Selenium Supplementation, Body Mass Composition, and Leptin Levels in Patients with Obesity on a Balanced Mildly Hypocaloric Diet: A Pilot Study.

BACKGROUND: Adequate levels of selenium (Se) have protective effects against several chronic diseases, such as obesity. The aim of this study was to assess the effect of Se supplementation in a selected group of patients with obesity. METHODS: This randomized prospective study included 37 overweight/obese individuals aged 18-65 years, who adopted a slightly hypocaloric diet for 3 months. An intervention group received 240 µg/day of L-selenomethionine for 3 months; a control group received a placebo. Clinical and biochemical parameters, body composition measurements, and the Psychological General Well-Being Index (PGWBI) questionnaire were tested at the beginning and end of the treatment. RESULTS: A comparison of the two groups showed a significant change in body composition, involving a decrease in body fat mass, between the baseline and the end of the follow-up, in the intervention group. Unlike the placebo group, the group given Se had a significant increase in lean body and muscle mass and a significant decrease in leptin levels after 3 months on diet. At the end of the follow-up, the group given Se scored higher on the PGWBI than those who did not. CONCLUSION: Se could reinforce the effects of diet for overweight and obesity. This work was registered in the ISRCTN registry with study ID ISRCTN6106073.

The Effects of Iodine Supplementation in Pregnancy on Iodine Status, Thyroglobulin Levels and Thyroid Function Parameters: Results from a Randomized Controlled Clinical Trial in a Mild-to-Moderate Iodine Deficiency Area.

BACKGROUND: Iodine supplementation during pregnancy in areas with mild-to-moderate iodine deficiency is still debated. METHODS: A single-center, randomized, single-blind and placebo-controlled (3:2) trial was conducted. We enrolled 90 women before 12 weeks of gestation. From enrollment up until 8 weeks after delivery, 52 women were given an iodine supplement (225 ug/day, potassium iodide tablets) and 38 were given placebo. At recruitment (T0), in the second (T1) and third trimesters (T2), and 8 weeks after delivery (T3), we measured participants' urinary iodine-to-creatinine ratio (UI/Creat), thyroid function parameters (thyroglobulin (Tg), TSH, FT3, and FT4), and thyroid volume (TV). The newborns' urinary iodine concentrations were evaluated in 16 cases. RESULTS: Median UI/Creat at recruitment was 53.3 ug/g. UI/Creat was significantly higher in supplemented women at T1 and T2. Tg levels were lower at T1 and T2 in women with UI/Creat ≥ 150 ug/g, and in the Iodine group at T2 (p = 0.02). There was a negative correlation between Tg and UI/Creat throughout the study (p = 0.03, r = -0.1268). A lower TSH level was found in the Iodine group at T3 (p = 0.001). TV increased by +Δ7.43% in the Iodine group, and by +Δ11.17% in the Placebo group. No differences were found between the newborns' TSH levels on screening the two groups. CONCLUSION: Tg proved a good parameter for measuring iodine intake in our placebo-controlled series. Iodine supplementation did not prove harmful to pregnancy in areas of mild-to-moderate iodine deficiency, with no appreciable harmful effect on thyroid function.

Biological Effects of EF24, a Curcumin Derivative, Alone or Combined with Mitotane in Adrenocortical Tumor Cell Lines.

BACKGROUND: Curcumin has numerous properties and is used in many preclinical conditions, including cancer. It has low bioavailability, while its derivative EF24 shows enhanced solubility. However, its effects have never been explored in adrenocortical tumor cell models. The efficacy of EF24 alone or combined with mitotane (reference drug for adrenocortical cancer) was evaluated in two adrenocortical tumor cell lines, SW13 and H295R. METHOD AND RESULTS: EF24 reduced cell viability with an IC50 (half maximal inhibitory concentration) of 6.5 ± 2.4 µM and 4.9 ± 2.8 µM for SW13 and H295R cells, respectively. Combination index (EF24 associated with mitotane) suggested an additivity effect in both cell lines. Cell cycle analysis revealed an increase in subG0/G1 phase, while motility assay showed a decrease in migratory cell capacity, and similarly, clonogenic assay indicated that EF24 could reduce colony numbers. Furthermore, Wnt/ß-catenin, NF-κB, MAPK, and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with EF24 alone or combined with mitotane. In addition, intracellular reactive oxygen species levels increased in both cell lines. CONCLUSION: This work analyzed EF24 in adrenocortical tumor cell lines for the first time. These results suggest that EF24 could potentially impact on adrenocortical tumors, laying the foundation for further research in animal models.

Crude extract of Origanum vulgare L. induced cell death and suppressed MAPK and PI3/Akt signaling pathways in SW13 and H295R cell lines.

