Weight – the NET Effect

Weight – The NET Effect

Firstly, let me say that I have no intention of advising you how to lose or gain weight!  Rather, I’d like to discuss what factors might be involved and why people with NETs might lose or gain weight either at diagnosis or after treatment.  Clearly I can talk freely about my own experience and associated weight issues. If nothing else, it might help some in thinking about what is causing their own weight issues.

I wrote a patient story for an organisation over 3 years ago and it started with the words  “Did you mean to lose weight”.  Those were actually the words a nurse said to me after I nonchalantly told her I thought I’d lost some weight (….about half a stone).  I answered the question with “no” and this response triggered a sequence of events that led to all the stories in all the posts in this blog (i.e. my diagnosis).

I annoyingly can’t remember at which point I started to lose the weight but I was initially reported to have Iron Deficiency Anemia due to a low hemoglobin result and my subsequent iron test (Serum Ferritin) was also low and out of normal range.  This, combined with the weight loss, the GP was spot on by referring me to a clinic.  The sequence of events during the referral led to a diagnosis of metastatic NETs (Small Intestine Primary). If I had been a betting man, I would have put money on my GP thinking “Colorectal Cancer”.  So my adage “If your doctors don’t suspect something, they won’t detect anything” applies.

I can also tell you that I weigh myself most days at the same time using the same scales. Weight loss or gain needs to be recorded.  Clearly 2 or 3 pounds is nothing to worry about, I found you could put on or lose that amount in a day, depending on time of weighing and food intake. I’m looking for downwards or upwards trends of 7lbs or more (3kg).

Why did I lose weight?

The drop from 12st to 11st was clearly something to do with the anemia symptom (the NETs). But after diagnosis, I had major surgery about 10 weeks later.  When I left the hospital after my 19 day stay, I was a whole stone lighter (14 lbs or 6.3 kg).  I guess 3 feet of intestine, the cecum, an ascending colon, a bit of a transverse colon together with an army of lymph nodes and other abdominal ‘gubbins’ actually weighs a few pounds.

However, add the gradual introduction of foods to alleviate pressure on the ‘new plumbing’, and this is also going to have an effect on weight.  I remember my Oncologist after the surgery saying to use full fat milk – the context is lost in memory but I guess he was trying to help me put weight back on.  I also vividly remember many of my clothes not fitting me after this surgery. In fact, since 2010, I’ve actually dropped 2 trouser sizes and one shirt/jumper size.  I did spend a lot of time in the toilet over the coming months, so I guess that also had an impact!  However, what I wasn’t aware of was the side effect of my surgery.  I started to put on some weight in time for my next big surgery – a liver resection.  The average adult liver weighs 1.5 kg so I lost another 1 kg in one day based on a 66% liver resection.

However, what was also going on was something that took me a while to figure out – malabsorption and vitamin/mineral deficiency. My new ‘plumbing’ wasn’t really as efficient as my old one, so the malabsorption. issues caused by a lack of terminal ileum was slowly starting to have an effect. The commencement of Lanreotide in Dec 2010 added to this complication. That knowledge led me to understand some of the more esoteric nutritional issues that can have a big effect on NET patients and actually lead to a host of side effects that might be confused with one of the several NET syndromes.  What it also confirmed to me was that I could still eat foods I enjoy without worrying too much about the effect on my remnant tumours or the threat of a recurrence of my carcinoid syndrome, something I was experiencing prior to and after diagnosis.

Armed with the ‘consequences of NETs’ knowledge, I did eventually adjust my diet and my weight has now ‘flat-lined’ at around 10 st 7 lbs (give or take 1 or 2 lbs fluctuation).  Amazingly, the same weight I was when I left hospital after major surgery, looking thin and gaunt and not very well at all!  The difference to day is that I have adapted to my new weight and look fit and healthy.

I actually lost another half a stone (7 lbs or 3.5 kg) in 2014 whilst training for an 84 mile charity walk – many commented that I looked thin and gaunt despite being extremely fit from all the training. Perspectives.  It took several months to put the weight back on but at least I knew what had caused the loss and then subsequent gain.

I don’t have any appetite issues although I try to avoid big meals due to a shorter gut, so I snack more.  With the exception of the 4 months of intense training for the 84 mile hike, I cannot seem to lose or gain weight.  As my current weight is bang in the middle of the BMI green zone (healthy), I’m content.

