The First Organ Disease of the Adrenal Gland

The adrenal gland had been associated with a specific disease entity by the British doctor Thomas Addison as early as 1855. Using the approach typical for medical science in his day, Addison combined clinical with anatomico- pathological observations. The disease he described was characterized by anemia, overall weakness, and a bronze-colored darkening of the skin. In autopsies he observed that patients with this set of symptoms exhibited lesions of the adrenal gland after death. Addison therefore made the organ damage responsible for the clinical picture.

Physiologists soon began to generate this clinical picture artificially by purposely destroying the adrenal glands in animals. In 1856 Brown-Séquard noticed how laboratory animals died after the experimental removal of their adrenal glands, and the symptoms they exhibited reminded him of Addison’s descriptions. When he observed that, furthermore, the injection of blood from a rabbit that had died as a result of adrenal gland extirpation caused the death of healthy animals, but that the transfusion of the blood of a healthy rabbit ensured the survival of animals lacking adrenal glands, he concluded that a toxic substance normally neutralized by the adrenal gland accumulated in the blood after the removal of the organ. Since other researchers came to different conclusions, however, it took over four decades to arrive at a general consensus on the connection between adrenal insufficiency and so-called Addison’s disease.

One major problem was to establish a constantly observable clinical picture. This task was difficult and controversial enough in the case of human patients, but developing an animal model for it caused even greater problems. Because the symptoms of patients with Addison’s disease were hard to compare with the symptoms that appeared after the destruction or removal of adrenal glands in animal test subjects, a laboratory animal’s death often served as the lone indicator of the glands’ failure. As in the ablation experiments with other organs, attributing the cause of the phenomena that appeared after ablation to the lack of the organ itself was disputed. At first, it looked as though other injuries caused by the operation could be responsible for the postoperative symptoms, and damage to nerve centers in the area of the operation—certain ganglia, the sympathetic trunk, and the like—was often used to explain them.