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Hashimoto thyroiditis is characterized by anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies that gradually lead to thyroid cell destruction. As hypothyroidism has been associated with insulin resistance (IR), we aimed to investigate whether IR is associated with thyroid antibody presence and whether the degree of IR correlates with their concentration in euthyroid individuals. A total of 164 non-diabetic, euthyroid individuals, average age 34 years, were included in the study, divided into two groups according to Hashimoto thyroiditis and underwent 5-hour oral glucose tolerance test. The degree of IR was evaluated by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The Hashimoto thyroiditis group had higher HOMA-IR (p=0.003) and lower glucose levels (p=0.04). HOMA-IR correlated positively with anti-TPO (p<0.001). Linear logistic regression revealed that anti-TPO concentration increased by 18.13 (p=0.001) with each HOMA-IR unit. IR might trigger thyroid antibody production and Hashimoto thyroiditis development, which needs to be evaluated in further larger scale follow up studies.

Adiposity is a chronic disease and one of the major modifiable risk factors for the development of type 2 diabetes mellitus (T2DM). Its prevalence in the world could be considered epidemic with 80% of patients with T2DM being obese. Novel antidiabetic drugs, such as glucagone-like peptide-1 (GLP-1) agonists have demonstrated benefitial effect on weight reduction. Nevertheless, in the last decades the need for new therapeutic strategies in the management of adiposity have emerged. Both adiposity and T2DM have negative effect on hypothalamic-pituitary-gonadal axis. Conversely, it has been known that sex hormone replacement therapy improves metabolic parameters in hypogonadal subjects. Recent research has found potential therapeutic effect of combination therapies with sex hormones and GLP-1 agonists in reducing body weight. Based on the aforementioned, we hypothesize that there is a possible synergistic effect of GLP-1 agonists and sex hormones on body mass reduction in patients with type 2 diabetes. The possible additional effect of sex hormones on weight loss could contribute to more effective treatment of T2DM and its complications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pituitary apoplexy may occur when a large tumor compresses or outgrows its nutrient supply, resulting in ischemic necrosis and hemorrhage. Although once deemed a neurosurgical emergency, increasing evidence suggests that conservative management of pituitary apoplexy leads to favorable neuro-ophthalmologic and endocrinologic outcomes as well. Spontaneous remission after pituitary apoplexy has been described in functioning pituitary adenomas, but it is a rare occurrence in nonfunctioning tumors., Case Description: We report a man that presented with pituitary apoplexy of a nonfunctioning pituitary macroadenoma that was managed conservatively and treated hormonally for hypopituitarism during a 2-year follow-up period, with serial neuroimaging demonstrating significant tumor volume reduction with almost complete resolution resulting in partial empty sella. In addition, a short literature review was performed pertaining to the management of pituitary apoplexy with emphasis on a more conservative approach., Conclusions: A subset of patients with pituitary apoplexy without altered consciousness and nonprogressive or mild ophthalmologic deficits may be managed conservatively; however, lifelong periodic assessment, preferably by a specialized multidisciplinary pituitary team, is essential until clinical outcomes become clear., (Copyright © 2019 Elsevier Inc. All rights reserved.)

BACKGROUNDAlthough it is considered that the pathogenesis of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) is primarily due to chronic hyperglycemia resulting in vascular changes and retinal ischemia, the red blood cells (RBCs) disorders might also represent an important pathophysiological risk factor.OBJECTIVETo evaluate whether the RBC properties contribute to DR development and progression in T2DM.METHODSThis prospective observational study comprised 247 persons with T2DM free of DR or with non proliferative DR without any signs of anaemia. The patients were reacessed after 60-months.RESULTSThe mean age of our study population was 56 years, 54.9% males with diabetes duration of 11,18±1,28 years. During the follow up, 16 (5.84%) participants developed non proliferative DR and 9 (3.64%) progressed to PDR while the mean corpuscular volume (MCV) and red cell distribution width (RDW) MCV rose. Both MCV and RDW correlated positively with HbA1c (r = 0,468, p = 0.003 and r = 0.521, p < 0.001), while Cox regression analysis revealed that besides age, diabetes duration, HbA1c, hypertension and dyslipidemia presence, MCV and RDW are also associated with the risk of DR development and progression (HR 1.057 and 1.237, p < 0.001).CONCLUSIONSWe clearly demonstrated that RBC's characteristics might represent a risk factor for DR development and progression.

