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.

Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births. More than 1000 individuals have been identified with thyroid hormone resistance, of which 85% had thyroid hormone beta receptor mutation.

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.

Growth hormone-releasing hormone (GHRH) is another releasing factor secreted by the hypothalamus. GHRH stimulates the pituitary gland to secrete growth hormone (GH), which has various effects on body growth and sexual development. Insufficient GH production may cause poor somatic growth, precocious puberty or gonadotropin deficiency, failure to initiate or complete puberty, and is often associated with rapid weight gain, low T, and low levels of sex hormones.

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.

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.

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 thyroid gland is an auxiliary organ to the hypothalamus-pituitary system. Thyrotropin-releasing hormone (TRH) produced by the hypothalamus signals to the pituitary to release thyroid-stimulating hormone (TSH), which then stimulates the thyroid to secrete T and T thyroid hormones. Secondary hypothyroidism occurs when TSH secretion from the pituitary is impaired, whereas tertiary hypothyroidism is the deficiency or inhibition of TRH.

Thyroid hormones are responsible for metabolic activity. Insufficient production of the thyroid hormones result in suppressed metabolic activity and weight gain. Hypothalamic disease may therefore have implications for obesity.

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.

Normal thyroid hormone function requires normal thyroid hormone transport across cell membrane, appropriate deiodination, thyroid hormone nuclear receptor, thyroid hormone response elements, co-activators, co-repressors, and normal histone acetylation. Any abnormalities in this chain can result in thyroid hormone resistance.

The most common cause of the syndrome are mutations of the β (beta) form ("THRB" gene) of the thyroid hormone receptor, of which over 100 different mutations have been documented.

Mutations in "MCT8" and "SECISBP2" have also been associated with this condition.

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.

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.

The incidence of SIADH rises with increasing age. Residents of nursing homes are at highest risk.

Insulin dysregulation is commonly seen in horses with PPID or equine metabolic syndrome, and is associated with obesity. It is of interest primarily because of its link to laminitis. Horses with ID will have an increased insulin response after they are given oral sugars, which will cause a subsequent rise in blood insulin levels, or hyperinsulinemia. Hyperinsulinemia results in decreased tissue sensitivity to insulin, or insulin resistance especially by the skeletal muscle, liver and adipose tissue. Tissue insulin resistance causes increased insulin secretion, which perpetuates the cycle.

The trigger to insulin resistance is not fully understood. Genetics is likely to have some impact on the risk of postprandial hyperinsulinemia. Obesity, pregnancy, PPID, and inflammatory states may contribute to tissue insulin resistance. PPID is thought to result in increased insulin secretion due to higher levels of CLIP produced by melanotrophs, and to cause insulin resistance secondary to hyperadrenocorticism.

The dexamethasone suppression test involves administering dexamethasone, a synthetic glucocorticoid, to the horse, and measuring its serum cortisol levels before and 19–24 hours after injection. In a normal horse, dexamethasone administration results in negative feedback to the pituitary, resulting in decreased ACTH production from the pars distalis and, therefore, decreased synthesis of cortisol at the level of the adrenal gland. A horse with PPID, which has an overactive pars intermedia not regulated by glucocorticoid levels, does not suppress ACTH production and, therefore, cortisol levels remain high. False negatives can occur in early disease. Additionally, dexamethasone administration may increase the risk of laminitis in horses already prone to the disease. For these reasons, the dexamethasone suppression test is currently not recommended for PPID testing.

80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones. Likewise, 20% of autoimmune thyroid patients also have pituitary antibodies. It follows that a subset of thyroid patients may have a disease related to autoimmune hypophysitis. Recent research has focused on a defect at the CTLA-4 gene which, coupled with other factors, may result in autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.

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.

