Endocrine-disrupting effects of bisphenol-A, thiamethoxam, and fipronil in hormone-naïve transmen compared to cis-women.

BACKGROUND: Current evidence suggests that the etiology of gender dysphoria (GD) is multifactorial: this, however, remains unclear. Endocrine-disrupting chemicals (EDCs) are one of the etiological hypotheses. OBJECTIVES: In this study, we aimed to evaluate the urinary levels of bisphenol A (BPA), thiamethoxam, and fipronil in hormone-naïve transmen compared with case-matched cis-women as well as the relation between sex hormone levels and EDCs. METHODS: Drug-naïve transmen diagnosed with GD and who were referred from the psychiatry outpatient clinic to the outpatient clinic of the Department of Endocrinology, Marmara University Hospital, were included in the study. These individuals were assessed for eligibility; 38 drug-naïve transmen and 22 cis-women were recruited as the control group. After anthropometric evaluation laboratory tests for FSH, LH, total testosterone, and estradiol were carried out, spot urine samples were collected to evaluate the urine metabolic excretion of BPA, thiamethoxam, and fipronil. RESULTS: We found that androgens, total testosterone, androstenedione, and DHEAS levels were significantly higher in transmen than in cis-women. Thiamethoxam was considerably higher in cis-women than in transmen, whereas fipronil and BPA levels were similar in both groups. A negative correlation was found between thiamethoxam and testosterone and between thiamethoxam and BPA levels. CONCLUSION: The available data suggest that the EDCs that we are most exposed to in our lives are not the only factor in GD development. Even transmen who have not taken hormone replacement have high testosterone levels; however, the mechanism has not as yet been elucidated. The challenge is to determine whether this is a factor leading to GD or a condition that develops in common with GD.

Hyperandrogenism-related metabolic changes in drug-naïve transmen compared to cisgender women: a case-controlled study.

INTRODUCTION: The aetiology of gender dysphoria is still unclear. Although prior studies have shown that trans men have higher androgen levels than cisgender women, they all concluded unselected populations. Our reason for performing this study is to evaluate trans men's hormone profile and metabolic status to compare with cisgender women in a more selected population. This is the first case-controlled study to compare anthropometric, metabolic, and endocrinological parameters of drug-naïve trans men with those of cisgender women. MATERIAL AND METHODS: We designed this study as a single-centre observational cohort study. We included 70 drug naïve trans men, and the control group comprised 34 healthy cisgender women. We measured and compared hormone profiles and metabolic parameters in the 2 groups. RESULTS: Of the 70 trans men individuals, 16 (22.85%) met the Rotterdam criteria and were diagnosed with polycystic ovary syndrome (PCOS); 4 individuals in the control group met the criteria (11.7%). Although we matched body mass index in the groups, total testosterone, free androgen index, androstenedione, 17 hydroxyprogesterone, muscle strength, triglyceride, and homeostatic model assessment of insulin resistance levels were significantly higher in the trans men than in the cisgender women (p < 0.05). Even after were excluded PCOS patients, hyperandrogenaemia was apparent in the trans men. CONCLUSION: Our study showed that trans men have clearly higher androgen levels, which may have been the reason for metabolic changes compared to cisgender women. However, the main reason for hyperandrogenism in drug-naïve trans men is still not known, and more comprehensive studies are needed.

Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension.

