Topic 48 Adrenal cortex

In bony fishes, corticosteroids are secreted from the interrenal tissues (analogous to the adrenal cortex) located in the head kidney region121 182. Cortisol is the major steroid released from these cells in response to neuroendocrine stimulation emanating from the hypothalamus and the pituitary (see Chapter 12). The release of cortisol in response to stress has been characterized in several species and also in response to different stressors and this topic has been extensively reviewed1011 70 182. Cortisol... 

The use of corticosteroids in the treatment of septic shock has been a topic of controversy for many years. A meta-analysis of early studies of steroids in sepsis demonstrated a lack of benefit and potential harm in sepsis and septic shock. There is a renewed interest in corticosteroid use because of the increased awareness of adrenocortical insufficiency in critically ill patients with septic shock. Relative adrenal insufficiency has been defined as a poor adrenal response [<250 nmol/L (9 mcg/dL) irrespective of the initial serum cortisol level] to a dose of synthetic adrenocorticotropic hormone (ACTH), indicating a low fnnctional reserve of the adrenal cortex. Although absolute insufficiency is rare, relative adrenocortical insufficiency in the presence of normal or high cortisol concentrations at baseline is present in 30% to 50% of patients with septic shock and is associated with a poor outcome. ... 

In 1948, Edward C. Kendall, who clarified steroid structures during the 1930s (see chapter 4), and Philip S. Hench (1896-1965), at the Mayo Clinic, demonstrated that the steroid hormone cortisone relieves symptoms of rheumatoid arthritis. Kendall, Hench, and Tadeus Reichstein would share the 1950 Nobel Prize in physiology or medicine. Although Lewis Sarett (1917-99) at Merck had accomplished a total synthesis of cortisone in 1944 (Woodward published a more elegant one in 1951), cortisone and its close derivatives would have remained extremely expensive were it not for the efforts of Percy L. Julian (1899-1975). As soon as he learned of the Mayo Clinic discovery, Julian developed a rapid, inexpensive synthesis of Reichstein s Substance S, also isolated ftom the adrenal cortex. This steroid is easily converted to dihydrocortisone and Julian s pathway remains today the major commercial route to this over-the-counter topical remedy for sunburn, mosquito bites, and other uncomfortable skin irritations. 

Cortisone is a natural steroid that can be isolated from the adrenal cortex. It has anti-inflammatory properties and is used to treat a variety of disorders (e.g., as a topical application for common skin diseases). The structure of cortisone is shown in Section 23-4D. (a) Identify all of the chirality centers in cortisone, (b) Assign the appropriate m or (5) designation for the configuration of each chirality center in cortisone. 

Side effects of topical administration of steroids have been reviewed recently (124 ). Further cases with Cushing s syndrome secondary to topical steroid therapy have been reported (131 ). It was shown that treatment with less than 50 g of clobetasol propionate ointment per week has no suppressive effect on the adrenal cortex. When more than SO g of ointment per week was used, a significant number of patients owed adrenocortical suppression (4 ). 

---