Adrenocortical Insufficiency: A Medical Emergency
LAURA M. LEE, RN, BSN,’ JULIE GUMOWSKI, RN, BSNt
Adrenal insufficiency is a deceptive disorder. Insidious in onset, chronic in nature, it can suddenly progress into an acute life-threatening condition that may mimic disorders of vastly different etiologies. The result can be a lethal delay in diagnosis. Prompt diagnosis and replacement of glucocorticoids and fluids are essential for survival. Acute adrenal insufficiency is frequently an exacerbation of an underlying chronic disorder of the adrenal cortex or pitu- itary gland. Yet any patient who has been treated with suppressive doses of glucocorticoids (e.g., cortisol, prednisone), experienced overwhelming sep- sis, has received anticoagulant therapy, or has endstage metastatic carcinoma may suddenly develop adrenal insufficiency along with its deadly sequela of hypovolemic shock, hyperkalemia, hyponatremia, and hypoglycemia. Suc- cessful management of this condition requires not only a heightened clinical awareness of adrenal insufficiency, but effective stress reduction interven- tions and a thorough patient and family teaching program to support lifelong control of the disease (KEYWORDS: glucocorticoids, Addison’s disease, hy- perkalemia, cortisol, aldosterone, hypovolemic shock).
CASE STUDY
Seventy-five-year-old Rhea was admitted to the intensive care unit with a left hip fracture, hypovolemia, and mental confusion. The pa- tient’s past medical history was unknown. The only information available was from her building superintendent who found her on her bathroom floor after becoming con- cerned that he had not seen her for 2 days. When he last had seen her, she had com- plained of having flu-like symptoms (e.g., vomiting, diarrhea). Rhea’s admission assess- ment is outlined in Table 1.
Interventions to correct the patient’s vol- ume depletion and electrolyte imbalances were initiated immediately. A rapid infusion of normal saline with 5% dextrose and an in-
fusion of dopamine, 6 ug/kg/minute, was started. Eighteen hours after initial therapy began, the patient continued to require vol- ume replacement and increasing doses of do- pamine to maintain her hemodynamic status.
It was later learned that the patient had been taking 30 mg prednisone daily for years to manage her rheumatoid arthritis. She had not taken her doses for several days because of nausea and vomiting. The patient was im- mediately started on intravenous replace- ment doses of hydrocortisone (Solu-Cortef, Upjohn, Kalamazoo, MI). With sufficient hor- mone replacement, her fluid and electrolyte status rapidly normalized and her cardiovascu- lar status stabilized.
Adrenal dysfunction is rarely an admitting diagnosis for the intensive care patient, how- ever underlying adrenal insufficiency (AI) can progress quickly to adrenal crisis when the patient is stressed or exogenous doses of glucocorticoids are stopped abruptly, as the case study illustrates. The incidence of AI in the intensive care setting is uncertain. Studies of patients admitted to the intensive care milieu cite a range of less than 1% to 28% in
From the Quality Assurance Service* and the tDe- partment of Nursing, Clinical Center, National Insti- tutes of Health, Bethesda, Maryland.
Reprint requests to Laura M. Lee, RN, BSN, Quality Assurance Service, Clinical Center, Building 10, Room 2C-144, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892.
| Laboratory values | |
| Sodium | 129 mmol/L |
| Potassium | 6 mmol/L |
| Glucose | 3.8 mmol/L |
| Blood urea nitrogen | 10.7 mmol/L |
| Creatinine | 116 mmol/L |
| Cardiac status | |
| Heart rate | 120 bpm |
| Rhythm | Sinus tachycardia |
| Central venous | 2 mmHg |
| pressure | |
| Pulmonary artery | 5 mmHg |
| wedge pressure | |
| Cardiac output | 3 L |
| Arterial blood pressure | 80/50 mmHg |
| Electrocardiogram | Peaked T waves, widening of QRS : complex |
| Neck veins | Flat, nondistended |
| Capillary refill | >3 s |
| Pulmonary status | |
| Respiratory rate | 22 breaths/min, regular and unlabored |
| Breath sounds | Clear, all fields |
| Arterial blood gases | |
| pH | 7.29 |
| PaO2 | 94 mmHg |
| PaCO2 | 33 mmHg |
| Bicarbonate | 17 mmol/L |
| SaO2 | 94% |
| Renal Status | |
| Urine output | 25 mL/hr |
| Urine specific gravity | 1.030 |
| Neurologic status | |
| Level of consciousness | Difficult to arouse, lethargic, follows commands |
| Sensorimotor | Marked muscle weakness, hyporeflexic |
| Gastrointestinal status | |
| Bowel sounds | Hyperactive |
| Stool | Watery diarrhea |
| Other | Complaints of abdominal cramping |
incidence of AI, depending on the group of patients tested. In studies performed to as- sess for de novo AI (patients without known AI and those not receiving glucocorticoid therapy), fewer than 3% of these patients had
AI.1 However, in a review by Drucker and Mclaughlin, 31% of patients admitted to an intensive care setting had been treated with glucocorticoid therapy, therefore placing them at risk for developing AI.2 Clearly, when one third of the intensive care population may be at risk for AI and possible adrenal cri- sis, an understanding of this potentially lethal medical emergency is crucial to ensure prompt and appropriate intervention.
