Thursday, December 24, 2009

Development of a Disease-Specific Quality of Life Questionnaire in Addison's Disease

Kristian Løvås*, Suzanne Curran, Marianne Øksnes, Eystein S. Husebye, Felicia A. Huppert,  and V. Krishna K. Chatterjee

 

Department of Medicine (K.L., S.C., V.K.K.C.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Institute of Medicine (K.L., M.Ø., E.S.H.), University of Bergen, 5020 Bergen, Norway; Department of Medicine (K.L., E.S.H.), Haukeland University Hospital, 5021 Bergen, Norway; and Department of Psychiatry (F.A.H.), University of Cambridge, Cambridge CB2 2QQ, United Kingdom

 

* To whom correspondence should be addressed. E-mail: Kristian.lovas@helse-bergen.no.

 

Context: Patients with Addison's disease reproducibly self-report impairment in specific dimensions of general well-being questionnaires, suggesting particular deficiencies in health-related quality-of-life (HRQoL).

 

Objective: We sought to develop an Addison's disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects.

 

Design, Setting, Patients, Intervention, and Outcomes: We reviewed the literature to identify HRQoL issues in Addison's disease and interviewed patients and their partners in-depth to explore various symptom domains. A list of items was generated, and nine expert clinicians and five expert patients assessed the list for impact and clarity. A preliminary questionnaire was presented to 100 Addison's outpatients; the number of items was reduced after analysis of the distribution of the responses. The final questionnaire responses were assessed by Cronbach's {alpha} and Rasch analysis.

 

Results and Interpretation: Published studies of HRQoL in Addison's disease indicated reduced vitality and general health perception and limitations in physical and emotional functioning. In-depth interviews of 14 patients and seven partners emphasized the impact of the disease on the emotional domain. Seventy HRQoL items were generated; after the expert consultation process and pretesting in 100 patients, the number of items was reduced to 36. Eighty-six patients completed the final questionnaire; the responses showed high internal consistency with Cronbach's {alpha} 0.95 and Person Separation Index 0.94 (Rasch analysis).

 

Conclusions: We envisage AddiQoL having utility in trials of hormone replacement and management of patients with Addison's disease, analogous to similar questionnaires in GH deficiency (AGHDA) and acromegaly (AcroQoL).

 

 

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-1711v1

Tuesday, December 22, 2009

(Addison’s) A piece of presidential history solved the puzzle

By Sandra G. Boodman
Special to the Washington Post
Tuesday, December 15, 2009

 

As she lay in a heap, trying to figure out how badly she had hurt herself falling headfirst down a flight of stairs in the middle of the night, Rebecca Woodings grasped just how sick she really was.

 

For months doctors had been ratcheting up the medicines used to treat her intractable allergies. At one point she was taking 10 drugs a day and getting allergy shots. An economist who works for a large Washington law firm, Woodings, 49, told doctors she was tired; she assumed her fatigue was a consequence of her allergies, which were also causing a persistent cough. She did not tell them she was so exhausted she had to sit on the sidewalk while waiting for a bus and couldn't stand long enough to cook a meal.

 

Hours before she tumbled down the stairs of her Takoma Park home last June, an astute pulmonologist had figured out what was wrong -- and it had nothing to do with her lungs. That night, as Woodings tried to move the wrist she had broken in the fall, she focused on her 6-year-old son, realizing that if she had smacked her head she could have died. "I kept thinking, what would have happened to my child?"

 

In the fall of 2008 Woodings began feeling unusually tired. Walking less than a mile to the Metro in the morning made her break into a sweat. "It was very tiring," she said, and she recalled feeling puzzled. "I'm not terribly out of shape and I'm not overweight." Once on the Metro, Woodings made sure to get a seat; standing for 20 minutes was unthinkable.

 

During her annual checkup in November, her long-time internist at George Washington University discovered a Vitamin D deficiency and prescribed a short course of high-dose supplements.

 

By December, the fatigue was worse. Woodings had to sit down in the middle of a hymn during a church service. "All these little white-haired people around me are standing, and I couldn't," she recalled. When she mentioned the incident to a friend who works at the National Institutes of Health, she was told the symptoms sounded like a heart attack. Alarmed, Woodings immediately headed to a nearby emergency room, where an EKG and a chest X-ray showed that her heart was fine and her lungs were clear. Her father, a retired physician, suggested that maybe an antihistamine was causing her fatigue. Woodings stopped taking it and felt slightly more energetic.

