New Bloggers!

Hello dearest readers! 

I just wanted to take a moment to draw your attention to two new bloggers that have been added to the sidebar to the right --------->

Brotha writes about Living with Acromegaly at acromegallic.blogspot.com.  "I'm trying to find a way to turn this into something positive, so I decided to write about it and share my day, feelings, fears, joys, and whatever else I may think of with you. And in turn my this will be therapeutic for me and entertaining to you."  Brotha is so inspiring!

Emer was diagnosed with a pituitary adenoma secreting thyroid-stimulating hormone less than a year ago, and she writes about all kinds of pituitary tumors in her incredibly humorous blog Pituitary Ademoaner (pituitaryademoaner.blogspot.com).  In her recent post profiling famous people with pituitary tumors, she writes,  "Acromegalicious folk are obviously awesome," and I think she's awesome too!

Check out both blogs when you have the chance, and make sure to introduce yourself or say hello to them in the comments!

If there's anyone else out there that wants to be added to the roster, just leave a comment on this blog with a link to yourself!

No more octreotide hydrogel implant

Endo Pharmaceuticals reportedly stopped development of their octreotide implant, despite studies that showed that it was safe and effective.  I wonder why?  I mentioned the discontinuation of the implant to my husband, and he suspected that everyone's focus has shifted to oral ocreotide (a pill that would deliver the same medication).  Maybe so, but with a pill you have to remember to take it every day (or however often), you'd probably have to keep it refrigerated so travel might be annoying, and of course there would still be the whole hassle of getting your prescription filled, etc, etc.  Don't get me wrong! The pill sounds great too!  But I really wanted to try the implant and I was waiting for it to become available.

I tried to join the clinical trial for the implant a few years ago, but I was disqualified because my growth hormone levels were beyond the allowable levels while on an alternate medication.  I was so disappointed!  That implant gave me the promise of being "normal" for 6 months at at time... no injections every few weeks, no visits to the medical center, and no struggles between the health insurance and pharmacy every time I had to refill my prescription.  No reminders that I'm different than everyone else for 6 months.

Earlier this year I met one person at the acromegaly community conference who had the implant, and she seemed pretty happy with it (she made it into the clinical trial plus they had an extension).  I looked at the place where her implant was inserted and it looked pretty subtle, it seemed comfortable enough, and if it's true that you don't have to think about it for 6 months, then I'd be so thrilled!

These days I have my intramuscular ocreotide injection administered at home, by my husband who has been trained by a nurse on how to do it properly.  I also have a short acting subcutaneous version I give myself in addition to the long acting one, just for days when I can feel my symptoms acting up (swelling, headaches, joint pain, acne, etc).  I just happened to have my intramuscular shot today and that's what reminded me of the article I saw about the implant being discontinued.  Even having the shot done at home is still a hassle, with the ordering/refilling, storing, scheduling, mixing and injecting.  I have a huge bin of "sharps" in one of my cabinets and every time I see the medication in the fridge I'm reminded that there's something wrong with me.  I worry about what people will think if they see all my sharps in the bin and the medication when they come over.  Oh yeah, and sometimes the injection hurts (although my husband has gotten really good at making it quick and relatively painless).

I wish they would have continued bringing the implant to the market.  If nothing else, it would have given acromegaly patients like us OPTIONS and potentially FREEDOM from a routine of ongoing injections.  I was so happy that people were at least trying to make our lives a little easier, as opposed to just accepting whatever existing treatments were out there already.  I appreciate the all the work that every researcher does towards creating new treatments (everything that's out there right now, things that are shelved like the implant, and the oral one that's in the works).  It's important that people keep working on better treatments, and don't forget that as the acromegaly treatment landscape more competitive, it could drive the prohibitively high price of treatment down for everyone.

Anyway, hopefully people are really just working on a real end-of-story CURE for all us.  There's some amazing research going on out there with viruses plus our own immune system that has shown to be effective for cancer.  It can't be that much further down the line before this knowledge is targeted towards pituitary tumors!  Till then, I hope we'll all be here for each other.

Woah!

via http://www.guardian.co.uk/science/2011/nov/09/pituitary-glands-embryonic-stem-cells

This could lead to some very interesting treatments for those who have hypo-pituitary symptoms after radiation or surgery.  And eventually, who knows how this could impact the treatment of acromegaly?

Pituitary glands grown from mouse embryonic stem cells

If the same trick can be repeated for human pituitary glands it could transform the treatment of debilitating hormone disorders

• David Derbyshire
• guardian.co.uk, Wednesday 9 November 2011 13.26 EST
• Article history

Mouse pituitary tissue grown from embryonic stem cells. Fully grown glands produced hormones when transplanted into mice. Photograph: Yoshiki Sasai/RIKEN

Scientists have grown working pituitary glands in the lab that could potentially transform the treatment of people with a range of debilitating hormone disorders.

The team of Japanese researchers grew the tiny hormone-secreting organs using stem cells taken from a mouse embryo. When the tissue was transplanted into mice with pituitary gland defects, it raised levels of the missing hormones in their bodies.

Dr Yoshiki Sasai, who led the study at the RIKEN Centre for Developmental Biology in Kobe, Japan, said: "It is difficult to guess how long it will take, but we hope that we can produce human pituitary tissue in the next three years." It would take longer to develop techniques to transplant the cells, he added.

The creation of spare body parts for transplant is one of the goals of stem cell science. Stem cells are the body's "master cells" and can turn into a range of different types of tissue, such as brain, muscle or pancreatic cells.

