Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Deferred revascularization in diabetic patient according to combined invasive functional and intravascular imaging data: A case report.

BACKGROUND: Invasive functional evaluation by fractional flow reserve (FFR) is considered as a gold standard for the evaluation of intermediate coronary stenosis. However, in patients with diabetes due to accelerated progression of atherosclerosis the outcome may be worse even in the presence of negative functional testing. CASE SUMMARY: We present a case of 55-year-old male diabetic patient who was admitted for chest pain. Diagnostic coronary angiography disclosed 2 intermediate stenoses of the obtuse marginal branch with no evidence of restenosis on previously implanted stent. Patient undergone invasive functional testing of intermediate lesion with preserved FFR (0.88), low coronary flow reserve (1.2) and very high index of microvascular resistance (84). Due to discrepancy in invasive functional parameters, intravascular imaging with optical coherence tomography showed fibrotic stenoses without signs of thin-sup fibroatheroma. Because of the preserved FFR and no signs of vulnerable plaque, the interventional procedure was deferred and the patient continued with optimal medications. CONCLUSION: Combined functional and anatomic imaging of intermediate coronary stenosis in diabetic patients represent comprehensive contemporary decision pathway in the management of the patients.

The Influence of Hyperthyroidism on the Coagulation and on the Risk of Thrombosis.

Introduction: Apart from the well-known fact that hyperthyroidism induces multiple prothrombotic disorders, there is no consensus in clinical practice as to the impact of hyperthyroidism on the risk of thrombosis. The aim of this study was to examine the various hemostatic and immunologic parameters in patients with hyperthyroidism. Methods: Our study consists of a total of 200 patients comprised of 64 hyperthyroid patients, 68 hypothyroid patients, and 68 euthyroid controls. Patient thyroid status was determined with standard tests. Detailed hemostatic parameters and cardiolipin antibodies of each patient were determined. Results: The values of factor VIII (FVIII), the Von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and anticardiolipin antibodies of the IgM class were significantly higher in the hyperthyroid patients than in the hypothyroid patients and euthyroid controls. The rate of thromboembolic manifestations was much higher in hyperthyroid patients (6.25%) than in hypo-thyroid patients (2.9%) and euthyroid controls (1.4%). Among hyperthyroid patients with an FVIII value of ≥1.50 U/mL, thrombosis was recorded in 8.3%, while in hyperthyroid patients with FVIII value ≤ 1.50 U/mL the occurrence of thrombosis was not recorded. The incidence of atrial fibrillation (AF) was significantly higher (8.3%) in the hyperthyroid patients compared to the hypothyroid patients (1.5%) and euthyroid controls (0%). Conclusions: High levels of FVIII, vWF, fibrinogen, PAI-1, and anticardiolipin antibodies along with other hemostatic factors contribute to the presence of a hypercoaguable state in patients with hyperthyroidism. The risk of occurrence of thrombotic complications is especially pronounced in patients with a level of FVIII exceeding 150% and positive anticardiolipin antibodies of the IgM class. Patients with AF are at particularly high risk of thrombotic complications due to a hyperthyroid prothrombotic milieu.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

BACKGROUND: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Specific impact of cardiovascular risk factors on coronary microcirculation in patients with subclinical hypothyroidism.

Background: Although thyroid hormones have significant effect on cardiovascular system, the impact of subtle thyroid dysfunction such as subclinical hypothyroidism (SCH) remains to be determined. We investigated coronary flow reserve (CFR) in patients with subclinical hypothyroidism. Methods: Thirty two subjects with SCH and eighteen control subjects with normal serum thyroid hormones and thyroid-stimulating hormone (TSH) levels were included in the study. TSH, free thyroxine, free triiodothyronine, glucose, insulin, HbA1c, cholesterol, triglyceride and plasma levels of C-reactive protein were measured. Coronary diastolic peak flow velocities in left anterior descending coronary artery were measured at baseline and after adenosine infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocity. Results: CFR values were not significantly different between the two groups (SCH 2.76±0.35 vs controls 2.76±0.42). There was a significant correlation of CFR with waist to hip ratio, hypertension, smoking habits, markers of glucose status (glucose level, HbA1c, insulin level, HOMA IR), cholesterol, LDL-cholesterol and triglyceride levels in SCH group, whereas only cholesterol level showed significant correlation with CFR in controls. There was no correlation between CFR and thyroid hormones. Conclusions: We concluded that there is a different impact of cardiovascular risk factors on CFR in SCH patients compared to healthy control and that these two groups behave differently in the same circumstances under the same risk factors. The basis for this difference could be that the altered thyroid axis "set point" changes the sensitivity of the microvasculature in patients with SCH to known risk factors.

Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy.

Background: Thyrotropin receptor autoantibodies (TSH-RAb) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO. Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and binding TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cellbased bioassay. Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001). Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays.

Antiphospholipid antibodies in patients with Graves' orbitopathy: preliminary data.

PURPOSE: Graves' orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (-) subgroups of GO patients. METHODS: Study included consecutive patients with GO (66 with Graves' (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aß2gpI) Abs were measured by ELISA. RESULTS: aPL Abs were present in 9/84 (10.71%) patients. The IgM aß2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aß2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aß2gpI IgM (p = 0.014). CONCLUSION: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations.

The Coronary ARteriogenesis with combined Heparin and EXercise therapy in chronic refractory Angina (CARHEXA) trial: A double-blind, randomized, placebo-controlled stress echocardiographic study.

BACKGROUND: Coronary collateral circulation exerts protective effects on myocardial ischaemia due to coronary artery disease and can be promoted by exercise with heparin co-administration. Whether this arteriogenetic effect is accompanied by functional improvement of left ventricle during stress and lessening of angina symptoms remains unknown. AIMS: To evaluate the anti-ischaemic efficacy of heparin plus exercise in coronary artery disease. METHODS: In a prospective, single-centre, randomized, double-blind study we recruited 32 'no-option' patients (27 males; mean age 61 ± 8 years) with stable angina, exercise-induced ischaemia and coronary artery disease not suitable for revascularization. All underwent a two-week cycle of exercise (two exercise sessions per day, five days per week) and were randomized (n = 16 per group) to intravenous placebo (0.9% saline) versus unfractionated heparin (5.000 IU intravenously), 10 min prior to exercise. We assessed Canadian Cardiovascular Society angina class, stress electrocardiogram and echo parameters (wall motion score index) and computed tomography angiography for collaterals. RESULTS: After two-week cycle, Canadian Cardiovascular Society class statistically decreased in both groups (heparin plus exercise group: 2.6 ± 0.7 to 1.9 ± 0.7, p < 0.001, exercise group: 2.4 ± 0.7 to 2.1 ± 0.9, p = 0.046). Only the heparin plus exercise group improved time-to-ST segment depression (before 270, 228-327 s vs. after 339, 280-360 s, p = 0.012) and wall motion score index (before 1.38 ± 0.25 vs. after 1.28 ± 0.18, p = 0.005). By multi-slice computed tomography angiography, collaterals improved in 12/15 (80%) in the heparin plus exercise group versus 2/16 (12.5%) in the exercise group (p < 0.001). CONCLUSION: A two-week, 10-test cycle of heparin plus exercise is better than exercise in improving angina class, myocardial ischaemia and collaterals by computed tomography angiography.

Biochemical and clinical characteristics of patients with primary aldosteronism: Single centre experience.

