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

Deficiency of all anterior pituitary hormones is more common than individual hormone deficiency.

Deficiency of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), together referred to as the gonadotropins, leads to different symptoms in men and women. Women experience oligo- or amenorrhea (infrequent/light or absent menstrual periods respectively) and infertility. Men lose facial, scrotal and trunk hair, as well as suffering decreased muscle mass and anemia. Both sexes may experience a decrease in libido and loss of sexual function, and have an increased risk of osteoporosis (bone fragility). Lack of LH/FSH in children is associated with delayed puberty.

Growth hormone (GH) deficiency leads to a decrease in muscle mass, central obesity (increase in body fat around the waist) and impaired attention and memory. Children experience growth retardation and short stature.

Adrenocorticotropic hormone (ACTH) deficiency leads to adrenal insufficiency, a lack of production of glucocorticoids such as cortisol by the adrenal gland. If the problem is chronic, symptoms consist of fatigue, weight loss, failure to thrive (in children), delayed puberty (in adolescents), hypoglycemia (low blood sugar levels), anemia and hyponatremia (low sodium levels). If the onset is abrupt, collapse, shock and vomiting may occur. ACTH deficiency is highly similar to primary Addison's disease, which is cortisol deficiency as the result of direct damage to the adrenal glands; the latter form, however, often leads to hyperpigmentation of the skin, which does not occur in ACTH deficiency.

Thyroid-stimulating hormone (TSH) deficiency leads to hypothyroidism (lack of production of thyroxine (T4) and triiodothyronine (T3) in the thyroid). Typical symptoms are tiredness, intolerance to cold, constipation, weight gain, hair loss and slowed thinking, as well as a slowed heart rate and low blood pressure. In children, hypothyroidism leads to delayed growth and in extreme inborn forms to a syndrome called "cretinism".

Prolactin (PRL) plays a role in breastfeeding, and inability to breastfeed may point at abnormally low prolactin levels.

The symptoms of Cushing's disease are similar to those seen in other causes of Cushing's syndrome.

Patients with Cushing's disease usually present with one or more signs and symptoms secondary to the presence of excess cortisol or ACTH.

Although uncommon, some patients with Cushing's disease have large pituitary tumors (macroadenomas). In addition to the severe hormonal effects related to increased blood cortisol levels, the large tumor can compress adjacent structures. These tumors can compress the nerves that carry information from the eyes, causing a decrease in peripheral vision. Glaucoma and cataracts also may occur in Cushing's syndrome. In children, the two main symptoms are obesity and decreased linear growth.

The clinical diagnosis must be based on the presence of one or more of the symptoms listed below, because the syndrome itself has no true pathognomonic signs or symptoms. The most common symptoms seen in male patients are purple striae, muscle atrophy, osteoporosis, and kidney stones.

The hormones of the pituitary have different actions in the body, and the symptoms of hypopituitarism therefore depend on which hormone is deficient. The symptoms may be subtle and are often initially attributed to other causes. In most of the cases, three or more hormones are deficient. The most common problem is insufficiency of follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) leading to sex hormone abnormalities. Growth hormone deficiency is more common in people with an underlying tumor than those with other causes.

Sometimes, there are additional symptoms that arise from the underlying cause; for instance, if the hypopituitarism is due to a growth hormone-producing tumor, there may be symptoms of acromegaly (enlargement of the hands and feet, coarse facial features), and if the tumor extends to the optic nerve or optic chiasm, there may be visual field defects. Headaches may also accompany pituitary tumors, as well as pituitary apoplexy (infarction or haemorrhage of a pituitary tumor) and lymphocytic hypophysitis (autoimmune inflammation of the pituitary). Apoplexy, in addition to sudden headaches and rapidly worsening visual loss, may also be associated with double vision that results from compression of the nerves in the adjacent cavernous sinus that control the eye muscles.

Pituitary failure results in many changes in the skin, hair and nails as a result of the absence of pituitary hormone action on these sites.

Features that result from high level of GH or expanding tumor include:

- Soft tissue swelling visibly resulting in enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin

- Soft tissue swelling of internal organs, notably the heart with attendant weakening of its muscularity, and the kidneys, also the vocal cords resulting in a characteristic thick, deep voice and slowing of speech

- Generalized expansion of the skull at the fontanelle

- Pronounced brow protrusion, often with ocular distension (frontal bossing)

- Pronounced lower jaw protrusion (prognathism) with attendant macroglossia (enlargement of the tongue) and teeth spacing

- Hypertrichosis, hyperpigmentation and hyperhidrosis may occur in these patients.

