At the start of the nineteenth century, when doctors were poetasters -
waffling about the "Five Essences" -
He was driven out to an annexe, Guy`s Hospital. He began to assemble
a new team which ultimately included
Addison discovered Pernicious Anaemia, and published a book. Then, in 1855, he wrote about a remarkable disease that causes reddish-brown pigmentation and death from no discoverable cause. The disease now bears his name.
It is arguable that because he drew attention to the adrenal
glands, research began into the chemistry of their cortices. In 1932,
The steroids had arrived on the market, in the nineteen fifties. The result was mass addiction, similar to the fate of Elvis Presley, and a new disease that loosely mimicked the real Addison disease.
Those who need to know should really refer back to the original text - to the days before addictive steroids were widespread. This can only simplify the picture. True Addison`s Disease is extremely rare - perhaps one in twenty million. Steroid addiction is common.
On this site is a copy of that book, which was hidden away in the Rare Books Section of the Humanities department of the British Library.
It was necessary to type in every word, and to proof-read repeatedly. The object is to create as closely as possible an exact facsimile of the original. However, active links - such as to the colour plates - will appear coloured and/or underlined on a browser, whereas the original text was black.
Working in an age before colour photography, Addison employed artists to draw his patients. Due to modern bureaucracy, it was necessary to obtain photocopies of the plates, and adjust the colours by computer. They are as accurate a reproduction as was possible under the circumstances.
Without photometry, no colours on monitors or printers can be guaranteed. Accordingly, the colour intensity and image brightness are for guidance only, and cannot be relied upon.
Similarly, as the Internet is designed to adapt to any screen-size or paper format, the line-breaks cannot be maintained. Instead, when quoting from the Internet edition, you are advised to quote page and paragraph number. The pages of the original book are reproduced each on its own file. Thus, page 19 is p19.htm for example. Nothing has been put on the page that was not there in the original, and nothing was left out.
Most pages were headed ON DISEASE OF THE SUPRA-RENAL CAPSULES. This was removed from the body text and transferred to the TITLE tag in the HEAD area. On Internet Explorer, one can generally customise the pages, such as by removing time-and-date stamping and the web address. With the title alone at top centre, the page as hard copy resembles the original.
One version of the MOSAIC Internet browser falsifies the colours badly until you move on to the next page and return. Similarly, it fails to give the full choice of font sizes. Most MS Internet Explorer browsers give a result close to the original.
The retype - into ASCII - now makes the text machine-readable, for example it allows a word-search for "Integument".
It will be necessary to print each page individually. The typeface was similar to "Times", 14 point on 19 point line-pitch. Wordspace was greater than is customary nowadays, so that 20 point on WordPerfect will match for line length, and a fixed line height of 0.357 is needed. The pages were ten by twelve-and-three-quarter inches (25.4 by 32.4 cm). The first line of the Preface ended on the word "appears"; the first text block had 15 lines (Page x2). Depending on your equipment, each page of the original may result in more than one page of Internet copy.
Each paragraph of text was double-edge justified. This has been implemented by the ALIGN=JUSTIFY command within the paragraph tag. Only the latest Internet browsers will recognise the command. However, it is possible to download the book onto disk, delete the HTML codes and re-typeset using WORD, WORDPERFECT or a similar desktop publishing system.
Another difficulty that arose was with the special symbol used by Dr. Addison
in the prescriptions. This is not one of the standard Internet characters.
A graphic could not have been used, as it would not adapt its size always
to match the text.
In its place, a standard letter R was substituted. If this is found to be
disturbing, the printed text may be modified by hand.
Yet again, there is another
special symbol similar to the figure shown here.
This was replaced by a Z. It was in the prescriptions, such as Zss, and once
in the body text.
Addison does not make clear why every tinge of yellow throws doubt upon the diagnosis (Top of P8). This is because, as an expert also on pernicious anaemia, he knew that the latter condition causes jaundice-like symptoms not displayed by adrenal insufficiency.