BACKGROUND: Primary aldosteronism (PA) is associated with increased prevalence of metabolic disorders (impaired glucose and lipid metabolism and insulin resistance), but also with more frequent cardiovascular, renal and central nervous system complications. METHODS: Biochemical and clinical parameters were retrospectively analysed for 40 patients with PA caused by aldosterone-producing adenoma (APA) and compared to the control groups of 40 patients with nonfunctioning adrenal adenoma (NFA) and essential hypertension (HT), and 20 patients with adrenal Cushing syndrome (CS) or subclinical CS (SCS). RESULTS: Systolic, diastolic and mean arterial blood pressures were significantly higher in the PA group (p=0.004; p=0.002; p=0.001, respectively) than in NFA+HT group. PA patients had longer hypertension history (p=0.001) than patients with hypercorticism and all had hypokalaemia. This group showed the smallest mean tumour diameter (p<0.001). The metabolic syndrome was significantly less common in the PA group (37.5% vs. 70% in CS+SCS and 65% in NFA+HT group; p=0.015), although there was no significant difference in any of the analysed metabolic parameters between groups. PA group was found to have the most patients with glucose intolerance (81.8%), although the difference was not significant. The mean BMI for all three groups was in the overweight range. Patients with PA had higher microalbuminuria and a higher tendency for cardiovascular, renal and cerebrovascular events, but the difference was not significant. CONCLUSIONS: Our results support the importance of the early recognition of primary aldosteronism on the bases of clinical presentation, as well as an increased screening intensity.

Comparison of efficacy and safety of parenteral versus parenteral and oral glucocorticoid therapy in Graves' orbitopathy.

BACKGROUND/AIMS: The most effective and safe treatment protocol for Graves' orbitopathy (GO) needs to be further assessed. The aim of the present study was to evaluate the efficacy, safety and outcome of parenteral versus parenteral and oral glucocorticoid (GC) protocols in euthyroid patients with untreated and active moderate to severe GO. METHODS: This was a retrospective observational study in 140 patients comparing intravenous GC pulses only (IVGC group, 74 patients, 51 ± 11 years) with historical controls of combined oral and intravenous GC therapy (CombGC group, 66 patients, 49 ± 10 years, P = ns). IVGC therapy included infusions of 500 mg of methylprednisolone weekly for the first six weeks, followed by infusions of 250 mg weekly for the remaining six weeks (cumulative dose 4.5 g). CombGC therapy included 500 mg of methylprednisolone in 500 mL of saline solution for two alternative days, followed by oral prednisone tapering dose repeated each month for the next 5 months (cumulative dose 10.2 g). RESULTS: The overall success of the treatment was 43/66 (65%) in the CombGC group and 37/73 (51%, P = .071) in the IVGC group. Deterioration of GO developed in four (6%) patients during CombGC therapy and in nine (12%, P = .214) patients during IVGC therapy. After 6 months, relapse of GO was observed in 10/37 (26%) in the IVGC group, whereas none of the patients in CombGC had a relapse (P < .001). There were significantly more side effects in the CombGC versus IVGC group (49/66, 74% vs 28/74, 38%, P < .001). CONCLUSIONS: Our data suggest that CombGC therapy was more efficient with significantly less relapse rate, but with more side effects in comparison to IVGC therapy.

Predictive score for the development or progression of Graves' orbitopathy in patients with newly diagnosed Graves' hyperthyroidism.

OBJECTIVE: To construct a predictive score for the development or progression of Graves' orbitopathy (GO) in Graves' hyperthyroidism (GH). DESIGN: Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. METHODS: 348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed. RESULTS: GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6-12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2-10 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1-4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20-0.37) and 0.91 (95% CI 0.87-0.94) respectively. CONCLUSIONS: In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will.

Variability of HOMA and QUICKI insulin sensitivity indices.

Assessment of insulin sensitivity based on a single measurement of insulin and glucose, is both easy to understand and simple to perform. The tests most often used are HOMA and QUICKI. The aim of this study was to assess the biological variability of estimates of insulin sensitivity using HOMA and QUICKI indices. After a 12-h fast, blood was sampled for insulin and glucose determination. Sampling lasted for 90 min with an intersample interval of 2 min. A total of 56 subjects were included in the study, and in nine subjects sampling was done before and after weight reduction, so total number of analyzed series was 65. To compute the reference value of the insulin sensitivity index, averages of all 46 insulin and glucose samples were used. We also computed point estimates (single value estimates) of the insulin sensitivity index based on the different number of insulin/glucose samples (1-45 consecutive samples). To compute the variability of point estimates a bootstrapping procedure was used using 1000 resamples for each series and for each number of samples used to average insulin and glucose. Using a single insulin/glucose sample HOMA variability was 26.18 ± 4.31%, and QUICKI variability was 3.30 ± 0.54%. For 10 samples variability was 11.99 ± 2.22% and 1.62 ± 0.31% respectively. Biological variability of insulin sensitivity indices is significant, and it can be reduced by increasing the number of samples. Oscillations of insulin concentration in plasma are the major cause of variability of insulin sensitivity indices.

