Understand the etiology and pathophysiology of adrenal cortex disorders.

  Identify the major manifestations of Addison’s disease and Cushing’s disease.

  Explain how corticotropin (ACTH) is used in the diagnosis of adrenocortical insufficiency.

  Explain how cosyntropin (Cortrosyn) is used in the diagnosis of adrenocortical insufficiency.

  Identify the prototypes and describe the action, use, adverse effects, contraindications, and nursing implications for the drugs used in the treatment of Addison’s disease.

  Identify the prototypes and describe the action, use, adverse effects, contraindications, and nursing implications for the drugs used in the treatment of Cushing’s disease.

  Implement the nursing process in the care of the patient with Addison’s disease or Cushing’s disease.

KEY TERMS

Addisonian crisis: acute adrenocortical insufficiency

Adrenocortical excess: increase in adrenocortical function

Adrenocortical insufficiency: decrease in adrenocortical function

Introduction

Chapter 15 discussed corticosteroids, and Chapter 41 addressed the types of hormones secreted by the hypothalamus, including corticotropin-releasing hormone (CRH). This chapter introduces the pharmacological care of the patient with adrenocortical insufficiency and the patient with adrenocortical excess. The adrenal glands are attached to the upper portion of each kidney. The adrenal cortex of each adrenal gland secretes steroid hormones. The hypothalamic–pituitary–adrenal (HPA) axis regulates hormone secretion. The hypothalamus secretes CRH, which in turn stimulates the pituitary gland to secrete adrenocorticotropic hormone (ACTH) (Fig. 43.1). The ACTH then stimulates the adrenal cortex to secrete glucocorticoid hormone (cortisol). As the levels of adrenal or steroid hormones increase, the levels of CRH and ACTH decrease; this is a negative feedback mechanism (Smeltzer, Bare, Hinkle, & Cheever, 2010).

Overview of Addison’s Disease

Etiology and Pathophysiology

There are two forms of adrenocortical insufficiency. Primary adrenal insufficiency, or Addison’s disease, occurs when adrenal cortical hormones are deficient. ACTH levels are elevated because the feedback mechanism is not working. Secondary adrenal insufficiency occurs when there is a disorder in the HPA system.

Primary adrenal insufficiency most commonly results from an autoimmune disorder that has destroyed the layers of the adrenal cortex. Other causes of adrenal cortex destruction include metastatic carcinoma, fungal infections such as histoplasmosis, cytomegalovirus, amyloid disease, and hemochromatosis. Hemorrhage of the adrenal cortex related to anticoagulant therapy, open heart surgery, giving birth, or trauma also leads to primary adrenal insufficiency.

Secondary adrenal cortical insufficiency results from hypopituitarism or surgical removal of pituitary gland (Porth & Matfin, 2009). The abrupt withdrawal of oral glucocorticoids also causes secondary adrenal insufficiency. Patients who have endogenous steroid production from a nonendocrine tumor have adrenocortical insufficiency.

Primary adrenocortical insufficiency is associated with the destruction of the adrenal cortex. The resulting deficiency in the mineralocorticoids causes an increase in the loss of urinary sodium, chloride, and water. The patient becomes hyponatremic, and the cardiac output decreases. This progression of the disease is known as Addisonian crisis. The loss of sodium leads to retention of potassium, resulting in symptoms of hyperkalemia.

Clinical Manifestations

Clinical manifestations of adrenocortical insufficiency are evident when approximately 90% of the adrenal cortex has been destroyed. These signs and symptoms reflect loss of sodium, water, and chloride. Findings include decreased cardiac output, dehydration, weakness, and fatigue. Excessive sodium loss results in cardiovascular collapse and shock. Other symptoms include lethargy, weakness, fever, anorexia, nausea, vomiting, and weight loss. Hyperkalemia and hypoglycemia are present. (Any patient with unexplained severe hypoglycemia requires assessment for adrenal insufficiency (Nieman, 2011).) Hyperpigmentation of the gums and mucous membranes is also present; they may be bluish black. Women have diminished axillary and pubic hair, but men have few effects from the lack of androgens due to the production of hormones by the testes (Porth & Matfin, 2009).

Acute adrenal crisis, or Addisonian crisis, is a life-threatening condition that occurs when Addison’s disease is the underlying problem and the patient is exposed to minor illness or increased stress. Nausea, vomiting, hypotension, muscle weakness, and vascular collapse are present (Smeltzer, et al., 2010; Porth & Matfin, 2009). There may be a craving for salt.

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Diagnosis

According to Smeltzer et al. (2010), patients commonly present to their primary health care provider with vague symptoms of adrenocortical insufficiency. However, as the adrenocortical insufficiency progresses, acute hypotension results and Addisonian crisis may develop. Making the diagnosis of adrenocortical insufficiency involves laboratory work. This includes early morning serum Cortisol and plasma ACTH levels. A serum Cortisol level less than 3 mcg/dL, or 80 nmol/L, is indicative of adrenocortical insufficiency. (The normal morning level of serum Cortisol is greater—10 to 20 mcg/dL, or 275 to 555 nmol/L.) An ACTH level greater than 22.0 nmol/L is indicative of (primary) adrenocortical insufficiency. (The normal morning level of ACTH is less than 18 nmol/L.)

Confirming the diagnosis of adrenocortical insufficiency requires a short plasma corticotropin stimulation test. The examiner administers corticotropin in the morning, and a subnormal blood Cortisol level in the morning and afternoon confirms the diagnosis. A higher Cortisol level in the morning is a sign that a person does not have adrenal insufficiency. In a patient with adrenal insufficiency, the response to the corticotropin, or ACTH, is the same both morning and afternoon.