Why do NET patients lose weight?

That’s a tricky one but any authoritative resource will confirm fairly obvious things such as (but not limited to) loss of appetite and side effects of cancer treatments.  NETs can be complex so I resorted to researching the ISI Book on NETs, a favourite resource of mine.  I wanted to check out any specific mentions of weight and NETs whether at diagnosis or beyond. Here’s some of the things I found out:

Carcinoid Syndrome.  Weight loss is listed but not as high a percentage as I thought – although it tends to be tied into those affected most with diarrhea.

Gastrinoma/Zollinger-Ellison Syndrome.  Up to half of these patients will have weight loss at diagnosis.

Glucagonoma.  90% will have weight loss.

Pheochromocytoma.   Weight loss is usual.

Somatostatinoma.  Weight loss in one-third of pancreatic cases and one-fifth in intestinal cases.

VIPoma.  Weight loss is usual.

MEN Syndromes.  One of the presentational symptoms can be weight loss.

Secondary Effects of NETs.

Many NETs can result in diabetes (particularly certain pNETs) and as somatostatin analogues can inhibit insulin, it could push those at borderline levels into formal diabetic levels (including any type of NET using long term somatostatin analogues).  In people with diabetes, insufficient insulin prevents the body from getting glucose from the blood into the body’s cells to use as energy. When this occurs, the body starts burning fat and muscle for energy, causing a reduction in overall body weight. 

Hypothyroidism is another potential issue. 

It must be emphasised that there will always be exceptions and the above will not apply to every single patient with one of the above.

What about weight gain?

You always associate weight loss with cancer patients but there are some types of NETs and associated syndromes which might actually cause weight gain.  Here’s what I found from ISI and other sources (as mentioned):

Cushing’s Syndrome.  Centripetal weight gain is mentioned.  (Centripetal – tends to the centre of the body).  I also noted that Cushing’s Syndrome tends to be much more prevalent in females. Cushing’s syndrome comprises the signs and symptoms caused by excessive amounts of the hormone cortisol (hypercortisolism) or by an overdosage of drugs known as glucocorticoids.

Insulinoma. Weight gain occurs in around 40% of cases, because patients may eat frequently to avoid symptoms.  However, according to an Insulinoma support group site, I did note that after treatment (some stability), things can improve.

Again, it must be emphasised that there will always be exceptions and the above will not apply to every single patient with one of the above.  As in weight loss scenarios, the Secondary Effects of NETs can have an effect.  Hypothyroidism is another potential issue and weight gain is a listed symptom.  I just been diagnosed with hypothyroidism this year but I was not gaining weight!  

The NETs Jigsaw

Like anything in NETs, things can get complex.  So it is entirely possible that weight loss or weight gain is directly caused by NETs, can be caused by side effects/secondary effects of treatment, and it’s also possible that it could be something unrelated to NETs (Dr Liu “Even NET patients get regular illnesses“).  I guess some people might have a good idea of the reason for theirs – my initial weight loss was without doubt caused by the cancer and the post diagnostic issues caused by the consequences of the cancer.

Summary

I guess that weight loss or weight gain can be a worry. I also suspect that people might be happy to lose or gain weight if they were under/over weight before diagnosis (every cloud etc).  However, if you are progressively losing weight, I encourage you to seek advice soonest or ask to see a dietician (preferably one who understands NETs).

Edit:  I changed my blood thinner in May 2017 and lost 2kg (4 pounds) after 6 months.

Edit: I started Creon at the beginning of 2018 (read about this here) and almost immediately put on 2kg (4 pounds) to offset the 2kg loss from 6 months prior.  However, no real change after 3 months of Creon (March 2018).

Edit: I was recently diagnosed with Hypothyroidism, one of the symptoms can be weight gain.  Clearly that has not applied to me.  Hyperthyroidism is the opposite condition where weight loss is a symptom.

Edit: Due to a bad chest infection in June 2018 and due to the consequences of the effects of that illness and most likely the treatments undergone, I have dropped three quarters of a stone (~10lbs).  My lightest weight for over 30 years.   To me that is a significant loss of weight in such a short space of time. Currently trying to put it back on again – I need the weight!

