Gelsy Arianna Lupoli

Effects of Treatment With Metformin on TSH Levels: A Meta-analysis of Literature Studies

CONTEXT Some data suggest that metformin affects the thyroid profile in patients with type 2 diabetes, but contrasting results are reported in different settings. OBJECTIVE The aim of this meta-analysis was to assess the effect of metformin treatment on TSH in subjects with or without thyroid dysfunction. DATA SOURCES We performed a systematic search of articles evaluating changes in TSH levels in patients receiving metformin. STUDY SELECTION Studies evaluating TSH levels before and after metformin treatment were included. DATA EXTRACTION Clinical data, demographic variables, and TSH levels before and after treatment with metformin were extracted. Data were analyzed according to the underlying thyroid disease. DATA SYNTHESIS A total of 7 datasets (206 patients) were included in the final analysis. After metformin treatment, a slight but significant reduction in TSH levels was found in 4 datasets on 119 patients with overt hypothyroidism receiving l-T4 replacement (mean difference, 1.08; 95% confidence interval [CI], 0.50, 1.65; P=.0003). Similarly, in 2 datasets reporting on a total of 33 patients with subclinical hypothyroidism not receiving treatment with l-T4, a significant reduction in TSH levels was reported (mean difference, 1.59; 95% CI, 1.32, 1.87; P<.00001) after treatment with metformin. In 1 dataset, including 54 euthyroid patients not receiving l-T4, no changes in TSH levels were reported after treatment with metformin (mean difference, 0.18; 95% CI, -0.20, 0.56; P=.35). CONCLUSIONS Metformin induces a reduction in TSH levels both in overt and in subclinical hypothyroidism. In contrast, no change in TSH levels is found in euthyroid patients.

Prevalence of Thyroid Autoimmunity in Patients with Spondyloarthropathies

Objective. To evaluate the prevalence of chronic autoimmune thyroiditis or Hashimoto’s thyroiditis (HT) in a group of patients with spondyloarthritis (SpA). Methods. We evaluated serum levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and titers of antithyroglobulin and antithyroid peroxidase (anti-TPO) antibodies in 357 consecutive patients with SpA. We also recruited 318 healthy age-matched controls. Ultrasonography of the thyroid gland was performed in all subjects and rheumatic activity was evaluated. Results. Indices of thyroid autoimmunity were significantly more frequent in patients with SpA than in controls (24.09% vs 10.69%, respectively; p < 0.05). In the SpA group, a higher prevalence of HT was found in patients with an active disease than in those with low-moderate disease levels. Also in the SpA group, patients with a disease duration > 2 years had a higher prevalence of HT and anti-TPO antibodies positivity than patients with a disease duration ≤ 2 years. Ultrasonography detected a significantly higher frequency of thyroid nodules and hypoechoic pattern in patients with SpA than in controls. Among patients with SpA, HT and anti-TPO antibodies positivity were significantly more frequent in patients with peripheral involvement (68.6%) than in patients with axial involvement (31.4%; p < 0.05). Conclusion. Our study shows a significantly higher prevalence of thyroid autoimmunity in patients with SpA as compared to controls. Thyroiditis occurs more frequently in patients with longer disease duration and active rheumatic disease. We suggest that thyroid function tests be part of the clinical evaluation in patients with SpA.

Impaired endothelial‐ and nonendothelial‐mediated vasodilation in patients with acute or chronic hypothyroidism

Objective  Vascular dysfunction and accelerated atherosclerosis are prominent features of hypothyroidism. The relative roles of thyroid hormone (TH) deficiency and the associated vascular risk conditions are still unclear. We studied the impact of acute and chronic hypothyroidism on vascular reactivity.

Side effects of TNF-α blockers in patients with psoriatic arthritis: evidences from literature studies

Psoriatic arthritis is an inflammatory rheumatic disorder, which occurs in patients with skin and/or nail psoriasis. In psoriatic arthritis, the importance of biologic mediators modulating inflammatory reaction, such as tumor necrosis factor, and the knowledge on their role in the pathogenesis of psoriatic arthritis influence the therapeutic choices. In the last years, the introduction of biologic drugs has greatly changed the treatment of psoriasis and psoriatic arthritis. In fact, tumor necrosis factor-α blockers demonstrated an effective action in the treatment of both skin and joint manifestations of psoriatic arthritis, but they have some adverse effects. The aim of this review is to revisit the literature data on adverse effects of tumor necrosis factor-α blockers in patients with psoriatic arthritis.

