#30831: Pituitary and Adrenal Disorders

The hypothalamus plays an important role in the regulation of homeostasis within the body. It is necessary for automatic functions of the nervous system, regulation of the glands of the endocrine system, emotional responses, and behaviors[1]. It may help to think of the hypothalamus as a control center—it monitors information about the body and makes necessary changes based on the information obtained.

The hypothalamus functions as an integral part of both the endocrine and nervous systems. In its neural role, it receives and processes innervations from the thalamus, cerebral cortex, spinal cord, and brainstem. This results in the control of such bodily functions as temperature, respiration, arterial blood pressure and circulation, and metabolism. The hypothalamus also controls certain behavioral functions, including the emotional states of fear, anxiety, anger, rage, pleasure, and pain, as well as the states of sleep, wakefulness, and alertness. The hypothalamus, as it is influenced by the autonomic nervous system, affects all the unconscious activities of the body [2,3]. In its endocrine role, the hypothalamus has two regulatory functions:

Hypothalamic-releasing factors are proteins that act on the anterior pituitary gland to stimulate or inhibit the release of tropic hormones. Other inhibiting factors and releasing factors have been identified; it is thought, although still unproven, that the hypothalamus may produce both an inhibiting and a releasing factor for each of the anterior pituitary hormones [2,3].

The release or inhibition of these hypothalamic hormones is controlled by various neurotransmitters, such as serotonin, acetylcholine, norepinephrine, and dopamine. The tropic hormones released from the anterior pituitary gland then act upon a target gland or tissues to produce a specific response. In regulating the secretion of these releasing factors, the hypothalamus processes input from both the circulatory and nervous systems [2,3].

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].

In response to the releasing factors from the hypothalamus, the anterior pituitary gland secretes several hormones, some of which control hormonal secretions by other glands. The anterior pituitary hormones secreted include thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), growth hormone, luteinizing hormone (also called interstitial cell-stimulating hormone in men), follicle-stimulating hormone, and prolactin. In general, growth hormone, ACTH, and TSH are concerned with metabolic activities, whereas luteinizing hormone, follicle-stimulating hormone, and prolactin are concerned with reproduction. ACTH, TSH, follicle-stimulating hormone, and luteinizing hormone exert their effects on target glands, either increasing their size or their secretions. Prolactin and growth hormone directly affect the metabolism of specific target tissues [5].

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 most common cause of hyperfunction of the anterior pituitary gland is a neoplastic secreting tumor, usually a benign adenoma. Tumors of the pituitary gland exert their effects through either pressure on structures in the brain, causing visual symptoms and headaches, or excessive secretion of one or more of the anterior pituitary hormones, which results in increased stimulation of one or more target glands.

One of the pathophysiologic manifestations of these tumors is hypersomatotropism, which can result in acromegaly in adults and gigantism in children. Other effects of hypersomatotropism include goiter (from stimulation of the thyroid) and diabetes mellitus (from the diabetogenic effect of growth hormone). Cardiomegaly and hypertension can also occur. Visual impairment and eventual blindness are possible because of compression of tissues by an expanding tumor. Amenorrhea in women and loss of libido and potency in men may occur because compression from the expanding tumor leads to gonadal deficiencies from loss of healthy gonadotropin-producing cells [6,7].

Hyperfunction of the anterior pituitary gland can be secondary to pathology of the anterior pituitary gland or to injury to the hypothalamus resulting in a decrease or absence of hypothalamic-releasing factors. Hypothalamism may be manifested by isolated hormonal deficiencies or by a deficiency of both the anterior and posterior pituitary hormones (panhypopituitarism). The exact hormonal deficit and its etiology are important to understanding patients' symptoms and signs [6,7].

The adrenal glands are paired and located in the retroperitoneal space at the upper pole of the kidney. Because of this position, they may be referred to as the suprarenal glands. Each adrenal gland consists of an outer portion (the cortex) and an inner portion (the medulla), which differ in both anatomic structure and function [8].

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].

In response to stimulation by ACTH from the anterior pituitary gland, the adrenal cortex secretes three major types of hormones: glucocorticoids (cortisol), mineralocorticoids (aldosterone), and sex hormones (androgens, estrogen, and progesterone). These hormones affect metabolism, fluid balance, and the development of secondary sex characteristics, respectively. All three types of hormones secreted by the adrenal cortex are structurally similar steroids, which results in some overlapping of their effects [5,9].

The primary causes of hypercortisolism (Cushing syndrome), originating from within the adrenal cortex itself, include neoplastic and bilateral hyperplasia. In iatrogenic hypercortisolism, an exogenous source (e.g., prolonged use of glucocorticoids or ACTH) is responsible for the hypercortisolism. The normal adrenal glandular tissue may be atrophic, and ACTH levels are suppressed [10].

Hyperfunction of the adrenal cortex results in three major disorders: Cushing syndrome, primary aldosteronism, and excessive production of sex hormones characterized by virilizing changes in women, feminizing changes in men, and precocious sexual development in children. These changes often cause serious psychologic issues related to self-esteem and body image.

Hypofunction of the adrenal cortex, or adrenal insufficiency, results in a decreased secretion of glucocorticoids, mineralocorticoids, and sex hormones. The causes of adrenal insufficiency can be grouped into two categories: primary (based on pathology occurring within the gland itself) and secondary (arising from an undersecretion of ACTH due to pathology in the pituitary gland or the hypothalamus). Primary causes may be acute or chronic [11].

Primary adrenal insufficiency (Addison disease) is characterized by a failure of the adrenal cortex to produce sufficient corticosteroids. Acute severe symptoms of Addison disease are referred to as addisonian or acute adrenal crisis.

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].

Pathophysiology of the adrenal medulla is rare and is usually associated with hyperfunction. The clinical manifestations seen in hyperfunction of the adrenal medulla are related to the excessive secretion of epinephrine and norepinephrine [12]. Pheochromocytoma is the most common cause of adrenal medulla hyperfunction. Other disorders associated with hyperfunction of the adrenal medulla include neurofibromatosis carcinomas (of the thyroid) and hyperparathyroidism [12].

A hormone may be defined as a "chemical substance synthesized by an endocrine gland and secreted into the bloodstream, which carries it to other sites in the body where its actions are exerted" [5]. Hormones may function independently, in conjunction with other hormones, or as a step in a series of related actions. They may influence the action, metabolism, synthesis, and/or transport of another hormone, which is one of the integrative aspects of the endocrine system. Hormones can be differentiated into two major categories: local (with specific local effects) and general (transported by the circulation to distant sites, where they have a physiologic effect) [13].

Only target cells have the capability to respond to a specific hormone in a characteristic way. Their response depends on the presence of specific receptors for a particular hormone. This response is called hormone-target cell specificity, and the process is known as hormone-receptor binding. The initial interaction between a hormone and its target cell receptor initiates a chain of biochemical events that eventually provokes a cellular response. This often involves a hormone-induced change in the activity of a specific enzyme found in the target cell that might change the rate of reactions within the cell, change the growth of the cell, or control the cell's secretion. Because cells are exposed to many hormones, complex hormone-hormone interactions can occur in target cells. These interactions may be inhibitory, synergistic, or permissive (i.e., one hormone, by its presence, potentiates the effect of the second hormone) [13].

Hormones include steroid, polypeptide, amino acid, catecholamine, or iodothyronine structures. The steroidal hormones are aldosterone, cortisol, and the estrogens and androgens. The receptors involved in hormonal-receptor binding differ for steroidal and nonsteroidal hormones. The receptors for most nonsteroidal hormones are located on the outer surface of the plasma membrane of the target cells, whereas the receptors for the steroidal hormones are soluble proteins within the cytoplasm of the target cell. The physiology of hormone receptors is an expanding area of research in endocrinology [13].

Most hormones are not secreted at a constant rate. After secretion into the bloodstream, they circulate in a free form or are bound to proteins. Polypeptide hormones and the catecholamines are essentially unbound in the circulation. These free hormones are directly available to the target tissues, and only they can affect the target cells. The protein-bound forms are thought to represent a hormonal reserve, because the protein binding may prevent excretion of the hormone by the kidney. The amount of circulating free hormone is usually quite small and exists in equilibrium with the bound fractions [13].