Edit: 4 Sep 2018. After the 10lbs (~4.5kg) loss following the chest infection, people who see me regularly have noticed the visible difference. I’m still struggling to get back beyond 10st after 2 months. I’m monitoring this really closely.

Edit: 28 Nov 2018. I’m back at 10st after increasing my dosage of Creon.

Edit: 10 Jan 2019.  I’m back at 10st 3lbs, my approximate weight before the chest infection.  It’s taken 7 months and the recent acceleration coincides with Creon dose increase.

Edit 7th Feb 2019.  Changed from Creon to Nutrizym.

Edit: 17 Mar 2019.  It appears my trouser waist size is back to 32″.  Is the use of Pancreatic Enzymes making me eat more, or getting more nutrients through, or making me eat food which makes me put on weight?

For those wishing to see the output from an online discussion with Tara Whyand on the subject of ‘Weight’ issues for NET patients – please see this link inside my closed Facebook group.

weight online chat
Click the Link to see the online event output

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

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Steve Jobs – the most famous Neuroendocrine Cancer Ambassador we NEVER had

steve jobs 2010
The last few years have reminded me that life is fragile

Steve Jobs died 5 Oct 2011.  RIP Steve, you certainly made a difference to the world of technology and that is still being felt today.  I have a number of google alerts setup and every day the emails arrive in my inbox. The longest email is always the Steve Jobs one, i.e. Steve Jobs is written about more than Neuroendocrine Cancer and other connected subjects. That’s interesting because Neuroendocrine Cancer is the type Steve had, not Pancreatic as is frequently reported.

There are huge differences between Pancreatic Cancer and Neuroendocrine Cancer with a pancreatic primary – click here to read more. 

pancreatic vs neuroendocrine

I’ve mentioned Steve Jobs a few times previously, mainly in my blog The Human Anatomy of Neuroendocrine Cancer. I wrote that blog when I was frustrated about the constant misreporting of Neuroendocrine Cancer as other types of cancer. Others included Nick Robinson (see blog The Devil is in the Detail) and Wilko Johnson (The Ecstasy of Wilko Johnson).  I’ve also suggested in my blog ‘Every Day is NET Cancer Day’ that we need high-profile patient Ambassadors and despite his death, Steve Jobs would have been quite a catch, had he been willing. Curiously, the same thing is happening with Dag Kittlaus (Siri creator) who was diagnosed with a pNET last year.  To add insult to injury, the 2018 death of Aretha Franklin is gong the same way.

A lot has been written about Steve’s cancer experience and much of it is full of ‘what ifs’. However, I’d like to focus on the facts that are known and we can be almost certain about. That said, the precise detail that we (as NET patients) might want, is probably only to be found in Steve Jobs’s medical documents. Many people say that Steve Jobs had a right to personal privacy and I agree, nothing I put here isn’t already in the public domain.

Diagnosis

How was it found?  In 2003, Steve was having a CT scan to examine his kidneys and ureter, as he had developed recurrent kidney stones beginning in the late 1990s. A suspicious lesion was spotted on his pancreas. To cut a long story short, he eventually had more specialist scans and then a biopsy which diagnosed a type of Neuroendocrine Tumour.  There are many mentions of Insulinoma, a pNET which is reported to have a 10% malignancy rate (ISI Book – Woltering et al). It isn’t clear whether Steve had any presentational symptoms of an Insulinoma at this point (i.e. hypoglycemia).  There is also some chatter online about his tumour being a Glucagonoma (another type of pNET).

Initial Treatment

Steve initially tried alternative medicine before having surgery 9 months after diagnosis. There are reports of his medical team urging surgery earlier and his biographer stated that Steve had later regretted this delay. One of his Doctors is reported to have said “Steve was a very thoughtful person. In deciding whether or not to have major surgery, and when, he spent a few months consulting with a number of physicians and scientists worldwide as well as his team of superb physicians. It was his decision to do this”.  He is reported to have gone on to have a ‘Whipple’ type operation in 2004.  It was only then, that his condition was made public.  During that operation, 3 lesions were reported on his liver.