BACKGROUND: The renin-angiotensin-aldosterone system was shown to be activated in severe COVID-19 infection. We aimed to investigate the relationship between angiotensin converting enzyme (ACE) levels, ACE gene polymorphism, type 2 diabetes (T2DM), and hypertension (HT) and the prognosis of COVID-19 infection. METHODS: This cross-sectional study analyzed the clinical features of adult patients with SARS-CoV-2 infection. ACE gene analysis and ACE level measurements were performed. The patients were grouped according to ACE gene polymorphism (DD, ID or II), disease severity (mild, moderate, or severe), and the use of dipeptidyl peptidase-4 enzyme inhibitor (DPP4i), ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARB). Intensive care unit (ICU) admissions and mortality were also recorded. RESULTS: A total of 266 patients were enrolled. Gene analysis detected DD polymorphism in the ACE 1 gene in 32.7% (n = 87), ID in 51.5% (n = 137), and II in 15.8% (n = 42) of the patients. ACE gene polymorphisms were not associated with disease severity, ICU admission, or mortality. ACE levels were higher in patients who died (p = 0.004) or were admitted to the ICU (p<0.001) and in those with severe disease compared to cases with mild (p = 0.023) or moderate (p<0.001) disease. HT, T2DM, and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission. ACE levels were similar in patients with or without HT (p = 0.374) and with HT using or not using ACEi/ARB (p = 0.999). They were also similar in patients with and without T2DM (p = 0.062) and in those with and without DPP4i treatment (p = 0.427). ACE level was a weak predictor of mortality but an important predictor of ICU admission. It predicted ICU admission in total (cutoff value >37.092 ng/mL, AUC: 0.775, p<0.001). CONCLUSION: Our findings suggest that higher ACE levels, but not ACE gene polymorphism, ACEi/ARB or DPP4i use, were associated with the prognosis of COVID-19 infection. The presence of HT and T2DM and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission.

Does total tumour diameter, multifocality, number of tumour foci, or laterality predict lymph node metastasis or recurrence in differentiated thyroid cancer?

INTRODUCTION: Data regarding laterality, focality, or total tumour diameter (TTD) in papillary thyroid cancer (PTC) are limited. We aimed to investigate the impact of focality, TTD, number of tumour foci, or laterality on aggressive features in PTC. MATERIAL AND METHODS: Patients were categorized based on maximum tumour diameter (MTD) (≤ 10 vs. > 10 mm), focality, laterality, or the number of tumour foci (1/2/ ≥ 3). We also categorized the patients as follows: Group 1, unifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 2, multifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 3, multifocal microcarcinoma (MTD ≤ 10/TTD > 10 mm); Group 4, unifocal macrocarcinoma (MTD > 10/TTD > 10 mm); Group 5, multifocal macrocarcinoma (MTD > 10/TTD > 10 mm). RESULTS: The mean diagnosis age (n = 511) was 44.7 (± 12.7) years, the majority of the patients were < 55 years old (n = 310) and female (n = 416). An increasing number of tumour foci were associated with a higher MTD or TTD, a higher ratio of extrathyroidal extension (ETE), vascular or lymphatic invasion, lymph node metastasis (LNM) or distant metastasis, or the need for radioactive iodine (RAI). There was no difference in the parameters between Group 3 and Group 2, or Group 4. Vascular invasion, American Thyroid Association high risk, LNM at diagnosis, and RAI total dose were higher in Group 5 than in Group 3. Microscopic or macroscopic ETE, T1b, and T4a were positive predictors for recurrence. Male sex, multifocality, number of tumour foci (≥ 3), MTD (> 10 mm), TTD (> 10 mm), Group 5, microscopic or macroscopic ETE, lymphatic or vascular invasion, RAI need, T2, and T4b were positive predictors for LNM. CONCLUSION: MTD and TTD increase the risk of LNM but not the recurrence in PTC. TTD, multifocality, and bilaterality can be considered risk factors in PTC staging systems and risk calculators.

Comparison of staging and recurrence predictors in patients with differentiated thyroid cancer between the 7th and 8th editions of the American Joint Committee on Cancer staging systems.