Teriparatide vs. Alendronate as a treatment for osteoporosis: Changes in biochemical markers of bone turnover, BMD and quality of life

Summary Background We studied the use of teriparatide in postmenopausal women with severe osteoporosis. Material/Methods Two groups (A and B) of patients affected by severe osteoporosis (T-score ⩽−2.5 at bone mineral density were analyzed and 2 vertebral fractures on radiograph). Group A was treated for 18 months with 20 μg/day of teriparatide. Group B was treated with bisphosphonates 70 mg/week. Every woman assumed 1 g of calcium and 800 IU of vitamin D3 daily. We evaluated the effects of therapy after 18 months (T18) from the beginning with bone turnover markers (alkaline phosphatase, procollagen type 1 N-terminal propeptide, and N-telopeptide cross-links) and dual-energy X-ray absorptiometry. Results Group A, at T18 procollagen type 1 N-terminal propeptide levels, increased 127%; bone alkaline phosphatase levels increased to 65%; N-telopeptide cross-links levels increased to 110%. Group B, at T18 procollagen type 1 N-terminal propeptide levels, decreased to 74%; bone alkaline phosphatase levels decreased to 41%; N-telopeptide cross-links levels decreased to 72%. After 18 months, lumbar bone mineral density increased to 12.4% and femoral bone mineral density increased to 5.2% in group A. Group B lumbar bone mineral density increased to 3.85% and femoral bone mineral density increased to 1.99%. Only a new vertebral fracture occurred in group A (2.4%), whereas 6 fractures occurred in group B (15.7%). The quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) revealed a significant improvement in daily living, performed domestic jobs, and locomotor function in groups A and B. Conclusions The use of rhPTH in patients with severe osteoporosis offers more protection against fractures and improves the QoL more than bisphosphonates.

Osteoporosis and Thyrotropin-Suppressive Therapy: Reduced Effectiveness of Alendronate

BACKGROUND Many reports of the effect of exogenous thyroxine therapy on bone mineral density (BMD) show a relationship between excess thyroid hormone administration and osteoporosis. The aim of this study was to evaluate the effect of antibone resorptive agents, in particular alendronate (ALN) on BMD in postmenopausal osteoporotic women with thyroid carcinoma who were receiving long-term thyrotropin (TSH)-suppressive therapy with thyroxine. METHODS Seventy-four postmenopausal women with low BMD (T-score < or =-2.5) and differentiated thyroid carcinoma on long-term TSH-suppressive therapy (TSH > or =0.05 and < or =0.1 microU/mL) for about 3-9 years were selected for the study. The patients were divided into three groups according to the length of levothyroxine (LT(4)) treatment prior to the beginning of the study: group A (TSH-suppressive therapy for about 3 years), group B (for about 6 years), and group C (for about 9 years). These patients were compared with 74 matched women not taking LT(4). All patients and controls were treated with bisphosphonates, calcium, and vitamin D for 2 years and evaluated. RESULTS After 24 months of treatment group A showed a 7.8% increase in lumbar BMD; group B, a 4.6% increase; and group C, a 0.86% increase. In the control group BMD increased 8.2%. A significant difference was found in both lumbar and femoral BMD increase among the three groups: group C had a lower BMD increase than group A (p < 0.001) and B (p < 0.001). CONCLUSIONS In postmenopausal women who were receiving adequate amounts of calcium and vitamin D in their diet ALN was less effective for those who were also receiving TSH-suppressive doses of LT(4) for either 6 or 9 years. The positive effect of ALN on BMD was less for longer periods of LT(4) treatment. It seems likely that other bisphosphonates would also be less effective in increasing BMD in postmenopausal women receiving TSH-suppressing doses of LT(4).

Recombinant human thyrotropin enhances endothelial-mediated vasodilation of conduit arteries.

CONTEXT Endothelial cells possess receptors to TSH. Their role is largely unknown. OBJECTIVES The objective of the study was to determine whether elevated serum TSH levels, as occur in hypothyroidism, affect endothelial function of large arteries and vascular risk biomarkers. SUBJECTS AND METHODS Thirty-four consecutively recruited patients, who had undergone thyroidectomy for thyroid carcinoma, were studied in connection with one of the monitoring procedures based on recombinant human (rh) TSH administration. Flow-mediated dilation (FMD) of the brachial artery and serum vascular risk markers were measured at baseline and for 5 d after the administration of rhTSH (0.9 mg im on d 1 and 2). Holter electrocardiogram and echocardiography were performed on d 2. RESULTS rhTSH caused a rapid increase in flow-mediated dilation from the basal value of 10.2 to 15.6% at 6 h (P < 0.0000001), to 16.1% on d 2 (P < 0.0000001), and to 14.9% on d 6 (P = 0.0015). The results were identical when the analysis was made in a subgroup of 19 patients free of vascular risk conditions. Vascular cell adhesion molecule-1, TNFalpha, IL-6, and high sensitive C-reactive protein were unaffected by rhTSH, whereas homocysteine was decreased. Arterial blood pressure, mean 24-h heart rate, and left ventricular function were unaffected by rhTSH. CONCLUSIONS rhTSH causes marked and persistent activation of the endothelial mediated vasodilation, independent of systemic hemodynamic changes.