Challenges in interpretation of thyroid hormone test results.

INTRODUCTION: In interpreting thyroid hormones results it is preferable to think of interference and changes in concentration of their carrier proteins. OUTLINE OF CASES: We present two patients with discrepancy between the results of thyroid function tests and clinical status. The first case presents a 62-year-old patient with a nodular goiter and Hashimoto thyroiditis. Thyroid function test showed low thyroid-stimulating hormone (TSH) and normal to low fT4. By determining thyroid status (TSH, T4, fT4,T3, fT3) in two laboratories, basal and after dilution, as well as thyroxine-binding globulin (TBG), it was concluded that the thyroid hormone levels were normal. The results were influenced by heterophile antibodies leading to a false lower TSH level and suspected secondary hypothyroidism.The second case, a 40-year-old patient, was examined and followed because of the variable size thyroid nodule and initially borderline elevated TSH, after which thyroid status showed low level of total thyroid hormones and normal TSH. Based on additional analysis it was concluded that low T4 and T3 were a result of low TBG. It is a hereditary genetic disorder with no clinical significance. CONCLUSION: Erroneous diagnosis of thyroid disorders and potentially harmful treatment could be avoided by proving the interference or TBG deficiency whenever there is a discrepancy between the thyroid function results and the clinical picture.

Efficacy and safety of combined parenteral and oral steroid therapy in Graves' orbitopathy.

OBJECTIVE: Glucocorticoids (GC) are the treatment of choice for moderate-to-severe and active Graves' orbitopathy (GO), but optimal treatment is still . The aim of the present study was to analyze the efficacy and tolerability of combined parenteral GC pulse therapy followed by oral GC in the interpulse period. DESIGN: The study included 50 patients (48 ± 10 years; 37 female) with untreated, active and moderate-to-severe GO. Patients received 500 mg of methylprednisolone in 500 ml of physiologic saline. Infusion was repeated after 48 h and then followed by tapering doses of oral prednisone and the cycle repeated each month for the next 5 months. The cumulative dose was 10.2g.Ophthalmic assessment was performed before and 6 months after start of treatment. Side effects of GC therapy were evaluated and recorded each month. RESULTS: GC showed the greatest effectiveness on soft tissue changes (incorporated in the CAS). Median CAS values decreased from 4.5 to 2 (p>0.001). Improvement was demonstrated in 37 patients (74%), there was no change in 13 patients (26%) and none of the patients presented with deterioration of inflammatory status. Diplopia improved in 21 patients (42%), was unchanged in 28 patients (56%) and deteriorated in 1 patient (2%). Improvement in visual acuity occurred in 36% of patients. At 6 months, 33/50 patients (66%) demonstrated overall treatment response. Response to GC therapy was influenced by CAS, TSHRAb and smoking behavior. The only independent parameter associated with positive treatment response was CAS ≥ 4 (p<0.001). Side effects occurred in 35/50 patients (70%) and the vast majority of them were mild to moderate. During the 6-months follow-up period, 2/33 patients (6%) had relapsing GO. CONCLUSION: With appropriate selection of patients and careful monitoring during and after treatment, combined parenteral and oral GC therapy is effective and safe.

[Orbital decompression in Graves' orbitopathy].