Aims: We compared characteristics of patients with hyperglycemic hyperosmolar state (HHS) and patients with severe hyperglycemia without the signs of hyperosmolarity and ketoacidosis; analyzed long-term all-cause mortality and potential prognostic factors., Methods: The studied population included 261 749 adults. HHS was diagnosed in patients with plasma glucose >33.0 mmol/L, ketonuria <1+, and serum osmolarity >320 mmol/L. Patients with plasma glucose >33.0 mmol/L, ketonuria <1+ and serum osmolarity <320 mmol/L were considered as controls (nHHS)., Results: During the 5-year period, we observed 68 episodes of HHS in 66 patients and 51 patients with nHHS. Patients with HHS were significantly older, had lower BMI, higher serum C-reactive protein and used diuretics and benzodiazepines more frequently. Mortality rates one, three and 12 months after admission were 19.0, 32.1 and 35.7% in the HHS group, and 4.8, 6.3 and 9.4% in the nHHS group (P<0.001). However, after adjustment for patient age, these differences were not statistically significant. In multivariate Cox regression in HHS group, mortality was positively associated with age, male gender, leukocyte count, amylase, presence of dyspnea and altered mental status, and the use of benzodiazepines, ACE inhibitors and sulphonylureas, while it was inversely associated with plasma glucose, bicarbonate, and the use of thiazides and statins. A nomogram derived from these variables had an accuracy of 89% in predicting lethal outcome., Conclusions: Infection, use of furosemide and benzodiazepines may be important precipitating factors of HHS. Prospective clinical trials are mandatory to analyze the safety of ACE-inhibitors and benzodiazepines in elderly patients with diabetes., Competing Interests: None., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs., Methods: This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs., Results: CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713-0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405-0.702, P = 0.430)., Conclusions: CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.

Insulin resistance (IR) is a common denominator of metabolic and hemodynamic disorders simultaneously present in one person and responsible for elevated risk of developing type 2 diabetes (T2DM) and cardiovascular incidents. According to the latest research, IR is present in 25-45% of the general population. Therefore, the mechanism of its development is in the center of scientific and professional interest. Established or acquired factors, or combinations thereof, which disturb any step of the physiological insulin action mechanism: its binding to the cellular receptor, through the complex cascade of intracellular signaling pathways might cause IR. Although the adiposity and its underlying risk factors are considered to be the primary cause of IR, it is present in a great porportion in lean individuals as well. There are insights of the possible role of psychological factors: exposure to stress and deprssion to IR development, although the mechanism of this relationship has not been comperhensively studied. Data driven from cell cultures and experimental animal models suggest that there is an elevated level of counter-regulatory insulin hormones: growth hormone, prolactin and cortisol due to acute stress exposure. However, the relationship between these psychological disorders with the hyperreactivity of the axis of the hypothalamic-pituitaryadrenal axis as the underlying mechanism in the patophysiology of IR in lean individuals has not been systematically investigated. Based on the aforementioned, we hypothesise that this mechanism would be responsible for the formation of IR, and consequently, T2DM in lean individuals. The possible effect of the amount of stress in conjunction with the serum concentration of growth hormone, cortisol, prolactin and dehydroepiandrostendone to the abnormal 5-h oral glucose tollerance test results could contribute to the primary prevention of diabetes and its complications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA., Methods: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration., Results: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%., Conclusions: AOST is a promising tool to increase the diagnostic accuracy of serum CgA., (©2018 S. Karger AG, Basel.)

Patients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department. Cox proportional hazard models were used to analyze the link between patient characteristics and mortality. During an observation time of 33.4 months, death of any cause occurred in 40.9 % of the non-ketotic hyperglycemia group and 30.2 % of the DK group (hazard ratio in the diabetic ketosis group, 0.63; 95 % confidence interval 0.48-0.82; P = 0.0005). Patients with diabetic ketosis had a lower incidence of symptomatic heart failure and had improved renal function. They used less furosemide and antihypertensive drugs, more metformin and lower insulin doses, all of which was independently associated with decreased mortality. Plasma glucose and glycated hemoglobin levels were similar in both groups. Patients with hyperglycemic crisis and diabetic ketosis have decreased all-cause mortality when compared to those with non-ketotic hyperglycemia. diabetic ketosis might be a compensatory mechanism rather than a complication in patients with hyperglycemic crises, but further prospective studies are warranted.