- Acrochordon (skin tags)

- Carpal tunnel syndrome

The various signs and symptoms in Sheehan's syndrome are caused by damage to the pituitary, which causes a decrease in one or more hormones it normally secretes (see Pathophysiology section). Since the pituitary controls many glands in the endocrine system, partial or complete loss of a variety of functions may result.

Most common initial symptoms of Sheehan's syndrome are agalactorrhea (absence of lactation) and/or difficulties with lactation. Many women also report amenorrhea or oligomenorrhea after delivery. In some cases, a woman with Sheehan syndrome might be relatively asymptomatic, and the diagnosis is not made until years later, with features of hypopituitarism. Such features include secondary hypothyroidism with tiredness, intolerance to cold, constipation, weight gain, hair loss and slowed thinking, as well as a slowed heart rate and low blood pressure. Another such feature is secondary adrenal insufficiency, which, in the rather chronic case is similar to Addison's disease with symptoms including fatigue, weight loss, hypoglycemia (low blood sugar levels), anemia and hyponatremia (low sodium levels). Such a woman may, however, become acutely exacerbated when her body is stressed by, for example, a severe infection or surgery years after her delivery, a condition equivalent with an Addisonian crisis. The symptoms of adrenal crisis should be treated immediately and can be life-threatening. Gonadotropin deficiency will often cause amenorrhea, oligomenorrhea, hot flashes, or decreased libido. Growth hormone deficiency causes many vague symptoms including fatigue and decreased muscle mass.

Uncommonly, Sheehan syndrome may also appear acutely after delivery, mainly by hyponatremia. There are several possible mechanisms by which hypopituitarism can result in hyponatremia, including decreased free-water clearance by hypothyroidism, direct syndrome of inappropriate antidiuretic hormone (ADH) hypersecretion, decreased free-water clearance by glucocorticoid deficiency (independent of ADH). The potassium level in these situations is normal, because adrenal production of aldosterone is not dependent on the pituitary.

Symptoms caused by hormone excess and associated mass effects include:

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 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 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 pituitary disease is a disorder primarily affecting the pituitary gland.

The main disorders involving the pituitary gland are:

Overproduction or underproduction of a pituitary hormone will affect the respective end-organ. For example, insufficient production (hyposecretion) of thyroid stimulating hormone (TSH) in the pituitary gland will cause hypothyroidism, while overproduction (hypersecretion) of TSH will cause hyperthyroidism. Thyroidisms caused by the pituitary gland are less common though, accounting for less than 10% of all hypothyroidism cases and much less than 1% of hyperthyroidism cases.

Sheehan's syndrome, also known as postpartum pituitary gland necrosis, is hypopituitarism (decreased functioning of the pituitary gland), caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth.

Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, deepening of the voice, headaches, and problems with vision. Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.

Acromegaly is typically due to the pituitary gland producing too much growth hormone. In more than 95% of cases the excess production is due to a benign tumor, known as a pituitary adenoma. The condition is not inherited from a person's parents. Rarely acromegaly is due to tumors in other parts of the body. Diagnosis is by measuring growth hormone after a person has drunk glucose or by measuring insulin-like growth factor I in the blood. After diagnosis, medical imaging of the pituitary is carried out to look for an adenoma. If excess growth hormone is produced during childhood the result is gigantism.

Treatment options include surgery to remove the tumor, medications, and radiation therapy. Surgery is usually the preferred treatment and is most effective when the tumor is smaller. In those in whom surgery is not effective, medications of the somatostatin analogue or GH receptor antagonist type may be used. The effects of radiation therapy are more gradual than that of surgery or medication. Without treatment those affected live on average 10 years less; however, with treatment life expectancy is typically normal.

Acromegaly affects about 6 per 100,000 people. It is most commonly diagnosed in middle age. Males and females are affected with equal frequency. The first medical description of the disorder occurred in 1772 by Nicolas Saucerotte. The term is from Greek "akron" meaning "extremity" and "mega" meaning "large".

Various psychiatric manifestations have been associated with pituitary disorders including pituitary adenomas. Psychiatric symptoms such as depression, anxiety apathy, emotional instability, easy irritability and hostility have been noted.

There are three major types of adrenal insufficiency.

- Primary adrenal insufficiency is due to impairment of the adrenal glands.

- 80% are due to an autoimmune disease called Addison's disease or autoimmune adrenalitis.

- One subtype is called idiopathic, meaning of unknown cause.

- Other cases are due to congenital adrenal hyperplasia or an adenoma (tumor) of the adrenal gland.

- Secondary adrenal insufficiency is caused by impairment of the pituitary gland or hypothalamus. Its principal causes include pituitary adenoma (which can suppress production of adrenocorticotropic hormone (ACTH) and lead to adrenal deficiency unless the endogenous hormones are replaced); and Sheehan's syndrome, which is associated with impairment of only the pituitary gland.

- Tertiary adrenal insufficiency is due to hypothalamic disease and a decrease in the release of corticotropin releasing hormone (CRH). Causes can include brain tumors and sudden withdrawal from long-term exogenous steroid use (which is the most common cause overall).

Signs and symptoms include: hypoglycemia, dehydration, weight loss, and disorientation. Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addison's disease can present with tanning of the skin that may be patchy or even all over the body. Characteristic sites of tanning are skin creases (e.g. of the hands) and the inside of the cheek (buccal mucosa). Goitre and vitiligo may also be present. Eosinophilia may also occur.

Hormone secreting pituitary adenomas cause one of several forms of hyperpituitarism. The specifics depend on the type of hormone. Some tumors secrete more than one hormone, the most common combination being GH and prolactin, which present as unexpected bone growth and unexpected lactation (in both men and women).

A patient with pituitary adenoma may present with visual field defects, classically bitemporal hemianopsia. It arises from the compression of the optic nerve by the tumor. The specific area of the visual pathway at which compression by these tumours occurs is at the optic chiasma.

The anatomy of this structure causes pressure on it to produce a defect in the temporal visual field on both sides, a condition called bitemporal hemianopsia. If originating superior to the optic chiasm, more commonly in a craniopharyngioma of the pituitary stalk, the visual field defect will first appear as bitemporal inferior quadrantanopia, if originating inferior to the optic chiasm the visual field defect will first appear as bitemporal superior quadrantanopia. Lateral expansion of a pituitary adenoma can also compress the abducens nerve, causing a lateral rectus palsy.

Also, a pituitary adenoma can cause symptoms of increased intracranial pressure.

Prolactinomas often start to give symptoms especially during pregnancy, when the hormone progesterone increases the tumor's growth rate.

Various types of headaches are common in patients with pituitary adenomas. The adenoma may be the prime causative factor behind the headache or may serve to exacerbate a headache caused by other factors. Amongst the types of headaches experienced are both chronic and episodic migraine, and more uncommonly various unilateral headaches; primary stabbing headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) - another type of stabbing headache characterized by short stabs of pain -, cluster headache, and hemicrania continua (HS).

Non-secreting adenomas can go undetected for an extended time because no obvious abnormalities are seen; the gradual reduction in normal activities due to decreased production of hormones is rather less evident. For example, insufficient adrenocorticotropic hormone means that the adrenal glands will not produce sufficient cortisol, resulting in slow recovery from illness, inflammation and chronic fatigue; insufficient growth hormone in children and adolescents leads to diminished stature but which can have many other explanations.

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.

Gigantism is characterized by an excess of growth hormone (GH). This overproduction of growth hormone that brings about gigantism is virtually always caused by pituitary growths (adenomas). These adenomas are on the anterior pituitary gland. They can also cause overproduction of GH's hypothalamic precursor known as growth hormone releasing hormone (GHRH).

As a result of the excessive amounts of growth hormone, children achieve heights that are well above normal ranges. The specific age of onset for gigantism varies between patients and gender, but the common age that excessive growth symptoms start to appear has been found to be around 13 years. Other health complications may occur in pediatric patients with hyper-secretion of growth hormone such as hypertension. Characteristics more similar to those seen in acromegaly may occur in patients that are closer in age to adolescence since they are nearing growth plate fusion.

Hypothalamic disease is a disorder presenting primarily in the hypothalamus, which may be caused by damage resulting from malnutrition, including anorexia and bulimia eating disorders, genetic disorders, radiation, surgery, head trauma, lesion, tumour or other physical injury to the hypothalamus. The hypothalamus is the control center for several endocrine functions. Endocrine systems controlled by the hypothalamus are regulated by anti-diuretic hormone (ADH), corticotropin-releasing hormone, gonadotropin-releasing hormone, growth hormone-releasing hormone, oxytocin, all of which are secreted by the hypothalamus. Damage to the hypothalamus may impact any of these hormones and the related endocrine systems. Many of these hypothalamic hormones act on the pituitary gland. Hypothalamic disease therefore affects the functioning of the pituitary and the target organs controlled by the pituitary, including the adrenal glands, ovaries and testes, and the thyroid gland.

