Could a nonfunctional adrenal incidentaloma be a risk factor for increased carotid intima-media thickness and 10-year cardiovascular mortality based on the SCORE algorithm? A study from a single centre in Poland.

INTRODUCTION: Adrenal incidentaloma (AI) secreting small amounts of glucocorticoids may cause morphological and functional changes in the blood vessels. Early stages of cardiovascular remodeling may be observed among asymptomatic patients with AI. But it is unclear whether the nonfunctional adrenal incidentalomas (NFAI) may also be a risk factor for cardiovascular diseases. The aim of this study was to determine the relationship between NFAI, carotid intima-media thickness (CIMT), and cardiovascular risk (CVR) based on Systematic Coronary Risk Evaluation (SCORE) prediction models for Europe. MATERIAL AND METHODS: This study from a single centre in Poland included 48 NFAI patients and 44 individuals in the control group matched for age, sex, and body mass index (BMI). All participants underwent adrenal imaging, biochemical evaluation, measurement of CIMT, and assessment of the 10-year risk of cardiovascular mortality based on the SCORE algorithm. Hormonal evaluation was conducted in AI patients. RESULTS: The NFAI group showed significantly higher sodium (p = 0.02) and glucose levels in the 2-h oral glucose tolerance test (OGTT) (p = 0.04), a higher CIMT (p < 0.01), and a higher CVR calculated according to the SCORE algorithm (p = 0.03). The estimated glomerular filtration rate (eGFR) was higher in the NFAI group (p = 0.015). Hypertension (p < 0.01) and IGT (p = 0.026) were more common in the NFAI group. Statistically significant positive correlations were found between CIMT and age (r = 0.373, p = 0.003), waist circumference (r = 0.316, p = 0.029), diastolic blood pressure (r = 0.338, p = 0.019), and CVR based on the SCORE algorithm (r = 0.43, p = 0.004). There was a statistically significant positive correlation between CIMT and serum cortisol levels after 1 mg dexamethasone suppression test (r = 0.33, p = 0.02). CONCLUSION: Non-functional adrenal adenomas are associated with increased CIMT and CVR. Early stages of cardiovascular remodelling can be observed in asymptomatic NFAI patients.

Do Non-Functional Adrenal Adenomas Affect Metabolic Profile and Carotid Intima-Media Thickness? A Single Centre Study from Poland.

Background: Compared to the general population, among people with adrenal incidentalomas (AIs) the diagnosis of obesity, hypertension, impaired carbohydrate and lipid metabolism is more common. The aformentioned disorders represent typical cardiovascular remodeling risk factors. The study was designed to assess the association between NFAIs, metabolic profile and carotid intima-media thickness (CIMT) as the predictive factor of atherosclerosis. Material: The study included 48 patients with NFAI (16 men, 32 women, mean age 58.6 +/- 9 years) and 44 control participants (15 men, 29 women, mean age 57 +/- 7 years). Both groups were matched for age, gender and BMI. Subjects with history of myocardial infarction, stroke or diabetes mellitus (DM) were excluded. Participants underwent adrenal imaging, biochemical evaluation, and measurement of CIMT. Hormonal evaluation was conducted in AI patients. Results: The NFAI group had significantly higher waist circumference (p < 0.01), higher systolic (p < 0.01) and diastolic blood pressure (p < 0.01), fasting insulin (p = 0.03) and glucose in the 2 h OGTT (p = 0.04) as well as higher CIMT (p < 0.01). Hypertension (p < 0.01) and IGT (p = 0.026) were more common in this group as well. There was a positive correlation between CIMT and cortisol levels in 1 mg dexamethasone suppression test (r = 0.33, p = 0.02). Conclusions: Patients diagnosed with NFAIs, despite normal cortisol inhibition in the 1 mg dexamethasone test, still presented a number of metabolic abnormalities. The assessment of IMT may proove valuable in indicate the presence of early vascular remodelling in asymptomatic patients. The underlying mechanisms of these findings are still unknown, hence further studies are required.

