Megaesophagus can also be a symptom of the disease myasthenia gravis. Myasthenia gravis is a neuromuscular disease where the primary symptom is weakness in various body parts of the dog. However, when myasthenia gravis occurs in older dogs it is thought of as an immune-mediated disease. Often when myasthenia gravis is diagnosed in older dogs the first symptom the dog may manifest is megaesophagus.

Myasthenia gravis occurs when acetylcholine receptors (nicotinic acetylcholine receptors) fail to function properly, so that the muslce is not stimulated to contract.

Megaesophagus may occur secondary to diseases such as achalasia or Chagas disease. Achalasia is caused by a loss of ganglion cells in the myenteric plexus. There is a marked lack of contraction within the muscles involved in peristalsis with a constant contraction of the lower esophageal sphincter. Dilation of the esophagus results in difficulty swallowing. Retention of food bolus is also noted.

Toxic megacolon is mainly seen in ulcerative colitis and pseudomembranous colitis, two chronic inflammations of the colon (and occasionally, in the other type of inflammatory bowel disease, Crohn's disease). Its mechanism is incompletely understood. It is probably due to an excessive production of nitric oxide, at least in ulcerative colitis. The prevalence is about the same for both sexes.

In patients with HIV/AIDS, cytomegalovirus (CMV) colitis is the leading cause of toxic megacolon and emergency laparotomy. CMV may also increase the risk of toxic megacolon in non-HIV/AIDS patients with IBD.

Risperidone, an anti-psychotic medication, can result in megacolon.

Besides complications of surgery and anesthesia in general, there may be drainage, swelling, or redness of the incision, gagging or coughing during eating or drinking, or pneumonia due to aspiration of food or liquids. Undesirable complications are estimated to occur in 10-30% of cases. If medical therapy is unsuccessful and surgery cannot be performed due to concurrent disease (such as heart or lung problems) or cost, euthanasia may be necessary if the animal's quality of life is considered unacceptable due to the disease.

Mild cases are managed by limiting activity, keeping a healthy body weight, and avoiding exposure to high ambient temperatures. Mild sedatives can be used to decrease anxiety and panting and therefore improve respiration. Corticosteroids may also be administered in acute cases to decrease inflammation and edema of the larynx.

Severe acute symptoms, such as difficulty breathing, hyperthermia, or aspiration pneumonia, must be stabilized with sedatives and oxygen therapy and may require steroid or antibiotic medications. Sometimes a tracheotomy is required to allow delivery of oxygen. Once the patient is stabilized, surgical treatment may be beneficial especially when paralysis occurs in both aretynoid cartilages (bilateral paralysis). The surgery (aretynoid lateralization, or a "laryngeal tieback") consists of suturing one of the aretynoid cartilages in a maximally abducted (open) position. This reduces the signs associated with inadequate ventilation (such as exercise intolerance or overheating) but may exacerbate the risk of aspiration and consequent pneumonia. Tying back only one of the aretynoid cartilages instead of both helps reduce the risk of aspiration. Afterwards the dog will still sound hoarse, and will need to be managed in the same way as those with mild cases of LP.

Recent studies have found that many dogs with laryngeal paralysis have decreased motility of their esophagus. Animals with a history of regurgitation or vomiting should be fully evaluated for esophageal or other gastrointestinal disorders. Dogs with megaesophagus or other conditions causing frequent vomiting or regurgitation are at high risk for aspiration pneumonia after laryngeal tie-back. Permanent tracheostomy is an alternative surgical option for these dogs to palliate their clincical signs.

Chagas disease affects 8 to 10 million people living in endemic Latin American countries, with an additional 300,000–400,000 living in nonendemic countries, including Spain and the United States. An estimated 41,200 new cases occur annually in endemic countries, and 14,400 infants are born with congenital Chagas disease annually. in 2010 it resulted in approximately 10,300 deaths up from 9,300 in 1990.

The disease is present in 18 countries on the American continents, ranging from the southern United States to northern Argentina. Chagas exists in two different ecological zones. In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where triatomines breed and feed on the more than 150 species from 24 families of domestic and wild mammals, as well as humans, that are the natural reservoirs of "T. cruzi".

Although Triatominae bugs feed on them, birds appear to be immune to infection and therefore are not considered to be a "T. cruzi" reservoir. Even when colonies of insects are eradicated from a house and surrounding domestic animal shelters, they can re-emerge from plants or animals that are part of the ancient, sylvatic (referring to wild animals) infection cycle. This is especially likely in zones with mixed open savannah, with clumps of trees interspersed by human habitation.

The primary wildlife reservoirs for "Trypanosoma cruzi" in the United States include opossums, raccoons, armadillos, squirrels, woodrats, and mice. Opossums are particularly important as reservoirs, because the parasite can complete its life cycle in the anal glands of this animal without having to re-enter the insect vector. Recorded prevalence of the disease in opossums in the U.S. ranges from 8.3% to 37.5%.

