HORMONES 291 



Note that the six substances differ chiefly in the presence or absence 

 of oxygen on carbons 11 and 17. They were first obtained as pure 

 chemical substances during the period 1935 to 1939. 



That the normal adrenal cortex has a number of functions has been 

 revealed by study of adrenalectomized animals and of human victims 

 of Addison's disease, a fatal illness caused by insufficient secretion of 

 adrenal hormones. In such cases there is a marked decrease in the ability 

 of the organism to work and to withstand stresses of any sort (for ex- 

 ample, fasting or exposure to cold). Sodium and chloride ions are ex- 

 creted in the urine in such excessive amounts that bodily supplies are 

 depleted, whereas excretion of potassium and urea are subnormal. Glyco- 

 gen disappears from the liver, great muscular weakness develops, and 

 growth ceases. 



The cortical hormones listed above differ in their ability to counteract 

 these symptoms. 11-Desoxycorticosterone is the most active member 

 of the group for regulating sodium, potassium, and chloride metabolism, 

 and for maintaining the life of adrenalectomized animals. Cortisone, 

 on the other hand, is relatively inactive in these respects, but it is the 

 most potent member of the group for increasing the ability to work and 

 resist stress and for stimulating glycogen formation. The other four 

 hormones have effects similar to one or the other of these two, or both. 



Addison's disease was for a time (and to some extent still is) treated with 

 cortical extracts following the work of Hartman and Brownell in 1930. 

 This treatment prolongs the life of the patients, but it is prohibitively 

 expensive and only partly successful. The use of 11-desoxycorticosterone, 

 after it became available about 1940, resulted in a major gain in life 

 expectancy, but even this hormone did not fully replace the missing 

 adrenal secretion. Most patients so treated lack normal vigor, and about 

 half die within seven years. The additional injection of cortisone may 

 quite possibly make up the deficiency, but sufficient amounts of cortisone 

 for clinical use have been produced only recently, and some years will 

 be needed to decide this question definitely. As might be expected from 

 the nature of their disturbed electrolyte metabolism, Addison's disease 

 patients are greatly benefited by diets low in potassium and high in 

 common salt. 



The opposite situation — oversecretion of adrenal cortical hormones — 

 is also a serious clinical condition. This may result from tumor growth 

 of the pituitary gland, which causes an increased secretion of a pituitary 

 hormone (adrenocorticotropic hormone, or ACTH) that stimulates the 

 adrenal cortex. In this condition (Cushing's syndrome) blood levels of 

 sodium are high and those of potassium low,, that is, just opposite from 

 the situation in Addison's disease. 



Tumor growth on the adrenal itself leads to secretion of male sex 

 hormones. If the patient happens to be an adult female, this results in 

 sex inversion (virilism) , which manifests itself by deepening of the voice, 



