Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

Objective: Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3.

Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study.

Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy.

Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.

Haptoglobin deficiency determines changes in adipocyte size and adipogenesis.

Haptoglobin (Hp) is an inflammatory and adiposity marker, its expression during obesity being specifically induced in the white adipose tissue (WAT). We previously reported that when challenged with a high fat diet (HFD) Hp mice are partially protected from the onset of insulin resistance and hepatosteatosis. The aim of the present study was to get further insights into Hp function in WAT.

Iodine fortification of vegetables improves human iodine nutrition: in vivo evidence for a new model of iodine prophylaxis.

Background: Iodine deficiency is the result of insufficient intake of dietary iodine and as a consequence causes multiple adverse effects. About 2 billion individuals in the world are affected by iodine deficiency. It has been found that the most effective way to control iodine deficiency is through the universal salt iodization.

New echocardiographic techniques in the evaluation of left ventricular function in obesity.

Objective: Obesity has reached global epidemic proportions and is associated with numerous comorbidities, including major cardiovascular (CV) diseases.

Design And Methods: It has many adverse effects on hemodynamics and CV structure and function: it increases total blood volume and cardiac output, and the cardiac workload is greater. Typically, obese patients have a higher cardiac output but a lower level of total peripheral resistance at any given level of arterial pressure.

Evidence of a low prevalence of RAS mutations in a large medullary thyroid cancer series.

Background: Approximately 60% of sporadic medullary thyroid carcinomas (sMTC) remain orphan of a recognized genetic cause. Recently, a high percentage of RAS point mutations have been described in RET-negative sMTC. The aim of this study was to assess the prevalence of RAS point mutations in a large series of MTC collected in four Italian centers.

Clinical characteristics and genetic analysis in women with premature ovarian insufficiency.

Objective: Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism.

Methods: We studied the clinical, biological, and genetic data related to 50 POI patients with a mean age of menopause of 29 years (94% with secondary amenorrhea, 6% with primary amenorrhea and 15% with a family history of POI). Seventeen patients were affected by endocrine autoimmune diseases, antral follicles were observed in 31 patients by ultrasonography.

Thyroid volume and severity of Graves' orbitopathy.

Background: Graves' orbitopathy (GO) is thought to be related to one or more autoantigens present in the thyroid and in orbital tissues. Although this may not imply a quantitative relation between thyroid antigens and degree of GO, which in turn is a risk factor for a more pronounced GO, we postulated that the severity of GO may parallel the amount of thyroid tissue, namely, the size of the thyroid gland. This hypothesis is also based on the observation that patients with Graves' disease presenting with large goiters tend to have more severe hyperthyroidism.

Rehabilitative orbital decompression for Graves' orbitopathy: risk factors influencing the new onset of diplopia in primary gaze, outcome, and patients' satisfaction.

Background: Patients with moderate to severe Graves' orbitopathy (GO) rather frequently require rehabilitative surgery after medical therapy. Diplopia is the most common side effect of orbital decompression (OD). The aim of this study was to evaluate the occurrence of postoperative diplopia in primary gaze after OD, and the influence of the surgical approach on this outcome.

The BRAF(V600E) mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: single-institution results from a large cohort study.

Background: The BRAF(V600E) mutation, the most frequent genetic alteration in papillary thyroid carcinoma (PTC), was demonstrated to be a poor prognostic factor. The aim of this study was to evaluate its prognostic significance in a large cohort of low-risk intrathyroid PTC.

Methods: Among the 431 consecutive PTC patients, we selected 319 patients with an intrathyroid tumor and no metastases (T1-T2, N0, M0).

Enalapril reduces proliferation and hyaluronic acid release in orbital fibroblasts.

Background: Orbital fibroblast proliferation and hyaluronic acid (HA) release are responsible for some of the clinical features of Graves' ophthalmopathy (GO). Thus, inhibition of these processes may be a possible therapeutic approach to this syndrome. Enalapril, a widely used antihypertensive drug, was found to have some inhibitory actions on fibroblast proliferation in cheloid scars in vivo, based on which we investigated its effects in primary cultures of orbital fibroblasts from GO patients and control subjects.

Thyroglobulin autoantibodies in patients with papillary thyroid carcinoma: comparison of different assays and evaluation of causes of discrepancies.

Context: Thyroglobulin autoantibodies (TgAb) have been proposed as a surrogate marker of thyroglobulin in the follow-up of differentiated thyroid carcinoma. Commercially available TgAb assays are often discordant. We investigated the causes of discrepancy.

Modifications in the papillary thyroid cancer gene profile over the last 15 years.

Background: Evidence for an increased prevalence of BRAF(V600E) mutations has been documented in recent decades. The aim of this study was to evaluate the prevalence of both RET/PTC rearrangements and BRAF(V600E) mutations in an Italian cohort of papillary thyroid carcinoma (PTC) patients followed at the Endocrine Units of Pisa, Milano, and Perugia from 1996-2010.

Patients And Methods: In total, 401 PTC patients were examined and grouped according to the time of surgery: group 1, 1996-2000; group 2, 2001-2005; and group 3, 2006-2010.

MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration.

Objective: MicroRNAs (miRNAs) are small endogenous noncoding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytological diagnosis remains undetermined for 20% of nodules.

