Blood pressure – The NET Effect

Blood pressure (BP) is a commonly discussed subject in my private group of over 13,000 members. But when you look at the prevalence of elevated BP beyond nationally stated thresholds (hypertension), it’s patently obvious that many people with a NET will have elevated BP issues regardless (see figures below). Nonetheless, patients often attempt to link it to NET, including when a diagnosis of NET comes after their hypertension diagnosis, although this is possible sequence in certain scenarios covered in this blog post. I also noted there were several causal sources of hypertension but with many other contributory factors.

Correlation vs causation. There’s no evidence that elevated blood pressure itself is a direct cause of neuroendocrine neoplasms (NENs). Elevated BP (Hypertension) can, however, be a consequence (secondary effect/side effect of certain hormone-secreting neuroendocrine tumours e.g. functioning pheochromocytoma/paraganglioma – but it does not ’cause’ the tumour.

Hypertension is, however, a direct cause of several serious illnesses, particularly those involving the heart, brain, kidneys, and blood vessels. It damages arteries and organs over time, leading to conditions such as heart disease, stroke, kidney disease, and heart failure.

The aim of this blog post is to look at known linkages to elevated BP and NETs. But to repeat above, there’s no evidence that elevated blood pressure itself is a direct cause of developing neuroendocrine neoplasms (NENs).

Prevalence of Hypertension

Clearly differences will emerge from country to country and region to region, but I found they are generally similar indicating similar factors may be involved. I’ll focus on two countries as these statistics are readily available to me online. What struck me was not only the high prevalence in the general population but also the projected number of undiagnosed on top of that.

According to NHS England, an estimated 32% of adults living in private households in England had high blood pressure (hypertension) and 3 in 10 of those were undiagnosed; this equates to approximately 4.2 million adults with undiagnosed hypertension. I think both of these figures confirm what I said above in that many people will have this issue even without NET. In this report, hypertension was defined as having a measured blood pressure of 140 over 90 millimetres of mercury (mmHg) or above.

According to US CDC, nearly half of adults have hypertension (48.1%, 119.9 million), defined as a systolic blood pressure greater than 130 mmHg or a diastolic blood pressure greater than 80 mmHg or are taking medication for hypertension. Additionally:

About 1 in 4 adults with hypertension have their hypertension under control (22.5%, 27.0 million).
About half of adults (45%) with uncontrolled hypertension have a blood pressure of 140/90 mmHg or higher. This includes 37 million U.S. adults.
About 34 million adults who are recommended to take medication may need it to be prescribed and to start taking it. Almost two out of three of this group (19 million) have a blood pressure of 140/90 mmHg or higher.

Both sources linked below.

The NET Effect

Syndrome/functional tumour related

Elevated blood pressure is known to exist in catecholamine secreting NETs i.e. Pheochromocytoma and Paraganglioma alongside sweating, headaches and palpitations amongst others.

Cushing’s Syndrome. In NETs, this is mainly related to ectopic NETs (i.e. outside pituitary) secreting ACTH (mainly thoracic (thymus/lung) but also possible in pancreas and Pheo/Para/Medullary Thyroid Cancer (MTC)). It also appears in small cell lung cancer, technically a Neuroendocrine Carcinoma. In fact, my sources indicate hypertension in ectopic NET cases is more common than regular (endogenous) Cushing’s.

Many people cite so called “carcinoid syndrome” (serotonin secreting NETs) but the majority of literature points to “changes in blood pressure” which appears to be inferring low blood pressure (hypotension). So called “carcinoid crisis” is also related to low blood pressure.

Treatment side effects and other issues

Some treatments may cause elevated blood pressure, and this may recede when the drug is stopped.

Somatostatin analogues. It’s possible that somatostatin analogues can cause levels to “fluctuate”. The Ipsen leaflet in the UK prescribed box gives a warning to those taking BP meds indicating it may affect those with existing BP issues, e.g. people are advised to talk to their doctor if they are already taking “Bradycardia inducing drugs (drugs slowing the heartbeat, such as beta blockers)”. The same leaflet also says to let your doctor know if “You feel faint, possibly as a result of a drop in blood pressure”. There is no mention of elevated or high blood pressure as a listed side effect. The Ipsen website in US clearly states “Somatuline Depot may cause serious side effects, including ………………. and high blood pressure” but do not list it as a side effect.

I found many links/issues saying similar in Octreotide (Sandostatin). But as above for Lanreotide – hypotension is listed in the side effects but not hypertension. On Mayo Clinic’s site, elevated blood pressure or hypertension is not listed against Sandostatin LAR but it does say “This medicine may increase your risk for heart and blood vessel problems, including hypertension and a slow heartbeat“. Ditto for Mayo and Lanreotide.

Thyroid issues

Another contributory cause is an over and underactive thyroid which affects many NET patients, perhaps exacerbated by the known inhibiting effect of somatostatin analogues – which is why a thyroid panel should be tested regularly in those prescribed with either lanreotide or octreotide.

Hypothyroidism (underactive) can affect the heart and circulatory system in a number of ways. Insufficient thyroid hormones slow your heart rate. Because it also makes the arteries less elastic, blood pressure rises in order to circulate blood around the body.

An overactive thyroid is less common but people with hyperthyroidism may also have high blood pressure. Excess thyroid hormone also causes the heart to beat harder and faster and may trigger abnormal heart rhythms. One is atrial fibrillation, a disorganized rhythm in the heart’s upper chambers. A related symptom is palpitations, a sudden awareness of your heartbeat.

Diabetes

Many sites link diabetes and elevated blood pressure. Many NET patients will succumb to diabetes through their treatment, particularly pancreatic NETs. According to John Hopkins Medicine, a person with diabetes is twice as likely to have high blood pressure, and a person with both diabetes and hypertension is also four times more likely to develop heart disease when compared to someone with neither of the conditions. The symptoms of blood pressure may not show unless blood pressure becomes very high and so it is important that your blood pressure level is checked each year.

Everolimus (Afinitor)

Listed side effect.

Sunitinib (Sutent)

Listed side effect.

Summary

Worth enquiring about some of those if your BP is suddenly (and consistently) high after diagnosis of NET and/or commencement of treatment. Note: Anxiety doesn’t cause long-term high blood pressure (hypertension). But episodes of anxiety can cause dramatic, temporary spikes in blood pressure. e.g. at appointments, infusions, injections etc. Read about “white coat hypertension” here. (this seems to happen to me, my BP is always higher at the doctors surgery than in home!).

Resources used:

Disclaimer

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