Can signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) be used as an indicator of endothelial dysfunction in acromegaly patients?

PURPOSE: Acromegaly is closely related to increased oxidative stress and endothelial dysfunction (ED). This study aimed to evaluate, for the first time in the literature, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and endothelial nitric oxide synthase e(NOS) levels in the setting of acromegaly. METHOD: A total of 56 acromegaly patients and a control group composed of 30 healthy volunteers were included in this study. In the postoperative follow-up, patients were grouped as active or in-remission according to their GH and IGF-1 levels in oral glucose stimulation test (OGST). After detailed physical examination of acromegaly patients and the control subjects, 8-hour fasting blood samples were collected to evaluate biochemical parameters including lipid profile, anterior pituitary hormones, and SCUBE-1 and e(NOS) levels. RESULTS: Inactive and active acromegaly was noted in 78.6% and 21.4% of patients, respectively. The median (min-max) SCUBE-1 levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (1.6(0.4-2.4) and 1.8(1.1-2.5) vs. 0.4(0.2-1.0) ng/mL, respectively, p < 0.001 for each). The median (min-max) e(NOS) levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (132.7 (26.8-602.9) and 137.3 (69.7-488.7) vs. 83.9 (16.4-218.7) pg/mL, p = 0.018 and p = 0.048, respectively). We have also detected positive correlations of e(NOS) with leukocyte (r = 0.307, p = 0.021) and neutrophil counts (r = 0.309, p = 0.021). CONCLUSION: Our study revealed for the first time in literature that SCUBE-1 levels, being a novel marker for ED, were significantly higher in acromegaly patients than in control subjects. When supported with clinical studies, SCUBE-1can be used as an early indicator of endothelial damage in acromegaly patients.

Evaluation of Adrenal Reserve in Patients with Differentiated Thyroid Cancer Receiving Thyroid Hormone Suppression Therapy- case-control Comparative Study.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) are exposed to subclinical exogenous hyperthyroidism for the suppression of thyroid-stimulating hormone (TSH). In this study, we aimed to evaluate the adrenal reserve in DTC patients receiving suppression therapy. MATERIALS AND METHODS: The study included 55 DTC patients on suppression therapy and 32 healthy volunteers. Basal serum cortisol of all participants and adrenocorticotropic hormone (ACTH) of the patient group were measured. A standard-dose ACTH test (0.25 mg) was performed in patients with a basal cortisol <14.5 mcg/dL. RESULTS: In the patient group, TSH was lower, free thyroxine (fT4) was higher, and free triiodothyronine (fT3) was similar to those of the control group (p < .01, p < .01, p = .140, respectively). The serum cortisol of the patient group was significantly lower than the control group (12.14 ± 5.12 mcg/dL vs 18.00 ± 5.56 mcg/dL, p < .001). A total of 34 (61.8%) patients with DTC had a basal cortisol <14.5 mcg/dL. Prolonged TSH suppression (≥5 years vs <5 years) was associated with lower basal cortisol (7.46 ± 2.63 mcg/dL vs 9.48 ± 2.65 mcg/dL, p = .022). The ACTH stimulation test showed that 2 (5.8%) patients had a cortisol response <18 mcg/dL. The rate of adrenal insufficiency was 3.6% in DTC patients. A moderate negative correlation was found between ACTH and fT3 of patients with low basal cortisol (r = -0.358, p = .038). CONCLUSION: Patients with DTC receiving TSH suppression therapy are at risk for adrenal insufficiency. The duration and severity of suppression might increase this possibility. Dynamic testing with synthetic ACTH can be used to reveal insufficient cortisol response in case of clinical suspicion.

Association of thiol/disulphide homeostasis with Bethesda classification of thyroid nodules and thyroid cancer.

