Countless articles and references describe the first recognised successful parathyroidectomy performed by Felix Mandl in 1925 on a Viennese streetcar conductor with osteitis fibrosa cystica. However that procedure may not have been the first successful removal of a parathyroid tumour associated with symptoms of hyperparathyroidism The following extract from Sir John Bland-Sutton’s 1917 textbook of pathology, “Tumours Innocent and Malignant” demonstrates that the first successful parathyroidectomy may well have unwittingly preceded any knowledge of the condition of hyperparathyroidism. “An enormous literature has grown up around the parathyroids. Some surgeons are of the opinion that the importance attached to these minute bodies is exaggerated. Berry regards the parathyroids as outlying portions of thyroid tissue, and believes that their tissue differs from that of the vesicular epithelium only in not having secreted colloid: similar tissue is found in great abundance in embryos and young animals generally; it is undeveloped thyroid tissue. Apart from the physiological aspect, the parathyroids are of interest to surgeons. These bodies lie close to the trachea, and it is obvious that if one should enlarge, even moderately, it would be in a position to exert harmful pressure on the trachea. I have seen two examples. A man aged 36 was found lying on his back in a street adjacent to Middlesex Hospital, apparently in a fit; when brought into the casualty-room he was dead. At post-mortem examination a tumour was found connected with the cervical portion of the windpipe, embedded in a thick fibrous capsule, its inner segment being firmly fixed to the trachea between the fourth and ninth semi-rings. This tumour had fatally compressed the trachea; its central portions had the microscopic structure of a parathyroid. the tumour could have been easily enucleated from its capsule. The second example occurred in a young married woman. She was on a ship in the Red Sea, and had great difficulty in breathing; a small rounded lump was detected in her neck below the thyroid gland. It increased in size and the dyspnoea became so urgent that one night the patient was prepared for tracheotomy and the ship’s surgeon remained by the bedside with his instruments. Fortunately the swelling subsided. On her return to England, I removed a rounded body, as big as a cherry, situated below the lower angle of the thyroid gland on the left side of the trachea. It had the microscopic features of a parathyroid gland.”

The first described operation for insulinoma was in an orthopaedic surgeon, Dr Dickinson Ober Wheelock. Wheelock was first seen at the Mayo Clinic in 1922 with “stomach trouble” and diagnosed as chronic cholecystitis. He had previously undergone a laparotomy and gastroenterostomy in 1918 for attacks of epigastric pain and ”shock”. He returned to the Mayo Clinic in 1926 with recurrent symptoms. His referral letter at the time from his GP, Dr McWhorter, stated that “he was at the Mayo Clinic earlier but did not receive any help and was quite dissatisfied. I think someone picked him for a ‘nut’ and he was sent home with advice to take a rest and the usual line of b.s. handed the ‘nuts’.” Dr McWhorter provided some family history. “Dr ES Muir of Winona, who died in 1919 was a cousin of Dr Wheelock and had the same symptoms. Dr. Muir’s wife stated that she could restore him to consciousness by giving him hot sweet coffee. Dr Muir died in coma following a maniacal attack after consultation by his doctors who decided that there was nothing wrong with him except nervousness. Wheelock is an exceptional case – try and get someone interested in him and don’t let him die because he sure will if he goes too long without carbohydrate.” Interestingly Wheelock also gave a history of having passed renal stones. His physicians realised that he needed up to 25 g glucose per hour to maintain an asymptomatic state and so he was referred for surgery which was undertaken by Will Mayo on December 4th 1926. At operation a malignant pancreatic tumour and liver metastasis were biopsied. Struck by the similarity of the attacks with insulin shock, his physician, Dr Russell Wilder, injected tumour extract into rabbits with intriguing results. Post-operatively Wheelock did poorly, dying of “no apparent reason than exhaustion”. Autopsy confirmed carcinoma of the pancreas with liver metastases but no mention was made about the presence of abnormal parathyroid glands, although this is not surprising as the first operation on the parathyroid glands at the Mayo Clinic would not occur for another 7 years. With hindsight, it more than likely that Wheelock had the MEN1 syndrome.

Condensed from - Van Heerden J. Mayo Clinic Proceedings 1999;74:73

The tubercle of Zuckerkandl is a distinct anatomical entity that was first described by Emil Zuckerkandl in 1902. The description, and the clinical significance of the tubercle, was lost to endocrine surgeons until the last decade when the tubercle was “rediscovered” by a number of authors. Thyroid development involves the midline descent of thyroid tissue from the foramen caecum to the level of the larynx along the thyroglossal tract, at which stage the left and right lobes develop. What is not as well appreciated is that there is, in addition, a lateral thyroid component arising from the 4th branchial cleft and ultimobranchial body which fuses with the median component to form the tubercle of Zuckerkandl. This fusion is not only the source of the thyroid’s C-cells, but is also essential in the process of follicular development. Emil Zuckerkandl studied medicine at the University of Vienna in 1867 and distinguished himself such that eventually, following the death of Langer in 1888, he assumed the Chair in Anatomy at Vienna. He was noted for his sharp observational powers and critical mind making significant contributions to normal and pathological anatomy. He is also one of the very few medical scientists who is remembered as much for his wife, Bertha Zuckerkandl-Szeps, one of the most remarkable personalities of intellectual Jewish society in Vienna during the last decades of the Austro-Hungarian empire. Their house became the meeting point for the avant garde in arts and science, including the sculptor Auguste Rodin and the composer Gustav Mahler. Zuckerkandl’s name is associated with seven eponymous anatomical/surgical entities:

• The Organ of Zuckerkandl – a mass of chromaffin tissue found adjacent to the anterior aspect of the aorta, between the inferior mesenteric artery and the aortic bifurcation
• Zuckerkandl's fascia - the posterior layer of the renal fascia
• Zuckerkandl's gyrus (Zuckerkandl's convolution) - the thin sheet of grey/white substance in front of, and ventral to, the genu of the corpus callosum
• The Concha of Zuckerkandl - a rarely found small nasal concha situated above the supreme nasal concha
• Zuckerkandl's dehiscence - small gaps occasionally seen in the layers of the ethmoid bone
• Zuckerlandl's operation - perineal prostatectomy
• The tubercle of Zuckerkandl – a posterolateral projection of the thyroid gland derived from the 4th branchial cleft

The importance of the tubercle of Zuckerkandl is that, if not looked for and removed during thyroid surgery, it may be a source of persistent unrelieved symptoms or recurrence. An understanding of the anatomy of the tubercle of Zuckerkandl is also central to safe surgical dissection. It usually enlarges lateral to the recurrent laryngeal nerve, with the nerve appearing to pass into a cleft medial to it – a situation that some surgeons used to describe as the nerve passing into the thyroid substance. Early elevation of the tubercle of Zuckerkandl usually allows the recurrent nerve to be easily and safely “encountered” even though not initially visible. However an uncommon but high risk situation is where the recurrent laryngeal nerve runs lateral to an enlarged Tubercle of Zuckerkandl, placing it at increased risk of damage during dissection. Another important point is that the normal superior parathyroid gland, also being derived from the 4th branchial cleft, is commonly found in close association, cephalad to the Tubercle of Zuckerkandl.

The first pituitary operation was performed by Victor Horsley, of London, in 1889. Horsley was a general surgeon who pioneered intracranial operations. By 1913 the results of his first four craniotomies were published: all had visual field defects and headaches. One died after six hours, and the other three had serious complications, however they survived between nine months and eight years. At this stage neurosurgeons began to devise extracranial approaches to the pituitary. There were three main problems: to discover the best route to the pituitary; to avoid serious infection; and to prevent disfigurement after removal of facial and nasal bones. Herman Schoffler, of Innsbruck, performed the first extracranial procedure on a patient with a large tumour by mobilising the nose on a pedicle, opening the entire nasal cavity, and removing the tumour piecemeal. The patient lost his headaches but did not recover his sight, living 10 weeks. Eiselberg, of Vienna, introduced a modification to reduce facial deformity, however infection remained a major problem, either causing death from meningitis, or a persistent offensive nasal discharge. A number of major improvements followed with Theodore Kocher, of Berne, introducing submucosal resection of the nasal septum and Albert Halstead, of Chicago, devising a gingival incision behind the upper lip. Harvey Cushing, of Baltimore, undertook his first transphenoidal operation in 1909 using a modification of Schloffer’s method. The patient, an acromegalic, improved greatly and lived for 21 years after partial hypophysectomy. The next year, by combining the two main modifications – an oral incision and submucosal resection of the septum – Cushing established an operation that he and others used successfully virtually unchanged for 50 years. By 1916 Cushing had done 106 operations with only 8 operative deaths (7.5%) and had established transphenoidal hypophysectomy as a relatively safe and effective procedure.

Condensed from - Welbourn R. The History of Endocrine Surgery. Praeger, New York 1990

The function of the thyroid glands was discovered as a direct result of the effects of total thyroidectomy in man. This soon resulted in a reappraisal of the surgical approach to goitre and the preparation of an active thyroid extract for the relief of hypothyroidism. Theodore Kocher, appointed Professor of Surgery in Berne in 1872, essentially perfected the operation of thyroidectomy and was the first surgeon to be awarded the Nobel Prize. He reported his first series of thirteen strumectomies which included two total extirpations. One was Marie Bischel, aged 11, who underwent operation in 1874 and whose behaviour changed with the surgery. While previously a “spirited and joyous creature” she became “peevish and dull” and was reluctant to work. Before the operation she and her younger sister had been taken for twins. In the ensuing nine years, the sister had blossomed into a very pretty young woman, while Marie had remained small and had an ugly, almost idiotic, appearance. He immediately recalled all his patients and found similar changes in all who had had total extirpation. He reported this to the Congress of German Surgeons in 1883, and suggested that the condition was caused by injury to the trachea which resulted in chronic asphyxia and, as a result ceased to perform total thyroidectomy from that time on. It was not until 1888 that a committee, appointed by the Clinical Society of London, concurred that the effects of total thyroidectomy were due to arrest of thyroid function. After attempts at transplantation and subcutaneous injection of thyroid extract by George Murray, Edward Fox of Plymouth introduced oral thyroxine therapy which proved effective. Recommended was “half a sheep’s thyroid, lightly fried and taken with currant jelly once a week”

Condensed from - Welbourn R. The History of Endocrine Surgery. Praeger, New York 1990