Zollinger-Ellison Syndrome

What is Zollinger-Ellison Syndrome?

Zollinger-Ellison syndrome (ZES) is a condition in which a neuroendocrine tumor called a gastrinoma releases gastrin on its own, which drives the stomach to produce too much acid. The result is severe peptic ulcer disease and often watery diarrhea.^{[1, 2]} It is rare and needs specialist medical care.

Common symptoms

The usual symptoms are burning upper abdominal pain, repeated peptic ulcers, reflux and chronic diarrhea.^[3] Nausea, weight loss and bleeding from ulcers can also occur. Because these symptoms overlap with common digestive problems, diagnosis is often delayed, with an average of more than 5 years between first symptoms and diagnosis in one review.^[3]

Causes and risk factors

Most gastrinomas arise in the duodenum or the pancreas, and most occur without a family history. A minority are part of an inherited condition called multiple endocrine neoplasia type 1 (MEN1).^[2] Many gastrinomas are malignant, and some have already spread when found.^[1]

How it is diagnosed and treated conventionally

Doctors measure fasting gastrin in the blood and stomach acidity, and may use a secretin test and scans such as endoscopic ultrasound or somatostatin-receptor PET/CT to find the tumor.^{[1, 2]} Acid-lowering medicines can distort the blood tests, so testing is planned by the physician.^[2]

Proton pump inhibitors (PPIs) are the cornerstone of treatment for symptoms. Surgery is the main option when the tumor is localized, and somatostatin analogs and other drugs are used for advanced disease.^{[2, 3]} When surgery cannot remove the tumor completely, people need lifelong acid control, and long-term outcomes depend on how far the tumor has spread.^{[1, 4]}

Why Zollinger-Ellison Syndrome calls for a whole-person approach

ZES is a tumor and acid disorder, so the tumor and the acid are treated first and by physicians. Living with a long-term illness and its treatment also affects pain, digestion, sleep, energy and mood, and these are the areas where supportive care may help.

The research described below is not about ZES itself. It comes from studies of related symptoms in other groups of patients, and we say so each time.

Persistent digestive symptoms

Acid hypersecretion leads to reflux, ulcers and diarrhea, which usually resolve with effective acid control.^[3] Some symptoms can persist or return, and the evidence-based plan for them rests with your gastroenterologist or endocrinologist.^[5]

Long-term medication

Many people with ZES need acid-lowering medicine for life, and doctors continue to study its long-term effects.^[4] Any herb or supplement you add needs to be reviewed with this in mind.

Pain, fatigue and sleep with a long-term tumor illness

Studies in people with cancer link acupuncture with benefits for pain, fatigue and insomnia, although the reviews are of low methodological quality.^[6] These findings are relevant only to the extent that a gastrinoma is a neuroendocrine tumor, and they have not been tested in ZES.

Acupuncture as supportive care in Zollinger-Ellison Syndrome

What the research shows

No clinical trials of acupuncture for ZES were found in PubMed. The following results come from other conditions and may or may not apply.

An overview of 51 systematic reviews of acupuncture for cancer-related conditions reported benefits for cancer pain, fatigue, insomnia, nausea and vomiting, but rated nearly all of the reviews as very low methodological quality.^[6] A meta-analysis of 17 trials found that acupuncture and acupressure were associated with less cancer pain, and the evidence level was moderate because results varied widely between studies.^[7] For chemotherapy-induced nausea and vomiting, a review of 38 trials found acupuncture added to usual care may improve control of vomiting, with very low-certainty evidence.^[8]

For reflux, a meta-analysis of 12 trials found that acupuncture alongside Western medicine gave better overall symptom improvement than medicine alone, but the trials were small and of poor quality.^[9] A review of 61 trials in functional digestive disorders (such as functional dyspepsia) found symptom relief with acupuncture, with moderate or low evidence quality.^[10] These are not conditions caused by a tumor, and reflux in ZES is driven by a much higher level of acid. These findings should not be read as showing that acupuncture lowers acid or treats gastrinoma.

How acupuncture may work

How acupuncture might act in ZES is unknown, and no mechanism studies in ZES were found. In chronic musculoskeletal, headache and osteoarthritis pain, a large pooled analysis of individual patient data found acupuncture outperformed sham needling, and the authors concluded its effects are not explained by placebo alone.^[11] Whether anything similar happens in digestive tumor symptoms has not been shown.

What treatment involves

Treatment uses fine, sterile, single-use needles, usually left in place for about 20 to 40 minutes, with a short course of visits and reassessment. Points on the abdomen are chosen with care when there is an active ulcer or tumor, and we would work around your medical findings.

Serious problems from acupuncture are rare. In prospective studies, about 9 in 100 patients had a minor reaction such as bleeding, soreness or redness at a needle site, and serious events occurred in about 1 in 10,000 patients.^[12] Tell the practitioner first if you have a bleeding disorder, anemia from ulcer bleeding, take blood thinners, are pregnant, or have a pacemaker (relevant to electroacupuncture). Tell us about any recent tumor treatment or low blood counts as well.

