The pituitary gland (hypophysis) is located in the sella turcica at the base of the skull. It lies just below the hypothalamus and is connected to it by a stalk containing blood vessels and nervous tissue. The pituitary gland is composed of an anterior and posterior lobe (adenohypophysis and neurohypophysis, respectively), each of which performs specific functions, as well as a rudimentary intermediate lobe [4].

Most of the disorders affecting the pituitary gland originate in the anterior lobe. The effects of pathology on the anterior pituitary gland can be broadly summarized as hyperpituitarism and hypopituitarism [6,7].

The adrenal cortex is composed of three zones, or groups of different cells: the zona glomerulus (the outer layer of cortical cells that secretes the mineralocorticoids), the zona fasciculate (the middle layer of cortical cells that secretes the glucocorticoids), and the zona reticularis (the layer of cortical cells proximal to the medulla that secretes the adrenal sex hormones androgens and estrogen). The adrenal glands receive an abundant blood supply. The medulla of the adrenal gland functions as part of the sympathetic nervous system, whereas the cortex has only minimal nervous system innervation [8].

The adrenal medulla is considered a part of the sympathetic division of the autonomic nervous system, which controls the secretion of its hormones. Because the functions of the sympathetic nervous system and the functions of the hormones of the adrenal medulla are the same, they can compensate for each other. Thus, the medullary hormones are not essential to life but play an important role in the body's response to stress. About 15% of the hormonal secretion by the adrenal medulla is norepinephrine and 75% is epinephrine [5].

There are five major influences of the secretion of hormones by the endocrine glands: the hypothalamus, hypothalamic-releasing factors, anterior pituitary hormones, the autonomic nervous system, and nutrient and ion concentrations in the plasma. The hypothalamus affects hormone secretion by secreting a series of peptides called releasing factors, which stimulate or inhibit the release of hormones by the anterior pituitary gland. The hypothalamus also directly manufactures oxytocin and antidiuretic hormones (ADH or vasopressin). The hypothalamic-releasing factors cause the interior pituitary gland to secrete growth hormone, prolactin, TSH, the gonadotropic hormones follicle-stimulating hormone, luteinizing hormone, and ACTH. The anterior pituitary hormones directly control the release of thyroid hormone (T3 and T4), cortisol, testosterone in men, and estrogen and progesterone in women [13]. In some patients with excessive hormone levels caused by a tumor of the involved endocrine gland, feedback inhibition does not suppress the overproduction of the hormone, and the tumor functions autonomously [14,15].

Growth hormone, also referred to as somatotropin, is produced in the pituitary gland [19]. An estimated 50% of the cells in the anterior pituitary are somatotrophs (cells that secrete growth hormone) [20]. Secretion of growth hormone by the anterior pituitary gland occurs in a pulsatile manner, and the majority (up to 70%) occurs at night during non-REM (typically stage 3) sleep [21,22]. Therefore, the amount and quality of sleep plays an important role in growth and development.

The glucocorticoids function in carbohydrate, fat, and protein metabolism and play an important role in the body's response to stress and emotional well-being. The principal glucocorticoid secreted by the adrenal cortex is cortisol, which constitutes 95% of cortical production; corticosterone and cortisone are also produced.

Aldosterone increases the reabsorption of sodium and the secretion of potassium. This is accomplished as an exchange of sodium ions for potassium or hydrogen ions, which results in the excretion of potassium and hydrogen into the urine and the retention of sodium. As sodium is reabsorbed into the blood, it brings with it water and chlorides, which mechanically increases the blood volume. This action of aldosterone is vital to the maintenance of the extracellular fluid volume. Aldosterone also promotes sodium reabsorption to a lesser degree from the sweat glands, salivary glands, and gastrointestinal (GI) tract [2,3].

The patient's heart rate and rhythm should be assessed, with attention to murmurs or extra heart sounds. In pheochromocytoma, hypertension, tachycardia, and atrial fibrillation may be noted. Cushing syndrome often leads to congestive heart failure, as manifested by lethargy, dyspnea on exertion, paroxysmal nocturnal dyspnea, and cough. Hypertension can accompany Cushing syndrome, and hypotension can accompany adrenal insufficiency. Because of the interrelation between cardiac and respiratory systems, cardiac pathology often produces changes in the lungs (e.g., pleural effusions, congestive heart failure). Therefore, the lungs should be assessed for abnormal breath sounds, rales, rhonchi, wheezes, and pleural friction rubs [30].