ETIOLOGY OF ADRENAL INSUFFICIENCY
Adrenal insufficiency is characterized by the absence or deficiency of adrenocortical hormones, specifically glucocorticoids (cor- tisol) and mineralocorticoids (aldosterone). These hormones are essential for physiologic and psychologic integrity (Tables 2 and 3). An insufficient circulating level of cortisol is virtually incompatible with life.
Cortisol is maintained at an adaptive level by the hypothalamus-pituitary-adrenal axis (H-P-A axis) via a negative feedback system. The hypothalamus and the pituitary gland continually survey and respond to circulating levels of cortisol. If the cortisol level drops, the hypothalamus secretes corticotropin re- leasing hormone into the hypothalamic-pitu- itary capillary system. Corticotropin releasing hormone stimulates the pituitary gland to se- crete adrenocorticotropic hormone (ACTH). The adrenal glands respond to the secretion of ACTH by increasing secretion of cortisol. The increased serum level of cortisol is sensed by the hypothalamus and corticotro- pin releasing hormone secretion is inhibited. The secretion of : Idosterone is controlled by the renin-angiot :nsin-aldosterone system. The H-P-A axis as well as the renin-angioten- sin-aldosterone mechanism are disrupted in AI, thus diminishing or obliterating cortisol and aldosterone secretion (Fig. 1).
Hypoadrenalism can be classified as pri- mary or secondary. Primary AI (Addison’s dis- ease) was first described by Thomas Addison in 1855.3 Primary AI results from the destruc- tion or primary dysfunction of the adrenal cortex (Fig. 2). Ninety percent of the adrenal cortex must be destroyed before hypoadre- nalism is manifested.4 The most common
| Category | Action | Category | Action |
|---|---|---|---|
| Carbohydrate metabolism | Increases blood glucose levels Increases hepatic glycogen and glucose production by increasing gluconeogenesis in the liver Decreases glucose uptake and utilization in peripheral tissues Enhances the ability of other hormones to stimulate gluconeogenesis Increase free fatty acids and enhances lipolysis Produces changes in the lipid distribution Influences muscle breakdown and protein conversion to glucose | Fibroblast/epithelial tissue responses Cardiovascular/ electrolyte responses | Inhibits fibroblast activity, causing bruising and diminished wound healing capacity |
| Decreases collagen synthesis Effects vascular responsiveness to pressor stimuli from catecholamines Acts directly on the heart by inducing protein synthesis | |||
| Lipid metabolism | Produces positive inotropic influence on the left ventricular work index because of increased beta adrenergic receptors Increases erythrocyte volume | ||
| Protein catabolism | |||
| Immunologic/ inflammatory response | Suppresses immunologic inflammatory activity Inhibits production and activity of vasoactive agents (prostaglandins, kinins, histamines) Inhibits movement of leukocytes to affected area | Bone metabolism | Partially blocks calcium absorption in the intestine Decreases renal reabsorption of calcium and phosphate Decreases bone formation |
| Enhances osteolysis | |||
| Inhibits the function of immune cells at the site of inflammation Decreases T-cell lymphocyte function | Ocular responses | Increases intraocular pressure Stimulates cataract formation |
| Category | Action |
|---|---|
| Sodium conservation | Sodium is reabsorbed in the distal collecting tubules of the kidney Sodium is also reabsorbed in the gastrointestinal tract |
| Potassium elimination | Potassium is secreted in the renal tubules and via feces, saliva, and sweat |
cause of primary AI is autoimmune adrenal- itis, accounting for approximately 70% of AI.4 Destruction of the adrenal glands and subse- quent atrophy result from circulating autoanti- bodies and sensitized T-lymphocytes to adre- nal tissue. This autoimmune process selec- tively targets the adrenal cortex, rarely involving the adrenal medulla.5
