High-Dose Intravenous Steroid Treatment Seems to Have No Long-Term Negative Effect on Bone Mineral Density of Young and Newly Diagnosed Multiple Sclerosis Patients: A Pilot Study.

High-dose intravenous steroid treatment (HDIST) represents the first choice of treatment for multiple sclerosis (MS) relapses. Chronic oral glucocorticoid (GC) administration correlates with bone loss whereas data regarding HDIST in MS are still conflicting. Twenty-five newly diagnosed MS patients (NDMSP) (median age: 37 years) were prospectively studied for the effects of HDIST on bone mineral density (BMD) and bone metabolism. Patients received 1000 mg methylprednisolone intravenously every day for 5 days followed by oral prednisolone tapering over 21 days. Bone metabolism indices were determined prior to GC, on days 2, 4, 6, and 90, and at months 6, 12, 18, and 24 post GC therapy. Femoral, lumbar-spine BMD, and whole-body measurement of adipose/lean tissue were assessed prior to GC-administration and then every six months. Ten patients completed the study. N-terminal-propeptide-procollagen-type-1 and bone-specific alkaline phosphatase showed a significant increase at day-90 (p < 0.05). A transient non-significant fall of BMD was observed at 6 months after GC-administration, which subsequently appeared to be restored. We conclude that HDIST seems not to have long-term negative effects on BMD, while the observed transient increase of bone formation markers probably indicates a high bone turnover phase to GC-administration. Additional prospective studies with larger sample size are needed.

Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI).

Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-not estimable [NE]) overall, 55.4 months (IQR 15.2-NE) in Cohort 1 (n = 169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n = 478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.

Advanced RAI-refractory thyroid cancer: an update on treatment perspectives.

During the last decades, the knowledge on follicular cell-derived thyroid cancer molecular biology has led to the evolution of a number of novel therapies for these tumors, mainly tyrosine kinase inhibitors. Lenvantinib, sorafenib and recently cabozantinib have been approved for differentiated thyroid cancer (DTC), while larotrectinib and entrectinib for neurotrophic-tropomyosin receptor kinase-fusion thyroid cancer. For radioiodine (RAI) refractory DTCs ongoing research aims to identify agents that may restore RAI-avidity via redifferentiation protocols (vemurafenib or dabrafenib and trametinib) or combination treatments. These treatments are based on the tumor molecular signature. The treatment with targeted therapies has changed the therapeutic strategies and the disease prognosis, however drug resistance remains the main reason for treatment failure. Thus, the understanding of both molecular pathways implicated in tumorigenesis, and tumoral escape mechanisms, are of paramount significance for the development of new therapies for DTC. The present review focuses on the molecular landscape of DTC, the approved targeted therapies as well as the mechanisms of drug resistance. Furthermore, it points to the ongoing research and the future perspectives for the development of more efficient drugs for DTC.

Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Hellenic Endocrine Society.

PURPOSE: To investigate current practices of specialists in the use of thyroid hormone preparations in Greece as part of an ongoing international survey, namely THESIS-Treatment of Hypothyroidism in Europe by Specialists: an International Survey. METHODS: An electronic link leading to an anonymized questionnaire was sent to all (n = 837) members of the Hellenic Endocrine Society. RESULTS: In total, 501 respondents participated in the survey, though only part of the questionnaire was filled in by some participants. A total of 88.2% were endocrinologists and 57.9% worked in private practice. Levothyroxine (LT4) was the first-line choice (98.6%) for the treatment of hypothyroid patients. In total, 70.2% preferred LT4 soft-gel capsules for patients reporting intolerance to various foods. Soft-gel capsules were the preferred LT4 formulation for patients on generic LT4 and with unexplained poor biochemical control of hypothyroidism (66.3%) or inability to take LT4 fasted and separate from food/drink (68.3%). It was found that 48.4% would never use combined LT4 + LT3. However, 25% would use combination therapy for a short period in patients recovering from protracted hypothyroidism or in patients with normal serum TSH but persistent symptoms. Concerning euthyroid individuals, 31.9% considered treatment with thyroid hormones in infertile females with positive thyroid antibodies and 24.4% in patients with growing goiter. Selenium or iodine supplementation was used occasionally, mostly in patients with coexisting autoimmune thyroiditis. CONCLUSIONS: LT4 tablets are the treatment of choice for hypothyroidism in Greece. Several conditions may lead to various other practices, some of which deviate from current evidence-based guidelines and need more scrutiny.

Minimally invasive parathyroidectomy in patients with previous neck surgery.

