Neuroendocrine Cancer – Clinical Esoterica

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One of the key awareness messages for Neuroendocrine Cancer is the hormonal syndromes that can often accompany the diagnosis for many people.  As it’s a difficult disease to diagnose, many people struggle with these syndromes for some time before formal diagnosis of Neuroendocrine Cancer.  Some continue to struggle after.

Neuroendocrine Cancer can often be uncannily quiet, but the tumours can be ‘functional’ and over-secrete certain hormones to add or introduce symptoms that mimic many other diseases or conditions, such as Irritable Bowel Syndrome, Menopause, Heart disease and Asthma.   In addition to common symptoms of flushing and diarrhea, others include generally feeling weak, fatigued, pain, agitated, anxious, dizzy, nauseous, acid reflux, skin irritation, anaemic, weight loss, weight gain, low blood sugar, high blood sugar, heart palpitations, headaches, sweating, high blood pressure. Its main trick is to prevent you from being correctly diagnosed and it’s pretty good at it.  For those looking for a diagnosis, it can be very frightening.

One or more of the NET syndromes can be a weird concoction of strange, powerful or terrifying ingredients, designed to make you very ill; and doctors will be confused.

(So called) Carcinoid Syndrome

Certain types of Neuroendocrine Cancer were once referred to by the archaic misnomer ‘Carcinoid‘ – now correctly referred to as a NET prefixed by its anatomical primary location. However, for the time being, the term Carcinoid Syndrome which can be associated with some of these types of NET persists. The classic carcinoid syndrome includes flushing (80%), diarrhea (70%), abdominal pain (40%), valvular heart disease (20% since the introduction of somatostatin analogues), telangiectasia (25%), wheezing (15%), and nowadays quite rarely – pellagra-like skin lesions (5%).  Carcinoid Syndrome is one of the most powerful and dangerous ‘witches brews’. 

Carcinoid syndrome, first described in 1954 by Thorson and co-workers, has the following features: malignant neuroendocrine tumour of the small intestine, normally with metastases to the liver, sometimes with valvular disease of the right side of the heart (pulmonary stenosis and tricuspid insufficiency without septal defects), peripheral vasomotor symptoms, bronchial constriction, and an unusual type of cyanosis. One year later, Dr. William Bean gave the following colourful description of carcinoid syndrome:

“This witch’s brew of unlikely signs and symptoms, intriguing to the most fastidious connoisseur of clinical esoterica—the skin underwent rapid and extreme changes resembling in clinical miniature the fecal phantasmagoria of the aurora borealis.” 

Certain Neuroendocrine Tumours are known to be capable of over secreting (amongst others) the vasoactive substance called serotonin – mainly midgut (carcinoid syndrome in hindgut and foregut is rare and atypical when it presents). It’s commonly thought that serotonin is the cause of the flushing, but this is only partially correct, the flushing also results from secretion of kallikrein, the enzyme that catalyses a conversion to bradykinin, one of the most powerful vasodilators known. Worth pointing out that flushing can be caused by other NET hormonal syndromes.

A 2023 review – how things have changed

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Serotonin is also thought to cause fibrotic lesions of the endocardium (Hedinger Syndrome), particularly on the right side of the heart resulting in insufficiency of the tricuspid valve and, less frequently, the pulmonary valve and, uncommonly, bronchoconstriction. Other fibrosis issues arising from excess secretion of serotonin include mesenteric and retroperitoneal desmoplasia which have the potential to dangerously obstruct important vessels and cause general discomfort at best.

Serotonin can sometimes be a wicked witch – click to read more

But it’s not all about (so-called) carcinoid syndrome

Other witch’s brew flavours include the group of NET syndromes associated with pancreatic NETs with over-secretions including (but not limited to) Insulin, Glucagon, Gastrin, Vasoactive Intestinal Peptide (VIP), Pancreatic Polypeptide (PP) and Somatostatin.   If you have a pancreatic NET and you are symptomatic and it’s not because of treatment, you might assume or have been told you have “carcinoid syndrome”, don’t accept this, look wider at one of the functional pancreatic NET syndromes. Flushing and diarrhea are not just the preserve of carcinoid syndrome.  If as a pancreatic NET you are simply told its carcinoid syndrome without the clinical evidence, read more here.

Other examples of clinical esoterica:

The relationship between hyperinsulinism and a functional pancreatic islet cell tumour was established by William J Mayo, who attempted the first operation for insulinoma in 1927. In 1966, the US pathologist Malcolm H. McGavran and his associates published the first report on a 42-year-old woman with glucagonoma who presented with a metastatic pancreatic tumour, skin eruption, diabetes mellitus, anemia, and elevated plasma glucagon levels in the blood. The journey of gastrinomas had its beginnings in 1955 when Zollinger and Ellison published their seminal paper (this syndrome is called Zollinger-Ellison Syndrome (ZES)).

Vasoactive intestinal peptide tumours (VIPoma) are neuroendocrine tumours secreting vasoactive intestinal peptide (VIP) in an unregulated manner. Verner and Morrison first described them in 1958 as a pancreatic tumour resulting in watery diarrhea and hypokalemia.  This is known as the Verner-Morrison Syndrome

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Read more about these and other syndromes here.

It gets everywhere ……

One of the scariest witch’s brews is the group of symptoms associated with one of the most uncommon types of NET, the catecholamine and metanephrine (adrenaline and noradrenaline) secreting tumours known as Pheochromocytoma and Paraganglioma. These tumours are likely to cause a barrage of symptoms such as High blood pressure, Heavy sweating, Headache, Rapid heartbeat (tachycardia), Tremors, Paleness in the face (pallor) and Shortness of breath (dyspnea).

Double, double toil and trouble

All of the above is a diagnostic nightmare for those who have the symptoms and remain undiagnosed – no fun for the doctors either – this is why we need so much more awareness and education – it’s one of the key aims of all my social media sites.  Another aim of my sites is to support those who are diagnosed as these symptoms can continue following diagnosis and treatment. Many NET patients need constant surveillance and follow-up, many for life.  Neuroendocrine Cancer can be like the Perfect Storm and definitely cause trouble (double toil and trouble).

And there are linkages to hereditary syndromes such as Multiple Endocrine Neoplasia which can sometimes include the familial variants of Pheochromocytoma/Paraganglioma and Medullary Thyroid Carcinoma.  Read more here.  

This is a very spooky disease, it will slowly grow without you knowing, it will mess with your body and mind, and if left alone to plot its devious and destructive course, it will kill.  Some are faster growing but they have the same traits – they just have the potential to kill faster.

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I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

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Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

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