Effect of post-transplant diabetes mellitus on cardiovascular events and mortality: a single-center retrospective cohort study.

PURPOSE: This study aims to investigate the impact of post-transplant diabetes mellitus (PTDM) on cardiovascular events, graft survival, and mortality and to determine the risk factors involved in developing PTDM. METHODS: A total of 703 patients who underwent kidney transplantation were included in the study. The total sample was subdivided into three groups: (i) patients with PTDM; (ii) patients who had diabetes before the transplantation (DM); and (iii) patients without diabetes (NoDM). The data on graft failure, cardiovascular events, all-cause mortality, and the potential risk factors that play a role in developing PTDM were recorded and analyzed. RESULTS: The patients were followed for a median of 80 (6-300) months after transplantation. Out of all patients, 41 (5.8%) had DM before transplantation, and 101 (14.4%) developed PTDM. Recipient BMI, post-transplant fasting plasma glucose, and hepatitis C seropositivity were independent risk factors for PTDM development. The incidence of cardiovascular events was 6.1% in the NoDM group, 14.9% in the PTDM group, and 29.3% in the DM group (p < 0.001). In PTDM patients, hepatitis C seropositivity and the recipient's age at transplant were independent predictors of a cardiovascular event. There were no significant differences between the groups regarding the risk of graft loss. PTDM had no significant effect on all-cause mortality. However, the survival rates of DM patients were significantly reduced compared to those with NoDM or PTDM. CONCLUSIONS: PTDM had no impact on patient survival. Hepatitis C seropositivity and recipient age at transplant predicted cardiovascular events in PTDM patients.

The prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome in treatment-naïve transgender people assigned female at birth.

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. We aimed to investigate the prevalence and phenotypic characteristics of PCOS in testosterone treatment-naïve transgender people assigned female at birth (AFAB), as well as to determine whether cardiometabolic risk factors vary based on the presence of PCOS and its components. METHODS: Evaluation of 112 testosterone treatment-naïve transgender adults AFAB for PCOS and its individual components, including androgen excess, ovulatory dysfunction and polycystic ovarian morphology (PCOM). RESULTS: In our cohort, 79.5% of transgender individuals AFAB had at least one component of PCOS. The prevalence of PCOS was 38.4% (43/112). Phenotype C was the most common phenotype (17.8%), followed by phenotype B (10.7%). Transgender individuals AFAB with at least one component of PCOS had higher blood pressure (BP) measurements and higher fasting plasma glucose levels compared to those with none. Sixty-one subjects (54%) had hyperandrogenism (HA), with 20 (17.9%) having HA without other components of PCOS. When compared to those without HA, transgender individuals AFAB with HA had higher body mass index (BMI), BP, triglyceride and lower HDL-cholesterol levels. CONCLUSION: PCOS and androgen excess appear to be prevalent among transgender people AFAB. Transgender individuals AFAB with HA or PCOS may exhibit an unfavorable cardiometabolic risk profile compared to those without any PCOS component. Assessment of androgen excess and the specific components of PCOS at baseline could inform long-term management.

COVID-19 vaccination and thyroiditis.

At the end of 2019, the world began to fight the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2. Many vaccines have quickly been developed to control the epidemic, and with the widespread use of vaccines globally, several vaccine-related adverse events have been reported. This review mainly focused on COVID-19 vaccination-associated thyroiditis and summarized the current evidence regarding vaccine-induced subacute thyroiditis, silent thyroiditis, Graves' disease, and Graves' orbitopathy. The main clinical characteristics of each specific disease were outlined, and possible pathophysiological mechanisms were discussed. Finally, areas lacking evidence were specified, and a research agenda was proposed.

Follow, consider, and catch: second primary tumors in acromegaly patients.

