Transglutaminase 2 expression is associated with increased risk of lymph node metastasis and recurrence in papillary thyroid cancer.

PURPOSE: Transglutaminase 2 (TG2) is associated with mobilization, invasion, and chemoresistance of tumor cells. We aimed to determine whether the immunohistochemical staining with TG2 antibody differs between metastatic and non-metastatic papillary thyroid cancer patients. METHODS: We included 76 patients with papillary thyroid cancer (72% female, median age 52 (24-81) years, follow-up time 107 (60-216) months). Thirty of them with no metastasis, 30 of them with only lymph node metastasis and 16 patients with distant ± lymph node metastasis. Immunohistochemical staining of TG2 antibody was evaluated in the primary tumor and extra-tumoral tissue. We also divided subjects into two groups according to their primary tumor TG2 staining score (group A, high risk group: ≥3, n = 43; group B, low risk group: <3, n = 33). RESULTS: Vascular invasion (p < 0.001), thyroid capsule invasion (p < 0.001), extrathyroidal extension (p < 0.001), intrathyroidal dissemination (p = 0.001), lymph node metastasis (p < 0.001), presence of aggressive histology (p < 0.001) were significantly higher in group A. No significant difference was found between the groups in terms of distant metastasis. Based on ATA risk classification 95.5% of patients with low risk were in group B but 86.8% of intermediate risk and 56.3% of high risk were in group A. In regression analysis, lymph node metastasis increased by 1.9 times with each one point increase in TG2 staining score. CONCLUSION: TG2 staining score of the primary tumor may be a predictive factor for lymph node metastasis. High or low TG2 scores may effect the frequency of follow-up and decision of treatment regimens.

A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission.

BACKGROUND: Transsphenoidal endoscopic surgery is the first-line treatment for growth hormone-secreting adenomas. OBJECTIVE: To analyse the results of the transsphenoidal endoscopic approach for acromegaly and to determine the predictive factors of remission. METHODS: A single-centre retrospective review was performed in patients who underwent endoscopic transsphenoidal surgery for acromegaly between January 2009 and January 2019. Demographic features, clinical presentation, histopathology records, complications and pre- and postoperative radiologic and endocrinological assessments were evaluated. The factors that influenced the remission rates were investigated. RESULTS: A total of 73 patients underwent surgery via the transsphenoidal endoscopic approach. Cavernous sinus invasion was detected in 32 patients (43.8%); and macroadenoma, in 57 (78%). The pathology specimens of the 27 patients (36.9%) showed dual-staining adenomas with prolactin. A total of 51 patients (69.8%) attained biochemical remission 1 year after surgery. A second operation was performed in 10 patients (13.6%) with residual tumours without biochemical remission in the first year. Six (60%) of the patients attained remission at the last follow-up. Transient diabetes insipidus was observed in 18 patients (24.6%); and rhinorrhoea, which was resolved with conservative treatment, in 4 (5.4%). None of the patients developed panhypopituitarism. The presence of cavernous sinus invasion and preoperative IGF-1, immediate postoperative GH and third-month IGF-1 levels were predictive of remission. CONCLUSION: Transsphenoidal endoscopic surgery is a safe and effective treatment for acromegaly. Reoperation should be considered in patients with residual tumours without remission.

A SOD2 Polymorphism is Associated with Abnormal Quantitative Sensory Testing in Type 2 Diabetic Patients.

INTRODUCTION: Diabetes mellitus (DM) affects peripheral nerves inducing diabetic polyneuropathy (DPN). Mitochondrial dysfunction and oxidative stress are potential causes of DPN. METHODS: Nerve conduction studies were performed in 20 type 2 DM patients (11 with DPN) and 15 healthy controls. Perception threshold values of cold, warm and vibration were measured by quantitative sensory testing. Variants of a superoxide dismutase 2 (SOD2) gene single nucleotide polymorphism (SNP) (rs5746136) were determined by polymerase chain reaction (PCR) and following NexteraXT DNA Library. RESULTS: DPN patients showed significantly increased threshold values. DM patients without DPN and healthy controls showed comparable values. TT variant of the SOD2 SNP was more prevalent in DM and DPN patients. DM patients with the TT variant displayed increased perception threshold values. CONCLUSIONS: Quantitative sensory testing is not superior to standard nerve conduction studies in DPN. Carriers of SOD2 SNP manifested increased sensory threshold levels which is important in further corroborating the link between oxidative stress and DPN.

Comorbidities and their impact on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a complex disease that is associated with devastating outcomes resulting from lung involvement and several comorbidities. Comorbidities could impact on symptomology, quality of life, the complications, the management, economic burden and the mortality of the disease. The importance of comorbidities originates from their impact on the outcome of COPD. The most frequent comorbidities in COPD are cardiovascular, endocrinological, musculoskeletal, phycological disorders and lung cancer. Almost 50% of the COPD patients have 3 or more comorbidities. The recent Global Initiative of Obstructive Lung Disease (GOLD) Guideline suggested proactive search and the treatment of the comorbidities. However, there is no certain evidence demonstrating that active treatment of comorbidities improve the outcomes of COPD. However, it is well known that several comorbidities such as cardiovascular disease and lung cancer have greater impact on mortality caused by COPD. Several studies have shown that Charlson Comorbidity index or more recenty COPD Specific Comorbidity Index (COTE) has been found to be related with mortality of COPD. This concise review intended to summarize the most frequent comorbidities in association with their impact on COPD.

Pelvic ultrasound findings in prepubertal girls with precocious adrenarche born appropriate for gestational age.

BACKGROUND: Precocious adrenarche (PA) refers to the clinical onset of excess androgen in girls before the age of 8. It is associated with an increased risk of functional ovarian hyperandrogenism after puberty. PA may be associated with polycystic ovary syndrome (PCOS). We compared pelvic ultrasound (US) findings of girls with PA born appropriate for gestational age (AGA) to healthy body mass index (BMI)-matched peers to determine whether US findings in AGA-born PA girls are associated with PCOS antecedents. SUBJECTS AND METHODS: We conducted a cross-sectional study on 56 AGA-born girls with PA (6·9 ± 0·6 years) and 33 BMI-matched prepubertal AGA-born peers (7·1 ± 1·0 years). Hormonal data, homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISIcomp ) and pelvic US findings were compared. Associations of pelvic US findings with clinical and metabolic data were investigated. RESULTS: Precocious adrenarche girls had greater height and bone age-adjusted uterine length (UL; P = 0·01) and UL standard deviation score (SDS) (P = 0·02) than BMI-matched peers. Mean ovarian volume (MOV), MOV SDS, uterine volume, uterine cross-sectional area and ovarian morphology were similar between the groups (P > 0·05). MOV and MOV SDS correlated with ISIcomp (r = -0·683, P < 0·001; r = -0·760, P < 0·001; respectively). Correlations of pelvic US findings with other biochemical data did not reach significance (P > 0·05). Multivariate regression analysis revealed that in girls with PA, ISIcomp had the most significant effect on MOV SDS (R(2) = 0·731, ß = -4·784, P = 0·001). CONCLUSIONS: Appropriate for gestational age-born PA girls have greater UL measurements than AGA-born BMI-matched peers. In AGA-born girls with PA, decreasing insulin sensitivity is strongly and independently associated with an increase in MOV. Longitudinal follow-up of our cohort after menarche will allow us to establish how many AGA-born girls with PA will ultimately develop PCOS.

Evaluation of the effect of L-thyroxin therapy on endothelial functions in patients with subclinical hypothyroidism.

Subclinical hypothyroidism (SH) is characterized by normal serum free T4 (FT4), free T3 (FT3) levels and increased serum thyroid-stimulating hormone (TSH) levels. Endothelial dysfunction, which is an early step of atherosclerosis, has been reported in patients with subclinical hypothyroidism. The aim of this study is to evaluate endothelial functions and the effect of L-thyroxin (L-T4) therapy on endothelial functions in SH. Twenty-seven patients with SH and 22 healthy controls were evaluated in terms of endothelial functions, using brachial artery Doppler ultrasonography. After restorating euthyroidism, measurements were repeated. Baseline and nitroglycerin induced diameter (NID) of brachial artery were similar in patients with SH and the control group. Compared to the control group, the patients with SH showed significantly reduced flow-mediated diameter (FMD). Baseline and NID values were significantly higher after LT4 therapy in SH group. FMD also significantly increased after LT4 therapy. Hypothyroidism accelerates atherogenesis through modification of atherosclerotic risk factors and direct effects on the blood vessels. In this study, we observed marked improvement in endothelial functions after L-T4 therapy in SH patients. We suggest that thyroid hormone replacement therapy may help to prevent atherosclerosis in this group of patients.

Transient gestational diabetes insipidus diagnosed in successive pregnancies: review of pathophysiology, diagnosis, treatment, and management of delivery.

Gestational diabetes insipidus (GDI) is a rare disorder characterised by polyuria, polydypsia, and excessive thirst usually manifesting in the third trimester of pregnancy. The etiology is thought to depend on excessive vasopressinase activity, a placental enzyme that degrades arginine-vasopressin (AVP), but not 1-deamino-8-D: -arginine vasopressin (dDAVP), which is a synthetic form. This is a transient syndrome and may be associated with acute fatty liver of pregnancy and preeclampsia. The use of dDAVP in symptomatic cases has been proven as a safe method for both the mother and the fetus during the pregnancy. We report a case of recurrent gestational diabetes insipidus in successive pregnancies, which responded to dDAVP and subsided after delivery.