INTRODUCTION: This paper was aimed at presenting our experience and results in the surgical management for proptosis in patients with Graves' orbitopathy. MATERIAL AND METHODS: This is a retrospective, interventional, non-comparative case series review. Seventeen eyes often patients underwent orbital decompression between 2008 and 2009. Depending on case, the surgery involved one to 3 orbital walls with or without fat removal, being approached through combined transcaruncular and lower fornix incision. RESULTS: All the operated patients were females, their mean age being 48, with proptosis ranging from 21 to 28 mm, and 18 to 22 mm three months after surgery. A mean reduction in proptosis of 4.59 +/- 1.58 mm was attained. Intra-operative course was uneventful and post-operatively transient infraorbital hypoesthesia was seen in twelve patients (70.57%). CONCLUSION: Orbital decompression proved to be a safe, reliable and effective way to reduce proptosis provided that the procedure is carefully planned and properly performed.

[Fifty years of subclinical primary aldosteronism: importance of early diagnosis].

Clinical presentation of excessive aldosterone secretion is often not specific. The presence of resistant severe hypertension (HT) and signs of hypokalemia is useful but inconsistent characteristic. Plasma aldosterone level in primary aldosteronism (PA) could be normal, although inappropriately high for a low plasma renin activity and not suppressed by sodium. Screening of hypertensive population with no obvious signs of PA has revealed an increased prevalence of idiopathic adrenal hyperplasia as a cause of aldosterone excess. Nowadays, PA is the most common endocrine form of secondary HT, with an estimated prevalence 5-10% of hypertensive population. The diagnosis of PA can lead to surgical cure in the case of aldosterone producing adenoma and unilateral adrenal hyperplasia. The aldosterone excess is responsible for vascular inflammation and end-organ damage. Left ventricular hypertrophy, cardiac arrhythmia and cerebral insult are frequently seen in PA and preventable by mineralocorticoid receptor blockers. For this reason, screening for PA in patients with HT and hypokalemia and/or adrenal incidentaloma, resistant and severe HT, and in patients with the onset of HT at young age is advisable.The most widely accepted screening for PA is serum aldosterone to plasma rennin activity (aldosterone: PRA) ratio, with the cut-off of 30 ng/dl:ng/ml/h. Serum aldosterone level could be included as an additional screening parameter. Confirmatory tests are crucial for the diagnosis of PA in patients with an increased aldosterone: PRA ratio and subtype differentiation for the choice of treatment.

Quantitative evaluation of collateral circulation in patients with previous myocardial infarction: relation to myocardial ischemia, angiographic appearance and functional improvement of myocardium.

Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts (mean age 53 +/- 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty. Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P(w)) and aortic pressure (P(a)). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional improvement of myocardium in the follow-up period. Mean P(w)/P(a) was 0.24 +/- 0.10 (range of 0.07-0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P(w)/P(a) was significantly higher in comparison to patients with ECG changes (0.28 +/- 0.09 vs. 0.15 +/- 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P(w)/P(a) was significantly higher than in the patients without echo improvement (0.26 +/- 0.10 vs. 0.18 +/- 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals. Low values of P(w)/P(a) are associated with ECG changes during balloon occlusion. Higher P(w)/P(a) was associated with better functional improvement of myocardium.

Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans.

OBJECTIVE: Interleukin 6 (IL6) has the ability to influence each level of the hypothalamo-pituitary-adrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation. DESIGN AND METHODS: Basal IL6 concentration was measured and a low dose (1 microg) ACTH test was performed to assess cortisol response. Twenty-seven apparently healthy subjects (11 male, 16 female, mean age 31.1 years, age range 22-47 years) were included in the study. RESULTS: Data are presented as mean+/-S.E.M. Basal IL6 level was 0.84+/-0.10 pg/ml. Basal cortisol was 351.9+/-18.3 nmol/l. Maximal cortisol during synacthen test was 653.0+/-20.6 nmol/l. Maximal cortisol increment was 301.1+/-20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration, but correlated significantly with cortisol increment (r=0.63, 95% confidence interval) 0.42-0.83). CONCLUSIONS: In our study, we found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore, it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions.