Salvatore Benvenga

Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury

objective  Acquired hypopituitarism in adults is obviously suspected in patients with primary hypothalamic–pituitary diseases, particularly after neurosurgery and/or radiotherapy. That brain injuries (BI) can cause hypopituitarism is commonly stated and has been recently emphasized but the management of BI patients does not routinely include neuroendocrine evaluations.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

BACKGROUND Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. METHODS A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. RESULTS These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. CONCLUSIONS In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry?

Autoimmune pancreatitis is a recently defined nosological entity, which accounts for 4.6‐6% of all forms of chronic pancreatitis and is often associated with other autoimmune diseases, particularly Sjögrens syndrome. Possession of the HLA DRB1*0405‐DQB1*0401 genotype confers a risk for the development of autoimmune pancreatitis. Autoantibodies against carbonic anhydrase II and lactoferrin are frequently present in affected subjects and are suspected to have a pathogenic role. A link between gastric infection by Helicobacter pylori and autoimmune pancreatitis has been hypothesized. We used in silico protein analysis and search for HLA binding motifs to verify this hypothesis. We found a significant homology between human carbonic anhydrase II and α‐carbonic anhydrase of Helicobacter pylori, an enzyme which is fundamental for the survival and proliferation of the bacterium in the gastric environment. Moreover, the homologous segments contain the binding motif of the HLA molecule DRB1*0405. Our data strengthen the hypothesis that gastric Helicobacter pylori infection can trigger autoimmune pancreatitis in genetically predisposed subjects.

Altered intestinal absorption of L-thyroxine caused by coffee.

OBJECTIVE To report eight case histories, and in vivo and in vitro studies showing coffees potential to impair thyroxine (T4) intestinal absorption. DESIGN Of eight women with inappropriately high or nonsuppressed thyroid-stimulating hormone (TSH) when T4 was swallowed with coffee/espresso, six consented to the evaluation of their T4 intestinal absorption. This in vivo test was also administered to nine volunteers. In three separate tests, two 100 microg T4 tablets were swallowed with coffee, water, or water followed, 60 minutes later, by coffee. Serum T4 was assayed over the 4-hour period of the test. Two patients and two volunteers also agreed on having tested the intestinal absorption of T4 swallowed with solubilized dietary fibers. In the in vitro studies, classical recovery tests on known concentrations of T4 were performed in the presence of saline, coffee, or known T4 sequestrants (dietary fibers, aluminium hydroxide, and sucralfate). MAIN OUTCOME For the in vivo test, average and peak incremental rise of serum T4 (AIRST4 and PIRST4), time of maximal incremental rise of serum T4 (TMIRST4), and area under the curve (AUC) were determined. In patients and volunteers, the four outcome measures were similar in the water and water + coffee tests. In patients and volunteers, compared to water, coffee lowered AIRST4 (by 36% and 29%), PIRST4 (by 30% and 19%), and AUC (by 36% and 27%) and delayed TMIRST4 (by 38 and 43 minutes); bran was a superior interferer. In the in vitro studies, coffee was weaker than known T4 sequestrants. CONCLUSION Coffee should be added to the list of interferers of T4 intestinal absorption, and T4 to the list of compounds whose absorption is affected by coffee.

Selenium: an element for life

This review aims to illustrate the importance of selenium (Se) for maintenance of overall health, especially for the thyroid, immunity, and homeostasis. Furthermore, it outlines the role of Se in reproduction and in virology and discusses the effects of Se supplementation in critical illness. The multifaceted aspects of this essential nutrient have attracted worldwide clinical and research interest in the last few decades. Se exerts its activity in the form of the aminoacid selenocysteine incorporated in selenoproteins. The impact of Se administration should be considered in relation to its apparent U shaped effects, i.e., exhibiting major advantages in Se-deficient individuals but specific health risks in those with Se excess. Addition of selenium to the administration of levothyroxine may be useful in patients with low Se intake and with mild-form or early-stage Hashimoto’s thyroiditis (HT). Serum Se concentration (possibly also at tissue level) decreases in inflammatory conditions and may vary with the severity and duration of the inflammatory process. In such cases, the effect of Se supplementation seems to be useful and rational. Meanwhile, Se’s ability to improve the activity of T cells and the cytotoxicity of natural killer cells could render it effective in viral disease. However, the evidence, and this should be stressed, is at present conflicting as to whether Se supplementation is of benefit in patients with HT, though there are indications that it is advantageous in cases of mild/moderate Graves’ Orbitopathy. The role of Se in type 2 diabetes mellitus (T2DM) is ambiguous, driven by both Se intake and serum levels. The evidence that insulin and glycaemia influence the transport and activity of Se, via regulatory activity on selenoproteins, and that high serum Se may have a diabetogenic effect suggests a ‘Janus-effect’ of Se in T2DM. Though the evidence is not as yet clear-cut, the organic form (selenomethionine), due to its pharmacokinetics, is likely to be more advantageous in long-term prevention, and supplementation efforts, while the inorganic form (sodium selenite) has proven effective in an acute, e.g., sepsis, clinical setting. Recent data indicate that functional selenoprotein single-nucleotide polymorphisms (SNPs) may interfere with Se utilization and effectiveness.

Changed presentation of Hashimoto's thyroiditis in North-Eastern Sicily and Calabria (Southern Italy) based on a 31-year experience.