BACKGROUND AND AIM: The risk of second primary tumors is increased in general cancer population, however, there is no data on acromegalic cancer patients in this regard. The aim of this study is to determine the prevalence of patients with two primary tumors among acromegalic cancer patients and to evaluate if patients with two primaries have distinct clinical characteristics or risk factors compared to those with one. METHODS: This is a single-center retrospective cohort study. The study included 63 patients with at least one malignant tumor out of a total number of 394 acromegaly patients. Patients with multiple primary neoplasms were evaluated in detail. RESULTS: This study revealed a 16% cancer prevalence in acromegaly patients, with 14% (9/63) having two primary neoplasms. Papillary thyroid carcinoma was the most prevalent tumor in the entire cancer cohort (41%, 26/63), and in the group of patients with two primaries (44%, 4/9). Patients with two primary tumors were older than those with one when diagnosed with acromegaly (48.3 ± 16.6 vs. 43.3 ± 10.7 years), which might be attributed to a longer diagnostic delay (median of 4.5 vs. 2 years). The period between the onset of acromegaly symptoms and diagnosis was not associated with earlier cancer diagnosis. No relationship between circulating GH or IGF-I levels and the number of neoplasms was found. CONCLUSION: The development of second primary tumors in acromegalic patients with cancer diagnosis is not rare. Acromegalic cancer patients should be closely monitored for new symptoms or signs that could be associated with second primary tumors.

Giant growth hormone-secreting pituitary adenomas from the endocrinologist's perspective.

OBJECTIVES: Since giant (≥40 mm) GH-secreting pituitary adenomas are rarely encountered, data on their characteristics and treatment outcomes are limited. We aimed to investigate the characteristics of giant GH-secreting pituitary adenomas and to compare their clinical, biochemical, imaging and histopathological features with non-giant macroadenomas. MATERIALS AND METHODS: We have evaluated 15 (six female/nine male) and 57 (29 female/28 male) patients with acromegaly in giant and <40 mm adenoma groups, respectively. Patients with <40 mm adenoma were further divided into subgroups with adenoma size 20-29 mm and 30-39 mm. RESULTS: In giant adenoma group, median (IQR) preoperative maximal diameter of adenoma was 40 mm (5 mm), median preoperative GH level was 40 (153.4) ng/mL and median baseline IGF-1 level was 2.19 (1.88) × ULN for age and sex. The number of surgeries was significantly higher in giant adenoma group (median 2, IQR 2) in which 66.7% of patients underwent repeated surgeries (p = 0.014). Residual tumor was detected after last operation in all patients with giant adenoma. Total number of treatment modalities administered postoperatively increased as adenoma size increased (p = 0.043). After a median follow-up duration of 10 years (IQR 10), hormonal remission was achieved in six patients (40%) of giant adenoma group, while the rate of hormonal remission in non-giant adenoma group was 37%. Although preoperative GH and IGF-1 levels and Ki-67 index tended to be higher with increasing adenoma size, there was no statistically significant difference between groups in terms of these variables, as well as age, sex and invasion status. CONCLUSION: Hormonal remission rates of acromegaly patients with ≥20 mm pituitary macroadenoma were comparable. However, giant GH-secreting pituitary adenomas require an aggressive multimodal treatment approach.

Endocrine Disorders and COVID-19.

The multifaceted interaction between coronavirus disease 2019 (COVID-19) and the endocrine system has been a major area of scientific research over the past two years. While common endocrine/metabolic disorders such as obesity and diabetes have been recognized among significant risk factors for COVID-19 severity, several endocrine organs were identified to be targeted by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). New-onset endocrine disorders related to COVID-19 were reported while long-term effects, if any, are yet to be determined. Meanwhile, the "stay home" measures during the pandemic caused interruption in the care of patients with pre-existing endocrine disorders and may have impeded the diagnosis and treatment of new ones. This review aims to outline this complex interaction between COVID-19 and endocrine disorders by synthesizing the current scientific knowledge obtained from clinical and pathophysiological studies, and to emphasize considerations for future research.

Anthropometric measurements and serum TNF-α, IL-6 and adiponectin in type 2 diabetes.

Objective: To investigate the effect of anthropometric measurements on serum adiponectin and inflammatory markers in Type 2 diabetes mellitus (T2DM). Methods: This study was conducted with 46 subjects newly diagnosed with T2DM and 30 healthy volunteers free from pre-existing inflammatory disease, cancer, Type 1 diabetes and using any medications. Demographic, clinical and anthropometric data were collected. The anthropometric measurements and insulin resistance components (fasting plasma glucose (FPG), HbA1c, fasting insulin, HOMA-IR) were analyzed. HOMA-ß values were calculated to measure pancreatic beta cell functions. Serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured to determine the presence of inflammation and serum adiponectin levels were assessed. Results: Individuals with T2DM showed higher body mass index (BMI), body fat percentage, waist circumference (WC), waist-to-hip ratio and waist-to-height ratio values. Serum cytokine levels were higher but adiponectin levels were lower in diabetic patients. Serum concentrations of CRP were found to be significantly correlated with WC and body fat mass (kg and %); TNF-α was significantly associated with WC and waist-to-hip ratio in individuals with T2DM. Adiponectin was negatively correlated with WC and waist-to-hip ratio in healthy subjects. Conclusions: Prevention of obesity and central adiposity is an important factor to prevent elevations in inflammatory cytokine levels in diabetic patients.