Ongoing Treatment and Surveillance

Most NET patients enter this phase after their initial treatment, it’s also the period where you learn about the cancer and how best to live with it.  There’s not much written about Jobs’ illness between his surgery and his liver transplant but my research uncovered a useful timeline from Bloomberg and other sources:

June 12, 2005: Jobs talks about his fight with cancer during a commencement speech at Stanford University. He says he was diagnosed about a year earlier and that doctors told him he wouldn’t live longer than six months. The cancer turned out to be a form that was treatable with surgery, “and I’m fine now,” he says. Source Bloomberg.  {Author’s note:  an indication he had been told, or his doctors knew, it was a Neuroendocrine Tumor}

January 24, 2006:  Walt Disney chief executive Bob Iger knew early on that Steve Jobs’s cancer had returned and kept it a secret before it became public knowledge, a new biography of Apple’s late chief executive reveals. The day the deal was officially announced, Mr Iger said he was at Pixar’s headquarters for the ceremony when Jobs asked to go for a private walk. On a secluded part of the Californian campus Jobs put his arm around Mr Iger’s shoulder and revealed his cancer was back. “Frankly, they tell me I’ve got a 50-50 chance of living five years,” the Disney CEO quoted Jobs as saying.

2007:  Not much out there except that he was busy launching what might be regarded as Apple’s most successful and iconic product ever – the iPhone.

June 9, 2008: Jobs, while introducing the iPhone 3G at Apple’s developers’ conference, appears thinner and frail. The company blames a “common bug.”

July 21, 2008: Responding to concerns about Jobs’s appearance, Apple says he has no plans to leave the company and that his health is a private matter. Investors aren’t reassured, and the shares fall 10 percent.

July 23, 2008: The New York Times reports that Jobs has been telling associates and Apple’s board he is cancer-free. Jobs had a surgical procedure earlier in the year to address a problem that contributed to his weight loss, the newspaper reports, citing unnamed people close to the executive. The shares climb 2.6 percent.

July 26, 2008: New York Times columnist Joe Nocera writes that he spoke two days earlier on the phone with Jobs, who said his health problems weren’t life-threatening. Jobs declines to go on the record about the nature of his ailment.

Sept. 9, 2008: Jobs, introducing new iPod media players at an event in San Francisco, still looks thin. “Reports of my death are greatly exaggerated,” Jobs jokes. Munster says that while the CEO’s appearance is unchanged since June, “Just the fact that Steve Jobs was up there was a positive.”

Oct. 3, 2008: A posting on CNN’s citizen journalist Web site, called iReport.com, says Jobs has been rushed to the hospital after a “major heart attack.” The shares fall 5.4pc. The stock rebounds after Apple says the report is false.

Dec. 16, 2008: Apple says that Jobs won’t be giving his usual speech at the Macworld conference, renewing concerns about his health. Jobs had used the forum to introduce new products for 11 straight years.

Jan. 5, 2009: Jobs says he is suffering from a hormone imbalance, causing him to lose weight. Jobs vows to remain CEO during treatment. “The remedy for this nutritional problem is relatively simple and straightforward,” Jobs says in an open letter.

Jan. 14, 2009: Jobs gives up day-to-day operations to Cook until June, saying his health problems are more complex than originally thought. Jobs says he will remain involved in major strategic decisions. “I look forward to seeing all of you this summer,” he says in a letter to employees.

By this stage, his cancer is already starting to take its toll on how he looks.

The disease takes its toll over the years

Liver Transplant 2009

It is common knowledge that Jobs had a liver transplant in 2009 in Tennessee (he was on the list in California and Tennessee).  In between his Whipple and then, he appears to have lived (and worked) with his disease and it’s consequences. His issues appear to have been exacerbated by his excessive vegan diet/fads and the effects of the Whipple surgery (many of you will be aware of these effects). For example, he would spend weeks eating the same thing and then suddenly change his mind and stop eating it. He’d also go on fasts. His condition immediately prior to the liver transplant was said to be ‘poor’ and losing more weight (he had been noticeably thinner for some time).

Did Steve Jobs get ‘experimental’ PRRT?

Jobs took a second medical absence for roughly six months in 2009. It wasn’t until June 20th, two months after the fact, that the Wall Street Journal uncovered the fact that Jobs had undergone a secret liver transplant at Methodist University Hospital in Memphis, Tennessee. However, during that absence, Fortune reported Jobs also took an unpublicized flight to Switzerland to undergo an ‘unusual radiological treatment’ (PRRT) at the University of Basel for neuroendocrine cancer, according to Jerry York, the Apple director who died in March 2010.