Prevalence of left ventricular hypertrophy and determinants of left ventricular mass in obese women.

Background: Obesity is frequently associated with left ventricular hypertrophy (LVH), a condition leading to an increased cardiovascular risk.

Aim: The objective of this study was to evaluate the prevalence of LVH in a cohort of obese women, with a main focus on the anthropometric and clinical parameters that are associated with an increased left ventricular mass (LVM).

Methods: The study was performed in 166 obese female patients.

Serum insulin-like growth factor-1 concentrations are reduced in severely obese women and raise after weight loss induced by laparoscopic adjustable gastric banding.

Background: Obesity is associated with abnormalities of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. The role of serum IGF-1 measurement for recognition of hypothalamic-pituitary diseases in obesity is still a matter of debate.

Methods: This study evaluated the serum levels of IGF-1 in a population of severely obese women before and after long-term weight loss obtained by laparoscopic adjustable gastric banding (LAGB).

Lymphocytic thyroiditis on histology correlates with serum thyroglobulin autoantibodies in patients with papillary thyroid carcinoma: impact on detection of serum thyroglobulin.

Context: Serum thyroglobulin (Tg), the marker of residual tumor in papillary thyroid carcinoma, can be underestimated in patients with Tg autoantibodies (TgAb). TgAb are due to a coexistent lymphocytic thyroiditis (LT) or the papillary thyroid carcinoma per se. TgAb assays are highly discordant.

Advances in the follow-up of differentiated or medullary thyroid cancer.

The long-term survival of patients with thyroid cancer and the possibility of tumour recurrence up to 30-40 years after the achievement of a disease-free status illustrate the importance of lifelong follow-up in these individuals. This Review discusses the most innovative aspects of follow-up protocols for patients with differentiated thyroid cancer, that is, of papillary or follicular hystotype, and those with medullary thyroid cancer. Particular focus is placed on the relevance of new ultrasensitive assays for thyroglobulin measurement and the option of using recombinant human TSH to stimulate thyroglobulin secretion.

Metabolic engineering of the iodine content in Arabidopsis.

Plants are a poor source of iodine, an essential micronutrient for human health. Several attempts of iodine biofortification of crops have been carried out, but the scarce knowledge on the physiology of iodine in plants makes results often contradictory and not generalizable. In this work, we used a molecular approach to investigate how the ability of a plant to accumulate iodine can be influenced by different mechanisms.

Low prevalence of the somatic M918T RET mutation in micro-medullary thyroid cancer.

Background: The prevalence of RET somatic mutations in sporadic medullary thyroid cancer (MTCs) is ∼40%-50%, and the most frequent somatic mutation is M918T. RET-positive MTCs have been demonstrated to have a more advanced stage at diagnosis and a worse outcome.

Aims: The aim of the present work was to compare the prevalence of RET somatic mutations in sporadic microMTCs (<1 cm) and in larger MTCs.

Sporadic congenital nonautoimmune hyperthyroidism caused by P639S mutation in thyrotropin receptor gene.

Germline mutations of thyrotropin receptor (TSHR) gene determining a constitutive activation of the receptor were identified as a molecular cause of familial or sporadic congenital nonautoimmune hyperthyroidism (OMIM: 609152) (Nat Genet 7:396-401, 1994; N Engl J Med 332:150-154, 1995; Acta Endocrinol (Copenh) 100:512-518, 1982). We report the case of an Italian child subjected to the first clinical investigation at 24 months for an increased growth velocity; biochemical investigation showed high FT4 and FT3 serum values and undetectable thyrotropin in the absence of anti-thyroid antibodies; the thyroid gland was normal at ultrasound examination. Treatment with methimazole was started at the age of 30 months when her growth velocity was high and the bone age was advanced.

The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center.

Background: Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-producing C-cell tumor. In hereditary cases, a germline RET mutation is found in 98% of families. Because MTC is cured only if intrathyroidal, prophylactic thyroidectomy is recommended in the gene carrier (GC).

Outcome of Graves' orbitopathy after total thyroid ablation and glucocorticoid treatment: follow-up of a randomized clinical trial.

Context: In a previous study, we found that total thyroid ablation (thyroidectomy plus (131)I) is associated with a better outcome of Graves' orbitopathy (GO) compared with thyroidectomy alone, as observed shortly (9 months) after glucocorticoid (GC) treatment.

Objective: The objective of the study was to evaluate the outcome of GO in the same patients of the previous study over a longer period of time.

Design: This was a follow-up of a randomized study.

Human leptin tissue distribution, but not weight loss-dependent change in expression, is associated with methylation of its promoter.

Leptin is a master regulator of energy homeostasis. Its expression, prevalently localized in adipocytes, is positively related to adipose mass. Epigenetics is emerging as an important contributor to the changes in gene expression undergone by adipose tissue during obesity.

Obesity-associated hepatosteatosis and impairment of glucose homeostasis are attenuated by haptoglobin deficiency.

Objective: Haptoglobin (Hp) is upregulated in both inflammation and obesity. The low chronic inflammatory state, caused by massive adipose tissue macrophage (ATM) infiltration found in obesity, and low adiponectin have been implicated in the development of insulin resistance and hepatosteatosis. The aim of this work was to investigate whether and how Hp interferes with the onset of obesity-associated complications.