Oregano (Origanum vulgare L.) is a common aromatic plant used in Mediterranean and Asian Regions for treating respiratory diseases, painful menstruation, rheumatoid arthritis, etc. Recently its role as an anticancer plant has been suggested, although oregano has been never evaluated into adrenocortical tumour cell models. This study analysed for the first time the anticancer effects of a crude extract of wild mountain oregano (Origanum vulgare L.) in SW13 and H295R cell lines. The crude extract was characterised by GC/MS and the toxic effects of oregano were first analysed by brine shrimp lethality assay. Our findings demonstrated that oregano decreased cell viability, survival, modified cell cycle and induced cell death (through necrotic process) and that the effects can be attributed to a blockade of MAPK and PI3 K/Akt pathways. These results suggest that oregano extract exerts anticancer activities in adrenocortical tumour cell lines, providing evidence for further research in higher models.

Anticancer Effects of Wild Mountain Mentha longifolia Extract in Adrenocortical Tumor Cell Models.

Mint [Mentha longifolia (L.) Hudson] is an aromatic plant that belongs to Lamiaceae family. It is traditionally used as herbal tea in Europe, Australia and North Africa and shows numerous pharmacological effects, such as spasmolytic, antioxidant, antimicrobial and anti-hemolytic. Recently, its antiproliferative role has been suggested in a small number of tumor cell models, but no data are available on adrenocortical carcinoma, a malignancy with a survival rate at 5 years of 20%-30% which frequently metastasize. This work aimed to study the effects of Mentha longifolia L. crude extract (ME) on two adrenocortical tumor cell models (H295R and SW13 cells). Chemical composition of ME was assessed by gas-chromatography/mass spectrometry and NMR spectroscopy analysis. Brine shrimp lethality assay showed ME effects at >0.5 µg/µl (p < 0.05). Cell viability and vitality were determined by MTT, SRB, and trypan blue assays in H295R and SW13 cells. The anti-proliferative effects of ME were more evident in SW13 cells at 72 h (ME > 0.5 µg/µl, p < 0.05). Combination of ME with mitotane (approved drug for adrenocortical carcinoma) seemed not to reinforce the efficacy of the herb. As control, human fibroblasts were treated with ME with no effect on cell viability. Clonogenic assay was concordant with previous cell viability tests (ME > 0.5 µg/µl, p < 0.05), while Wright staining demonstrated the presence of both necrotic and apoptotic cells. Cell cycle analysis showed a strong increase in subG0/G1 phase, related to cell death. Furthermore, MAPK and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with ME alone or combined with mitotane. The crude methanolic extract of wild mountain mint can decrease cell viability, vitality and survival of adrenocortical tumor cell models, in particular of SW13 cells. These data show the potential anticancer effects of ME, still more work is needed to corroborate these findings.

Iodine status from childhood to adulthood in females living in North-East Italy: Iodine deficiency is still an issue.

PURPOSE: This survey aimed to assess iodine status in a female population at different ages, also investigating their eating habits. METHODS: We measured urinary iodine concentrations (UIC) in: 634 females at puberty and 361 fertile women in 246 of whom were considered also their children (134 daughters and 120 sons). All subjects completed a food frequency questionnaire. RESULTS: Median UIC decreased from childhood to adulthood (median UIC 107, 77 and 55 µg/l in the young girls, females at puberty and fertile women, respectively). Though using iodized salt improved iodine status in all groups, a significantly higher UIC was only noted in females at puberty. Milk consumption significantly increased UIC at all ages. In mother-child (both daughters and sons) pairs, the children's median UIC was nearly twice as high as their mothers' (UIC 115 vs. 57 µg/l). Milk consumption varied significantly: 56% of the mothers and 76% of their children drank milk regularly. The children (both daughters and sons) and mothers who drank milk had UIC ≥100 µg/l in 59 and 34% of cases, respectively, among the pairs who did not drink milk, 44% of the children and 19% of the mothers had UIC ≥100 µg/l. On statistical regression, 3.6% of the variability in the children's UIC depended on that of their mothers. CONCLUSIONS: Dietary iodine status declines from childhood to adulthood in females due to different eating habits. A mild iodine deficiency emerged in women of child-bearing age that could have consequences during pregnancy and lactation.

Transient hypercortisolism and symptomatic hyperthyroidism associated to primary hyperparathyroidism in an elderly patient: case report and literature review.