The language is quaint, the science surprisingly modern and prescient. For example, on P21 he states "How far .. (gastritis) .. depends on .. essential gastric inflammation .. a more extended observation will probably determine hereafter". Essential in this context means inflammation by gastric juices, or essences. YES! Modern science reveals that due to aldosterone deficiency, the gastric juices become alkaline. The Na+ ions used by the ion pump to carry bile, mucus, enzymes and bicarbonate into the digestive system are not reclaimed.
The molar ratio of sodium to potassium remaining in the blood is an important parameter in Addison`s disease, and not a dangerous test - unlike so many others.
Yet he missed the sodium loss. Tiny amounts of urine are passed because the bladder has only one sensation - FULL. Strong alkali irritate the bladder (Na+ is not reclaimed from urine either). Addison failed to spot these drops of powerful alkali. Cl- stays in the blood, which becomes acid. During partial remission, a large volume of urine is passed. This has, as Addison observed, an acid reaction.
AFTER the book was published, Addison`s last case was a boy of 13. Dr. Samuel Wilks described him as having "a dribbling of urine", which Wehner understands not in the sense of incontinence but as urination being a few drops at a time, which Wehner himself experienced and which was reported for Gaget (below) also.
Clinical Endocrinology, 3rd Edition, 1965, Hoeber, Harper and Row
quotes alkaluria and acidaemia as symptoms.
This is particularly important for negroes, because the existing skin colour will hide the effects of Addison`s disease. An impartial and scientifically valid test is essential.
Addison knew NOTHING about steroids, and that glucocorticoids cause leucopenia. Yet, he spotted the opposite effect, caused by glucocorticoid deficiency - plasma cell proliferation. See the second paragraph of page four ("Leucocythaemia,") and the end of page eight, for example. He also spotted haemoconcentration on page eleven. The precision of his observations is stunning.
In an age when burning objects gave out phlogiston instead of taking in oxygen, when chemistry was nonsense - long before Mendeleev published his periodic table - Addison said nothing that would clash with modern science.
Endocrinology,
This is the bovine case, from Sawyer et al. as quoted by Mac E. Hadley. The human case is still being investigated.
Addison failed to notice at any time the sensitivity of the skin to
trauma. Pressure or injury causes pigmentation, as shown here for one
of two insect bites to the legs.
Charles Douglas Wehner observes that the scar and then the new skin - after the injury is fully healed - both become pigmented, and that the effect is due a combination of those seven amino-acids, of the properties of the MSH receptors in the skin and of the trauma. It is less likely in Addison remission, more likely in crisis when ACTH levels are high.
The patient Gaget of Dr. Frémy at Beaujon hospital and others reported this phenomenon, and Louis Martineau put it in his thesis of 1863. Then Greenhow reported it in his survey of 1866, saying that deep wounds are not discoloured.
Wehner observes that deep wounds that destroy the melanocytes cannot be discoloured. This is only obvious after Greenhow noticed the fact. Melanocytes are known in modern medical science to be the pigment-forming cells. Of these things Addison knew nothing, but he speculated on page 6 that the whiteness is caused by a deficiency of pigment, a hair`s-breadth away from postulating a deficiency of pigment cells.
A suntan under the armpit of John Iveson or Elizabeth Lawrence
cannot be a suntan, so Addison pondered other aspects
of pigmentation, such as pinhead-sized jet-black spots. According
to Fagge, these also occur in healthy people. Shown here is Wehner`s
groin.
Lentil-sized spots, like large freckles, shown in these two pictures
of Wehner (hand and arm), and in Addison`s plate of Lawrence`s torso,
also occur - but can be found in healthy people.
All that can be said is that Addison`s disease pre-disposes
to such natural pigmentation, whilst it is the armpit suntan
and other examples of irritation causing pigment that are
truly pathognomic.
In modern terms, ACTH - the stress hormone which is elevated in Addison`s disease - behaves like MSH, and encourages pigmentation as might be found in healthy people. However, it also promotes pigment at sites of trauma - which is a unique property.