If any of the following develop during a water deprivation, the test should be halted [35]:

For the 24-hour urinary free-cortisol test, urine is collected over 24 hours to measure the amount of unbound cortisol filtered by the urinary system [41]. The accuracy of this test is dependent on the patient's glomerular filtration rate and urinary volume [41]. Normal cortisol levels in a 24-hour urine collection are 450–700 nmol/L [42]. Elevated levels indicate Cushing syndrome, while low levels could indicate Addison disease.

Bilateral inferior petrosal sinus sampling (IPSS) can be used to distinguish Cushing disease from ectopic ACTH secretion [43]. This test is guided by fluoroscopy, typically while the patient is under general anesthesia, and will take 60 to 90 minutes [43,44]. Catheters are inserted through both the left and right femoral veins and advanced to the petrosal sinuses [43]. Samples are drawn simultaneously from the inferior petrosal sinus and the peripheral veins for plasma ACTH five minutes and one minute before administration of 1–100 mcg corticotropin-releasing hormone in a peripheral vein. Samples for plasma ACTH are collected at 2, 5, and 10 minutes after administration. A peripheral sample for plasma cortisol is also taken along with each sample for plasma ACTH.

Approximately 50% of patients have primary central diabetes insipidus, also known as pituitary or primary diabetes insipidus. This form is associated with familial and congenital factors as well as with subclinical encephalitis. Secondary diabetes insipidus is diabetes insipidus arising from a variety of causes, including hypophysectomy, tumors (e.g., metastatic carcinoma of the breast, craniopharyngiomas), trauma (e.g., basilar skull fractures), vascular lesions (e.g., hemorrhage, aneurysm), infection (e.g., syphilis, encephalitis, meningitis), histiocytosis, and granulomatous disease (e.g., sarcoidosis, tuberculosis) [46,47].

This condition can be seen in patients with a variety of mental health disorders, including autism, schizophrenia, schizoaffective disorder, and bipolar disorder [53]. Schizophrenia is a common cause, with 11% to 20% of patients with schizophrenia developing psychogenic diabetes insipidus [53].

Patients with diabetes insipidus present with polyuria, nocturia, polydipsia, increased serum osmolality, decreased urine osmolality, and decreased urine specific gravity [16,26]. Many report extreme thirst, even at night, leading to increased fluid intake at all hours [52]. In addition to drinking throughout the day, patients with diabetes insipidus often have a preference for cold or ice water [18]. An intact thirst drive will often prevent severe dehydration and maintain homeostasis in those affected [48]. In some cases, the thirst mechanism is faulty because of damage to osmoreceptors in the hypothalamus, leading to decreased fluid intake and severe dehydration [49].

The diagnosis of diabetes insipidus can be a challenge, and misdiagnosis carries the risk for severe complications [35]. Diabetes insipidus is diagnosed by routine screening tests, such as specific gravity of urine, plasma sodium levels, osmolality tests, and water-deprivation and water-loading tests. If serum osmolality is greater than 300 mOsm/kg and urine osmolality is less than 300 mOsm/kg, the diagnosis is likely diabetes insipidus [48]. Diagnosis is confirmed if a deficiency of ADH is demonstrated and the patient's kidneys are shown to respond normally to ADH. In response to a water-deprivation challenge, patients with diabetes insipidus will demonstrate an inability to increase the specific gravity and osmolality of the urine [54,55]. Differential diagnosis involves other causes of polyuria. A brain scan, skull x-rays, visual field testing, and full neurologic examination may be indicated to rule out the presence of a tumor.

For patients with mild cases of central diabetes insipidus, treatment may be as simple as increasing fluid intake [56]. However, most patients will require ADH replacement therapy. In acute cases, patients are given intravenous or subcutaneous vasopressin [16]. Long-term treatment involves the administration of desmopressin orally, subcutaneously, or intranasally [16]. The most common adverse effect of desmopressin administration is hyponatremia, although fluid retention can also develop [48]. Intranasal desmopressin can result in eye irritation, headaches, dizziness, rhinitis, epistaxis, coughing, and flushing [48]. If diabetes insipidus is caused by pituitary tumor, hypophysectomy may be required [16].