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].

Diurnal variation is another of the control mechanisms affecting hormonal secretion. A 24-hour cyclical variation in the secretory rates of certain hormones can be seen. For example, growth hormone levels are highest in the first 90 minutes after sleep begins. These circadian rhythms have been found to be different for each hormone. It is evident that the endocrine system affects all aspects of the organism. Through the hormonal secretion of its glands, the system controls and regulates the metabolic processes of anabolism and catabolism, the function of muscles, growth and reproduction, energy production, stress reactions, electrolyte balances, and personality development [14,15].

Single measures of endocrine function are rarely sufficient to support a diagnosis but nevertheless should be an integral part of the whole data base. In pituitary and adrenal testing, be aware of the importance of patient preparation and adhere strictly to the testing protocols. Patient and environmental influences that might modify the test results are important nursing considerations [31]. This section will focus on some of the most commonly used tests; general screening tests, such as complete blood count and basic metabolic panel, will not be discussed but are usually part of the workup.

Because of the profound physiologic and psychosocial stresses on the patients with these conditions, it is not unusual for them to be fearful and have difficulty coping. Feelings of anxiety can be directly related to the disorder (as in pheochromocytoma) or exogenous, resulting from feelings of unexplained apprehension about the situation [45].

Pituitary/adrenal disorders often require the patient and family to make major changes in lifestyle. Patients may require lifelong pharmacotherapy and medical/nursing supervision. They also may face the possibility of major surgery and may have some degree of transitory or permanent sensory loss [45].

Central nervous system involvement may produce a variety of problems in patients, ranging from headaches and lethargy (e.g., with pheochromocytoma) to outright psychosis (e.g., Cushing syndrome). Alterations in thought processes and perception pose difficulties not only for patients but for their families and friends as well [46].

Some patients with pituitary or adrenal dysfunction will have problems with thermal regulation. For example, patients with pheochromocytoma or hypoglycemia often experience excessive sweating. Those with acromegaly often experience joint pain [45,46].

Changes in the skin and hair occur in patients with pituitary or adrenal dysfunction and can contribute to disturbances in body image. Increases in skin pigmentation may occur in patients with Addison disease. Ecchymosis develops in patients with Cushing syndrome due to changes in the fragility of the capillaries. Facial flushing is often a sign of pheochromocytoma. Hirsutism is a problem for patients with adrenal tumor or hyperplasia and is an especially bothersome body image issue for women [45,46].

Patients with these disorders may have an impaired ability to manage self-care or maintain their home environment. They are at increased risk for injury because of weakness, fatigue, and visual disturbances. For example, weakness of the musculoskeletal system is seen in patients with acromegaly and Cushing syndrome. Patients with Cushing syndrome have an increased incidence of fractures. Fatigue often accompanies adrenal insufficiency, hypoglycemia, and acromegaly. Patients with pituitary tumors may have some level of visual impairment [45,46].

Sexual dysfunction may occur as loss of libido or impotence. Menstrual problems are also relatively common [45,46].

Anorexia and weight loss are common in patients with adrenal insufficiency, pheochromocytoma, and hyperkalemia [45,46]. Alteration in bowel elimination, specifically diarrhea, may be seen in patients with Addison disease, while constipation can occur in patients with hypercalcemia and pheochromocytoma [45,46].

Actual or potential fluid volume deficits occur in patients with posterior pituitary disorders. In addition, patients with Cushing syndrome may develop congestive heart failure. Patients with hypercalcemia and hyperaldosteronism may have polydipsia and polyuria [45,46].

The underlying cause of diabetes insipidus is generally either pituitary (central) or nephrogenic. More rarely, it may develop during pregnancy or related to a mental disorder.

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].

Patients with diabetes insipidus will have dilute and light-colored urine. Polyuria will develop regardless of normal contributing factors to urine output, such as fluid intake. Patients may urinate as much as 10–20 L/day [26]. In most cases, the urine will be hypotonic and serum osmolality will increase [16,26]. In patients with a serum osmolality of 300–330 mOsm/kg, symptoms may not be apparent [49]. Patients with severe dehydration may develop weakness, postural dizziness, confusion, azotemia, hyperglycemia, secondary hyperaldosteronism with hypokalemia, and coma [49]. Under normal circumstances, an increase in serum osmolality would result in a drop in blood pressure and subsequent secretion of ADH [16]. Additionally, when a patient has increased serum osmolality they will often be very thirsty [16]. Thirst will lead to increased fluid intake, which increases fluid in the vasculature and restores fluid balance. However, in patients with diabetes insipidus, this does not occur, further increasing the risk for dehydration and hypovolemic shock [16].

Serum sodium levels will be normal or increased, with hypernatremia typically developing if the patient does not drink enough water to account for the increased urine output [26]. Patients with hypernatremia may present with altered mental status, myoclonus (muscle jerking), seizures, and focal deficits [26]. If untreated, the patient may progress to an altered level of consciousness or death [16].

Infants with congenital nephrogenic diabetes insipidus present with enuresis, poor intake, poor weight gain, poor growth (failure to thrive), irritability, fevers, diarrhea, and vomiting [50]. If a child with this condition develops dehydration on multiple occasions, it can lead to problems with growth and development [50].

As many as 50% of patients with underlying diabetes insipidus will have increased signs and symptoms during pregnancy [51]. Patients with underlying diabetes insipidus do not have increased levels of ADH during pregnancy, so the symptoms of diabetes insipidus may become apparent [51]. Patients are at increased risk for dehydration and hypernatremia if they experience diabetes insipidus during pregnancy [51]. However, during pregnancy, thirst is triggered at lower serum osmolality levels, which can act as a protective factor [51].

Patients with an exacerbation of a mental illness may also increase their fluid intake; this increase is not related to the regulation or maintenance of homeostasis [53]. Patients with psychogenic diabetes insipidus drink more than 3L of fluids per day [52]. In patients with compulsive fluid intake, drinking fluids calms an acute anxiety and the compulsion can be so strong that they will drink from inappropriate and unhealthy water sources (e.g., toilets) [53]. Individuals who compulsively drink fluids may also have comorbid nicotine, alcohol, and/or eating disorders [53]. Patients with psychogenic diabetes insipidus urinate as often as every 30 minutes, and the urine is dilute, with decreased specific gravity and decreased osmolality [52]. These patients may also report fatigue and constipation [52].

Patients with psychogenic diabetes insipidus typically do not drink fluids at night, which can help differentiate it from true cases of diabetes insipidus [53]. Most patients with diabetes insipidus will develop hypernatremia due to the fluid deficit, but patients with psychogenic diabetes insipidus may develop hyponatremia [53]. If hyponatremia develops in these patients, it is important to determine if it is the result of excessive fluid intake or another cause (e.g., medication) [53]. Patients with schizophrenia and diabetes insipidus typically have lower body weight and increased rates of alcohol consumption and smoking compared with patients without diabetes insipidus [53].

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.

Differentiation between the types of diabetes insipidus can be a challenge but is essential because treatment will vary based on the type identified [18]. Patients with central diabetes insipidus will respond to vasopressin with decreased urine output and increased urine osmolality [48]. If the patient has nephrogenic diabetes insipidus, there will be no response to the vasopressin [48].

A newer diagnostic tool is copeptin, a surrogate marker for ADH [18]. High basal copeptin levels are accurate in diagnosing nephrogenic diabetes insipidus [18]. The copeptin test can also be used during pregnancy, unlike the water deprivation test [51]. In nonpregnant patients, the copeptin test can be combined with the water deprivation test, which increases diagnostic accuracy of both tests [18]. It can also be combined with the administration of hypertonic saline [18].

Diagnosis of psychogenic diabetes insipidus usually requires a multidisciplinary approach [52]. The care team may include primary care, endocrinologists, nephrologists, and psychologists.

