OI is "notoriously difficult to diagnose." As a result, many patients have gone undiagnosed or misdiagnosed and either untreated or treated for other disorders. Current tests for OI (Tilt table test, autonomic assessment, and vascular integrity) can also specify and simplify treatment. (See Dr. Julian Stewart's article, "Orthostatic Intolerance: An Overview" for a more detailed description of OI tests.)

There are no characteristic laboratory abnormalities to diagnose CFS; testing is used to rule out other conditions which could be responsible for the symptoms. When symptoms are attributable to certain other conditions, the diagnosis of CFS is excluded. As such, a diagnosis of CFS/ME is generally one of exclusion (of alternative diagnoses).

Notable definitions include:

- Centers for Disease Control and Prevention (CDC) definition (1994), the most widely used clinical and research description of CFS, is also called the Fukuda definition and is a revision of the "Holmes" or "CDC 1988" scoring system. The 1994 criteria require the presence of four or more symptoms beyond fatigue, while the 1988 criteria require six to eight.

- The ME/CFS 2003 Canadian Clinical working definition states: "A patient with ME/CFS will meet the criteria for fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; have two or more neurological/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendocrine, and immune manifestations; and the illness persists for at least 6 months".

Clinical practice guidelines are generally based on case descriptions, with the aim of improving diagnosis, management and treatment. An example is the CFS/ME guideline for the National Health Services in England and Wales, produced in 2007 by the National Institute for Health and Clinical Excellence (NICE).

Most patients experience an improvement of their symptoms, but for some, OI can be gravely disabling and can be progressive in nature, particularly if it is caused by an underlying condition which is deteriorating. The ways in which symptoms present themselves vary greatly from patient to patient; as a result, individualized treatment plans are necessary.

OI is treated both pharmacologically and non-pharmacologically. Treatment does not cure OI; rather, it controls symptoms.

Physicians who specialize in treating OI agree that the single most important treatment is drinking more than two liters (eight cups) of fluids each day. A steady, large supply of water or other fluids reduces most, and for some patients all, of the major symptoms of this condition. Typically, patients fare best when they drink a glass of water no less frequently than every two hours during the day, instead of drinking a large quantity of water at a single point in the day.

For most severe cases and some milder cases, a combination of medications are used. Individual responses to different medications vary widely, and a drug which dramatically improves one patient's symptoms may make another patient's symptoms much worse. Medications focus on three main issues:

Medications that increase blood volume:

- Fludrocortisone (Florinef)

- Erythropoietin

- Hormonal contraception

Medications that inhibit acetylcholinesterase:

- Pyridostigmine

Medications that improve vasoconstriction:

- Stimulants: (e.g., Ritalin or Dexedrine)

- Midodrine (ProAmatine)

- Ephedrine and pseudoephedrine (Sudafed)

- Theophylline (low-dose)

- Selective serotonin reuptake inhibitors (SSRI's - Prozac, Zoloft, and Paxil)

Behavioral changes that patients with OI can make are:

- Avoiding triggers such as prolonged sitting, quiet standing, warm environments, or vasodilating medications

- Using postural maneuvers and pressure garments

- Treating co-existing medical conditions

- Increasing fluid and salt intake

- Physical therapy and exercise unless contraindicated by an underlying condition such as chronic fatigue syndrome where traditional exercise can worsen the condition

Recent studies have explored the connection between DβH deficiency, Droxidopa treatment, and the effect on orthostatic tolerance and glucose homeostasis. It was found that Droxidopa increased acute and late glucose-stimulated insulin secretion and improved patients' insulin sensitivity. However, the use of Droxidopa was found to only produce "modest changes in glucose homeostasis" overall. This shows that treatment modalities other than Droxidopa should be pursued as possible adjuncts for the hyperinsulinemia seen in DβH deficiency.

This is a form of dysautonomia but differentiated from familial dysautonomia by a lack of familial dysautonomic symptoms such as loss of sense of pain and smell. While L-threo-DOPS has been described as being "very effective for restoring noradrenergic tone and correcting postural hypotension, response to treatment is variable and the long-term and functional outcome is unknown."

Researchers have put together retrospective data collections in order to better under the progression of this orphan disease. Most studies show a perinatal period marked by inadequacy of the ANS to control blood pressure, blood sugar, and body temperature. The experiences of orthostatic hypotension, exercise intolerance, and "traumatic morbidity related to falls and syncope" have been documented later in lives of people with this condition. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation, outcome of these diseases, their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies, a patient registry was established by the non-commercial International Working Group on Neurotransmitter Related Disorders (iNTD).