The risk of osteoporosis in patients with liver cirrhosis: a meta-analysis of literature studies

Data about the association between cirrhosis and osteoporosis are contrasting. Thus, we have performed a meta‐analysis of literature studies on this topic.

Prognostic Significance of Thyroglobulin Antibody Epitopes in Differentiated Thyroid Cancer

CONTEXT Thyroglobulin antibodies (TgAbs) are surrogate markers of disease recurrence or persistence in differentiated thyroid cancer (DTC). However, the prognostic significance of TgAb heterogeneity in DTC has not been investigated. OBJECTIVE To evaluate the relationship between TgAb epitope specificities and clinical outcomes in DTC patients. DESIGN We studied 61 TgAb-positive patients with DTC, post-thyroidectomy and remnant ablation (7 males, 54 females; age-range 16-80 years, median follow-up duration 8.9 years). TgAb epitope reactivities were mapped using a panel of 10 thyroglobulin (Tg) monoclonal antibodies delineating six antigenic Tg clusters in competitive ELISA studies. Sera from 45 patients with Hashimotos thyroiditis (HT) and 22 TgAb-positive healthy subjects served as autoimmune and healthy controls. Tg was measured by immunoradiometric assay (IRMA), electrochemiluminescence immunoassay (ECLIA), and RIA, while TgAbs was measured by ELISA and ECLIA methods. RESULTS Samples from 26 DTC patients showed TgAb epitope restriction similar to HT patients, while 35 patients exhibited nonspecific reactivity comparable to healthy controls. DTC patients with epitope restriction had higher rates of recurrent/persistent disease (81% vs 17%, P < .001), higher median TgAb concentration (887.0 vs 82.0 kIU/L; P < .001), and a higher prevalence of thyroid lymphocytic infiltration (71.4% vs 26.8%; P < .001) compared to patients with nonspecific reactivity. Samples with epitope restriction also had a lower median Tg-IRMA/RIA ratio (3.0% vs 36.0%; P < .001) denoting greater degrees of Tg assay interference. CONCLUSIONS TgAb epitope restriction is associated with a less favorable prognosis than nonspecific reactivity in DTC patients. TgAb epitope specificities may have prognostic value in DTC.

Early carotid atherosclerosis in normotensive severe obese premenopausal women with low DHEA(S)

The aim of this study was to investigate the direct involvement of hyperinsulinaemia, DHEA and DHEA-S [DHEA(S)] in severe obesity in early carotid atherosclerosis, measured as intima-media thickness (IMT). Seventeen normotensive premenopausal women with very high BMI (43.5±1.6 kg/m2) were recruited for the study. Six women were also evaluated 12 months after laparoscopic adjustable silicone gastric banding (LASGB). Dietary intake, fasting plasma lipid profile, glycemic and insulinemic response to the OGTT, adrenal secretion, at baseline and after ACTH stimulation test, were measured. IMT, common carotid diameter (CD) and left ventricular mass index (LVMi) were measured by B-mode echotomography. All obese subjects showed higher fasting and stimulated insulin levels, but lower DHEA(S) levels than controls, showing a negative correlation between both fasting and stimulated insulin and DHEA(S), either at baseline or after ACTH testing. IMT was higher (p<0.05) than controls, with a positive correlation with stimulated insulin (p<0.05) and a strong negative correlation with DHEA(S) (p<0.001). In a multiple linear regression analysis, insulin response to OGTT maintained an association with DHEA(S) independent of fasting insulin, while DHEA maintained the association with IMT independent of stimulated insulin (p<0.0001). In the six patients evaluated 12 months after LASGB, fasting insulin levels decreased, while DHEA(S) levels increased (p<0.05). In conclusion, an early cardiovascular involvement was detected in this group of severe obese with hyperinsulinaemia and low DHEA(S), even in the absence of other well known CVD risk factors.