Endocrine

Vitamin D deficiency is a major health problem which affects about one billion people in the world. Although, vitamin D supplementation is recommended as standard treatment of vitamin D deficiency, there are controversies on dose response relationship. In this regard, the present study aimed to determine the impact of vitamin D3 supplement on raising of serum 25 hydroxyvitamin D[25(OH)D] in healthy subjects with varying degrees of vitamin D deficiency. In this clinical trial 114 subjects with varying degrees of vitamin D deficiency were entered and divided into three groups: serum levels of 25(OH) D less than 10 ng/ml, 10–20 ng/ml, and 20–30 ng/ml. All of the participants were given 50,000 units vitamin D3 per week for 8 weeks, thereafter, changes in serum levels of vitamin D and PTH were evaluated at week twelve. The results were analyzed using SPSS version 16 and P < 0.05 was considered to be significant. Of the 114 vitamin D deficient subjects, serum level of vitamin D was below 10 ng/ml in 22 persons (19.3%), 10–20 ng/ml in 52 persons (45.6%) and 20–30 ng/ml in 40 persons (35.1%). Following vitamin D prescription all people with varying degrees of vitamin D deficiency obtained a favorable serum level. The increase in vitamin D levels were 26.4, 18.5, and 8.3 ng/ml, in individuals with baseline vitamin D levels below 10 ng/ml, 10–20 ng/ml and 20–30 ng/ml, respectively. The changes in 25(OH) vitamin D in all three groups were significant (P < 0.05), nonetheless no significant alterations in serum levels of PTH were observed (P > 0.05). Our results indicated an inverse relationship between baseline serum levels of 25(OH) D and its increment following treatment with vitamin D3. Therefore, the magnitude of increments in serum 25(OH) D is greater in subjects with lower baseline levels of 25(OH) D.

Repetitive Transcranial Magnetic Stimulation (rTMS) has been demonstrated to be effective in body weight control in individuals with obesity. Most clinical trials on rTMS provided a reassuring safety profile. In the present work, we present an extensive analysis on both severe and mild Adverse Events (AEs) in obese individuals treated with rTMS. We examined the intensity, duration, correlation with the treatment, up to 1 year after the end of rTMS treatment. Descriptive analysis included a total of 63 subjects undergoing a 5-week deep rTMS experimental treatment for obesity (age 48.3 ± 10.4 years; BMI 36.3 ± 4.4 kg/m2): 31 patients were treated with high-frequency rTMS (HF), 13 with low-frequency rTMS (LF), and 19 were sham treated (Sham). Thirty-two subjects (50.8%) reported a total of 52 AEs, including mainly moderate (51.9%) events. The most frequently reported side effects were headaches of moderate intensity (40.4%) and local pain/discomfort (19.2%) and resulted significantly more frequent in HF group compared to other groups (p < 0.05). No significant differences among groups were found for the other reported AEs: drowsiness, insomnia, paresthesia, vasovagal reactions, hypertensive crisis. No AEs potentially related to the rTMS arised up to 1 year from the end of the treatment. This is the first comprehensive safety analysis in obese patients treated with rTMS. The analysis did not reveal any unexpected safety concerns. Only headaches and local pain/discomfort have been significantly more frequent in the HF group, confirming the good tolerability of rTMS even in the obese population potentially more susceptible to side effects of brain stimulation.