The treatment plan for patients with diabetes insipidus depends on the type and the associated signs and symptoms.

Central Diabetes Insipidus

The Society for Endocrinology recommends that for those patients with central diabetes insipidus and normal serum sodium and who require maintenance intravenous fluid therapy, the type and volume administered should be equivalent to the daily requirements appropriate for other patients without central diabetes insipidus. This should be given together with the agreed, prescribed dose of desmopressin.

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013691 Last Accessed: July 19, 2024)

Level of Evidence: Expert Opinion/Consensus Statement

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].

For infants with congenital central diabetes insipidus, the preferred treatment is usually thiazide diuretics [48]. Thiazide diuretics work by inhibiting the amount of sodium lost by the kidneys, which can lead to decreased water loss [57]. However, thiazide diuretics can paradoxically decrease urine flow in some [16]. As such, urine output should be closely monitored in these patients.

The syndrome of inappropriate antidiuretic hormone, or SIADH, is a condition characterized by autonomous release of ADH without regard to plasma osmolality. The body is unable to dilute the urine appropriately, so fluid is retained, which expands the extracellular fluid compartment and leads to hyponatremia. There may also be sodium loss by the kidneys because of a lack of aldosterone [26].

The cause of SIADH is multifactorial and may include genetic, nervous system, malignancy, pulmonary disease, surgery, and medication factors [16]. Hereditary SIDAH is referred to as nephrogenic SIADH and is the result of a functional mutation in the vasopressin 2 receptors in the kidneys that leads to these receptors staying in an active state [17].

Conditions that increase intracranial pressure can lead to the development of SIADH, including head trauma, stroke, meningitis, lesions, hemorrhage, and hydrocephalus [16,24,26]. Vasopressin-secreting tumors of the lung and brain are another potential cause of SIADH; small cell lung cancer is responsible for 70% of the cancer-related causes of SIADH [16,26,63]. Pulmonary disease (e.g., cystic fibrosis, chronic obstructive pulmonary disease) can lead to SIADH, although the exact mechanism is not fully understood [16].

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].

SIADH is also associated with serum hypo-osmolality, concentrated urine, increased urine specific gravity, decreased urine output, weakness, lethargy, headache, anorexia, nausea, vomiting, mental status changes, seizures, cerebral edema, cerebral hemorrhage, asterixis, myoclonus, pulmonary edema, and coma [26,64]. Hyponatremia and decreased extracellular fluid volume lead to a fluid shift into the cells [17]. The osmotic fluid shifts associated with this condition cause cerebral edema and subsequent increased intracranial pressure [26]. When cerebral edema occurs, there is also a loss of potassium and amino acids from brain cells [24].

In patients with chronic SIADH, solute loss is more prominent than water retention [17]. This can lead to the development of hyponatremia in a euvolemic state. In those with SIADH, ADH is secreted even in instances in which the ADH should be decreased, leading to the reabsorption of water, increased fluid in the bloodstream, dilutional hyponatremia, and an increase in the extracellular fluid volume. Dilutional hyponatremia may be manifested by a bounding pulse, increased or normal blood pressure, muscle weakness, headache, personality changes, nausea, diarrhea, convulsions, and coma [16]. The patient with hyponatremia may also develop gait disturbance, memory and cognition problems, dizziness, and an increased risk for falls.

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].

Hyponatremia that develops quickly can lead to cerebral edema and potential brain herniation [63]. When the body has time to adapt to the cerebral edema, it displaces solutes (e.g., potassium) from the brain and into the extracellular spaces [63]. In those with chronic hyponatremia, the body adapts and the condition can be asymptomatic, even with serum sodium levels less than 120 mEq/L [17]. Although these patients may be asymptomatic, nausea and vomiting are seen in approximately one-third of patients [17]. However, rapid drops in sodium levels can result in delirium, confusion, and seizures, even if the drop is minimal [17].

The European Society of Endocrinology recommends that if clinical assessment indicates that the volume of extracellular fluid is not overtly increased and the urine sodium concentration is >30 mmol/L, other causes of hypotonic hyponatremia should be excluded before implicating SIADH.

(https://academic.oup.com/ndt/article/29/suppl_2/i1/1904943 Last Accessed: July 19, 2024)

Level of Evidence: Expert Opinion/Consensus Statement

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]:

Selection of appropriate diagnostic tests is vital, because it will affect the successful correction of hyponatremia and patient success rates [65]. Although a variety of tests are used, the three cardinal tests assess urine osmolality, plasma osmolality, and urine sodium [65]. Patients with SIADH will have decreased serum sodium, increased urine sodium, decreased serum osmolality, increased urine osmolality, decreased blood urea nitrogen (BUN), and concentrated urine [16,66]. Urine osmolality will be greater than 50 mOsm/Kg, and often greater than 100 mOsm/kg [64]. Serum ADH will also be increased.

Treatment of SIADH is directed toward its underlying cause. Approaches will differ for acute and chronic disease [63]. One of the main goals of treatment is the correction of hyponatremia, with a target serum sodium level of more than 130 mEq/L [17]. Even mild cases of hyponatremia are associated with a variety of safety risks, including gait instability, falls, osteoporosis, bone fractures, attention deficit, and increased mortality [67]. Although these risks are known, many patients admitted to the hospital with SIADH are discharged with continued hyponatremia [65].

In elderly patients a common cause of hyponatremia is chronic SIADH, and these patients may have aging-related safety risks exacerbated by low serum sodium levels [67]. Additionally, chronic SIADH is associated with a decreased bone mass, increasing the risk for fractures [63].

It is important to slowly increase sodium levels, because increasing the concentration too quickly can lead to osmotic demyelination syndrome and poor outcomes [17,64]. Osmotic demyelination syndrome, also known as central pontine myelinolysis, is seen more often in those treated with hypertonic saline or tolvaptan [65,68]. Rapid correction of sodium leads to a fluid shift and essentially dehydration of the brain cells, which causes degeneration and demyelination of the myelin [68]. Patients with euvolemic hyponatremia (as opposed to hypervolemic hyponatremia) have an increased risk for rapid sodium correction and the development of osmotic demyelination syndrome [66]. Other risk factors include alcohol use disorder, malnutrition, liver disease, hypokalemia, hyponatremia lasting longer than two days, and decreased serum sodium concentration in conjunction with decreased BUN prior to the start of therapy [66,68]. With this in mind, these laboratory values should be assessed/considered prior to initiating treatment.

The signs and symptoms associated with osmotic demyelination typically arise in two to six days. The first signs and symptoms include changes in level of consciousness and difficulty or inability to speak [68]. Patients may also develop dysarthria, dysphagia, paraparesis, quadriparesis, spastic quadriplegia, confusion, disorientation, obtundation, pseudobulbar palsy, encephalopathy, and coma [68]. These signs and symptoms are the result of noninflammatory demyelination of the pons [68]. In severe cases, a type of locked-in syndrome can develop, whereby the patient is paralyzed and unable to communicate but fully awake [17]. The effects of this condition may be partially reversible, but in many instances, they are permanent. Prevention involves avoidance of sodium increases of more than 8 mEq/L in 24 hours or 0.5–1 mEq/L per hour [17]. Treatment focuses on addressing symptoms and lowering the serum sodium concentration [68].

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.

If fluid restriction is unsuccessful or if the patient is acutely ill and symptomatic, hypertonic 3% saline may be administered to help increase serum sodium levels; this is typically reserved for patients with severe hyponatremia [17]. This intervention should be completed cautiously, because when the solution is administered too rapidly the fluid shifts can damage the brain [24]. The initial dose is 100 mL hypertonic 3% saline bolus in the first three to four hours [17]. Serum sodium levels are then checked within two to three hours, and the results will help to guide continued treatment [17]. These patients should be closely monitored for fluid overload. Because of the risks of severe side effects, isotonic saline should only be used in hyponatremic emergencies [65].