BACKGROUND: The predictive value of American Joint Committee on Cancer (AJCC) 8 for recurrence in differentiated thyroid cancer (DTC) is not known. We aimed to compare AJCC 7 and 8 regarding the differences in staging and recurrence predictors in DTC. METHODS: Demographic, clinical (duration of disease and follow-up, the extent of surgery), laboratory (TSH, fT4, thyroglobulin, and antithyroglobulin), pathological (type of thyroid cancer, localization, multifocality, diameter, extrathyroidal extension [ETE], and lymph node [LN] metastasis), and imaging findings (sonography, and whole-body scan), and follow-up features (metastases, recurrence and/or persistence, and RAI need) were retrospectively analyzed in adult patients with DTC followed-up for at least six months. Staging was determined in accordance with AJCC 7 and AJCC 8, prediction of recurrence and persistence by ATA risk stratification, and death risk by AMES systems. The alterations in staging and recurrence predictors were analyzed. RESULTS: A majority of study patients (N.=524) were female (N.=424) and diagnosed with papillary cancer (N.=511), the median age at diagnosis was 44. 97.89% (N.=93) of stage 2-4 patients (N.=95) in AJCC 7 were down-staged in AJCC 8. We down-staged 41 patients of 45-55 years of age into stage 1 in AJCC 8 independent of LN status. A percentage of 26.71% of patients (N.=140) did have persistence, 9.54% (N.=50) persistence at the last follow-up, and 9.54% (N.=50) had recurrence. According to AJCC 8, T4 and AMES high risk were predictors for recurrence (hazard ratio: 3.053, P=0.023; hazard ratio:2.465, and P=0.005; respectively). Both AJCC 7 and 8 were associated with recurrence (P=0.008 and P<0.001, respectively). Stage 4 in AJCC 7, and stages 3 and 4 in AJCC 8 better predicted the probability of recurrence. CONCLUSIONS: Our findings suggest that AJCC 8 better predicted the recurrence in DTC than AJCC 7. In AJCC 8, T4 tumor, AMES high risk, stages 3 and 4 predicted recurrence. The vast majority of patients with stages 2-4 in AJCC 7 were down-staged in AJCC 8.

Accurate interpretation of thyroid dysfunction during pregnancy: should we continue to use published guidelines instead of population-based gestation-specific reference intervals for the thyroid-stimulating hormone (TSH)?

BACKGROUND: Considering the changes in thyroid physiology associated with pregnancy and poor outcomes related to abnormal maternal thyroid function, international guidelines recommend using population-based trimester-specific reference intervals (RIs) for thyroid testing. If these RIs are not available in the laboratory, implementing recommended fixed cut-off values globally is still controversial. To address this issue, we aimed to establish appropriate RI of thyroid-stimulating hormone (TSH) in pregnant Turkish women for our laboratory and compare the prevalence of thyroid dysfunction based on the established and recommended criteria. METHODS: Of 2638 pregnant women, 1777 women followed in the obstetric outpatient were enrolled in the reference interval study after applying exclusion criteria related to medical and prenatal history. A retrospective study was conducted by collecting data from July 2016 to March 2019. Serum TSH was measured by UniCel DxI 800 Immunoassay System (Beckman Coulter Inc., Brea, CA, USA). The study design relied on two approaches in order to classify pregnant women: trimester-specific and subgroup-specific; the latter involved dividing each trimester into two subgroups: T1a, T1b, T2a, T2b, T3a, T3b. The lower and upper limits of the RIs were derived by the parametric method after normalizing the data distribution using the modified Box-Cox power transformation method. RESULTS: The lowest TSH value was detected at 8-12 weeks in early pregnancy, and the median value of TSH in the T1b subgroup was significantly lower than the T1a subgroup (P < 0.05). TSH levels showed a gradual trend of increase along with the pregnancy and increased significantly in the T2a, T2b, and T3b subgroups compared to the preceding subgroups (P < 0.05). Compared to the diagnostic criteria recommended by American Thyroid Association (ATA), the prevalence of thyroid dysfunction was significantly different from the established trimester- and subgroup-specific RIs throughout the pregnancy (P < 0.001). CONCLUSIONS: We conclude that establishing gestation- and laboratory-specific RIs, especially for TSH, is essential for diagnosing thyroid disorders in pregnancy, and the recommended universal cut-off values, which may contribute to the risk of a misdiagnosis or a missed diagnosis, should be taken with caution in the clinical setting. However, regarding the fluctuation of thyroid function tests throughout pregnancy, trimester-specific RIs are insufficient, and implementing split phases is required.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

ABSTRACT Objetivo: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. Subjects and methods: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. Results: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. Conclusion: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.