Tuberculosis is responsible for approxi- mately 20% of all cases of AI and is the lead- ing cause of AI associated with infectious agents.º Fungal infections are also responsi- ble for infectious adrenalitis.5 Cytomegalovi-
HYPOTHALAMUS
CRH
ANTERIOR PITUITARY
[-]
ACTH
ADRENAL CORTEX
GLUCOCORTICOIDS (CORTISOL)
rus infection also has been linked to primary AI. There have been several reports of cyto- megalovirus infection of the adrenal glands in patients with HIV-1 infection. This infec- tion has led to adrenal necrosis and Addison’s disease in this patient population.4,7,8 Metasta- sis of malignant neoplasms to the adrenal glands also can result in Addison’s disease.9 Drug-induced AI usually results from a delib- erate attempt to produce a hypoadrenal state -a medical adrenalectomy. However, cer- tain drugs may adversely induce AI, particu- larly in patients with compromised adrenal function (Table 4).10-12
Secondary AI is associated with hyposecre- tion of ACTH from the anterior pituitary gland because of dysfunction of the hypothal- amus and/or the anterior pituitary gland (Fig. 3). There are two causes of secondary adrenal AI. First, suppression of adrenal function can be attributed to prolonged exposure to high doses of exogenous corticosteroids or high levels of endogenous corticosteroids. This elevated level of circulating glucocorticoids effects a reduction in ACTH secretion and subsequent adrenal atrophy via the negative feedback pathway of the H-P-A axis. A dose of 20 mg hydrocortisone for greater than 7 to 10 days can suppress the H-P-A axis.13 These pa- tients are at significant risk for developing AI
when steroids are abruptly withdrawn. Pa- tients with elevated levels of endogenous glucocorticoids include patients with Cush- ing’s syndrome. Adrenal insufficiency often develops after resection of the ACTH secret- ing tumor. Iatrogenic causes account for the majority of cases of secondary AI. This type of AI is usually transient, however the H-P-A axis can remain suppressed for up to 3 to 12 months after correction of either endogenous or exogenous hypercortisolism.13,14
Secondary AI can also occur if there is hy- posecretion of ACTH resulting from destruc- tion or dysfunction of the hypothalamus and/ or the anterior pituitary gland. Glucocorti- coid deficiency results from lack of ACTH stimulation of the adrenal glands. Table 5 outlines the causes of primary and second- ary AI.
ETIOLOGY OF ACUTE ADRENAL INSUFFICIENCY OR ADRENAL CRISIS
Acute AI or adrenal crisis is an emergency situation characterized by exaggeration of symptoms associated with AI. An acute adre- nal crisis can occur spontaneously or when a patient with compromised adrenal function
[+]
HYPOTHALAMUS
1
& CR4
[+]
ANTERIOR PITUITARY
1
1 ACTH
+
ADRENAL CORTEX
TAIPOFMYT
GLUCOCORTICOIDS ICORTISOL3
MINERALOCORTICOIDES CALDOSTERZWEI
| Medication | Pharmacologic Action |
|---|---|
| Steroid synthesis inhibitors Ketoconazole | An imidazole derivative traditionally used as an antifungal agent. At high doses, this drug also blocks steroid synthesis in the gonads and the adrenal cortex by interrupting the steroid pathway at the 11-beta-hydroxylase level. |
| Aminoglutethamide | A drug used primarily in the treatment of hypercortisolism associated with Cushing's syndrome. It blocks cortisol production at the delta-5 pregnenolone level. |
| Metyrapone | A drug used as a medical treatment for hypercortisolism. It reduces cortisol production by inhibiting the 11-beta- hydroxylation in the cortex.21 |
| Trilostane | An antiadrenal agent that suppresses adrenal cortex function by inhibiting the enzymatic conversion of steroids by 3-beta- hydroxsteroid dehydrogenase.22 |
| Adrenalytics O,p'DDD (mitotane) | An adrenal cytotoxic agent that also inhibits adrenal function. It acts by destroying adrenal tissues and by modifying peripheral metabolism of cortisol. Extra-adrenal metabolites of the drug cause a reduction in 17-hydroxycorticosteroid even though plasma cortisol levels do not decrease.23 |