 

By February, she was forced to sleep propped up on pillows and was taking a prescription cough syrup, which had little effect. The mother of a typically energetic kindergartner, she had started falling into bed around 8:30, when her son did. One night, she was so tired she told him to put himself to bed and crawled into bed at 8. Her allergist began administering allergy shots, which didn't help. Another doctor -- not her regular internist -- suggested she cut back on her sleep and get more exercise. Woodings replied that she was so tired she worried she might fall off a treadmill.

 

Routinely she arrived at the office at 9 a.m., already worn out. "It's really difficult to talk about being exhausted at a law firm," she said. "It sounds wimpy," so she didn't mention it.

 

In March, when she was handed a demanding new assignment with multiple deadlines, two new symptoms surfaced: Woodings began retching unpredictably -- "that damn cough," she remembered thinking -- and developed ferocious leg cramps at night. By then she noticed another peculiarity: Although she literally could not stand long enough to wait for a light to change while crossing the street, she could manage if she kept moving, walking slowly in a circle.

 

In early April, she went back to the allergist. He diagnosed a bad sinus infection and doubled the medications she was taking to 10 per day, including a short course of prednisone, a corticosteroid sometimes used to treat severe sinus infections.

 

After the first day, Woodings said, she felt markedly better. A week later the cough had disappeared and her energy slowly returned.

 

But by Memorial Day the fatigue was back and Woodings realized her problem wasn't allergies. She had stopped taking the allergy drugs, deciding that they might be the cause; her cough was gone. Woodings called her internist, whom she had not seen in six months. The doctor was heading out of town and Woodings decided to wait until her return rather than see a covering physician. In the meantime her physician ordered several tests, including those for Lyme disease and HIV, as well as CT scans of her lungs and sinuses.

 

On June 5, Woodings was told she had a possible bacterial infection in her lungs -- but not tuberculosis -- and was referred to GWU pulmonologist Susan Hasselquist. When she called to make an appointment, she was told that Hasselquist's first opening was a month away.

 

Desperate, Woodings decided to lie. "I said, 'I can't wait. The potential diagnosis is active TB.' " She was given an appointment for the next day.

 

On June 10 Woodings met with Hasselquist, who listened intently as Woodings recounted the events of the previous seven months. Unable to obtain a blood pressure using an automated cuff, Hasselquist measured it manually and found it was an alarmingly low 90/55. The lung specialist recalled being struck by how weak Woodings was: She lay down on the examining table while they talked because sitting up was too tiring. Hasselquist said she kept thinking of, and discarding, possible diagnoses. "I knew if we just kept talking I'd figure it out," she said.

 

Her eureka moment occurred when she zeroed in on Woodings's deep tan and asked her about it. Woodings, who is normally very fair, said that other people had remarked on it and that she hadn't spent much time in the sun.

 

Suddenly, Hasselquist said, she was certain what was wrong, a hunch triggered by photographs she'd seen of a ruddy-looking President John F. Kennedy, who had Addison's disease, a rare endocrine disorder that occurs when the adrenal glands become damaged and fail to produce enough cortisol and aldosterone, hormones vital for metabolic function. Most cases are the result of an autoimmune attack in which the immune system slowly destroys the adrenal glands. Woodings's dramatic improvement while taking prednisone, the steroid prescribed to treat her sinus infection, was a vital clue: It is one of the medicines used to treat Addison's.

 

Kennedy received an Addison's diagnosis at age 30; his sister, the late Eunice Kennedy Shriver, is also believed to have suffered from the disorder, which affects one to four of every 100,000 people, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

 

Woodings had the classic symptoms of Addison's: progressive fatigue, muscle weakness, low blood pressure that falls further during a change in positions, and hyperpigmentation, which resembles a dark tan. The retching and legs cramps are also symptoms, although her allergies and cough are not.

 

Hasselquist did not mention her suspicion to Woodings because it would require confirmation from an endocrinologist. She said she suggested hospitalizing Woodings because she was so weak. When Woodings declined, Hasselquist warned her against standing up too quickly, which could cause dizziness.

 

After the appointment with Hasselquist, Woodings went straight home, ordered a pizza and went to bed. She awoke several hours later and headed for the bathroom to urinate. She remembers feeling dizzy, and then realizing she was at the bottom of the stairs, her wrist shattered. She managed to get up, call 911 and wake her son. Doctors in the ER set her wrist, told her to see an orthopedist because she would need surgery, then sent her home.

