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.

The co-occurrence of SAT, hypophysitis, and Schnitzler syndrome after COVID-19 vaccination: the first described case.

Subacute thyroiditis (also known as granulomatous thyroiditis, giant cell thyroiditis, de Quervain's disease, or SAT) is an inflammatory disease of the thyroid gland, usually spontaneously remitting, that lasts for weeks to months. However, recurrent forms sometimes occur which may have a genetic basis. In our paper, we have focused on the pathogenetics, symptoms, and treatment of SAT. We have described the 17-month disease course of a woman with persistent recurrent steroid-resistant SAT. SAT was well established and the patient's symptoms were not only recurrent neck pain with fever, but also recurrent chronic urticaria, which are symptoms that fulfil the criteria for the diagnosis of Schnitzler syndrome. Schnitzler syndrome occurred after vaccination with COVID-19 in the mechanism of ASIA syndrome. In our patient, Schnitzler syndrome involved the thyroid gland, causing persistent subacute thyroiditis, and the pituitary gland, causing transient swelling of the pituitary, which, to our knowledge, is the first reported case in the literature. Also unprecedented, as far as we know, is the fact that we performed thyroidectomy in the above patient, which reduced systemic inflammation and caused SAT to resolve, although only the inclusion of anakinra treatment resulted in resolution of the underlying condition.

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.

Can Iron Play a Crucial Role in Maintaining Cardiovascular Health in the 21st Century?

In the 21st century the heart is facing more and more challenges so it should be brave and iron to meet these challenges. We are living in the era of the COVID-19 pandemic, population aging, prevalent obesity, diabetes and autoimmune diseases, environmental pollution, mass migrations and new potential pandemic threats. In our article we showed sophisticated and complex regulations of iron metabolism. We discussed the impact of iron metabolism on heart diseases, treatment of heart failure, diabetes and obesity. We faced the problems of constant stress, climate change, environmental pollution, migrations and epidemics and showed that iron is really essential for heart metabolism in the 21st century.

Evaluation of Morphological Changes in Retinal Vessels in Type 1 Diabetes Mellitus Patients with the Use of Adaptive Optics.

INTRODUCTION: Diabetes mellitus contributes to the development of microvascular complications in the eye. Moreover, it affects multiple end organs, including brain damage, leading to premature death. The use of adaptive optics technique allows to perform non-invasive in vivo assessment of retinal vessels and to identify changes in arterioles about 100 µm in diameter. The retinal vasculature may be a model of the cerebral vessels both morphologically and functionally. Aim. To evaluate morphological parameters of retinal arterioles in patients with type 1 diabetes mellitus (DM1). Material and methods. The study included 22 DM1 patients (13 females) aged 43.00 ± 9.45 years with a mean diabetes duration of 22.55 ± 10.05 years, and 23 healthy volunteers (10 females) aged 41.09 ± 10.99 years. Blood pressure, BMI, waist circumference, and metabolic control markers of diabetes were measured in both groups. Vascular examinations were performed using an rtx1 adaptive optics retinal camera (Imagine Eyes, Orsay, France); the vessel wall thickness (WT), lumen diameter (LD), wall-to-lumen ratio (WLR), and vascular wall cross-sectional area (WCSA) were assessed. Statistical analysis was performed with the application of IMB SPSS version 23 software. Results. The DM1 group did not differ significantly in age, BMI, waist circumference, blood pressure, or axial length of the eye compared to the control group. Intraocular pressure (IOP) in both groups was normal, but in the DM1 group it was significantly higher. The DM1 group had significantly higher WT, WLR, and WCSA. These parameters correlated significantly with the duration of diabetes, but not with IOP. Conclusions. The presented study demonstrates the presence of significant morphological changes in retinal vessels in DM1 patients without previously diagnosed diabetic retinopathy. Similar changes may occur in the brain and may be early indicators of cardiovascular risk, but further investigation is required to confirm that.

Iron: Not Just a Passive Bystander in AITD.