The association of free testosterone levels with coronavirus disease 2019.

BACKGROUND: Angiotensin-converting enzyme 2 and transmembrane protease serine 2 are critical factors of virus transmission. Expression of angiotensin-converting enzyme 2 is highest in testes, and testicular function and testosterone levels were affected by coronavirus disease 2019. Low testosterone levels are related to infections, especially respiratory tract infections, and could worsen clinical conditions by exacerbating cytokine storms and increasing pro-inflammatory cytokines. OBJECTIVES: We aimed to evaluate the acute and chronic effects of coronavirus disease 2019 on gonadal functions. Our second aim was to detect the relationship between free testosterone levels and disease prognosis and determine the impact of low-free testosterone on admission to the intensive care unit. METHODS: Eighty-one patients with reverse-transcription polymerase chain reaction-confirmed coronavirus disease 2019 were enrolled. Twenty-nine patients were assessed again for 6 months post-coronavirus disease 2019 follow-up, and seven of them had a semen analysis. Serum follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin, and total testosterone levels were measured. RESULTS: In this observational study, 71.6% (n = 58) of patients had low free testosterone levels at baseline, in which 69% were considered secondary hypogonadism. A longer length of hospitalization and increased inflammatory markers (d-dimer, high-sensitive C-reactive protein, and procalcitonin) were detected in the low-free testosterone group. Follicle-stimulating hormone, total, free, and bioavailable testosterone levels were lower in patients who required admission to the intensive care unit. Free testosterone levels were inversely correlated with the length of hospitalization and prognostic disease factors. Oligozoospermia and impaired progressive motility were present in 42.8% (3/7) of the patients. In 6 months post-coronavirus disease 2019 follow-up, out of 29 patients, 48.2% still had low testosterone levels. CONCLUSION: A high rate of hypogonadism (71.6%) was found, especially secondary hypogonadism, and about half of the patients had hypogonadism in the sixth months' follow-up. Low free testosterone levels were correlated with inflammatory parameters, and it is related to the intensive care unit admission. Studies with long-term follow-up data in larger groups are needed to determine persistent hypogonadism and impaired spermatogenesis.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

OBJECTIVE: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. METHODS: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. RESULTS: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. CONCLUSION: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.

Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID-19.

PURPOSE: Vitamin D deficiency has emerged as another potential risk factor for coronavirus disease (COVID-19) due to the immunomodulatory effects of 25 hydroxyvitamin D [25 (OH)D]. Vitamin D receptor (VDR) gene polymorphisms such as Fok I, Bsm I, Apa I, and Taq I are also associated with different courses of viral infections. This study aimed to evaluate the association between the VDR gene polymorphism at Fok I, Taq I, Bsm I, and Apa I genotypes and the prognosis of COVID-19 in respect to vitamin D deficiency. METHODS: Two-hundred ninety-seven patients with COVID-19 were enrolled. Serum 25 (OH)D levels were measured. Four variant regions of the VDR gene, FokI, BsmI, ApaI, and TaqI were determined. RESULTS: Eighty-three percent of subjects had vitamin D deficiency, and 40.7% of the whole group had severe deficiency. Median 25 (OH)D level was 11.97 ng/ml. Vitamin D levels were not related to inflammatory markers, disease severity, admission to intensive care unit (ICU), and mortality. While disease severity was related to Fok I Ff genotype, it was Taq TT genotype for ICU admission. Moreover, the ApaI aa genotype was common among the patients who were died. None of the deceased subjects had the Fok I FF genotype. CONCLUSION: 25 (OH)D levels were not related to the severity and mortality of COVID-19. VDR gene polymorphisms are independently associated with the severity of COVID-19 and the survival of patients.