124I-PET/CT can be used for pre-therapeutic assessment of radioactive iodine uptake in benign thyroid disorders, however systematic comparisons with intra-therapeutic uptake are still lacking for these disorders. The goals of this study were to compare 124I RAIU and conventional 131I RAIU tests with each other; to compare both tests with intra-therapeutic uptake (reference); and to verify the time course of radioactive iodine uptake at three time points (30, 102, and 336 h [14 days] post administration; p.a.). Thirteen patients with benign thyroid diseases underwent 131I RAIU test and 124I RAIU test one after another before the intra-therapeutic 131I uptake (reference) was measured via short-range and long-range measurements. After correction for decay, relative uptake differences were calculated and subjected to the Bland-Altman method for the evaluation of levels of agreement. Radioactive iodine uptake tests with 124I-PET/CT and 131I probe did not show systematic deviations at any time point. Likewise, at 30 and 102 h p.a. there was no systematic discrepancy between pre-therapeutic and intra-therapeutic uptake levels. At 14 days p.a., however, both pre-therapeutic tests tended to overestimate the uptake compared to reference. Findings showed, for the first time with 124I, that radioiodine therapy has some early radiobiological effects possibly limiting the accuracy of pre-therapeutic dosimetry. 124I RAIU tests represent a feasible alternative to standard 131I RAIU tests. The additional benefits of 124I-PET/CT (e.g., functional topography, inclusion of retrosternal areas, possibility to enable fusion imaging) may thus increase the scope of this technology in benign thyroid disorders.

The aim of this study was to examine a homogeneous, consecutive recent series of patients who underwent reoperation on the thyroid bed to assess the incidence of the complications commonly correlated with resurgery. We reviewed clinical charts of 233 patients who underwent resurgery taken from a total of 4,752 patients previously operated on for benign and malignant thyroid diseases from 2006 to 2010 by the same surgical team. We evaluated the incidence of postoperative hemorrhage, hypoparathyroidism, and recurrent laryngeal nerve (RLN) palsy. Analyses were done separately in relation to the type of the type of resurgery adopted: (A) monolateral completion; (B) bilateral completion, after monolateral (B1) or bilateral prior surgery (B2); and (C) lymph node dissection. We also separately analyzed patients according to their final histological diagnosis of benign or malignant disease. Regarding hemorrhage, 6/233 patients (2.5 %) underwent surgical revision of the thyroid within 12 h for postoperative hemorrhage. They included 2 (1.5 %) of the 129 monolateral reoperations (A), 3 (4 %) of the 74 bilateral reoperations (B), and 1 (3.3 %) of the 30 central dissections for nodal relapse (C). Transient and definitive postoperative hypoparathyroidism was recorded in 78 (36.4 %) and 7 (3.3 %) of the 214 eligible patients. Transient RLN palsy occurred in 21 RLNs at risk (7 %) and definitive RLN palsy in 5 (1.7 %). Elective total thyroidectomy cannot always be supported as an effective policy for preventing recurrences in patients with a single, benign node: lobectomy, preferably with extemporaneous histological examination, unquestionably represents the best minimal approach to thyroid resection.

We explored whether testosterone influences circulating leptin turnover in rats. Sham-operated male and female rats and 21-d gonadectomized rats treated or not treated with testosterone propionate were used. Anesthetized rats were implanted with an iv catheter, and then blood samples were drawn before and throughout a 60-min period following systemic leptin administration. Plasma testosterone, estradiol, and leptin concentrations were monitored. The results indicated that while gonadectomy blunted circulating concentrations of the homologous sex steroid, testosterone therapy, in gonadectomized rats, restored plasma testosterone concentrations to values found in normal male rats. Pharmacokinetic parameters evaluated during the test indicated the following: First, in the overall pharmacokinetic analyses, testosterone therapy in gonadectomized rats induced a more rapid disappearance of leptin from the circulation. Second, orchidectomy significantly enhanced the area under the curve (AUC) of circulating leptin, an effect fully reversed by testosterone treatment. Third, testosterone treatment in ovariectomized rats significantly decreased the AUC of leptin concentrations. Fourth, while gonadectomy alone did not modify circulating leptin half-life, conversely, testosterone therapy in gonadectomized rats decreased leptin half-life in the circulation. Finally, while orchidectomy reduced leptin body clearance, this parameter was increased by androgen therapy in gonadectomized rats. Our results strongly support that testosterone could play a main role in plasma leptin turnover by increasing leptin clearance rate and shortening plasma leptin half-life.