BACKGROUND: Primary hyperparathyroidism (PHPT) is often found on routine blood tests, at a relatively asymptomatic stage. However many studies suggest different systemic effects related to PHPT, which could be enhanced by an abnormal cortisol release due to chronic stress of hyperparathyroidism. Being PHPT frequently found in the 6(th) to 7(th) decade of life, a careful and multifaceted approach should be taken. CASE PRESENTATION: We report the case of an elderly patient with symptomatic PHPT and incidental pulmonary embolism. He was treated with hydration, zoledronic acid, cinacalcet and high-dose unfractionated heparin. Parathyroid surgery was successfully performed, but patient's conditions suddenly worsened because of a transient thyrotoxicosis, probably induced by a previous exposure to iodine load and/or thyroid surgical manipulation. A short-term treatment with beta-blockers was introduced for symptomatic relief. The patient also presented a transient hypercortisolism with elevated ACTH, likely due to stress related not only to aging and hospitalization but also to PHPT, resolved only four months after parathyroid surgery. CONCLUSION: Chronic hyperparathyroidism has been linked with increased all-cause mortality. A functional chronic hypercortisolism could be established, enhancing PHPT related disorders. Only parathyroid surgery has been demonstrated to cure PHPT and complications related, showing similar outcome between older and younger patients. However, the management of post-operative period should be more careful in fragile patients. In particular, the early diagnosis and treatment of a transient post-operative thyrotoxicosis could improve recovery. Due to the increase in prevalence and the evidence of many related complications even in asymptomatic PHPT, expert opinion-based guidelines for surgical treatment of PHPT should be developed especially for elderly patients.

Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety.

CONTEXT: Calcitonin (CT) measurement is crucial to the early diagnosis and the follow-up of medullary thyroid cancer (MTC). If the evaluation of stimulated CT levels is required, a provocative test can be performed, being the high-dose Ca test recently reintroduced in clinical practice. OBJECTIVE: Our objective was to identify gender-specific thresholds for MTC diagnosis in a large series of patients who underwent the Ca test. PATIENTS AND METHODS: A total of 91 patients (49 females and 42 males) underwent the Ca test (calcium gluconate, 25 mg/kg) before thyroidectomy and both basal CT (bCT) and stimulated CT (sCT) were compared with histological results by receiver operating characteristic plot analyses. To evaluate possible side effects of Ca administration, cardiac function has been extensively studied. RESULTS: bCT levels were found to harbor the same accuracy as sCT in the preoperative diagnosis of MTC. The best Ca thresholds for the identification of MTC were >26 and >68 for bCT and >79 and >544 pg/mL for sCT in females and males, respectively. The high tolerability and safety of the Ca test was demonstrated and advice offered to be followed before and during the test. CONCLUSIONS: Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test.

Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer.

CONTEXT: The evaluation of basal calcitonin (bCT) and stimulated calcitonin (sCT) can be used for the diagnosis and follow-up of medullary thyroid cancer (MTC). OBJECTIVE: The aim of this study was to evaluate the reliability of high-calcium (Ca) test and to identify gender-specific thresholds for MTC diagnosis. PATIENTS: Patients with MTC in remission (n=24) or in persistence (n=18), RET gene mutations carriers (n=14), patients with nodular goiter (n=69), and healthy volunteers (n=16) were submitted to pentagastrin and Ca (25 mg/kg) tests. RESULTS: In all groups, the levels of calcitonin (CT) stimulated by either pentagastrin or Ca were significantly correlated. The prevalence of both C-cell hyperplasia (CCH) and MTC in women and men paralleled the increasing basal and peak CT levels in a gender-specific manner. Receiver operating characteristic plot analyses showed that the best levels of bCT to separate normal and CCH cases from MTC patients were above 18.7 pg/ml in females and above 68 pg/ml in males. Furthermore, Ca sCT above 184 pg/ml in females and above 1620 pg/ml in males had the highest accuracy to distinguish normal and CCH cases from patients with MTC. At the C-cell immunohistochemical examination, Ca sCT below 50 pg/ml corresponded to a mean number of 30 cells per 10 fields, whereas higher sCT associated with a mean number of 400 cells per 10 fields, often displaying a diffuse and nodular distribution pattern. CONCLUSIONS: High-dose Ca test is a potent and well-tolerated procedure that can be applied worldwide at a low cost. Reference ranges for Ca sCT levels in different groups of patients and CT thresholds to diagnose CCH/MTC have been identified.

Influence of physiological dietary selenium supplementation on the natural course of autoimmune thyroiditis.

