homeostatic model assessment of insulin resistance (HOMA-IR). Conclusion: Although statin treatment decreases serum VEGF levels in dyslipidemic patients without thyroid nodules, it has no lowering effect on serum VEGF levels in patients with thyroid nodules. The decrease in thyroid nodule volume with statin treatment was associated with neither metabolic parameters nor serum VEGF levels.

Chemerin is not associated with subclinical atherosclerosis markers in prediabetes and diabetes.

OBJECTIVE: Chemerin is a novel adipokine that is correlated with adipocyte differentiation, glucose metabolism, and inflammation. We aimed to investigate the relation between serum chemerin level and subclinical atherosclerosis markers as exemplified by brachial artery pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), epicardial fat thickness (EFT), and carotid plaque presence in diabetes and prediabetes. METHODS: Age-, body mass index (BMI)-, and gender-matched patients with type 2 DM (n=30), prediabetes (n=25), and normal glucose tolerance (n=25) were included in this cross-sectional study. Serum chemerin level, lipid parameters, glucose metabolism marker, baPWV, CIMT, EFT, and anthropometric were recorded. The independent risk factors for atherosclerosis markers were determined by linear and/or multiple logistic regression analysis. RESULTS: baPWV and carotid plaque presence were higher in the diabetes group than in prediabetes and control groups (p=0.039 and p=0.035 respectively), whereas serum chemerin levels were similar among groups (p=0.338). Chemerin levels were not correlated with PWV, CIMT, and epicardial fat thickness overall or in the subgroups. Overall and in the diabetes group, chemerin levels were positively correlated with the key components of metabolic syndrome as BMI, total body fat percentage, waist circumference, triglyceride, and systolic and diastolic blood pressure (BP). After adjusting for age, gender, and BMI, only the association between chemerin and systolic BP remained significant. Chemerin was not found as an independent risk factor for predicting atherosclerosis in diabetes and prediabetes. CONCLUSION: Chemerin is not a predictive marker for atherosclerosis in diabetes and prediabetes, but correlates well with key aspects of the metabolic syndrome particularly in diabetes.

Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study.

Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly.We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants.We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes in found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic of familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases.In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing.

Reasons and results of endoscopic surgery for prolactinomas: 142 surgical cases.

BACKGROUND: We report herein a retrospective analysis of the results of 142 consecutive prolactinoma cases operated upon using an endoscopic endonasal trans-sphenoidal approach over a period of 6 years. METHODS: Medical records of 142 cases were analysed with respect to indications for surgery, duration of hospital stay, early remission rates, failures and recurrence rates during a median follow-up of 36 months. RESULTS: On the basis of magnetic resonance imaging (MRI) data, 19 patients (13.4 %) had microadenoma, 113 (79.6 %) had macroadenoma, and the remaining 10 (7.0 %) had giant adenomas. Cavernous sinus invasion was identified in 25 patients by MRI and confirmed during surgery. Atypical adenoma was diagnosed in 16 patients. Sparsely granulated prolactin adenoma was identified in 99 patients (69.7 %). Our results demonstrate that male sex and higher preoperative prolactin levels are independent factors predicting persistent disease. The post-surgical complications are as follows: 2.8 % patients had meningitis, 2.1 % patients had postoperative cerebrospinal fluid leak and 2.1 % patients had panhypopituitarism. At the end of follow-up, 74.6 % patients went into remission. During follow-up period, five patients who had initial remission developed recurrence. CONCLUSIONS: Our series together with literature data suggest that an endoscopic endonasal trans-sphenoidal approach in the treatment of proloctinomas has a favourable rate of remission. According to the findings of this study, endoscopic endonasal trans-sphenoidal surgery might be an appropriate therapy choice for patients with prolactinoma who could not have been managed with recommended therapeutic modalities.

The association between thyroid volume, L-thyroxine therapy and hepatocyte growth factor levels among patients with euthyroid and hypothyroid goitrous and non-goitrous Hashimoto's thyroiditis versus healthy subjects.

OBJECTIVE: Hashimoto's thyroiditis (HT) is the most common etiology of hypothyroidism in regions where iodine deficiency is not a concern. To date, many clinical investigations have been conducted to elucidate its pathogenesis. Several growth factors have been shown to have a role in its development. Hepatocyte growth factor (HGF) is one of the aforementioned molecules. We aimed to demonstrate whether HGF is responsible for HT and goiter development. Also, we aimed to test the hypothesis that levo-thyroxine sodium therapy will suppress HGF levels. MATERIALS AND METHODS: Sixty-one premenopausal women who were admitted to our outpatient clinic between November 2010 and September 2011 were enrolled. Three groups were determined according to their thyroid function tests (TFTs) as euthyroid Hashimoto's, control and subclinical hypothyroid Hashimoto's groups. Basal TFTs, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-tg), thyroid ultrasonography (USG) and HGF were studied and recorded. Subclinical hypothyroid HT patients received levo-thyroxine sodium replacement therapy, and were re-assessed for the same laboratory and radiologic features after a median 3.5 month follow-up. RESULTS: Basal HGF levels were not different between groups. In the subclinical hypothyroidism group, HGF levels (752.75 ± 144.91 pg/ml vs. 719.37 ± 128.05 pg/ml; p = 0.496) and thyroid volumes (12.51 ± 3.67 cc vs. 12.18 ± 4.26 cc; p = 0.7) before and after treatment did not change significantly. No correlations were found between HGF and other parameters. HGF levels were similar between subjects with nodular goiter and normal thyroid structure. CONCLUSIONS: HGF was not shown to be associated with HT and goiter development. In addition, levo-thyroxine sodium replacement therapy did not alter serum HGF levels significantly.

Epicardial Fat Thickness is Increased in Vitamin D Deficient Premenopausal Women and does not Decrease after Short-term Replacement.

AIM: Vitamin D deficiency, which is prevalent among young women in Middle Eastern populations, has been linked to cardiovascular disease. Epicardial adipose tissue (EAT) has also been found to be associated with coronary artery disease. However, data on the relationship between vitamin D status and epicardial adiposity is limited. This study aims to investigate the effect of vitamin D deficiency and replacement therapy on EAT thickness in healthy, young premenopausal women. METHODS: Thirty-one premenopausal women with vitamin D deficiency and 31 age-matched women with normal vitamin D levels were enrolled in this study. EAT thickness was measured echocardiographically. Measurements were performed at baseline in both groups and were repeated at the 6-month follow-up in vitamin D deficient subjects after vitamin D replacement therapy. RESULTS: The baseline plasma 25-hydroxyvitamin D levels were lower in the vitamin D deficient group compared to the control group and were significantly improved following replacement therapy. EAT thickness was significantly higher in the vitamin D deficient group, and no significant change occurred following replacement therapy. In the linear regression analysis, waist circumference (ß=0.031 [0.005-0.057], p=0.020) and 25(OH)D level (ß=－0.020 [(－0.028)－(－0.013)], p＜0.001) independently correlated with EAT thickness. CONCLUSION: Vitamin D deficiency is associated with a significant increase in EAT thickness in premenopausal women; however, a net beneficial response to adequate replacement therapy was not observed during the short period of therapy during our study. Longer periods of replacement therapy and follow-up may be useful to demonstrate the potential beneficial effects of vitamin D replacement on epicardial adiposity.

Markers of subclinical atherosclerosis in premenopausal women with vitamin D deficiency and effect of vitamin D replacement.

BACKGROUND: Recent studies have revealed a relationship between vitamin D deficiency and atherosclerosis. This study aims to investigate the impact of vitamin D deficiency and replacement on markers of subclinical atherosclerosis in young premenopausal women in whom vitamin D deficiency is prevalent. METHODS: Thirty-one premenopausal vitamin D deficient women and 27 age and gender-matched control subjects were enrolled in this study. Markers of subclinical atherosclerosis including carotid intima-media thickness (cIMT), flow-mediated dilatation (FMD), endothelial progenitor cell (EPC) count and cytokine levels were determined at baseline. All measurements were repeated at 6-month follow-up in vitamin D-deficient subjects after vitamin D replacement. RESULTS: Vitamin D deficient premenopausal women had lower FMD (9.9 ± 1.3 vs. 13.8 ± 1.7%, p < 0.001) and EPC counts at baseline. This population also had lower IL-10 and higher IL-17 levels. A 6-month vitamin D replacement therapy resulted in a significant increase in FMD (9.9 ± 1.3 vs. 11.4 ± 1.4%, p < 0.001) and EPC counts. Furthermore, cytokine profile shifted toward a more anti-inflammatory phenotype including elevated IL-10 and decreased IL-17 levels. cIMT was not different between patient and control groups and did not change following vitamin D replacement. Change in 25(OH)D and IL-17 levels were independent predictors of the change in FMD measurements following vitamin D replacement. CONCLUSION: This study demonstrates that endothelial function is impaired in otherwise healthy vitamin D deficient young premenopausal women and improves with 6-month replacement therapy. Immune-modulatory effects of vitamin D may, at least partly, be responsible for its beneficial effects on vascular health.

The performance of hemoglobin A1c against fasting plasma glucose and oral glucose tolerance test in detecting prediabetes and diabetes.

BACKGROUND: In recent years, hemoglobin A1c (HbA1c) is accepted among the algorithms used for making diagnosis for diabetes and prediabetes since it does not require subjects to be prepared for giving a blood sample. The aim of this study is to assess the performance of HbA1c against fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) in detecting prediabetes and diabetes. MATERIALS AND METHODS: A total of 315 subjects were included in this study. The success of HbA1c in distinguishing the three diagnostic classes was examined by three-way receiver operating characteristic (ROC) analysis. The best cut-off points for HbA1c were found for discriminating the three disease status. RESULTS: The performance of HbA1c, measured by the volume under the ROC surface (VUS), is found to be statistically significant (VUS = 0.535, P < 0.001). The best cut-off points for discriminating between normal and prediabetes groups and between prediabetes and diabetes groups are c1 = 5.2% and c2 = 6.4% respectively. CONCLUSION: The performance of HbA1c in distinguishing between the prediabetes and diabetes groups was higher than its ability in distinguishing between healthy and prediabetes groups. This study provides enough information to understand what proportion of diabetes patients were skipped with the HbA1c especially when the test result is healthy or prediabetes. If a subject was diagnosed as healthy or prediabetes by HbA1c, it would be beneficial to verify the status of that subject by the gold standard test (OGTT and FPG).

Early promising results for the endoscopic surgical treatment of Cushing's disease.

High levels of endogenous cortisol due to Cushing's disease cause significant mortality and morbidity. Treatment of Cushing's disease is challenging. For many years, transsphenoidal microsurgical resection of the adenoma has been the treatment of choice. However, recently, neuroendoscope has taken its place in the neurosurgeon's armamentarium, and the endoscopic transsphenoidal resection of pituitary tumors has become a familiar approach. Our aim was to present the results of pure endoscopic surgery in the treatment of corticotropinomas for comparison with the results of previous endoscopic and microsurgical series. We present a retrospective analysis of 90 patients with diagnosis of Cushing's disease who were operated between 2006 and 2012. Among 90 patients, a total of 81 (90.0 %) had a remission (28 out of 29 macroadenomas (96.6 %) and 53 out of 61 microadenoma patients (86.9 %)). Of note is that 66 out of 69 (95.7 %) primary patients (i.e., those who were operated in our center) and 15 out of 21 (71.4 %) patients previously operated in other centers reached a hypo/eucortisolemic state. A remission rate comparable with previous endoscopic series was achieved. In nine patients, it was not possible to achieve remission at all. On the other hand, only four of our cases (5.6 %) had a recurrence, and with reoperation, all of these patients entered a re-remission. To our knowledge, our series is the largest series studying endoscopically operated adrenocorticotropic hormone-secreting adenomas. Our results suggest that the endoscopic approach has opened a new avenue in the treatment of Cushing's disease, previously a therapeutic challenge for both the clinician and the neurosurgeon. Endoscopic approach in the treatment of Cushing's disease is clearly better for patients because of its low morbidity rates and short duration of hospital stay. On the other hand, long-term follow-up of our patients will show whether these favorable observations will persist.

Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria.

OBJECT: Acromegaly is a disease that has significant morbidity and mortality related to high levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I), and is usually caused by pituitary adenomas. The goal in this study was to investigate the role of endoscopic transsphenoidal surgery and surgical experience in the treatment of GH adenoma cases in relation to surgical results and hormonal cure rates, and to perform a review of the literature. METHODS: The authors present a retrospective analysis of 214 GH adenoma cases. Restoration of IGF-I levels to normal for age and sex, suppression of GH levels below 0.4 µg/L on the oral glucose tolerance test, and demonstration of the total removal of the tumor on MRI studies obtained after administration of contrast material at the 3-month postoperative follow-up visit were the criteria for cure. RESULTS: In total 214 patients with a mean age of 41.9 ± 12 years (range 17-75 years) and a male/female ratio of 106/108 were enrolled in the study. Cure was achieved in 134 (62.6%) of 214 patients. One hundred sixty-nine patients were primary cases, and of these 109 (64.5%) were cured, whereas 61 patients were previously operated cases and of these 25 (41%) were cured. With a 51.1% decrease in the 1st month postoperatively, IGF-I levels were found to be predictive of cure (74.4% sensitivity and 73.7% specificity). Cut-off values for GH levels in predicting cure for the 1st day, 1st week, and 1st month postoperatively were 2.33, 2.05, and 2.25 µg/L, respectively. The cut-off value for surgical experience was 57 for primary surgeries (58.5% cure rate before this cut-off value compared with 72.6% after it; p = 0.025) and 108 for all operations (45.8% vs. 79.4%, p = 0.037). Although 28 patients were found to be in remission according to the criteria in 2000, they were not in remission according to the new consensus criteria. Nine of these cases (32.1%) had random GH levels < 1 µg/L at the 1-year follow-up. The 1-year IGF-I and GH levels in these 28 patients showed no significant difference when compared with the cases defined as cured according to the current criteria. CONCLUSIONS: In acromegaly treatment, transsphenoidal endoscopic surgery performed by an expert senior surgeon and increased surgical experience are important for higher cure rates. Random GH levels < 2.33 µg/L after the 1st day postoperatively and a > 50% decrease in IGF-I levels after the 1st month postoperatively are predictive of cure. Moreover, there is no urgency for additional therapy in patients with GH levels of 0.4-1 µg/L and MRI sequences showing no tumor at the 3-month follow-up, because for these cases remission can be achieved at the 1-year follow-up.

Association between novel adipocytokines adiponectin, vaspin, visfatin, and thyroid: An experimental and clinical update.

Adipose tissue secretes a variety of active biological substances, called adipocytokines, that act in an autocrine, paracrine, and endocrine manner. They have roles in appetite control, thermogenesis, and thyroid and reproductive functions. All these molecules may lead to local and generalized inflammation, mediating obesity-associated vascular disorders including hypertension, diabetes, atherosclerosis, and insulin resistance. Thyroid dysfunction is associated with changes in body weight, thermogenesis, and energy expenditure. The connections between cardiovascular risk factors such as dyslipidemia, impaired glucose tolerance, insulin resistance, atherosclerosis, and thyroid dysfunction have been reported in several studies. The adipocytokines serve as causative or protective factors in the development of these disorders in the states of thyroid dysfunction. Abnormal levels of adipocytokines (adiponectin (ADP), leptin, resistin, vaspin, and visfatin) in hypo- and hyperthyroidism have been reported with controversial results. This review aims to update the implication of novel adipokines ADP, vaspin, and visfatin in thyroid dysfunction.