The report of Da Costa shows that patients recovered from the more severe symptoms when removed from the strenuous activity or sustained lifestyle that caused them. A reclined position and forced bed rest was the most beneficial.

Other treatments evident from the previous studies were improving physique and posture, appropriate levels of exercise where possible, wearing loose clothing about the waist, and avoiding postural changes such as stooping, or lying on the left or right side, or the back in some cases, which relieved some of the palpitations and chest pains, and standing up slowly can prevent the faintness associated with postural or orthostatic hypotension in some cases.

Pharmacological intervention came in the form of digitalis, or "fox glove", which acts as a sodium-potassium ATPase inhibitor, increasing stroke volume and decreasing heart rate.

There is emerging evidence from studies of cord bloods that both sensitization and the acquisition of tolerance can begin in pregnancy, however the window of main danger for sensitization to foods extends prenatally, remaining most critical during early infancy when the immune system and intestinal tract are still maturing. There is no conclusive evidence to support the restriction of dairy intake in the maternal diet during pregnancy in order to prevent. This is generally not recommended since the drawbacks in terms of loss of nutrition can out-weigh the benefits. However, further randomised, controlled trials are required to examine if dietary exclusion by lactating mothers can truly minimize risk to a significant degree and if any reduction in risk is out-weighed by deleterious impacts on maternal nutrition.

A Cochrane review has concluded feeding with a soy formula cannot be recommended for prevention of allergy or food intolerance in infants. Further research may be warranted to determine the role of soy formulas for prevention of allergy or food intolerance in infants unable to be breast fed with a strong family history of allergy or cow's milk protein intolerance. In the case of allergy and celiac disease others recommend a dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4–6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.

Genetic tests may be useful in assessing whether a person has primary lactose intolerance. Lactase activity persistence in adults is associated with two polymorphisms: C/T 13910 and G/A 22018 located in the "MCM6" gene. These polymorphisms may be detected by molecular biology techniques at the DNA extracted from blood or saliva samples; genetic kits specific for this diagnosis are available. The procedure consists of extracting and amplifying DNA from the sample, following with a hybridation protocol in a strip. Colored bands are obtained as final result, and depending on the different combination, it would be possible to determine whether the patient is lactose intolerant. This test allows a noninvasive definitive diagnostic.

Diagnosis of food intolerance can include hydrogen breath testing for lactose intolerance and fructose malabsorption, professionally supervised elimination diets, and ELISA testing for IgG-mediated immune responses to specific foods. It is important to be able to distinguish between food allergy, food intolerance, and autoimmune disease in the management of these disorders. Non-IgE-mediated intolerance is more chronic, less acute, less obvious in its clinical presentation, and often more difficult to diagnose than allergy, as skin tests and standard immunological studies are not helpful. Elimination diets must remove all poorly tolerated foods, or all foods containing offending compounds. Clinical investigation is generally undertaken only for more serious cases, as for minor complaints which do not significantly limit the person's lifestyle the cure may be more inconvenient than the problem.

IgG4 tests are invalid; IgG4 presence indicates that the person has been repeatedly exposed to food proteins recognized as foreign by the immune system which is a normal physiological response of the immune system after exposure to food components. Although elimination of foods based on IgG-4 testing in IBS patients resulted in an improvement in symptoms, the positive effects of food elimination were more likely due to wheat and milk elimination than IgG-4 test-determined factors. The IgG-4 test specificity is questionable as healthy individuals with no symptoms of food intolerance also test positive for IgG-4 to several foods.

Diagnosis is made using medical history and cutaneous and serological tests to exclude other causes, but to obtain final confirmation a Double Blind Controlled Food Challenge must be performed.

Treatment can involve long-term avoidance, or if possible re-establishing a level of tolerance.

Today there are many methods available such as Cytotoxic testing, MRT testing, Elisa Testing and Microarray Elisa Testing. Allergy US reviewed these methods and Microarray technology appears to be the most reliable among them. http://allergyus.com/food-intolerance-tests-in-usa/.

When lactose intolerance is due to secondary lactase deficiency, treatment of the underlying disease may allow lactase activity to return to normal levels. In people with coeliac disease, lactose intolerance normally reverts or improves several months after starting a gluten-free diet, but temporary dietary restriction of lactose may be needed.

People with primary lactase deficiency cannot modify their body’s ability to produce lactase. In societies where lactose intolerance is the norm, it is not considered a condition that requires treatment. However, where dairy is a larger component of the normal diet, a number of efforts may be useful. There are four general principles in dealing with lactose intolerance: avoidance of dietary lactose, substitution to maintain nutrient intake, regulation of calcium intake, and use of enzyme substitute. Regular consumption of dairy food by lactase deficient individuals may also reduce symptoms of intolerance by promoting colonic bacteria adaptation.