Genetic and Clinical Characterization of Patients with Maturity-Onset of Diabetes of the Young (MODY): Identification of Novel Variations.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is a rare monogenic type of diabetes, and accounts for 2-5% of all diabetes cases. An early age of onset, a family history supporting autosomaldominant inheritance, insulin resistance, and the absence of autoimmunity are the major characteristics of MODY. However, genetic testing is crucial for diagnosis. AIMS: To investigate the 7 MODY-related genes and clinical findings of patients with a preliminary clinical diagnosis of MODY. STUDY DESIGN: Retrospective cross-sectional study. METHODS: In this study, 7 genes (KCNJ11, ABCC8, INS, GCK, HNF4A, HNF1A, and HNF1B) related to MODY were screened via targeted sequencing in 182 cases with a confirmed pre-diagnosis of MODY. The clinical characteristics of the patients were evaluated retrospectively. RESULTS: A total of 182 patients, 48% of whom were women, between the ages of 18-62 were included in the study. In 30 cases (16.4%), 28 different pathogenic variations were found, of which 20 were previously reported and 8 were novel variations segregated by disease within the family. Pathogenic variations were detected in the following genes in order of mutation frequency; GCK, HNF1A, ABCC8, HNF4A, HNF1B and KCNJ11. Interestingly, six of the 30 cases (20%) carried a pathogenic variation in the ABCC8 gene. No mutation was detected in the INS gene. A family history of vertically transmitted diabetes and elevated HbA1C at the time of diagnosis were found in 20 (66%) and 16 (52%) cases, respectively. CONCLUSION: In this series, 28 different pathogenic variations are identified, 8 of which are novel. The rate of pathogenic variation in the ABCC8 gene is unexpectedly high. Two-thirds of cases have a family history of vertically transmitted diabetes.

The Association of Thyroid Hormone Changes with Inflammatory Status and Prognosis in COVID-19.

BACKGROUND: COVID-19 infection may have multiorgan effects in addition to effects on the lungs and immune system. Recently, studies have found thyroid function abnormalities in COVID-19 cases which were interpreted as euthyroid sick syndrome (ESS) or destructive thyroiditis. Therefore, in this study, we aimed to evaluate the thyroid function status and thyroid autoimmunity in COVID-19 patients. Material and Method. 205 patients were included. The medical history and laboratory parameters at admission were collected from medical records. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, and thyroglobulin antibody were measured, and patients were classified according to thyroid function status. RESULTS: 34.1% of the patients were euthyroid. Length of hospitalization (p < 0.001), rate of oxygen demand (p < 0.001), and intensive care unit (ICU) admission (p=0.022) were lower, and none of the euthyroid patients died. 108 (52.6%) patients were classified to have ESS, 57 were classified as mild, and 51 were moderate. The inflammatory parameters were higher in patients with moderate ESS. In cluster analysis, a high-risk group with a lower median FT3 value (median = 2.34 ng/L; IQR = 0.86), a higher median FT4 value (median = 1.04 ng/dL; IQR = 0.33), and a lower median TSH value (median = 0.62 mIU/L; IQR = 0.59) included 8 of 9 died patients and 25 of the 31 patients that were admitted to ICU. Discussion. Length of hospitalization, oxygen demand, ICU admission, and mortality were lower in euthyroid patients. Moreover, none of the euthyroid patients died. In conclusion, evaluation of thyroid function tests during COVID-19 infection may give information about the prognosis of disease.

