Iatrogenic Cushing's syndrome (caused by treatment with corticosteroids) is the most common form of Cushing's syndrome. Cushing's disease is rare; a Danish study found an incidence of less than one case per million people per year. However, asymptomatic microadenomas (less than 10 mm in size) of the pituitary are found in about one in six individuals.

People with Cushing's syndrome have increased morbidity and mortality as compared to the general population. The most common cause of mortality in Cushing's syndrome is cardiovascular events. People with Cushing's syndrome have nearly 4 times increased cardiovascular mortality as compared to the general population.

The most common cause of Cushing's syndrome is the taking of glucocorticoids prescribed by a health care practitioner to treat other diseases (called iatrogenic Cushing's syndrome). This can be an effect of corticosteroid treatment of a variety of disorders such as asthma and rheumatoid arthritis, or in immunosuppression after an organ transplant. Administration of synthetic ACTH is also possible, but ACTH is less often prescribed due to cost and lesser utility. Although rare, Cushing's syndrome can also be due to the use of medroxyprogesterone acetate. In this form of Cushing's, the adrenal glands atrophy due to lack of stimulation by ACTH, since glucocorticoids downregulate production of ACTH. Cushing's syndrome in childhood usually results from use of glucocorticoid medication.

Endogenous Cushing's syndrome results from some derangement of the body's own system of secreting cortisol. Normally, ACTH is released from the pituitary gland when necessary to stimulate the release of cortisol from the adrenal glands.

- In pituitary Cushing's, a benign pituitary adenoma secretes ACTH. This is also known as Cushing's disease and is responsible for 70% of endogenous Cushing's syndrome.

- In adrenal Cushing's, excess cortisol is produced by adrenal gland tumors, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.

- Tumors outside the normal pituitary-adrenal system can produce ACTH (occasionally with CRH) that affects the adrenal glands. This etiology is called ectopic or paraneoplastic Cushing's disease and is seen in diseases such as small cell lung cancer.

- Finally, rare cases of CRH-secreting tumors (without ACTH secretion) have been reported, which stimulates pituitary ACTH production.

Cases of Cushing's disease are rare, and little epidemiological data is available on the disease. An 18-year study conducted on the population of Vizcaya, Spain reported a 0.004% prevalence of Cushing's disease. The average incidence of newly diagnosed cases was 2.4 cases per million inhabitants per year. The disease is often diagnosed 3–6 years after the onset of illness.

Several studies have shown that Cushing's disease is more prevalent in women than men at a ratio of 3-6:1, respectively. Moreover, most women affected were between the ages of 50 and 60 years.

The prevalence of hypertension, and abnormalities in glucose metabolism are major predictors of mortality and morbidity in untreated cases of the disease. The mortality rate of Cushing's disease was reported to be 10-11%, with the majority of deaths due to vascular disease Women aged 45–70 years have a significantly higher mortality rate than men.

Moreover, the disease shows a progressive increase with time. Reasons for the trend are unknown, but better diagnostic tools, and a higher incidence rate are two possible explanations.

Carcinomas that metastasize into the pituitary gland are uncommon and typically seen in the elderly, with lung and breast cancers being the most prevalent, In breast cancer patients, metastases to the pituitary gland occur in approximately 6-8% of cases.

Symptomatic pituitary metastases account for only 7% of reported cases. In those who are symptomatic Diabetes insipidus often occurs with rates approximately 29-71%. Other commonly reported symptoms include anterior pituitary dysfunction, visual field defects, headache/pain, and ophthalmoplegia.

The cause of hyperpituitarism in most cases is due to pituitary adenomas. They usually come from the anterior lobe, are functional and secrete the hormone, GH and prolactin.

Adenomas of the anterior pituitary gland are a major clinical feature of multiple endocrine neoplasia type 1 (MEN1), a rare inherited endocrine syndrome that affects 1 person in every 30,000. MEN causes various combinations of benign or malignant tumors in various glands in the endocrine system or may cause the glands to become enlarged without forming tumors. It often affects the parathyroid glands, pancreatic islet cells, and anterior lobe of the pituitary gland. MEN1 may also cause non-endocrine tumors such as facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas. Approximately 25 percent of patients with MEN1 develop pituitary adenomas.

