Most Cushing's syndrome cases are caused by corticosteroid medications, such as those used for asthma, arthritis, eczema and other inflammatory conditions. Consequently, most patients are effectively treated by carefully tapering off (and eventually stopping) the medication that causes the symptoms.

If an adrenal adenoma is identified, it may be removed by surgery. An ACTH-secreting corticotrophic pituitary adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients require steroid replacement postoperatively at least in the interim, as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative.

In those patients not suited for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy. Mifepristone is a powerful glucocorticoid type II receptor antagonist and, since it does not interfere with normal cortisol homeostatis type I receptor transmission, may be especially useful for treating the cognitive effects of Cushing's syndrome. However, the medication faces considerable controversy due to its use as an abortifacient. In February 2012, the FDA approved mifepristone to control high blood sugar levels (hyperglycemia) in adult patients who are not candidates for surgery, or who did not respond to prior surgery, with the warning that mifepristone should never be used by pregnant women.

Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation. This clinical situation is known as Nelson's syndrome.

Life long hormone replacement therapy for the hormones that are missing.

Treatment (for hyperpituitarism) in the case of prolactinoma consists of long-term medical management. Dopamine agonists are strong suppressors of PRL secretion and establish normal gonadal function. It also inhibits tumor cell replication (in some cases causes tumor shrinkage) Treatment for gigantism begins with establishing target goals for IGF-1, transsphenoidal surgery (somatostatin receptor ligands- preoperatively) and postoperative imaging assessment. For Cushing's disease there is surgery to extract the tumor; after surgery, the gland may slowly start to work again, though not always.

Pituitary tumors require treatment when they are causing specific symptoms, such as headaches, visual field defects or excessive hormone secretion. Transsphenoidal surgery (removal of the tumor by an operation through the nose and the sphenoidal sinuses) may, apart from addressing symptoms related to the tumor, also improve pituitary function, although the gland is sometimes damaged further as a result of the surgery. When the tumor is removed by craniotomy (opening the skull), recovery is less likely–but sometimes this is the only suitable way to approach the tumor. After surgery, it may take some time for hormone levels to change significantly. Retesting the pituitary hormone levels is therefore performed 2 to 3 months later.

Prolactinomas may respond to dopamine agonist treatment–medication that mimics the action of dopamine on the lactrotrope cells, usually bromocriptine or cabergoline. This approach may improve pituitary hormone secretion in more than half the cases, and make supplementary treatment unnecessary.

Other specific underlying causes are treated as normally. For example, hemochromatosis is treated by venesection, the regular removal of a fixed amount of blood. Eventually, this decreases the iron levels in the body and improves the function of the organs in which iron has accumulated.

Through multiple advancements within the medical field, care-givers have been able to stray away from utilizing bilateral adrenalectomy as the treatment for Cushing's disease. This has decreased the risk of patients presenting with Nelson's syndrome. Alternative treatments for Nelson's syndrome have been discovered. The most utilized technique for Nelson's syndrome has been transsphenoidal surgery. In addition, pharmacotherapy, radiotherapy, and radiosurgery have been utilized accompanying a surgical procedure. Pharmalogical drugs can also be given accompanying a transsphenoidal surgery including the following: pasireotide, temozolomide and octreotide. Within rats/mice, rosiglitazone has been an effective measure, however this has not been discovered in humans yet.

After diagnosis, it is important for patients to be continually monitored. The most common treatment for PPNAD is bilateral laparoscopic adrenalectomy; the process by which both adrenal glands are removed by a small incision.

Patients who have received this treatment will be prescribed mineralocorticoid and glucocorticoid steroids as they are no longer being naturally produced.

This is a treatment which has been used and refined since 1984.

Most pituitary hormones can be replaced indirectly by administering the products of the effector glands: hydrocortisone (cortisol) for adrenal insufficiency, levothyroxine for hypothyroidism, testosterone for male hypogonadism, and estradiol for female hypogonadism (usually with a progestogen to inhibit unwanted effects on the uterus). Growth hormone is available in synthetic form, but needs to be administered parenterally (by injection). Antidiuretic hormone can be replaced by desmopressin (DDAVP) tablets or nose spray. Generally, the lowest dose of the replacement medication is used to restore wellbeing and correct the deranged results, as excessive doses would cause side-effects or complications. Those requiring hydrocortisone are usually instructed to increase their dose in physically stressful events such as injury, hospitalization and dental work as these are times when the normal supplementary dose may be inadequate, putting the patient at risk of adrenal crisis.