| Suramin | A reverse transcriptase inhibitor that has been used in the treatment of AIDS and various cancers. |
| Receptor antagonists RU 486 | A progesterone and glucocorticoid antagonist that blocks the action of cortisol at the cellular level.24 |
| Adverse side effects Etomidate Rifampin | An intravenous sedative/hypnotic used as an anesthetic for unstable cardiac patients and for sedation of critically ill, ventilator-dependent patients. Etomidate is a substitute for imidazole, similar to ketoconazole. This drug blocks steroid synthesis at the 11-beta-hydroxylase and cholesterol side-chain cleaving enzyme. Several studies describe an association between etomidate infusion (both bolus and continuous) and suppression of cortisol secretion.25 Patients receiving this medication need to be assessed closely for a competent hypothalamus-pituitary-adrenal axis and for the development of adrenal insufficiency. An antituberculin medication that increases the catabolismof cortisol by inducing hepatic microsomal enzymatic activity (specifically, 6-beta-hydroxylase) in the liver. This accelerated catabolismof cortisol complicates the therapy of adrenal insufficiency.26 |
| Phenytoin | An anticonvulsant that increases steroid catabolismby inducing hepatic microsomal enzymes.27 While this medication will not cause adrenal insufficiency in a patient with an intact hypothalamus-pituitary-adrenal axis, a patient with underlying adrenal insufficiency may be compromised.28 |
suffers significant emotional or physiologic stress. Stressors might include infection, minor surgery, general anesthesia, trauma, withdrawal from alcohol or narcotics, or ex- treme psychologic distress.15,16 In these situa-
tions, the patient is unable to secrete ade- quate amounts of cortisol to maintain homeo- stasis. An adrenal crisis can also be precipitated by inadequate glucocorticoid re- placement therapy or abrupt withdrawal of
[+]
CAN
ANTERIORIL, TILITARE
[+]
W ACTH +
ADRENAL CORTEX CA TROPHYS
MINERALOCORTICOIDS TAL DOSTFRONTS
glucocorticoids. Both primary or secondary AI can progress into adrenal crisis; however, patients with chronic primary AI are at greater risk of developing adrenal crisis because of the absolute deficiency in glucocorticoids and mineralocorticoids.17
CLINICAL MANIFESTATIONS OF ADRENAL INSUFFICIENCY
In 1855 Thomas Addison described a group of patients as having “anaemia, general lan- guor and debility, remarkable feebleness of the heart’s action, irritability of the stomach and peculiar change of color in the skin.”3 He was describing patients with adrenal dys- function-later named Addison’s disease. These observations continue to accurately describe patients who present with acute or chronic AI.
Clinical manifestations of acute AI include fluid and electrolyte abnormalities, cardiovas- cular changes, gastrointestinal symptoms, weakness, fever, abdominal pain, mental sta- tus changes, and skin changes4,16-18 (Fig. 4).
Acute Adrenal Insufficiency
Adrenal crisis can precipitate dramatic, life- threatening fluid and electrolyte imbalances.
The combination of severe hyponatremia, fluid loss, hyperkalemia and subsequent de- creased cardiac output, tachycardia, and hy- potension can lead to the most lethal se- quelae of adrenal crisis: hypovolemic shock.4,16,17
The cause of this hyponatremia is twofold. Glucocorticoid deficiency causes a disrup- tion in the kidneys’ ability to excrete free water by lowering the glomerular filtration rate as well as by increasing vasopressin re- lease. In addition, the hyponatremia asso- ciated with mineralocorticoid deficiency re- sults from renal excretion of sodium in the absence of aldosterone.17 This hyponatremia left untreated can rapidly lead to volume de- pletion.
