This is the second part of our two-part series, where we present five additional differential diagnoses for Inflammatory Bowel Syndrome (IBS) patients. In part 1 we addressed the primary symptoms and laboratory tests for differentiating between Inflammatory Bowel Disease, Cholecystitis, Bile Acid Diarrhea, Microscopic Colitis, and Celiac disease. In this part 2, we will discuss five additional conditions to rule out before diagnosing IBS, including Hypothyroidism, Hyperthyroidism, Small Intestinal Bacterial Overgrowth, Lactose or fructose intolerance, and Gastritis.

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Hypothyroidism

There is a condition named hypothyroidism that involves the insufficient production of hormones by the thyroid gland. In the early stages, the underactive thyroid can go undetected. It is estimated that 60% of people with a thyroid condition are unaware of it. However, with time, untreated hypothyroidism can cause health issues involving high cholesterol and heart problems. Women are much more likely to develop thyroid disorders during their lifetime.

Key Stand-Out Symptoms of Hypothyroidism

The common symptoms of underactive thyroid are similar to those of other conditions. So, they can be confused with other disorders. Symptoms often develop over several years, making it difficult for people to know that they have hypothyroidism.

Common symptoms include:

• Constipation
• Tiredness
• Being more sensitive to cold
• Dry skin
• Weight gain
• Hoarse voice
• Puffy face
• Coarse hair and skin
• Muscle weakness
• Loss of libido
• Menstrual cycles that are heavier than usual or irregular
• Thinning hair
• Muscle aches, tenderness, and stiffness
• Slowed heart rate, also called bradycardia
• Depression and memory problems in older adults

Key Lab Test Markers For Diagnosis of Hypothyroidism

The similarity of the symptoms of hypothyroidism with other conditions makes the diagnosis rely mainly on the results of blood tests. There are several Lab tests that a practitioner can use for thyroid testing:

TSH: The Thyroid Stimulating Hormone is released from a gland located in the brain named the pituitary gland. TSH is the hormone that induces the thyroid gland to produce and release two hormones called T4 and T3. High levels of TSH in the blood indicate hypothyroidism.

Total T3: Total T3 is the combination of Bound T3 and Free T3, making it a more reliable indicator of the active form of this thyroid hormone. Unless otherwise specified as "Free T3" or "fT3, T3 in a lab report always refers to Total T3.

Free T3: Free T3 is a crucial hormone that impacts the body's metabolic control. It is unbound, allowing it to be quickly utilized by tissues, but only represents a small portion of total T3 levels, about 0.04%.

Reverse T3: Reverse T3 (rT3) is a form of the hormone T4 that has the same number of iodine molecules as T3, but is inactive. Elevated levels of rT3 can interfere with T3's function by binding to the receptors in its place, potentially causing hypothyroidism symptoms.

Total T4: Thyroxine, also known as the T4 hormone, is a thyroid hormone produced by the thyroid gland. It makes up 90% of all thyroid hormones, with the remaining being T3. The Total T4 measurement includes both bound T4 (to Thyroxine-Binding Globulin) and unbound T4. Nearly 99% of Total T4 binds to TBG for transport throughout the body, making Total T4 a good indicator of thyroid hormone levels. In laboratory reports, T4 always refers to Total T4 unless labeled as "Free T4" or "fT4".

Free T4: Free T4 (fT4) is not bound to TBG and is free to travel into body tissues. However, fT4 is still inactive and must be converted to T3 to affect cellular metabolism. Because most of our thyroid hormone production is in the T4 form, and because fT4 is the form that is readily available to convert to T3 (which is the active form of the thyroid hormone), fT4 is, therefore, a good representation of the amount of thyroid hormone available for the cells. If ft4 is low and total t4 is low, it indicates low overall thyroid hormone production at the thyroid gland level (hypothyroidism). If total t4 is normal and ft4 is low, that suggests dysfunction with the transportation of T4. If fT4 is high, it could indicate hyperthyroidism.

Anti-TPO: Anti-TPO is a test to detect the antibodies against Thyroid Peroxidase (TPO), an enzyme critical for producing thyroid hormones. If sufficient antibodies to TPO are found in your blood work, it could indicate an autoimmune disorder at the root of the thyroid dysfunction. Hashimoto's and Graves' diseases are two examples of autoimmune conditions that can trigger your immune system to attack normal thyroid tissue.

