Addison's Disease and two of its famous sufferers

From http://www.abc.net.au/rn/science/ockham/stories/s18569.htm

with Robyn Williams
on Sunday 31/01/1999
Addison's Disease and two of its famous sufferers
Summary:
John F. Kennedy and Jane Austin both had Addison's Disease. While John F. Kennedy survived the disease, Jane Austin died from it.

Transcript:

Robyn Williams: This week Ockham's Razor is presented by one of its great stalwarts: Dr Jim Leavesley, a great expert in the indispositions of the famous. He's now retired in the beautiful Margaret River south of Perth. Jim.

Jim Leavesley: It is not now fashionable in medical circles to call diseases by their eponymous names. To do so is said to be confusing to those not in the know. So pathologically descriptive names are used, the Greek or Latin bases which are supposed to be universally understood.

For we old fogies, the passing of a named disease is a pity, for not only do we honour the person who first described the condition, but eponymous names are often much more mellifluous than dry descriptive tags. For instance, it is much more satisfying to say someone has Charcot Marie Tooth syndrome, or von Recklinghausen's Disease, rather than the politically correct peroneal muscular atrophy or multiple neurofibromatosis.

But one or two have slipped through the net. Meniere's syndrome, Alzheimer's disease, Parkinson's disease, spring to mind as well as the one I wish to look at in conjunction with two of its victims, Addison's disease.

In 1795 at Long Benton, a village just outside Newcastle-on-Tyne, in northern England, the wife of the local grocer, Joseph Addison, was delivered of a second son. They called him Thomas.

A bright lad, he went on to Edinburgh to do medicine and qualified in 1815. From thence to Guy's Hospital, London, where he became an assistant physician in 1824 and the full works in 1837.

He was a contemporary of Richard Bright, of Bright's disease, and of Thomas Hodgkin, of Hodgkin's disease. What a trio.

Anyway, whatever mental jousting went on, it did not lift Addison's mood, for he was a chronic depressive. He made several attempts on his life until in 1860, he retired to Brighton, disturbed enough to have need of two constant attendants. Despite the care, within months he managed to elude them, flung himself down a stairwell and died of a fractured skull.

But let's go back a bit. On 15th March 1849, Addison had read a paper to the South London Medical Society entitled 'A Remarkable Form of Anaemia'. He cited three cases of increasing lethargy, but made no mention of those characteristic features we associate with his disease, skin pigmentation and low blood pressure. He didn't know how to measure that, anyway. He did note, however, that at post mortem there was a disease of the suprarenal glands, situated just above the kidney.

He did not connect the anaemia and suprarenal condition and said he had stumbled on a second condition, which he called 'melasma suprarenale.' It is this we now call Addison's disease. However, it did show for the first time that the adrenals were necessary for life, and it has been said that the whole of endocrinology dates from 15th March, 1849.

He did not publish until 1855, by which time he had separated the two anaemias, one he called 'pernicious', later known as Addisonian anaemia. The other he associated now with bronzed skin and suprarenal pathology, true Addison's disease. Publication produced no fanfares, no royal honours and his fame has been mainly posthumous. In any case, he was too late for our first famous patient with Addison's disease, who was that model of sense and sensibility, Jane Austin.
Like its houses, its chairs and its coffee pots, 18th century England has managed to convey to us a society which was at once both sensible and elegant. It seemed to manifest good manners, piety, and cultivated discernment.

At least it did if you were of 'the gentry', which was the case with Jane Austen, one of the greatest writers in the English language. It was a lifestyle which provided the ideal ambience in which her genius could flourish.

Daughter of a clergyman, the seventh of eight children, she led a life of gentility and ease spent entirely in the quieter rural southern England. She drew her characters from her own circle and never strayed from the world in which she moved.

Further, she was much too well bred to let her own name grace the title-page of her novels. All her books were styled as being written, 'By a Lady', as indeed they were.

Her towering reputation is based on only six works of fiction written between the ages of 34 until her death at 41. They have never been out of print in 175 years, and have flourished even more during the last decade or so.

She never married, and it appears the creative impulse, then customarily fulfilled by the task of being a wife and mother, was in her attained through her art. She took considerable pains to conceal from her friends and visitors the nature of her life's work, and wrote on small pieces of paper, the more easily to slip under a blotter or into a drawer if chanced upon. She said her books were her children and she was later remembered as the caring wit of the family.

Jane Austen was born 20 years before Addison, in 1775, into a closely-knit family in which she led a sheltered home life, interspersed with occasional visits to Bath to take the waters, or to the nearby houses of her elder brothers.

It all sounds like a rural idyll, and so it was, until June 1816, when at the age of 40, she had an attack of nausea and vomiting and low backache.

In July she was depressed and felt weak. This was put down to her dissatisfaction with the book, 'Persuasion', which she had just completed. Two months later it was noted she tired easily, had uncharacteristic mood swings and further back pains. She improved and life progressed in its customary premeditated way.
In December she declined an invitation to dinner, saying 'The walk is beyond my strength, though I am otherwise very well.'

The following months she wrote to a friend that she was stronger but felt 'bile' was at the bottom of her nausea and malaise.

All pretty vague so far. Then in March 1817 Jane wrote to her favourite niece, Fanny, and in it gave the clue which could lead us to the likely diagnosis. She wrote, 'I certainly have not been very well for many weeks; I have a good deal of fever at times, but am considerably better now and recovering my looks a little, which have been black and white and every wrong colour. Sickness is a dangerous indulgence at my time of life.'