 

A few days later GWU endocrinologist Michael Irwig, to whom Hasselquist referred Woodings, confirmed the Addison's diagnosis. He prescribed prednisone and another drug Woodings will have to take for the rest her life to replace the hormones her body no longer produces.

 

Within a few weeks, Woodings said, she felt much better. Her energy level returned to normal, as did her blood pressure. Her tan is fading, and surgery on her wrist was successful.

 

"I can't fault any of the doctors," Woodings said, adding that she believes she should have called her internist early on, instead of consulting other physicians. "I think I could have described my condition a little better. I never said, 'I have to sit on the sidewalk waiting for a bus,' but rather, 'I'm tired all the time.' "

 

If you have a Medical Mystery that has been solved, e-mail medicalmysteries@washpost.com. To read previous mysteries, go to http://www.washingtonpost.com/health.

 

From http://www.washingtonpost.com/wp-dyn/content/article/2009/12/14/AR2009121402863.html

 

~~~~~~~~~~~~~~~

 

Feedback:

Woman's tale of Addison's disease proves the value of primary-care physicians

 

Tuesday, December 22, 2009

 

Of primary importance

 

"A piece of presidential history solved the puzzle" [Dec. 15], about the lady found to have Addison's disease, points out how crucial it is to have a primary-care focus in evaluating patients. Often patients scramble through a maze of specialists, as she did, without a strong primary-care clinician coordinating care.

 

My hope is that health reform will recognize the essential perspective that primary-care physicians from family medicine, geriatrics and internal medicine bring to patient care. They can save patients and the health-care system heartache and money. It is the most challenging field in medicine and the most holistic.

 

Our system should provide incentives for new medical school graduates to join these fields and reward these physicians appropriately. These doctors work very, very hard. Good primary-care clinicians are worth their weight in gold.

 

Christine Butler

Coordinator, Palliative Care Service

Sibley Memorial Hospital

Washington

 

From http://www.washingtonpost.com/wp-dyn/content/article/2009/12/18/AR2009121803706.html

Thursday, December 17, 2009

Diagnosis and Treatment of Adrenal Tumors: A Single-Center Experience with 238 Cases

Abdul-Monem Gomha, Yasser Osman, Mohsen El-Mekresh, Mohamed Abou El-Ghar, Ibrahim Eraky
Urology Department, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt

Address of Corresponding Author

Urol Int 2009;83:433-437 (DOI: 10.1159/000251184)


 Key Words

  • Adrenal mass
  • Adrenalectomy

 Abstract

Objective: It was the aim of this study to review and analyze clinical data on the diagnosis and management of patients with adrenal masses.

 

Patients and Methods: Between 1976 and 2005, 238 patients admitted to our institute with adrenal masses were reviewed. Incidence, clinical features, imaging technique findings, surgical approaches, morbidity and mortality, as well as pathological diagnoses were reported.

 

Results: The series comprised 134 males and 104 females (mean age 33.3 ± 20.3 years). Right-sided masses were more common (63.4%), with a mean size of 7.7 ± 4 cm. Pain was the most frequent presenting symptom (53.4%), while 62 (26%) had a functional tumor. Incidentaloma was diagnosed in 49 patients (20.6%). Both computed tomography and magnetic resonance imaging showed a high diagnostic yield (sensitivities of 98.9 and 100%, respectively). Open adrenalectomy was performed in 153 patients (64.3%), while a laparoscopic approach was employed in 53 patients (22.3%). The intraoperative complication rate was 14.7%, the postoperative complication rate 6.1% and perioperative mortality 1.7%. Most of the excised masses were pheochromocytomas (26.4%). Conclusions: Computed tomography is recommended as the first diagnostic modality to define and characterize adrenal masses. Laparoscopic adrenalectomy is currently replacing open surgery as the standard surgical management of adrenal masses.

Copyright © 2009 S. Karger AG, Basel


 Author Contacts

Yasser Osman, MD
Urology and Nephrology Center
Mansoura University
Mansoura (Egypt)
Tel. +20 50 226 2222, Fax +20 50 226 3717, E-Mail y_osman99@yahoo.com


 Article Information

Received: October 20, 2008
Accepted: December 9, 2008
Published online: December 08, 2009
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 3, Number of References : 20

 

From http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=251184&Ausgabe=253627&ProduktNr=224282

Wednesday, December 16, 2009

Epidemiology of adrenal crisis in chronic adrenal insufficiency – the need for new prevention strategies

European Journal of Endocrinology (2009) In press
DOI: 10.1530/EJE-09-0884
Copyright © 2009 by European Society of Endocrinology

Stefanie Hahner, Melanie Loeffler, Benjamin Bleicken, Christiane Drechsler, Danijela Milovanovic, Martin Fassnacht, Manfred Ventz, Marcus Quinkler and Bruno Allolio

S Hahner, Endocrinology and Diabetes Unit, University of Wuerzburg, Wuerzburg, D-97080 , Germany
M Loeffler, University of Wuerzburg, Endocrinology and Diabetes Unit, Würzburg, Germany
B Bleicken, Dept. of Medicine I, University of Wuerzburg, Würzburg, Germany
C Drechsler, Dept. of Nephrology, University of Würzburg, Würzburg, Germany
D Milovanovic, University of Wuerzburg, Endocrinology and Diabetes Unit, Würzburg, Germany
M Fassnacht, Dept. of Medicine I, University of Würzburg, Würzburg, Germany
M Ventz, Dept. of Medicine I, University of Wuerzburg, Würzburg, Germany
M Quinkler, Dept. of Medicine I, University of Wuerzburg, Würzburg, Germany
B Allolio, University of Wuerzburg, Endocrinology and Diabetes Unit, Würzburg, Germany

 

Correspondence: Stefanie Hahner, Email: hahner_s@medizin.uni-wuerzburg.de

 

Objective: Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI). Here we evaluated frequency, causes and risk factors of AC in patients with chronic AI.

Methods: In a cross-sectional study 883 patients with AI were contacted by mail. 526 patients agreed to participate and received a disease specific questionnaire.

 

Results: 444 data sets were available for analysis (primary adrenal insufficiency, PAI n=254, secondary adrenal insufficiency, SAI n=190). 42% (PAI 47%, SAI 35%) reported at least one crisis. 384 AC in 6092 patient years were documented (frequency of 6.3 crises/100 patient years). Precipitating causes were mainly gastrointestinal infection and fever (45%) but also other stressful events (e.g. major pain, surgery, psychic distress, heat, pregnancy). Sudden onset of apparently unexplained AC was also reported (PAI 6.6%, SAI 12.7%). Patients with PAI reported more frequent emergency glucocorticoid administration (42.5% vs 28.4%, p=0.003)) Crisis incidence was not influenced by educational status, BMI, glucocorticoid dose, DHEA treatment, age at diagnosis, hypogonadism, hypothyroidism or growth hormone deficiency. In PAI, patients with concomitant non-endocrine disease were at higher risk of crisis (OR=2.02, 95% CI 1.05-3.89, p=0.036). In SAI, female sex (OR=2.18, 95%CI 1.06-4.5, p=0.035) and diabetes insipidus (RR=2.71, 95%CI 1.22-5.99, p=0.014) were associated with higher crisis incidence.

 

Conclusion: AC occurs in a substantial proportion of patients with chronic AI, mainly triggered by infectious disease. Only a limited number of risk factors suitable for targeting prevention of AC were identified. These findings indicate the need for new concepts of crisis prevention in patients with AI.

 

From http://www.eje.org/cgi/content/abstract/EJE-09-0884v1

Tuesday, December 08, 2009

Adrenal Insufficiency: University company wins healthy £300k for new Cardiff-based drug

A UNIVERSITY spin-out venture yesterday won a £300,000 investment to support the commercialisation of its product.

 

Fusion IP, the university commercialisation company which turns university research into business, is investing the money into Diurnal, an innovative, early stage Fusion portfolio company from the University of Sheffield.

 

Cardiff-based Diurnal is developing a novel approach to drug delivery which will help patients suffering from reduced cortisol and testosterone levels.

 

The investment is part of a £600,000 funding round in which Finance Wales has also invested £300,000 under its memorandum of understanding with Fusion. Diurnal will have a post-money valuation of £2m.

 

Diurnal has developed a delayed and sustained release therapy to deliver hydrocortisone in a manner that mimics the body’s normal circadian rhythm – the body’s natural 24 hour hormone cycle.

 

This therapeutic approach has the potential to help patients with deficiencies in steroid hormones, testosterone, thyroid hormones and associated conditions by regulating metabolism, growth development and puberty, tissue function and in determining mood.

Each of these deficiencies requires life-long treatment and Diurnal’s approach to drug delivery has the potential to drastically improve patients’ lives, according to the company.

 

Working closely with Penn Pharma, the Tredegar-based pharmaceutical services company, and Simbec Research in Merthyr Tydfil, Diurnal will use the funding to continue to develop its new formulation approach to endocrine therapy and to complete phase one clinical trials of its lead product Chronocort, for adrenal insufficiency in the first half of next year.

 

The product has already received two related Orphan Drug designations from the European Medicines Agency, which affords 10 years of market exclusivity after the grant of marketing authorisation in Europe.

 

Martin Whitaker, general manager at Diurnal, said: “Diurnal’s product pipeline has the potential to help many patients with hormone deficiencies that disrupt the body’s natural clock.

 

“Our lead compound Chronocort is focused on delivering a delayed and sustained release therapy. Following positive pre-clinical results and today’s fundraising, Chronocort is poised to enter phase one clinical trials next year.

 

“In addition, it has significant market potential and has already received Orphan Drug Designation potentially giving it market exclusivity in Europe.”

 

Following the fundraising Fusion will have a 51.6% shareholding in Diurnal.

David Baynes, chief executive officer of Fusion IP, said: “Diurnal’s endocrine therapies have great potential for patients suffering from hormone deficiencies.

 

“Taking Chronocort into phase I clinical trials next year is a major step forward for Diurnal and we are delighted to see the company making such positive progress.”

 

Jocelyn Brown, Associate at Finance Wales, said: “This latest funding round accelerates Diurnal’s commitment to creating niche therapeutics targeting areas of greatest unmet patient need.

 

“The continuing success of Diurnal is underpinned by their strong partners within the Welsh biosciences community, and we’re pleased to be investing in such a dynamic, forward-looking company.”

 

 

From http://www.walesonline.co.uk/business-in-wales/business-news/2009/12/08/university-company-wins-healthy-300k-for-new-cardiff-based-drug-91466-25341981/

Thursday, December 03, 2009

Online Survey for Adrenal Insufficiency

Eric Fiedler, founder and co-leader of the Baltimore/D.C. Addison's Support Group, is conducting a survey of adrenal insufficient (Addison's disease and secondary adrenal insufficiency) patients.


Eric is a senior at Johns Hopkins University in Baltimore, Maryland, working toward degrees in neuroscience. This survey is being used as Eric's Undergraduate Research Project. He has the backing of Johns Hopkins University and is conducting the survey under the supervision of Dr. Roberto Salvatori.


Dr. Salvatori is an endocrinologist at Johns Hopkins University who specializes in adrenal and pituitary diseases. He also is one of the foremost researchers in adrenal disease as well as control of growth hormone secretion, genetic causes of growth hormone deficiency, consequences of growth hormone deficiency.


Access Eric's survey here "Qualitative Study on Cushingoid Syndrome Associated with Corticosteroid Replacement Therapy" or on the NADF Website (www.nadf.us).


The survey should be completed by patients who have adrenal insufficiency, with the exclusion of those who have adrenal insufficiency due to adrenoleukodystrophy, adrenomyeloneuropathy, congenital adrenal hyperplasia (all types) and/or AIDS.


Thank you so much for your participation!

Wednesday, December 02, 2009

Diagnosis of Adrenal Insufficiency Using the GHRP-6 Test: Comparison with the Insulin Tolerance Test in Patients with Hypothalamic-Pituitary-Adrenal Disease

B. Alaioubi1, K. Mann1, S. Petersenn1

1 Department of Endocrinology and Division of Laboratory Research, University of Duisburg-Essen, Essen, Germany

Abstract

The insulin tolerance test (ITT) is considered the gold standard for the diagnosis of adrenal insufficiency (AI). However, the test is unpleasant to perform and has the risk of serious complications. We therefore evaluated the clinical applicability of GHRP6, which is a known activator of the hypothalamic-pituitary-adrenal (HPA) axis, to test for AI. For this purpose a comparative clinical study was designed.

 

Forty-nine patients with suspected dysfunction of the HPA axis and 20 healthy controls were enrolled. The ITT was performed in patients, and GHRP6 (1 μg/kg) testing in patients and controls. Serum cortisol over 90 min after GHRP6, in comparison to the ITT, was the main outcome measure.

 