For a condition like this, we ask that you are under a physician's care for it and that your treating team knows you are receiving complementary care.

Ayurvedic medicine as supportive care in Zollinger-Ellison Syndrome

The Ayurvedic view

Ayurveda has no classical name for ZES. Traditional texts describe burning stomach discomfort and sour reflux as Amlapitta, a pattern attributed to excess Pitta, the principle linked to heat and digestion. This is a traditional framework, not a biomedical diagnosis, and it does not describe a tumor that makes gastrin.

Therapies that may be used

Care is individualized and may include:

• Diet and daily routine advice, such as regular meal times, avoiding foods that you find trigger your symptoms, and steady sleep
• Stress-reducing practices such as gentle yoga, breathing exercises and meditation
• Individually prescribed herbs, such as ashwagandha, which has been studied for stress and anxiety,^[13] only after review of your medicines, tumor treatment and liver and kidney function

Herbal products sold as Ayurvedic medicines can carry toxic metals, so sourcing matters.^[14] Panchakarma is a traditional set of cleansing procedures. Panchakarma is not appropriate during pregnancy, acute illness or frailty, and we would not use it for someone with active ulcers, bleeding, significant diarrhea or dehydration, or serious tumor illness.

What the research shows

No studies of Ayurvedic treatment for ZES were found in PubMed. For this reason we make no claim for Ayurveda in ZES itself.

One Ayurvedic herb with a systematic review for a related symptom is ashwagandha, which is not specific to digestive disease. A meta-analysis of 12 randomized trials in 1,002 adults found it reduced anxiety and stress compared with placebo, but rated the certainty of the evidence as low.^[13] The trials did not involve people with ZES.

Herbal medicine as supportive care in Zollinger-Ellison Syndrome

Herbs and formulas that have been studied

No herbal formula has been studied as a treatment for ZES or gastrinoma. Chinese herbal formulas and Ayurvedic herbs are used traditionally for digestive discomfort, stress and low energy, and a practitioner would choose any of them for you individually. Transdermal medication therapy, in which an herbal preparation is applied to the skin, may be discussed where it is relevant, but no evidence in ZES supports it.

What the research shows

We found no trials of herbal medicine in ZES. For anxiety and stress, ashwagandha has some randomized trial support with low-certainty evidence, as above.^[13] No herbal product has been shown to lower gastric acid enough to replace PPIs in ZES, and none should be used for that purpose.

Safety and herb-drug interactions

Safety deserves extra attention in ZES. Reviews of case reports describe herb-drug interactions with serious consequences, including added bleeding with warfarin and lowered blood levels of several drugs with St. John's wort.^[15] Herbal and dietary supplements account for about 20% of drug-induced liver injury cases in the United States according to research data, and multi-ingredient products are the most common cause.^[16] About one fifth of Ayurvedic products bought online contained detectable lead, mercury or arsenic.^[14]

Please tell us about every medicine you take, including PPIs, somatostatin analogs and any chemotherapy or targeted drug, and whether you are pregnant, breastfeeding or have liver or kidney disease. Herbs should come from tested sources, and none should be started or stopped without your physician knowing.

Translating traditional medicine into modern biological language

This is interpretation, not equivalence. Chinese medicine would describe ZES-type symptoms as a pattern such as stomach heat or Liver qi attacking the Stomach. The modern equivalent ideas are acid, inflammation of the stomach and duodenum, and the way stress and the nervous system affect digestion and pain perception. None of these patterns identifies or treats the gastrin-secreting tumor.

Ayurveda's Pitta imbalance corresponds loosely to the idea of heat, acid and inflammation in the digestive tract. No study has shown that a dosha corresponds to a measurable biological process, and we do not use these terms to explain a tumor.

How this care fits with your medical care

Supportive care for ZES is complementary and never a substitute for your physicians. Keep your gastroenterologist, endocrinologist and surgeon or oncologist involved, and do not stop, reduce or change your PPI or any other prescribed medicine on your own. Reducing acid control can lead to ulcers, bleeding and perforation.

We do not diagnose or manage ZES, test gastrin or monitor the tumor. Please bring your diagnosis, recent test and imaging results, a full list of medicines and supplements, and the contact details of your treating team.

When to seek urgent medical care

Ulcers in ZES can bleed, perforate or block the digestive tract, which are emergencies.^[3]

• Vomiting blood or material that looks like coffee grounds
• Black, tarry or bloody stools
• Sudden, severe abdominal pain, or a hard, rigid abdomen
• Repeated vomiting or being unable to keep fluids down
• Severe diarrhea with dizziness, fainting or signs of dehydration
• Fast heartbeat, shortness of breath or extreme weakness from suspected blood loss

If any of these occur, call 911 or go to the nearest emergency department.