People with POTS will show a marked rise in heart rate within 10 minutes of standing or being tilted 60° head-up on a tilt table, without a corresponding decrease in blood pressure. A variety of autonomic tests are employed to exclude autonomic disorders that could underlie symptoms, while endocrine testing is used to exclude hyperthyroidism and rarer endocrine conditions. Electrocardiography is normally performed on all patients to exclude other possible causes of tachycardia. In cases where a particular associated condition or complicating factor are suspected, other non-autonomic tests may be used: echocardiography to exclude mitral valve prolapse, and thermal threshold tests for small-fiber neuropathy.

Testing the cardiovascular response to prolonged head-up tilting, exercise, eating, and heat stress may help determine the best strategy for managing symptoms. POTS has also been divided into several types (see § Causes), which may benefit from distinct treatments. People with neuropathic POTS show a loss of sweating in the feet during sweat tests, as well as impaired norepinephrine release in the leg, but not arm. This is believed to reflect peripheral sympathetic denervation in the lower limbs. People with hyperadrenergic POTS show a marked increase of blood pressure and norepinephrine levels when standing, and are more likely to suffer from prominent palpitations, anxiety, and tachycardia.

Depending on whether the salicylate is a component of food or medicine, salicylate intolerance is a form of food intolerance or of drug intolerance.

Salicylate sensitivity is a pharmacological reaction, not a true IgE-mediated allergy. However, it is possible for aspirin to trigger non-allergic hypersensitivity reactions. About 5–10% of asthmatics have aspirin hypersensitivity, but dietary salicylates have been shown not to contribute to this. The reactions in AERD (Samter's triad) are due to inhibition of the COX-1 enzyme by aspirin, as well as other NSAIDs that are not salicylates. Dietary salicylates have not been shown to significantly affect COX-1.

Samter's triad refers to aspirin sensitivity in conjunction with nasal polyps and asthma.

There are no laboratory or skin testing methods for testing salicylate sensitivity. Provocative challenge is one method of obtaining reliable diagnosis. Provocative challenge is intended to induce a controlled reaction as a means of confirming diagnosis. During provocative challenge, the person is given incrementally higher doses of salicylates, usually aspirin, under medical supervision, until either symptoms appear or the likelihood of symptoms appearing is ruled out.

Severe heat intolerance (e.g., nausea, dizziness, and headache), and tingling, pricking, pinchy or burning pain over the entire body on exposure to hot environments or prolonged exercise which improve after cooling the body. Occurs in the absence of any causative skin, metabolic, or neurological disorders.

Although it is listed in the ICD-10 under "somatoform autonomic dysfunction", the term is no longer in common use by any medical agencies and has generally been superseded by more specific diagnoses.

The orthostatic intolerance observed by Da Costa has since also been found in patients diagnosed with chronic fatigue syndrome, postural orthostatic tachycardia syndrome (POTS) and mitral valve prolapse syndrome. In the 21st century, this intolerance is classified as a neurological condition. Exercise intolerance has since been found in many organic diseases.

Opinions differ about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs. The most elaborate regimen entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks' gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, a woman may be tested earlier.

In the United States, most obstetricians prefer universal screening with a screening glucose challenge test. In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the woman is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors) The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening. The U.S. Preventive Services Task Force found there is insufficient evidence to recommend for or against routine screening.

Some pregnant women and careproviders choose to forgo routine screening due to the absence of risk factors, however this is not advised due to the large proportion of women who develop gestational diabetes despite having no risk factors present and the dangers to the mother and baby if gestational diabetes remains untreated.

It is important for MADD patients to maintain strength and fitness without exercising or working to exhaustion. Learning this balance may be more difficult than normally, as muscle pain and fatigue may be perceived differently from normal individuals.

Symptomatic relief from the effects of MADD may sometimes be achieved by administering ribose orally at a dose of approximately 10 grams per 100 pounds (0.2 g/kg) of body weight per day, and exercise modulation as appropriate. Taken hourly, ribose provides a direct but limited source of energy for the cells. Patients with myoadenylate deaminase deficiency do not retain ribose during heavy exercise, so supplementation may be required to rebuild levels of ATP.

Creatine monohydrate could also be helpful for AMPD patients, as it provides an alternative source of energy for anaerobic muscle tissue and was found to be helpful in the treatment of other, unrelated muscular myopathies.