Long-term follow up by specialists in endocrinology is generally needed for people with known hypopituitarism. Apart from ensuring the right treatment is being used and at the right doses, this also provides an opportunity to deal with new symptoms and to address complications of treatment.

Difficult situations arise in deficiencies of the hypothalamus-pituitary-gonadal axis in people (both men and women) who experience infertility; infertility in hypopituitarism may be treated with subcutaneous infusions of FSH, human chorionic gonadotropin–which mimics the action of LH–and occasionally GnRH.

The first-line treatment of Cushing's disease is surgical resection of ACTH-secreting pituitary adenoma; this surgery involves removal of the tumor via transsphenoidal surgery (TSS).

There are two possible options for access to sphenoidal sinus including of endonosal approach (through the nostril) or sublabial approach (through an incision under the upper lip); many factors such as the size of nostril, the size of the lesion, and the preferences of the surgeon cause the selection of one access route over the other.

Some tumors do not contain a discrete border between tumor and pituitary gland; therefore, careful sectioning through pituitary gland may be required to identify the location of tumor. The probability of successful resection is higher in patients where the tumor was identified at initial surgery in comparison to patients where no tumor was found initially; the overall remission rates in patients with microadenomas undergoing TSS are in range of 65%-90%, and the remission rate in patients with macroadenomas are lower than 65%. patients with persistent disease after initial surgery are treated with repeated pituitary surgery as soon as the active persistent disease is evident; however, reoperation has lower success rate and increases the risk of pituitary insufficiency.

Pituitary radiation therapy is another option for treatment of postoperative persisting hypercortisolemia following unsuccessful transsphenoidal surgery. External-beam pituitary RT is more effective treatment for pediatric CD in children with cure rates of 80%-88%. Hypopituitarism specifically growth hormone deficiency has been reported as the only most common late morbidity of this treatment; GHD has been reported in 36% and 68% of the patients undergoing post pituitary RT for Cushing's disease.

Bilateral adrenalectomy is another treatment which provides immediate reduction of cortisol level and control of hypercortisolism. However, it requires education of patients, because lifelong glucocorticoid and mineralocorticoid replacement therapy is needed for these patients. One of the major complications of this treatment is progression of Nelson's syndrome which is caused by enhance level of tumor growth and ACTH secretion post adrenalectomy in 8%-29% of patients with CD.

During post surgical recovery, patients collect 24-hour urine sample and blood sample for detecting the level of cortisol with the purpose of cure test; level of cortisol near the detection limit assay, corresponds to cure. Hormonal replacement such as steroid is given to patients because of steroid withdrawal. After the completion of collecting urine and blood samples, patients are asked to switch to glucocorticoid such as prednisone to decrease symptoms associated with adrenal withdrawal.

A study of 3,525 cases of TSS for Cushing's disease in the nationally representative

sample of US hospitals between 1993 and 2002 was conducted and revealed the following results: the in-hospital mortality rate was 0.7%; the complication rate was 42.1%. Diabetes insipidus (15%), fluid and electrolyte abnormalities (12.5%), and neurological deficits (5.6%) were the most common complications reported. The analyses of the study show that complications were more likely in patients with pre-operative comorbidities. Patients older than 64 years were more likely to have an adverse outcome and prolonged hospital stay. Women were 0.3 times less likely to have adverse outcomes in comparison to men.

Treatment for Addison's disease involves replacing the missing cortisol, sometimes in the form of hydrocortisone tablets, or prednisone tablets in a dosing regimen that mimics the physiological concentrations of cortisol. Alternatively, one-quarter as much prednisolone may be used for equal glucocorticoid effect as hydrocortisone. Treatment is usually lifelong. In addition, many patients require fludrocortisone as replacement for the missing aldosterone.

People with Addison's are often advised to carry information on them (e.g., in the form of a MedicAlert bracelet or information card) for the attention of emergency medical services personnel who might need to attend to their needs. It is also recommended that a needle, syringe, and injectable form of cortisol be carried for emergencies. People with Addison's disease are advised to increase their medication during periods of illness or when undergoing surgery or dental treatment. Immediate medical attention is needed when severe infections, vomiting, or diarrhea occur, as these conditions can precipitate an Addisonian crisis. A patient who is vomiting may require injections of hydrocortisone instead.