Thirty-one patients had a peak cortisol response of less than 500 nmol/l during ITT and were considered adrenal insufficient. For GHRP6, the mean cortisol peak was 227±25.7 nmol/l in the AI group versus 395±35.3 nmol/l in the adrenal sufficient (AS) group. ROC analysis of peak cortisol levels during GHRP6 test suggested an optimal threshold of 299 nmol/l for the diagnosis of AI (Sens. 71.0%, Spec. 77.8%). Applying upper (416 nmol/l) and lower (137 nmol/l) thresholds with high specificities in combination with early morning cortisol established the diagnosis in nearly half of the patients, even when the GHRP6 test is limited to 30 min duration. GHRP6 led to significant activation of the HPA axis with no detectable side effects, but had limited accuracy in comparison to the ITT.

Key words

growth hormone secretagogues - ghrelin - insulin tolerance test

 

From http://www.thieme-connect.de/ejournals/abstract/hmr/doi/10.1055/s-0029-1243184

Tuesday, December 01, 2009

Jane Austen 'died of tuberculosis not hormonal disorder'

Jane Austen probably died of tuberculosis after drinking unpasteurised milk rather than falling victim to a rare hormonal disorder as is generally assumed, research shows.

 

By Matthew Moore
Published: 8:00AM GMT 01 Dec 2009

 

 

The Pride and Prejudice novelist's premature death aged just 41 has long fascinated medical historians, with several explanations offered for her assorted and curiously mild symptoms.

 

Most biographers have accepted a posthumous diagnosis published in 1964 that she was one of the first known sufferers of Addison's disease, in which patients' adrenal glands fail to produce sufficient steroid hormones.

 

But a new reading of Austen's letters indicates that the Emma and Persuasion author was far too lucid in her final days in 1817 to have been dying of Addison's, whose victims usually endure a loss of concentration bordering on delirium as their condition worsens.

 

Austen was part way through her seventh novel Sandition when she succumbed to the sickness that had dominated her past two years, and was cogent enough to dictate lines of comic verse from her sick bed just 48 hours before her death.

 

Two months earlier she had written to a friend: "My head was always clear, and I had scarcely any pain."

 

Katherine White, a scholar and Addison's sufferer, wrote in the Medical Humanities journal that this evidence alone appears to rule out Addison's.

 

"While Austen was undoubtedly an exceptional intellect, this clarity of thought is not typical of advanced adrenal failure," she wrote.

 

"Extreme sleepiness, slurred speech, confusion or a semi-conscious state of characteristic of adrenal crises."

 

Addison's was first proposed as the cause of Austen's death by Sir Zachary Cope, a respected surgeon who specialised in abdominal conditions.

 

He based his diagnosis – proposed nearly 150 years after her death – on letters sent by the author in which she lamented her bed-ridden exhaustion, bilious attacks and rheumatic pains. Austen's skin also changed tone, turning "black and white and every wrong colour" as she wrote in a letter to her niece.

 

While acknowledging that these symptoms could indicate Addison's, Mrs White argues that an apparent improvement in Austen's condition as death approached pointed to alternative explanations.

 

"The absence of pain during her final months is revealing: intense migraine-like headache and generalised arthralgias are the norm for contemporary patients." she wrote.

 

That the comic writer did not appear to suffer severe weight loss further undermines the Addison's diagnosis, according to White.

 

She suggests that disseminated tuberculosis affecting the joints and liver – which Sir Zachary proposed as a possible cause of the Addison's – offers a "simpler" and sufficient explanation for Austen's symptoms, particularly as it was rife in the early 19th Century.

 

The infection likely had bovine origins, she adds, suggesting Austen may have ingested bacteria by drinking milk that had not been treated, like many of her contemporaries.

Austen died in the Hampshire town of Winchester where she had travelled for medical treatment. She was buried in Winchester Cathedral.

 

Historians have struggled to decipher the private life of the woman behind some of the most enigmatic characters in English literature because her sister Cassandra burned many of her letters and documents after her death.

 

Tuberculosis was the biggest killer in 19th century Britain, but today almost all strains can be controlled by antibiotics. Addison's disease used to be fatal but steroid replacement therapy now allows most sufferers to live a normal life.

 

From http://www.telegraph.co.uk/culture/books/booknews/6692503/Jane-Austen-died-of-tuberculosis-not-hormonal-disorder.html