Effects of concomitant obesity and diabetes on the aggressiveness and outcomes of differentiated thyroid cancer patients

ABSTRACT Objective: Obesity and diabetes are the risk factors for cancer development including differentiated thyroid cancer (DTC). Contradictory accumulated data indicates the possible negative effects of obesity and hyperglyceamia as a factor for aggressiveness of DTC. The aim of the present study is to investigate the association of high body mass index (BMI) and presence of type 2 diabetes mellitus (T2DM) on the histological aggressiveness and clinical outcomes in DTC patients followed for over 4 years in a single center. Materials and methods: Consequative 526 DTC patients who had undergone total thyroidectomy and/or radioactive iodine (RAI) ablation were reviewed retrospectively. Patients were divided into groups based on their BMI: normal weight, overweight, obese and also were evalauted in 3 groups presence of diabetes, prediabetes and nomoglyceamia. Histological aggressiveness of DTC at the time of diagnosis and clinical response at the time of last clinical visit were reassessed according to the criteria suggested by ATA 2015 guideline. Results: No differences in histopathologic features, risk of recurrence, cumulative dose of RAI ablation and prevalence of 131I avid metastatic disease were demonstrated among the groups both classified according to BMI and hyperglycemia. Mean of 3.4 year follow-up also showed no differences in the clinial repsonse to therapy and percentage of nonthyroid primary cancer in DTC patients. Conclusion: In this retrospective study we demonstrated that obesity and T2DM have no additive effect on DTC aggressiveness and response to therapy. DTC patients with obesity and diabetes can be treated according to present guidelines without requirement for spesific attention.

Effects of concomitant obesity and diabetes on the aggressiveness and outcomes of differentiated thyroid cancer patients.

OBJECTIVE: Obesity and diabetes are the risk factors for cancer development including differentiated thyroid cancer (DTC). Contradictory accumulated data indicates the possible negative effects of obesity and hyperglyceamia as a factor for aggressiveness of DTC. The aim of the present study is to investigate the association of high body mass index (BMI) and presence of type 2 diabetes mellitus (T2DM) on the histological aggressiveness and clinical outcomes in DTC patients followed for over 4 years in a single center. METHODS: Consequative 526 DTC patients who had undergone total thyroidectomy and/or radioactive iodine (RAI) ablation were reviewed retrospectively. Patients were divided into groups based on their BMI: normal weight, overweight, obese and also were evalauted in 3 groups presence of diabetes, prediabetes and nomoglyceamia. Histological aggressiveness of DTC at the time of diagnosis and clinical response at the time of last clinical visit were reassessed according to the criteria suggested by ATA 2015 guideline. RESULTS: No differences in histopathologic features, risk of recurrence, cumulative dose of RAI ablation and prevalence of 131I avid metastatic disease were demonstrated among the groups both classified according to BMI and hyperglycemia. Mean of 3.4 year follow-up also showed no differences in the clinial repsonse to therapy and percentage of nonthyroid primary cancer in DTC patients. CONCLUSION: In this retrospective study we demonstrated that obesity and T2DM have no additive effect on DTC aggressiveness and response to therapy. DTC patients with obesity and diabetes can be treated according to present guidelines without requirement for spesific attention.

Preoperative plasmapheresis experience in Graves' disease patients with anti-thyroid drug-induced hepatotoxicity.

Hepatotoxicity is a rare but serious side effect of antithyroid drug (ATI) therapy in Graves' disease patients. Cessation of ATI drug is needed in most of the patients if liver enzymes highly elevated or in case of agranulocytosis. Permanent therapy, surgery or radioactive iodine ablation are the treatment choices to ensure euthyroidism in active Graves' disease patients. Therapeutic plasma exchange (TPE) can be an option to ensure euthyroidism, especially in patients scheduled for urgent surgery. In the present study, we present consecutive five cases of methimazole related severe hepatotoxicity that underwent TPE before thyroid surgery. The median number of apheresis sessions was 3 (range: 2-5). Free triiodothyronine (FT3) 65-83 %, free thyroxine (FT4) 22-66 %, thyrotropin receptor antibodies (TRAB) 55-96 % decreases were observed. All patients underwent total thyroidectomy. TPE is an effective method to reduce serum FT3, FT4, TRAB levels in the short term to provide better thyroid hormone status before urgent surgery in ATI induced toxic hepatitis patients.