Several studies have shown that hypopituitarism is associated with an increased risk of cardiovascular disease and some also an increased risk of death of about 50% to 150% the normal population. It has been difficult to establish which hormone deficiency is responsible for this risk, as almost all patients studied had growth hormone deficiency. The studies also do not answer the question as to whether the hypopituitarism itself causes the increased mortality, or whether some of the risk is to be attributed to the treatments, some of which (such as sex hormone supplementation) have a recognized adverse effect on cardiovascular risk.

The largest study to date followed over a thousand people for eight years; it showed an 87% increased risk of death compared to the normal population. Predictors of higher risk were: female sex, absence of treatment for sex hormone deficiency, younger age at the time of diagnosis, and a diagnosis of craniopharyngioma. Apart from cardiovascular disease, this study also showed an increased risk of death from lung disease.

Quality of life may be significantly reduced, even in those people on optimum medical therapy. Many report both physical and psychological problems. It is likely that the commonly used replacement therapies do not completely mimic the natural hormone levels in the body. Health costs remain about double those of the normal population.

Hypopituitarism is usually permanent. It requires lifelong treatment with one or more medicines.

Symptoms caused by hormone excess and associated mass effects include:

All causes in this category are genetic, and generally very rare. These include mutations to the "SF1" transcription factor, congenital adrenal hypoplasia due to "DAX-1" gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple A or Allgrove syndrome). "DAX-1" mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when "DAX-1" is deleted together with a number of other genes.

There is only one study that has measured the prevalence (total number of cases in a population) and incidence (annual number of new cases) of hypopituitarism. This study was conducted in Northern Spain and used hospital records in a well-defined population. The study showed that 45.5 people out of 100,000 had been diagnosed with hypopituitarism, with 4.2 new cases per year. 61% were due to tumors of the pituitary gland, 9% due to other types of lesions, and 19% due to other causes; in 11% no cause could be identified.

Recent studies have shown that people with a previous traumatic brain injury, spontaneous subarachnoid hemorrhage (a type of stroke) or radiation therapy involving the head have a higher risk of hypopituitarism. After traumatic brain injury, as much as a quarter have persistent pituitary hormone deficiencies. Many of these people may have subtle or non-specific symptoms that are not linked to pituitary problems but attributed to their previous condition. It is therefore possible that many cases of hypopituitarism remain undiagnosed, and that the annual incidence would rise to 31 per 100,000 annually if people from these risk groups were to be tested.

Causes of acute adrenal insufficiency are mainly sudden withdrawal of long-term corticosteroid therapy, Waterhouse-Friderichsen syndrome, and stress in people with underlying chronic adrenal insufficiency. The latter is termed critical illness–related corticosteroid insufficiency.

For chronic adrenal insufficiency, the major contributors are autoimmune adrenalitis (Addison's Disease), tuberculosis, AIDS, and metastatic disease. Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis, and sarcoidosis.

Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome, which can include type 1 diabetes, hyperthyroidism, and autoimmune thyroid disease (also known as autoimmune thyroiditis, Hashimoto's thyroiditis, and Hashimoto's disease). Hypogonadism may also present with this syndrome. Other diseases that are more common in people with autoimmune adrenalitis include premature ovarian failure, celiac disease, and autoimmune gastritis with pernicious anemia.

Adrenoleukodystrophy can also cause adrenal insufficiency.

Adrenal insufficiency can also result when a patient has a craniopharyngioma, which is a histologically benign tumor that can damage the pituitary gland and so cause the adrenal glands not to function. This would be an example of secondary adrenal insufficiency syndrome.

Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to glandular damage).

Outcomes are typically good when treated. Most can expect to live relatively normal lives. Someone with the disease should be observant of symptoms of an "Addison's crisis" while the body is strained, as in rigorous exercise or being sick, the latter often needing emergency treatment with intravenous injections to treat the crisis.