TABLE 5. Causes of Adrenal Insufficiency
Primary adrenal insufficiency Autoimmune, idiopathic atrophy Tuberculosis
Fungal infections Histoplasmosis
Coccidiodomycosis
Blastomycosis Cytomegalovirus Metastasis
Infiltrative diseases Sarcoidosis Amyloidosis
Adrenal hemorrhage from use of anticoagulants Adrenalectomy
Pharmacologic suppression Secondary adrenal insufficiency Hypothalamus-pituitary-adrenal Pituitary adenomas/tumors Craniopharyngioma, chromophobe adenoma Lymphoid hypophysitis Pituitary trauma or surgery Infectious diseases
Tuberculosis Actinomycosis Nocardiosis
Postpartum necrosis (Sheehan’s syndrome)
Infiltrative diseases Sarcoidosis
Suppression of hypothalamus-pituitary-adrenal axis Discontinuation of high dose steroids Resection of adrenocorticotropic hormone secreting tumor
CARDIOVASCULAR
Orthostatic hypotension Tachycardia ECG changes Hypovolemia
LABORATORY FINDINGS
GASTROINTESTINAL
Hyponatremia Hyperkalemia Hypoglycemia Anemia
Nausea, Vomiting Diarrhea Abdominal pain Anorexia, Weight loss
ADRENAL INSUFFICIENCY
MUSCULOSKELETAL
Joint pain Muscle pain Muscle weakness Fatigue
INTEGUMENTARY Hyperpigmentation
PSYCHIATRIC
Depression Apathy Psychosis Self-mutilation
Mineralocorticoid deficiency also leads to increased renal reabsorption of potassium, resulting in hyperkalemia. The patient with an elevated serum potassium level is at risk for developing life-threatening cardiac dys- rhythmias. Electrocardiogram changes may include prolonged QT intervals, low QRS voltage, peaked T waves, widened QRS, ven- tricular dysrhythmias, and first-degree heart block.16,20 Cardiac status is compromised fur- ther because of the decreased arteriolar re- sponsiveness to pressor stimuli and de- creased cardiac output arising from glucocor- ticoid deficiency. These physiologic changes may result in orthostatic hypotension and tachycardia.4,15,17 Patients with primary AI, and the resulting glucocorticoid and miner- alocorticoid deficiencies, are particularly at risk for these complications.
Hypoglycemia is often present, especially in children or underweight patients. Cortisol deficiency leads to a decrease in hepatic glu- cose production and an increase in periph- eral utilization of glucose.16 Fasting is poorly tolerated in this patient population. Patients with AI are markedly weak, lethargic, and fa- tigued. These symptoms are also caused by
the lack of energy production associated with hypoglycemia.
Gastrointestinal manifestations occur in ap- proximately one third to one half of all AI pa- tients. Gastrointestinal symptoms include an- orexia, weight loss, nausea, vomiting, and di- arrhea. The physiologic mechanism that causes these symptoms is unclear, but may be the result of electrolyte imbalances and the loss of the anabolic pathway resulting from a glucocorticoid deficiency.18,19 Underlying vol- ume depletion is often compounded by the accompanying nausea, vomiting, and/or diar- rhea.
Approximately 60% to 80% of patients with AI experience mental status changes asso- ciated with the disease. The most common psychiatric manifestations are depression, apathy, and confusion. In addition, patients present in psychotic and paranoid states.21 This is an important but often overlooked sign to assess for in the adrenally insufficient patient. Management and treatment will need to be sensitive to the patient’s potentially ten- uous mental status. The cause of these distur- bances is unclear and is subject to great de- bate.
Fever and abdominal, flank, or back pain and/or tenderness are signs and symptoms typical of patients who present with adrenal hemorrhage as a result of overwhelming sepsis.15,16
Chronic Adrenal Insufficiency
Many of the same signs, symptoms, and lab- oratory findings associated with acute AI are present in patients with chronic AI. The ma- jority of patients presenting with chronic AI complain of excessive weakness and fatigue, and before diagnosis, many of these patients are labeled as chronic malingerers.4 Although the gastrointestinal manifestations of chronic AI are less intense and debilitating than those experienced during a crisis, nausea, vomit- ing, weight loss, and anorexia are common problems associated with chronic AI.18
The hallmark of chronic primary AI is hy- perpigmentation. This darkening of the skin is most likely caused by betalipotropin or ACTH stimulation of melanocyte activity; therefore, hyperpigmentation is absent in pa- tients with secondary AI because of de- creased ACTH levels.16,22 Hyperpigmentation is apparent diffusely on exposed and unex- posed areas of the body as well as on the buc- cal mucosa, in creases in the palms, and on old scars. Vitiligo, a patchy depigmentation of the skin, may also be present. This depigmen- tation is associated with an autoimmune pro- cess that often accompanies AI. While the cli- nician may see hyperpigmentation in a pa- tient with acute AI, this symptom is usually an indicator of disease chronicity.5 Patients also may complain of muscle and joint pain, how- ever the etiology of this discomfort is un- clear.14 Mild hypogonadism is often a feature of chronic AI because of the absence of adre- nal androgens. Amenorrhea and/or de- creased libido may be present.5,15 Abnormal laboratory findings may include mild hypona- tremia and hypoglycemia along with hemato- logic changes such as with normocytic, nor- mochromic anemia, moderate lymphocyto- sis, and eosinophilia.4,14,15 Mild orthostatic hypotension and tachycardia also may be pres- ent in a patient with chronic AI.4,15
DIAGNOSIS OF ADRENAL INSUFFICIENCY
Diagnosis of AI is often complicated by the nonspecific nature of the disorder’s clinical
presentation. Laboratory values, signs and symptoms, past medical, surgical, and phar- macologic history as well as specific diagnos- tic tests are central to identifying AI before a crisis occurs.