Autoimmune thyroid disease (AITD) is the most prevalent autoimmune disease all over the world and the most frequent cause of hypothyroidism in areas of iodine sufficiency. The pathogenesis of AITD is multifactorial and depends on complex interactions between genetic and environmental factors, with epigenetics being the crucial link. Iron deficiency (ID) can reduce the activities of thyroid peroxidase and 5'-deiodinase, inhibit binding of triiodothyronine to its nuclear receptor, and cause slower utilization of T3 from the serum pool. Moreover, ID can disturb the functioning of the immune system, increasing the risk of autoimmune disorders. ID can be responsible for residual symptoms that may persist in patients with AITD, even if their thyrometabolic status has been controlled. The human lifestyle in the 21st century is inevitably associated with exposure to chemical compounds, pathogens, and stress, which implies an increased risk of autoimmune disorders and thyroid dysfunction. To summarize, in our paper we discuss how iron deficiency can impair the functions of the immune system, cause epigenetic changes in human DNA, and potentiate tissue damage by chemicals acting as thyroid disruptors.

"Ferrocrinology"-Iron Is an Important Factor Involved in Gluco- and Lipocrinology.

"Ferrocrinology" is the term used to describe the study of iron effects on the functioning of adipose tissue, which together with muscle tissue makes the largest endocrine organ in the human body. By impairing exercise capacity, reducing AMP-activated kinase activity, and enhancing insulin resistance, iron deficiency can lead to the development of obesity and type 2 diabetes mellitus. Due to impaired browning of white adipose tissue and reduced mitochondrial iron content in adipocytes, iron deficiency (ID) can cause dysfunction of brown adipose tissue. By reducing ketogenesis, aconitase activity, and total mitochondrial capacity, ID impairs muscle performance. Another important aspect is the effect of ID on the impairment of thermogenesis due to reduced binding of thyroid hormones to their nuclear receptors, with subsequently impaired utilization of norepinephrine in tissues, and impaired synthesis and distribution of cortisol, which all make the body's reactivity to stress in ID more pronounced. Iron deficiency can lead to the development of the most common endocrinopathy, autoimmune thyroid disease. In this paper, we have discussed the role of iron in the cross-talk between glucocrinology, lipocrinology and myocrinology, with thyroid hormones acting as an active bystander.

Is there a relationship between the prevalence of autoimmune thyroid disease and diabetic kidney disease?

Autoimmune thyroid disease (AITD) is more common among diabetes mellitus (DM) patients and may impact its microvascular complications. The present study aimed to assess the relationship between AITD and the prevalence of diabetic kidney disease (DKD) in patients with diabetes mellitus type 1 (DM1). Anthropometric parameters, parameters of metabolic control of DM, thyreometabolic status, and the UACR were assessed. DKD was diagnosed if patients' UACR level was ≥30 mg/g or eGFR level was <60 mL/min. This study involved 144 patients with DM1 aged 36.2 ± 11.7 years: 49 men and 95 women. Significant differences in creatinine, eGFR, and UACR levels were found in patients with DKD. fT3 concentration was significantly lower among DKD patients. A significantly higher probability of DKD was found in DM1 patients with lower fT3 levels. Patients with DM1 and AITD had significantly lower creatinine levels than the control group. However, the study did not show any significant relationship between AITD and the occurrence of DKD in patients with DM1. Significantly lower fT3 concentrations in DKD patients may be caused by metabolic disorders in the course of DKD and require further cohort studies in a larger population of patients with DM1 and AITD.

The Safety of Pharmacological and Surgical Treatment of Diabetes in Patients with Diabetic Retinopathy-A Review.

BACKGROUND: Diabetes mellitus (DM) is a non-infectious pandemic of the modern world; it is estimated that in 2045 it will affect 10% of the world's population. As the prevalence of diabetes increases, the problem of its complications, including diabetic retinopathy (DR), grows. DR is a highly specific neurovascular complication of diabetes that occurs in more than one third of DM patients and accounts for 80% of complete vision loss cases in the diabetic population. We are currently witnessing many groundbreaking studies on new pharmacological and surgical methods of treating diabetes. AIM: The aim of the study is to assess the safety of pharmacological and surgical treatment of DM in patients with DR. MATERIAL AND METHODS: An analysis of the data on diabetes treatment methods currently available in the world literature and their impact on the occurrence and progression of DR. RESULTS: A rapid decrease in glycaemia leads to an increased occurrence and progression of DR. Its greatest risk accompanies insulin therapy and sulfonylurea therapy. The lowest risk of DR occurs with the use of SGLT2 inhibitors; the use of DPP-4 inhibitors and GLP-1 analogues is also safe. Patients undergoing pancreatic islet transplants or bariatric surgeries require intensive monitoring of the state of the eye, both in the perioperative and postoperative period. CONCLUSIONS: It is of utmost importance to individualize therapy in diabetic patients, in order to gradually achieve treatment goals with the use of safe methods and minimize the risk of development and progression of DR.

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.