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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.

Purpose While obesity is related to more severe outcomes of coronavirus disease 2019 (COVID-19), factors leading to poor prognosis still remain unclear. The present study evaluated the outcomes of COVID-19 patients who were overweight or obese and variables associated with severe disease in a large group of consecutive cases. Methods A nationwide retrospective cohort study was performed using the Turkish National Healthcare Database. Demographic characteristics, laboratory tests, comorbidities, and medications of patients registered between March 11 and May 30, 2020, were recorded. Results A total of 14, 625 patients (median age:42, IQR:26 years; female 57.4%) with normal weight (34.7%), overweight (35.6%), and obesity (29.7%) were included. Hospitalization, ICU admission, intubation/mechanical ventilation, pulmonary involvement, and mortality were significantly higher in patients who were overweight or obese. In adjusted analyses, both overweight (OR, 95% CI: 1.82, 1.04–3.21; p=0.037) and obesity (OR, 95% CI: 2.69, 1.02–1.05; p Conclusions COVID-19 patients who were overweight or obese were more likely to have adverse outcomes but only obesity was a predictor of mortality. Such patients should receive urgent medical attention and active management, especially the elderly, men, and people with chronic kidney disease.

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.To investigate the auto-oxidized oxysterols, 7-ketocholesterol (7-KC) and cholestane-3β,5α,6β-triol (chol-triol), in patients with subclinical hypothyroidism, as well as to evaluate the impact of restoring euthyroidism on oxysterol concentrations.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-3β,5α,6β-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.Concentrations of 7-ketocholesterol and cholestane-3β,5α,6β-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-3β,5α,6β-triol decreased significantly and reached similar concentrations observed in healthy controls (p 0.001 for both oxysterols).Auto-oxidized oxysterol species are higher in patients with mild thyroid dysfunction, and supported the rationale for treating subclinical-hypothyroidism.

Purpose New coronavirus disease 2019 (COVID-19) has a worse prognosis in patients with diabetes. However, there are insufficient data about the effect of hyperglycemia on COVID-19 prognosis in non-diabetic patients. This study aimed to investigate the relationship between random blood glucose levels measured at the time of diagnosis and prognosis of COVID-19 disease in non-diabetic patients. Methods A nationwide retrospective cohort of non-diabetic patients with confirmed COVID-19 infection from 11 March to 30 May 2020 in the Turkish Ministry of Health database was investigated. The patients were stratified into three groups according to blood glucose levels which were Results A total of 12,817 non-diabetic patients (median age [IQR]: 44 [25] years, females: 50.9%) were included. Patients in group-2 (5%) and group-3 (14%) had higher mortality rates than patients in group-1 (2.1%). The rates of hospitalization, hospital stays longer than 8 days, intensive care unit (ICU) admission, ICU stay more than 6 days, and mechanical ventilation were also significantly higher in group-3 patients. Likewise, glucose levels in the range of 140-199 mg/dL were an independent associate of mortality and composite of ICU admission and/or mechanical ventilation. ConclusionHyperglycemia at the time of COVID-19 diagnosis is associated with poor prognosis in non-diabetic patients. Clinicians should be more careful in the treatment of non-diabetic COVID-19 patients with hyperglycemia.

BACKGROUND Non-invasive methods for periodontitis diagnosis would be a clinically important tool. This cross-sectional study aimed to investigate the association between oxidative stress, glycation, and inflammation markers and periodontal clinical parameters in periodontitis and periodontally healthy patients with type 2 diabetes and corresponding systemically healthy controls. METHODS Sixty-seven periodontally healthy (DM-H, n = 32) and periodontitis (DM-P, n = 35) patients with type 2 diabetes, and 54 systemically healthy periodontitis (H-P, n = 26) and periodontally healthy (H-H, n = 28) controls were included. Clinical periodontal parameters, body mass index, fasting glucose, hemoglobin A1c (HbA1c), along with saliva and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), advanced glycation end products (AGE), AGE receptor (RAGE) and high sensitivity C-reactive protein (hsCRP) levels were recorded and analyzed. RESULTS Salivary 8-OHdG levels were significantly higher in periodontitis compared to periodontally healthy patients, regardless of systemic status (P

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 i...

Metabolic dysfunction, although not included in the diagnostic criteria, is very common in polycystic ovary syndrome (PCOS), especially in overweight/obese patients. Because metabolic disorders may not be as noticeable and/or disturbing as the other features of PCOS, it is important for physicians to inform and evaluate the patients in this regard. Insulin resistance and resulting hyperinsulinemia, which are aggravated by androgen excess, play a key role in several pathways leading to metabolic disorders such as glucose intolerance, diabetes and dyslipidemia. Lifestyle modifications including a healthy diet and regular exercise should be the main part of all intervention strategies targeting metabolic dysfunction in PCOS. Metformin is recommended in the treatment guidelines for overweight/obese PCOS, especially in patients with high metabolic risk. In line with recent advances in the treatment of hyperglycemia and/or obesity, newer agents targeting metabolic dysfunction in PCOS have become available. This chapter aims to provide up-to-date information about all the interventions targeting metabolism in PCOS.