Studies on raccoons in the Southeast have yielded infection rates ranging from 47% to as low as 15.5%. Armadillo prevalence studies have been described in Louisiana, and range from a low of 1.1% to 28.8%. Additionally, small rodents, including squirrels, mice, and rats, are important in the sylvatic transmission cycle because of their importance as bloodmeal sources for the insect vectors. A Texas study revealed 17.3% percent "T. cruzi" prevalence in 75 specimens representing four separate small rodent species.

Chronic Chagas disease remains a major health problem in many Latin American countries, despite the effectiveness of hygienic and preventive measures, such as eliminating the transmitting insects. However, several landmarks have been achieved in the fight against it in Latin America, including a reduction by 72% of the incidence of human infection in children and young adults in the countries of the Southern Cone Initiative, and at least three countries (Uruguay, in 1997, and Chile, in 1999, and Brazil in 2006) have been certified free of vectorial and transfusional transmission. In Argentina, vectorial transmission has been interrupted in 13 of the 19 endemic provinces, and major progress toward this goal has also been made in both Paraguay and Bolivia.

Screening of donated blood, blood components, and solid organ donors, as well as donors of cells, tissues, and cell and tissue products for "T. cruzi" is mandated in all Chagas-endemic countries and has been implemented. Approximately 300,000 infected people live in the United States, which is likely the result of immigration from Latin American countries, and there have been 23 cases acquired from kissing bugs in the United States reported between 1955 and 2014. With increased population movements, the possibility of transmission by blood transfusion became more substantial in the United States. Transfusion blood and tissue products are now actively screened in the U.S., thus addressing and minimizing this risk.

There is currently no vaccine against Chagas disease. Prevention is generally focused on decreasing the numbers of the insect that spreads it ("Triatoma") and decreasing their contact with humans. This is done by using sprays and paints containing insecticides (synthetic pyrethroids), and improving housing and sanitary conditions in rural areas. For urban dwellers, spending vacations and camping out in the wilderness or sleeping at hostels or mud houses in endemic areas can be dangerous; a mosquito net is recommended. Some measures of vector control include:

- A yeast trap can be used for monitoring infestations of certain species of triatomine bugs ("Triatoma sordida", "Triatoma brasiliensis", "Triatoma pseudomaculata", and "Panstrongylus megistus").

- Promising results were gained with the treatment of vector habitats with the fungus "Beauveria bassiana".

- Targeting the symbionts of Triatominae through paratransgenesis can be done.

A number of potential vaccines are currently being tested. Vaccination with "Trypanosoma rangeli" has produced positive results in animal models. More recently, the potential of DNA vaccines for immunotherapy of acute and chronic Chagas disease is being tested by several research groups.

Blood transfusion was formerly the second-most common mode of transmission for Chagas disease, but the development and implementation of blood bank screening tests has dramatically reduced this risk in the 21st century. Blood donations in all endemic Latin American countries undergo Chagas screening, and testing is expanding in countries, such as France, Spain and the United States, that have significant or growing populations of immigrants from endemic areas. In Spain, donors are evaluated with a questionnaire to identify individuals at risk of Chagas exposure for screening tests.

The US FDA has approved two Chagas tests, including one approved in April 2010, and has published guidelines that recommend testing of all donated blood and tissue products. While these tests are not required in US, an estimated 75–90% of the blood supply is currently tested for Chagas, including all units collected by the American Red Cross, which accounts for 40% of the U.S. blood supply. The Chagas Biovigilance Network reports current incidents of Chagas-positive blood products in the United States, as reported by labs using the screening test approved by the FDA in 2007.

Hypoadrenocorticism is typically a disease of young to middle-aged female dogs, although Standard Poodles and Bearded Collies of both sexes are prone to the condition.

Hypoadrenocorticism is an inherited disease in the following breeds (and therefore a higher proportion of dogs within these breeds are affected, compared to other breeds):

- Bearded Collie

- Nova Scotia Duck Tolling Retriever

- Portuguese Water Dog

- Standard Poodle

Some breeds are at increased risk of hypoadrenocorticism:

- Airedale Terrier

- Basset Hound

- Bearded Collie

- Great Dane

- Rottweiler

- Springer Spaniels: English Springer Spaniel and Welsh Springer Spaniel

- Saint Bernard

- Soft-Coated Wheaten Terrier

- West Highland white terrier

Some breeds have a reduced risk of hypoadrenocorticism:

- Boxer

- Cocker Spaniel

- Golden Retriever

- Pit Bull Terrier

- Lhasa Apso

- Yorkshire Terrier

Primary adrenocortical insufficiency is the more common form of hypoadrenocorticism. All layers of the adrenal gland stop functioning; the problem is with the adrenal gland. This causes a deficiency of both mineralocorticoid and glucocorticoid secretion. Most cases are classified as idiopathic, although immune-mediated adrenocortical destruction is a likely cause. Bilateral destruction of the adrenal cortex by neoplasia (e.g. lymphosarcoma), granulomatous disease, or arterial thrombosis can also cause primary adrenocortical insufficiency. The destruction is progressive, although variable in rate, ultimately leading to complete loss of adrenocorotical function. A partial deficiency syndrome may occur initially, with signs manifested only during times of stress (e.g., boarding, travel, surgery).