OBJECTIVE: Previous neck surgery (PNS) in patients with primary hyperparathyroidism (PHP) is considered as a contraindication for minimally invasive parathyroidectomy (MIP). The purpose of our study was to determine the effectiveness of MIP in such patients. DESIGN: From January 2003 to June 2011, 380 patients with PHP were treated in our department; 42 had had previous neck surgery. Twenty-seven (27/42) were selected to have MIP; the remaining 15 patients had traditional neck explorations. Selection criteria for MIP were unilateral single or two gland disease localized preoperatively with at least two imaging techniques and patient's informed consent. Imaging studies included high resolution neck ultrasound and sestamibi scan in the majority, and CT scan, selective venous sampling and MRI in seven patients. The type of operation done included unilateral approach under local anesthesia (UALA) (22 cases) with one conversion to general anesthesia and minimally invasive parathyroidectomy under general anesthesia (MIPG) (5 cases). RESULTS: Twenty-six of the 27 patients became normocalcemic after the operation. The patient with persistent hypercalcemia underwent successful parathyroidectomy 8 months later via mesothoracoscopy, since the parathyroid gland was localized correctly but was beyond access via neck. A single adenoma was found in 21 cases and hyperplasia in six. There were no conversions to traditional exploration and no postoperative complications. Mean duration of the procedure and length of stay were similar to MIP in patients without PNS. Mean follow-up of 40 months (4-89 months) did not reveal any recurrence. CONCLUSION: These results illustrate that MIP is a valuable option in selected patients with PHP and PNS associated with no morbidity (0%), high biochemical cure rate (96.3% in this series) and rapid recovery, while it also substantially lowers the cost of the procedure. Preoperative localization with two or more agreeing imaging techniques eliminates the need for intraoperative sestamibi or qPTH test.

The role of diet and lifestyle in primary, secondary, and tertiary diabetes prevention: a review of meta-analyses.

Prevention of diabetes is crucial to lowering disease incidence, and thus minimizing the individual, familial, and public health burden. The purpose of this review is to gather current information from meta-analyses on dietary and lifestyle practices concerning reduction of risk to develop type 2 diabetes. Low glycemic index dietary patterns reduce both fasting blood glucose and glycated proteins independent of carbohydrate consumption. Diets rich in whole-grain, cereal high fiber products, and non-oil-seed pulses are beneficial. Whereas, frequent meat consumption has been shown to increase risk. Regarding non-alcoholic beverages, 4 cups/day of filtered coffee or tea are associated with a reduced diabetes risk. In contrast, the consumption of alcoholic beverages should not exceed 1-3 drinks/day. Intake of vitamin E, carotenoids, and magnesium can be increased to counteract diabetes risk. Obesity is the most important factor accounting for more than half of new diabetes' cases; even modest weight loss has a favorable effect in preventing the appearance of diabetes. Also, physical exercise with or without diet contributes to a healthier lifestyle, and is important for lowering risk. Finally, there is a positive association between smoking and risk to develop type 2 diabetes. As far as secondary and tertiary prevention is concerned, for persons already diagnosed with diabetes, there is limited evidence of the effectiveness of diet or lifestyle modification on glycemic control, but further studies are necessary.

Thyroid volume, selenium levels and nutritional habits in a rural region in Albania.

OBJECTIVE: Environmental factors are involved in goiter development. An increased number of goitrous patients were identified among outpatients in Gyrocaster, a mountainous region in Southwestern Albania. We examined possible associations of thyroid enlargement with nutritional factors. DESIGN: 112 consecutive patients, 104 females, aged 52.8 +/-12.1 (mean+/-SD), who either were taking thyroxine (n=27) or were suspected to have thyroid disease were examined. Thyroid parameters and nutritional habits were recorded and serum selenium and urine iodine levels were determined; thyroid ultrasound was performed. RESULTS: The median thyroid volume (TV) was 20.4 ml (range 4.4-97.6). All consumed food was home-produced. TV correlated negatively with the frequency of lamb-goat meat and vegetables consumption (p=0.05 and p=0.03, respectively). Mean TV was significantly lower in those eating lamb-goat >1 times/week (21.4+/-13.3 vs 31.9+/-23 ml, p<0.01). The association of TV with lamb meat consumption was independent of sex, education or occupation (p < 0.009). Selenium levels ranged from 30.6-138 microg/L (reference range 43-190). There was no association between selenium levels and TV. 43% of the subjects had TSH < 0.3 mU/L (those on thyroxine were excluded). Log TSH correlated negatively with TV and fT4 levels (p < 0.007), indicating the presence of autonomy (TSHRab positive in two subjects). Mean urinary iodine excretion was 99.8+/-35.3 microg/gr creatinine (normal >100). CONCLUSIONS: Nutritional factors may be involved in the development of goiter in Southwestern Albania. No role of selenium was found. The higher consumption of lamb-goat meat and vegetables, all non-industrialized, appeared to be protective. This finding may reflect better socioeconomic status, although this was not identified. Unrecognized subclinical hyperthyroidism, probably due to thyroid autonomy, was quite common.