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.

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

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

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

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.)

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

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

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.

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.

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.

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:

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.

Malignant acanthosis nigricans refers to acanthosis nigricans occurring as a paraneoplastic syndrome associated with a cancer. Malignant acanthosis nigricans is most commonly associated with gastrointestinal adenocarcinomas, as well as genitourinary cancers such as those of the prostate, breast, and ovary. Other cancers, such as those of the lung, stomach, and lymphoma, are occasionally associated with acanthosis nigricans.

This form of acanthosis nigricans is more likely to involve mucous membranes (25-50% of cases) Malignant acanthosis nigricans that may either precede (18%), accompany (60%), or follow (22%) the onset of an internal cancer. Malignancy-associated acanthosis nigricans is usually rapid in onset and may be accompanied by skin tags, multiple seborrheic keratoses, or tripe palms.

Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds, such as the posterior and lateral folds of the neck, the armpits, groin, navel, forehead, and other areas.

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

Adrenal Adenomas are benign tumors on the adrenal gland. In most cases the tumors display no symptoms and require no treatment. In rare cases, however, some Adrenal Adenomas may become activated, in that they begin to produce hormones in much larger quantities than what adrenal glands tend to produce leading to a number of health complications including Primary aldosteronism and Hyperandrogenism.

Hyperandrogenism, especially high levels of testosterone, can cause serious adverse effects on women’s bodies if left untreated. High testosterone levels have been seen to be associated with obesity, hypertension, amenorrhea(stop of menstrual cycles), and ovulatory dysfunction, which can lead to infertility. The more prominent signs of hyperandrogenism are hirsutism (unwanted growth of hair especially in the abdominal region and places on the back), acne after adolescence, deepening of voice, and alopecia(balding). Hyperandrogenism has also been seen to cause individuals to have a high tolerance to insulin, which can lead to type two diabetes, and dyslipidemia, such as high cholesterol. These effects have also been seen to have a large psychological impact on the individual, sometimes often leading to societal anxiety and depression, especially in adolescent girls and young women. Paired with obesity and hirsutism, it can cause the individual to have low self-esteem, and a poor view of oneself.

Pseudo-Cushing's syndrome is a medical condition in which patients display the signs, symptoms, and abnormal hormone levels seen in Cushing's syndrome. However, pseudo-Cushing's syndrome is not caused by a problem with the hypothalamic-pituitary-adrenal axis as Cushing's is; it is mainly an idiopathic condition, however a cushingoid appearance is sometimes linked to excessive alcohol consumption.

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.

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.

Multiple endocrine neoplasia or MEN is part of a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia involves tumors in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, some cases can be life-threatening.

The two major forms of multiple endocrine neoplasia are called type 1 and type 2. These two types are often confused because of their similar names. However, type 1 and type 2 are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.

These disorders greatly increase the risk of developing multiple cancerous and noncancerous tumors in glands such as the parathyroid, pituitary, and pancreas. Multiple endocrine neoplasia occurs when tumors are found in at least two of the three main endocrine glands (parathyroid, pituitary, and pancreatico-duodenum). Tumors can also develop in organs and tissues other than endocrine glands. If the tumors become cancerous, some cases can be life-threatening. The disorder affects 1 in 30,000 people.

Although many different types of hormone-producing tumors are associated with multiple endocrine neoplasia, tumors of the parathyroid gland, pituitary gland, and pancreas are most frequent in multiple endocrine neoplasia type 1. MEN1-associated overactivity of these three endocrine organs are briefly described here:

- Overactivity of the parathyroid gland (hyperparathyroidism) is the most common sign of this disorder. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of the bones (osteoporosis), high blood pressure (hypertension), loss of appetite, nausea, weakness, fatigue, and depression.

- Neoplasia in the pituitary gland can manifest as prolactinomas whereby too much prolactin is secreted, suppressing the release of gonadotropins, causing a decrease in sex hormones such as testosterone. Pituitary tumor in MEN1 can be large and cause signs by compressing adjacent tissues.

- Pancreatic tumors associated with MEN-1 usually form in the beta cells of the islets of Langerhans, causing over-secretion of insulin, resulting in low blood glucose levels (hypoglycemia). However, many other tumors of the pancreatic Islets of Langerhans can occur in MEN-1. One of these, involving the alpha cells, causes over-secretion of glucagon, resulting in a classic triad of high blood glucose levels (hyperglycemia), a rash called necrolytic migratory erythema, and weight loss. Another is a tumor of the non-beta islet cells, known as a gastrinoma, which causes the over-secretion of the hormone gastrin, resulting in the over-production of acid by the acid-producing cells of the stomach (parietal cells) and a constellation of sequelae known as Zollinger-Ellison syndrome. Zollinger-Ellison syndrome may include severe gastric ulcers, abdominal pain, loss of appetite, chronic diarrhea, malnutrition, and subsequent weight loss. Other non-beta islet cell tumors associated with MEN1 are discussed below.

Pituitary tumors occur in 15 to 42% of MEN 1 patients. From 25 to 90% are prolactinomas. About 25% of pituitary tumors secrete growth hormone or growth hormone and prolactin. Excess prolactin may cause galactorrhea (see Pituitary Disorders: Galactorrhea), and excess growth hormone causes acromegaly clinically indistinguishable from sporadically occurring acromegaly. About 3% of tumors secrete ACTH, producing Cushing's disease. Most of the remainder are nonfunctional. Local tumor expansion may cause visual disturbance, headache, and hypopituitarism. Pituitary tumors in MEN 1 patients appear to be larger and behave more aggressively than sporadic pituitary tumors.