Many signs are associated with PPID, but only a subset of these are displayed in any single horse. Some horses may present with chronic laminitis without other overt signs of the disease.

- Hypertrichosis (hirsutisim) produces a long, thick, wavy coat that often has delayed shedding or fails to shed completely, and may lighten in color. Hirsutism has been suggested to be pathognomonic for PPID, with up to 95% of horses having PPID.

- Laminitis

- Increased drinking and increased urination

- Pot-bellied appearance

- Weight loss

- Redistribution of fat, leading to bulging supraorbital fat pad, a "cresty" neck, and fat over the tail head or in the sheath of males

- Lethargy

- Behavioral changes, often an increased docility

- Muscle wasting, especially along the top line

- Increased sweating, or less commonly, decreased sweating

- Increased appetite

- Decreased sensitivity to pain

- Recurrent infections due to immune impairment

- Rarely neurologic signs such as narcolepsy, blindness, or seizures

- Suspensary ligament degeneration

Complete blood counts and serum chemistry profiles may be normal in affected horses. Persistent hyperglycemia and glucosuria are very commonly seen. Hyperlipidemia may be present, especially in ponies. Other abnormalities associated with the disease include mild anemia, neurophilia, lymphopenia, eosinopenia, and increased liver enzymes.

Because of the ubiquity of arsenic in ground water supplies and its effect on cardiovascular health, low dose arsenic poisoning should be inferred as a part of the pathogenesis of idiopathic hypertension. Idiopathic and essential are both somewhat synonymous with primary hypertension. Arsenic exposure has also many of the same signs of primary hypertension such as headache, somnolence,

confusion, proteinuria

visual disturbances, and nausea and vomiting

Common signs and symptoms of Cushing's disease include the following:

- weight gain

- high blood pressure

- poor short-term memory

- irritability

- excess hair growth (women)

- Impaired immunological function

- red, ruddy face

- extra fat around neck

- moon face

- fatigue

- red stretch marks

- poor concentration

- irregular menstruation

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). Common signs include the growth of fat pads along the collarbone, on the back of the neck ("buffalo hump" or lipodystrophy), and on the face ("moon face"). Other symptoms include excess sweating, dilation of capillaries, thinning of the skin (which causes easy bruising and dryness, particularly the hands) and mucous membranes, purple or red striae (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs, or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth), baldness and/or extremely dry and brittle hair. In rare cases, Cushing's can cause hypocalcemia. The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, inhibited aromatase, reduced libido, impotence in men, and amenorrhoea/oligomenorrhea and infertility in women due to elevations in androgens. Studies have also shown that the resultant amenorrhea is due to hypercortisolism, which feeds back onto the hypothalamus resulting in decreased levels of GnRH release.

Cognitive conditions, including memory and attention dysfunctions, as well as depression, are commonly associated with elevated cortisol, and may be early indicators of exogenous or endogenous Cushing's. Depression and anxiety disorders are also common.

Other striking and distressing skin changes that may appear in Cushing's syndrome include facial acne, susceptibility to superficial fungus (dermatophyte and malassezia) infections, and the characteristic purplish, atrophic striae on the abdomen.

Other signs include increased urination (and accompanying increased thirst), persistent high blood pressure (due to cortisol's enhancement of epinephrine's vasoconstrictive effect) and insulin resistance (especially common with ACTH production outside the pituitary), leading to high blood sugar and insulin resistance which can lead to diabetes mellitus. Insulin resistance is accompanied by skin changes such as acanthosis nigricans in the axilla and around the neck, as well as skin tags in the axilla. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cortisol can also exhibit mineralocorticoid activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion). Furthermore, excessive cortisol may lead to gastrointestinal disturbances, opportunistic infections, and impaired wound healing related to cortisol's suppression of the immune and inflammatory responses. Osteoporosis is also an issue in Cushing's syndrome since osteoblast activity is inhibited. Additionally, Cushing's syndrome may cause sore and aching joints, particularly in the hip, shoulders, and lower back. Cushing’s syndrome includes all the causes of increased cortisol leading to the diseased state. Cushing’s disease is a specific type of Cushing’s syndrome caused by a pituitary tumor leading to excessive production of ACTH (adrenocorticotropic hormone). Excessive ACTH stimulates the adrenal cortex to produce high levels of cortisol, producing the disease state. Cushing's disease due to excess ACTH may also result in hyperpigmentation. This is due to Melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from Pro-opiomelanocortin (POMC). Alternatively, it is proposed that the high levels of ACTH, β-lipotropin, and γ-lipotropin, which contain weak MSH function, can act on the melanocortin 1 receptor. A variant of Cushing's disease can be caused by ectopic, i.e. extrapituitary, ACTH production from, for example, a small-cell lung cancer. When Cushing's syndrome is caused by an increase of cortisol at the level of the adrenal glands (via an adenoma or hyperplasia), negative feedback ultimately reduces ACTH production in the pituitary. In these cases, ACTH levels remain low and no hyperpigmentation develops. While all Cushing’s disease gives Cushing’s syndrome, not all Cushing’s syndrome is due to Cushing’s disease.

Brain changes such as cerebral atrophy may occur. This atrophy is associated with areas of high glucocorticoid receptor concentrations such as the hippocampus and correlates highly with psychopathological personality changes.

- Rapid weight gain

- Moodiness, irritability, or depression

- Muscle and bone weakness

- Memory and attention dysfunction

- Osteoporosis

- Diabetes mellitus

- Hypertension

- Immune suppression

- Sleep disturbances

- Menstrual disorders such as amenorrhea in women

- Decreased fertility in men

- Hirsutism

- Baldness

- Hypercholesterolemia

The less-common signs and symptoms of Cushing's disease include the following:

- insomnia

- recurrent infection

- thin skin and stretch marks

- easy bruising

- weak bones

- acne

- balding (women)

- depression

- hip and shoulder weakness

- swelling of feet/legs

- diabetes mellitus

- erectile dysfunction

Another common and under-recognized sign of hypertension is sleep apnea, which is often best treated with nocturnal nasal continuous positive airway pressure (CPAP), but other approaches include the Mandibular advancement splint (MAS), UPPP, tonsillectomy, adenoidectomy, septoplasty, or weight loss.

Another cause is an exceptionally rare neurological disease called Binswanger's disease, causing dementia; it is a rare form of multi-infarct dementia, and is one of the neurological syndromes associated with hypertension.

Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

Cushing's syndrome is caused by either excessive cortisol-like medication such as prednisone or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands. Cases due to a pituitary adenoma are known as Cushing's disease. It is the second most common cause of Cushing's syndrome after medication. A number of other tumors may also cause Cushing's. Some of these are associated with inherited disorders such as multiple endocrine neoplasia type 1 and Carney complex. Diagnosis requires a number of steps. The first step is to check the medications a person takes. The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone. If this test is abnormal, the cortisol may be measured late at night. If the cortisol remains high, a blood test for ACTH may be done to determine if the pituitary is involved.

Most cases can be treated and cured. If due to medications, these can often be slowly stopped. If caused by a tumor, it may be treated by a combination of surgery, chemotherapy, and/or radiation. If the pituitary was affected, other medications may be required to replace its lost function. With treatment, life expectancy is usually normal. Some, in whom surgery is unable to remove the entire tumor, have an increased risk of death.

About two to three people per million are affected each year. It most commonly affects people who are 20 to 50 years of age. Women are affected three times more often than men. A mild degree of overproduction of cortisol without obvious symptoms, however, is more common. Cushing's syndrome was first described by Harvey Cushing in 1932. Cushing's syndrome may also occur in other animals including cats, dogs, and horses.

Pituitary ACTH hypersecretion (or Cushing disease) is a form of hyperpituitarism characterized by an abnormally high level of ACTH produced by the anterior pituitary. It is one of the causes of Cushing's syndrome. (However, Cushing's syndrome can be caused by many other causes, including exogenous administration.)

Hypoglycemia in early infancy can cause jitteriness, lethargy, unresponsiveness, or seizures. The most severe forms may cause macrosomia in utero, producing a large birth weight, often accompanied by abnormality of the pancreas. Milder hypoglycemia in infancy causes hunger every few hours, with increasing jitteriness or lethargy. Milder forms have occasionally been detected by investigation of family members of infants with severe forms, adults with the mildest degrees of congenital hyperinsulinism have a decreased tolerance for prolonged fasting. Other presentations are:

The variable ages of presentations and courses suggest that some forms of congenital hyperinsulinism, especially those involving abnormalities of K channel function, can worsen or improve with time the potential harm from hyperinsulinemic hypoglycemia depends on the severity, and duration. Children who have recurrent hyperinsulinemic hypoglycemia in infancy can suffer harm to the brain

Hyperpituitarism is a condition due to the primary hypersecretion of pituitary hormones, it typically results from a pituitary adenoma. Children with hyperpituitarism is rare, disruption of growth regulation, either because of hormone hypersecretion or because of manifestations caused by local compression of the adenoma can occur.

Symptoms caused by hormone excess and associated mass effects include:

Adrenocortical hyperfunction is a condition where there is an overexpression of products of the adrenal cortex.

When cortisol is overproduced, it is called Cushing's syndrome.

When aldosterone is overproduced, it is called hyperaldosteronism.

There are differenct types of congenital hyperinsulinism as "diffuse and focal" indicated below:

PPNAD is a rare cause of high cortisol levels in the blood and often manifests as ACTH-independent Cushing's syndrome. The effects of PPNAD can often be cyclical so the symptoms of Cushing's syndrome will not always be as severe, which may complicate diagnosis. The classic symptoms of Cushing's syndrome include rapid central weight gain, a puffy red face and a buffalo hump at the back of the neck due to fat deposits. Skin changes in Cushing's syndrome include thinning and bruising easily, developing striae and hyperpigmentation at skin folds. The hormonal changes can lead to hirsuitism, males developing breast tissue, females no longer having periods and both sexes may become infertile. High cortisol levels can lead to psychological disturbances such as anxiety or depression and insomnia. Bone health can deteriorate, leading to an increased fracture risk in people with Cushing's syndrome. PPNAD is unique as it often causes Cushing's at a young age, in children and adolescents. In addition to the other symptoms of Cushing's syndrome, the patient may have a short stature due to interrupted growth because of ACTH suppression.

In 90% of people with PPNAD it is associated with Carney Complex. Carney Complex is usually inherited, however it can also occur sporadically. A visible sign of Carney complex is abnormal skin hyperpigmentation. There may also be myxomas which can appear as lumps in the skin and breast as well as often being present in the heart, which can lead to multiple cardiovascular problems. The majority of people with PPNAD will have some of these signs/symptoms due to the strong association between PPNAD and Carney Complex.

The common symptoms include:

- hyper-pigmentation of the skin

- visual disturbances

- headaches

- abnormal high levels of beta-MSH and ACTH

- abnormal enlargements of the pituitary gland,

- interruption of menstrual cycles in women

A adrenocortical adenoma (or adrenal cortical adenoma, or sometimes simply adrenal adenoma) is a benign tumor of the adrenal cortex.

It can present with Cushing's syndrome or primary aldosteronism. They may also secrete androgens, causing hyperandrogenism. Also, they are often diagnosed incidentally as incidentalomas.

Is a well circumscribed, yellow tumour in the adrenal cortex, which is usually 2–5 cm in diameter. The color of the tumour, as with adrenal cortex as a whole, is due to the stored lipid (mainly cholesterol), from which the cortical hormones are synthesized. These tumors are frequent incidental findings at post mortem examination, and appear to have produced no significant metabolic disorder; only a very small percentage lead to Cushing's syndrome. Nevertheless, these apparently non-functioning adenomas are most often encountered in elder obese people. There is some debate that they may really represent nodules in diffuse nodular cortical hyperplasia.

Very occasionally, a true adrenal cortical adenoma is associated with the clinical manifestations of Conn's syndrome, and can be shown to be excreting mineralocorticoids.

These depend on poorly understood variations in individual biology and consequently may not be found with all people diagnosed with insulin resistance.

- Increased hunger

- Lethargy (tiredness)

- Brain fogginess and inability to focus

- High blood sugar

- Weight gain, fat storage, difficulty losing weight – for most people, excess weight is from high subcutaneous fat storage; the fat in IR is generally stored in and around abdominal organs in both males and females; it is currently suspected that hormones produced in that fat are a precipitating cause of insulin resistance

- Increased blood cholesterol levels

- Increased blood pressure; many people with hypertension are either diabetic or pre-diabetic and have elevated insulin levels due to insulin resistance; one of insulin's effects is to control arterial wall tension throughout the body

Primary pigmented nodular adrenocortical disease (PPNAD) was first coined in 1984 by Carney et al. it often occurs in association with Carney complex (CNC). CNC is a rare syndrome that involves the formation of abnormal tumours that cause endocrine hyperactivity.

PPNAD arises due to the enlargement of the cortex of the adrenal glands, resulting in Cushing's syndrome that is independent of the pituitary hormone ACTH.

Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. The body produces insulin when glucose starts to be released into the bloodstream from the digestion of carbohydrates in the diet. Normally this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy. The concentration of glucose in the blood decreases as a result, staying within the normal range even when a large amount of carbohydrates is consumed. When the body produces insulin under conditions of insulin resistance, the cells are resistant to the insulin and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level. This often remains undetected and can contribute to the development of type 2 diabetes or latent autoimmune diabetes of adults. Although this type of chronic insulin resistance is harmful, during acute illness it is actually a well-evolved protective mechanism. Recent investigations have revealed that insulin resistance helps to conserve the brain's glucose supply by preventing muscles from taking up excessive glucose. In theory, insulin resistance should even be strengthened under harsh metabolic conditions such as pregnancy, during which the expanding fetal brain demands more glucose.

People who develop type 2 diabetes usually pass through earlier stages of insulin resistance and prediabetes, although those often go undiagnosed. Insulin resistance is a syndrome (a set of signs and symptoms) resulting from reduced insulin activity; it is also part of a larger constellation of symptoms called the metabolic syndrome.

Insulin resistance may also develop in patients who have recently experienced abdominal or bariatric procedures. This acute form of insulin resistance that may result post-operatively tends to increase over the short term, with sensitivity to insulin typically returning to patients after about five days.

Steroid-induced osteoporosis (SIOP) is osteoporosis arising due to use of glucocorticoids (steroid hormones) - analogous to Cushing's syndrome and involving mainly the axial skeleton. The synthetic glucocorticoid prescription drug prednisone is a main candidate after prolonged intake. Bisphosphonates are beneficial in reducing the risk of vertebral fractures. Some professional guidelines recommend prophylactic calcium and vitamin D supplementation in patients who take the equivalent of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially when this is in excess of three months. The use of thiazide diuretics, and gonadal hormone replacement has also been recommended, with the use of calcitonin, bisphosphonates, sodium fluoride or anabolic steroids also suggested in refractory cases. Alternate day use may not prevent this complication.

Mechanisms of SIOP include:

- Direct inhibition of osteoblast function

- Direct enhancement of bone resorption

- Inhibition of gastrointestinal calcium absorption

- Increased urine calcium loss

- Inhibition of sex steroids

Metabolic alkalosis is usually accompanied by low blood potassium concentration, causing, e.g., muscular weakness, muscle pain, and muscle cramps (from disturbed function of the skeletal muscles), and muscle spasms (from disturbed function of smooth muscles).

It may also cause low blood calcium concentration. As the blood pH increases, blood transport proteins, such as albumin, become more ionized into anions. This causes the free calcium present in blood to bind more strongly with albumin. If severe, it may cause tetany.

Nelson's syndrome is a rare disorder and occurs in patients who have had both adrenal glands removed owing to Cushing's disease. During the disorder the patient develops macroadenomas that secrete adrenocorticotropic hormone (ACTH). The severity of the disease is dependent upon the effect of ACTH release on the skin, pituitary hormone loss, and the effect the tumor has on the surrounding structures within the body.

The first case of Nelson’s syndrome was reported in 1958 by Nelson et al. Dr. Don Nelson, an endocrinologist, named the disease. In comparison to the 1980s there have been fewer published cases in the 1990s. Thus, Nelson’s syndrome has become less prevalent. The disease becoming less prevalent is supported by much advancement in the medical field. Within the past ten to twenty years, improvements have been made with identification and care for patients with Cushing’s disease. Improvements have been made with techniques such as pituitary radiation therapy, ACTH assay, transsphenoidal pituitary surgery, higher resolution MRIs, and sampling of the inferior petrosal sinus. The advancements mentioned prior are what have allowed physicians to pursue other routes for Cushing’s disease therapy that don’t involve bilateral adrenalectomy.

Nelson’s syndrome is also referred to as post adrenalectomy syndrome and is a result of an adrenalectomy performed for Cushing’s disease. Corticotroph adenomas are detected in more females than males. Therefore, Nelson’s syndrome is observed in more females than males. Corticotroph adenomas are also detected in the younger population compared to the older population. Earlier, Nelson's syndrome was observed in 20-40% of patients who had a bilateral adrenalectomy with a pituitary adenoma. Nelson's syndrome is observed in 8-44% of the population who have undergone bilateral adrenalectomy treatment for Cushing's disease.

Alkalosis is the result of a process reducing hydrogen ion concentration of arterial blood plasma (alkalemia). In contrast to acidemia (serum pH 7.35 or lower), alkalemia occurs when the serum pH is higher than normal (7.45 or higher). Alkalosis is usually divided into the categories of respiratory alkalosis and metabolic alkalosis or a combined respiratory/metabolic alkalosis.

The adrenal cortex is composed of three distinct layers of endocrine cells which produce critical steroid hormones. These include the glucocorticoids which are critical for regulation of blood sugar and the immune system, as well as response to physiological stress, the mineralcorticoid aldosterone, which regulates blood pressure and kidney function, and certain sex hormones. Both benign and malignant tumors of the adrenal cortex may produce steroid hormones, with important clinical consequences.