Any tissue or organs grown from patients' own stem cells would not be rejected by the body, doing away with the need for immunosuppressant drugs.

Pituitary glands – the oval, pea-sized organs at the base of the brain – are a particular challenge for stem cell researchers because they are so complex. They have two distinct parts and secrete at least eight hormones regulating growth, fertility, breast milk production, blood pressure, contractions during childbirth, temperature and water balance.

Using mouse stem cells arranged in a three dimensional culture, Dr Sasai's team mimicked the way pituitary glands develop in the embryo. The resulting tissue contained all five types of cell found in a normal gland and took around three weeks to grow, the scientists report in the journal Nature.

"We have made hundreds of pituitary glands from embryonic stem cells," said Dr Sasai. When the tissue was transplanted into mice with pituitary defects, levels of missing hormones in their bodies rose to normal.

Although the researchers used embryonic stem cells in their experiment, they believe the technique could work with stem cells derived from adult tissue – so-called induced pluripotent stem cells. That would avoid the ethical concerns some people have about using human embryos in research and therapies.

Even if the scientists can grow a human pituitary, they still face major obstacles in creating a safe and efficient way to transplant it, Dr Sasai said. However, he believes lab-grown glands could lead to treatments for growth hormone deficiencies and damage to the pituitary glands caused by surgery and Sheehan's syndrome.

Women with Sheehan's syndrome, which results from blood loss during childbirth, have problems breastfeeding, suffer tiredness, weight gain, constipation, low blood pressure and slowed thinking.

Prof Robin Lovell-Badge, one of Britain's leading stem cell experts at theMedical Research Council's National Institute for Medical Research in London, said: "It is unlikely that these in vitro-derived pituitaries are fully developed and make hormones in precisely the same way as normal.

"However, the fact that they got as far as they did is impressive. It suggests that there is a fair amount of self-organisation, which means that it might be easier than we thought to build not just pituitaries, but also other organs from embryonic stem cells and induced pluripotent stem cells – as long as they are not too complex.

"It also opens up new possible ways for treating patients with defective or missing pituitary glands."

2nd California Hormonal & Pituitary Health Symposium

2nd California Hormonal & Pituitary Health Symposium
 

Saturday, October 22, 2011
7:30AM-4:00PM
Santa Monica College Performing Arts Center
The Edye Second Stage
1310 11th Street, Santa Monica, CA 90401

THERE IS NO CHARGE TO ATTEND THIS EVENT
Continental Breakfast and Box Lunch included. Seating is limited!
You must pre-register to attend !

To register, go to

https://www.academiceventmanagement.com/event_detail.php?id=31

or call Pat Fitzwater at 805-300-9154
or email pat@academiceventmanagement.com

For more info, please visit the web @

http://brain-tumor.org/files/Patient%20Symposium%20Oct%2022%20Agenda%20for%20BTC%20Website%20PDF.pdf

(PDF file)

Raw Food Diet

I've been trying to change my diet for my health the last few years since I've had Acromegaly and as a result, high blood pressure. I grew up on a high dairy diet (I loved milk, cheese, ice cream and eggs), then as an adult I transitioned to a higher protein, higher fat diet (thank you fast food) which also included high dairy. It seems a 100% raw food diet may be much more beneficial than I first thought. When I tried to go raw before I didn't stick with it, in part due to habit and societal reasons. What I didn't realize at the time, was that I was also probably in a detox phase that was uncomfortable. If I can find the motivation I'm going raw/organic. It's sobering to think my own diet may have caused my Acromegaly. I wish there was a way to cure or reverse the condition without medications. I've already transitioned to a very low salt diet (way under 1500mg/day) and have lowered my blood pressure to a normal level so that I don't need blood pressure medication anymore. My skin also looks better, it's no longer super dry to the point of flaking, and I have less acne.

Why Raw Food?

New guidelines for the treatment of acromegaly, a serious growth hormone disorder

By Jon Danzig, award-winning medical journalist [email Jon Danzig]

Introduction

It’s said a lot can happen in seven days. In seven years, a lot has happened in the understanding of acromegaly, a debilitating condition that causes a patient to have too much growth hormone.
It’s seven years since the American Association of Clinical Endocrinologists last produced guidelines for the diagnosis and treatment of acromegaly. Their 2004 guidelines were just 13 pages long. Their latest, the 2011 guidelines, have grown – to 44 pages.
In 2004, the Association reported acromegaly as an “uncommonly diagnosed” disorder with an annual estimated incidence of 3-4 cases per 1 million people. In the 2011 guidelines, it’s added that newer studies suggest a much higher incidence (although I believe the authors meant prevalence, not incidence). A Belgian study proposing 130 cases per million; a German study concluding 1,034 cases per million. This, reports the Association, suggests that acromegaly “may often be under-diagnosed”.

In 2004, the guidelines made no mention of the psychological damage caused by acromegaly. In contrast, the new 2011 guidelines discuss possible irreversible “psychological alterations” associated with the disease, including depression, mood swings and personality changes. Similarly, the 2004 guidelines made no reference to acromegaly patients ‘quality of life’. By comparison, the new guidelines acknowledge that patients with active acromegaly, and even those in remission, can have significant quality-of-life issues that it recommends should be addressed.

The 2004 guidelines agreed that the gold standard check for acromegaly was an oral glucose tolerance test, with a normal result being a growth hormone level of less than 1 ng/mL. The Association now suggests that be changed – to less than 0.4 ng/mL.
Although the 2011 guide doesn’t report any new drugs since 2004, novel ways of combining the existing drugs are featured, with efficacious and cost benefits.
And yet...

