Arterial hypertension represents a major global health concern; more than one fourth of the population is affected by high blood pressure. Albeit the underlying cause of the disease remains unclear in the vast majority of the cases, ~10% are of secondary origin. Endocrine disorders are common illnesses and some of them may lead to elevated blood pressure, among which thyroid diseases are of high prevalence and often overlooked, especially in mild cases. Overt and subclinical hyper- and hypothyroidism can both lead to (mostly mild) hypertension; however, the underlying mechanisms are only partially understood. The results of clinical studies are often controversial. During the past decades, some genetic mutations in the hypothalamus-pituitary-thyroid axis with cardiovascular consequences were revealed. Atherosclerotic changes resulting from lipid abnormalities due to thyroid dysfunction also affect the vasculature and can cause elevated blood pressure. The review gives a synopsis of our knowledge how thyroid hormone metabolism and functional thyroid diseases affect the cardiovascular system, their negative impact and causative role in the development of hypertension.

Impaired cytokine balance has been observed in tears of GO patients. Secretion of IL-6 into tears might be a useful indicator of disease activity in GO.

Corticosteriod treatment is associated with a decline in DTPA uptake in a fraction of GO patients. GO patients with a DTPA uptake above 12.28 MBq/cm(3) are more likely to have a favorable response to corticosteroid therapy while patients with lower values are less likely to have this potentially favorable response. An elevated DTPA uptake may identify patients who are most likely to benefit from immunosuppressive treatment.

Abstract:Objective: The aim of this study was to investigate aortic stiffness and left ventricular systolic and diastolic function in patients with differentiated thyroid cancer (DTC) on thyroxin (L-T4) therapy and after L-T4 withdrawal in order to assess the cardiovascular impact of long-term subclinical hyperthyroidism and short-term overt hypothyroidism. Design: Twenty four patients who had had total thyroidectomy and radioiodine ablation for differentiated thyroid cancer were studied on two occasions: on TSH suppressive L-T4 therapy (sTSH 0.24±0.11 mU/L), and four weeks after L-T4 withdrawal (sTSH 89.82±29.36 mU/L). Echocardiography was performed and thyroid function, serum thyroglobulin, lipid parameters, homocystine, C-reactive protein, fibrinogen and von Willebrandt factor activity (vWF) were measured. Twenty two healthy volunteers matched for age and sex served as euthyroid controls. Results: Aortic stiffness was increased both in hypothyroidism (6.04±2.88 cm2/dyn/103, p< 0.05) and subclinical hyperthyroidism (9.27±4.81 cm2/dyn/103, p<0.05) vs. controls (3.92±1.84 cm2/dyn/103). Subclinical hyperthyroidism had a more marked effect (p<0.05). LV dimensions and ejection fractions were similar before and after L-T4 withdrawal. The E'/A' was higher in euthyroid controls (1.34±1.02) as compared to both subclinical hyperthyroidism (1.0±0.14, p<0.05) and overt hypothyroidism (1.13±0.98, p<0.05). Change of aortic stiffness correlated with change of free-thyroxine (fT4), vWF and fibrinogen levels in a positive manner. Conclusion: Long-term thyrotropin-suppression therapy has continuous adverse effects on the arterial wall. The degree of TSH suppression in patients with DTC should be kept at the possible minimum, based on individually determined potential benefits and risks of treatment, especially in patients with cardiovascular comorbidities. Dear Professor Bartalena,We would like to thank you for the suggestions which have contributed to the improvement of our paper entitled "Aortic stiffness and left ventricular function in patients with differentiated thyroid cancer", JENI-D-14-00120 .We have corrected the manuscript and we hope that you will find it worth publishing in the Journal of Endocrinological Investigation.We provide a detailed point-by-point response to each of the referees' concerns, describing exactly how we responded to each point and where you can find the amendment in the revised manuscript.Thank you very much for your patience and kind help. •How many time elapsed from thyroidectomy/RAI ablation and the current tests?20±12,6 months elapsed before the start of this study. This information has been added to page 4, line 47.•What was the thyroglobulin serum level at the time of aortic examination? In other words, were all the patients without evidence of persistent/recurrent disease (also by the biochemical point of view)? / Did the Authors evaluate the level of serum anti-Tg antibodies?The first off-T4 Tg measurrment was at least 6 months after RAI in parallel with anti-Tg antibody. Four of twenty...

The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves' orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), (99m)Tc-labeled diethylene triamine pentaacetic acid ((99m)Tc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375 mg/m(2) body surface area for four weeks. The mean follow-up period was 67 (range 58-81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5 ± 1.7 and decreased to 3.4 ± 1.6 by one month (p < 0.05) and remained unchanged (3.2 ± 1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52 ± 4.51 MBq/cm(3) and decreased to 11.97 ± 2.36 MBq/cm(3) at one year (p < 0.002). The mean of T2 relaxation times before and one year after therapy were 96.91 ± 17.61 ms and 84.29 ± 9.41 ms, respectively (p < 0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4 ± 3.4 U/L, 5.6 ± 4.5 U/L and 1.7 ± 1.5 U/L, respectively (p < 0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.