In the acutely ill patient, AI is a life-threat- ening event. Corrective therapy must be initi- ated immediately and is guided by hyponatre- mia, hyperkalemia, and hypoglycemia as well as the associated signs and symptoms. Plasma cortisol and ACTH levels may be drawn dur- ing a crisis to assist in initial diagnosis. Dur- ing a medical crisis, a serum cortisol level be- low 276 nmol/L (10 µg/dL) is suggestive of AI. A serum cortisol level below 138 nmol/L (5 µg/dL) is virtually diagnostic of AI, particu- larly when the patient is experiencing the ex- treme amount of physical stress associated with a medical crisis.15 After resolution of the crisis, a complete investigation into the etiol- ogy of it should be initiated.
If AI is suspected, the best screening tool for diagnosis is the rapid ACTH stimulation test. The test is easily performed in the inten- sive care setting and has virtually no side ef- fects. The test assesses adrenal response to excessive ACTH stimulation (Table 6).14
| Uses | To assess adrenal cortical function and screen for adrenal steroid biosynthesis abnormalities |
| Procedure | Administer 250 µg cosyntropin intravenously; at times 0, 30, and 60 min, obtain plasma for cortisol 17- hydroxypregnenolone, 17-hydroxyprogesterone, and 11-deoxycortisol |
| Normal response | If the plasma cortisol level reaches >18 µg/dL, adrenal function is adequate If steroid precursors are elevated, adrenal enzyme alterations may be present |
| Abnormal response | Adrenal insufficiency is confirmed if the response is blunted or absent |
While the rapid ACTH test is an excellent tool in identifying the presence of AI, it does not differentiate between primary and secondary. A useful test in making this distinction is the prolonged ACTH stimulation test (Table 7).14
Random serum ACTH levels are also useful in differentiating between primary and sec- ondary AI. In patients with confirmed AI, ACTH levels greater than 88 pmol/L (400 pg/ mL) are indicative of primary AI. These ele- vated ACTH levels are due to a lack of adrenal response to ACTH stimulation, resulting in increased ACTH secretion by the pituitary gland. Adrenocorticotropic hormone levels less than 11 pmol/L (50 pg/mL), in the face of AI, point to secondary AI and the asso- ciated hyposecretion of ACTH.15
THERAPEUTIC MANAGEMENT OF ADRENAL INSUFFICIENCY
Acute Adrenal Insufficiency and Adrenal Crisis
Adrenal crisis can progress rapidly. There- fore, early recognition and prompt interven- tion is essential to ensure an optimal out- come. Adrenal crisis is a medical emergency and must be treated without delay for pro- longed diagnostic testing.15 Therapy is di- rected at rapidly increasing circulating levels of cortisol and replacing extracellular volume deficit. Intravenous (IV) replacement of cor- tisol is essential as death will ensue despite symptomatic treatment for volume depletion and electrolyte imbalance.
If AI is suspected, plasma cortisol and ACTH levels may be drawn as a baseline be- fore initiating therapy. Electrolyte levels, complete blood count, glucose, blood urea nitrogen, and creatinine are obtained to as- sess for sodium depletion, potassium reten- tion, and hypoglycemia.
