It is possible that the first description of the adrenal glands was by Claudius Galen (c. 130-201). It is apparent that Galen encountered the adrenal glands in his numerous dissections of animals, but he only described the left gland in his writings, and thought it to be accessory renal tissue. While the gland is described as "loose flesh," he clearly described the left adrenal vein connected to the left renal vein.
The first anatomist to give a detailed description of the human adrenal glands, was Bartholomeus Eustachius (1520- 1574), who was professor at the Collegio della Sapienza in Rome. In his publication of 1563 he described the "glandulae renibus incumbentes" and thought they had been overlooked, but in 1586, Piccolomini, who named the glands the suprarenals, disputed whether they were of any importance and felt they were merely "renal excrescences". Highmore suggested in 1651 that the suprarenals act to absorb exudates from the large vessels, and Thomas Wharton in 1656 suggested that the adrenals took something from the nerves and secreted it into the circulation. This was a surprisingly prescient suggestion as it mirrors the current concept of the neuroendocrine function of the adrenal medulla today. The Academy of Sciences in Bordeaux conducted an essay competition in 1716 to determine the function of the adrenal glands, but none of the entries were considered worthy of the prize. Many 17th and 18th century investigators felt that the adrenals altered the blood in some way, but their true function remained unknown until the 19th century.
In 1805 Cuvier defined the medulla and cortex of the adrenal gland, but the first complete description of the microscopic anatomy of the adrenal gland was by Albert von Kölliker (1817-1905) in 1852, after improvements in microscope technology. The central physiological role for the glands was not identified until 1849, when Thomas Addison presented a paper on the clinical features of patients with adrenal disease. In 1856, Charles Brown-Séquard provided experimental proof of the vital role of the adrenals by performing adrenalectomies (removing the adrenals) from several species of animals.
In 1886 Felix Fraenkel was the first to describe a patient with an adrenal tumour, a phaeochromocytoma in the adrenal medulla. Ten years later, Sir William Osler found that symptoms of adrenal insufficiency (Addison's disease) could be temporarily improved by an adrenal extract. Smith showed in 1926 that when the pituitary was removed, the adrenals atrophied. In the same year, Evans was able to prevent this by administration of a pituitary extract.