In some cases, loop or thiazide diuretics may be ordered to help rid the body of excess fluid. Use of diuretics is often reserved for patients with cardiac symptoms [24]. Patients prescribed diuretics may take oral salt tablets or increase dietary salt intake to decrease the urine concentration [17].

Conivaptan is a vasopressin 2 receptor antagonist that may be ordered for severe cases of hyponatremia [16]. This agent is given intravenously and blocks the action of ADH at the kidney level [16,66].

Tolvaptan is also a vasopressin 2 receptor antagonist, but it is given orally [17]. This medication is hepatotoxic and should be avoided in patients with pre-existing liver disease. Tolvaptan increases sodium levels at a faster rate than other methods, but it can increase the rates too rapidly, leading to osmotic demyelination syndrome [65]. Potential side effects include dry mouth, polydipsia, liver toxicity, and polyuria [63]. It is also important to consider that this medication can be quite costly.

Other medications that may be used in the treatment of this condition are lithium and demeclocycline [17]. Demeclocycline, an antibiotic that blocks the action of ADH at the tubules of the kidney, is administered at a dose of 600–1,200 mg/day in divided doses [24]. Both of these medications are nephrotoxic and associated with undesirable side effects.

If a secreting tumor is the underlying cause of SIADH, the tumor may need to be removed [16]. The removal and additional treatment of the tumor will depend on a variety of factors, including whether the tumor is malignant or benign. If medications are associated with this condition, they should be stopped, if possible.

Patients with SIADH should be monitored for patent airway. For patients without respiratory symptoms, the head of the bed should be kept low (i.e., 10 degrees or less) [24]. Keeping the head of the bed low will enhance venous return and left atrial filling pressure, leading to a decrease in the release of ADH [24].

Other nursing interventions include closely monitoring intake and output, daily weight checks, assisting with hemodynamic monitoring, and neurologic checks. Because the most common indicator of SIADH is decreased serum sodium levels, the patient's laboratory values should be monitored closely [24]. Urinary output may be monitored hourly, with notation of color, clarity, and odor. In most patients with SIADH, urinary output will be decreased and urine will appear concentrated. If the patient on fluid restrictions complains of a dry mouth, hard candies, dry mouth lozenges, or moisturizing mouth swabs may be offered. Patients should also be educated on SIADH and treatment, with an emphasis on the importance of adhering to fluid restriction and increased salt intake.

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].

Genetic causes of growth hormone deficiency include growth hormone deficiency IA, IB, IIB, and III [69]. Growth hormone deficiency IA is an autosomal recessive disorder in which the fetus develops growth retardation in utero [69]. When these children are initially given growth hormone, they respond appropriately, but over time, they create antibodies to the growth hormone [69]. Growth hormone deficiency IB is an autosomal recessive disorder in which the child has some growth hormone and will respond to the administration of growth hormone [69]. Growth hormone IIB is an autosomal dominant disorder, and III is an x-linked disorder [69]. Both of these genetic disorders are similar to growth hormone deficiency IB [69].

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].

Treatment of acromegaly suppresses growth hormone secretion and reduces insulin-like growth factor levels [22]. An estimated 30% to 75% of patients undergoing radiation therapy for acromegaly develop growth hormone deficiency, with increased risk associated with younger age, high doses of radiotherapy, and extended treatment [22]. This effect will be discussed in greater detail later in this course.

TBI has been associated with growth hormone deficiency; more severe TBI increases this risk [70]. However, growth hormone deficiency after a TBI is not well-known and can be easily missed [70]. The reported prevalence is variable due to a multitude of factors, but an estimated 2% to 30% of patients who have experienced a TBI will develop growth hormone deficiency within one month [25]. Further, an estimated 10% to 63.6% of patients in the chronic phase of TBI will develop growth hormone deficiency [25]. The underlying cause in these patients is ischemic injury to the pituitary gland, particularly the pituitary stalk, which is fragile and prone to injury [25]. In the secondary phase of TBI, ischemic, cytotoxic, and inflammatory changes can increase the risk for the development of a growth hormone deficiency [25].

In some cases, malnutrition, neglect, and/or emotional/environmental stress can lead to delayed growth [71]. This may be related to inflammation that develops due to chronic stress; increased inflammation is associated with decreased levels of insulin-like growth factor and growth hormone resistance [71].

The signs and symptoms observed with growth hormone deficiency will vary depending on the age of the individual affected.

The Endocrine Society recommends recommend that the insulin tolerance test and the GHRH-arginine test have sufficient sensitivity and specificity to establish the diagnosis of growth hormone deficiency in adults.

(https://academic.oup.com/jcem/article/96/6/1587/2833853 Last Accessed: July 19, 2024)

Strength of Recommendation/Level of Evidence: 1/⊕⊕⊕⊕ (Strong recommendation based on high-quality evidence)

The diagnosis of congenital causes of growth hormone deficiency is often delayed until slow growth is observed in a child [69]. It is common to see initial diagnosis around 5 years of age, when children start school or when puberty is delayed (10 to 13 years of age for girls, 12 to 16 years of age for boys) [69]. Diagnostic tests for a growth hormone deficiency include serum growth hormone levels, growth hormone stimulation test, pituitary MRI, and bone density tests.

Although growth hormone levels can be measured, these tests can be unreliable because hormones are not secreted in consistent amounts throughout the day. Additionally, a variety of medications can affect growth hormone levels and interfere with diagnostic testing [32]. As such, a medication review should be conducted to determine if any could interfere with testing. Medications that can affect the results include insulin, estrogen, amphetamines, oral contraception, and corticosteroids; the herbal supplement St. John's wort can also impact findings [33].

A more reliable test is the growth hormone stimulation test, which measures the response of growth hormone to hypoglycemia [16]. Medications that may be used in stimulation testing are clonidine, arginine, and glucagon [20]. In the patient with a growth hormone deficiency, growth hormone levels would not elevate as expected.

An MRI is usually completed to assess for tumors, and a bone density test will provide information about bone strength and possible disorders (e.g., osteopenia, osteoporosis). In patients with congenital growth hormone deficiency, an MRI will help to identify abnormal pituitary anatomy rather than for definitive diagnosis. However, conducting an MRI can be challenging for pediatric patients and may require sedation to remain calm and still for approximately 45 minutes.

Diagnosis of a growth hormone deficiency after TBI can be challenging because many of the signs and symptoms associated with each condition overlap [25]. It is important to consider that increases in the severity of TBI likewise increase the risk of growth hormone deficiency [25]. As such, patients with a severe TBI should be evaluated. In these patients, plasma insulin growth factor is not a useful measure, because it lacks sensitivity and accuracy [25]. Instead, an insulin tolerance test, GHRH levels, and/or glucagon stimulation test should be used [25].

The diagnosis of growth hormone deficiency due to Sheehan syndrome is often delayed, in some instances for many years [72]. This is often because it is overlooked by healthcare professionals, and it should be considered as part of the differential diagnosis in women presenting with suggestive signs and symptoms [72].

The treatment of growth hormone deficiency is most commonly the administration of synthetic human growth hormone. If hormone replacement is initiated during childhood, the patient will usually reach a normal height in adulthood; even those with short stature can catch up [71,74]. The goal is to start hormone replacement before the child drops below the third percentile for height [21].

Growth hormone replacement is also appropriate therapy for adults and can lead to increased bone turnover, expanded remodeling space, decreased fracture risk, and over time, increased bone density [23]. It is interesting to note that some research has shown that the positive effect on bone density is more pronounced in men than women [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].

During somatropin treatment, children should have growth (height and weight) assessed every three to six months [75]. In adolescence, patients' growth and puberty should be monitored every six months [74]. Because this medication has been linked to hypothyroidism, thyroid function should be periodically checked. Somatropin treatment is ineffective in the presence of hypothyroidism, so treatment of the condition is vital [75]. Patients should also be monitored for hyperglycemia, especially patients diagnosed with diabetes. In addition, patients given somatropin after epiphyseal closure should be monitored for signs and symptoms of acromegaly.