To correct dehydration and hypovolemia, rapid infusion of IV fluids is necessary. Nor- mal saline with 5% dextrose is the IV fluid of choice in an effort to reverse the hypoglyce- mia and dehydration. Constant and Barth4 site the infusion of only isotonic saline to replace the urinary salt losses and to support blood pressure (they recommend the use of normal saline with 5% dextrose if the patient is also hypoglycemic). The rate of IV fluid and elec- trolyte replacement depends on the severity
| Uses | To distinguish between primary and secondary adrenal insufficiency |
| Procedure | Intravenous adrenocorticotropic hormone is continuously infused over a 2- to 3-day period at a dose of 800 µg over 24 hrs; 24-hr urine collections for creatinine and 17-hydroxycorticosteroids should be collected at baseline and during the infusion |
| Normal responses | The 17-hydroxycortico- steroid value level should be increased two to three times the baseline values during the first day of the test |
| Abnormal responses | Patients with primary adrenal insufficiency will not respond to the infusion; patients with secondary adrenal insufficiency will have a blunted response on the first day of the test, followed by a continually increasing response throughout the test |
of the fluid volume deficit, the serum electro- lyte values, and the patient’s clinical response to therapy.17,23 Up to 3 L may be given in 2 to 3 hours. During a crisis, up to 20% of circulat- ing volume can be lost. This severe volume depletion can develop quickly into hypovole- mic shock with resultant tissue hypoperfu- sion and lactic acidosis.4,17 Correcting the fluid volume deficit in this case is of great importance.
For a patient with a known diagnosis of AI, hydrocortisone is given as a 100-mg IV bolus.4,15 A maintenance dose of 100 mg hy- drocortisone is given every 6 to 8 hours by IV bolus or continuous infusion.4,15-17 Since hy- drocortisone has mineralocorticoid proper- ties, a mineralocorticoid hormone replace- ment is not generally required as long as the patient is receiving IV fluids (normal saline with 5% dextrose) and the replacement hy- drocortisone.
For a patient with no documented history of AI, the administration of 4 mg dexametha-
sone as an IV bolus is recommended. Dexa- methasone does not alter or interfere with the serum cortisol levels4,15 and can be given while diagnostic testing for AI is being per- formed. A maintenance dose of dexametha- sone is given every 8 hours as either a bolus or a continuous infusion. It should be noted that dexamethasone has no aldosterone activ- ity and fludrocortisone, a mineralocorticoid, may be needed additionally. Fluid and corti- sol replacements will restore blood pressure to normal as well as correct the dysrhythmias associated with hyperkalemia; thus, vasopres- sors usually are not required. Patients usually respond quickly to the initial therapies and improvement is seen within the first several hours.
Chronic Adrenal Insufficiency
Chronic AI, resulting from destruction or permanent dysfunction of the adrenal glands, the hypothalamus, or the pituitary gland re- quires lifelong hormone replacement. In most cases of primary AI, there is a deficiency of both glucocorticoids and mineralocorti- coids. Therefore, cortisol and aldosterone need to be replaced. Glucocorticoid activity is achieved by administration of oral hydro- cortisone (cortisone acetate). The daily dose of hydrocortisone is usually 20 to 30 mg daily. This may be given in divided doses (e.g., 20 mg in the morning and 5 mg in the evening), to mimic the body’s natural diurnal pattern of cortisol secretion.4
Hydrocortisone possesses inadequate min- eralocorticoid activity for long-term replace- ment; therefore, the patient with chronic AI requires medication to replace absent miner- alocorticoids. Fludrocortisone acetate (Flor- inef, Squibb Mark, Princeton, NJ) is the drug of choice for mineralocorticoid replace- ment.4 The dose should be individualized with requirements ranging from 0.05 to 0.2 mg daily.
Mineralocorticoid activity is spared in chronic secondary AI. Therefore the patient requires only hydrocortisone replacement. Hydrocortisone replacement doses for sec- ondary AI are the same as for primary AI.