Post-Liver Transplant

In 2010, Jobs started to feel sick again. He would lose his appetite and begin to feel pains throughout his body. His doctors would do tests, detect nothing, and reassure him that he still seemed clear.  In early November 2010, he was in pain, stopped eating and had to be fed intravenously by a nurse who came to his house. The doctors found no sign of more tumours, and they assumed that this was just another of his periodic cycles of fighting infections and digestive maladies.

Heres’ a great bunch of TV interviews (something Jobs didn’t do very often).  “The last few years have reminded me that life is fragile”.  Click here (worth watching the whole 10 minutes). His final TV appearance was in June 2011 to the Cupertino City Council about the acquisition of land for their new campus.  Worth watching some of it: Click here.

The End

In early 2011, doctors detected the recurrence that was causing these symptoms. Ultimately, he developed liver, bone, and other metastases.  He had a further extended leave of absence from his job before stepping down as Apple CEO in Aug,  Steve Jobs eventually died 5 Oct 2011.

steve jobs 2010
The last few years have reminded me that life is fragile

References

Notwithstanding the Pancreatic Cancer vs Neuroendocrine Cancer issue, I carried out my research mainly using two articles of the many you can find out there:

  1.  “And one more thing” about Steve Jobs’ battle with cancer
    This is a long article and totally fascinating.  Some of the evidence is presented using extracts from Walter Isaacson’s book ‘Steve Jobs’
  2. A Tumor Is No Clearer in Hindsight.  This article comes to similar conclusions than the one above but it’s shorter and easier to read. It’s from the New York times and was written after the dust settled on Jobs’ death (i.e. when more facts were available). There is also input to this article from NET specialists Dr Wolin and Dr Libutti.

  3. Apple chief Steve Jobs: Health timeline since 2003.  This article is from a UK National Newspaper (The Telegraph) but via US Business Publication Bloomberg.

Personal Summary

“A tumor is no clearer in hindsight” is a good summary on the basis that I would have liked much more detail!  During my research, I found many mentions of Insulin as stated above but only one or two mentioning Glucagon, a hormone associated with another pNET type – Glucagonoma. However, looking at this tumor type in the ISI Book (Woltering et al) and the Jobs diagnostic and treatment story, I have some doubts whether this was the precise tumor type. I have some other searches in progress hoping to find something concrete.

Thinking Differently There is no doubt that Steve Jobs was an amazing and very interesting character.  You just can’t see Apple being the Apple it is today without his intervention.  He was famous for being ‘unconventional’ and ‘thinking different’ and I get that element of his character.  I just can’t help thinking that perhaps he should have been more ‘conventional’ with this thinking and approach to treating his cancer. However, we just don’t know what advice he was receiving and what advice he accepted or rejected.  As for the ‘Pancreatic Cancer’ thing – I’ve said this before, I believe patients only say or interpret what their doctors say to them in regards cancer type.

“The most famous patient ambassador we never had”.  I don’t mean any disrespect by that, I’m just emphasising that we need so much more awareness of our cancer and a high-profile patient could do so much to help in this area. If he was so inclined, Steve would have been a fantastic advocate for Neuroendocrine Cancer and there’s an area where perhaps thinking different might be the way ahead. However, I have a suspicion that very famous people don’t really want to talk about their illness and Steve Jobs might even perceive that as a weakness.

And one more thing …….  you may also find this article useful.  It’s titled “And one more thing”

 

Neuroendocrine Cancer Syndromes – Early Signs of a Late Diagnosis

Early signs of a late diagnosis (2)One of the curious things about Neuroendocrine Cancer (NETs going forward) is that it can very often exhibit one or more vague symptoms collectively known as a ‘syndrome’.  Syndrome is an apt word to describe these complications as the most general meaning in medical terms is a group of symptoms that together are characteristic of a specific disorder or disease”.  Having a syndrome can often be the difference between having a ‘functional’ condition or a non-functional’ condition – see more below.

This frequently makes Neuroendocrine Cancer very difficult to diagnose quickly.  It’s a very devious disease.

It’s not all about Carcinoid Syndrome!