The surgical approach is most commonly trans­sphenoidal selective tumor resection guided by fluoroscopy [58]. With this type of surgery, the tumor is approached through the sphenoid sinus, avoiding brain tissue. A cut is made along the nasal septum or under the upper lip, near the base of the nose. In addition to the avoidance of brain tissue, this procedure is often associated with fewer side effects and cosmetic effects compared with other surgery types [59]. Drawbacks are that it is more time-consuming and is difficult to perform on large tumors, which often require craniotomy for removal [59]. After a transsphenoidal approach, the patient may report sinus congestion and headaches lasting for one to two weeks postoperatively [59].

Transfrontal craniotomy is indicated when the tumor extends beyond the pituitary fossa and is impinging on the optic chiasm, because this procedure provides the best view of the operative field [60]. With this technique, an opening is made in the skull and the pituitary is accessed through the brain, increasing the risk of brain injury [59]. Complications can include brain damage, stroke, blindness, meningitis, leakage of cerebrospinal fluid, bleeding, diabetes insipidus, and adverse reactions to anesthesia [59].

Clinically, SIADH is the opposite of diabetes insipidus, with ADH levels increased as opposed to decreased. It is seen more commonly as an individual ages but can develop at any age [17]. A major risk factor for SIADH is hospitalization, and a high number of SIADH cases develop in hospitalized patients older than 30 years of age [24].

Medications associated with SIADH include carbamazepine, oxcarbazepine, chlorpropamide, cyclophosphamide, selective serotonin reuptake inhibitors (SSRIs), antipsychotics, hormones (i.e., vasopressin, desmopressin, and oxytocin), and antihistamines [16,26]. Of these medications, SSRIs and carbamazepine are the most commonly associated medications [24]. The illicit drug 3,4-methylenedioxy-methamphetamine (MDMA or Ecstasy/E/Molly) induces release of ADH and increases thirst, which causes SIADH and is linked to more severe signs and symptoms [17].

Hyponatremia can be classified as mild (130–134 mEq/L), moderate (125–129 mEq/L), or profound (less than 125 mEq/L) [64]. In patients with mild-to-moderate hyponatremia, the only signs and symptoms may be nausea and malaise [17]. As hyponatremia worsens, patients will develop additional signs and symptoms, and serum sodium levels less than 120 mEq/L can lead to coma and respiratory arrest [17]. The speed at which the hyponatremia develops is correlated with the neurologic manifestations [26]. If the patient develops acute hyponatremic encephalopathy, the condition may be reversible, but it could also lead to permanent deficits [17]. Vomiting is considered an ominous sign [17].

In all patients with suspected SIADH, hypothyroidism and adrenal insufficiency should be ruled out [17]. Patients should be asked about a history of head injury, chronic pain, smoking, weight loss, respiratory symptoms, drug use, and any new symptoms experienced [17]. The physical exam should include an assessment of the patient's volume status, skin turgor, mucous membranes, neurologic status, and vital signs. There is no specific diagnostic tool or test for SIADH, but the Bartter-Schwartz criteria, developed in 1967, are still used today to aid in diagnosis [17]. The following are the criteria for this tool [17]:

In all patients with suspected SIADH, hypothyroidism and adrenal insufficiency should be ruled out [17]. Patients should be asked about a history of head injury, chronic pain, smoking, weight loss, respiratory symptoms, drug use, and any new symptoms experienced [17]. The physical exam should include an assessment of the patient's volume status, skin turgor, mucous membranes, neurologic status, and vital signs. There is no specific diagnostic tool or test for SIADH, but the Bartter-Schwartz criteria, developed in 1967, are still used today to aid in diagnosis [17]. The following are the criteria for this tool [17]:

Patients with mild-to-moderate SIADH may require fluid restriction, which will lead to the release of aldosterone and the conservation of sodium by the kidneys [17,24]. The recommended fluid intake is often 600–800 mL per day, which can be a significant challenge for many patients [24,67]. In fact, the major challenge with fluid restriction is non-compliance, and patient education will play an important role in the patient's plan of care. Fluid restriction should be used cautiously in patients with an increased risk for hypovolemia.