A Brief Look at Hashimoto's Disease, Adrenal Incidentalomas, Obesity and Insulin Resistance-Could Endocrine Disruptors Be the Other Side of the Same Coin?

Hashimoto's disease (HD) is the most common cause of hypothyroidism in developed countries. The exact pathomechanism behind it has not been clearly established; however, an interplay of genetic susceptibility, environmental triggers (including diet) and epigenetic factors seems to be involved. Among the latter, increasingly more attention has been paid to some hormonally active substances, known as endocrine disruptors, which are commonly used worldwide. HD has become a condition widely reported in the media, acting as a culprit for inexplicable weight gain, chronic fatigue or weakness. Nevertheless, the recognition of HD is undeniably increasing and represents a major public health burden. At the same time, improving access to imaging tests has increased the number of incidentally diagnosed adrenal tumors. Above all, the widespread use of chest computed tomography (CT) due to the COVID-19 pandemic has contributed to frequent incidental detection of adrenal lesions. Fortunately, a vast majority of these findings are asymptomatic benign tumors with no excessive hormonal activity, and therefore, they are defined as adrenal incidentalomas (AIs). Interestingly, recent studies have indicated that patients with AIs are more prone to obesity and insulin resistance. Although mutual relationships between the thyroid and the adrenal glands have been studied widely, still, little is known about the possible pathophysiological associations between thyroid autoimmunity and the occurrence of adrenal incidentalomas. This article presents a brief review of the common endocrine disorders with a special focus on the frequently coexisting insulin resistance and/or obesity. Furthermore, in response to the recent growing interest in endocrine disruptors, with their transgenerational epigenetic effects that influence hormonal system function, a concise overview of the topic has also been included.

Current Knowledge on Graves' Orbitopathy.

(1) Background: Graves' orbitopathy (GO) is an autoimmune inflammation of the orbital tissues and the most common extra-thyroid symptom of Graves' disease (GD). Mild cases of GO are often misdiagnosed, which prolongs the diagnostic and therapeutic process, leading to exacerbation of the disease. A severe course of GO may cause permanent vision loss. (2) Methods: The article presents an analysis of GO-its etiopathogenesis, diagnostics, current treatment and potential future therapeutic options based on a review of the currently available literature of the subject. (3) Results: Current treatment of the active GO consists predominantly in intravenous glucocorticoids (GCs) administration in combination with orbital radiotherapy. The growing knowledge on the pathogenesis of the disease has contributed to multiple trials of the use of immunosuppressive drugs and monoclonal antibodies which may be potentially effective in the treatment of GO. Immunosuppressive treatment is not effective in patients in whom a chronic inflammatory process has caused fibrous changes in the orbits. In such cases surgical treatment is performed-including orbital decompression, adipose tissue removal, oculomotor muscle surgery, eyelid alignment and blepharoplasty. (4) Conclusions: Management of GO is difficult and requires interdisciplinary cooperation in endocrinology; ophthalmology, radiation oncology and surgery. The possibilities of undertaking a reliable assessment and comparison of the efficacy and safety of the therapeutic strategies are limited due to the heterogeneity of the available studies conducted mostly on small group of patients, with no comparison with classic systemic steroid therapy. The registration by FDA of Teprotumumab, an IGF1-R antagonist, in January 2020 may be a milestone in future management of active GO. However, many clinical questions require to be investigated first.

Differences in Risk Factors for Diabetic Retinopathy in Type 1 and Type 2 Diabetes Mellitus Patients in North-East Poland.