Background: Although various metabolic hormones have been implicated in bariatric-related weight loss, their use as predictors of weight loss is unknown. Our study evaluates changes in metabolic hormones after bariatric surgery, and their role as predictors of weight loss., Methods: This nonrandomized study included 51 patients, 21 underwent laporascopic adjustable gastric banding (LAGB), 15 laparoscopic sleeve gastrectomy (LSG) and 15 Roux-en Y gastric bypass (RYGB). Serum ghrelin, leptin, insulin, growth hormone, HOMA-IR and HOMA-β was recorded at baseline and 1, 3, 6 and 12 months, and correlated with weight loss. Successful weight loss was defined as excess weight loss >50% at 12 months for all groups., Results: Weight loss pattern was similar in all groups. Ghrelin increased only in the LAGB group (P = 0·016). However, baseline ghrelin concentrations >664·6 pg/mL in the LSG group predicted successful weight loss with 81·8% sensitivity and 100·0% specificity, and ghrelin >969·8 pg/mL in the 1st postoperative month predicted success with 83·3% sensitivity and 83·3% specificity in the LAGB group. Insulin and HOMA-IR decreased significantly in the LSG and RYGB group, HOMA-β increased in the LAGB and LSG group. Serum leptin decreased and GH increased in all groups (P < 0·001 for all changes). Changes in insulin, leptin and growth hormone were not predictors, but a consequence of weight loss., Conclusions: LSG is the most effective procedure for improvement of beta-cell function. High baseline ghrelin in the LSG group and an adequate 1st month increase in the LAGB group are associated with greater weight loss. Validation studies are required to confirm the role of ghrelin in predicting weight loss after bariatric surgery, but also in selecting candidates for specific bariatric procedures., (© 2016 John Wiley & Sons Ltd.)

Purpose: Increasing evidence exists that hyperprolactinemia alters metabolic profile. The mechanism of this effect is unknown. We aimed to investigate the differences between the metabolic profile of patients with prolactinomas and nonfunctional pituitary adenomas and to evaluate the impact of other pituitary hormones on their metabolic profile., Methods: Our retrospective study included 86 consecutive patients with prolactinomas and nonfunctional adenomas (29 prolactinomas and 57 adenomas). Body mass index (BMI), blood pressure, serum prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), adrenocorticotropic hormone (ACTH), cortisol, urinary free cortisol, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), dehydroepiandrosterone-sulfate (DHEA-S), testosterone in men, triglycerides, total cholesterol, HDL (high-density lipoprotein) cholesterol, LDL (Low-density lipoprotein) cholesterol, alanine-transaminase, aspartate-transaminase, fasting glucose, and C-reactive protein (CRP) were obtained for all patients. Regression analyses were performed on log-transformed data., Results: After adjustment for age, gender, and tumor size, prolactinomas were associated with higher BMI (OR 5.61, 95%CI 1.70-9.51, p = 0.005), LDL cholesterol (OR 3.60, 95%CI 1.35-5.93, p = 0.015), DHEA-S (OR 1.97, 95%CI 1.23-3.72, p = 0.026), and lower GH levels (OR 0.43, 95%CI 0.03-0.84, p = 0.037). In a linear multivariate regression, the association between DHEA-S, GH, and prolactin remained significant even after adjustment for BMI. GH and IGF-I were associated with BMI and LDL cholesterol, but the association diminished after adjustment for serum prolactin., Conclusions: Prevalence of obesity is four times higher in patients with prolactinomas than in patients with nonfunctional adenomas. Higher DHEA-S and lower GH levels in patients with prolactinomas may have an important role in prolactin-induced metabolic effects. Further studies are needed.

The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The addition of baseline LH to CORT3, increased sensitivity to 100.0%, specificity to 88.9%, PPV to 90.4%, and NPV to 100.0%. Besides CORT3, tumor size, thyroid hormones, and gonadotropins can serve as predictors of AI. LH in postmenopausal female patients with NPA has similar diagnostic accuracy as CORT3. Further studies are needed in order to validate the scoring system proposed by this study.