Congenital growth hormone deficiency can be genetic or the result of structural changes in the brain. It appears to have a hereditary factor; approximately 5% to 30% of children with growth hormone deficiency have a first-degree relative with the disorder [20]. These patients have an increased risk for other pituitary hormone abnormalities and anatomic differences of the pituitary gland [20]. Three abnormalities are commonly seen in patients with congenital growth hormone deficiency: interrupted or thin pituitary stalk; absent or ectopic posterior pituitary gland (i.e., the posterior portion of the pituitary gland is in an abnormal position); and anterior hypoplasia or aplasia of the pituitary gland [20].

Adult-onset growth hormone deficiency is typically caused by a pituitary tumor or brain trauma, but less common causes include surgery, radiation, infection, and hemorrhage [23,69]. These contributing factors cause damage to the pituitary gland, leading to a growth hormone deficiency. Deficiency in adults can also be caused by persistent childhood growth hormone deficiency [23]. It is also important to consider that growth hormone secretion decreases with age [22].

Sheehan syndrome is characterized by hypopituitarism caused by ischemic pituitary necrosis developing after blood loss associated with childbirth [72]. The pituitary gland is susceptible to injury during and immediately after pregnancy because the anterior pituitary gland enlarges during pregnancy but does not develop an increased blood supply [72].

Adults with a growth hormone deficiency may present with fatigue, weakness, obesity, decreased muscle mass, weakened bones, sexual dysfunction, elevated cholesterol levels, and insulin resistance [16,69]. Decreased bone turnover and decreased bone mass are common, and adults with a growth hormone deficiency have a risk for fracture that is two to three times higher than their counterparts without growth hormone deficiency [23]. Early onset of deficiency (i.e., in childhood) and cigarette smoking can further increase this risk [23].

Somatropin, a recombinant growth hormone, may be used for both children and adults with a growth hormone deficiency. This medication increases skeletal growth in children and increases bone density in adults [75]. Somatropin is administered as a subcutaneous injection, usually in the evening to mimic the body's normal rhythm [21]. The onset of action is typically within three months of the initiation of treatment [75]. Starting treatment early will help prevent delayed growth in children. In most cases, somatropin is administered to children when delayed growth is identified, with doses increased when the child is going through puberty and discontinued when skeletal maturation is reached [69]. However, testing should be completed to determine if the patient should continue treatment, as early cessation can lead to negative consequences in adulthood [69]. Adverse effects of somatropin include edema of the hands and feet, hyperglycemia, hypothyroidism, insulin resistance, pancreatitis, pain at the injection site, lipodystrophy, carpal tunnel syndrome, and arthralgia [21,75]. Lipodystrophy can be prevented by rotating injection sites. Concurrent use of corticosteroids can decrease the effectiveness of somatropin [75].

The majority of cases of growth hormone hypersecretion (more than 90%) are caused by benign pituitary adenomas [19]. In the United States, it is estimated that about 16% of the population (more than 50 million people) have pituitary tumors, although most are undiagnosed. Approximately 13,000 people are diagnosed with pituitary tumors each year; 25% of these tumors will lead to acromegaly [21]. It is possible for patients to develop a malignant pituitary adenoma that is responsible for acromegaly, but this occurs in less than 1% of cases [24]. The disorder may also be caused by hypothalamic adenomas that increase the amount of GHRH, which, in turn, increases growth hormone levels [19]. Other types of tumors, such as those found in the hypothalamus, pancreas, lungs, chest, or abdomen, can also lead to acromegaly [80]. These tumors can secrete their own growth hormone, although it is more common for them to produce GHRH [80]. Additional possible causes include pituitary hyperplasia and excess GHRH [16].

Autoimmune disease is the most common cause of Addison disease, accounting for approximately 80% to 90% of all cases [37]. Autoimmune Addison disease, also referred to as autoimmune adrenalitis, results in atrophied adrenal glands and an inability to produce hormones in sufficient amounts. Cells destroyed by the inflammatory response are replaced by fibrotic tissue [83]. In these patients, the cells in the adrenal cortex are damaged but the medulla remains intact [83].

When a patient develops Addison disease, glucocorticoids are typically prescribed. Those with autoimmune Addison disease will require lifelong glucocorticoid treatment, and even with steroid replacement, these patients have an increased risk for morbidity, mortality, and decreased quality of life [83].