Background There are scarce published data in differentiated thyroid cancer patients about new coronavirus disease 2019 (COVID‐19) disease outcomes and mortality. Here, we evaluated COVID‐19 infection outcomes and mortality in thyroid cancer patients with COVID‐19 infection. Design and methods We included a cohort of patients with thyroid cancer with PCR‐confirmed COVID‐19 disease from 11 March to 30 May 2020 from the Turkish Ministry of Health database in our nationwide, retrospective study. We compared the mortality and morbidity of COVID patients with or without thyroid cancer. Univariate and multivariate analyses were used to assess the independent factors for mortality, length of hospital stay and intensive care unit (ICU) admission and mechanical ventilation. We also analysed the effect of radioiodine treatment on severity and death rate of COVID‐19 disease. Results We evaluated 388 COVID‐19 patients with thyroid cancer [median age: 54 years, interquartile range (IQR) 18 years, males: 23%] and age and gender‐matched 388 COVID‐19 patients without thyroid cancer. Patients with thyroid cancer had a similar mortality ratio compared with the non‐cancer group. Among patients with thyroid cancer, age, presence of diabetes mellitus, asthma/COPD, heart failure, chronic kidney disease, prior coronary artery disease, RAS blocker usage and low lymphocyte count were associated with mortality. Radioactive iodine (RAI) treatment and cumulative radioactive iodine dosage did not negatively affect the severity and mortality of COVID‐19 disease in our patient group. Conclusions Our study indicated that history of thyroid cancer did not have an increased risk of mortality or morbidity in COVID‐19 disease. Besides, RAI therapy history and doses of radioactive iodine did not affect mortality or outcome.

PURPOSE To assess polar vessel presence and enhancement 4DCT imaging and their relation with biochemical and histopathological features. METHODS Patients with primary hyperparathyroidism and preoperative 4DCT imaging were screened retrospectively and those with histopathologically proven diagnosis of PA were included. Biochemical findings, densitometric measurements (HUprecontrast, HUarterial, HUvenous, HUwash-in, HUwash-out, HUretained) and CTvolume of PA on 4DCT, presence of a polar vessel (PV), and histopathological features were recorded. Correlations between serum PTH, calcium levels and densitometric measurements of PA on 4DCT were investigated. Differences between subgroups created according to PV presence were also evaluated. RESULTS Thirty-nine patients were enrolled (F/M = 32/7, median age = 57, interquartile range = 50-62 years). In all patients, serum PTH levels positively correlated with CTvolume (r = 0.398, p = 0.012) but negatively correlated with HUarterial (r = - 0.366; p = 0.022), HUvenous (r = - 0.452; p = 0.004) and HUretained (r = - 0.421; p = 0.008). In PV (-) PAs, PTH levels were positively correlated with CTvolume (r = 0.608, p ≤ 0.002) and negatively with HUarterial (r = - 0.449, p ≤ 0.028), HUvenous (r = - 0.560, p = 0.004), HUwash-in (r = - 0.460, p = 0.024), and HUretained (r = - 0.539, p = 0.007). No correlation between PTH levels and densitometric measurements was found in PV (+) PAs. HUwash-in and HUwash-out were significantly higher in PV (+) PAs compared to PV (-) PAs (p = 0.021 and p = 0.033, respectively). Histopathologic features revealed no difference according to the presence of PV. CONCLUSION PTH levels might have an association with imaging findings of PAs, especially when categorized with respect to PV presence. PTH levels were negatively correlated with degree of enhancement in PV (-) PAs. Therefore, radiologists should be aware that in patients with high serum PTH levels and without a discernible PV, PA might be difficult to localize.

PurposeCOVID-19 disease has a worse prognosis in patients with diabetes, but the comparative data about the course of COVID-19 in patients with type 1 (T1DM) and type 2 diabetes (T2DM) are lacking. The purpose of this study was to find out the relative clinical severity and mortality of COVID-19 patients with T1DM and T2DM.MethodsA nationwide retrospective cohort of patients with confirmed (PCR positive) COVID-19 infection (n=149,671) was investigated. After exclusion of individuals with unspecified diabetes status, the adverse outcomes between patients with T1DM (n=163), T2DM (n=33,478) and the non-diabetics (n=115,108) were compared by using the propensity score matching method. The outcomes were hospitalization, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality.ResultsThe patients with T1DM had higher mortality than the age and gender matched patients with T2DM (n=489) and the non-diabetics (n=489) (pConclusionAccording to the results, patients with T1DM had poorer COVID-19 prognosis than those with T2DM or the non-diabetics. These patients should be cared diligently until more data will be available about the causes of increased COVID-19 mortality in T1DM.