The symptoms depend on what part of the pituitary is affected. Lymphocytic adenohypophysitis (LAH) occurs when the anterior pituitary cells are affected by autoimmune inflammation resulting in either no symptoms, adrenal insufficiency (if the ACTH producing cells are affected), hypothyroidism (if the TSH producing cells are damaged), or hypogonadism (if the LH and/or FSH producing cells are involved). In some cases, the presence of inflammation within the pituitary gland leads to interruption of dopamine flow from the hypothalamus into the pituitary causing high levels of the hormone prolactin and, often as a consequence, milk production from the breasts (in older girls and women). Lymphocytic Infundibuloneurohypophysitis (LINH) occurs when the posterior pituitary is affected resulting in diabetes insipidus. Both LAH and LINH may also lead to symptoms of an intracranial mass such as headache or disturbance of vision, i.e. bitemporal hemianopia.

The pituitary produces multiple hormones relating to various metabolic functions. Sufficiently low production of certain pituitary hormones can be fatal resulting in the failure of the thyroid or adrenal glands.

It is estimated that, typically, it takes from 12 to 40 years for autoimmune destruction to present symptoms. However, there have been cases of isolated attacks as a result of drug reactions (i.e., use of blocking antibody ipilimumab) or idiopathic events that have presented symptoms which may disappear after relatively short term treatment (i.e., 1 year on corticoids or other immune suppressants). However, more rapid development of the disorder is the rule when it occurs during, or shortly after, pregnancy (even after miscarriage or abortion). Indeed, autoimmune hypophysitis occurs more commonly during and shortly after pregnancy than at any other time.

Hypogonadotropic hypogonadism (HH), also known as secondary or central hypogonadism, as well as gonadotropin-releasing hormone deficiency or gonadotropin deficiency (GD), is a medical condition characterized by hypogonadism due to an impaired secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), by the pituitary gland in the brain, and in turn decreased gonadotropin levels and a resultant lack of sex steroid production.

Androgen deficiency is not usually checked for diagnosis in healthy women.

The most rare form of central DI is familial neurogenic diabetes insipidus. This form of DI is due to an inherited mutation of the arginine vasopressin-neurophysin II (AVP-NPII) gene, inherited in an autosomal dominant manner. At one point, only 45 families worldwide were known to possess this genetic trait. It is now more widely recognized, although the precise number of people affected with this form of DI is unknown at the present time.

There is also an X-linked familial form.

Wolfram Syndrome (also called DIDMOAD) is characterised by DI, diabetes mellitus nerve deafness and optic atrophy.

Treatment may consist of hormone replacement therapy with androgens in either sex. Alternatively, gonadotropin-releasing hormone (GnRH)/GnRH agonists or gonadotropins may be given (in the case of "hypogonadotropic" hypoandrogenism). The Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging. The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke.

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.

The lack of vasopressin production usually results from some sort of damage to the pituitary gland. It may be caused due to damage to the brain caused by:

- Benign suprasellar tumors (20% of cases)

- Infections (encephalitis, tuberculosis etc.)

- Trauma (17% of cases) or neurosurgery (9% of cases)

- Non-infectious granuloma (sarcoidosis, Langerhans cell histiocytosis etc.)

- Leukaemia

- Autoimmune - associated with thyroiditis

- Other rare causes which include hemochromatosis and histiocytosis.

Vasopressin is released by the posterior pituitary, but unlike most other pituitary hormones, vasopressin is produced in the hypothalamus. Neurogenic diabetes insipidus can be a failure of production at the hypothalamus, or a failure of release at the pituitary.

There are several causes for this condition, including adrenal insufficiency, congenital adrenal hyperplasia, and medications (certain diuretics, NSAIDs, and ACE inhibitors).

- Primary Aldosterone deficiency

1. Primary adrenal insufficiency

2. Congenital adrenal hyperplasia (21 and 11β but not 17)

3. Aldosterone synthase deficiency

- Secondary Aldosterone deficiency

1. Secondary adrenal insufficiency

2. Diseases of the pituitary or hypothalamus

- Hyporeninemic hypoaldosteronism (due to decreased angiotensin 2 production as well as intra-adrenal dysfunction)

1. Renal dysfunction-most commonly diabetic nephropathy

2. NSAIDs

3. Ciclosporin