Cushing syndrome is further classified as iatrogenic (or exogenous), primary, secondary, or ectopic [24]. Iatrogenic Cushing syndrome is the most common form and is the result of long-term glucocorticoid therapy [21]. Both primary and secondary Cushing syndrome develop as a result of endogenous causes (e.g., adrenal tumor). Primary Cushing syndrome is typically caused by adrenal gland malignancy, while secondary Cushing syndrome (also referred to as Cushing disease) is the result of excessive secretion of ACTH by a pituitary tumor, usually an adenoma [24]. Ectopic Cushing syndrome arises from the endogenous production of ACTH by one of at least 25 different extrapituitary malignancies, including carcinoma of the lung and of several organs in the GI tract. Secondary Cushing syndrome is the most common (66%) endogenous type of the disease. When this condition is seen in infants, it is most commonly caused by an adrenal carcinoma [24].

A variety of signs and symptoms may be observed in patients with Cushing syndrome, including round ("moon") face; flushed face; weight gain above the collarbone and/or on the back of neck ("buffalo hump"); purple striae on the chest, armpits, and abdomen; acne; excessive facial hair; easy bruising; thin skin; rapid central weight gain; thin extremities; hypertension; skin ulcers; headache; muscle weakness; weak bones; menstrual irregularities; decreased libido; erectile dysfunction; hyperglycemia; emotional disturbances; and slowed growth in children [29,88,89]. Visceral fat deposits are one of the most common and often one of the first symptoms [21]. The distribution of fat deposits is different than what is typically seen with obesity [21]. For example, fat deposits are commonly seen on the face and clavicular area, both anterior and posterior; extremities often remain thin unless edema develops [21].

The greatest postoperative concern after adrenalectomy is adrenal insufficiency. Also important are possible hypotension caused by the rapid withdrawal of mineralocorticoids, electrolyte imbalances, and infection resulting from suppression of the immune system. The surgical hazards associated with adrenalectomy include possible injury to the spleen, liver, duodenum, and common bile duct as well as hemorrhage [54].

The major clinical manifestations of primary aldosteronism are hypertension, excessive urinary loss of potassium resulting in hypokalemia, and retention of sodium (hypernatremia). The hypertension is usually a moderate elevation in diastolic blood pressure. Patients may complain of headaches, and on physical examination, early hypertensive retinopathy and cardiomegaly may be noted [95,96].

Surgical resection of a pheochromocytoma is considered high-risk due to the potential impact on heart rate and blood pressure. The Endocrine Society recommends that all patients with hormonally functional pheochromocytoma undergo preoperative blockade to prevent perioperative cardiovascular complications. The recommended preoperative treatment of choice is alpha-adrenergic receptor blockers [107]. This treatment should continue for 7 to 14 days before surgery. During this period, patients should also be instructed to adhere to a high-sodium diet and to increase fluid intake. Adjustments should be made prior to surgery in response to blood pressure, heart rate, and blood glucose level monitoring.

Often in disorders affecting the creation of the adrenocortical sex hormones, changes in libido and sexual potency concern patients and their sexual partner. Sensitive intervention by the nurse may relieve anxiety in the couple [79]. Unfortunately, sexual dysfunction is rarely addressed in the treatment plan for these patients. Research indicates that different domains of sexual health are affected by different disease processes, particularly in women. Specifically, hypercortisolism is associated with impaired lubrication, orgasm, sexual arousal, and satisfaction, while hyperprolactinemia and hypoandrogenism are associated with decreased sexual desire and arousal [108]. Treatment of the underlying condition may help, but if sexual dysfunction persists, it should be addressed by pharmacotherapy, adaptive practices, and psychotherapy. It is important to remember that pharmacotherapy cannot address important psychosocial factors of performance anxiety, poor self-confidence, partner sexual dysfunction, relationship conflict or poor communication, sexual factors in the relationship (e.g., sexual scripts, sexual satisfaction), and contextual factors (e.g., life stressors) [109]. Even when sexual dysfunction is primarily physiologic, virtually all patients experience negative psychologic and interpersonal effects. These include interpersonal conflict, depression, performance anxiety, and avoidance of sex.