Individuals with Addison's disease have more than a doubled mortality rate. Furthermore, individuals with Addison's disease and diabetes mellitus have an almost 4 time increase in mortality compared to individuals with only diabetes.

Cushing's disease is a cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary (secondary hypercortisolism). This is most often as a result of a pituitary adenoma (specifically pituitary basophilism) or due to excess production of hypothalamus CRH (corticotropin releasing hormone) (tertiary hypercortisolism/hypercorticism) that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome, when excluding Cushing's syndrome from exogenously administered corticosteroids.

This should not be confused with ectopic Cushing syndrome or exogenous steroid use.

The frequency rate of Addison's disease in the human population is sometimes estimated at roughly one in 100,000. Some put the number closer to 40–144 cases per million population (1/25,000–1/7,000). Addison's can affect persons of any age, sex, or ethnicity, but it typically presents in adults between 30 and 50 years of age. Research has shown no significant predispositions based on ethnicity.

Pheochromocytoma is seen in between two and eight in 1,000,000, with approximately 1000 cases diagnosed in United States yearly. It mostly occurs in young or middle age adults, though it presents earlier in hereditary cases.

- About 10% of adrenal cases are bilateral (suggesting hereditary disease)

- About 10% of adrenal cases occur in children (also suggesting hereditary disease)

- About 15% are extra-adrenal (located in any orthosympathetic tissue): Of these 9% are in the abdomen, and 1% are located elsewhere. Some extra-adrenal pheochromocytomas are probably actually paragangliomas, but the distinction can only be drawn after surgical resection.

- About 11.1% of adrenal cases are malignant, but this rises to 30% for extra-adrenal cases

- About 15–20% are hereditary

- About 5% are caused by VHL disease

- About 3% recur after being resected

- About 14% of affected individuals do not have arterial hypertension (Campbell's Urology)

The condition is due to:

- Bilateral idiopathic (micronodular) adrenal hyperplasia (66%)

- Adrenal adenoma (Conn's syndrome) (33%)

- Primary (unilateral) adrenal hyperplasia—2% of cases

- Aldosterone-producing adrenocortical carcinoma—<1% of cases

- Familial Hyperaldosteronism (FH)

- Glucocorticoid-remediable aldosteronism (FH type I)—<1% of cases

- FH type II (APA or IHA)—<2% of cases

- Ectopic aldosterone-producing adenoma or carcinoma—< 0.1% of cases

In a study of 1,034 symptomatic adults, Sheehan syndrome was found to be the sixth most frequent etiology of growth hormone deficiency, being responsible for 3.1% of cases (versus 53.9% due to a pituitary tumor).

Almost all cases of pituitary apoplexy arise from a pituitary adenoma, a benign tumor of the pituitary gland. In 80%, the patient has been previously unaware of this (although some will retrospectively report associated symptoms). It was previously thought that particular types of pituitary tumors were more prone to apoplexy than others, but this has not been confirmed. In absolute terms, only a very small proportion of pituitary tumors eventually undergoes apoplexy. In an analysis of incidentally found pituitary tumors, apoplexy occurred in 0.2% annually, but the risk was higher in tumors larger than 10 mm ("macroadenomas") and tumors that were growing more rapidly; in a meta-analysis, not all these associations achieved statistical significance.

The majority of cases (60–80%) are not precipitated by a particular cause. A quarter has a history of high blood pressure, but this is a common problem in the general population, and it is not clear whether it significantly increase the risk of apoplexy. A number of cases has been reported in association with particular conditions and situations; it is uncertain whether these were in fact causative. Amongst reported associations are surgery (especially coronary artery bypass graft, where there are significant fluctuations in the blood pressure), disturbances in blood coagulation or medication that inhibits coagulation, radiation therapy to the pituitary, traumatic brain injury, pregnancy (during which the pituitary enlarges) and treatment with estrogens. Hormonal stimulation tests of the pituitary have been reported to provoke episodes. Treatment of prolactinomas (pituitary adenomas that secrete prolactin) with dopamine agonist drugs, as well as withdrawal of such treatment, has been reported to precipitate apoplexy.