She wrote to a friend two months later, recounting details of recurrent vomiting, concluding, 'My chief sufferings were from feverish nights, weakness and languor.'

We know the slightly built Austen was bright eyed and had an olive complexion, certainly not 'black and white and every wrong colour.' A visitor in May observed the author was looking very pale and spoke in a weak, low voice.

A concerned family moved her to Winchester to be nearer expert medical help. It was of no avail. Over a six weeks period she became progressively weaker and had a number of fainting fits, until on July 18th, 1817, after several hours of unconsciousness, Jane Austen died in the arms of her only sister, Cassandra.
So what did she have? Well I don't think she died of boredom, as someone unkindly suggested. The story is one of unimpaired intellect but increasing languor and intermittent backache, fainting attacks, gastrointestinal disturbances, and fever, especially at night. Night sweats are a well-known feature of tuberculosis. Added to all that, and crucially, is a darkening of the face. The delicacy of the era regrettably precludes us from knowing about skin changes elsewhere, especially the vagina, in the mouth or where pressure was applied to the skin, at the waist, for instance.

A number of conditions come to mind, but probably only one fits the whole scenario.

The lassitude could have been due to a rare neuromuscular condition, myasthenia gravis, but there seems to have been no speech or swallowing problems. Maybe the heart could be implicated with an infection of its valves, or bacterial endocarditis, but fainting crises are not a feature of this. Perhaps cancer of the stomach with anaemia from the slight but persistent blood loss which characterises the condition. The digestive problems did not seem either very great or progressive.

Skin discolouration occurs in a number of general diseases: the rare so-called bronzed diabetes, or haemochromatosis, but the other symptoms do not fit; chronic inorganic arsenic poisoning with its raindrop pigmentation and abdominal symptoms, or indeed poisoning from any of the heavy metals, lead especially, possibly from medication or water pipes. But the other history is inappropriate and no other family member was affected.

No, none of these seem right. From the admittedly rather thin records, coupled with the melancholy fact that living in the country she did have ready access to almost certainly tubercular contaminated milk, the most likely diagnosis is Addison's disease due to TB of the hormone producing suprarenal glands.

As we have seen, it was not until 1849 that Thomas Addison first described the malady. It's best known features are weakness and skin discolouration which he described as 'various tints of deep amber or chestnut brown.'

One alleged feature was not displayed. My old forthright chief used to claim, rightly or wrongly, that tubercular patients, possibly due to their low grade persistent fever, were almost always more sexually charged than the general run of the population. No hint of sexual impropriety in Miss Austen has come down to us.

Whatever her private life, we know from her books that Jane Austen was a consummate writer whose genius was tempered with gentle humour and a subtle insight into the nature of humankind. It is better we remember her thus, rather than someone who suffered from an uncommon and debilitating medical disorder.

Until the mid-20th century, tuberculosis was the prime cause of Addison's disease. Now it is likely to be an auto immune reaction, as was believed to be the case in that other famous sufferer and quite different personality, John F. Kennedy.

I have spoken before in this place about Kennedy, so will not burden you with the details again. But briefly, during the 1960 Presidential campaign, a Republican questioned the candidate about an article in the November 1955 edition of the American Medical Association's Archives of Surgery, and which was concerned with operating for one reason or other, on sufferers from Addison's disease. The questioner wondered if JFK was one of these cases.

The piece was entitled 'Management of Adrenocortical Insufficiency During Surgery'. Of the three listed cases, one told of an unnamed man in for a bone fusion, and insertion of a metal plate who had had Addison's for seven years, and who was managed by desoxycorticosterone pellets every three months and 25 milligrams of cortisone daily by mouth.

It was a typical bread and butter piece for that journal, but suddenly became hot political property when at the end of the piece the authors inserted a quite unnecessary throwaway line which sparked off the question. They simply wrote, 'The operation was accomplished on October 21st, 1954.'

Now on October 11th, on page 39 of The New York Times, it was reported that 37-year-old Senator Kennedy was entering hospital for spinal surgery. On the 21st it wrote he had undergone the operation that day. On February 26th 1955 it saw fit to record that the plate had been removed.

Now you don't need much nous to conclude that two people of the same age, with the same spinal condition, having undergone similar surgery in the same hospital and who returned on exactly the same day four months later to have the plate removed, were in fact one and the same. So we know for certain John Kennedy had Addison's.

His treatment was successful, but in those days, dosage of cortisone was chancy. Accumulating drug gave a fullness of the face, a so-called moon face, which in the President gave him those boyish good looks and appearance of rude good health which made him the darling of the chattering classes.

It increased energy and JFK's well-known bedroom athleticism may have been enhanced by the treatment, though his back will have suffered.

Kennedy did not die of the disease, Jane Austen did. Treatment was relatively unrefined in one and non-existent in the other. The basic cause in one was probably tuberculosis; in the other, an auto immune reaction. The victims had widely differing personalities, but both had one thing in common, and something which indeed they shared with Thomas Addison: they touched the lives of countless people in all corners of the globe and have gone on doing so long after their deaths.

Robyn Williams: Jim Leavesley, in forensic mood, as always. His book is called 'What Killed Jane Austen, and Other Medical Mysteries', published by Harper Collins.
Next week, Sue Taylor has trouble with elephants. I'm Robyn Williams.
Guests on this program:

Dr. James Leavesley
Margaret River
Western Australia
Author of the book: "What killed Jane Austen and other Medical Mysteries", published by Harper & Collins