Somapacitan, a long-acting human growth hormone analog, was approved for use in adults with growth hormone deficiency in 2020 [76]. This medication is administered as a once-weekly injection [76,77]. The initial dose is 1.5 mg, but the dose can be increased by 0.5–1.5 mg per week (to a maximum 8 mg per week) every two to four weeks based on clinical response and insulin-like growth factor-1 levels. Potential adverse effects include back pain, joint pain, indigestion, sleep disorders, dizziness, tonsillitis, edema of the extremities, vomiting, adrenal insufficiency, hypertension, increased blood creatinine phosphokinase, weight gain, and anemia [76]. The dose should be reduced if needed for adverse reactions or elevated insulin-like growth factor-1 levels. Somapacitan is contraindicated in patients with malignancy, diabetic retinopathy, and acute critical illness [76,77]. Discontinuation of therapy should be considered if no apparent benefits are achieved after 12 to 18 months.

In 2021, the FDA approved lonapegsomatropin (Skytrofa) for treatment of pediatric patients 1 year of age and older who weigh ≥11.5 kg and who have growth hormone deficiency. Lonapegsomatropin is administered subcutaneously once weekly. Lonapegsomatropin is initially dosed at 0.24 mg once weekly, then titrated based on individualized patient response [78,79,80]. The FDA approved lonapegsomatropin based on one clinical trial of 161 patients with growth hormone deficiency and short stature. The trial was conducted at 54 sites in 14 countries around the world, including in the United States, to assess efficacy and safety [80]. Common side effects include viral infection, fever, cough, nausea and vomiting, diarrhea, arthralgia, arthritis, and increased blood phosphate levels [80].

Growth hormone replacement therapy should continue over a prolonged period of time, in some cases for the patient's entire life. Patients receiving this treatment should be taught self-administration techniques.

Due to the length of treatment, adherence can be a challenge. Factors that may affect adherence include cost, length of treatment, and decreased understanding of treatment. Transition to adolescence is an important challenge to adherence [74]. Factors that may negatively affect adherence in adolescence include peer group conflict and loss of a sense of control. This is also a period of increased independence during which adolescents may want to take a more central role in managing their own care.

Poor compliance with or delayed therapy can lead to poor growth in children and to increased weight, changes to bone metabolism and density, and changes to cardiac structure and function (e.g., exercise intolerance, bradycardia, dilated cardiomyopathy) in adults [74]. Cognitive/psychological changes associated with poor compliance may include fatigue, sleep disturbance, decreased motivation, decreased self-esteem, and isolation [74].

With adherence in mind, empowering patients is important. For pediatric patient, parents/caregivers and the patient should be educated, offering choices (whenever possible), rewards, and age-appropriate educational materials [74]. Adolescent patients should be asked how they feel about their treatment and allowed to make decisions so they feel a sense of control. Adult patients should be encouraged to attend regular follow-up appointments and be provided with education on the benefits of treatment. Phone alerts or text or e-mail reminders may be beneficial [74]. Because cigarette smoking can increase the risk for fracture in adults with a growth hormone deficiency, patients should be advised to quit smoking and provided with cessation tools and resources.

Acromegaly is a rare condition, with approximately 3 to 14 of every 100,000 people diagnosed [83]. It is seen most commonly in adults between 30 and 40 years of age and more frequently in women than men [16,24]. Acromegaly is most commonly caused by pituitary tumors (e.g., adenomas, hypothalamic adenomas), but pituitary hyperplasia and genetic mutation are other possible etiologies.

Signs and Symptoms

The term acromegaly refers to enlargement of the acral parts—the head, hands, and feet—and these patients often present with enlargement of facial features, excessive growth of the hands and feet, and hypertrophy of soft tissues. The signs and symptoms may develop slowly and not become apparent for years [19].

Patients with acromegaly will have lateral changes to the bones of the face, and the mandible will enlarge and protrude. The space between the patient's teeth may widen and teeth may become displaced, which can lead to problems chewing and eating. The tongue and salivary glands often enlarge, leading to trouble with speaking and eating [16,21]. In addition to the tongue thickening, the lips and nose also enlarge, impeding breathing and possibly causing sleep apnea [83]. The patient's hair and skin may become thick, coarse, and oily [83]. Approximately 70% of patients with acromegaly report oily skin with increased sweating and unpleasant odor [21]. Some patients describe skin tags that become larger and darker [83]. Joint changes are seen in approximately 70% of patients with acromegaly, and joint pain and osteoarthritis often develop [19]. Growth hormone can increase bone resorption and turnover, increasing the risk for fracture [21].

The Endocrine Society suggests evaluating all patients presenting with acromegaly for associated comorbidities, including hypertension, diabetes mellitus, cardiovascular disease, osteoarthritis, and sleep apnea.

(https://academic.oup.com/jcem/article/99/11/3933/2836347 Last Accessed: July 19, 2024)

Strength of Recommendation/Level of Evidence: 2|⊕⊕○○ (Weak recommendation based on low-quality evidence)

Patients with pituitary enlargement may complain of headaches and visual disturbances (e.g., diplopia) as a result of the adenoma pushing on the brain and cranial nerves III, IV, and VI [16,19,24]. If the tumor presses on other pituitary tissue, it can lead to menstrual changes, erectile dysfunction, thyroid hormone changes, and decreased circulating cortisol [83]. The headaches may be severe and can interfere with the patient's ability to perform daily tasks [21]. If cranial nerve V is involved, the patient may also complain of facial pain [21].

Patients with acromegaly often have a reduced life expectancy because of associated cardiovascular, respiratory, metabolic, and neoplastic conditions [22]. Cardiac disease, including cardiomyopathy, arrhythmias, hypertension, and diastolic overload, is seen in approximately 60% of patients with acromegaly [21]. As many as 50% of patients will develop hypertension [21].

Gigantism starts in infancy or childhood and is characterized by continuous growth of the body until epiphyseal closure occurs. In adults, it is defined as a height greater than 80 inches; in children, it is defined as three standard deviations above the mean for the child's age as measured on a growth curve. Adults with gigantism may be as tall as 8 feet and weigh more than 300 pounds. Some individuals may develop associated acromegaly features (i.e., very large heads, hands, and feet) in adulthood [82].

As discussed, the adrenal glands are found above each kidney and produce cortisol, a glucocorticoid and aldosterone, a mineralocorticoid. In patients with Addison disease, an abnormality of the adrenal cortex leads to inadequate amounts of circulating cortisol and, in some cases, aldosterone [86].

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 [87]. In these patients, the cells in the adrenal cortex are damaged but the medulla remains intact [87].

Risk for Addison disease is increased in those with a family history of the disease, with heritability accounting for 97% of cases in a Swedish twin study [24]. In addition, other autoimmune conditions have been associated with an increased risk of Addison disease, including vitiligo, type 1 diabetes, and hypothyroidism [45].

Viral, bacterial, or fungal infection or parasitic infestation of the adrenal glands can lead to changes, and childhood infections may predispose a patient to Addison disease [87]. Worldwide, tuberculosis is the most common cause of Addison disease, although this is not routinely seen as a cause in developed countries [45,87]. Many infections that damage the adrenal glands are opportunistic, meaning they develop in immunocompromised individuals [87]. Serious infections (e.g., sepsis) require that the body be able to rapidly activate glucocorticoid production, which can lead to adrenal failure and, in some instances, adrenal crisis [87]. However, it has been hypothesized that infections highlight or exacerbate existing adrenal insufficiency rather than initiating it [87].

Patient who undergo bilateral adrenalectomy, as may occur with Cushing syndrome treatment, require steroid replacement or they will develop adrenal insufficiency and subsequent adrenal crisis. However, unilateral adrenalectomy rarely causes Addison disease unless the patient experiences severe adrenal stress, in which case the reduced adrenal reserve may be depleted [88]. Conditions that increase the risk for adrenal stress include sepsis, cardiopulmonary disturbance, trauma, and postoperative complications [88].