OBJECTIVE To quantify the yearly prevalence of Hashimotos thyroiditis at our Division and evaluate changes in its clinical presentation over the period 1975-2005. DESIGN We have reviewed retrospectively the clinical records of patients admitted to a university hospital located in Messina, Sicily (Italy), from January 1, 1975, through December 31, 2005. This facility attracts patients from North-Eastern Sicily and most of Calabria, the Italian region across the Straits. HT was diagnosed based on various combinations of clinical, laboratory, and instrumental findings. The study group consisted of 4064 HT patients diagnosed during these 31 years. MAIN OUTCOME We evaluated these indexes on a yearly basis: number of new HT diagnoses; age at presentation; male-to-female ratio; functional status; goitrous or nongoitrous variants with or without nodule(s); above-normal titers or levels of serum thyroid autoantibodies (thyroglobulin antibodies and thyroperoxidase antibodies). Several indexes have changed over those 31 years. Particularly, HT has become 10 times more common than it was until the early 1990s and males are relatively more represented. Patients are relatively younger, with a nongoitrous thyroid; the rate of S-Hypo exceeds largely the rate of O-Hypo. Serum thyroid autoantibodies have become less frequently positive, and when positive, they are present at a lower concentration. CONCLUSIONS Only environmental changes, as opposed to genetic changes, can account for such alterations in the presentation of HT in our geographical area.

Environmental factors and genetic background that interact to cause autoimmune thyroid disease.

Purpose of reviewTo provide an updated list of genetic and environmental causative factors of autoimmune thyroid disease, and report about the recent discoveries concerning their interaction in the pathogenesis of thyroid autoimmunity. Recent findingsAlthough significant discoveries have been made on genetic and environmental factors underlying the development of autoimmune thyroid disease, few data are available about the mechanisms by which they interact. The most interesting news in this field comes from research on molecular mimicry between microbial antigens and thyroid autoantigens. The molecular mimicry model postulates that, in predisposed subjects, a microbial antigen could trigger autoimmunity because of its structural similarity to an autoantigen of the host, and is a paradigmatic example of the multifactorial interaction of several genes and environmental factors to cause autoimmune diseases, including thyroid diseases. SummaryRecent findings help us to better understand the functional mechanisms of the immune system, which are still only partially known. Beyond the scientific interest, this knowledge has immediate repercussions on clinical practice because it can suggest possible therapeutic targets for new treatments, as well as better and more specific uses of currently available drugs and resources.

Improvement of Primary Dysmenorrhea Caused by a Single Oral Dose of Vitamin D: Results of a Randomized, Double-blind, Placebo-Controlled Study

P rimary dysmenorrhea is a common disorder characterized by painful uterine cramping, just before or during menstruation, in the absence of any pelvic pathologic conditions. It is frequently accompanied by other symptoms such as nausea, vomiting, diarrhea, asthenia, and insomnia. Primary dysmenorrhea affects almost half of menstruating women, often resulting in school and work absenteeism with major educational and economic consequences. An excessive uterine production of prostaglandins (PGs) is the pathogenetic trigger of dysmenorrhea. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the currently accepted drugs for the management of this disorder. Because the vitamin D receptor is widespread and the mitochondria l cytochrome P450 enzyme 25hydroxyvitamin D3 (25[OH]D)-1 -hydroxylase (1 OHase), which catalyzes the synthesis of 1 ,25dihydroxyvitamin D3 (1,25[OH]2D) from its precursor 25(OH)D, is expressed in the human uterus and in immune system cells, and because vitamin D reduces the synthesis of PGs, a beneficial effect of vitamin D in the uterus pathophysiology is possible. The aim of this prospective intervention study was to evaluate the effect of a single-loading oral dose of cholecalciferol (300 000 IU) on primary dysmenorrhea.

Changes in thyroid function tests induced by 2 month carbamazepine treatment in l-thyroxine-substituted hypothyroid children

In five l-thyroxine-substituted hypothyroid children with partial epilepsy serum total thyroxine (T4) and free T4 (FT4) significantly (P<0.01) decreased following 2 months of carbamazepine (CBZ) administration (20 mg/kg per BW per day) from mean (±SD) values of 12.7±1.1 μg/dl and 15.5±1.8 pg/ml to mean values of 7.5±2.3 and 10.1±1.7, respectively. In all but one patient important changes in both serum total and free triiodothyronine (T3, FT3) were not observed; consequently T3∶T4 and FT3∶FT4 ratios significantly (P<0.05) increased in the whole series. Three subjects had post-treatment serum TSH that rose to hypothyroid levels parallel to a T4 decrease. The negligible thyroid hormone secretion and the unmodified T3-uptake (T3U) or T4-binding globulin (TBG) exclude direct effects of CBZ on thyroid gland and on carrier serum proteins, respectively. The findings observed, instead, might be due to accelerated T4 metabolic clearance together with augmented T4 to T3 conversion rate, as previously demonstrated for diphenylydantoin. The sharp reduction in T4 and FT3 concentrations is the peripheral display of this event, which is associated with a decompensation of the metabolic status, as indicated by serum TSH enhancement. In all cases a supplement of l-thyroxine by itself was able to restore euthyroid TSH serum concentrations, suggesting that hypothyroidism in patients with partial epilepsy to whom CBZ had been administered requires a higher l-T4 substitutive regimen.

Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS.

In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).