BACKGROUND: Ultrasonography and fine-needle aspiration biopsy are frequently used to diagnose thyroid cancer. However, supportive data might be required in case of diagnostic difficulty. This study investigated whether there is a relationship between thiol/ disulphide homeostasis and cytological and histopathological diagnosis of thyroid nodules. METHODS: The patient group consisted of 81 individuals with euthyroid nodular (single/multiple) goiter scheduled for thyroidectomy, and the control group consisted of 28 age- and sex-matched healthy volunteers who had no thyroid nodule on ultrasonographic evaluation. All participants were selected among the admissions to the study clinic between June 2017 and June 2018, and venous blood samples were collected. The samples of the patients were taken before surgery. Thiol and disulphide levels were analysed with the automated spectrophotometric method. RESULTS: The mean age of the patient group was 45.66 ± 10.45 years, and the mean age of the control group was 43.53 ± 11.49 years (p = 0.365). The increasing Bethesda categories were positively correlated with the disulphide level (r = 0.281, p = 0.011), disulphide/native thiol ratio (r = 0.241, p = 0.030) and disulphide/total thiol ratio (r = 0.250, p = 0.024). Disulphide/native thiol ratio and disulphide/ total thiol ratio were significantly higher in the histopathologically malignant (euthyroid nodular goiter but final pathology reported malignant) compared to histopathologically benign (euthyroid nodular goiter but final pathology reported benign) (p = 0.012; p = 0.007, respectively) and control groups (p = 0.006; p = 0.004, respectively), but no significant difference was found in these ratios between benign and control group (p = 0.711; p = 0.749, respectively). DISCUSSION: Oxidative stress parameters were significantly higher in thyroid cancer. A positive correlation was detected between Bethesda categories with increased risk of malignancy and the disulphide/native thiol ratio and the disulphide/total thiol ratio.

Thicknesses of the retinal layers in patients with Graves' disease with or without orbitopathy.

PURPOSE: Graves' orbitopathy (GO) is an inflammatory process that may involve the ocular surface, orbital fat, extraocular muscles, and optic nerves in patients with Graves' disease (GD). We aimed to compare thicknesses of retinal layers in patients with GD with and without GO. METHODS: One hundred seven patients with GD [23 with GO (Group 1), 84 without GO (Group 2)] and eighteen volunteers (Group 3) were enrolled. The spectral-domain optical coherence tomography (SD-OCT) was used for ophthalmologic evaluation. Seven retinal layers including retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE) were assessed. The thicknesses of layers were compared in groups. RESULTS: The median GCL thickness values in groups 1, 2, and 3 were 14 µm, 15 µm, and 17.5 µm, respectively (p = 0.02). The median IPL thickness was 20 µm in group 1, 21 µm in group 2, and 22 µm in group 3 (p = 0.038). The median RPE thickness values in groups 1, 2, and 3 were 16 µm, 17 µm, and 18.5 µm, respectively (p = 0.001). GCL in group 1 was thinner than in group 3 (p = 0.02), while similar in groups 2 and 3 (p = 0.06). IPL in group 1 was thinner than in group 3 (p = 0.035), while similar in groups 2 and 3 (p = 0.13). RPE in groups 1 and 2 was thinner than in group 3 (p = 0.009, p = 0.001, respectively), while it was similar in groups 1 and 2 (p = 0.93). RNLF, INL, OPL, ONL were similar in all three (p > 0.05 for each). CONCLUSION: Ganglion cell layer and IPL were thinner in patients with GO than in healthy controls, while both were similar in patients without GO and healthy controls. RPE was thinner in all Graves patients than in healthy controls. Early detection of changes in retinal layers of GD may guide the physician to prevent significant vision problems.

Assessment of calcium and vitamin D medications adherence in patients with hypoparathyroidism after thyroidectomy.

In this study, we found that patients with hypoparathyroidism had a problem with calcium medication compliance, and this problem increased with the duration of the disease. We also showed that patients are concerned about the possible side effects of drugs. INTRODUCTION: In this study, we aimed to evaluate adherence to active vitamin D and calcium replacement in patients with post-surgical hypoparathyroidism. METHODS: To elucidate the medication adherence, we performed a questionnaire survey using the six-item "Medication adherence questionnaire"(MAQ). The first, second, and sixth questions reflect the motivation status of the patients whereas the third, fourth, and fifth questions reflect the knowledge about the medication that is received. The responses are scored and patients are classified regarding their motivation to and knowledge about the particular drug. RESULTS: Totally, 64 patients (male: 12/female: 52; mean age 48.6±11.6 years) who had post-operative hypoparathyroidism were included in our study. Median disease durance was 60 months (min-max: 12-295 months). We found that motivation score of calcium usage was significantly lower compared to vitamin D usage (p<0.001). The calcium motivation score was reversely correlated with disease duration (r= -0.256 and p=0.046). The most common worry about calcium usage was nephrotoxicity, and the most common worries about calcitriol treatment were kidney damage and polyuria. One-third of the patients were taking oral calcium and calcitriol less than the recommended dose. CONCLUSION: One-third of patients lack motivation to use calcium whereas half of the patients experiences anxiety about drug-related side effects. This is a preliminary study showing that vital calcium and active vitamin D intake may be interrupted due to side effect anxiety.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

Organ-specific autoimmune markers in adult patients with type 1 diabetes mellitus.