Background and objective: Nowadays, diabetes is one of the main causes of blindness in the world. Identification and differentiation of risk factors for diabetic retinopathy depending on the type of diabetes gives us the opportunity to fight and prevent this complication. Aim of the research: To assess differences in the risk factors for diabetic retinopathy in type 1 and type 2 diabetes mellitus patients in Warmia and Mazury Region, Poland. Materials and Methods: Risk factors for diabetic retinopathy (DR) were assessed on the basis of an original questionnaire, which included: personal data, clinical history of diabetes and eye disease. Elements of clinical examination: blood pressure, BMI, waist circumference. Indicators of diabetes metabolic control: mean glycemia, glycated hemoglobin (HbA1c), total cholesterol and triglycerides, creatinine, glomerular filtration rate (GFR), albumin-creatinine ratio in urine. Results: The study group included 315 (26%) patients with DM1 and 894 (74%) patients with DM2. Risk factors were estimated on the basis of logistic regression and verified with Student's t-test. Statistically significant dependencies were found in both groups between the occurrence of diabetic retinopathy and diabetes duration, HbA1c, triglyceride concentrations, indicators of kidney function and cigarette smoking status. In the DM2 group, the development of DR was significantly influenced by the implemented models of diabetic treatment. Conclusions: In the whole study group, the risk of DR was associated with the duration of diabetes, HbA1c, triglyceride concentrations and smoking. In DM1 patients, the risk of DR was associated with diabetic kidney disease in the G1A1/A2 stage of chronic kidney disease, and in DM2 patients with the G2 stage of chronic kidney disease. An important risk factor for DR in DM2 patients was associated with late introduction of insulin therapy.

Markers of Subclinical Cardiovascular Disease in Patients with Adrenal Incidentaloma.

Due to the growing availability of imaging examinations the percentage of patients with incidentally diagnosed adrenal tumors has increased. The vast majority of these lesions are benign, non-functioning adenomas, although according to various estimates even up to 30%-50% of patients with adrenal incidentaloma may present biochemical hypercortisolemia, without typical clinical features of Cushing's syndrome. Adrenal adenomas secreting small amounts of glucocorticoids may cause morphological and functional changes in the myocardium and blood vessels. Early stages of cardiovascular remodeling may be observed among asymptomatic patients with adrenal adenoma. Vascular changes precede the development of cardiovascular diseases and can increase morbidity and mortality in patients with adrenal incidentaloma. This risk may result not only from the traditional risk factors. Seemingly hormonally inactive adrenal tumors can indeed produce small amounts of glucocorticoids that have metabolic implications. Therefore, evaluation of patients with incidental adrenal findings presenting with subclinical cardiovascular disease seems of particular importance.

ACTH-dependent Hypercortisolemia in a Patient with a Pituitary Microadenoma and an Atypical Carcinoid Tumour of the Thymus.

Cushing's syndrome (CS) is a set of clinical symptoms which occur as a result of hypercortisolemia. Endogenous ACTH-dependent CS related to an ectopic ACTH-secreting tumour constitutes 12%-17% of CS cases and is one of the most common causes of paraneoplastic syndromes. This study presents a case of a 31 year-old man with diabetes, hypertension, rosacea, purple stretch marks and hypokalemia. Findings of diagnostic procedures include high concentrations of cortisol and ACTH, pituitary microadenoma and a tumour in the anterior mediastinum. Dynamic hormone tests determined the source of excess hormone secretion and ectopic ACTH-dependent CS was diagnosed. Due to increasing symptoms of superior vena cava syndrome, an emergency resection of almost the whole tumour was performed, with only a small part of the upper pole left because of the proximity of large vessels and a risk of damaging them. On the basis of histopathological tests, an atypical carcinoid tumour of the thymus was identified. Immediately after the surgical procedure, there was a significant reduction of clinical and laboratory traits of hypercortisolemia, yet, during the 46 weeks of postoperative observation, despite chemotherapy, the progression of residual masses of the tumour occurred with metastases and increased hormone indices. The presented case shows and discusses the differentiation of ACTH-dependent hypercortisolemia and its causes, difficulties in surgical therapy and chemotherapy, as well as prognosis for atypical carcinoid of the thymus, which is a rare disease.