Hemorrhage from a Rathke's cleft cyst, a remnant of Rathke's pouch that normally regresses after embryological development, may cause symptoms that are indistinguishable from pituitary apoplexy. Pituitary apoplexy is regarded by some as distinct from Sheehan's syndrome, where the pituitary undergoes infarction as a result of prolonged very low blood pressure, particularly when caused by bleeding after childbirth. This condition usually occurs in the absence of a tumor. Others regard Sheehan's syndrome as a form of pituitary apoplexy.

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.

In larger case series, the mortality was 1.6% overall. In the group of patients who were unwell enough to require surgery, the mortality was 1.9%, with no deaths in those who could be treated conservatively.

After an episode of pituitary apoplexy, 80% of people develop hypopituitarism and require some form of hormone replacement therapy. The most common problem is growth hormone deficiency, which is often left untreated but may cause decreased muscle mass and strength, obesity and fatigue. 60–80% require hydrocortisone replacement (either permanently or when unwell), 50–60% need thyroid hormone replacement, and 60–80% of men require testosterone supplements. Finally, 10–25% develop diabetes insipidus, the inability to retain fluid in the kidneys due to a lack of the pituitary antidiuretic hormone. This may be treated with the drug desmopressin, which can be applied as a nose spray or taken by mouth.

The massive release of catecholamines in pheochromocytoma can cause damage to heart cells. This damage may be due to either compromising the coronary microcirculation or by direct toxic effects on the heart cells.

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.

The transition from hyperthyroidism to thyroid storm is typically triggered by a non-thyroidal insult including, but not limited to fever, sepsis, dehydration, myocardial infarction, and psychiatric diseases. Individuals are at higher risk of thyroid storm if their hyperthyroidism is incompletely treated or if their anti-thyroid drugs are discontinued. Many of these individuals have underlying primary causes of hyperthyroidism (Graves disease, toxic multi-nodular goiter, solitary toxic adenoma). However, thyroid storm can occur in individuals with unrecognized thyrotoxicosis experiencing non-thyroid surgery, labor, infection, or exposure to certain medications and radiocontrast dyes.

Drug induced (iatrogenic) hypoadrenocorticism is caused during abrupt cessation of a steroid medication. During steroid treatment, the adrenal glands do not function fully. The body senses the levels of the exogenous steroids in the system and therefore does not signal for additional production. The usual protocol for stopping steroid medications is not to eliminate them suddenly, but to withdraw from them gradually in a "tapering off" process, which allows the production to adjust to normal. If steroids are abruptly withdrawn, the dormant adrenal glands may not able to reactivate, and the body will need to have its adrenal glucocorticoid hormones replaced by medication.

According to newer theories, thyroid storm results from allostatic failure in a situation were thyrotoxicosis hampers the development of non-thyroidal illness syndrome, which would help to save energy in critical illness and other situations of high metabolic demand.

Usually, in critical illness (e.g. sepsis, myocardial infarction and other causes of shock) thyroid function is tuned down to result in low-T3 syndrome and, occasionally, also low TSH concentrations, low-T4 syndrome and impaired plasma protein binding of thyroid hormones. This endocrine pattern is referred to as "euthyroid sick syndrome" (ESS), "non-thyroidal illness syndrome" (NTIS) or "thyroid allostasis in critical illness, tumours, uraemia and starvation" (TACITUS). Although NTIS is associated with significantly worse prognosis, it is also assumed to represent a beneficial adaptation (type 1 allostasis). In cases, where critical illness is accompanied by thyrotoxicosis, this comorbidity prevents the down-regulation of thyroid function. Therefore, the consumption of energy, oxygen and glutathione remains high, which leads to further increased mortality.

These new theories imply that thyroid storm results from an interaction of thyrotoxicosis with the specific response of the organism to an oversupply of thyroid hormones.