A positive diagnosis test for thiamine deficiency can be ascertained by measuring the activity of the enzyme transketolase in erythrocytes (Erythrocyte Transketolase Activation Assay). Thiamine, as well as its phosphate derivatives, can also be detected directly in whole blood, tissues, foods, animal feed, and pharmaceutical preparations following the conversion of thiamine to fluorescent thiochrome derivatives (Thiochrome Assay) and separation by high-performance liquid chromatography (HPLC). In recent reports, a number of Capillary Electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as potential alternative techniques for the determination and monitoring of thiamine in samples.

The normal thiamine concentration in EDTA-blood is about 20-100 µg/l.

Drugs in systemic circulation have a certain concentration in the blood, which serves as a surrogate marker for how much drug will be delivered throughout the body (how much drug the rest of the body will "see"). There exists a minimum concentration of drug within the blood that will give rise to the intended therapeutic effect (minimum effective concentration, MEC), as well as a minimum concentration of drug that will give rise to an unintended adverse drug event (minimum toxic concentration, MTC). The difference between these two values is generally referred to as the therapeutic window. Different drugs have different therapeutic windows, and different people will have different MECs and MTCs for a given drug. If someone has a very low MTC for a drug, they are likely to experience adverse effects at drug concentrations lower than what it would take to produce the same adverse effects in the general populace; thus, the individual will experience significant toxicity at a dose that is otherwise considered "normal" for the average person. This individual will be considered "intolerant" to that drug.

There are a variety of factors that can affect the MTC, which is often the subject of clinical pharmacokinetics. Variations in MTC can occur at any point in the ADME (absorption, distribution, metabolism, and excretion) process. For example, a patient could possess a genetic defect in a drug metabolizing enzyme in the cytochrome P450 superfamily. While most individuals will possess the effective metabolizing machinery, a person with a defect will have a difficult time trying to clear the drug from their system. Thus, the drug will accumulate within the blood to higher-than-expected concentrations, reaching a MTC at a dose that would otherwise be considered normal for the average person. In other words, in a person that is intolerant to a medication, it is possible for a dose of 10 mg to "feel" like a dose of 100 mg, resulting in an overdose—a "normal" dose can be a "toxic" dose in these individuals, leading to clinically significant effects.

There is also an aspect of drug intolerance that is subjective. Just as different people have different pain tolerances, so too do people have different tolerances for dealing with the adverse effects from their medications. For example, while opioid-induced constipation may be tolerable to some individuals, other people may stop taking an opioid due to the unpleasantness of the constipation even if it brings them significant pain relief.

Sweat is readily visualized by a topical indicator such as iodinated starch or sodium alizarin sulphonate. Both undergo a dramatic colour change when moistened by sweat. A thermoregulatory sweat test evaluates the body’s response to a thermal stimulus by inducing sweating through the use of a hot box ⁄ room, thermal blanket or exercise. Failure of the topical indicator to undergo a colour change during thermoregulatory sweat testing can indicate anhidrosis and/or hypohidrosis (see Minor test).

A skin biopsy may reveal cellular infiltrates in sweat glands or ducts.

Drug intolerance or drug sensitivity refers to an inability to tolerate the adverse effects of a medication, generally at therapeutic or subtherapeutic doses. Conversely, a patient is said to be "tolerating" a drug when they can tolerate its adverse effects. It is not to be confused with a drug allergy, which is a form of drug intolerance, but requires an immune-mediated component. It is also not to be confused with drug tolerance ("drug resistance," or tachyphylaxis) which refers to a "lack" of adverse effects even at higher than average doses. Some instances of drug intolerance are known to result from genetic variations in drug metabolism.

The prevalence of POTS is unknown. One study estimated a minimal rate of 170 POTS cases per 100,000 individuals, but the true prevalence is likely higher due to underdiagnosis. Another study estimated that there were between 500,000 and 3,000,000 cases in the United States. POTS is more common in women, with a female-to-male ratio of 5:1. Most people with POTS are aged between 20 and 40, with an average onset of 30. Diagnoses of POTS beyond age 40 are rare, perhaps because symptoms improve with age.

A neurological condition or another medical problem may be suspected, in which case, blood tests, a CT scan or an MRI may be used. An overnight sleep study is usually not needed to detect this disorder, but may be indicated if other sleep disorders, such as sleep apnea and periodic limb movement disorder, seem likely. The overnight sleep study is called polysomnography. It charts brain waves, heart beat, muscle activity, and breathing during sleep. It also records arm and leg movement. It will show if there are other sleep disorders that are causing or increasing the problems with ISWD.

Sudden cessation of high-dose corticosteroids, opioids, barbiturates, benzodiazepines, caffeine or alcohol can induce myalgia in many respects.