Most people think of Carcinoid Syndrome when they discuss NETs. Anyone suggesting that all NET patients get carcinoid syndrome or that all symptoms of NETs are caused by carcinoid syndrome, is WAY off the mark. Firstly, not everyone will have a ‘syndrome’ in addition to their tumours – the percentage is actually well below 50%. Secondly, there are in actual fact, several associated syndromes depending on the anatomical location and type of NET. As an example of one syndrome, statistics vary from source to source but it is estimated that around a 30-45% of all ‘midgut’ patients will present with metastatic disease and around a third of those (∼10-15% of all midgut) will exhibit Carcinoid Syndrome indicating their tumours are ‘functional’ (secreting excess hormones, particularly serotonin).  It follows that Carcinoid Syndrome itself is not that common and it could be the same with other types of NET (even though it can appear more prevalent on forums).

Diagnostic Challenges in NETs (this graphic only covers so-called Carcinoid Syndrome).  Inner segments are the key symptoms, outer segments are some of the potential misdiagnosis/delayed diagnosis. Graphic courtesy of Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128: 1717-1751

Functional / Non-Functional

These tumours and associated syndromes are treatable for most but the difficult part can be arriving at a diagnosis. Moreover, without a syndrome, some of these tumours can be silently growing and as they grow slowly, the ‘silence’ can go on for some years. Even with a syndrome, the root cause can remain disguised as the symptoms are similar to many day-to-day illnesses, again the reason for the title of this blog. Curiously, the lack of a syndrome can sometimes lead to an even later presentation and the consequences that arise (i.e. no signs to aid a diagnosis). In fact a large proportion of Pancreatic NETs are non-functional at diagnosis. There can be the odd exception but in general terms, NETs are either functional (with a syndrome) or non-functional (no syndrome). It’s also possible that patients can move from one state to another.

It’s useful to know about the range of tumor markers and hormone markers – read more here

Syndrome and Tumors – ‘Chicken or Egg’ ?

I’m always confused when someone says they have been diagnosed with a Syndrome rather than a NET type.  You normally need a tumor to produce the symptoms of a syndrome.

The exception might be hereditary syndromes e.g. MEN.  MEN syndromes are genetic conditions. This means that the cancer risk and other features of MEN can be passed from generation to generation in a family. A mutation (alteration) in the various MEN genes gives a person an increased risk of developing endocrine/neuroendocrine tumors and other symptoms of MEN. It’s also possible that the tumors will be discovered first.  It’s complex!

Major NET Syndromes  

(information mainly taken from the ISI Book on NETs with a cross-reference from ENETS and UKINETS Guidelines)

The ISI Book on Neuroendocrine Tumors 2016 (Woltering et al) confirms there are a number of syndromes associated directly and indirectly with NETs and are described as individual syndromes according to their secretory hormones and peptides. The reference publication expands on this list to aid diagnoses by including common presentations, associated tumour types and locations and the offending secreting hormones. You can see why Neuroendocrine Cancer is a diagnostic challenge!

Carcinoid – a syndrome connected with (mainly) serotonin secreting tumours in certain locations (mainly small intestine, lung, stomach, appendix, rectum). The key symptoms include diarrhoea, flushing of the skin (particularly the face), stomach cramping, heart problems such as palpitations, and wheezing. The syndrome is actually caused by the release of a number of hormones, in particular Serotonin, Bradykinin, Tachykinin (Substance P), Histamine, and Prostaglandins.

(there’s also a very rare instance of pancreatic based tumours producing carcinoid syndrome effects – according to ENETs less than 1% of all tumours associated with carcinoid syndrome)

Whipple’s Triad – Whipple’s Triad is the classic description of insulinoma which includes symptoms of hypoglycemia with a low blood glucose concentration relieved by the ingestion of glucose. These tumours can be located anywhere within the pancreas in the cells that make insulin. Insulin is a hormone that controls the amount of  glucose (sugar) in the blood. It moves glucose into the cells, where it can be used by the body for energy. Insulinomas are usually slow-growing tumors that rarely spread. Some of these tumours will be associated with MEN1 syndrome.

Zollinger-Ellinson SyndromeA tumour that forms in cells that make gastrin and can be known as a Gastrinoma. Gastrin is a hormone that causes the stomach to release an acid that helps digest food. Both gastrin and stomach acid are increased by gastrinomas.  This is a condition in which one or more tumours form in the pancreas, the upper part of the duodenum or the stomach (these organs are very close and tightly packed together). These tumours secrete large amounts of the hormone gastrin, which causes your stomach to produce too much acid. The excess acid can lead to peptic ulcers, in addition to diarrhea and other symptoms.  Associated with Gastrinoma (pNET) and Gastric NETs.  Some of these tumours may be associated with MEN1 syndrome.

Werner-Morrison SyndromeVasoactive Intestinal Peptide (VIP) is secreted thus the pNET term – VIPoma –  Sometimes the syndrome is referred as WDHA – Watery Diarrhea, Hypokalemia (potassium deficiency), and Achlorhydria (absence of hydrochloric acid in gastric secretions).  Sometimes known as Pancreatic Cholera. Some of these tumours may be associated with MEN1 syndrome

Glucagonoma.  A tumour that forms in cells that make make glucagon. Glucagon is a hormone that increases the amount of glucose in the blood. It causes the liver to break down glycogen. Too much glucagon causes hyperglycemia (high blood sugar) rendering most patients diabetic. A glucagonoma usually forms in the tail of the pancreas.  Some of these tumours may be associated with MEN1 syndrome.  See also Sweet’s Syndrome below.  Sometimes known as the 4D syndrome – Dermatological, Diabetes, DVT, Depression.

Somatostatinoma is a very rare type of NET, with an incidence of one in 40 million persons. These tumours produce excess somatostatin arise from the delta cells in the pancreas, although these cells can also be present in duodenal/jejunum tissue where around 44% of these tumours occur. Somatostatin is a naturally occurring peptide that inhibits the function of almost all gut hormones (author’s note – this fact should give you an appreciation of how somatostatin analogues tackle associated syndromes whilst giving you certain side effects as a result!)

Pancreatic Polypeptide (PP)PPoma A complicated one and not too much information (even in the ISI book or ENETS Guidelines). However, it’s the third most common type of islet cell tumour (i.e. pNET).  The function of pancreatic polypeptide is not completely understood. Patients present with weight loss, jaundice, and abdominal pain. The diagnosis is confirmed by pancreatic polypeptide levels > 300 pg/ml. Some of these tumours may be associated with MEN1 syndrome.

Hedinger Syndrome – the technical name for Carcinoid Heart Disease and an ideal replacement term now that Carcinoid is being phased out.

Cushing’s – also known as hypercortisolism.  A collection of symptoms caused by very high levels of a hormone called cortisol in the body.   In Cushing’s disease, oversecretion of pituitary ACTH induces bilateral adrenal hyperplasia. This results in excess production of cortisol, adrenal androgens, and 11-deoxycorticosterone. Cushing’s disease, a subset of Cushing’s syndrome, is due to a pituitary corticotroph adenoma and results in a partial resistance to the suppression of ACTH by cortisol so that secretion is unrestrained. In contrast, causes of Cushing’s syndrome may include the following:

•   Adrenal adenoma or carcinoma arise spontaneously. ACTH levels are undetectable.

•   Non-pituitary (ectopic) tumours produce ACTH. They most frequently originate in the thorax and are highly aggressive small cell carcinomas of the lung or slow- growing bronchial or thymic carcinoid tumours. Some produce corticotropin- releasing hormone (CRH) instead, which stimulates pituitary ACTH secretion and can therefore mimic a pituitary tumour.

•   Other causes include NETs of the gastric, pancreatic, and intestinal organs; Pheochromocytomas, and MCT.

The hallmark of Cushing’s syndrome is that ACTH levels are partially resistant to suppression with dexamethasone, even at very high doses. Some MEN patients with pituitary tumours may have Cushing’s Syndrome. AdrenoCorticoTropic Hormone (ACTH) releasing tumours are somerimes known as ACTHoma.

Sweet’s – Dermatitis/rash associated with Glucagonomas.  Not to be confused with Pellagra (B3 deficiency)

Neuroendocrine / Endocrine tumors can be seen in several inherited familial syndromes, including but not limited to:

  • Multiple Endocrine Neoplasia type 1 (MEN1)
  • Multiple Endocrine Neoplasia type 2 (MEN2)
  • Multiple Endocrine Neoplasia type 4 (MEN4)
  • SDHx mutations – Hereditary Pheochromocytoma/Paraganglioma Syndromes.
  • Pituitary.
  • Von Hippel-Lindau (VHL) Disease
  • Neurofibromatosis Type 1 (also known as Recklinghausen’s Disease). Not covered further.
  • Tuberous Sclerosis (not covered further)
  • Carney Complex

see Genetics and Neuroendocrine Tumors

MEN1 – Mainly involved the 3 Ps, Pituitary, Pancreas and Parathyroid.  The pituitary tumours are primarily Prolactinomas, the pancreatic tumours are mainly PPomas, Gastrinomas and Insulinoma.  Many also have association with Zollinger-Ellinson  syndrome (ZES).  Sometimes known as Wermer Syndrome.  Associated with the MEN1 gene.

MEN2A – associated with the RET gene, can result in Medullary Thyroid Carcinoma, Pheochromocytoma, and overactive parathyroid glands characterised by a high calcium level.

MEN2B. An inherited disorder characterised by the certain development of Medullary Thyroid Carcinoma, plus the possible development of pheochromocytomas and characteristic tumours (mucosal neuromas) of the lips, tongue and bowels. Parathyroid disease is extremely rare in MEN2B.  Also connected with the RET gene.

MEN4.  A relatively new MEN variant and related to the CDKN1B gene.  Similar to MEN1 but normally only 2 of the 3 Ps, parathyroid and pituitary; and potentially other places.

SDHx mutations/Hereditary pheochromocytoma/paraganglioma syndromes

  • Succinate dehydrogenase (SDH) is an enzyme which is important for the metabolic function of mitochondria. Patients with mutations of these genes have increased risk of pheochromocytomas, paragangliomas, stomach tumors and kidney tumors.
  • SDHx mutations (SDHA, SDHB, SDHC, and SDHD) can present as Pheochromocytomas/Paragangliomas and other non-NET conditions.  If this interests you see site http://www.SDHcancer.org

Von Hippel-Lindau (VHL) – not an exclusively NET syndrome. VHL is a rare disorder caused by a faulty gene. It is named after the two doctors who first described the disease, and affects about one in 35,000 people. Tumours develop in one or more parts of the body. Many of these tumours involve the abnormal growth of blood vessels in parts of the body which are particularly rich in blood vessels. Areas most frequently affected are the eyes, the back of the brain (cerebellum), the spinal cord, the kidneys, the adrenal glands and the pancreas. People are affected differently, even within the same family. The only VHL tumour which tends to run in families affects the adrenal glands (Pheochromocytoma). Different VHL features tend to develop at different ages. The eye angiomas often develop in childhood. Others, including tumours found in the cerebellum, spinal cord or adrenal glands (Haemangioblastomas and Pheochromocytomas) can develop from late childhood onwards. The kidney tumours are usually the last things that develop, from the mid-twenties onwards.  Most VHL related tumours are benign.

Summary

As for my own experience of syndromes, I did once show symptoms of the most common NET syndrome (currently known as Carcinoid syndrome) where the key symptoms include diarrhoea, flushing of the skin (particularly the face), stomach cramping, heart problems such as palpitations, and wheezing.  You can see why those symptoms are frequently and easily confused with other conditions. If you have a similar diagnosis, you may benefit from looking at something known as The 5 E’s which is a useful list of things to be wary of.

I did have issues for a year or two in 2010 leading up to diagnosis and until my treatment was underway.  I was experiencing flushing and infrequent bouts of diarrhea but I totally ignored it (hear me talk about this). However, it ended up being instrumental in my diagnosis albeit some good luck was involved in getting to that point.  My twist of fate which involved a low hemoglobin score led me to a scan and ‘bingo’.  I had a ‘gastrointestinal blip’ some 18 months previously but that proved colonoscopy negative.  Despite my distant and metastatic tumour disposition and seemingly late diagnosis, I’m current non-syndromic due to “early” intervention and good treatment.  However, my ongoing treatment continues to play its part.

For many, the vague and routine symptoms generated by a syndrome contribute to the fact that NET Cancer is frequently misdiagnosed with some people suffering from the side effects for many years before a correct diagnosis is made.

There are many other less known syndromes that appear to be directly or indirectly connected with Neuroendocrine Tumours and I may update this post if I discover they are more prevalent than I think.  Please let me know if you’ve been told you have a NET related syndrome not listed.

Neuroendocrine Cancer – shh! Can you hear it? 

Thanks for reading

Ronny

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