History of Adrenal Surgery

Adrenal anatomy

Claudius Galen (c. 130-201) appears to have given the first description of the adrenal glands, having encountered them in his numerous dissections of animals. He only described the left gland in his writings, and thought it to be accessory renal tissue, but while the gland is described as "loose flesh," he in fact clearly described the left adrenal vein connected to the left renal vein. 

Fig.1: Bartholomeus EustachiusFig.2: Tabulae Anatomicae published 1714The 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 (Fig. 1).  In his publication of 1564 he described the "glandulae renibus incumbentes" and thought they had been overlooked by other anatomists (perhaps referring to Vesalius, who had missed them in his seminal work of anatomy "De Humanis Corporis Fabrica" of 1543. 

Eustachius had planned his own anatomical work to rival that of Vesalius, and had prepared 47 engraved copper plates by Roman artist Pier Matteo Pini to illustrate the text. Eustachius died before completing this project, so that only the first 8 plates were published in the preliminary Opuscula Anatomica, with a clear illustration of the adrenals sitting atop the kidneys.

Pini’s engraved plates found their way to the papal library, where they remained for about 150 years, until Pope Clement XI gave them to his personal physician, Giovanni M. Lancisi, who published all 47 plates, plus his own notes, in 1714 as "Tabulae Anatomicae Clarissimi viri Bartholomaei Eustacci" (Fig. 2). Eustachius’ work was not widely known and most anatomists became familiar with his work following its publication by Lancisi in 1714.

In 1627, Giulio Cesare Casseri (1552-1616) published an illustration of the adrenals atop the kidneys, which may have been the first widely seen illustration of the correct anatomy.

Between 1650 and 1750, multiple anatomists described the adrenals as hollow, fluid-filled organs. The Danish anatomist Caspar Bartholin the Elder (1585-1629), who described the adrenals as filled with “black bile,” probably was actually referring to the medulla undergoing postmortem autolysis. His son, Thomas Bartholin, who followed his father as professor of anatomy at the University of Copenhagen, described different anatomic appearances of the adrenal, including the hollow adrenal filled with “black bile”. 

In 1805 Georges Cuvier, Professor of Animal Anatomy at the Museum of Natural History in Paris, showed that the adrenal gland was in fact a solid organ, and defined the medulla and cortex. However, 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. 

Adrenal Function

In 1586, Piccolomini, who named the glands the suprarenals, disputed whether they were of any importance at all, and even if they existed, feeling that 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.

Fig.3: Thomas AddisonThe 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.

The central physiological role for the glands was not identified until 1849, when Thomas Addison (Fig. 3) presented a paper on the clinical features of patients with adrenal disease. Addison was one of the famous physicians and scientists of Guy's Hospital in London, describing not only adrenal gland insufficiency (which came to be known as Addison's Disease) but also the features of pernicious anaemia.

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.

Fig.4: Harvey CushingAlthough the famous Thomas Addison described his disease in 1849, it was another 60 years before the American Harvey Cushing (Fig. 4) described the disease which bears his name - Cushing's disease. In 1912 he reported in a study an endocrinological syndrome caused by a malfunction of the pituitary gland which he termed "polyglandular syndrome". He published his findings in 1932, as "The Basophil Adenomas of the Pituitary Body and Their Clinical Manifestations (Pituitary Basophilism)".

Regardless of whether the primary lesion was in the pituitary (Cushing's Disease) or in the adrenal, the symptoms and signs were due to excessive secretion by the adrenal cortex, which came to be known as Cushing's Syndrome.

Treatment by surgery seemed appropriate but without replacement of adrenal function the operation proved fatal. Work on adrenocortical extracts to use as replacement therapy continued through the 1930s under Kendall and Reichstein, with the realisation that the essential components were steroids.

The structures of the adrenal steroids were gradually established during the 1930s and 1940s. The biochemical studies of the structure and synthesis of adrenocortical steroids by Reichtenstein in Switzerland, and Kendall and Hench in the U.S.A., resulted in the award of the Nobel Prize in physiology and medicine in 1950. In 1948, the first steroid, cortisone, was used clinically for its anti-inflammatory properties. The following year it was successfully used to cover adrenalectomy for Cushing's syndrome.

Fig.5: Jerome ConnIt was more than 100 years after Addison that Jerome Conn first described the syndrome of primary hyperaldosteronism in 1955 (Fig. 5). Conn had taken over the Division of Endocrinology and Metabolism at the University of Michigan in 1943, conducting a series of acclimatisation experiments looking at the hormonal regulation of salt excretion.

Although aldosterone was first isolated in 1950, Conn used the occasion of his presidential address to the Central Society for Clinical Research on October 29, 1954, to present his extensive clinical investigations of a  patient with this new syndrome, which he called primary aldosteronism. The following December the patient had a surgical exploration of her adrenal glands and a 4-centimeter tumor was found.

The system that controlled it (the renin-angiotensin system) was worked out over the following decade.

Adrenocortical syndromes had been recognised long before the hormones were discovered, but the adrenal medullary hormone adrenaline was discovered long before any pathological role was found for it.

The clinical features of phaeochromocytoma had been described some years before that, but it was a long time before the hormone, the tumour and the clinical manifestations were found to be related. Surgical removal of a phaeochromocytoma was always fatal until 1926, but after this time mortality steadily improved, with better anaesthesia, intensive care and new surgical techniques, to its very low rate today.

Finally, the part played by the pituitary as the master controller of  adrenal gland function was first deduced by Smith in 1930, and ACTH, the ptuitary's controlling hormone, purified in 1943.

Adrenal surgery

The first successful adrenalectomy was carried out by Knowsley-Thornton as early as 1889, but before the relatively modern developments of adrenal imaging and the understanding of hormonal function, adrenal surgery was generally confined to large, symptomatic tumours felt on abdominal examination. The first successful operations for phaeochromocytoma were not in fact carried out until 1926, by Charles Roux in Switzerland and Charles Mayo in the USA.

Early approaches were transabdominal, via large incisions similar to those used for gall bladder and stomach surgery. The high retroperitoneal position of the adrenals however, led to the description of a posterior approach in 1932 by Broster of London. The flank approach was described by George Crile of the Cleveland Clinic, and Charles Mayo used this approach to successfully remove a phaeochromocytoma in 1927.

Further developments in the twentieth century, and the refinement in the use of the laparoscope, has culminated in the current safe, and preferred, method of laparoscopic adrenalectomy, by either transabdominal and posterior routes.