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.

Discrimination between non-functioning pituitary adenomas and hypophysitis using machine learning methods based on magnetic resonance imaging­derived texture features.

PURPOSE: Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas. METHODS: The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy. RESULTS: A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types. CONCLUSIONS: Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.

Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis.

CONTEXT: Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. OBJECTIVE: This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. METHODS: A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. RESULTS: We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. CONCLUSION: Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.

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.

Aging versus youth: Endocrine aspects of vulnerability for COVID-19.

Coronavirus Disease 2019 (COVID-19) is characterized with a wide range of clinical presentations from asymptomatic to severe disease. In patients with severe disease, the main causes of mortality have been acute respiratory distress syndrome, cytokine storm and thrombotic events. Although all factors that may be associated with disease severity are not yet clear, older age remains a leading risk factor. While age-related immune changes may be at the bottom of severe course of COVID-19, age-related hormonal changes have considerable importance due to their interactions with these immune alterations, and also with endothelial dysfunction and comorbid cardiometabolic disorders. This review aims to provide the current scientific evidence on the pathogenetic mechanisms underlying the pathway to severe COVID-19, from a collaborative perspective of age-related immune and hormonal changes together, in accordance with the clinical knowledge acquired thus far.

Clinical course and management of pembrolizumab-associated isolated adrenocorticotrophic hormone deficiency: a new case and literature review.

Hypophysitis is rarely reported in patients receiving pembrolizumab-only immunotherapies. Since the clinical presentation is usually as isolated adrenocorticotrophic hormone (ACTH) deficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy. A 49-year-old male with laryngeal cancer applied to our clinic just after the tenth cycle of his pembrolizumab treatment, with weakness and nausea/vomiting. Serum morning cortisol and ACTH were 0.47 mcg/dl and 10.1 pg/ml, respectively; the remaining anterior pituitary hormone levels were normal. Pituitary MRI revealed mild glandular enlargement and loss of posterior pituitary bright-spot. All symptoms and signs improved with low-dose prednisolone. This is the second reported case of pembolizumab-associated isolated ACTH deficiency having abnormal pituitary MRI findings as we have reviewed all reported cases in the literature.

Lay abstract Immune check point inhibitors (ICIs) are used in order to enhance antitumoral immune mechanisms in certain cancers. As a result, immune-related side effects have commonly been reported in patients taking ICIs, one of which is hypophysitis. Pembrolizumab is a type of ICI which has rarely been associated with hypophysitis. Since the clinical presentation of pembrolizumab-associated hypophysitis is usually as isolated adrenocorticotrophic hormone deficiency and related cortisol insufficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy, due to shared symptoms such as fatigue, loss of appetite and nausea. Here we have reported a case with pembrolizumab-associated isolated adrenocorticotrophic hormone deficiency and reviewed all other cases available in the literature to improve our understanding of such patients.

An Update on Contraception in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology. Combined oral contraceptives (COCs), along with lifestyle modifications, represent the first-line medical treatment for the long-term management of PCOS. Containing low doses of estrogen and different types of progestin, COCs restore menstrual cyclicity, improve hyperandrogenism, and provide additional benefits such as reducing the risk of endometrial cancer. However, potential cardiometabolic risk associated with these agents has been a concern. COCs increase the risk of venous thromboembolism (VTE), related both to the dose of estrogen and the type of progestin involved. Arterial thrombotic events related to COC use occur much less frequently, and usually not a concern for young patients. All patients diagnosed with PCOS should be carefully evaluated for cardiometabolic risk factors at baseline, before initiating a COC. Age, smoking, obesity, glucose intolerance or diabetes, hypertension, dyslipidemia, thrombophilia, and family history of VTE should be recorded. Patients should be re-assessed at consecutive visits, more closely if any baseline cardiometabolic risk factor is present. Individual risk assessment is the key in order to avoid unfavorable outcomes related to COC use in women with PCOS.