Internal hernias have an overall incidence of less than 1% and are difficult to diagnose clinically due to their nonspecific presentation. Most internal hernias present as strangulating closed-loop obstruction and delay in surgical intervention is responsible for a high mortality rate (49%). We present a case of ileal herniation through the foramen of Winslow. A 29-year-old previously healthy female presented with acute onset right upper quadrant pain, abdominal fullness, and nausea. The pain was sudden in onset and began shortly after a dinner party where she consumed larger portions of food. Laboratory investigations revealed mild leukocytosis with left shift. Dual-phase multi-detector computed tomography disclosed herniation of the small bowel into the lesser sac. The patient underwent an emergency median laparotomy that revealed ileal herniation through the foramen of Winslow. Adhesiolysis and manual reduction of the bowel was performed, and the reduced bowel showed only congestive changes. The postoperative recovery was uneventful and the patient was discharged on the third postoperative day. Risk factors for internal herniation still remain unclear, although excessively mobile bowel loops and an enlarged foramen of Winslow have been described. Our case demonstrated that overeating could be an additional risk factor for internal herniation. We describe our clinical and radiology findings, as well as surgical management. Due to the high rates of morbidity and mortality, it is imperative that clinicians be aware of the possible risks factors for internal herniation. Internal hernias should be included in the differential diagnosis of small bowel obstruction so that appropriate steps can be made in the work-up of these patients, followed by timely surgical intervention.

Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia., Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines., Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations., Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes.

We report a case of a 49-year-old woman with biopsy-proven multisystemic Langerhans cell histiocytosis (LCH) with hypothalamic involvement documented on F-FDG PET/CT. Chemotherapy with a combination of vinblastine, prednisolone, methotrexate, and 6-mercaptopurine was carried out. Two months later, a 90% reduction of the hypothalamic tumor mass was noted on magnetic resonance imaging, but with no signs of pathological F-FDG accumulation. The patient died 4 months later, and we found no signs of LCH on autopsy. Our case highlights the need for further studies regarding the role of F-FDG PET/CT in the assessment of treatment response in patients with LCH.

Background: Bariatric procedures are effective options for weight loss (WL) in the morbidly obese. However, some patients fail to lose any weight after bariatric surgery, and mid-term weight maintenance is variable. The aim of this study was to investigate whether initial WL could predict mid-term weight maintenance. Methods: Eighty patients were enrolled, of whom 44 were treated with the BioEnterics Intragastric Balloon (BIB), 21 with laparoscopic adjustable gastric lap-banding (LAGB), and 15 with laparoscopic sleeve gastrectomy (LSG). Percentage of body WL and percentage of excess weight loss (EWL) were calculated at baseline and after 1, 3, 6, and 12 months. Successful WL was defined as EWL >20% for patients treated with BIB and >50% for patients treated with LAGB and SG. Results: Success in the 6th and 12th month was achieved in 80% and 58% of patients in the BIB group, 33% and 40% in the LAGB group, and 60% and 73% in the LSG group. In the BIB group, WL in the 1st month correlated positively with WL at the 6th and 12th month, and an initial WL >6.5% best predicted success (sensitivity 50%, specificity 80%). A similar association was observed in the LAGB group at the 6th and 12th month and an initial WL >9.4% best predicted success (sensitivity 90.0%, specificity 81.2%). In patients treated with LSG, WL in the 3rd month correlated positively with EWL at the 6th and 12th month, with a cutoff value of 17% (sensitivity 66.7%, specificity 100%). Conclusions: WL in the 1st month in patients treated with BIB and LAGB and WL in the 3rd month in patients treated with LSG could be used as a prognostic factor to predict mid-term weight maintenance.