Standard therapy involves intravenous injections of glucocorticoids and large volumes of intravenous saline solution with dextrose (glucose). This treatment usually brings rapid improvement. If intravenous access is not immediately available, intramuscular injection of glucocorticoids can be used. When the patient can take fluids and medications by mouth, the amount of glucocorticoids is decreased until a maintenance dose is reached. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.

The primary treatment of PPID is pergolide, a dopamine agonist that provides suppression to the pars intermedia in place of the dysfunctional hypothalamus. Horses should be reassessed in 30 days following the start of treatment, though evaluation of clinical signs and by baseline diagnostic testing, to ensure the appropriate dose is being prescribed. Results from that test dictate changes in dose. Horses that are responding to treatment should be retested every 6 months, including a test in the autumn when there is a seasonal increase in ACTH, to ensure their ACTH levels are appropriately suppressed during this time. Drug side effects include a transient decrease in appetite, which can be reduced by slowly increasing the dose to therapeutic levels, and by breaking up the daily dose into twice-daily administrations.

Attitude, activity levels, hyperglycemia, and increased drinking and urination are usually improved within 30 days of initiating treatment. Other clinical signs, such as hirsutism, potbellied appearance, muscle wasting, laminitic episodes, and increased predisposition to infection usually take between 30 days and 1 year to improve.

Cyproheptadine may be added to the treatment regime in horses that are inadequately responding to pergolide, but is usually only used in horses with advanced PPID on high doses of pergolide.

Common treatments for Nelson's syndrome include radiation or surgical procedure. Radiation allows for the limitation of the growth of the pituitary gland and the adenomas. If the adenomas start to affect the surrounding structures of the brain, then a micro-surgical technique can be adapted in order to remove the adenomas in a transsphenoidal (bone at base of the skull) process. Death may result with development of a locally aggressive pituitary tumor. However, does not commonly occur with pituitary diseases. In the rare case, ACTH-secreting tumors can become malignant. Morbidity from the disease can occur due to pituitary tissue compression or replacement, and compression of structures that surround the pituitary fossa. The tumor can also compress the optic apparatus, disturb cerebrospinal fluid flow, meningitis, and testicular enlargement in rare cases.

Treatment options depend on the type of tumor and on its size:

- Prolactinomas are most often treated with cabergoline or quinagolide (both dopamine agonists), which decrease tumor size as well as alleviates symptoms, followed by serial imaging to detect any increase in size. Treatment where the tumor is large can be with radiation therapy or surgery, and patients generally respond well. Efforts have been made to use a progesterone antagonist for the treatment of prolactinomas, but so far have not proved successful.

- Somatotrophic adenomas respond to octreotide, a long-acting somatostatin analog, in many but not all cases according to a review of the medical literature. Unlike prolactinomas, thyrotrophic adenomas characteristically respond poorly to dopamine agonist treatment.

- Surgery is a common treatment for pituitary tumors. The normal approach is Trans-sphenoidal adenectomy, which usually can remove the tumor without affecting the brain or optic nerves.

- Danazol is a steroid compound that has been labelled as an "Anterior pituitary suppressant".

As with other forms of CAH, the primary therapy of 11β-hydroxylase deficient CAH is lifelong glucocorticoid replacement in sufficient doses to prevent adrenal insufficiency and suppress excess mineralocorticoid and androgen production.

Salt-wasting in infancy responds to intravenous saline, dextrose, and high dose hydrocortisone, but prolonged fludrocortisone replacement is usually not necessary. The hypertension is ameliorated by glucocorticoid suppression of DOC.

Long term glucocorticoid replacement issues are similar to those of 21-hydroxylase CAH, and involve careful balance between doses sufficient to suppress androgens while avoiding suppression of growth. Because the enzyme defect does not affect sex steroid synthesis, gonadal function at puberty and long-term fertility should be normal if adrenal androgen production is controlled. See congenital adrenal hyperplasia for a more detailed discussion of androgen suppression and fertility potential in adolescent and adult women.

Treatment is directed towards (1) correcting hypotension, hypovolemia, electrolyte imbalances, and metabolic acidosis; (2) improving vascular integrity, and (3) providing an immediate source of glucocorticoids. Rapid correction of hypovolemia is the first priority.