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.

Tissue fat quantification by magnetic resonance imaging: proton density fat fraction in polycystic ovary syndrome.

RESEARCH QUESTION: What are the potential differences between lean women with and without polycystic ovary syndrome (PCOS) in fat content in liver, vertebrae, paraspinal muscles, pancreas, subcutaneous (SCAT) and visceral adipose tissue (VAT)? Magnetic resonance imaging proton density fat fraction (PDFF) was used to establish these differences. This is a novel, non-invasive, operator-independent method with comparable diagnostic sensitivity and specificity to histologic examination for fatty liver disease, and strong correlation with muscle strength in neuromuscular studies. DESIGN: Twenty lean women with PCOS (mean age 23.9 ± 2.3; body mass index [BMI] 22.4 ± 2.0) and 20 age- and BMI-matched healthy women (mean age 24.9 ± 1.5; BMI 21.5 ± 1.9) were enrolled in this cross-sectional study. Anthropometric, biochemical and hormonal evaluations along with magnetic resonance imaging proton density fat fraction were carried out. RESULTS: PDFF% measurements of liver, SCAT and VAT were higher in the PCOS group, indicating increased fat content in these areas in lean women with PCOS compared with controls (P = 0.045, 0.030 and 0.037, respectively). In contrast, PDFF% values of vertebrae and paraspinal muscles in the PCOS group were lower than controls (P = 0.038 and 0.05, respectively). Pancreatic PDFF% measurements were similar between the groups. In the PCOS group, PDFF% of VAT was positively correlated with free androgen index (r = 0.69, P = 0.002). CONCLUSIONS: PDFF% measurement, an MRI-based novel biomarker, reveals increased fat in liver, SCAT and VAT, and decreased fat in vertebral bones and paraspinal muscles of lean women with PCOS.

Clinical Characteristics, Management, and Treatment Outcomes of Primary Hypophysitis: A Monocentric Cohort.

Primary hypophysitis (PH) is a rare autoimmune inflammatory disease of the pituitary gland. The aim of the study was to evaluate clinical characteristics, disease management, and outcomes of cases with PH. Medical records of PH patients admitted to Hacettepe University Hospital between 1999 and 2017 were analyzed retrospectively. Paraffin-embedded pathology blocks were obtained for both re-examination and IgG4 immunostaining. Twenty PH patients (15 females, 5 males) were evaluated. Mean age at diagnosis was 41.5±13.4 years. Some form of hormonal disorder was present in 63.2% of cases, hypogonadism (66.6%) being the most common. Panhypopituitarism was present in 36.8%. All patients had pituitary gland enlargement on magnetic resonance imaging; stalk thickening and loss of neurohypophyseal bright spot were present in 17.6 and 23.5%, respectively. Lymphocytic hypophysitis was the most common histopathological subtype (50%). Among pathology specimens available for IgG and IgG4 immunostaining (n=10), none fulfilled the criteria for IgG4-related hypophysitis. Four patients were given glucocorticoid treatment in diverse protocols; as initial therapy in 3. Sixteen cases underwent surgery, 7 of whom due to neuro-ophthalmologic involvement. Only 1 patient was observed without any intervention. Reduction of pituitary enlargement was seen in all surgical and glucocorticoid treated cases. None of the surgical patients showed hormonal improvement while one case in glucocorticoid group improved. PH should be considered in the differential diagnosis of sellar masses causing hormonal deficiencies. MRI findings are usually helpful, but not yet sufficient for definitive diagnosis of PH. Treatment usually improves symptoms and reduces sellar masses while hormonal recovery is less common.

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.

A case of atypical macroprolactinoma presenting with pituitary apoplexy during pregnancy and review of the literature.

Pituitary apoplexy (PA) during pregnancy is a rare acute clinical situation which could have life-threatening consequences. Here we reported a case of 26-year-old nulliparous woman presenting with PA at the second trimester of her pregnancy. We also have reviewed reported cases of PA during pregnancy and conducted a detailed discussion on presenting symptoms, underlying pituitary pathology, management of apoplexy during pregnancy and outcomes.

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.