Background Coronavirus disease 2019 (COVID‐19) has been reported to be associated with a more severe course in patients with type 2 diabetes mellitus (T2DM). However, severe adverse outcomes are not recorded in all patients. In this study, we assessed disease outcomes in patients with and without T2DM hospitalized for COVID‐19. Methods A nationwide retrospective cohort of patients with T2DM hospitalized with confirmed COVID‐19 infection from 11 March to 30 May 2020 in the Turkish Ministry of Health database was investigated. Multivariate modeling was used to assess the independent predictors of demographic and clinical characteristics with mortality, length of hospital stay, and intensive care unit (ICU) admission and/or mechanical ventilation. Results A total of 18 426 inpatients (median age [interquartile range, IQR]: 61 [17] years; males: 43.3%) were investigated. Patients with T2DM (n = 9213) were compared with a group without diabetes (n = 9213) that were matched using the propensity scores for age and gender. Compared with the group without T2DM, 30‐day mortality following hospitalization was higher in patients with T2DM (13.6% vs 8.7%; hazard ratio 1.75; 95% CI, 1.58‐1.93; P, Highlights Coronavirus disease 2019 (COVID‐19) takes an unfavorable course in patients with type 2 diabetes mellitus (T2DM), and the risk increases in individuals with certain conditions, some of which are not modifiable.This study showed significantly higher mortality due to COVID‐19 in hospitalized patients with T2DM than without (13.6% vs 8.7%; hazard ratio 1.75; 95% CI, 1.58‐1.93).Older age, male gender, obesity, preexisting insulin treatment, low lymphocyte count, and pulmonary involvement on admission were the significant associates of COVID‐19 mortality.

Background: Endocrine disorders are among the most common complications in thalassemia patients. Although cardiac complications are the main cause of mortality, endocrinological disturbances have a significant impact on morbidity and quality of life. Methods: Sixty-eight patients (35 F, 33 M; 60 thalassemia major, 8 thalassemia intermedia) admitted to our outpatient clinic between August 2015 - December 2017 were included in the study. Patients were evaluated for short stature, hypogonadism, glycemic abnormalities, hypoparathyroidism, hypothyroidism and osteoporosis. Results: The average height of thalassemia major patients was 165.67±8.8 cm in men and 155.6±6.6 cm in women. Nine patients had short stature (4 F, 5 E), but 91.5% (54/59) of the whole group had low IGF-1 levels. There were 23 thalassemia major patients (11 F, 12 M) who had a history of hormonal induction therapy for delayed puberty. Overall, 60% (n = 36) of the patients were currently receiving hormone replacement therapy for central hypogonadism (19 F, 17 M). The median age at diagnosis of central hypogonadism was 22.5 years in men (IQR: 16.5-27.5) and 18 years in women (IQR: 16-25). There were five diabetic thalassemia major patients in study group whose median age at diagnosis was 20 (16-36). Of the 47 patients who underwent OGTT, 13 thalassemia major patients had prediabetes (27.7%). None of the thalassemia intermedia patients had glycemic abnormalities. Subclinical hypothyroidism was present in 19.7% (13/66) of the whole group, hypoparathyroidism was found in 8.5% (9/59) of thalassemia major patients, and vitamin D deficiency (25OH D < 20 ng/ml) was found in 70.8% (46/65) of all patients. Of 64 patients who underwent BMD, 25 had osteoporosis (39.1%) while 23 hadosteopenia (35.9%). The incidence of pathological fractures in thalassemia major patients was 20% (11/55). Conclusions: The incidence of endocrine disorders may increase in thalassemia patients due to prolonged duration of lifespan. Regular screening for newly emerging endocrinopathies during adulthood has great value. In our study, the most common endocrine disorders were vitamin D deficiency, hypogonadism, osteoporosis and glycemic abnormalities; respectively. Early diagnosis and treatment would prevent patients from having related morbidities and therefore increase quality of life.

Introduction: Telmisartan is an angiotensin-II receptor type-1 blocker and a partial agonist for peroxisome proliferator-activated receptor-γ. The aim of this study was to determine the potential effects of telmisartan on bone metabolism and turnover markers. Methods: Forty-two patients with newly diagnosed stage I hypertension who were prescribed telmisartan 80 mg/day or losartan 100 mg/day were included. Serum levels of calcium, phosphorus, 25-hydroxy vitamin D, bone-specific alkaline phosphatase, osteocalcin, interleukin 6 and 24-hour urinary N-terminal telopeptide were measured at the beginning and after 12 weeks of treatment. Results: When treatment arms were evaluated together, significantly increased 25-hydroxy vitamin D levels ( p=0.01), and decreased parathormone (PTH) ( pConclusions: Neither telmisartan, despite its partial peroxisome proliferator-activated receptor-γ agonistic effect, nor losartan treatment had significant effects on bone turnover markers in newly diagnosed stage I hypertensive patients.