Hyperthyroidism

Hyperthyroidism involves the overproduction and release of thyroid hormones by the thyroid gland, which speed up the body's metabolism. This can result in symptoms such as weight loss, tremors, and a rapid or irregular heartbeat. Treatment options for hyperthyroidism include anti-thyroid medication and radioiodine to reduce hormone production by the thyroid gland. A partial or complete surgical removal of the thyroid gland may also be necessary. In some instances, hyperthyroidism may improve without medication or treatment.

Key Stand-Out Symptoms of Hyperthyroidism

Hyperthyroidism can be challenging to diagnose as its symptoms may resemble other health issues. Symptoms of hyperthyroidism include:

• Changes in bowel patterns, especially more-frequent bowel movements
• Fast heartbeat
• Irregular heartbeat
• Losing weight without trying
• Pounding of the heart
• Increased hunger
• Tremor, usually a small trembling in the hands and fingers
• Sweating
• Increased sensitivity to heat
• Changes in menstrual cycles
• Nervousness, anxiety, and irritability
• Enlarged thyroid gland
• Thinning skin
• Tiredness
• Sleep problems
• Muscle weakness
• Warm and moist skin
• Fine, brittle hair

Key Lab Test Markers For Diagnosis of Hyperthyroidism

The diagnosis of hyperthyroidism can be confirmed through the above-described blood tests that measure TSH, Total T3, Total T4, and  Free T4 hormones. High T4 and low TSH levels are typical indicators of the condition.

These tests are essential for the elderly, who may not exhibit classic symptoms of hyperthyroidism. Practitioners and patients should note that taking biotin supplements or multivitamins containing biotin can affect the accuracy of thyroid blood tests. To ensure an accurate result, biotin consumption should be discontinued two days before the test.

Lactose or Fructose Intolerance

Adverse reactions to food are a widespread problem. Confirming food hypersensitivity can be challenging, but avoiding specific foods often reduces symptoms. Fructose and lactose are two sugar types naturally found in fruit and milk, respectively. Carbohydrate and sugar intolerance can be caused by various genetic enzyme and transporter deficiencies and is prevalent in individuals with or without digestive symptoms. For those who experience symptoms can lead to bloating, flatulence, abdominal pain, and diarrhea. These general symptoms overlap with other health issues, making it difficult for medical professionals to diagnose and treat carbohydrate intolerance.

Key Stand-Out Symptoms of Lactose or Fructose Intolerance

A person with lactose or fructose intolerance may experience symptoms within 30 minutes to 2 hours after eating or drinking anything with lactose or fructose. These symptoms can include:

• Bloating
• Diarrhea
• Nausea
• Stomach cramps
• Gas
• Vomiting

Key Lab Test Markers For Diagnosis of Lactose or Fructose Intolerance

Lactose and fructose intolerance can cause abnormal hydrogen levels in the gut, which can then be measured in the breath. Lab tests that measure hydrogen in the breath test are usually ordered to confirm intolerance to lactose, fructose, sorbitol, or sucrose.

Lactose Malabsorption Breath Test: The lactose intolerance test helps diagnose lactose malabsorption. The test measures the levels of Hydrogen, methane, and carbon dioxide in the breath.

SIBO 2-hour Test: SIBO (Small Intestinal Bacterial Overgrowth) can sometimes cause food intolerances, like lactose intolerance. This non-invasive breath test measures hydrogen and methane gases in the breath after ingesting a lactulose solution.

Lactose tolerance test: a person can be tested 2 hours after drinking a high-concentration lactose solution. The tolerance test evaluates the levels of glucose in the blood. If glucose levels do not increase, it may indicate lactose intolerance and malabsorption.

Small Intestinal Bacterial Overgrowth (SIBO)

Small Intestinal Bacterial Overgrowth (SIBO) involves the unusual increase in the overall number of bacteria in the small intestine. SIBO occurs when something slows down the movement of food and waste in the digestive tract, providing an environment for bacteria to thrive. This can lead to symptoms such as diarrhea, weight loss, and malnutrition. SIBO can be caused by surgery or diseases but is commonly seen as a complication of abdominal surgery. Antibiotics are the most used treatment for SIBO, but surgery may be required in some cases.