Another test that confirms the diagnosis of adrenocortical insufficiency is the standard high-dose test. It is a three-step process:

An increase of at least 18 to 20 mcg/dL is considered normal. No increase in serum cortisol indicates the presence of adrenocortical insufficiency.

Diagnosis of secondary adrenocortical insufficiency in its early stages requires the low-dose test. It is also used for the diagnosis of chronic partial pituitary ACTH deficiency. This test involves the administration of 1 mcg of cosyntropin (Cortrosyn) as an IV bolus. Normally, an increase in cortisol occurs in 20 minutes. In patients with adrenocortical insufficiency, there is no increase in the serum cortisol level.

Overview of Cushing’s Disease

Etiology and Pathophysiology

The cause of Cushing’s disease is adrenocortical excess. In the majority of patients, the increased adrenocortical function results from excessive corticotropin, leading to hyperplasia of the adrenal cortex. In a smaller percentage of patients, it is the result of a cortisol-secreting adrenal tumor, whether from too much corticotropin (ACTH) or a primary tumor of the adrenal gland. A malignant tumor of the adrenal gland can produce many corticosteroids, whereas the benign adrenal tumor only produces one corticosteroid that is secreted by the adrenal gland. Other, much less common causes are hyperplasia of the adrenal gland or ectopic production of ACTH by malignancies such as bronchogenic carcinoma (Smeltzer et al., 2010). Long-term treatment with pharmacological glucocorticoids leads to iatrogenic Cushing’s syndrome.

Clinical Manifestations

Patients with Cushing’s disease often present with classic signs and symptoms. These include obesity, with a heavy trunk and thin extremities; a fatty “buffalo hump” at the neck and supraclavicular region; and a moon-faced appearance. The skin becomes fragile and tears easily, and broad purple striae and bruises may develop. Wound healing may be impaired. The hair is thin. Women have virilization with the appearance of masculine traits such as increased facial hair, breast atrophy, enlarged clitoris, disrupted menses, and voice deepening. Libido is diminished or absent in men and women. Depression, weakness, and lassitude may also occur.

The excessive secretion of corticotropin leads to osteoporosis and fractures, which are caused by the increase in calcium reabsorption from the bone. Blood glucose levels are also increased, and glucose intolerance may occur as a result of increased hepatic gluconeogenesis and resistance to insulin. Peptic ulcers may develop because of increased secretion of gastric acid and pepsin.

Diagnosis

The diagnosis of Cushing’s disease requires an overnight dexamethasone suppression test. The patient takes dexamethasone, a synthetic glucocorticoid, 1 mg orally at 11 PM. He or she then has a serum Cortisol level drawn at 8 AM. A cortisol level of less than 5 mcg/dL indicates that the HPA axis is functioning normally. Cortisol levels are higher in patients with adrenal or ectopic tumors.

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Drugs Used to Treat Addison’s Disease

The goal of treatment for Addison’s disease is to replace the adrenocorticoids to correct adrenal insufficiency. It is important to replace both the mineralocorticoid and adrenocorticoid. Lifetime hormone replacement is necessary. Table 43.1 summarizes the adrenocorticoid and mineralocorticoids administered for the treatment of adrenocortical insufficiency.

ADRENOCORTICOIDS/MINERALOCORTICOIDS

Hydrocortisone cypionate (Cortef) or hydrocortisone sodium succinate (Solu-Cortef) is a combination of a mineralocorticoid and adrenocorticoid. Both of these drugs are useful in acute and chronic adrenal insufficiency.

Pharmacokinetics and Action

The oral preparation of hydrocortisone has a 1 to 2-hour onset of action, a peak of action in 1 to 2 hours, and a duration of action of 1 to 1.5 days. The parenteral preparation of the drug has an immediate onset of action, an unknown peak of action, and a duration of action of 1 to 1.5 days. Metabolism occurs in the liver. Excretion is in the kidneys.

Action

Hydrocortisone enters the cells and binds to the receptors in the cytoplasm to decrease inflammation; it suppresses the migration of polymorphonuclear lymphocytes and decreases capillary permeability. The mineralocorticoid in the drug increases the retention of sodium.

Use

Health care providers used hydrocortisone to replace adrenocorticoids and mineralocorticoids in patients with Addison’s disease. The drug is also useful in congenital adrenal hyperplasia. Table 43.2 gives route and dosage information for adrenocorticoids and mineralocorticoids.

Use in Children

It is necessary to individualize the dose depending on the severity of the adrenal insufficiency and the response to the medication. The drug may affect growth velocity, and it is important to carefully assess growth and development with infants and children. Also, the nurse assesses neonate’s respiratory status closely after the administration of parenteral hydrocortisone. Some preparations contain benzyl alcohol, which may cause gasping syndrome in neonates.

Use in Older Adults

Elderly people should receive the lowest possible dosage because of the increased risk of adverse effects with systemic corticosteroids.

Adverse Effects

Hydrocortisone has significant adverse effects, including the following:

Contraindications

Contraindications to hydrocortisone include a known hypersensitivity to the drug or any component of the formulation as well as a serious infection. A BLACK BOX WARNING ♦ states that patients who are being treated with hydrocortisone should not receive live virus vaccines.

Nursing Implications

Preventing Interactions

Several medications and herbal supplements interact with hydrocortisone, increasing or decreasing its effects (Boxes 43.1 and 43.2). Hydrocortisone has numerous other interactions. Combination of hydrocortisone with certain drugs may result in the following effects: