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Background: Single-center trials demonstrated moderate-substantial level of interobserver agreement in the evaluation of ultrasound (US) features of thyroid nodules. Multicenter studies on US agreement, however, are scanty, and data on intraobserver agreement are poor. Aim of the study was to assess inter- and intraobserver agreement between different thyroid centers and different specialists. Methods: A blinded analysis of 100 electronically recorded thyroid nodule US images was conducted in three large-volume thyroid centers by seven radiologists and endocrinologists. The evaluation was repeated after randomization 4 months later. The following US characteristics were evaluated: composition, echogenicity, margins, intranodular echogenic spots, vascularity, and shape. Thyroid nodules were also classified according to AACE/ACE/AME, EU-TIRADS, ATA, and ACR-TIRADS US classifications. Intra- and interobserver agreement was calculated using cross-tabulation expressed as mean Cohen's Kappa. Results: Interobserver agreement for US features: K-coefficient was 0.53 for composition, 0.47 for echogenicity, 0.46 for intranodular vascularity, and 0.33 for margins of the nodules. For echogenic foci, the K-coefficient was 0.47 for microcalcifications, 0.38 for macrocalcifications, 0.11 for the subcategory comet-tail artifacts, and 0.42 for shape. Operators resulted uncertain on hyperechoic foci definition in 16% of cases and described them as "hyperechoic foci of uncertain significance." Interobserver Cohen-K for US classification systems was 0.44 for AACE, 0.42 for ACR-TIRADS, 0.39 EU-TIRADS, and 0.34 for ATA. Intraobserver agreement: the K-coefficient for nodule US features was 0.62 for intranodular vascularity, 0.58 for composition, 0.60 for echogenicity, 0.54 for macrocalcifications, 0.55 for microcalcifications, 0.47 for comet tails, 0.39 for margins, and 0.35 for shape. Intraobserver Cohen-K for US classification systems was 0.54 for AACE, 0.49 for ACR-TIRADS, 0.38

Hyperthyroidism related to Graves' disease is associated with a suppression of TSH values which may persist after surgery in spite of a LT4 replacement therapy at non-TSH-suppressing doses. The aim of this retrospective study was to evaluate the time to TSH normalization in a group of patients who underwent total thyroidectomy for Graves' disease receiving a LT4 therapy dose regimen based on a previously published nomogram, and to identify possible correlations between the time to normalization of post-operative TSH values and preoperative clinical and biochemical parameters. 276 patients affected by Graves' disease who underwent surgery between 2010 and 2015, were retrospectively evaluated for clinical and biochemical parameters as well as post-surgical LT4 treatment regimen. Of the 276 subjects, 174 had initiated LT4 dosage corresponding to a previously published nomogram. 59 patients were excluded because their LT4 requirement (in mcg/kg/day) changed and deviated from the nomogram during the follow-up period, 15 patients were excluded because their TSH level was >4 mcU/ml during the first biochemical evaluation and 2 patients were excluded because they had low TSH levels potentially related to central hypothyroidism due to concomitant hypopituitarism. Therefore, 98 patients were included in our statistical analysis. TSH and FT4 were evaluated at the first post-operative assessment and during follow up until the normalization of TSH values was achieved, and then included in the analysis. During the first post-operative evaluation 2 months after surgery, 59/98 patients had TSH values in the normal range (0.4 to 4.0 mcU/ml), while 39/98 patients had a TSH value < 0.4 mcU/mL. The persistence of post-operative TSH levels < 0.4 mcU/ml was significantly correlated (p = 0.022) with longer duration of the disease. The value of anti-TSH receptor autoantibodies (TrAb) at the diagnosis of hyperthyroidism, significantly correlated (p = 0.002) with the time to TSH nor

The current approach for calculating the starting dose of levothyroxine (LT4) after total thyroidectomy is based on the patient's body weight (BW). The aim of the study was to identify the major predictive factors of LT4 requirement and to elaborate a new method to improve the accuracy of the LT4 starting dose after total thyroidectomy.

The scientific community is very interested in the biological aspects of gender disorders and sexual orientation. There are different levels to define an individual's sex: chromosomal, gonadic, and phenotypic sex. Concerning the psychological sex, men and women are different by virtue of their own gender identity, which means they recognize themselves as belonging to a determinate sex. They are different also as a result of their own role identity, a set of behaviors, tendencies, and cognitive and emotional attitudes, commonly defined as "male" and "female". Transsexuality is a disorder characterized by the development of a gender identity opposed to phenotypic sex, whereas homosexuality is not a disturbance of gender identity but only of sexual attraction, expressing sexual orientation towards people of the same sex. We started from a critical review of literature on genetic and hormonal mechanisms involved in sexual differentiation. We re-examined the neuro-anatomic and functional differences between men and women, with special reference to their role in psychosexual differentiation and to their possible implication in the genesis of homosexuality and identity gender disorders. Homosexuality and transsexuality are conditions without a well defined etiology. Although the influence of educational and environmental factors in humans is undeniable, it seems that organic neurohormonal prenatal and postnatal factors might contribute in a determinant way in the development of these two conditions. This "organicistic neurohormal theory" might find support in the study of particular situations in which the human fetus is exposed to an abnormal hormonal environment in utero.

The role of adrenal steroids in antioxidant regulation is not known. Previously, we demonstrated some Coenzyme Q(10) (CoQ(10)) alterations in pituitary diseases, which can induce complex pictures due to alterations of different endocrine axes. Therefore we determined CoQ(10) and Total Antioxidant Capacity (TAC) in pituitary-dependent adrenal diseases: 6 subjects with ACTH-dependent adrenal hyperplasia (AH); 19 with secondary isolated hypoadrenalism (IH), 19 with associated hypothyroidism (multiple pituitary deficiencies, MPH). CoQ(10) was assayed by HPLC; TAC by the system metmyoglobin-H(2)O(2), which, interacting with the chromogenous 2,2(I)-azinobis-(3-ethylbenzothiazoline-6-sulphonate), generates a spectroscopically revealed radical compound after a latency time (Lag) proportional to the antioxidant content. CoQ(10) levels were significantly lower in IH than AH and MPH, with a similar trend when adjusted for cholesterol. Also TAC was lower in IH than in AH and MPH, suggesting that adrenal hormones can influence antioxidants. However, since thyroid hormones modulate CoQ(10) levels and metabolism, when thyroid deficiency coexists it seems to play a prevalent influence.

Oxidative stress, a condition defined as unbalancing between production of free radicals and antioxidant defenses, is an important pathogenetic mechanism in different diseases. Despite the abundant literature, many aspects of hormone role in regulating antioxidant synthesis and activity still remain obscure. Therefore, we reviewed experimental data, in vivo and in vitro, about the effects of the different pituitary- dependent axes on antioxidant levels, trying to give a broad view from hormones which also have antioxidant properties to the classic antioxidants, from the lipophilic antioxidant Coenzyme Q10, strictly related to thyroid function, to total antioxidant capacity, a measure of non-protein non-enzymatic antioxidants in serum and other biological fluids. Taken together, these data underline the importance of oxidative stress in various pituitary-dependent disorders, suggesting a possible clinical usefulness of antioxidant molecules.

Infertility is associated with oxidative stress, normally counterbalanced by different antioxidant systems. In order to explore the hormonal control of seminal plasma total antioxidant capacity (TAC) we evaluated TAC and hormone patterns in a group of unselected infertile patients and control subjects. One hundred and ten infertile patients (divided in three groups: inflammation, varicocele, other etiologies) and 31 fertile men were examined, evaluating blood serum gonadotropins, testosterone, estradiol, FT3, FT4, TSH, PRL, seminal parameters and TAC. TAC was measured using the H2O2-metmyoglobin system which generates the spectroscopically detectable radical cation of the chromogenous compound 2,2I-Azinobis (3-ethylbenzothiazoline-6-sulphonate) (ABTS). The lag time of its appearance is proportional to the antioxidant activity. Lag phase was significantly higher in varicocele vs controls, whereas it was lower in patients with inflammation vs varicocele or other kinds of infertility. The correlation analysis between hormones and seminal parameters showed an inverse correlation between PRL and sperm motility, and a direct correlation of TAC with PRL and FT4, but not with gonadotropins or gonadal steroids. Our data suggest that systemic hormones may play a role in regulating seminal antioxidant capacity. This is interesting also because some hormones, such as thyroid and pituitary ones, are not usually tested in the first level evaluation of male patients with fertility problems.

Biliopancreatic diversion (BPD) is a surgical procedure performed in patients with untreatable obesity and insulin resistance. The demonstrated metabolic and hormonal results of this procedure include: the reversal of insulin resistance, an increase in diet-induced thermogenesis and modifications of gut hormones, such as gastrin, enteroglucagone, neurotensin and cholecystokinin. On the other hand, obesity is a condition of increased oxidative stress; however few studies have investigated antioxidant systems in obese persons with BPD. In order to evaluate the metabolic status and antioxidant systems in such patients, we studied a group of 11 morbidly obese patients, aged 28-62 years, with a mean BMI of 54.71± 2.52 kg/m2, before and after successful BPD (mean post-BPD BMI 44.68 ± 1.51 kg/m2). A control group composed of ten slightly overweight women, with a mean BMI of 28.5±0.72 kg/m2, was also studied. Coenzyme Q10 (CoQ10) levels (also normalized for cholesterol levels) and Total Antioxidant Capacity (TAC) in blood plasma were assessed in these populations. The most striking datum was the extremely low level of CoQ10 in postoperative period (0.34±0.16 vs 0.66±0.09µg/ml, p=0.04); also the data corrected for cholesterol levels presented the same pattern, with a more marked significance (152.46±11.13 vs 186.4±17.98 nmol/mmol, p=0.001).This could be due to lipid malabsorption after surgery. In fact, the pre-BPD data present all the metabolic and hormonal characteristics of severe obesity and, after BPD, there was a net improvement in the metabolic parameters. The first pathophysiological phenomenon seems to be lipid malabsorption that has been argued to be cause of insulin resistance reversion. This metabolic interpretation is also confirmed by the absence of significant variations of TAC (57.5±5.3 vs 66±5.3). The mechanisms of these phenomena remain to be established. These data suggest the importance of correcting post-surgical metabolic complications, in these clinica