Most patients show dramatic improvement within 24 to 48 hours of appropriate fluid and glucocorticoid therapy. Over the ensuing 2 to 4 days, a gradual transition from IV fluids to oral water and food is undertaken, and maintenance mineralocorticoid and glucocorticoid therapy is initiated. Failure to make this transition smoothly should raise suspicion of insufficient glucocorticoid supplementation, concurrent endocrinopathy (e.g. hypothyroidism), or cocurrent illness (especially renal damage).

The main methods of management in involve exercise and diet change, in addition to treatment of PPID. The primary goal is reduction of weight in an obese animal. Diet changes include limiting pasture access and reducing or eliminating grain. Obese animals are often best maintained on a diet consisting ration balancer and hay, fed at 1.5% body weight and decreased if needed. Feed should be selected based on low non-structural carbohydrate levels. Hay NSC levels may be reduced by soaking it in cold water for 30 minutes.

Exercise is increased in non-laminitic horses. Animals resistant to weight loss, despite diet and exercise changes, can be placed on levothyroxine to increase metabolism. Metformin can also be used to reduce glucose absorption through the intestinal tract.

XX females with lipoid CAH may need estrogen replacement at or after puberty. Active intervention has been used to preserve the possibility of fertility and conception in lipoid CAH females. In a case report in 2009, a woman with late onset lipoid CAH due to StAR deficiency underwent hormone replacement therapy in combination with an assisted fertility technique, intracytoplasmic sperm injection. This led to ovulation and with implantation of the in vitro fertilized egg, a successful birth.

The first priority in suspected or confirmed pituitary apoplexy is stabilization of the circulatory system. Cortisol deficiency can cause severe low blood pressure. Depending on the severity of the illness, admission to a high dependency unit (HDU) may be required.

Treatment for acute adrenal insufficiency requires the administration of intravenous saline or dextrose solution; volumes of over two liters may be required in an adult. This is followed by the administration of hydrocortisone, which is pharmaceutical grade cortisol, intravenously or into a muscle. The drug dexamethasone has similar properties, but its use is not recommended unless it is required to reduce swelling in the brain around the area of hemorrhage. Some are well enough not to require immediate cortisol replacement; in this case, blood levels of cortisol are determined at 9:00 AM (as cortisol levels vary over the day). A level below 550 nmol/l indicates a need for replacement.

The decision on whether to surgically decompress the pituitary gland is complex and mainly dependent on the severity of visual loss and visual field defects. If visual acuity is severely reduced, there are large or worsening visual field defects, or the level of consciousness falls consistently, professional guidelines recommend that surgery is performed. Most commonly, operations on the pituitary gland are performed through transsphenoidal surgery. In this procedure, surgical instruments are passed through the nose towards the sphenoid bone, which is opened to give access to the cavity that contains the pituitary gland. Surgery is most likely to improve vision if there was some remaining vision before surgery, and if surgery is undertaken within a week of the onset of symptoms.

Those with relatively mild visual field loss or double vision only may be managed conservatively, with close observation of the level of consciousness, visual fields, and results of routine blood tests. If there is any deterioration, or expected spontaneous improvement does not occur, surgical intervention may still be indicated. If the apoplexy occurred in a prolactin-secreting tumor, this may respond to dopamine agonist treatment.

After recovery, people who have had pituitary apoplexy require follow-up by an endocrinologist to monitor for long-term consequences. MRI scans are performed 3–6 months after the initial episode and subsequently on an annual basis. If after surgery some tumor tissue remains, this may respond to medication, further surgery, or radiation therapy with a "gamma knife".

The primary goals of hormone replacement are to protect from adrenal insufficiency and to suppress the excessive adrenal androgen production.

Glucocorticoids are provided to all children and adults with all but the mildest and latest-onset forms of CAH. The glucocorticoids provide a reliable substitute for cortisol, thereby reducing ACTH levels. Reducing ACTH also reduces the stimulus for continued hyperplasia and overproduction of androgens. In other words, glucocorticoid replacement is the primary method of reducing the excessive adrenal androgen production in both sexes. A number of glucocorticoids are available for therapeutic use. Hydrocortisone or liquid prednisolone is preferred in infancy and childhood, and prednisone or dexamethasone are often more convenient for adults.

The glucocorticoid dose is typically started at the low end of physiologic replacement (6–12 mg/m²) but is adjusted throughout childhood to prevent both growth suppression from too much glucocorticoid and androgen escape from too little. Serum levels of 17α-hydroxyprogesterone, testosterone, androstenedione, and other adrenal steroids are followed for additional information, but may not be entirely normalized even with optimal treatment. ("See Glucocorticoid for more on this topic.")