Hemorrhage (usually in response to infection or trauma) or malignant cells in the adrenal glands can cause damage and negatively affect the glands' ability to secrete cortisol and aldosterone [85]. Amyloidosis is a condition whereby the protein amyloid accumulates and causes damage to the adrenal glands, leading to decreased amounts of cortisol in the body [85]. Medications (e.g., antifungals, general anesthesia) can also lead to the development of Addison disease [37,85].

Adrenal crisis is a serious complication of Addison disease that can result in death if not identified and treated appropriately. Anything that increases the cortisol needs of the body can lead to this condition. In the patient with Addison disease, the body is unable to increase the amount of circulating cortisol in the body, leading to a cortisol deficit. The decline in cortisol and aldosterone directly affects the liver, stomach, and kidneys [89].

Addison disease is associated with vague, gradually developing (insidious) symptoms that can make diagnosis a challenge [37]. Signs and symptoms associated with this disorder are due to hormone deficiency, with the majority being attributable to decreased cortisol levels, although aldosterone plays a role as well [86]. In many cases, signs and symptoms do not develop until approximately 90% of the adrenal cortex is destroyed, and in some patients, symptoms are not recognized until adrenal crisis develops [85,86].

The most common signs and symptoms of Addison disease are chronic fatigue, lethargy, muscle weakness, loss of appetite, weight loss, increased urination, increased thirst, and abdominal pain [37,85]. Other potential signs and symptoms include nausea, vomiting, diarrhea, hypotension, irritability, depression, joint pain, salt cravings, hypoglycemia, dizziness, reduction in underarm and pubic hair, muscular pain, irregular or no menstruation, decreased libido, darkening of the skin, slowed growth in children, neurologic disturbances, depression, impaired concentration, and hypersensitivity to tastes and smells [37,90].

Cortisol plays a significant role in glucose metabolism, and decreases in cortisol levels can lead to hypoglycemia. Aldosterone acts on the kidneys to increase water retention and blood volume, and decreases in aldosterone levels can lead to hypotension, tachycardia, and salt cravings [16,32,86].

Melanodermia, color changes of the skin, is a potential side effect of Addison disease and most often presents in areas of the body most exposed to sunlight, such as the face, neck, knuckles, elbows, knees, and creases of the palms [24,90]. Darkening of scars may also be seen [89]. Pigment changes seen with Addison disease are due to the stimulant effect of excess ACTH on the melanocytes to produce melanin [86].

Electrolyte changes (e.g., hyponatremia, hyperkalemia, hypercalcemia) may occur with Addison disease [90]. As such, these patients should be closely monitored and may require supplementation and/or a modified diet. The patient with this disorder may also develop lymphocytosis and anemia [86].

Late symptoms of adrenal insufficiency are hypotension, dizziness, syncope, nausea, vomiting, diarrhea, abdominal pain, joint pain, back pain, muscle cramps, chronic exhaustion, skin changes, and decreased libido [85]. Signs and symptoms of adrenal crisis are hypotension, hypoglycemia, hyponatremia, hyperkalemia, vomiting, diarrhea, weakness, confusion, severe dehydration, severe pain in the lower back and abdomen, GI pain, and loss of consciousness [37,90]. Patients with later stage Addison disease may present with pale, cold, clammy skin; sweating; rapid, shallow breathing; and severe muscle weakness [85]. Untreated, adrenal crisis can lead to coma and death.

Patients in adrenal crisis lose large amounts of sodium and water, causing a fluid deficit with resulting hypotension and tachycardia [16]. The patient will often present with hyperkalemia, which can lead to cardiac abnormalities. The decreased cortisol levels in Addison disease will cause decreased glucose output by the liver and decreased digestive enzymes [89].

For most patients with Addison disease, diagnosis will be made around 40 years of age, and it is not uncommon for these patients to see multiple physicians before a diagnosis is made [86]. In cases of primary adrenal insufficiency, diagnosis of Addison disease may be delayed up to one year in as many as half of all cases [90]. Misdiagnosis is also common due to the vague signs and symptoms associated with the condition [86].

As discussed, the diagnostic tests that may be used for suspected Addison disease include ACTH stimulation test, serum cortisol levels, insulin tolerance test, antibody testing, and a CT scan or MRI. Aldosterone, serum cortisol, urine cortisol, blood glucose, and electrolyte levels may also be assessed [16,85]. In these patients, cortisol, aldosterone, sodium and glucose levels would all be low in persons with Addison disease; potassium will be elevated [85]. If the patient becomes dehydrated, BUN and hematocrit levels should be checked and will likely both be elevated. A complete blood count may be checked to determine if the patient has lymphocytosis or anemia.

After completion of the ACTH stimulation and insulin tolerance tests, an antibody test may be ordered. If the antibody test is positive, diagnosis of autoimmune Addison disease may be made with no further testing [37]. The CT scan or MRI may be helpful to evaluate the adrenal glands and/or pituitary gland. These imaging studies can determine if the glands are small in size or if they are enlarged due to infection, bleeding, or malignancy [37]. If tuberculosis is suspected, testing to rule out tuberculosis should be conducted.

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 [87].

Hormone replacement should be carefully planned to ensure the best outcome for the patient. Under typical circumstances, two-thirds of the daily dose is given in the morning and one-third in the evening to mimic the natural circadian rhythm of cortisol levels [16]. Increased doses of hormones are required during times of stress, as this will mimic what normally happens in the body; this includes during illness, infection, accident, injury, invasive medical procedures, and strenuous exercise [85]. If the patient is vomiting, IV or intramuscular hydrocortisone may be necessary [27]. Patients should be educated on self-administration of injectable medications.

The most often prescribed corticosteroid for the treatment of Addison disease is hydrocortisone; however, prednisone or dexamethasone may be used [37]. In patients who are deficient in both cortisol and aldosterone, fludrocortisone is the agent of choice [37]. Fludrocortisone aids in the retention of sodium and loss of potassium, and patients taking this medication should be monitored for signs and symptoms of fluid overload. This involves daily weights and assessment of new onset of edema in the lower extremities. Patients who do not make sufficient amounts of aldosterone should be advised to consume high-salt foods, especially if they are craving salt and on hot days.

One side effect of long-term corticosteroid therapy is an increased risk for osteoporosis [37]. As such, calcium and vitamin D supplementation may be necessary, and patients should be educated about incorporating these nutrients into the diet. Corticosteroids can also lead to mood swings and insomnia [85]. Treatment for these side effects is guided by impact on the patient's life and patient preference.

It may also be necessary to restore fluid, electrolyte, and hormone imbalances [24]. The IV fluid typically used for these patients is 5% dextrose in 0.9% sodium chloride to address glucose and sodium imbalances [24]. Electrolyte disturbances are addressed by adding electrolytes to IV fluid, hanging individual bags of specific electrolyte(s), or oral supplementation.

Nursing assessments should include questions about any recent stressors, such as illness, infection, or traumatic events. It is important to inquire regarding the use of steroids or recent surgery, particularly on the adrenal and/or pituitary glands. Identifying associated signs and symptoms (e.g., increased urination, salt cravings) is important. Standard nursing care includes monitoring vital signs, daily weights, intake and output, and laboratory values. Patients who report increased urination should be monitored for dehydration and signs/symptoms of hypovolemia (e.g., hypotension, tachycardia). Understanding that stress can play a role in this disorder, patients should be assessed for coping abilities and educated about stress reduction strategies. It may also be helpful to ask about the patient's support systems. Patients should be encouraged to wear a medical alert bracelet or necklace to help ensure appropriate care, such as the administration of glucocorticoids if the patient is ill or injured and unable to provide a medical history [85].

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].

As noted, Cushing syndrome is most commonly caused by long-term, high-dose glucocorticoid (e.g., prednisolone, dexamethasone) therapy, often used for the treatment of chronic conditions, such as asthma and chronic obstructive pulmonary disease (COPD) [21,28]. Symptoms associated with exogenous Cushing syndrome typically do not develop until the patient has been taking corticosteroids for at least one month [24].

