The following paper aims at describing the pathophysiology of Addison’s disease (ADD) which occurs due to insufficient production of steroid hormones. The paper will utilise an article titled “Autoimmune Addison’s disease- An update on pathogenesis” authored by Hellesen, Bratland, and Husebye (2018). The title is based on the pathogenesis of adrenocortical insufficiency. The article aims to highlight the role of immune-mediated attack on adrenocortical cells causing ADD. The authors explain that autoantibody against adrenal antigens leads to the immune-mediated destruction of the adrenal cortex. Also, genetic susceptibility, environmental triggering events, and intrinsic factors of the adrenal cortex play a significant role in ADD. Therefore, the article satisfactorily addresses the pathophysiology of Addison’s disease.
Article Summary
Hellesen, Bratland, and Husebye (2018) discuss that lymphocyte infiltration into the adrenal cortex causes adrenal glands to degenerate, leading to adrenal insufficiency. Lymphocytic cells form autoantibody which targets the steroids-synthesizing enzymes and affect the function of the adrenal gland in the secretion of hormones. The argument of the authors is based on data collected from an experiment on the effect of lymphocyte cell infiltration.
The inheritance of human leukocyte antigen (HLA) class II alleles leads to alteration of genetic makeup increasing the risk for autoimmune attack. Also, damage of the immune-related genes in the adrenal cortex responsible for the regulation of the activation of T cells and B cells are associated with an increased risk of autoimmune attack (Hellesen, Bratland, " Husebye 2018). The argument of the authors is theoretical with use of data collected from a meta-analysis of cohorts with ADD in Europe.
Hellesen, Bratland, and Husebye (2018) also explain that adrenocortical cells respond to inflammation caused by the lymphocytic cells by producing immune mediators necrotic tissue factor (TNF), cytokines and interleukin (IL) which cause tissue damage in the adrenal cortex resulting to adrenocortical insufficiency. The argument of the authors on the response of adrenocortical cells to lymphocytic cell infiltration is theoretical and provides adequate evidence and discussion to support the aims of this paper.
Article Critique
The objective of the study was to highlight the relationship existing between the adrenal cortex and the immune system in ADD. The title did not state the subject of the paper precisely because it focused on the autoimmune aspect of the pathogenesis whereas the article addressed the treatment (preventive and regenerative) strategies for adrenal insufficiency. The statement of purpose in the abstract was expounded in the introduction coherently. The researchers contextualized the paper by providing a background that focused on ADD pathogenesis and its connections to autoimmune factors and the adrenal cortex (Hellesen, Bratland, " Husebye 2018).
The method used in the study to elaborate the effect of lymphocyte cell infiltration on the adrenal cortex was valid for the study. Hellesen, Bratland, and Husebye (2018) isolated peripheral blood mononuclear cells (PBMCs) of both ADD patients and healthy individuals and stimulated them with enzyme 21 hydroxylase (21OH). The study indicated that among the patients with ADD, T-cells targeted at the enzyme site and damaged 21OH, whose primary role is the synthesis of steroid hormones (Dawoodji, Chen, Shepherd, Dalin, Tarlton, Alimohammadi, M " Bratland, 2014). The study positively indicated altered steroid synthesis as a result of lymphocyte cell infiltration. According to Eriksson, Bianchi, Landegren, Nordin, Dalin, Mathioudaki, and Karlsson (2016), antibodies against 21OH were detected in 85% of ADD patients.
The study was based on the diverse population of Norwegian and European cohorts; the study considered factors such as race that Skov, Höijer, Magnusson, Ludvigsson, Kämpe, and Bensing (2017) explain their significance in ADD pathogenesis. However, the study methodology failed to highlight the role of congenital hyperplasia which is relevant in the pathogenesis of ADD (Pazderska, Pearce " Mitchell, 2018). Eriksson et al., (2016) explained that congenital adrenal hyperplasia accounted for 72% of ADD diagnosis in the past.
The results of the study presented in the graph accurately described the content of the paper. The findings indicated the presence of 21OH specific T-cells in the PBMCs of ADD patients. Charmandari, Nicolaides, and Chrousos (2014) discussed that anti-adrenal autoimmunity leads to the production of 21OH antibodies. Furthermore, Michels A. and Michels N. (2014) explained that autoantibodies against 21OH are present in 90% of patients with ADD. Also, the researchers noted 86% of Norwegian patients as indicated by other studies were positive of autoantibodies against 21OH (Andreassen, Bratland, Reiner, Islam, Husebye " Bakke, 2014). The discussion of the study logically addresses the role of autoantibodies on the adrenal cortex leading to adrenal insufficiency as evidenced by the information in the study. Bjanesoy, Andreassen, Bratland, Reiner, Islam, Husebye, and Bakke (2014), similarly indicate autoantibody production against 21OH as the primary cause of adrenal insufficiency.
Conclusion
The research reported in the article failed to provide comprehensive information on the precise cause of autoantibody production against 21OH and why the enzyme was the primary target by the T cells. However, the study made a significant contribution to the knowledge and understanding of ADD pathophysiology. The analysis provided a practical approach of the pathogenesis of ADD through the use of cohorts and lab experiment. The study helps in improving the medical approach towards preventive and regenerative strategies in the management of ADD. Also, the research is subsequently supported by other conducted investigations on the pathogenesis of ADD. The study is effective in improving the understanding of ADD.
References
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Charmandari, E., Nicolaides, N. C., " Chrousos, G. P. (2014). Adrenal insufficiency. The Lancet, 383(9935), 2152-2167.
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Skov, J., Höijer, J., Magnusson, P. K., Ludvigsson, J. F., Kämpe, O., " Bensing, S. (2017). Heritability of Addison’s disease and prevalence of associated autoimmunity in a cohort of 112,100 Swedish twins. Endocrine, 58(3), 521-527.