Purpose. In low-income countries, prolactinomas are difficult to manage with dopamine agonists (DA). We compared the effectiveness of DA in microprolactinomas as a first line treatment and as adjuvant therapy for residual macroprolactinomas treated surgically. Methods. Our retrospective study analyzed 78 patients, 38 with microprolactinomas and 40 with macroprolactinomas. Microprolactinomas were treated with DA. Macroprolactinomas were treated with microsurgical or endoscopic adenomectomies and adjuvant DA. Surgical remission was defined as normoprolactinemia three months postoperatively, and long-term remission as normoprolactinemia at the last control. Results. Surgical remission was achieved in 9 patients (23%). Postsurgical tumor mass was reduced by 50% (34-68). Residual macroprolactinoma size was greater than microprolactinoma size prior to treatment (10 mm versus 4 mm, P < 0.001). Both groups received similar doses of DA. Long-term remission occurred in 68% of microprolactinomas and 43% of macroprolactinomas (P = 0.102). Prolactin (PRL) levels at the last control were similar in both groups (23.1 versus 32.9 mcg/L, P = 0.347). Conclusion. Comparable remission rates and PRL levels were reached in microprolactinomas and macroprolactinomas using similar doses of DA. Although complete tumor resection is the goal of surgery, our study suggests that even partial surgical removal has a role in treatment of prolactinomas since it may enhance the response to DA.

Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates immune and inflammatory responses, and its overproduction is a hallmark of inflammatory diseases. Inhibition of IL-6 signaling with the anti-IL-6 receptor antibody tocilizumab has provided some clinical benefit to patients; however, direct cytokine inhibition may be a more effective option. We used the systematic evolution of ligands by exponential enrichment (SELEX) process to discover slow off-rate modified aptamers (SOMAmers) with hydrophobic base modifications that inhibit IL-6 signaling in vitro. Two classes of IL-6 SOMAmers were isolated from modified DNA libraries containing 40 random positions and either 5-(N-benzylcarboxamide)-2'-deoxyuridine (Bn-dU) or 5-[N-(1-naphthylmethyl)carboxamide]-2'-deoxyuridine (Nap-dU) replacing dT. These modifications facilitate the high affinity binding interaction with IL-6 and provide resistance against degradation by serum endonucleases. Post-SELEX optimization of one Bn-dU and one Nap-dU SOMAmer led to improvements in IL-6 binding (10-fold) and inhibition activity (greater than 20-fold), resulting in lead SOMAmers with sub-nanomolar affinity (Kd = 0.2 nm) and potency (IC50 = 0.2 nm). Although similar in inhibition properties, the two SOMAmers have unique sequences and different ortholog specificities. Furthermore, these SOMAmers were stable in human serum in vitro for more than 48 h. Both SOMAmers prevented IL-6 signaling by blocking the interaction of IL-6 with its receptor and inhibited the proliferation of tumor cells in vitro as effectively as tocilizumab. This new class of IL-6 inhibitor may be an effective therapeutic alternative for patients suffering from inflammatory diseases.

Laparoscopic gastric banding (LAGB) is one of the most common surgical procedures in the treatment of morbid obesity since it provides good long-term outcomes in weight loss and decrease of comorbidities associated with obesity. Although the procedure has low morbidity and almost none-existing mortality, certain complications can occur. Erosion of the band into the gastric wall is one of the rare complications in LAGB. The reported incidence varies from 1 to 11%, however the largest study reported an incidence of 1.6%. This is in accordance with the incidence in our Centre for obesity, where only one case of erosion occurred among 112 operative procedures. The aim of this paper is to present a patient with gastric band erosion and it's removal by using the endoscopic techniques as a minimally invasive management method.

Pituitary apoplexy (PA) typically results from infarction or hemorrhage in a pituitary adenoma, while PA in nonadenomatous pituitary gland is uncommon. Prothrombotic states have never been recognized as precipitating factors for PA. The authors report a case of an elderly female who received prophylactic fractionated heparin therapy due to sepsis, consequent rhabdomyolysis, and overt disseminated intravascular coagulation. On the seventh day of heparin therapy, she reported sudden vision loss, ptosis, diplopia, and severe headache. Severe thrombocytopenia and positive antibodies to the complex of platelet factor 4 and heparin confirmed heparin-induced thrombocytopenia type 2 (HIT). Magnetic resonance imaging disclosed a homogenous pituitary tumor mass with pronounced sphenoid sinus mucosa thickening and two hypointense zones within the tumor mass on contrast-enhanced images consistent with focal ischemic necrosis. The tumor was confirmed to be squamous cell carcinoma with no signs of necrosis. Ischemic necrosis was found within marginal pituitary tissue. This is the first reported case of ischemic PA associated with pituitary metastasis and the first case in which HIT triggered PA. Our case demonstrates that prothrombotic states such as HIT can precipitate ischemic PA. Pituitary metastasis can present with ischemic PA, but radiological features differ from those described in pituitary adenomas. Segregated low-signal intensity zones within the tumor mass on postcontrast images indicate partial infarction of the tumor, which could be a special feature of ischemic PA in pituitary metastasis and has never been described in pituitary adenomas. These are all novel findings and might enlighten the pathogenesis of PA.

Aim: To analyze early remission, complications, and pituitary function recovery after pure endoscopic endonasal transsphenoidal surgery (PEETS), a novel method in pituitary adenoma treatment., Methods: Testing of all basal hormone values and magnetic resonance imaging (MRI) were performed preoperatively and postoperatively (postoperative MRI only in nonfunctioning adenomas) in 117 consecutive patients who underwent PEETS in the period between 2007 and 2010. The series consisted of 21 somatotroph adenomas, 61 prolactinomas, and 4 corticotroph and 31 nonfunctioning adenomas. Sixty-three were macroadenomas and 54 were microadenomas. Remission was defined as hormonal excess normalization on the seventh postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas. The presence of hypogonadism, growth hormone deficiency, and hypothyroidism was assessed on the seventh postoperative day. Hypocortisolism was assessed through necessity for replacement therapy within 18 months postoperatively., Results: Remission was achieved in 84% of patients: in 100% of microadenoma and 70% of macroadenoma patients (P<0.001, odds ratio [OR], 28.16, 95% confidence interval [CI], 1.61-491.36), respectively. Endocrinological complications occurred in 17.1% of patients: in 9% of microadenoma and 24% of macroadenoma patients (P=0.049, OR, 3.06; 95% CI, 1.03-9.08). Duration of empirical hydrocortisone replacement therapy was significantly shorter in microadenoma patients (P<0.001). Thirty-five percent of preoperatively present hormonal deficiencies improved after the surgery. Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery., Conclusion: Patients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas. PEETS is a discussion-worthy method for microprolactinoma treatment.

Glucose metabolism disorders in acutely ill patients include oscillations in plasma glucose concentration outside the range of reference values. These disorders include both hyperglycemia and hypoglycemia, regardless of previous diagnosis of diabetes in a particular patient. Hyperglycemia is frequent in acute patients due to the increased release of stress hormones such as catecholamines and cortisol, but also as an effect of a cascade of proinflammatory cytokines in emergencies such as acute coronary syndrome, pulmonary edema, pulmonary embolism, injuries, severe infections and sepsis. Hyperglycemia occurs often even in patients in whom diabetes was not previously diagnosed, and in diabetic patients requirement for hypoglycemic medication may be temporarily increased. Hyperglycemia in cardiac emergencies is associated with more frequent adverse major cardiovascular events and worse prognosis. Hypoglycemia occurs seldom in these patients, its origin is almost always iatrogenic, and it worsens the patient's prognosis even more than moderate hyperglycemia. Good regulation of glycemia is necessary in the management of these patients; therefore plasma glucose determination and close monitoring are obligatory, and therapy with short acting insulin should be introduced if plasma glucose concentration exceeds 10 mmol/L, regardless of the risk of hypoglycemia. It is also useful to determine the acid-base status and blood or urine ketones.

The working group of the Croatian Society of Endocrinology met in September 2011 to discuss the diagnostic and therapeutic dilemmas in patients with acromegaly. The group comprised 9 pituitary specialists including endocrinologists, neurosurgeons, and medical biochemistry specialist. After a critical analysis of published scientific papers the group has developed guidelines for the diagnosis and treatment of acromegaly.

Intrathyroidal parathyroid carcinoma is extremely rare clinical entity with potentially multiple diagnostic pitfalls. We report a case of 40-year-old man presented with classical manifestations of primary hyperparathyroidism, severe hypercalcemia and profoundly increased serum parathyroid hormone level. Neck ultrasonography demonstrated multinodular goiter with predominant 34 mm nodule in left thyroid lobe. Additional 16 mm nodule was found beneath the left lobe. Routine percutaneous fine-needle aspiration of predominant nodule indicated follicular thyroid carcinoma, while left inferior nodule was confirmed to be of parathyroid origin. The patient underwent surgery, during which frozen sections identified medullary thyroid carcinoma with metastasis to upper mediastinal lymph node. Permanent sections of the predominant left lobe nodule revealed intrathyroidal parathyroid carcinoma surrounded with multiple microscopic metastases. Left inferior nodule was metastatic lymph node. Additional 10 mm intrathyroidal metastasis of primary parathyroid carcinoma was found within right thyroid lobe. This case indicates that fine-needle-aspiration and intraoperative biopsy are of limited value in diagnosing parathyroid carcinoma, especially if localized intrathyroidally. Oncological en-block resection is treatment of choice, implying ipsilateral lobectomy in case of thyroid invasion. This firstly described case of intrathyroidal parathyroid carcinoma causing intrathyroidal dissemination may influence future treatment strategies.

Gout is the most common type of inflammatory arthritis in man caused by deposition of urate crystals into the joints as the result of elevated serum urate levels. A case of a 59-year-old patient with untreated, long-lasting gout and clinical manifestation of decompensated global dilated cardiomyopathy is presented. Examination revealed generalized pitting edema extending from both lower extremities to the sacrum, abdominal, and thoracic wall, with scrotal swelling and upper extremity involvement, an exceptionally vast generalized edema, i.e. anasarca. Proximal and distal interphalangeal joints of the hands and feet were swollen and deformed, with marked yellow tophi nodules. Laboratory studies revealed high serum uric acid concentration (546 micromol/L), decreased creatinine clearance (0.8 mL/s) and albumin concentration (27.4 g/L), as well as increased total urine protein mass (0.35 g/24 h). X-rays of the affected feet and fists showed punched-out lesions of the subchondral bone with overhanging bony margins in the first metatarsophalangeal, proximal, and distal interphalangeal joints of both hands. The extreme clinical presentation resolved upon intravenous administration of diuretics and pleurocentesis, followed by oral medications including furosemide, angiotensin-converting enzyme inhibitor, spironolactone and digoxin. Since serum urate level has been identified as an independent risk factor for the development of ischemic heart and chronic kidney disease, regulation of urate concentration is necessary, especially in patients diagnosed with gout.

PATH (Performance Assessment Tool for Quality Improvement in Hospitals), a project of the World Health Organization (WHO) for Europe offers hospitals a comprehensive and standardized tool (a set of indicators) to evaluate their own performance and development of measures for quality improvement. PATH Program was launched in Croatia in 2008, and it was conducted in 2009 in hospitals that have voluntarily decided to be involved. Here we present the results of the first phase of pilot experience of establishing the program, based on data collected in 22 Croatian hospitals. Analysis of the first results indicated the existence of marked differences among the hospitals that have taken the example of the percentage of cesarean sections ranging from 1.1% to 21.4%. The mortality rate of myocardial infarction ranged from 1.9 to 21.4%, while the mortality of stroke ranged from 12.5 to 45.5%. The highest percentage of needle-stick injuries reported for physicians was 16.2% of entire hospital staff in one year, 6.1% for nurses and 4.6% for the supportive staff. The result suggests the existence of many problems and limitations in data collection at hospital level, limitations in their analysis and creates recommendations for quality improvements, which must be taken into account when hospitals are compared on the national or international level.

Background: The interrogation of proteomes ("proteomics") in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine., Methodology/principal Findings: We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (~100 fM-1 µM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states., Conclusions/significance: We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine.

Intracranial metastases from laryngeal carcinoma are rarely clinically diagnosed. To our knowledge, this is the first report of hypopituitarism due to pituitary metastasis from laryngeal carcinoma. We report on a 70-year-old man who had a supraglottic squamous cell carcinoma, which was resected surgically followed by local full dose radiation therapy. Four months later, he presented with a sudden onset of diplopia, syncope, headache, general malaise and loss of appetite. Magnetic resonance imaging of the brain revealed a tumorous process of the sellar region. Endocrinological tests disclosed the presence of hypopituitarism. The tumor was subtotally resected endoscopically via endonasal transsphenoidal approach. Histopathology of tumor specimens indicated squamous cell carcinoma. Tumors of the sellar and parasellar region as in the case presented may easily be confused with pituitary adenoma. Pituitary metastases should be considered on differential diagnosis of unusual pituitary tumors, especially in patients with as well as in those without a history of malignant disease.