In comparison, endogenous Cushing syndrome is relatively rare, occurring in 2 to 3 out of every 1 million people [41]. Cushing disease (secondary Cushing syndrome) makes up approximately 70% of all endogenous cases [21]. It is important to note that the terms Cushing syndrome and Cushing disease are not synonymous. Cushing syndrome encompasses cortisol changes from a variety of internal (endogenous) or external (exogenous) causes, while Cushing disease is only endogenous disease caused by a pituitary tumor or hyperplasia of the pituitary gland [29,92].

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 [29,92,93]. 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].

Many of the signs and symptoms associated with this disorder are due to the protein-wasting effect of cortisol [21]. Muscle wasting, thin skin, and striae develop because of the catabolic effect of cortisol on the tissues [16]. Purple/red striae occur then the skin becomes thin and stretched over areas of fat deposits [21]. This sign is most commonly seen on the abdomen, flank, breast, hips, and axillae [21]. The patient's skin may be red and warm to the touch due to inflammatory changes [21]. Patients with Cushing syndrome bruise easily and have fragile skin that is prone to tears. Wound healing is slowed due to the increased cortisol levels and subsequent hyperglycemia [21]. Lower extremity edema may develop and is often due to increased capillary permeability and sodium/fluid retention [21].

Children and adolescents with Cushing syndrome may present with growth delay or arrest (most common), weight gain/obesity, virilism, hirsutism, delay of secondary sexual development, and muscle weakness [94].

Women with Cushing syndrome may display signs of androgen imbalance, including oligomenorrhea or amenorrhea; infertility; excess hair on the face, neck, chest, abdomen, and thighs; thinning of the hair on the scalp; and polycystic ovary syndrome [16,28,94]. In addition to increasing the risk for infertility, Cushing syndrome may also increase the risk for miscarriage, perinatal death, premature birth, intrauterine growth restriction, pre-eclampsia, and eclampsia [21,58]. Men may experience erectile dysfunction and decreased fertility and libido [28].

The symptoms of Cushing syndrome often overlap significantly with metabolic syndrome [41]. These symptoms include obesity, glucose impairment, insulin resistance, dyslipidemia, and hypertension, all of which may persist after diagnosis and treatment of Cushing syndrome [41]. Patients with Cushing syndrome will have an increased risk for heart attack, cardiac failure, and left ventricular hypertrophy [41]. These persisting conditions can lead to a decreased quality of life and an increased risk morbidity and mortality.

Patients with this condition may also present with emotional, behavioral, and cognitive effects, such as mood changes, increased irritability, anxiety, depression, sleep problems, memory problems, and fatigue [29,93]. Anxiety and bipolar disorder are the most common psychiatric disorders associated with Cushing syndrome [41]. In children, obsessive compulsive disorder may be seen, as well as a declining school performance [41].

The catabolic effect of cortisol can cause changes to the patient's bones [16]. Up to 40% of patients with Cushing syndrome will develop osteoporosis and 20% of patients with this disorder will develop compression fractures of the spine [21]. Patients may also have a spontaneous rupture of the Achilles tendon [94]. The patient may also develop kyphosis and decreased height. Individuals with Cushing disease are more prone to opportunistic infections [94].

Many patients with Cushing syndrome report a decreased quality of life. Appropriate diagnosis and treatment can lead to improvements in patient health and well-being.

Diagnosis of Cushing syndrome may be difficult because cortisol levels are variable and will fluctuate throughout the day [93]. Misdiagnosis is common because the disease typically progresses slowly, making symptom identification more difficult [92]. Diagnosis is based on a medical history, physical exam, and laboratory tests. Through the diagnostic process, differential diagnosis is a consideration, as several conditions can mimic the syndrome. Patients should be evaluated for recent use of oral, cream, or inhaled steroids, most commonly hydrocortisone, prednisone, and dexamethasone [92]. Estrogen-containing oral contraceptive pills can increase cortisol and glucose levels, making diagnosis a challenge [21]. When testing for Cushing syndrome, estrogen therapy should be discontinued for six weeks prior to the test, if possible [21].

Diagnosis is especially challenging during pregnancy, because cortisol and glucose levels normally increase during this time [21]. Understanding that pregnancy and oral contraceptives may increase blood glucose and cortisol levels, Cushing syndrome testing should utilize saliva or urine samples in these patients [21].

After Cushing syndrome is diagnosed, it is necessary to determine the underlying cause [41]. This can often be accomplished with a dexamethasone-corticotropin-releasing hormone test [28]. This test can distinguish Cushing syndrome from non-Cushing causes of elevated cortisol. Similarly, bilateral inferior petrosal sinus sampling can be used to differentiate pituitary from ectopic Cushing syndrome [41].

CT or MRI is necessary to identify pituitary or adrenal tumors; MRI is the preferred imaging technique for Cushing syndrome [21]. CT scan can be used, but it is less reliable and may lead to false positive findings [21]. Additional laboratory tests may show neutrophilia and decreased lymphocytes and eosinophils [21].

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 [98,99].

Symptoms of hypokalemia range from mild fatigue to profound weakness. Patients may complain of paresthesia, loss of stamina, muscular weakness, and intermittent periods of paralysis. If hypokalemia alkalosis occurs, resulting in tetany, physical examination may elicit positive Trousseau and Chvostek signs [98,99].

Because of the increased reabsorption of sodium and water, hypernatremia and hypervolemia occur. Generally, edema is not present. The hematocrit may appear abnormally low as a result of the hemodilution. In addition to these major clinical signs, the patient with primary aldosteronism may also have severe polydipsia, polyuria, and nocturia resulting from the renal tubules' inability to respond appropriately to ADH [98,99].

Primary aldosteronism should be suspected in all patients with hypertension, particularly the young. Findings of comorbid hypertension, hypokalemia (potassium level less than 3.5 mEq/L), and excessive mineralocorticoid production (increased serum aldosterone levels) suggest the diagnosis. These findings become more significant if an excessive excretion of urinary potassium is found along with hypernatremia and decreased excretion of urinary sodium [98,99].

For the diagnosis of primary aldosteronism, a spironolactone test may be used in conjunction with assessment of serum potassium levels. Spironolactone is an aldosterone antagonist and, when given orally for three to four days, will stop the urinary excretion of potassium and restore serum levels to normal. Serum potassium levels have been shown to drop again five to seven days after the drug is halted [98,99].

To identify and localize an aldosterone-producing adenoma, various techniques may be used. Noninvasive procedures such as CT, MRI, and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT are the most commonly used imaging studies to assess potential adrenal masses. Invasive procedures, such as arteriography and retrograde adrenal venography, are rarely used for this purpose [98,99].

In patients with primary aldosteronism due to bilateral adrenal disease, the Endocrine Society recommends medical treatment with a mineralocorticoid receptor antagonist (e.g., spironolactone).

(https://academic.oup.com/jcem/article/101/5/1889/2804729 Last Accessed: July 19, 2024)

Strength of Recommendation/Level of Evidence: 1|⊕⊕○○ (Strong recommendation based on low-quality evidence)

The two main approaches to the treatment of primary aldosteronism are surgery and pharmacotherapy. Surgery is indicated when there is a unilateral aldosterone-producing tumor. In cases of hyperplasia, a subtotal or total adrenalectomy may be performed. Postoperatively, the return of normal aldosterone secretion by the remaining adrenal tissue may take several months. Following resection of the tumor, blood pressure will return to normal in most patients, but in one-third it may be lowered only slightly [100,101].

If surgery is not possible or declined by the patient, mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone) and lifestyle changes may be necessary to help control symptoms [102,103]. Possible side effects of these medications include gynecomastia, hyperkalemia, and hyperglycemia. Lifestyle changes, including weight loss, exercise, and low-sodium diet, and smoking cessation, will also be necessary.

Both epinephrine- and norepinephrine-producing tumors may secrete catecholamines paroxysmally, episodically, or continuously. The most severe symptoms are usually seen in patients with paroxysmally functioning tumors because of the rapid and marked changes in serum catecholamine levels. About 40% of patients with pheochromocytoma have paroxysmal hypertension, whereas the remainder experience either sustained or labile elevations in blood pressure [105].

