Parathyroid History

Early Descriptions

Fig.1: Sir Richard OwenThe parathyroids are four small glands in the neck that lie next to the thyroid. They were the last grossly visible mammalian organs of the body to be discovered.

In May 1834 the Zoological Society of London had purchased its first Great Indian Rhinoceros (Rhinoceros unicornis). When the animal died, puncturing a lung with a fractured rib after an altercation with an elephant, on the evening of 19 November 1849, its carcass was offered to Sir Richard Owen (1804–1892), Hunterian Professor and Conservator of the Museum in the Royal College of Surgeons of England (Fig. 1). Owen welcomed the ‘rare opportunity’, and the dissection took place in the winter months of 1849 to 1850 at the Conservator’s resident quarters. 

He described ‘a small compact yellow glandular body attached to the thyroid at the point where the vein emerged’—a structure now identified as the parathyroid gland. This explains why many endocrine societies related to parathyroid disease have the rhinoceros as their mascot or as part of their logos.

Sir Richard Owen is probably best remembered today for coining the word ‘Dinosauria’ (meaning ‘Terrible reptile’) and for his outspoken opposition to Charles Darwin's theory of evolution by natural selection. He agreed with Darwin that evolution had occurred, but thought it was more complex than outlined in the Origin. He was the driving force behind the establishment of the British Natural History Museum in 1881 in London.

Fig. 2: Ivar SandströmIn 1880, Ivar Sandström, a 25 year old medical student working in Uppsala, described the glands in man. In his classic monograph ‘On a New Gland in Man and Fellow Animals’ he described what he called the ‘glandulae parathyroidae’ in the dog, cat, rabbit, ox, horse and man. 

Sandström was not aware of Owen’s description, which had been published in a journal with a limited circulation. Sandström's report was not well received and his work remained barely noticed for several years. He suffered from a hereditary mental illness and unfortunately took his own life aged only 37 years.

The Role of Parathyroids in Calcium Metabolism

The significance of Sandström’s discovery was not appreciated until Eugene Gley (1857–1930), a French physiologist, observed that the tetany and death caused by experimental thyroidectomy in dogs occurred only if the excised material included the glands described by Sandström. This was confirmed by several workers during the first decade of the 20th century, but the role of the parathyroid glands in calcium metabolism was still not recognised.

Halsted had stated that “it hardly seems credible that the loss of bodies so tiny as the parathyroids should be followed by a result so disastrous.” Over the next 70 years investigation and experiment began to elucidate the glands' role in the regulation of calcium metabolism.

Fig.2: Portrait of Freidrich von RecklinghausenIn 1891 Friedrich Daniel von Recklinghausen (1833–1910) reported on a patient who had experienced recurrent fractures of several bones with negligible trauma and had subsequently shown ‘bending’ of the long bones with extensive fibrosis, cysts and brown tumours (Fig. 2).

This group of findings was subsequently termed ‘osteitis fibrosa cystica of von Recklinghausen’, now recognised as one of the most severe findings in advanced parathyroid disease.

However, von Recklinghausen did not himself couple the bone disease with any parathyroid disorder, and it was not until 1915 that Friedrich Schlagenhaufer (1866–1930), professor of pathology in Vienna, suggested that an enlarged parathyroid might be the cause of bone disease and not the result of it.

In 1906 Erdheim had described an overgrowth (hyperplasia) of the parathyroids in the calcium-deficient state of osteomalacia, and was the first to describe a relationship between bone disease and abnormalities of the parathyroid glands.

William MacCallum and Carl Voegtlin initially felt that the parathyroids neutralised a circulating toxin, but subsequent careful experimentation led them to the correct conclusion that the parathyroids controlled calcium metabolism. They demonstrated in the early part of the 20^th century that the low blood calcium (hypocalcaemia) and tetany that followed removal of the parathyroids could be controlled by calcium administration, concluding that parathyroid tetany was a direct result of calcium deficiency.

Parathyroidectomy

Felix Mandl (Fig. 3) is widely credited with performing the first parathyroidectomy at the University Surgical Clinic in Vienna in July 1925, on a patient named Albert Gahne, a tram car conductor. There is some evidence however that the procedure was in fact performed earlier by Bland Sutton at London's Middlesex Hospital.

Fig.3: Felix MandlMandl removed under local anaesthesia, a ‘yellowish-brown almond shaped tumour’ measuring 25×15×12 mm from the left inferior area behind the thyroid gland. There was immediate improvement. Within a few days the blood and urine calcium content was considerably lower and the patient was soon able to walk.

He was well for the next six years before developing recurrent hypercalcaemia and a renal calculus. Mandl operated once again but this time could not find any abnormal parathyroid tissue. There was no postoperative improvement and the patient died in February 1936. The recurrence was probably due to aberrant parathyroid tissue, but none was found at autopsy.

Fig.4: Captain Charles Martell before hyperparathyroidism and after the disease had affected his skeletonIn 1926 the first parathyroidectomy in the USA was performed by EJ Lewis at the Cook County Hospital in Chicago.

The most notable American case of hyperparathyroidism however was that of Captain Charles Martell, a New York City mariner who had become disabled by demineralization of the skeleton over many years (Fig. 4). Between 1926 and 1932 his case graphically illustrated many of the features of the disease and its management. He was investigated initially in New York in 1926-7 and subsequently in Boston before undergoing a series of six neck operations without success.

It was Martell himself, who having read extensively in the Harvard Medical Library about ectopic parathyroid disease, suggested to his surgeons that he undergo a mediastinal exploration where he anticipated the tumour would be located. The final and seventh operation in 1932 found the 3cm parathyroid tumour in the mediastinum, curing the Captain's hypercalcaemia, but leading to postoperative tetany. Sadly he died only 6 weeks later from hypocalcaemic-induced laryngospasm after having a ureteric stone removed.

Parathyroid hormone assay

Adolf Hanson, another medical student like Sandström, working in the University of Minnesota developed a method of extracting a stable substance from bovine parathyroid glands that could successfully treat tetany. James Collip of Alberta, was also convinced that the parathyroid glands contained a calcium-regulating hormone. He independently developed his own technique for extracting this substance, like Hanson.

Finally the development of an immunoassay for the measurement of parathyroid hormone by Berson and Yalow in 1963 earned them the Nobel Prize.