Key Stand-Out Symptoms of SIBO

Common symptoms of SIBO are:

• Nausea
• Constant Burping
• Bloating worse at the end of the day
• Patient feels better on Low FODMAP diet
• Patients’ symptoms get better after antibiotic treatment
• Feel worse after taking probiotics
• An uncomfortable feeling of fullness or gas immediately after eating
• Diarrhea
• Malnutrition
• Unintentional weight loss
• Feeling worse after eating fermented foods or taking probiotics

Key Lab Test Markers For Diagnosis of SIBO

SIBO 2-hour test: The SIBO 2-Hour Test is a non-invasive breath examination that measures the levels of hydrogen and methane in a patient's breath after consuming a lactulose solution.

SIBO 3-hour test: This test offers a comprehensive understanding of gas levels over a longer duration. It is suggested for individuals with a slower gut transit time or constipation.

SIBO/IMO Glucose Breath Test: This test assists in the diagnosis of SIBO and Intestinal Methanogen Overgrowth (IMO). When bacteria typically found in the large intestine migrate to the small intestine, the digestive system can produce excessive hydrogen and methane gas, leading to gastrointestinal symptoms such as bloating, diarrhea, and constipation. The test includes a glucose substrate.

SIBO/IMO Lactulose Breath Test: This test is similar to the SIBO/IMO glucose breath test but uses a lactulose substrate. Glucose breath tests have been shown to work better than lactulose for the non-invasive diagnosis of SIBO. The primary advantage of the Lactulose Test over the Glucose Test is the belief that Glucose cannot accurately diagnose distal SIBO because it is quickly absorbed in the proximal small intestine. On the other hand, lactulose is a non-absorbable sugar that moves through the whole small intestine making it more suitable for diagnosing distal SIBO.

The Trio-smart SIBO Breath Test: can be performed at home. It measures the three primary fermented gases present in the gut microbiome: hydrogen, methane, and hydrogen sulfide.

Gastritis

Gastritis refers to a set of conditions characterized by inflammation of the stomach lining. This inflammation is often caused by infection with bacteria responsible for most stomach ulcers or prolonged use of certain pain relievers. Excessive alcohol consumption can also contribute to gastritis. It can be acute or chronic, developing gradually over time. Although gastritis can lead to ulcers and raise the risk of stomach cancer for some people, it is usually not severe and can be treated effectively.

Key Stand-Out Symptoms of Gastritis

The common symptoms of gastritis are:

• A gnawing or burning discomfort or pain (heartburn) in the upper abdomen that may be alleviated or exacerbated by eating
• Vomiting
• Feeling full after eating
• Nausea
• Loss of appetite
• Dark stools

Gastritis can occur without producing any noticeable symptoms.

Key Lab Test Markers For Diagnosis of Gastritis

Different laboratory tests can be used for diagnosing gastritis:

Helicobacter Pylori or H. Pylori profile: This test utilizes a qPCR technology to detect H. pylori infections. This test is also helpful in tracking H. pylori levels after treatment. This bacterium is linked to causing ulcers, chronic gastritis, and stomach cancer. The H. pylori profile includes information on antibiotic resistance genes for Amoxicillin, Clarithromycin, Fluoroquinolones, and Tetracycline, providing practitioners with important information for their treatment plans. Additionally, the test checks for virulence factor genes, which can indicate a higher risk for severe H. pylori infections.

GI Effects® Comprehensive Profile 3 day: This is a set of stool tests to evaluate the digestive function, intestinal inflammation, and gut microbiome to support gastrointestinal health management. The intestinal microorganisms have a reciprocal relationship with their human host, where the health of one influences the other. The test measures over 70 biomarkers of digestion and absorption, inflammation and immunology, and the gut microbiome (including Helicobacter pylori). The GI Effects® Comprehensive Profile- 1-day test is suggested if there is no suspicion of parasitic infection.

Summary

Differential diagnosis is essential in evaluating patients with symptoms suggestive of inflammatory bowel syndrome because it helps to distinguish IBS from other gastrointestinal diseases that may present similarly. Accurate diagnosis is crucial in managing IBS because the treatment approaches for IBS and other gastrointestinal disorders can differ significantly. A misdiagnosis can result in inappropriate treatment and delay in appropriate therapy, leading to worse outcomes and increased healthcare costs. Therefore, a thorough evaluation, including a differential diagnosis, is essential in ensuring proper and effective management of patients with suspected IBS.