Mineralocorticoids are replaced in all infants with salt-wasting and in most patients with elevated renin levels. Fludrocortisone is the only pharmaceutically available mineralocorticoid and is usually used in doses of 0.05 to 2 mg daily. Electrolytes, renin, and blood pressure levels are followed to optimize the dose.

Treatment of hyperandrogenism varies with the underlying condition that causes it. As a hormonal symptom of polycystic ovary syndrome, menopause, and other endocrine disorders, it is primarily treated as a symptom of these disorders. Systemically, it is treated with antiandrogens such as cyproterone acetate, flutamide and spironolactone to control the androgen levels in the patient's body. For Hyperandrogenism caused by Late-Onset Congenital Adrenal Hyperplasia (CAH), treatment is primarily focused on providing the patient with Glucocorticoids to combat the low cortisol production and the corresponding increase in androgens caused by the swelling of the Adrenal Glands. Oestrogen-based oral contraceptives are used to treat both CAH and PCOS caused hyperandrogenism. These hormonal treatments have been found to reduce the androgen excess and suppress adrenal androgen production and cause a significant decrease in hirsutism.

Hyperandrogenism is often managed symptomatically. Hirsutism and acne both respond well to the hormonal treatments described above, with 60-100% reporting an improvement in hirsutism. Androgenic alopecia however, does not show a significant improvement with hormonal treatments and requires other treatments, such as hair transplantation.

Aggressiveness of therapy depends on the clinical status of the patient and the nature of the insufficiency (glucocorticoid, mineralocorticoid, or both). Many dogs and cats with primary adrenal insufficiency are presented in Addisonian crisis and require immediate, aggressive therapy. In contrast, secondary insufficiency often has a chronic course.

Hypoadrenocorticism is treated with fludrocortisone (trade name Florinef) or a monthly injection of Percorten-V (desoxycorticosterone pivalate, DOCP) and prednisolone or Zycortal. Routine blood work is necessary in the initial stages until a maintenance dose is established. Most of the medications used in the therapy of hypoadrenocorticism cause excessive thirst and urination. It is absolutely vital to provide fresh drinking water for a canine suffering from this disorder.

If the owner knows about an upcoming stressful situation (shows, traveling etc.), the animals generally need an increased dose of prednisone to help deal with the added stress. Avoidance of stress is important for dogs with hypoadrenocorticism. Physical illness also stresses the body and may mean that the medication(s) need to be adjusted during this time. Most dogs with hypoadrenocorticism have an excellent prognosis after proper stabilization and treatment.

In GRA, the hypersecretion of aldosterone and the accompanying hypertension are remedied when ACTH secretion is suppressed by administering glucocorticoids.

Dexamethasone, spironolactone and eplerenone have been used in treatment.

Some of the childhood management issues are similar those of 21-hydroxylase deficiency:

- Replacing mineralocorticoid with fludrocortisone

- Suppressing DHEA and replacing cortisol with glucocorticoid

- Providing extra glucocorticoid for stress

- Close monitoring and perhaps other adjunctive measures to optimize growth

- Deciding whether surgical repair of virilized female genitalia is warranted

However, unlike 21-hydroxylase CAH, children with 3β-HSD CAH may be unable to produce adequate amounts of testosterone (boys) or estradiol (girls) to effect normal pubertal changes. Replacement testosterone or estrogen and progesterone can be initiated at adolescence and continued throughout adult life. Fertility may be impaired by the difficulty of providing appropriate sex hormone levels in the gonads even though the basic anatomy is present.

Diagnosis of cortisone reductase deficiency is done through analysis of cortisol to cortisone metabolite levels in blood samples. As of now, there is no treatment for cortisone reductase deficiency. Shots of cortisol are quickly metabolised into cortisone by the dysregulated 11β-HSD1 enzyme; however, symptoms can be treated. Treatment of hyperandroginism can be done through prescription of antiandrogens. They do so by inhibiting the release of gonadotropin and luteinizing hormone, both hormones in the pituitary, responsible for the production of testosterone.

Management of salt-wasting crises and mineralocorticoid treatment are as for other forms of salt-wasting congenital adrenal hyperplasias: saline and fludrocortisone.

Glucocorticoids can be provided at minimal replacement doses because there is no need for suppression of excessive adrenal androgens or mineralocorticoids. As with other forms of adrenal insufficiency, extra glucocorticoid is needed for stress coverage.