• Both the 2004 and the 2011 guidelines report no change in the delayed diagnosis for acromegaly – it’s still up to ten years.
• Both the 2004 and 2011 guidelines report no change to the proportion of patients found with large tumours – it’s still around 80%. For them, surgical cure rate, even in the best hands, is still 50% or less.
• Many patients with acromegaly still have uncontrolled disease.
• Even those in remission can suffer “quality-of-life” issues years later.
• Most people with acromegaly, of which there may be many more thousands than previously realised, remain undiagnosed.

So, despite the impressive increase in size of the growth-disorder-guidelines over seven years, the improvements seem to have been more subtle and slow.
Below I have presented my own stylised summary of the 2011 guidelines. This I’ve put together mainly for patients, their families and friends, and primary care attendants, all of whom can play a vital role in the earlier detection of this potentially life-threatening condition.

Defining

The definition of acromegaly is clear enough: it’s the excess secretion of growth hormone, causing “multi-system associated morbidities” and “increased mortality.” In almost all cases, the cause is a non-cancerous tumour of the pituitary, a pea-sized gland that’s situated at the front base of the brain and responsible for producing hormones that drive many vital functions of the body.

There’s no doubt that acromegaly is a serious illness, with a long list of debilitating and often disfiguring symptoms. (Hardly “relatively symptom-free” – the claim made by one ‘expert’ doctor that caused me considerable problems when I objected. See The Guardian newspaper report:  ‘Charity accused of mistreating its members.’)

The Association’s new guide reports that acromegaly can lead to “a myriad of soft tissue and bone overgrowth” problems. Most patients (86%) will present with enlargement of their extremities (hands, feet, nose), excessive perspiration (up to 80%), thyroid nodules (73%), joint pains (75%), facial changes (74%), sleep apnoea (70%), carpal tunnel syndrome (up to 64%), type 2 diabetes mellitus (56%), and headaches (55%).

About half of patients will have a pituitary tumour that also secretes excess prolactin, a hormone primarily responsible for stimulating milk production after childbirth. This hormone, in surplus, contributes to menstrual problems in women and testosterone deficiency and sexual dysfunction in men.

Almost half of patients will present with high blood pressure, impaired glucose tolerance and heart disease. Many acromegaly patients commonly report fatigue and weakness. And new for the 2011 guidelines, the Association reports that acromegaly appears to be associated with psychological changes and alterations in personality. Patients often have depression, apathy and considerable mood changes. One study suggested that acromegaly could cause cognitive impairment, but the Association advises that further investigations need to be undertaken.
Other factors include an increased risk of cancer, although a possible connection with colon cancer remains unclear. The tumour itself can also cause visual defects. My summary isn’t exhaustive. The list of recognised symptoms associated with acromegaly has grown since the 2004 guidelines. I suspect even more will be discovered in the next seven years.

The biggest risk of all, however, remains the same: untreated acromegaly is associated with a 2 to 2.5 times increased mortality compared to healthy people. Fortunately, this risk is abrogated – or cancelled – once acromegaly is properly controlled. What is the correct definition of ‘properly controlled’ is still being continuously debated and refined.

Finding

Finding and diagnosing acromegaly patients as early as possible is still the best way to achieve an outright cure and avoid the long-term disabilities associated with the disease’s progression. Yet the 2011 report states that diagnosis is typically delayed by 7 to 10 years in most patients. By then, the pituitary tumour is usually large and more difficult to completely remove with surgery.

Even in the best hands, surgical cure rates of patients with a large pituitary tumour are only between 40% and 50% (and surgery is usually considerably less successful if the tumour is very large and/or the growth hormone levels are very high).

There’s also a financial incentive to ‘find and fix’ acromegaly patients as soon as possible. Acromegaly is a disease “with a substantial financial economic burden”. In Canada, ongoing treatment for patients who had large tumours cost on average CAN $11,425 per year (about £7,000 per year; 1998 figures, no doubt higher now).

Early diagnosis of acromegaly is rarely achieved, however. That’s because, states the 2011 report, the onset of acromegaly is insidious and often non-specific, with symptoms such as lethargy, headache and increased sweating – signs often mistaken for ageing.

Surprisingly, only a fraction of patients are discovered because of the classic signs of acromegaly, that slowly develop over years (enlarged feet, hands, lips, nose and jaw; often protruding forehead and rough, pronounced facial features). Most often patients themselves are not even aware of the harmful changes happening to them, because they are so gradual.
There’s a need, reports the 2011 guidelines, for primary care physicians and other medical groups to be better educated to watch out for the signs and symptoms of acromegaly so that earlier diagnosis can be achieved.

The dentist, for example, could be suspicious of a patient whose lower jaw is protruding further than the upper jaw – a typical symptom of acromegaly patients. The optician should be alerted by a visual field defect that might be caused by a pituitary tumour. Rheumatologists often test for disorders that might also lead to a diagnosis of acromegaly.
The new guidelines propose that doctors should consider acromegaly when two or more of the following 12 symptoms are present:

1. New onset diabetes
2. Wide spread joint pains
3. New or difficult to control high blood pressure
4. Heart disease
5. Fatigue
6. Headaches
7. Carpal tunnel syndrome (pain in hand and fingers)
8. Sleep apnoea (snoring with breathing difficulties)
9. Excessive sweating
10. Loss of vision
11. Colon polyps
12. Increasing difficulties in closing the jaw

Once suspected, acromegaly is easy to diagnose. A simple and quick blood test to check for abnormally high serum IGF-1 levels is reported in the new guidelines to be “excellent for diagnosis, monitoring and especially screening” for acromegaly. It’s vital, however, that the IGF-1 test is age and sex matched to normal subjects.

