Review of literature
This review describes the lesions of the endocrine system that occur as a result of immunotherapy of cancer. This phenomenon is associated with the inhibition by monoclonal antibodies of checkpoints, which do not allow the immune system to affect tumor cells: CTLA-4, PD-1 and PD-L1. Immunotherapy by this group of drugs allows to increase the life expectancy of patients with cancer, but it also leads to the development of autoimmune endocrinopathies (thyroiditis, adrenalitis, diabetes mellitus, hypophysitis), which often manifest by life-threatening conditions. In view of the above, the necessity to carry out regular monitoring of the function of target organs in patients receiving immunotherapy for malignant tumors is discussed.
On the other hand, the phenomenon of developing the autoimmune endocrinopathies during therapy with immunological checkpoints inhibitors is of fundamental interest to endocrinologists. Iatrogenic lesions of the endocrine system are unique models of initiation of immune autoagression. Thus, the development of adrenalitis in patients receiving treatment with a PD-1 inhibitor suggests that the PD-1 is involved in the pathogenesis of autoimmune adrenal insufficiency in patients not receiving treatment with this drug. Thus, clarification of the role of PD-1 in the development of adrenalitis is required. The results of such investigations will allow to identify the risk groups for the development of autoimmune adrenal insufficiency and, accordingly, timely diagnosing it and beginning treatment.
Endocrine ophthalmopathy (EOP) is a chronic disease characterized by progressive autoimmune inflammation of the soft retrobulbar tissues in thyroid dysfunction. The orbital fibroblasts with their unique morphofunctional properties are very important in the pathogenesis of the infiltrative process and fibrosis of the extraocular muscles and/or retrobulbar tissue. They, unlike other localization fibroblasts, have not mesodermal, but neuro-ectodermal origin. The review acquaints with the immunological aspects of the regulation of these cells in different activity phases of disease. Intercellular interaction with T-lymphocytes (CD40-CD154) leads to orbital fibroblasts activation with increased expression of pathological receptors for thyroid-stimulating hormone, as well as production of intercellular matrix components, adhesion molecules, growth factors, cytokines and prostaglandins. Detailed morphofunctional characteristics of the orbit fibroblast subpopulations and mechanisms regulating their transdifferentiation into adipocytes and myofibroblasts are given. The analysis of literature data on the effect of T-helper type 17 on the functional activity of Thy1+/Thy1- (CD90+/CD90-) orbital fibroblasts is presented. The importance of the further study of the orbital fibroblasts characteristics in EOP and their intercellular interaction with various immune cells was noted, which may be able to uncover new pathogenetic mechanisms of this pathology.
The past few years have been actively discussing the role of individual macro- and micronutrients as factors regulating the functional activity of organs and systems and reducing the risk of developing a number of diseases, including thyroid diseases.
Selenium is one of the most important and intensively studied at present microelements. According to several studies, its low plasma level is associated with an increased risk of developing autoimmune thyroid diseases. In animal experiments, it was shown that a combined deficiency of selenium and iodine leads to more pronounced hypothyroidism than iodine deficiency alone. Some authors believe that cretinism in the newborn is a consequence of the combined deficiency of these two elements in the mother. It is also important that the optimal level of selenium is necessary both to initiate an immune response and to regulate an excessive immune response, as well as chronic inflammation.
The review article discusses the relationship between selenium and thyroid pathology, discusses the role of selenium in the physiology of the thyroid gland and in the development of autoimmune diseases. The biochemical aspects of the pathogenesis of thyroid disease are presented.
Case Report
Diabetes mellitus and primary hypothyroidism, in the outcome of chronic autoimmune thyroiditis, the two most common diseases in endocrinology and the practicing doctor are important not to forget about the possible association of these pathologies. This applies to patients with diabetes mellitus, both 1 and 2 types. However, the combination of these two pathologies is more common in type 1 diabetes, which is due to the autoimmune nature of these diseases. A clinical case of a patient with type 1 diabetes mellitus, which is on pump insulin therapy, is presented, which, in the background of previously selected therapy, during the last 2 months, episodes of hypoglycemia increased. In the course of the survey, primary subclinical hypothyroidism was identified, in the outcome of chronic autoimmune thyroiditis. Against the background of the achievement of euthyroidism, it was possible to achieve compensation of carbohydrate metabolism without correction of previously selected insulin therapy. The high incidence of thyroid dysfunction in patients with diabetes mellitus, and as a consequence, the deterioration in the compensation of carbohydrate metabolism, requires a systematic screening of thyroid disorders in the presence of diabetes mellitus.
Short messages
On the basis of the linear no-threshold theory, the Chernobyl accident was predicted to result in an incidence increase of various malignancies. In fact, there has been no cancer increase proven to be a consequence of the radiation exposure after the accident except for thyroid carcinoma in people exposed at a young age. Prior to the accident, thyroid cancer had been rarely diagnosed in children and adolescents. The ability of screening to enhance the registered incidence of thyroid tumors is known. The screening after the accident detected not only small tumors but also large neglected ones, sometimes misclassified as aggressive radiogenic cancers, which contributed to the concept of their aggressive behavior and early metastasizing. This had consequences for the practice: some experts recommended a more radical surgical treatment of supposedly radiogenic thyroid cancers. Such recommendations are generally not in agreement with the international practice. In conclusion, the treatment of Chernobyl-related thyroid carcinoma should not be different from that of sporadic one.
On June 14, 2018, at the age of 85, Maria Bronstein, a remarkable pathologist, died. The entire professional life of M. Bronstein was associated with the Endocrinology Research Centre (the Institute of Experimental Endocrinology and Chemistry of Hormones of the Russian Academy of Medical Sciences).
ISSN 2310-3787 (Online)