One might imagine that Addison - an insomniac according to Wilks - lay awake trying to simplify the specification to the one given here. However, he was reluctant to talk to his patients. As a result, John Iveson never told him that he carried stone slabs under that armpit, and Addison never realised the pigment was due to massage.
Breathlessness on exertion is due to shock and not to lack of air. In modern terms, the lack of aldosterone causes the victim to breathe more deeply. This changes angiotensin 1 (from the liver) to angiotensin 2 (in the lungs). Angiotensin 2 in turn stimulates the zona glomerulosa of the adrenals to produce more aldosterone. See the book Endocrinology (Mac E. Hadley).
The semi-torpid state described by Addison, or semi-comatose in his earlier work on circulation, and in Greenhow`s reports, has nothing to do with coma. The patient is stunned, and too exhausted to speak.
The oedema about the ankles might accur as with Bright`s disease of the kidneys - but Wehner experiences over forty years of disease, with several near-encounters with death, before the right ankle became swollen without apparent reason in the year 2000.
Wehner`s lymph-node biopsy (from the inguinal region) in 1979 showed lipomatosis, fibrosis and plasma-cell proliferation. ACTH is known to be lipolytic - turning dense fat into softer lipids, so Addison`s speculation about fatty degeneration (page 3) having a share in the illness shows remarkable clarity of perception.
A brown or light-brown or yellow fur on the tongue, now known to be due to hæmosiderin - a breakdown product of the blood, was also detected several times.
This substance, accompanied by a "spirity" taste which ultimately turns acidic like vinegar, shows that iron is being lost. It explains why Addison put the emphasis on anæmia as the main characteristic of the disease.
We can see what is so important about this book. Whilst having no knowledge
whatsoever about endocrinology, Addison succeeded in covering just about
every observable symptom of the disease - with very few mistakes - and with
a thoroughness that puts many present-day observers to shame.
Addison loathed doubt. Medication, in an age before proper chemistry, was riven with doubt - so Addison did not bother to medicate patients. When he himself became ill with jaundice and gallstones, it seems that he despaired and committed suicide. Despite the problems of diagnosing Addison`s disease, there is no evidence of professional criticism as a suicide motive. He was highly repected by his colleagues.
Addison`s book is brilliant for its day. It is not the last word, but the first. For example, on page 7 he states the disease is irremediable. Today, in 2001, nobody has ever been cured. There is a tendency to rush ahead with hormone replacement therapy, even for the mis-diagnosed, before the most likely cause - infection - has been tackled.
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Addisons Buch wurde auch auf Deutsch übersetzt:- "Die Erkrankung der Nebennieren und ihre Folgen (1855)", Leipzig: Johann Barth, 1912. Wellcome Library, London.
Also republished in Croatian and English on opposite pages, 1953, Belgrade. Wellcome Library, London.
The perfect companion to this book is the 1866 pan-European survey of Addison`s disease by Edward Headlam Greenhow. Click the entry in the list below.
Addison Thomas, M.D. Observations on the Disorders of Females,
connected with uterine irritation. pp.viii.96 S. Highley, London 1830
Bright, Richard and Addison, Thomas Elements of the Practice of
Medicine Vol 1 pp.vi.vi.613 Longman and Co. London, 1839
Greenhow, Edward Headlam
On Addison`s Disease: clinical lectures
and reports on diseases of the supra-renal capsules [with comments on
Dr. Addison`s treatment and theory] pp.vii.64 London 1866
Addison, Thomas A collection of published writings of... T. Addison
... Edited, with introductory preface... by Dr Wilks and Dr Daldy
London 1868
©
2001 Charles Douglas Wehner.
Further reading in the British Library
Addison, Thomas and Morgan, John F.L.S. An essay on the Operation
of Poisonous Agents upon the living body. pp.viii.91 Longman and Co.
London, 1829.
Greenhow observes pigmentation occurs on superficial but not deep wounds.
He also observed intermittent disease (remissions) and Addison`s
disease without pigment.
Use freely but do not plagiarise.