Addison’s disease is a slowly by steadily progressing disorder affecting adults mostly in developed countries. The main chain of the pathogenesis is in the hypofunction of the suprarenal cortex occurs due to various reasons. Cortisol, the hormone produced by the adrenal cortex, affects different systems and organs in the human body. It impacts the level of blood pressure, metabolism, and digestion. Glucocorticoids and mineralocorticoids define the level of electrolytes in the circulation, and when imbalanced, it leads to various signs. That is why the symptoms of the disorder are wide and diverse, and a physician with sufficient knowledge should be able to identify them and unite them into one. The condition that has to increase the attention levels toward such patients is the adrenal crisis which is an acute state that can be seriously affecting human systems and organs. This assignment will disclose the etiology, pathogenesis, and clinical features of Addison’s disease.
The reasons that cause hypoadrenocorticism, or hypofunction of the adrenal cortex, are many. However, the exact triggering factors that lead to the destruction of the adrenal cortex cells are not yet known. One of the most frequent reasons for Addison’s disease is autoimmune mechanism solely or as a part of various polyglandular syndromes. Infections such as tuberculosis and other bacterial, viral, fungal, and parasitic agents are other reasons that can destroy the tissue of the cortex. According to the data provided by Hellesen and Bratland, tuberculosis was more important for the etiology of the disease in earlier years, when the world population was striving significantly from the pathogenic effects of Mycobacteria (52). Currently, the infection is under more control than in the previous century, and the autoimmune character is the primary mechanism of Addison’s disease.
Other factors can also play an important role in the initiation of the disorder. Betterle et al. state that various essential infectious agents there are Neisseria meningitides, Pseudomonas aeruginosa, Haemophilus influenza, Treponema pallidum, and Escherichia coli, HIV, HSV, and Toxoplasma gondii (1410). Dysmetabolic disorders that lead to infiltrations and various granulomas in the cortex are amyloidosis, sarcoidosis, xanthogranulomatosis, and hemochromatosis (Betterle et al. 1410). There is also a variety of genetic and neonatal pathologies, vascular diseases, pharmacological specialties, neoplastic, and surgical reasons leading to the development of Addison’s disease (Betterle et al. 1410). In general, the pathogenesis can take roots from the hypofunction of the hypophysis, and it is significant to understand the level of disorder and differentiate Addison’s disease from other endocrinological disease areas.
As it became clear above, the key to the pathogenesis is the destruction of the adrenal cortex tissue due to various factors. The adrenal cortex synthesizes corticosteroids and mineralocorticoids that realize different effects. Cortisol is an essential corticosteroid that realizes anti-inflammatory and antiallergic effects, accelerates the synthesis of glucose in the liver, glucose synthesis from proteins, and stimulates glycogenesis (Napier et al. 2323). Mineralocorticoid aldosterone is responsible for water-electrolyte metabolism by saving sodium, chlorine, and water molecules in blood flow and tissues and fosters the filtration of potassium with urine. As a result, deficiency of these hormones and their metabolites are causing metabolic and water-electrolyte disbalances leading to various signs and symptoms.
The elevation of potassium in blood flow and the excretion of sodium, chlorine, and water molecules decrease the circulating blood volume and consequently lower blood pressure. The latter inevitably leads to heart insufficiency, tachycardia, and hypotension. The lack of aldosterone deteriorates glucose, protein, and fat metabolism elevating the sensitivity to insulin, hypoglycemia, and the decrease of glucose storage in the liver (glycogen) (Hellesen and Bratland 56). Due to these mechanisms, the efficient work of nervous and muscular systems lowers. The lack of adrenal cortex hormones, with the help of a negative feedback mechanism sends signals to superior organs of the hypothalamic-pituitary-adrenal system (Hellesen and Bratland 56). As a result, the adrenocorticotropic hormone is being produced in larger amounts, as well as beta-lipotropin (a melanocyte-stimulating hormone). The latter leads to hyperpigmentation of the skin and mucosae of the patients.
The difficulty in diagnostic search is the unspecific signs of the disease, such as fatigue, malaise, nausea, and weight loss. The other major symptom is the pigmentation of the skin and mucous membranes, which is a darkening of the skin, especially in the palmar folds, on the interphalangeal joints, scars, and oral mucosa. The hyperpigmentation is located in the areas protected from the insolation, which is a significant differentiative sign that the patient was on vacation in a warm country. Later, orthostatic hypotension and hypoglycemia appear in the later stages of the disease, and it still is not simple to recognize the origin of the pathology.
As autoimmune genesis is currently believed to be the most frequently met, there is data proving that Addison’s disease tends to be a part of polyglandular syndromes. The disease is believed to be associated with chronic hypoparathyroidism, autoimmune thyroid disease, diabetes mellitus type 1, vitiligo, and alopecia areata (Betterle et al. 1413). Autoantibodies synthesis could take similar mechanisms with similar receptors and signal molecules. Current medicine has already identified four autoimmune polyglandular syndromes, which represent a variety of combinations of Addison’s disease with other pathologies. Knowing the tendency of the nosology to unite with other diseases should be essential for the physician and his tactics in diagnostic search.
Therefore, this paper studied the specialties of Addison’s disease. During the disorder, the damage to adrenal cortex tissue occurs, which consequently ends in the lack of essential hormones, cortisol and aldosterone. Lack of cortisol impacts the metabolism of glucose, protein, and fat; leads to the possible elevation of inflammatory and allergic reactions. Aldosterone deficiency increases potassium levels in blood flow which ends in severe tachycardia, hypovolemia, low blood pressure, and postural hypotension.
The major clinical complication is in the slow and non-specific initiation of the symptoms as fatigue, nausea, and weight loss can occur as features of oncology, hypothyroidism, and other disorders. The physician should pay attention to any signs and patient complaints that could lead to the diagnosis. The major concern should be focused on an acute and life-threatening condition called adrenal crisis with severe hypoglycemia, hypotension, and a rapidly increasing level of urea in the blood. Additionally, as various factors can cause Addison’s disease, a thorough history of the patient has to be gathered to understand the possible reasons for the development of the disorder.
Autoimmune Addison’s disease is currently dominating out of all etiological agents, and the possible convergence with other disorders should be expected. Diagnostic searches can be focused on thyroid gland disorders, chronic hypoparathyroidism, and other autoimmune pathologies such as vitiligo and alopecia areata. Most likely, the treatment of one nosology together with another autoimmune disease can show promising results and prognosis.
Betterle, Corrado, et al. “Epidemiology, Pathogenesis, and Diagnosis of Addison’s Disease in Adults.” Journal of Endocrinological Investigation. vol. 42, no. 12, 2019, pp. 1407-1433.
Napier, Catherine, et al. “Natural History of Adrenal Steroidogenesis in Autoimmune Addison’s Disease Following Diagnosis and Treatment.” The Journal of Clinical Endocrinology & Metabolism, vol. 105, no. 7, 2020, pp. 2322–2330.
Hellesen, Alexander, and Eirik Bratland. “The Potential Role for Infections in the Pathogenesis of Autoimmune Addison’s Disease.” Clinical and Experimental Immunology, vol. 195, no. 1, 2019, pp. 52–63.