Numerous dysfunctions manifest as a result of hypothalamic disease. Damage to the hypothalamus may cause disruptions in body temperature regulation, growth, weight, sodium and water balance, milk production, emotions, and sleep cycles. Hypopituitarism, neurogenic diabetes insipidus, tertiary hypothyroidism, and developmental disorders are examples of precipitating conditions caused by hypothalamic disease.

The pituitary gland consists of two parts, the anterior (front) and posterior (back) pituitary. Both parts release hormones that control numerous other organs. In pituitary apoplexy, the main initial problem is a lack of secretion of adrenocorticotropic hormone (ACTH, corticotropin), which stimulates the secretion of cortisol by the adrenal gland. This occurs in 70% of those with pituitary apoplexy. A sudden lack of cortisol in the body leads to a constellation of symptoms called "adrenal crisis" or "Addisonian crisis" (after a complication of Addison's disease, the main cause of adrenal dysfunction and low cortisol levels). The main problems are low blood pressure (particularly on standing), low blood sugars (which can lead to coma) and abdominal pain; the low blood pressure can be life-threatening and requires immediate medical attention.

Hyponatremia, an unusually low level of sodium in the blood that may cause confusion and seizures, is found in 40% of cases. This may be caused by low cortisol levels or by inappropriate release of antidiuretic hormone (ADH) from the posterior pituitary. Several other hormonal deficiencies may develop in the subacute phase. 50% have a deficiency in thyroid-stimulating hormone (TSH), leading to undersecretion of thyroid hormone by the thyroid gland and characteristic symptoms such as fatigue, weight gain, and cold intolerance. 75% develop a deficiency to gonadotropins (LH and FSH), which control the reproductive hormone glands. This leads to a disrupted menstrual cycle, infertility and decreased libido.

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.

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 initial symptoms of pituitary apoplexy are related to the increased pressure in and around the pituitary gland. The most common symptom, in over 95% of cases, is a sudden-onset headache located behind the eyes or around the temples. It is often associated with nausea and vomiting. Occasionally, the presence of blood leads to irritation of the lining of the brain, which may cause neck rigidity and intolerance to bright light, as well as a decreased level of consciousness. This occurs in 24% of cases.

Pressure on the part of the optic nerve known as the chiasm, which is located above the gland, leads to loss of vision on the outer side of the visual field on both sides, as this corresponds to areas on the retinas supplied by these parts of the optic nerve; it is encountered in 75% of cases. Visual acuity is reduced in half, and over 60% have a visual field defect. The visual loss depends on which part of the nerve is affected. If the part of the nerve between the eye and the chiasm is compressed, the result is vision loss in one eye. If the part after the chiasm is affected, visual loss on one side of the visual field occurs.

Adjacent to the pituitary lies a part of the skull base known as the cavernous sinus. This contains a number of nerves that control the eye muscles. 70% of people with pituitary apoplexy experience double vision due to compression of one of the nerves. In half of these cases, the oculomotor nerve (the third cranial nerve), which controls a number of eye muscles, is affected. This leads to diagonal double vision and a dilated pupil. The fourth (trochlear) and sixth (abducens) cranial nerves are located in the same compartment and can cause diagonal or horizontal double vision, respectively. The oculomotor nerve is predominantly affected as it lies closest to the pituitary. The cavernous sinus also contains the carotid artery, which supplies blood to the brain; occasionally, compression of the artery can lead to one-sided weakness and other symptoms of stroke.

Finding a specific genetic cause for gigantism has proven to be difficult. Gigantism is the primary example of growth hormone hyper-secretion disorders, a group of illnesses that are not yet deeply understood.

Some common mutations (errors in DNA) have been associated with gigantism. Pediatric gigantism patients have shown to have duplications of genes on a specific chromosome, Xq26. Typically, these patients also experienced an onset of typical gigantism symptoms before reaching the age of 5. This indicates a possible linkage between gene duplications and the gigantism.

Additionally, DNA mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are common in gigantism patients. They have been found to be present in about 29 percent of patients with gigantism. AIP is labeled as a tumor suppressor gene and a pituitary adenoma disposition gene.

Mutations in AIP sequencing can have deleterious effects by inducing the development of pituitary adenomas which in turn can cause gigantism.

Two specific mutations in the AIP gene have been identified as possible causes of pituitary adenomas. These mutations also have the ability to cause adenoma growth to occur early in life. This is typical in gigantism.

Additionally, a large variety of other known genetic disorders have been found to influence the development of gigantism such as multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, X-linked acrogigantism (X-LAG).

Although various gene mutations have been associated with gigantism, over 50 percent of cases cannot be linked to genetic causes, showing the complex nature of the disorder.