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

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.

Most affected cats are over 10 years old. No breed or sex is predisposed to hyperadlosteronism.

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 If steroids are abruptly withdrawn, the dormant adrenal glands may not able to reactivate, and the body will need to have its adrenal glucocorticoid hormones replaced by medication.

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.

Autoimmune adrenalitis is the most common cause of Addison's disease in the industrialised world. Autoimmune destruction of the adrenal cortex is caused by an immune reaction against the enzyme 21-hydroxylase (a phenomenon first described in 1992). This may be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2), in which other hormone-producing organs, such as the thyroid and pancreas, may also be affected.

Adrenal destruction is also a feature of adrenoleukodystrophy (ALD), and when the adrenal glands are involved in metastasis (seeding of cancer cells from elsewhere in the body, especially lung), hemorrhage (e.g. in Waterhouse-Friderichsen syndrome or antiphospholipid syndrome), particular infections (tuberculosis, histoplasmosis, coccidioidomycosis), or the deposition of abnormal protein in amyloidosis.

In secondary hypoadrenocorticism (also known as atypical hypoadrenocorticism) the problem is not in the adrenal gland but in the pituitary gland. Usually, the anterior portion of the pituitary gland produces a hormone, adrenocorticotropic hormone (ACTH), that signals the zona fasciculata and zona reticularis to produce their steroids. When the pituitary is unable to produce ACTH, these zones stop production of their hormones. The zona glomerulosa is not controlled by ACTH, and remains able to produce a normal amount of mineralocorticoids. A dog with secondary hypoadrenocorticism is not at risk of an Addisonian crisis, and only needs to have medication to replace the glucocorticoid steroid cortisol. One dog in every 42 diagnosed with hypoadrenocorticism has the secondary form of the disease where mineralocorticoid production remains intact.

Secondary adrenocortical insufficiency involves only a deficiency of glucocorticoid secretion. Destructive lesions (e.g. neoplasia, inflammation) in the pituitary gland or hypothalamus and chronic administration of exogenous glucocorticoids or megestrol acetate (cats) are the most common causes.

In some dogs with secondary hypoadrenocorticism, the disease progresses to primary hypoadrenocorticism, and mineralocorticoid replacement becomes necessary, while others retain their ability to continue production of mineralocorticoids for years, requiring glucocorticoid replacement only.

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.

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.

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).

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.

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.

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.

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.

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.

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.

40% of people with an adrenal aldosterone producing adenoma have somatic gain-of-function mutations in a single gene (KCNJ5). This gene is mutated in inherited cases albeit less frequently. These mutations tend to occur in young women with the adenoma in the cortisol secreting zona fasciculata. Adenomas without this mutation tend to occur in older men with resistant hypertension.

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)

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.

Primary hyperaldosteronism (PHA) is a disorder of the adrenal cortex that causes increased circulating aldosterone levels. There are two types of PHA. One type is caused by a unilateral aldosterone-producing adenoma or adenocarcinoma. The other type, known as idiopathic hyperaldosteronism, occurs with bilateral adrenal hyperplasia.

Common causes include bilateral adrenalectomy for the treatment of Cushing's disease, and hypopituitarism. The onset of the disease can occur up to 24 years after a bilateral adrenalectomy has been performed, with an average of up to 15 years after. A preventative measure that can be utilized is prophylactic radiotherapy when a bilateral adrenalectomy is being performed in order to prevent Nelson's syndrome from manifesting. Screening can also be done with the help or an MRI in order to visualize the pituitary for tumors. If tumors are not present then an MRI should be performed at intervals. Hyper-pigmentation and fasting ACTH levels within plasma above 154 pmol/l are predictive of Nelson's syndrome after an adrenalectomy. Risk factors include being younger in age and pregnancy.

Glucocorticoid deficiency 1 (FGD or GCCD) is an adrenocortical failure characterized by low levels of plasma cortisol produced by the adrenal gland despite high levels of plasma ACTH. This is an inherited disorder with several different causes which define the type.

FGD type 1 (FGD1 or GCCD1) is caused by mutations in the ACTH receptor (melanocortin 2 receptor; MC2R). FGD type 2 is caused by mutations in the MC2R accessory protein (MRAP). These two types account for 45% of all cases of FGD.

Some cases of FGD type 3 are caused by mutations in the steroidogenic acute regulatory protein (StAR), with similarity to the nonclassic form of lipoid congenital adrenal hyperplasia. In this case, a general impairment in not just adrenal steroid production, but gonadal steroid production can affect sexual development and fertility.

The causes of other cases of FGD type 3 not due to StAR are currently unknown.

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.

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 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.