Objective: The aim of this study was to assess and compare the diagnostic power of B-mode ultrasonography (US), power Doppler US (PD), and ultrasound elastography (USE) in detecting malignant lymph nodes (LNs) during follow-up of patients who were operated on for differentiated thyroid cancer (DTC). Methods: In this prospective study, a total of 103 cervical LNs having suspicious malignant features from 72 patients with DTC were examined using US, PD, and USE. USE scores were classified from 1 to 3 according to the presence of elasticity (1, soft; 2, intermediate; 3, hard). The strain ratios (SRs) of all LNs were calculated according to adjacent muscle tissue. Results: The most-sensitive ultrasonographic features were hilum loss and hypoechogenicity, with 94.4% and 80.6% sensitivity and 93.5% and 84.4% negative predictive value, respectively. The most-specific feature was the presence of cystic component, with 98.5% specificity and 85.7% positive predictive value. Presence of diffuse/chaotic or irregular vascularity in PD had 47.2% sensitivity and 83.6% specificity in predicting metastasis. In USE, the sensitivity and specificity of score 3 were 56.7% and 74.2%, respectively. The median SR of metastatic LNs was higher than that of benign LNs (median SR [min-max], 3.0 [0.16 and 29] vs. 1.89 [0.26 and 37.9]), but the difference was not significant (P = .07). Multivariate logistic regression analyses revealed 4.9-, 6.6-, and 10-fold increases in metastasis risk for short/long axis ratio ≥0.5, nodal vascularity, and score 3 USE, respectively (P

Aims: Type 2 diabetes mellitus (T2DM) is a risk factor for severe COVID-19. Our aim was to compare the clinical outcomes of patients with and without T2DM during the first hit of COVID-19 in Istanbul.& nbsp; Methods: A retrospective population-based study was conducted including all consecutive adult symptomatic COVID-19 cases. Patients were confirmed with rt-PCR; treated and monitored in accordance with standard protocols. The primary endpoints were hospitalization and 30-day mortality.& nbsp; Results: Of the 93,571 patients, 22.6% had T2DM, with older age and higher BMI. Propensity Score matched evaluation resulted in significantly higher rates of hospitalization (1.5-fold), 30-day mortality (1.6-fold), and pneumonia (1.4-fold). They revealed more severe laboratory deviations, comorbidities, and frequent drug usage than the Non-DM group. In T2DM age, pneumonia, hypertension, obesity, and insulin-based therapies were associated with an increased likelihood of hospitalization; whereas age, male gender, lymphopenia, obesity, and insulin treatment were considerably associated with higher odds of death.& nbsp; Conclusions: COVID-19 patients with T2DM had worse clinical outcomes with higher hospitalization and 30-day mortality rates than those without diabetes. Compared to most territories of the world, COVID-19 mortality was much lower in Istanbul, which may be associated with accessible healthcare provision and the younger structure of the population.& nbsp; (C)& nbsp;2021 Elsevier B.V. All rights reserved.

Polycystic ovary syndrome (PCOS) is a common and complex genetic disorder that develops under varying degrees of hyperandrogenemic and hyperinsulinemic conditions that cause phenotypic variability ranging from mild hirsutism to anovulation and infertility. In addition to increased risk of reproductive disability, PCOS is associated with metabolic diseases including type 2 diabetes, dyslipidemia, and cardiovascular disease. Similar prevalence rates and shared genetic susceptibility of PCOS among different populations suggest that genetic risk factors were already present in the ancestors of humans. Contemporary human genetic studies inform us that the origin of human ancestors is from Africa. Sharing common susceptibility loci between Chinese and European ancestry suggests that PCOS may have persisted for more than 50,000 years, before the migration of humans out of Africa. Although PCOS is the most common cause of anovulatory infertility, its high prevalence is still a paradox. From an evolutionary perspective, the pathogenic mechanisms underlying PCOS might be candidate factors for survival advantage of the human being. Former compensatory advantageous factors may become pathogenic mechanisms underlying complex metabolic disease with prolonged life expectancy and transition to sedentary lifestyle.