Acromegaly is characterized by a broad range of manifestations. Early diagnosis is key to treatment success, but is often delayed as symptomatology overlaps with common disorders. We investigated sign-and-symptom associations, demographics, and clinical characteristics at acromegaly diagnosis. Observational, cross-sectional, multicenter non-interventional study conducted at 25 hospital departments in France that treat acromegaly (ClinicalTrials.gov: NCT02012127). Adults diagnosed with acromegaly < 5 years were enrolled. Demographic and clinical data were obtained from medical reports and patient questionnaires. Sign-and-symptom associations were assessed by multiple correspondence analysis (MCA). Overall, 472 patients were included in the analyses. MCA was unsuccessful in identifying sign-and-symptom associations at diagnosis. Endocrinologists (29.5% patients) and other clinical specialists (37.2% patients) were commonly first to suspect acromegaly. Morphologic manifestations (83.7–87.9% patients), snoring syndrome (81.4% patients), and asthenia (79.2% patients) were frequently present at diagnosis; differences were found between sexes for specific manifestations. Rates of discrepancy between patient- and physician-reported manifestations were highest for functional signs. Earliest manifestations prior to diagnosis, according to how they were detected, were enlarged hands and feet (6.4 ± 6.8 and 6.2 ± 6.9 years, functional signs), hypertension (6.6 ± 7.5 years, complementary examination) and carpal/cubital tunnel syndrome (5.7 ± 6.7 years, functional signs with complementary examination). Results confirm the broad range of manifestations at diagnosis and delay in recognizing the disease. We identified early manifestations and sex differences that may aid physicians in diagnosing acromegaly. Discrepancy rates suggest physicians should obtain the patient’s perspective and seek functional signs during diagnosis.

Agouti-related protein (AgRP), is a signaling peptide that affects feeding behavior, energy homeostasis, and has also been shown to stimulate the hypothalamic–pituitary–adrenal axis. The purpose of this study was to determine the effects of 90 min of treadmill exercise on circulating AgRP concentrations and the relationship of AgRP responses to cortisol. Seven young males completed a preliminary trial followed by counterbalanced experimental and control trials 4–5 weeks apart. The experimental trial began 2.5 h after consumption of a standard nutrient beverage and consisted of treadmill exercise at 60 % of previously determined VO2max for 90 min. Blood samples were collected before (−30 and 0 min), during (18, 36, 54, 72, and 90 min), and following exercise (20, 40, and 60 min). Blood samples were collected in a resting, control trial at the same time points as the experimental trial. Plasma lactate was significantly higher in the exercise than the control trial. Although AgRP increased from 18 min of exercise to peak at 90 min, these increases were not significantly different than values in the control trial. Cortisol responses during the exercise trial were significantly higher than the control trial. AgRP concentrations during early exercise were positively correlated with cortisol levels later in recovery. The obtained data suggest that AgRP concentrations during prolonged steady-state exercise are associated with subsequent cortisol increases, but further study is required to determine whether there is a causal effect.

Given the multiple targets of metformin within cells, the mechanism by which it may exert a growth-inhibitory action on pituitary tumor cells in vitro remains to be explored. Previous research stressed metformin-induced changes in the activity of signaling pathways regulating cell growth and cell death. In this work, we investigated the effects of metformin on cell viability markers related to cell metabolic activity in rat pituitary tumor cells versus rat myogenic precursors as a model of normal proliferating somatic cells. We designed our experiments in order to use the MTT reduction as a marker of cellular reductive activity and the total cellular ATP levels as a marker of energy supply during short incubations with different metabolic substrates (sodium pyruvate, D-glucose, L-glutamine, sodium citrate). Then, we extended the analysis to extracellular glucose consumption, extracellular medium acidification and pyruvate dehydrogenase (PDH) complex activity. Metformin was found to be effective in both cell types at the same concentrations, although the outcome of the treatment was quite the opposite. Unexpectedly, metformin increased the viability of subconfluent rat myoblasts. Rat pituitary tumor cells and myoblasts differed in the utilization of distinct metabolic substrates and the PDH complex activity. Metformin actions on reductive activity and ATP production were substrate-dependent. Overall, this work points out that metformin actions at the cellular level depend on metabolic features and metabolic requirements of cells. The pyruvate metabolic branch point is most likely to play a main role in the variability of cell response to metformin.