Ilias Perogamvros

Introduction: Thyroglobulin antibodies (Tg-Abs) are often thought to be associated with thyroid autoimmunity, and as such, a link with thyroid cancer has been found in some, but not all, studies. Tg-Abs are also found in non-autoimmune thyroid-follicular destruction. Given these contradictory results, we designed the present study. Methods: We reviewed data from patients undergoing thyroidectomy for different indications in multiple centers across Greece and the US over 10 years. We compared the incidence of thyroid cancer and its features of tumor aggressiveness among patients with positive (≥30 IU/mL) and negative (p < 0.05. Tumor size was larger, and capsular invasion and lymph node involvement were significantly more common in Tg-Abs+ subjects. Mean Tg-Abs were higher in subjects with tumors with extrathyroidal extension, capsular invasion, and lymph node involvement. On regression, Tg-Abs positivity was not associated with thyroid cancer incidence or aggressiveness, though, with the important exception of lymph node involvement (p < 0.001). Conclusions: Elevated preoperative thyroglobulin-antibody titers do not seem to affect the likelihood of developing thyroid cancer, even though they seem to be a surrogate for lymph node metastasis (as opposed to thyroid peroxidase antibodies, TPO-Abs). Further work is needed to clarify the interplay of this immune response on thyroid cancer metastatic behavior.

Purpose: Lipid lowering treatments (LLTs) can reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Despite the availability of potent LLTs, our clinical observations suggest an inadequate use of such agents. To evaluate this treatment deficit, we designed the present study. Methods: We reviewed the charts of all patients with a history of ASCVD (coronary artery disease—CAD; carotid stenosis—CS; or peripheral artery disease—PAD) diagnosed prior to their first visit to one of our clinics. We recorded their gender, age, ASCVD risk factors (diabetes, hypertension, tobacco use, body mass index), lipid values during that visit and the LLT used. We estimated the rates of the attainment of guideline-specific lipid goals by year, and assessed factors influencing the likelihood of treatment success. Results: Overall, n = 1003 subjects were recruited: CAD n = 703 (70.1%), PAD n = 168 (16.8%), CS n = 325 (32.4%); age 64.7 ± 11.2 years; n = 376 (37.5%) females; n = 642 (64.0%) had diabetes; n = 740 (73.8%) had hypertension; n = 299 (29.8%) were former and n = 367 (36.6%) were current smokers. An appropriate LLT was used in 361 (36.0%) subjects, n = 159 (15.9%) were on no treatment, n = 483 (48.2%) were receiving inadequate therapy, n = 434 (43.3%) were on a high-intensity LLT and n = 361 (36.0%) had achieved the year-specific LDL goals. Success rates ranged from 5.7% to 81.5%, with the lowest being 2020–2023 (5.7–14.5%), p < 0.001. The use of a combination of LLTs and PCSK9 inhibitors led to higher rates of LDL-C goals achievement (p < 0.001). Discussion: Recent secondary ASCVD risk prevention guidelines’ goals are rarely achieved in daily clinical practice, producing a major treatment deficit in this population. Newer systematic interventions are needed to curb this public health issue.

Purpose: This study aimed to evaluate various therapeutic approaches, identify potential predictive factors for the recurrence and development of hypothyroidism, and examine specific clinical and laboratory characteristics of patients with subacute thyroiditis (SAT) due to SARS-CoV-2 infection. Methods: We retrospectively analyzed the medical records of 226 patients with confirmed SAT diagnosed from January 2020 to November 2022. Results: The mean age was 48.01 ± 0.75 years, and the F/M ratio was 2.3/1. At the end of the follow-up period, 69 patients (32.1%) had developed hypothyroidism. Treatment duration was significantly shorter with nonsteroidal anti-inflammatory drugs (NSAIDs) (17.40 ± 2.56 days), while time-to-symptom relief was shorter with glucocorticoids (CGs). Recurrence was observed only in those treated with corticosteroid preparations (14.1%). C-reactive protein levels at treatment discontinuation were higher in patients who experienced SAT recurrence, while the coexistence of Hashimoto’s thyroiditis was a significant predictive factor for the development of hypothyroidism. The TSH value at the time of treatment withdrawal >4.12 μIU/mL showed optimal sensitivity and specificity for the prediction of permanent hypothyroidism. Regarding COVID-19, 34 patients (15%) experienced related SAT, with similar clinical manifestations of the disease but a higher BMI and shorter time-to-symptom relief. Conclusion: In conclusion, GCs administration alleviated acute symptoms earlier during the onset of SAT, whereas NSAIDs had a shorter treatment duration, and both regimens could not prevent the development of delayed hypothyroidism. The clinical characteristics of SAT due to COVID-19 infections were similar to those of typical SAT disease.