Werner syndrome (WS) is a rare autosomal recessive adultonset progeroid disorder characterized by the early onset of aged-appearance and age-related metabolic disorders caused by homologous mutations at the WRN helicase locus (1). The features of the syndrome were first described as sclerodermalike skin changes, short stature, gray hair and genital hypoplasia (2). Later, other endocrinological manifestations, including osteoporosis and glucose metabolism abnormalities have been shown to be the components of this syndrome. Generally, the first manifestation of the disease is absence of growth spurt (3). The incidence of WS is one per million. It is known that the frequency of this syndrome is higher in Japan as 75% of patients were reported from Japan between 1904 and 2008 (4). Case reports from Turkey are extremely rare (5,6,7,8). Symptoms of premature aging usually first develop in the third decade of life (3). Herein, we present an atypical case of WS with early onset of premature aging-related metabolic disorders. Werner syndrome (WS) is a rare autosomal recessive adult-onset progeroid disorder characterized by the early onset of aged-appearance and age-related metabolic disorders. Symptoms of premature aging usually first develop in the second-third decades of life. We report a 27-year-old female who was admitted to our clinic at the age of eighteen with hyperglycemia. She was diagnosed with diabetes and type 4 dyslipidemia at the age of seven. In her family history, her parents were first cousins and she had three healthy brothers. On her first physical examination; she had bird-like face appearance, global hair loss, beaked nose, short stature and she was overweight. She had global hair loss with gray and thin hair. Hoarseness of voice and hyperkeratosis of skin were observed. She had bilateral cataracts and moderate sensorineural hearing loss. On psychiatric examination, borderline mental retardation was detected. She had severe insulin resistance and hypertriglyceridemia despite levothyroxine, gemfibrozil, omega-3 and intensive insulin treatment. Routine lipid apheresis was performed to lower the triglyceride levels reaching 5256 mg/dL. She also had focal segmental glomerulosclerosis, hepatosteatosis, osteoporosis and epilepsy. Disease was accompanied by several congenital deformities, such as Rathke’s cleft cyst, angiomyolipoma and femoral neck hypoplasia. WS is a rare genetic disorder characterized by multiple endocrine manifestations as well as soft tissue changes. We present a case of early disturbances that were diagnosed before typical clinical signs and symptoms. We propose that WS should be kept in mind when type 2 diabetes and hyperlipidemia are diagnosed early in childhood. Turk Jem 2015; 19: 99-104

Treatment of aggressive pituitary tumors may be challenging. Temozolomide (TMZ) is a promising agent when conventional treatment methods fail. We present three patients with aggressive pituitary tumors with atypical morphology, who were resistant to conventional treatments and treated with TMZ. First case had a somatotroph adenoma, second a corticotroph adenoma, and the third a macroprolactinoma. We also reviewed the literature reporting TMZ efficacy in somatotroph, corticotroph and mammotroph tumors of pituitary. TMZ, 150-200 mg/m2 for 5 days in 28 days schedule was given to all patients. Among our patients, even though only the case of macroprolactinoma had a favorable response to TMZ treatment, both radiological and hormonal recurrences occurred 30 months after cessation of TMZ treatment. Then TMZ treatment was applied again. Cases of somatotroph and corticotroph adenomas had progressed under TMZ treatment and patients were lost due to mass effect of the tumor. Review of the literature demonstrated 67.3%, 60% and 26.7% overall response rates to the TMZ treatment in prolactinoma, corticotropinoma and somatostatinoma cases, respectively. There is still need to define response criteria uniformly to TMZ treatment in aggressive pituitary tumors and duration of response should be reported for reliable evaluation of results.

have been estimated to afflict 3% of the population (2). Therefore, clinical presentation of the autoimmune diseases may have a wide spectrum. For example, celiac disease is said to be a clinical chameleon that may be presented with osteoporosis, anemia, growth retardation, fatty liver, etc. (3). Similarly, the less prevalent lymphocytic hypophysitis (LYH) is probably underestimated rather than being a rare disease (4). It has to be suspected when other Isolated adrenocorticotropic hormone (ACTH) deficiency is a rare cause of hypocortisolism, mostly associated with lymphocytic hypophisitis (LYH). Autoimmune miyelofibrosis is another rare autoimmune disease causing bone marrow fibrosis. Here, we report the case of a patient who presented with common symptoms (weakness, fatigue, weight loss, vague pain) and anemia and was diagnosed with both rare autoimmune disorders (lymphocytic hypophisitis and autoimmune myelofibrosis). A 34-year-old male presented with weakness, fatigue, weight loss, and diffuse musculoskeletal pain. He had mild normochromic normocytic anemia. Further investigations revealed bone marrow fibrosis. The World Health Organization criteria were not fulfilled for the diagnosis of primary myelofibrosis. Since his symptoms could not be explained by mild anemia, a thorough evaluation was performed which revealed hypocortisolism associated with undetectable ACTH. Insulin-induced hypoglycemia test yielded insufficient response of ACTH and cortisol. Sellar MRI demonstrated typical features of LYH. Resolution of all the symptoms and anemia was achieved with low-dose glucocorticoid replacement therapy. In conclusion, when evaluating a patient presenting with fatigue, weight loss, vague pain, backache, and mild anemia, hypocortisolism also should be kept in mind in the differential diagnosis. If the case is isolated ACTH deficiency, the most probable cause is LYH. In such a case, additional endocrinological or non-endocrinological autoimmune disorders are likely to be present. We report the first case of lymphocytic hypophysitis coexisting with autoimmune myelofibrosis. Turk Jem 2014; 2: 47-51

Annexin V (AnxV) has potent anticoagulant properties and regulatory functions for apoptosis and inflammation. Antibodies against annexin V (anti-AnxVs) may inhibit AnxV functions, leading to thrombosis during autoimmune diseases. Type 1 diabetes is an autoimmune disease and related with an ongoing autoimmune inflammation and thrombotic complications. There is no study evaluating anti-AnxVs/AnxV in a disease setting.The aim of this study was to evaluate the status of AnxV and anti-AnxVs in patients with type 1 diabetes.One hundred twenty-one patients with type 1 diabetes and 92 healthy controls were included in this study. Serum levels of AnxV and anti-AnxVs and expression of the AnxV gene and its common polymorphism in Kozak sequence (-1CT) were studied. As a functional assay, the binding capacity of AnxV to platelets was evaluated.As compared with controls, type 1 diabetic patients had significantly low serum AnxV levels and AnxV gene expression. The number of anti-AnxV positivity and their serum levels were significantly higher in type 1 diabetic patients than controls. AnxV binding to platelets were significantly decreased in the type 1 diabetic patients. The frequencies of the -1CT polymorphism of AnxV gene did not differ between groups.This study demonstrated the significant changes in AnxV levels and its function in type 1 diabetic patients. These results support the hypothesis that the defective AnxV system may have a role in ongoing autoimmune activity and the development of thrombotic complications in type 1 diabetes. Further studies are necessary to elucidate the clinical impact of anti-AnxVs and dysregulated AnxV function in type 1 diabetes.

The thyroid gland is remarkably resistant to infectious agents owing to several protective mechanisms. Acute suppurative thyroiditis after fine-needle aspiration (FNA) in an immunocompetent patient is very rare. We report the case of a 50-year-old immunocompetent male patient who presented with painful cervical swelling, fever, and chills after an FNA of the thyroid. His physical and laboratory examination suggested an acute suppurative thyroiditis. Repeat FNA results were consistent with thyroid abscess. Physicians should be aware of the probability of acute bacterial thyroiditis after FNA.

Aim: Type 1 diabetes mellitus (T1DM) is an autoimmune disease, and autoimmunity related prothrombotic factors might contribute to the hypercoagulable state seen in T1DM. The aim of this study is to investigate the presence of anti-prothrombin (aPT) antibodies as a prothrombotic risk factor in patients with T1DM. Materials and Methods: The study was performed with 121 type 1 diabetic patients, who were admitted to the Endocrinology and Metabolism outpatient clinic, and 92 healthy volunteers without history of any vascular, thromboembolic or hemorrhagic disease were included as controls. The quantitative determination of aPT IgG, IgM and anti-beta 2-glycoprotein-1 (anti-beta 2GP1) IgG antibodies in plasma samples were performed using commercially available ELISA kits according to manufacturer's instructions. Results: aPT IgG antibodies present for the type 1 diabetic and control groups were 52.06% and 2.16% respectively. The circulating levels of aPT IgG was significantly higher in type 1 diabetics (20.17 +/- 8.28 AU/ml) when compared to controls (4.47 +/- 2.01 AU/ml, p Conclusion: aPT antibody levels are significantly increased in patients with T1DM when compared to controls. Similarly, the plasma levels of anti-beta 2GP1 IgG antibodies, an important marker of coagulation cascade, were found significantly elevated in type 1 diabetic group. These data suggest that the higher levels of aPT antibodies seen in type 1 diabetic patients may contribute to the development of hypercoagulability in T1DM.

Several studies have evaluated the ability of ultrasound elastography (USE) to diagnose malignant nodules. However, these studies had important limiting factors, selection bias and small sample size. The aims of the present study were to prospectively assess, in a large group of patients, the diagnostic power of USE for detecting malignancy in thyroid nodules, and to compare this technique with B-mode grayscale ultrasonography (BUS) and power Doppler ultrasonography (PD).There were 194 patients with 237 thyroid nodules who were examined using BUS, PD, and USE. USE scores were classified according to the elasticity: score 1 as high, score 2 as intermediate, and score 3 as low (i.e., a high degree of stiffness). Fine-needle aspiration cytology (FNAC) was performed in all nodules at least two different times. Nodules having two benign FNAC readings that did not change the diameter during a 6-month follow-up period were classified as benign. Patients having thyroid nodules with indeterminate, suspicious, or malignant cytology had total or hemithyroidectomy to remove the nodule and treat the malignancy.Fifty eight (25%) nodules in 45 (23%) patients were found to be malignant. USE had a limited sensitivity and a positive predictive value in detecting malignant thyroid nodules and was not superior to BUS. USE had almost the same specificity and a negative predictive value as BUS. A power Doppler type-3 pattern was not of sufficient sensitivity to detect malignancies in thyroid nodules.In contrast to earlier reports, this current study noted a lower sensitivity and specificity of USE for the diagnosis of malignancy in thyroid nodules than previously reported.