IGF-1 (insulin-like growth factor 1) is produced by the liver in response to growth hormone secreted by the pituitary gland. IGF-1 then circulates in the body and stimulates cell growth. In acromegaly, excessive growth hormone generated by the pituitary tumour leads to the liver over-producing IGF-1.

A random one-off measurement of growth hormone itself is not helpful as it’s too variable. Measuring growth hormone levels to diagnose acromegaly requires a more specialist procedure, called an Oral Glucose Tolerance Test, and is still considered the ‘gold standard test’ for acromegaly.

After drinking the glucose following over-night fasting, blood is taken every half-an-hour for two hours. In patients without acromegaly, serum growth hormone levels will fall to 1 ng/mL or less (although the Association is now considering a new cut-off point of 0.4 ng/mL). In patients with acromegaly, the glucose fails to suppress growth hormone levels and they remain above 1 ng/mL.

However, the new guidelines also state that this ‘gold standard test’ can be skipped altogether if IGF-1 is elevated and there are signs and symptoms of acromegaly. That certainly makes diagnosis simpler, quicker and cheaper.

Following confirmation of acromegaly, an MRI-scan should be ordered to check the size and exact location of the tumour attached to the pituitary gland.

Patients diagnosed with acromegaly need to be regularly re-tested for the rest of their lives. The pituitary tumour has been known to recur, sometimes many years later.

‘Fixing’

Most patients with acromegaly are never fully ‘fixed’ or entirely free of the disease and its long term damage. Some may disagree, but I believe it can be postulated. After all, it’s rare for chronic internal medical diseases to be 100% ‘fixed’; more usually it’s hoped that they can be improved or put into remission or controlled.

As Professor Laurence Katznelson, Chair of the committee that drew up the new guidelines, wrote to me, “Many patients with acromegaly are left with residual difficulties."

Subsequently, some acromegaly patients have also written to me saying it’s inappropriate for doctors to use the term ‘biochemical cure’ - meaning their blood test results no longer show signs of acromegaly – when they continue to suffer debilitating symptoms.

Out of 100 patients discovered with acromegaly, about 20 will have a small pituitary tumour and about 80 a large one. Depending on which surgeon operates, surgery alone will result in a ‘biochemical cure’ in only about half, more or less, of the 100 patients. Medication or radiation will achieve ‘biochemical cure’ in many, but not all, of the rest.

Although ‘biochemical cure’ is now much more achievable than previously, and can result in considerable improvements for patients, it’s agreed that it doesn’t necessarily equate to satisfactory elimination of the disease and its consequences in many patients.

This is discussed in the new guidelines, which report that many patients who have been in ‘biochemical remission’ for years continue to suffer quality-of-life issues, especially relating to musculoskeletal complications resulting in significant joint pains. Adverse changes to appearance caused by the disease can also cause profound difficulties. Unlike soft tissue changes in acromegaly, bone enlargement caused by the disease is permanent.
Significant psychological issues can also persist despite the biochemistry apparently being in normal range. The new guidelines raise the possibility that acromegaly can cause irreversible changes to mood and behaviour. The authors recommend that all acromegaly patients, whether with active disease or in remission, have attention to quality-of-life issues.

New theory on why ‘cured’ acromegaly patients still suffer New research conducted jointly in the Netherlands, Denmark and the USA proposes a novel theory as to why so many acromegaly patients apparently under ‘biochemical control’ still have ongoing symptoms. If the theory transpires to be true, it could radically change the medical treatment for all acromegaly patients who fail to be cured by surgery alone. The international team of doctors put forward a new paradigm – or model – for ‘systematic acromegaly’ that affects patients who are treated with an acromegaly medicine that’s widely used called ‘long acting somatostatin analogues’ . According to the new theory, these patients could still have acromegaly in many parts of the body, other than the liver, because of the way this particular medicine works. Consequently, this ‘remaining acromegaly’ is hidden as it doesn’t show up in IGF-1 testing. It means, say the researchers, that these patients continue to suffer the damaging effects of excess growth hormone, even though their biochemistry indicates that they are in ‘normal range.’ The research team, led by Dr Sebastian Neggers of Erasmus University in the Netherlands, has named this ‘peripheral’ or ‘extra-hepatic acromegaly’ (i.e. acromegaly outside the liver). He claims that this ‘peripheral’ form of acromegaly has, “a significant negative impact on the quality of life of many patients who were previously considered to be biochemically cured.” The authors of the concept claim that, if their hypothesis is correct, it could mean that the medical treatment for acromegaly patients will require “a significant update”. In particular, their theory challenges whether IGF-1 is a reliable marker of disease activity in acromegaly patients. There is a need, the researchers believe, for newer measures of acromegaly to be developed, “either genomic, metabolomic, proteomic, or others” which integrate both ‘hepatic’ and ‘peripheral’ or ‘non-hepatic’ forms of the disease. Such new markers of the disease could also help to optimise treatment on a more individual basis, especially with regard to ‘quality of life’ issues. Dr Neggers and his co-workers also conducted additional research indicating that if treatment with ‘long-acting somatostatin-analogues’ is combined with another drug, called pegvisomant, this can successfully resolve the “remaining, peripheral form of acromegaly.” (See section on ‘medication’ below). However, the new theory does not appear in the new American guidelines for acromegaly, and Dr Neggers admits that, “around the world there are some non-believers.” One leading professor of endocrinology told me he remained “agnostic” about the hypothesis. The American Association of Clinical Endocrinologists advised me that they only included data in their latest guidelines that had achieved “general consensus”, but if the new theory proved to be accurate, it could appear in the Association’s next guidelines. Dr Neggers and his team are now calling for other scientists, clinicians and pharmaceutical companies to conduct further studies to test whether their theory is correct.