Disclosure: R.D. Paparodis: None. I. Androulakis: None. D.P. Askitis: None. I. Perogamvros: None. N. Angelopoulos: None. A. Rizoulis: None. S. Livadas: None. A. Boniakos: None. Background: The increasing availability of aggressive lipid lowering therapies (LLTs) worldwide is expected to produce a significant decline in cholesterol concentrations worldwide and a more successful attainment of LDL lowering goals (LLGs), especially in those who need them most: patients with established atherosclerotic cardiovascular disease (ASCVD). Aims: To assess the long-term changes in the rate of attainment of LGs according to the European Society of Cardiology Guidelines nationwide, with the use of different LLTs during 12 consecutive years. Methods: We reviewed the charts of all patients initially seen between 2010-2022 who returned for care follow up at our 8 busy Endocrinology clinics, located in 6 cities in Greece, between Sep-1-2022 and Nov-30-2022. We enrolled those with recorded diagnosis of ASCVD [coronary artery disease (CAD), peripheral arterial disease (PAD) or carotid stenosis >50% (CS)] prior to our initial visit. For the present work, we reviewed data on tobacco use, intake of LLTs, and LDL-cholesterol concentrations as recorded during our initial clinic visit. We excluded all patients referred to our clinics for lipids management. Data are presented as means ± standard deviation. Means are compared with Kruskal Wallis test and pResults: We enrolled n=890 consecutive patients, age 63.9 ± 11.4 years, n=339 were women (38.1%), n=529 (59.4%) had diabetes, n=672 (75.5%) had hypertensions and all had ≥1 forms of established ASCVD: n=630 with CAD, n=279 with CS and n=151 with PAD. Out of these, n=144 (16.2%) were on no LLTs, n=334 (37.5%) continued to smoke, n=381 (42.8%) were on guidelines-based appropriate LLT strategy, n=248 (27.9%) reached LLGs and n=318 (35.7%) fulfilled the year-specific guidelines requirements. Of note is, that this rate dropped to 2.4-20.4% in the years 2019-2022. The likelihood of achieving LDL goals was not statistically significantly different among patients with different forms of ASCVD (p=0.42). Overall, the mean LDL was 88.2 ± 32.1mg/dl, and was not different between patients with different forms of ASCVD (p=0.75). Mean LDL concentrations have only started to drop between 2020-2022 as compared to 2019 (pConclusions: Our study reveals a large care gap in patients with established ASCVD, which did not seem to improve significantly over the past 12 years, despite the excellent availability of aggressive LLT strategies in Greece. Intervention studies are urgently needed to enhance adherence to updated international guidelines and reduce the extremely high ASCVD risk in this fragile population. Presentation: Friday, June 16, 2023

Context Estimated rates of cortisol elimination and appearance vary according to the model used to obtain them. Generalizability of current models of cortisol disposition in healthy humans is limited. Objective Development and validation of a realistic, mechanistic model of cortisol disposition that accounts for the major factors influencing plasma cortisol concentrations in vivo (Model 4), and comparison to previously described models of cortisol disposition in current clinical use (Models 1-3). Methods The four models were independently applied to cortisol concentration data obtained for the hydrocortisone bolus experiment (20 mg) in two clinical groups: healthy volunteers (HV, n = 6) and CBG-deficient (n = 2). Model 4 used Fick’s first law of diffusion to model free cortisol flux between vascular and extravascular compartments. Pharmacokinetic parameter solutions for Models 1-4 were optimized by numerical methods, and model-specific parameter solutions were compared by RM-ANOVA. Models and respective parameter solutions were compared by mathematical and simulation analyses, and an assessment tool was used to compare performance characteristics. Results Cortisol half-lives differed significantly between models (all P < 0.001) with significant model-group interaction (P = 0.02). In comparative analysis, Model 4 solutions yielded significantly reduced free cortisol half-life, improved fit to experimental data (both P < 0.01), and superior model performance. Conclusions The proposed 4-compartment diffusion model (Model 4) is consistent with relevant experimental observations and met the greatest number of empiric validation criteria. Cortisol half-life solutions obtained using Model 4 were generalizable between HV and CBG-deficient groups and bolus and continuous modes of hydrocortisone infusion.

Routine assessment of the hypothalamic-pituitary-adrenal axis relies on the measurement of total serum cortisol levels. However, most cortisol in serum is bound to corticosteroid-binding globulin (CBG) and albumin, and changes in the structure or circulating levels of binding proteins markedly affect measured total serum cortisol levels. Furthermore, high-affinity binding to CBG is predicted to affect the availability of cortisol for the glucocorticoid receptor. CBG is a substrate for activated neutrophil elastase, which cleaves the binding protein and results in the release of cortisol at sites of inflammation, enhancing its tissue-specific anti-inflammatory effects. Further tissue-specific modulation of cortisol availability is conferred by corticosteroid 11β-dehydrogenase. Direct assessment of tissue levels of bioavailable cortisol is not clinically practicable and measurement of total serum cortisol levels is of limited value in clinical conditions that alter prereceptor glucocorticoid bioavailability. Bioavailable cortisol can, however, be measured indirectly at systemic, extracellular tissue and cell levels, using novel techniques that have provided new insight into the transport, metabolism and biological action of glucocorticoids. A more physiologically informative approach is, therefore, now possible in the assessment of the hypothalamic-pituitary-adrenal axis, which could prove useful in clinical practice.