Pigment epithelium-derived factor increases in type 2 diabetes after treatment with metformin.

OBJECTIVE: Pigment epithelium-derived factor (PEDF) has anti-angiogenic, immunomodulatory and anti-inflammatory properties. In addition to the significant role it plays in reducing diabetic complications, PEDF is now used in the treatment of certain cancers. It possibly plays a role in insulin resistance cases, too. However, whether metformin treatment has any significant effects on PEDF levels is not known. In this study, we investigated the regulation of PEDF in type 2 diabetes in relation to fat mass and insulin resistance before and after the use of metformin for treatment. DESIGN: Prospective cohort study. SUBJECTS: Thirty-six patients with newly diagnosed type 2 diabetes and 33 healthy individuals. MEASUREMENTS: Baseline weight, waist circumference (WC), fasting (FPG) and postprandial (PPPG) glucose, insulin, HbA1c, HOMA, PEDF and total/truncal fat mass were determined both in the diabetic and control subjects. Procedures were repeated in the diabetic group after a 6-month metformin treatment. RESULTS: Baseline FPG, PPPG, HbA1c, HOMA, weight, WC and truncal fat mass were higher in patients with diabetes whereas PEDF levels were found to be comparable with the controls. We completed the study with 31 of the 36 patients with diabetes we had selected for the study. We observed a decrease in the weight, WC, FPG, PPPG, HOMA, total and truncal fat mass of the patients while there was a significant rise in the PEDF levels (P = 0·002) after the metformin treatment. On the other hand, no significant correlation was observed between the change in PEDF levels and the clinical and laboratory findings. CONCLUSION: Our study is the first to identify a metformin-related increase in PEDF levels in diabetes. The increase observed in PEDF levels after the metformin treatment does not seem to be related to the changes in insulin resistance, fat mass or glycemic control. Hence, our results suggest that further investigation is necessary to determine the direct effects of metformin on PEDF gene and protein expression in vitro.

Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature.

Endoscopic transsphenoidal surgery is emerging as a minimally invasive and maximally effective procedure for pituitary adenomas. In this report we analyzed the complications in 624 procedures of endonasal transsphenoidal endoscopic surgery in the treatment of 570 patients with pituitary adenomas. The leading author (MB) operated pituitary adenomas via pure endoscopic endonasal transsphenoidal surgery between January 2006 and August 2011 at the Hacettepe University, Department of Neurosurgery in Ankara. Complications were assessed in 624 surgical procedures under five groups; rhinological, CSF leaks, infection, vascular and endocrinologic complications. We observed a total of 76 complications (12.1%). Rhinological complications occurred in 8 patients (1.3%): 4 epistaxis (0.6%) and 4 hyposmia (0.6%). Postoperative CSF leaks occurred in 8 patients (1.3%), and infectious complications occurred in 8 patients: 3 cases of sphenoidal sinusitis (0.4%), 5 cases of meningitis (0.8%). Only 1 case of internal carotid aneurysm rupture during the opening of sellar floor (0.16%) was observed. Endocrinologic complications occurred in 51 (8.1%) patients: Anterior pituitary deficiency in 12 (1.9%), transient diabetes insipidus (DI) in 29 (4.6%), permanent DI in 3 (0.4%) and inappropriate antidiuretic hormone secretion syndrome occurred in 7 (1.1%). There was no mortality directly related to the surgical procedure. The complication rates observed in our study suggests that the endoscopic pituitary surgery is at least as safe as microscopic transphenoidal surgery. These rates were obtained with due experience and well-coordinated teamwork. To further improve these rates, new technological developments will be helpful.