New research in Germany indicates that acromegaly might affect millions more people than previously thought. In the past, it was estimated that the world-wide prevalence of acromegaly was only about half-a-million. But if the German study quoted in the new American guidelines is correct, the worldwide prevalence of acromegaly might be as high as 7 million.

Also of interest, acromegaly appears to affect both sexes and all races in equal proportions.
There’s no known way to avoid getting acromegaly, since so far we are not even sure what causes it in the first place. The best chance for patients is to be discovered in the very early stages of the disease, when the tumour is small and there’s the highest chance of a real cure through surgery alone. For the rest, the majority, the doctor’s toolbox is limited: to surgery, medication or radiation.

The new guidelines report five goals in the treatment of acromegaly:

1. To bring the chemical measures of acromegaly to normal
2. To control the size of the tumour
3. To reduce the signs and symptoms of the disease
4. To prevent or improve medical conditions related to the disease
5. To prevent premature mortality

The following methods can be used alone or in combination to try and achieve these goals:

Surgery – it remains the most effective option to achieve rapid and complete cure for all patients who can have surgery. Even if cure doesn’t occur, the reduction in tumour mass can result in considerable recovery and also improve the response of subsequent medication. These days most pituitary surgery is endoscopic transsphenoidal through the nose, which is minimally invasive. The most experienced surgeons – those performing at least 50 transsphenoidal procedures a year – have the best outcomes with low mortality and morbidity.

Medication – for those who cannot have surgery, and for those for whom surgery did not result in a ‘cure’. There is also some evidence, according to the new guidelines, that medication taken prior to surgery might result in a better post-operative outcome.
There are three classes of medical therapy: dopamine agonist, somatostatin analogues and a growth hormone receptor antagonist:

*Dopamine agonist – (tablets) usually cabergoline. Sometimes used as a first-line medical therapy because it’s taken orally and inexpensive. However, it’s only effective in a minority of patients, and usually only considered for patients with ‘mild’ acromegaly.

*Somatostatin analogues – (injections) usually octreotide LAR or lanreotide autogel. The new guidelines report that with this medical therapy, about 55% of patients achieve normal growth hormone and IGF-1 levels. The medication can also result in modest or significant reduction in tumour size in some patients. There have been mixed studies of whether treating with somatostatin analogues prior to surgery improves the results, and the guidelines authors state that further study is needed on this.

*Growth hormone receptor antagonist – (injection) known as pegvisomant, this is the most efficacious but unfortunately the most expensive of the drugs available. It works in a completely different way to the other medications. In patients treated with pegvisomant for a year, the new guidelines report that IGF-1 levels were normalised in 97% of patients, confirming it to be the most effective drug currently available. Patients also reported improvements in their signs and symptoms of acromegaly. To be cost effective, however, the guidelines report that the price of pegvisomant needs to be reduced by one third.

*Combination therapy: the new guidelines describe some success with combining the medications when one alone didn’t work sufficiently. For those who only partially responded to somatostatin analogue treatment, the addition of cabergoline helped 42% of them to achieve normal IGF-1 levels. The guidelines also reported that the combination of somatostatin analogues with pegvisomant often appeared to be more effective in normalising IGF-1 levels than either drug used on its own. In one study (featured in the guidelines) the addition of weekly pegvisomant to somatostatin analogue treatment resulted in IGF-1 levels becoming normal in 95% of patients. Another study (not in the new guidelines) demonstrated that this combination resulted in significant improvements to patients’ quality-of-life. Since this combined therapy usually involves lower doses of both drugs, it’s been argued that this can result in cost savings over the use of one drug alone.

Radiotherapy – usually used as a last resort, when surgery and medication haven’t worked. However, the guidelines report that with the availability of effective medication, the role of radiotherapy has subsequently diminished. It is, though, still used to reduce the need for (expensive) lifelong medication and with a goal of ‘disease cure’.
One downside is that it takes a long time for the radiation to work – from several years to over a decade. The guidelines state that techniques for radiotherapy have improved in recent years, with better targeting to the tumour and subsequently less radiation exposure to surrounding tissue.
The results of the more old fashioned ‘conventional radiotherapy’ have recently been reassessed to take account of the stricter criteria of ‘biochemical cure’ for acromegaly. Whereas previously it was thought that conventional radiotherapy resulted in a remission rate of over 80%, that’s now been revised considerably downwards to just 10 to 60%. Furthermore, conventional radiotherapy can take about ten years to be effective – even longer in patients with initially higher IGF-1 and growth hormone levels.

The more modern radiotherapy is called stereotactic radiosurgery, of which there are several versions, but the new guidelines concentrate on reporting ‘gamma knife’ radiosurgery, because it’s the one most referred to in the medical literature for acromegaly. With this newer, more precise form of radiation, remission can sometimes be achieved in two years, rather than ten for the conventional form of radiotherapy. Earlier studies reported remission rates of 90% for gamma knife radiosurgery, but again, with the stricter definitions of cure, this has now been revised to just 17 to 50% remission rates during two to five years of follow-up. The guidelines state that further studies are needed over a longer time-frame.

There are, however, significant drawbacks to radiotherapy, report the 2011 guidelines. One is the development of hypopituitarism –or failure of the pituitary gland – in more than half of patients after five to ten years. Hypopituitarism has been linked to increased mortality. The authors also point out that similar prevalence of hypopituitarism has been found with the more modern stereotactic radiosurgery, although most studies so far have only reported on less than six-years average follow up for gamma knife radiosurgery.

In a recent talk to doctors (not mentioned in the new guidelines) by Professor John Wass, one of the world’s foremost experts in acromegaly, he said, “In the olden days people gave radiotherapy, really without thinking, to patients with pituitary tumours.” He added that the side effects of conventional radiotherapy include hypopituitarism; some patients develop tumours in the field of the radiotherapy; mental agility was also thought to be interfered with; and radiotherapy may also cause acromegaly patients, ironically, to become growth hormone deficient.

Regarding the newer form of radiotherapy, Professor Wass commented, “I don’t think that the data that have been provided for gamma knife radiotherapy are particularly good.”

The new guide also raises similar concerns about radiotherapy, and points out that acromegaly patients who received conventional radiotherapy were at significant greater risks of “all-cause mortality” than those who did not receive the treatment. The 2011 guidelines advise that long-term data of such risks for patients undergoing the more modern gamma knife radiosurgery are not yet available, since most of the data relates to the older forms of radiation delivery. The newer systems may potentially yield better results, but we will not know until longer-term data become available.

My conclusions

The goal of the new guidelines is to, “update clinicians regarding all aspects in the current management of acromegaly...” Patients also need updating, and I’ve tried my best to summarise the latest recommendations primarily for the benefit of patients, although hopefully physicians will find this summary helpful too.

Given a choice, this is actually the best time ever to have acromegaly. You only have to go back to the middle of the last century – within the lifetimes of many of us – when the prospects for acromegaly patients were much grimmer, with fewer therapeutic options and more premature deaths. We’ve come a long way, but not far enough. Most acromegaly patients remain undiagnosed, and most of those who have been diagnosed had to wait an awful long time, and still suffer long term symptoms.

Doctors and drug companies supply, but often only after patients demand. With doctors, patients and drug companies working together, I’m hopeful that the next guidelines issued by the American Association of Clinical Endocrinologists will be able to report faster diagnosis times, a more realistic definition of ‘cure’ and better therapies to achieve either a real cure, or at least substantially improved outcomes.

---

Jon Danzig is a medical journalist and writer/director of short films. He won a Lilly Medical Journalism Research Award for his medical articles, primarily about amniocentesis, episiotomy and women being sterilised ‘against their will’. He was an investigative journalist on the prestigious BBC Checkpoint programme; a freelance correspondent in the USA, and ran his own successful media business, Look-Hear.com. Jon’s growing list of short films can be seen on his new YouTube channel at JonDanzig.com Jon was recently interviewed on BBC Radio about his life and career: Jon Danzig BBC Radio Interview. Click here to view Jon’s Linkedin profile.
Jon’s favourite quote: “Knowledge is power” – Sir Francis Bacon
Declared interest:
The author has acromegaly, and has written extensively about how the illness has affected his life and career. ‘My DIY Diagnosis’ – The Independent Newspaper;‘Acromegaly – A Patient’s Journey’ – British Medical Journal; ‘Challenging Doctors’ – Acromegaly.org; ‘Challenging Sleep’ – Pituitary Network Association. ‘No rest for the wilted’ – The Guardian newspaper

 (via NewsMedical)

A Revision of the Treatment Options in Acromegaly

This is a most interesting and accomplished talk by Professor John Wass, one of the world’s foremost experts in acromegaly, a serious illness caused by a tumour of the pituitary gland, that results in too much growth hormone.

It’s a ‘must view’ video for all physicians who treat patients with acromegaly. It’s also important for acromegaly patients to watch, although some may be upset by parts of the content. That, I am sure, was not the intention of Professor Wass, especially as his talk was aimed at medics, not patients.

During the talk Professor Wass commented that, despite the UK being a developed nation, the rate of control of acromegaly patients is “really very poor”, a situation he described both as “salutary” and “humbling”. For patients with uncontrolled acromegaly it will be even more humbling, since they will know first-hand that the condition can dramatically impair their quality of life, as well as potentially shortening it.

Professor Wass conceded that if surgery fails to control acromegaly, patients are often treated next with cabergoline, a drug that only works in about 20% of cases and might cause heart problems. It’s used because it’s the cheapest option; an indication that in the UK at least, cost more than clinical efficaciousness can influence treatment options. Does this provide a clue as to why so many patients with acromegaly are not adequately controlled? Certainly, if my car broke under warranty and the manufacturer offered a cheap replacement part that only worked in 20% of cases, and could at the same time damage the engine, I would not be happy. Patients are not happy to be offered the cheapest, least effective option, especially in the world’s sixth richest economy.

Neither will acromegaly patients derive much comfort if they learn after-the-event that they were treated by an inexperienced surgeon, now it’s understood, as Professor Wass’s talk demonstrated, that their operations mostly failed as a result. Nor those who were urged to have radiotherapy, only to discover from this talk, maybe for the first time, that doctors gave this treatment “without thinking”. With the benefit of hindsight, as Professor Wass advised in his talk, it’s now known that conventional radiotherapy often doesn’t work, and even years later, can cause serious brain and pituitary damage, as well as result in tumours in some patients.

Of course, doctors have to learn, but often its patients who are the guinea pigs for that learning and who pay the highest price for the gaining of the new knowledge. Armed with this knowledge, however, patients also need to be alert. Ignorance in the past may have been an excuse for doctors offering acromegaly patients cheap, ineffective or potentially harmful treatments and procedures, but this can no longer be acceptable. In the internet and YouTube age, information provided to doctors is now available to patients too. We all have to use it wisely.

      -Jon Danzig

Faces of Acromegaly

There was a study published recently about how a computer can be better than a doctor at diagnosing acromegaly (Early diagnosis of acromegaly: computers vs clinician, PDF) based on photos of acromegaly patients.  I thought that study was really exciting, because it means that potentially one day, anyone with a webcam can be diagnosed!  Of course, the system is not perfect yet, but if it helps encourage people who suspect acromegaly to get a blood test and/or MRI, that means their diagnosis and potential for a cure is that much closer. On the second page of the report, there is a photo of a pair of twins, one who has acromegaly and one who does not, which I thought was fascinating.  There's lots of really interesting info about acromegaly in general, such as, "As the prevalence of a disease in a population rises, the outcome of screening becomes more successful. In the last few years, the presumed prevalence of acromegaly has risen from about 50 per million subjects to 106, 124 and 1034 per million in three separate investigations."  The article is well written and surprisingly easy to read, even for those without a medical/computer science background so give it a look.

The New York Times published an article about faces last week, which briefly mentioned acromegaly as one of the diseases that can be diagnosed by looking at the face: "... a very broad forehead and large nose may signal acromegaly, a dangerous condition caused by too much growth hormone."  I wish they also mentioned jaw enlargement, but I'm glad it was mentioned at all.  Hopefully the article will still help raise awareness of the disease, and someone can get diagnosed earlier.  I wonder if plastic surgeons know about acromegaly, and they refer their patients to an endocrinologist before going ahead with performing their nose jobs/botox or whatever.

Sandostatin LAR injection in Japan

Hello, big wave from Japan! ^^/~~

I've been on Sandostatin LAR for about four years now.

In my hospital, patients who are on this medication use the "Sandostatin LAR Administration Calendar,"provided by Novartis.  I've never seen one of these when I was getting the treatment in the US in 2007, and I like this material quite a lot because it's easy to keep track on the injection site each time.

Anyway, I was quite amazed when I got this injection in Japan for the first time in 2008.

Here is what happened.

The nurse asked me, "Last time you got the shot, where was your injection site?"

I answered, "Right."

Then, she said, "Where in right, upper or lower?"

"?????? (What the...? Isn't right is just 'right,' Miss?)"

I gazed at her, feeling quite confused.

"There are four sites, you know. Which one was it?"

She continued.

"Four? I thought there are only two; right and left."

Then, she brought this "Administration Calendar."

She is right... There are four sites.

I thought two was enough, but here, we are alternating four injection sites.
Is it just Japanese thing?

"Alone in My Universe" - Finally in my hands!!

Hi, I'm Ayaka (Sara) from Japan.

Last week, I ordered the book, "Alone in My Universe: Struggling with an Orphan Disease in an Unsympathetic World." I was initially told that it may take up to 3-4 weeks to Japan, so I thought the books will be delivered in April. Yet, they got here in Tokyo today, March 31st.  SUPER!!

I will give several copies to my primary physicians. I'm sure they will love it.

I scanned the book, and it seems to have wonderful stories from patients and useful information from professionals.

I'm so excited to start reading the entire book.

Thank you, Wayne, for all the work to make this project possible!

Purchase from Amazon.com

Purchase from iUniverse

No Levothyroxine?

Hi, I'm an acro buddy in Tokyo, Japan.
I can't believe one week has already passed since the quake.
You probably know about scheduled blackout and all that, but beside, I'm now very concerned for some pituitary/thyroid patients.

Levothyroxine may become unavailable in Japan.

Here is what is going on...

ASKA Pharmaceutical's Thyradin has a 98% share of levothyroxine in Japan.  Their plant is in Iwaki City in Fukushima Prefecture, where the quake hit massively.  What happened was that there were some damages in the facility, so they cannot produce this medication at this point.

We do have one week month of stock in the nation, but it is clear that we are going to run out pretty soon.  I heard Japan will import levothyroxine from other countries. I hope this problem is going to get solved very soon for all the patients who take this medication.

Fascinating glimpse into the life of a doctor with Acromegaly

from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1825563/pdf/canmedaj00702-0063.pdf (PDF), via Jon

ACROMEGALY AND DR. MARK
S. S. B. GILDER, M.B., Toronto

ON FEBRUARY 4, 1855, an individual was born whose chief claim to fame is that he later developed acromegaly and left us a detailed account of his sufferings. Dr. Leonard Portal Mark was the son of the British Consul at Marseilles and was educated in France and at St. Bartholomew's Hospital, London, which he later served as Draughtsman of Pathology-a forerunner of our present race of medical illustrators.  