Diabet. Med. 29, e133–e137 (2012) Abstract Background Insulinomas, although they are rare, are the most common of pancreatic islet cell tumours. The incidence is estimated at only four per million person-years and only 5–12% of reported cases are malignant. Distinction between malignant and benign tumours can only be made by the presence of metastasis, as there are no specific morphologic, biochemical or genetic features distinguishing them. Most patients with malignant insulinoma have lymph node or liver metastases and, rarely, bone involvement. The coincidence of insulinoma and diabetes mellitus is an extremely rare condition and reported only in a few cases. Case report We report a 45-year-old woman who was diagnosed with insulinoma on the basis of clinical and laboratory findings and endoscopic examination. Histopathological diagnosis revealed well-differentiated endocrine carcinoma of the pancreas with lymph node metastase. The case was accepted as malignant insulinoma and the patient underwent surgery. Interestingly, hyperglycaemia occurred after the removal of the insulinoma, with the requirement for insulin in the post-operative 3 weeks, which was changed to oral anti-diabetic agents as a permanent treatment. The patient is still being treated with oral anti-diabetic agents. We think that the patient might have had diabetes mellitus, because of insulin resistance that developed with a high-caloric intake stimulated by hypoglycaemia, and which had been masked for many years, but manifested overtly after removal of the tumour. Conclusions Although this is a rare condition, clinicians should bear in mind that insulinomas may exist together with diabetes mellitus, and it is important to have this suspicion when considering the perioperative approach and for the prevention of morbidities.

Summary Background After the definition of minimally invasive procedures, preoperative localization of parathyroid lesions is now crucial. False-positive results up to 30% were reported by B-mode grayscale ultrasonography (US) in localization of parathyroid lesions. Parathyroid adenomas are relatively stiff lesions. Ultrasound elastography (USE) can accurately evaluate tissue stiffness and might detect the stiff parathyroid lesions. Objective The aim of this study is to demonstrate whether USE can detect the level of the stiffness and help the preoperative localization of parathyroid lesions during parathyroid ultrasonography examination. Patients The patients who were candidates for parathyroidectomy were prospectively enrolled to this study and were evaluated by USE. Results Seventy-two patients with 93 parathyroid lesions underwent parathyroidectomy. Sixty-three patients including three multiple endocrine neoplasia type-1 patients had primary hyperparathyroidism, three patients with chronic renal disease (CRD) had tertiary hyperparathyroidism, three patients with CRD and two renal transplanted patients had persistent secondary hyperparathyroidism. One patient was excluded. While all parathyroid adenomas exhibited high levels of stiffness (score 3 and 4), 17 (63%) out of 27 parathyroid hyperplasia lesions were shown to have significantly higher elasticity. The evaluation of median strain ratios of parathyroid lesions revealed that parathyroid adenomas demonstrated significantly higher levels of stiffness than hyperplasias (P ≤ 0·001). Conclusions This is the first study that evaluates the ultrasound elastographic features of parathyroid lesions. Parathyroid adenomas were shown to appear as stiff lesions, and half of the hyperplasias showed high elasticity. Parathyroid elastography is a novel technique to evaluate parathyroid lesions and might be a guide for surgeons to determine the type of operation to apply.

Tryptophan, an essential amino acid, can be metabolized to several kinds of physiologically active metabolites. Accumulating data indicate that an altered metabolism of tryptophan and its active metabolites have important roles for the pathogenesis and development of complications of diabetes mellitus. Changes in tryptophan–kynurenine and tryptophan–methoxyindole pathways are related to several pathophysiological mechanisms of type 1 or type 2 diabetes. Particularly, serotonin, melatonin, and their receptors would be novel targets not only to better understand the pathogenesis of diabetes but also to develop new antidiabetic agents.

An increased or normal serum TSH concentration, despite elevated thyroid hormone levels, is observed in resistance to thyroid hormone (RTH) and TSH-secreting adenomas (TSHomas). When coexistent with a differentiated thyroid cancer (DTC), maintenance of a suppression of TSH is challenging.The aim of the study was to discuss the pitfalls arising from the failure to suppress TSH secretion in DTC and the strategies for proper treatment of DTC in association with RTH and TSHoma.Four unusual cases of DTC associated with TSHoma (2 cases), RTH (1 case), and an elevated TSH of unknown etiology (1 case) are presented, and the literature is reviewed.Although a persistent mild TSH elevation may not be a risk factor for the development of DTC, it represents an important problem during the treatment of DTC. Aggressive treatment options should be applied in the proper order to prevent tumor recurrence and persistence in the absence of ideal TSH suppression.Although there is no agreed consensus regarding the management of DTC in the presence of persistent hyperthyrotropinemia, complete tumor removal followed by radioablation and attempts to reduce the serum TSH to the lowest tolerable level are recommended. The outcomes in the reported cases have not been unfavorable, despite the persistence of nonsuppressed TSH.