AIM: We aimed to investigate the presence of thyroid, celiac disease (CD) and anti-parietal cell antibodies (APCA) in adult type 1 diabetes (T1DM) patients. METHODS: Data of 287 T1DM patients >16 years old were reviewed retrospectively. Thyroid disease related, CD related antibodies and APCA were evaluated. Patients were divided into early onset (<30 years old) and late-onset (≥30 years old) TIDM, and ≤10 years, 11-20 years and >20 years according to disease duration. RESULTS: There were 142 (49.5%) female and 145 (50.5%) male patients. The median age at diagnosis and disease duration were 21 (2-53) and 6.91 (0-50.8) years, respectively. Antibody positivity rates were anti-glutamic acid decarboxylase (anti-GAD) 72.8%, anti-insulin 9.1%, anti-islet cell 25.7%, antithyroid peroxidase (anti-TPO) 34.8%, anti-thyroglobulin 19.9%, anti-endomysial IgA (EMA-IgA) 7.6%, anti-gliadin IgA (AGA-IgA), 12.2%, AGA-IgG 13.0%, tissue transglutaminase IgA 7.1% and APCA 14.4%. One hundred twenty-eight (44.6%) patients had at least one non-diabetes autoantibody. Thyroid autoantibodies and dysfunction were significantly higher in women than men. Anti-TPO positivity was higher in the late-onset group (P = .044). Anti-GAD level was correlated with thyroid related antibody positivity in male patients with positive anti-GAD (r: .340, P: .006). The positivity of EMA-IgA and AGA-IgA was higher in patients with disease duration >20 years (P = .017 and .039, respectively). CONCLUSION: Almost half of the adult T1DM patients were positive for at least one non-diabetic antibody. It is important to investigate thyroid autoimmunity in patients diagnosed with T1DM at any age, including advanced age. CD associated antibody positivity increases with disease duration, suggesting that they should be re-evaluated at clinical suspicion, even if prior tests were negative.

Low rate of latent autoimmune diabetes in adults (LADA) in patients followed for type 2 diabetes: A single center's experience in Turkey.

OBJECTIVE: In this study, we aimed to determine the frequency of and the clinical and metabolic features of patients with latent autoimmune diabetes in adults (LADA) at a single center in Turkey. METHODS: Patients over 30 years of age diagnosed with type 2 diabetes who did not require insulin for a minimum of 6 months following diagnosis were included. Data from 324 patients (163 women; 161 men), with a mean age of 54.97 ± 7.53 years, were analyzed in the study. Levels of antibodies to glutamate decarboxylase (anti-GAD) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. RESULTS: Anti-GAD positivity was identified in 5 patients (1.5%). Family history of diabetes, body mass index (BMI), age, sex distribution, insulin resistance, serum triglycerides, high-density lipoprotein, and low-density lipoprotein were similar in the LADA and type 2 diabetes patients. Median HbA1c was significantly higher (10.8% vs. 7.38%, p = 0.002) and fasting C-peptide was lower (0.75 ng/mL vs. 2.82 ng/mL, p = 0.009) in patients with LADA compared to in those with type 2 diabetes. Among the 5 patients with LADA, 4 were positive for antithyroid peroxidase antibodies. The median disease duration was relatively shorter among patients with LADA (4 years vs. 7 years, p = 0.105). CONCLUSION: We observed a LADA frequency of 1.5% among Turkish patients followed for type 2 diabetes. The presence of obesity and metabolic syndrome did not exclude LADA, and patients with LADA had worse glycemic control than patients with type 2 diabetes did.

Low rate of latent autoimmune diabetes in adults (LADA) in patients followed for type 2 diabetes: A single centers experience in Turkey

ABSTRACT Objective In this study, we aimed to determine the frequency of and the clinical and metabolic features of patients with latent autoimmune diabetes in adults (LADA) at a single center in Turkey. Subjects and methods Patients over 30 years of age diagnosed with type 2 diabetes who did not require insulin for a minimum of 6 months following diagnosis were included. Data from 324 patients (163 women; 161 men), with a mean age of 54.97 ± 7.53 years, were analyzed in the study. Levels of antibodies to glutamate decarboxylase (anti-GAD) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. Results Anti-GAD positivity was identified in 5 patients (1.5%). Family history of diabetes, body mass index (BMI), age, sex distribution, insulin resistance, serum triglycerides, high-density lipoprotein, and low-density lipoprotein were similar in the LADA and type 2 diabetes patients. Median HbA1c was significantly higher (10.8% vs. 7.38%, p = 0.002) and fasting C-peptide was lower (0.75 ng/mL vs. 2.82 ng/mL, p = 0.009) in patients with LADA compared to in those with type 2 diabetes. Among the 5 patients with LADA, 4 were positive for antithyroid peroxidase antibodies. The median disease duration was relatively shorter among patients with LADA (4 years vs. 7 years, p = 0.105). Conclusion We observed a LADA frequency of 1.5% among Turkish patients followed for type 2 diabetes. The presence of obesity and metabolic syndrome did not exclude LADA, and patients with LADA had worse glycemic control than patients with type 2 diabetes did.

ABO Blood Groups, Rh Factor, and Thyroid Cancer Risk: To 'B' or Not to 'B'.

Purpose: In this study, we aimed to evaluate ABO blood groups and Rh factor in patients with thyroid cancer.Methods: Demographical and clinical features, cytological results, ABO blood groups, and Rh factor status of patients with benign and malignant thyroid disease were evaluated. Histopathological features of thyroid cancer were compared in Rh positive and negative patients, and patients with different ABO blood groups.Results: Histopathological diagnosis was benign in 1,299 (63.5%) and malignant in 744 (36.5%) patients. There was no significant difference between benign and malignant patients in terms of age, sex, thyroid autoantibody positivity, and ABO blood groups (p > .05 for each). A significantly higher rate of patients with malignant disease were Rh positive compared to patients with benign disease (91.8% vs. 88.1%, p = .046). In thyroid cancer patients, extrathyroidal extension and advanced stage (3-4) were observed more frequently in patients with B compared to non-B blood groups (p = .028 and 0.042, respectively). The likelihood of the extrathyroidal extension was 4.272 (95%: 1.816-10.049) times higher in B blood group compared to non-B blood groups in patients with multifocal disease (p < .001). Patients with O blood group had lower rate of capsular invasion than patients with non-O blood groups (p = .018).Conclusion: Patients with B blood group had higher risk of extrathyroidal extension and advanced stage compared to patients with non-B blood group.

Is ultrasonographically detected nodule diameter concordant with pathological tumor size?

INTRODUCTION: We aimed to compare preoperative ultrasonographical and postoperative histopathological diameters of differentiated thyroid cancer (DTC) lesions and investigate possible factors that can predict the discordance between two measurements. METHODS: Data of patients with histopathologically confirmed DTC were reviewed retrospectively. Nodules evaluated by preoperative US were matched with histopathologically examined nodules. Incidental tumors and nodules that can not be matched in US and histopathology reports were excluded. Preoperative US diameter and postoperative histopathological size were compared and percentage difference between two measurements was calculated for each lesion. RESULTS: There were 607 DTC foci in 562 patients. Mean US diameter was significantly higher than histopathological diameter (21.0 ± 15.6 mm vs 17.3 ± 13.6, p < 0.001). US diameter was higher than tumor size in 444 (73.1%), equal in 15 (2.5%) and lower in 148 (24.4%) nodules. Marginal irregularity was observed in 253 (57%) lesions with US diameter > tumor size and 108 (73%) lesions with US diameter < tumor size (p = 0.010). Rate of nodules with peripheral halo was higher in lesions with US diameter > tumor size (30.6% vs 20.3%, p = 0.015). In nodules with US diameter > tumor size, percentage difference was lower in nodules with microcalcification (p = 0.020) and higher in cytologically benign nodules (p < 0.001). Among nodules with US diameter < tumor size, <1 cm nodules had significantly higher percentage difference compared to 1-1.9, 2-3.9 and ≥ 4 cm nodules (p = 0.005). CONCLUSION: Ultrasonographically determined diameter is higher than histopathologically determined size in a considerable ratio of DTCs. It might be helpful to consider this discordance while deciding surgical extent in these patients.