Paroxysmal attacks vary in frequency, severity, and duration. Both the onset and resolution tend to be abrupt, with the average attack lasting a few minutes to a few hours. In many patients, these attacks may occur without warning, but others may be able to identify a prodrome of dermal paresthesia and increasing anxiety. Paroxysmal attacks may be precipitated by emotional changes (e.g., laughing, sexual activity, pain), postural changes (especially flexion or bending of the body), and/or physical exertion. Attacks may increase in frequency and duration over time and can result in pulmonary edema, cerebral hemorrhage, or ventricular fibrillation [105].

Symptoms of pheochromocytoma include headache, diaphoresis, and intense palpitations. The patient may also complain of extreme anxiety, tinnitus, excessive weakness, tremor, blurred vision, vertigo, dyspnea, and angina. After the attack, the patient may report a feeling of extreme weakness and exhaustion [100,106,107].

Signs of pheochromocytoma include marked elevation of the diastolic and systolic blood pressure (which may rise as high as 200 to 300/150 mm Hg), often with excessive diaphoresis, anxiety, dilation of the pupils, and tachycardia. Orthostatic hypotension and hypertensive retinopathy may occur in patients with persistently functioning tumors. Hyperglycemia and glycosuria are also frequently associated with pheochromocytoma because catecholamines can inhibit insulin production [100,106,107].

Pheochromocytoma should be suspected in patients with hypertension who have symptoms and signs of sympathetic hyperactivity, although only an estimated 0.2% of hypertension is related to pheochromocytoma. Diagnosis of pheochromocytoma is based on the presence of symptoms, laboratory confirmation, and imaging modalities. Biochemical testing of the serum and/or urine will reflect continuous production of catecholamines and their metabolites (metanephrines) [108]. In the past, pharmacologic tests (e.g., histamine test, phentolamine-blocking test) were used, but these have largely been replaced by more reliable and safer urinary assays [102].

After excessive catecholamine secretion has been determined, imaging studies are done to confirm the diagnosis and localize the tumor [100,107]. PET is the preferred approach, coupled with CT. The American College of Radiology recommends FDG-PET/CT scan to detect metastatic disease [109].

The definitive treatment of pheochromocytoma is surgical excision of the tumor. In the 10% of patients who are not surgical candidates (because of malignant pheochromocytoma with metastases or serious medical problems), control of symptoms is attempted with cytoreductive techniques, radiopharmaceuticals, chemotherapy, radiotherapy, and experimental therapies.

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 [110]. 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.

The usual operative approach is minimally invasive (laparoscopic) adrenalectomy. Open resection is reserved for large (i.e., >6 cm) or invasive pheochromocytomas to ensure complete tumor resection, prevent tumor rupture, and avoid local recurrence [110]. Partial adrenalectomy may be appropriate for selected patients.

Because of the possibility of extreme fluctuations in the blood pressure in the immediate postoperative period, blood pressure should be monitored every 15 minutes until stabilized; the time to stabilization may be extended in patients with pheochromocytoma. Nurses should be alert for sudden elevation in blood pressure in the early postoperative period, which may reflect a release of epinephrine and norepinephrine from the tumor as it was being excised. An alpha-adrenergic blocking agent may be used intravenously if the blood pressure rises excessively [60].

For patients who have undergone treatment for pheochromocytoma, the Endocrine Society suggests lifelong annual biochemical testing to assess for recurrent or metastatic disease.

(https://academic.oup.com/jcem/article/99/6/1915/2537399 Last Accessed: July 19, 2024)

Strength of Recommendation/Level of Evidence: 2|⊕⊕○○ (Weak recommendation based on low-quality evidence)

Severe hypotension may also develop postoperatively and can lead to shock. Metaraminol or norepinephrine, usually administered via IV infusion, may be used to help stabilize the patient. The dosage and flow rate will depend on accurate blood pressure measurements [60]. All patients who have undergone resection of a pheochromocytoma should be advised to change positions slowly to avoid orthostatic hypotension.

Discharge planning should stress the need for lifelong medical supervision. Following successful resection, patients should undergo regular follow-up, including measuring plasma or urine levels of metanephrines, to diagnose persistent (recurrent or metastatic) disease. Pheochromocytomas recur in 10% to 13% of cases [55].

Patients with pituitary or adrenal dysfunction are often confronted with a change in self-concept and a loss of self-esteem arising from changes in body image, decreased functional abilities, sexual dysfunction, loss of autonomy, and limitations in the decision-making processes. Changes in self-concept and loss of self-esteem can interfere with the patient's ability to adhere with the treatment plan and accept the diagnosis and its implications. For example, patients with Cushing syndrome will often require time and support to adjust to the cosmetic implications of the "moon" face, upper back/neck fat deposits, and truncal obesity associated with that disorder. Some conditions will also affect patients' ability to participate in activities as they once had or wish to. Individuals with Addison disease are required to take steps to avoid stressful situations. These pathophysiologic changes affect the patient's ability to function in normal situations, causing further stress and anxiety [81,82].

Certain disorders, including pituitary tumor and dysfunction of the adrenal cortex and medulla, cause emotional liability and personality changes. This presents serious concerns for the patient, who often feels out of control or unrecognizable. The nurse can help both the patient and family to understand the relationship between the physiologic condition problem and the psychological changes [81,82].

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 [82]. 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 [111]. 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) [112]. 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.

Occupational implications of pituitary/adrenal disorders include the possible need to change occupations or limitations in one's ability to work because of a physical disability. Patients with visual loss or changes in mentation often must make significant occupational adjustments. Patients may require adaptive equipment or may move to a different area to be closer to a source of health care or to access a special living environment. Economic factors may include the necessity for lifelong medications and medical supervision along with the increasing costs of diagnostic tests and hospitalizations [104,105].

The adjustment to new dietary requirements is a major challenge for patients with pituitary/adrenal disease. Patients who previously gave little thought to nutrition or balanced meals are often introduced into a life of fluid restrictions, special diets, and dietary supplements. These changes add extra strain to an already stressful situation and can also be an economic burden. Nurses should acknowledge the importance of dietary challenges and understand how they affect the patient and family, with particular consideration of how food features in the patient's culture. Patient teaching should include an exploration of dietary customs and how changes will be linked to improved health and quality of life [104,105].

As society becomes increasingly diverse, nurses are encountering a wide variety of cultural values and perceptions that influence health behavior in individuals and families. Because culture can have a strong influence on a patient's response to nursing interventions, nurses should be continually aware of these influences.

Cultural competence means being sensitive to differences in the values and beliefs that are shared by the members of an ethnic, cultural, racial, religious, or lifestyle preference of a group. Components of effective transcultural nursing include communication style, use of personal space, eye contact, and understanding of biologic variations. It is important to keep in mind, however, that there can be great variation among individuals within cultures. Therefore, stereotyping and making assumptions about an individual patient's beliefs based solely upon ethnic identification should be avoided.

In most cases, it is not necessary to develop a thorough understanding of each and every culture encountered in diverse healthcare settings. However, a certain degree of cultural competence can and should be developed. The first step in doing this is to recognize that cultural differences do exist. How these variations impact self-management can be explored in the needs assessment. This may include a sensitive exploration of the person's healthcare practices and the role of family members. Other culturally impacted areas may include beliefs about illness, diet, the role of the patient in self-care, gender roles, religious rituals, and communication styles.

Dietary preferences, meal preparation practices, and the symbolism of food represent an especially important area. When giving diet instructions, efforts should be made to consider the food preferences of the cultural group.

Cultural competence includes recognizing that cultural healthcare practices may differ from one's own beliefs about how an illness should be treated. Furthermore, cultural influences may not always be consistent with healthcare recommendations. This may be especially true for diseases that require significant behavioral adaptations. Americanized versions of traditional foods are high in salt, fat, and calories and are not recommended for people with restricted diets. Therefore, patients may experience a conflict between cultural values and those of the mainstream healthcare system.