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Adrenal insufficiency There are two forms of adrenal insufficiency: primary and secondary. Primary adrenal insufficiency, or Addison’s Pathophysiology 180 disease, is due to the destruction of the adrenal gland. Secondary adrenal insufficiency is due to a disorder of the HPA system. Primary adrenal insufficiency (Addison’s disease) Addison’s disease is a relatively rare disorder in which all the layers of the adrenal cortex are destroyed. Most often the underlying problem is ideopathic adrenal atrophy, which probably has an auto immune basis. Addison’s disease is a chronic metabolic disorder that requires lifetime hormone replacement therapy. The adrenal cortex has a large reserve capacity, and the manifestations of adrenal insufficiency do not usually became apparent until about 90% of the gland has been destroyed. These manifestations are primarily related to: – hyperpigmentation resulting from elevated ACTH levels – mineralo corticoid deficiency and – glucocorticoid deficiency Hyperpigmentation in addison’s disease, ACTH levels are elevated in response to the fall in cortisone. It is important to note that the amino acid sequence of ACTH is strikingly similar to that of melanocyte stimulating hormone (MSH): thus, hyperpigmentation is seen in about 98% of persons with Addison’s disease and is helpful in distinguishing the primary Pathophysiology 181 and secondary forms. This hyperpigmenation becomes more pronounced during periods of stress.