OBJECTIVE: Our study aimed to investigate whether physiological doses of selenium (Se) influence the natural course of autoimmune thyroiditis (AIT). DESIGN AND PATIENTS: A total of 76 consecutive patients (65 F, 11 M, median 43, range 15-75 years) with AIT, normal or slightly elevated TSH and fT4 within the normal range were divided into two groups: Group 0 (30 cases) was given no treatment while Group 1 (46 cases) was treated with sodium selenite 80 µg/day as a single oral dose for 12 months. Thyroperoxidase and thyroglobulin autoantibodies (TPO-Ab; Tg-Ab), TSH, fT4 and urine iodine concentrations (UIC) were measured at baseline and after 6 and 12 months of follow-up. Thyroid ultrasonography (US) was performed at each follow-up point. Echogenicity was measured by histographic analysis of gray-scale pixels (gsp) ranging from 0 = black to 255 = white. RESULTS: Thyroid echogenicity decreased significantly in both groups after 6 months, but after 12 months, it had changed no more in Group 1, whereas it had dropped further in Group 0. No significant variation in TPO-Ab or Tg-Ab levels was observed between the two groups after 6 months, but both values decreased significantly after 12 months in Group 1, and five patients in this group became negative for TPO-Ab. TSH and FT4 showed no significant variations in either group. CONCLUSIONS: Dietary supplementation with physiological doses of Se seems to be effective in preventing a reduction in thyroid echogenicity after 6 months of treatment and in reducing TPO-Ab and Tg-Ab after 12 months, but does not modify TSH or FT4.

Iodine status in pregnancy: role of dietary habits and geographical origin.

OBJECTIVES: A study was conducted on iodine status during pregnancy and its dependence on dietary habits, racial and geographical origin, and time since arrival in Italy. DESIGN AND METHODS: We enrolled 322 consecutive pregnant women: 217 Italians, 62 Eastern Europeans and 43 from Northern and Central Africa. All women completed a food frequency questionnaire on their dietary habits. The urinary iodide concentration (UIC) was determined in spot morning urine samples. RESULTS: In the group as a whole, the median UIC was 83 microg/l; the UIC was < 50 in 33% and of 150 microg/l or more in 27%; it was significantly lower in Africans and Eastern Europeans than in Italians (medians 45 and 46 vs. 100 microg/l, respectively, P = 0.005). For the foreign women, there was a significant correlation between UIC and time since arrival in Italy (r = 0.22, P = 0.02). A significant link emerged between UIC and cow's milk intake (P = 0.0001). Iodine supplements were used by 40% of the women, and UIC were higher in those who did so than in those who did not (median 103 vs. 75 microg/l, P = 0.03), particularly if the latter did not drink milk (median 98 vs. 42 microg/l, P = 0.01). Multivariate analysis showed that milk was the only variable influencing UIC (OR 1.29, P = 0.0005). CONCLUSIONS: (i) Iodine levels are too low among pregnant women in our region, and particularly in foreign women. (ii) Cow's milk intake is their main source of iodine. (iii) Iodine supplementation is mandatory during pregnancy, particularly for women do not drink milk.

Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study.

BACKGROUND: In the USA, about 30 200 well-differentiated thyroid carcinomas were diagnosed in 2007, but the prevalence of thyroid nodules is much higher (about 5% of the adult population). Unfortunately, the preoperative characterisation of follicular thyroid nodules is still a challenge, and many benign lesions, which remain indeterminate after fine-needle aspiration (FNA) cytology are referred to surgery. About 85% of these thyroid nodules are classified as benign at final histology. We aimed to assess the diagnostic effect of galectin-3 expression analysis in distinguishing preoperatively benign from malignant follicular thyroid nodules when FNA findings were indeterminate. METHODS: 544 patients were enrolled between June 1, 2003, and Aug 30, 2006. We used a purified monoclonal antibody to galectin-3, a biotin-free immunocytohistochemical assay, and a morphological and phenotypic analysis of FNA-derived cell-block preparations. Galectin-3-expression analysis was applied preoperatively on 465 follicular thyroid proliferations that were candidates for surgery, and its diagnostic accuracy was compared with the final histology. FINDINGS: 31 patients were excluded because they had small galectin-3-negative thyroid nodules; we did not have data for 47 patients; and one patient with an oncocytic nodule was excluded. 331 (71%) of the assessable 465 preoperative thyroid FNA samples did not express galectin-3. 280 (85%) of these galectin-3-negative lesions were classified as benign at final histology. Galectin-3 expression was detected, instead, in 134 of 465 (29%) thyroid proliferations, 101 (75%) of which were confirmed as malignant. The overall sensitivity of the galectin-3 test was 78% (95% CI 74-82) and specificity was 93% (90-95). Estimated positive predictive value was 82% (79-86) and negative predictive value was 91% (88-93). 381 (88%) of 432 patients with follicular thyroid nodules who were referred for thyroidectomy were correctly classified preoperatively by use of the galectin-3 test. However, 29 (22%) of 130 cancers were missed by the galectin-3 method. INTERPRETATION: Our findings show that if the option of surgery was based theoretically on galectin-3 expression alone, only 134 thyroid operations would have been done in 465 patients; therefore a large proportion (71%) of unnecessary thyroid surgical procedures could be avoided, although a number of galectin-3-negative cancers could be potentially missed. The galectin-3 test proposed here does not replace conventional FNA cytology, but represents a complementary diagnostic method for those follicular nodules that remain indeterminate.