Dr. Mark, who in spite of his acromegaly lived to the age of 75, appears to have been a charming Victorian gentleman, bilingual in French and English, cultured, of considerable artistic talent, and with a good athletic background in his youth. After qualification and the completion of his intern appointments Dr. Mark seemed destined to become a fashionable London practitioner. In his book, "Acromegaly. A Personal Experience," he shows how this pleasant outlook was marred by the insidious onset of acromegaly, which gradually took from him much of the enjoyment of life. He begins his book by saying: "When Fate, shaping my 'ends,' decreed that I was to suffer from the malady Acromegaly (akra = ends, itiega big), she perhaps gave me the greatest compensation possible by causing me to enter the medical profession. After the distress caused bv the one and the enjoyment due to the otherboth extending over more than a quarter of a century-I find myself in the unique position of being able to relate a personal experience of this rare complaint as it affected one with some medical knowledge." 

There are several interesting features of this book. In the first place, it did not appear until 1912. when Dr. Mark had had the disease for some 30 years, because for a very long time the stufferer failed completely to diagnose his own case. Fortunately, he had, as a good Victorian, kept a diary from the age of 14 and was able in retrospect to place the date of commencement as 1879 when he was a man of 24. It must be remembered, of course, that the condition was described by Pierre Marie of Paris only seven years later, in 1886, but the striking appearance of acromegalics ensured a rapid diffusion of knowledge of Marie's contribution. 

Although Dr. Mark took about 25 years to diagnose his own condition, others had been aware of it for some years. It was probably first discovered by a friend, Dr. Lloyd, who had to give Mark gas for a dental extraction and called the attention of the dentist to the typically acromegalic lower jaw. A little later, Dr. Archibald Carrod, the Barts' physician, made the diagnosis in a teashop. Mlost dramatic of all, Pierre Marie Canad. M. A. J. Feb. 1, 1955, vol. 72 himself picked Mark out of a crowd at an AngloFrench Medical Congress in London as a typical acromegalic. Yet nobody thought of telling poor Mark what was the matter with him though he lhad an impressive list of symptoms for which he consulted medical colleagues fairly frequently. Some, of course, ssumed that the diagnosis was so obvious that Mark must be aware of it. For example, his brother-in-law, who had been let into the secret, called on him one day and discovered a reprint of an article on acromegaly lving on Mark's table; he drew the natural conclusion that Mark had been studying his own case. 

The most astonishing feature of the situation is Dr. Mlark's own diagnostic blindness, in spite of a very human preoccupation with his many disabling symptoms. He says, "For some 15 or 20 years, each day when I looked into the glass to brush my hair or to shave, there was a typical acromegalic literally staring me in the face. Yet 1 never recognized the fact." He had noticed for years that his hands were getting bigger, yet he never guessed the reason. When he got out his last winter's gloves, and was unable to get them on, he assumed that they had shrunk in the interval. He had arguments with his bootmaker because his boots appeared to shrink, and this malady unaccountably afflicted his hats as well.
The progressive protrusion of the lower jaw made it impossible to chew anything, and his dentist had to fit a denture over the upper teeth to establish contact with the lowers. He remarks that he lost his ability to whistle, and also that his enlarged tongue interfered with his breathing at night (indeed, it almost led to his death under general anaesthesia). And still the diagnosis eluded him. 

At last, one day when he was already 50, the diagnosis came to him while he was walking in the street. He at once discovered that his secret was a secret de polichinelle, and was at first somewhat annoyed at the attitude of his friends. He says, "I felt somehow that I had been duped, that things which I ought to have known, and which by right were mine, had been kept from me. I amn glad to say that this feeling passed away in a few days, and I realized that my friends acted for the best." "Every day since then I . . . . have been more and more convinced that I got my knowledge quite soon enough. 

There are some interesting points of ethics arising from this story. Resisting the temptation to reopen the question of the patient's right to know the truth, we may however note the relation of this case history (which, by the way, includes such classical symptoms as headache, visual disturbances, increasing weakness, and disturbance of sleep rhythm) to the common insistence on early diagnosis. Here is the extraordinary spectacle of an intelligent and well-read clinician failing to make a diagnosis which a finalyear student should be able to make at a glance. Dr. Mark sums up the situation with one of his characteristic touches of humour. "We often pray for 'the gift to see ourselves as others see us.' A vain prayer, methinks, when we realize how blind we would still be if it were granted."  

To close the story, it should be recorded that from the time when Dr. Mark made the diagnosis to the end of his life at the age of 75 he devoted much of his time to attempts to further the knowledge of acromegaly. His name should be added to the roll of those who out of affliction have drawn profit for their fellow-men.

A simple questionnaire to detect acromegaly

A simple questionnaire given to 17,000 patients has revealed a practical and cost effective way to discover undiagnosed acromegaly patients.  The study also suggested a much higher prevalence of acromegaly than previously considered.  The simplest question asked: Has your shoe size increased over the past five years?   (I’ve been suggesting this routine question for many years).

A simple questionnaire to screen for acromegaly

via Jon - thanks!

BBC Radio Documentary: "A Tall Story"

This new BBC radio documentary reveals how it was discovered that, in extremely rare cases, acromegaly/gigantism can have an hereditary cause.  For over 99% of patients, however, the cause is still unknown.

BBC Radio Documentary: A Tall Story

The programme will only be available on the internet for the next 7 days, so make sure to listen and share with those you think might be interested right away!

(Thanks to Jon for sending!)

Patient Voices: Rare Diseases

Listen to Wayne talking to the New York Times about his experience with Acromegaly:

http://www.nytimes.com/interactive/2011/01/20/health/healthguide/te_rare_diseases.html