WOS: 000303914800032, PubMed ID: 22493418, …

Objective To describe a case of hyalinizing trabecular tumor (HTT) in a background of lymphocytic thyroiditis that was misdiagnosed as papillary thyroid carcinoma (PTC) based on fine-needle aspiration (FNA) cytologic findings and overtreated with total thyroidectomy. Methods We present a case report, including the imaging and pathologic findings, of a 68-year-old woman who presented with a multinodular goiter that was suspicious for PTC. Results On the basis of FNA cytologic findings, she underwent a total thyroidectomy, and histologic examination of the thyroid gland revealed HTT in a background of lymphocytic thyroiditis. Radioiodine treatment was not administered because of the tumor’s low risk profile. No metastatic foci were established under nonsuppressive levothyroxine therapy after 3 years of follow-up. Conclusions HTT is a challenging entity because of the uncertainty of its nature, the diagnostic challenges,and the mimicry of other types of thyroid tumors. In order to avoid overtreatment, endocrinologists and thyroid surgeons should be aware of the features of HTT, and suspicious cases should be evaluated by experienced cytopathologists. (Endocr Pract. 2011;17:e140-e143)

Summary Background High molecular weight adiponectin (HMWA) is the active circulating form of adiponectin. Nampt/visfatin is the enzyme secreted from adipocytes in an active form and is one of the putative regulators of insulin secretion. Objective To investigate the dynamics of total adiponectin (TA), HMWA and Nampt/visfatin in obese and lean women during oral glucose tolerance test (OGTT). Methods We studied normal glucose-tolerant (NGT), age-matched, 30 obese and 30 lean women. All subjects underwent a standard 75 g, 2-h OGTT, and area under the curve (AUC) during OGTT for glucose, insulin, Nampt/visfatin, TA and HMWA was calculated. Body fat mass was assessed by bioimpedance analysis. Results Obese women had significantly higher basal and AUC values for insulin and Nampt/visfatin, whereas basal and AUC-HMWA were significantly lower in this group. Alternatively, obese and lean groups had similar basal and AUC values for glucose and TA. Basal insulin levels were negatively correlated with HMWA levels, but not with basal Nampt/visfatin. AUC-insulin was correlated positively with AUC-visfatin, and negatively with AUC-HMWA. Total and truncal body fat mass showed positive correlation with basal and AUC-visfatin, and negative correlation with basal and AUC-HMWA. Conclusion In the NGT state, obese women have higher Nampt/visfatin and lower HMWA levels, both basally and in response to oral glucose challenge. The dynamics of Nampt/visfatin and HMWA during OGTT appear to be linked with insulin and adiposity. Counter-regulatory adaptations in HMWA and Nampt/visfatin might have an impact on suggested adipoinsular axis, contributing to maintenance of normal glucose tolerance.

We describe a patient who presented with epileptic seizures unresponsive to anticonvulsive treatment. Laboratory investigations demonstrated epileptiform seizure activity in the brain but also revealed severe hypocalcemia, hyperphosphatemia, and elevated serum parathyroid hormone. In addition, the patient showed a reduced serum level of 25-[OH]-vitamin D. The diagnosis of pseudohypoparathyroidism type-Ib (PHP-Ib) was made based on these clinical findings and upon identification of a 3-kb deletion within the STX16 locus, a genetic defect frequently associated with autosomal dominant PHP-Ib. This mutation was also present in the patient’s unaffected mother and her affected sister. Despite the molecular diagnosis of PHP-Ib, which is characterized by parathyroid hormone resistance in the absence of Albright’s hereditary osteodystrophy (AHO), the patient had a round face, slightly short stature, and short fourth metacarpals, which were consistent with mild AHO. The patient and her affected sister, who lacked AHO-like features, showed reduced serum levels of uric acid and increased fractional excretion of uric acid, a finding that was reported only once previously for PHP-Ib. Unlike the previous report, the fractional uric acid excretion and serum uric acid levels returned to normal in our patient and her sister after 3 months of treatment period. These findings underscore several important points with respect to the pathogenesis and clinical presentation of PHP-Ib. Furthermore, the findings in the index case present interesting novel aspects, including a previously undescribed coexistence of the 3-kb STX16 deletion and AHO-like features and a clinical course complicated by concomitant 25-[OH]-vitamin D deficiency, which may have resulted, at least partly, from long-term use of antiepileptic drugs.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the women of reproductive age. Familial clustering of PCOS has been consistently reported suggesting that genetic factors play a role in the development of the syndrome although PCOS cases do not exhibit a clear pattern of Mendelian inheritance. It is now well established that PCOS represents a complex trait similar to type-2 diabetes and obesity, and that both inherited and environmental factors contribute to the PCOS pathogenesis. A large number of functional candidate genes have been tested for association or linkage with PCOS phenotypes with more negative than positive findings. Lack of universally accepted diagnostic criteria, difficulties in the assignment of male phenotype, obscurity in the mode of inheritance, and particularly small sample size of the study populations appear to be major limitations for the genetic studies of PCOS. In the near future, utilizing the genome-wide scan approach and the HapMap project will provide a stronger potential for the genetic analysis of the syndrome.