Patient education is a crucial element in the management of a patient with chronic AI. The patient will need information about life- time hormone replacement therapy as well as
information about stress doses of replace- ment therapy. The latter refers to the in- creased doses of daily replacement medica- tions necessary to respond to stresses such as surgery, infection, dental work, or childbirth. Further, instruction about self-administration of intramuscular hydrocortisone is needed for situations when the patient is unable to take the usual oral dose of hydrocortisone be- cause of nausea, vomiting, or altered menta- tion. The patient must also avoid fasting, and in the case of primary AI, the patient may need to increase dietary salt intake. An emer- gency injection kit of hydrocortisone must be carried with the patient at all times and extra kits must be kept in the car and/or at the workplace. A Medic-Alert bracelet can also be worn by the patient to ensure prompt and ap- propriate medical attention. Education of the patient’s family members and/or significant others is essential. These individuals need to be instructed about the varied manifestations of AI and in the techniques of intramuscular injection of hydrocortisone.
NURSING IMPLICATIONS
The critical care nurse plays a crucial role in the management of a patient in adrenal cri- sis. Nursing priorities are aimed at establish- ing and maintaining fluid and electrolyte bal- ance, maintaining nutritional status, and pro- viding psychologic and education support for the patient and the family. A comprehensive plan of care for the adrenal crisis patient is outlined in Table 8.
The nursing assessment of the patient’s he- modynamic status will guide therapy; there- fore, signs of fluid and electrolyte imbalance and ensuing hypovolemia must be aggres- sively monitored. Heart rate, orthostatic blood pressure changes, urine output, and the patient’s mentation are important parame- ters to monitor. For cases in which manage- ment indicates invasive hemodynamic moni- toring through a Swan-Ganz catheter, mea- surement of the pulmonary artery wedge pressure, central venous pressure, and car- diac output are essential and should be con- tinually assessed. It is important to remember that tissue signs such as decreased turgor or dry mucous membranes are not useful early indicators of volume status as these signs usually are not manifested until at least 24
| Nursing Diagnosis | Expected Outcomes | Nursing Interventions |
|---|---|---|
| Alteration in electrolyte status related to hyponatremia associated with glucocorticoid and mineralocorticoid deficiency | Serum sodium levels will be >135 mmol/L, <145 mmol/L. Serum potassium levels will be 3 to 5 mmol/L | Monitor serum electrolyte levels: assess serum potassium levels every 4 hrs and assess for signs and symptoms of hyperkalemia |
| Absence of cardiac dysrhythmias associated with hyperkalemia Fluid volume status is adaptive | Assess neuromuscular status: weakness, twitching, parasthesis, and hyperreflexia Assess cardiovascular function: dysrhythmias and bradycardia | |
| Alteration in coping related to Glucocorticoid and mineralocorticoid deficiency Overwhelming physical, emotional, and environmental stressors | Decreased level of anxiety Use of effective coping mechanisms | Maintain calm, quiet controlled environments |
| Provide simple clear instructions Instruct patient in stress- reduction techniques | ||
| Alteration in fluid volume related to renal loss of sodium and water associated with glucocorticoid and mineralocorticoid deficiency | Serum sodium will be within normal limits. Hemodynamic status will return to adaptive parameters: arterial blood pressure to baseline levels; central venous pressure to 2 to 10 mmHg; and cardiac output to 4 to 8 L Absence of orthostatic hypotension Renal perfusion will be maintained: urine output, >30 mL/hr and specific gravity, 1.010 to 1.025 Mental status will return to baseline | Continuously monitor and assess hemodynamic parameters: arterial blood pressure, peripheral pulses, central venous pressure, pulmonary capillary wedge pressure, orthostatic hypotension, and cardiac output Monitor renal status: assess urine output hourly and assess specific gravity every 4 hrs Monitor electrolyte status: assess serum sodium and serum potassium every 4 hrs Maintain fluid status: maintain intravenous fluid replacement based on assessment of hemodynamic parameters Assess for signs of fluid volume excess: hypertension, neck vein distension, pulmonary edema, peripheral edema, and signs of congestive heart failure Weigh daily |
| Alteration in nutritional status, less than body requirements, related to decreased glucose production | Blood glucose levels will be within normal limits Body weight will be stabilized and maintained | Monitor for hypoglycemia using accucheck and serum blood glucose every 4 hrs Provide adequate carbohydrate and protein intake Weigh daily |
| Knowledge deficit related to life-long management of adrenal insufficiency | Patient will verbalize understanding of daily replacement medications, intramuscular injection technique, dietary modifications, and importance of compliance | Instruct patient about glucocorticoid and mineralocorticoid replacement medications; intramuscular injection of hydrocortisone; necessary dietary modifications, such as avoiding fasting, eating frequent snacks, and increasing sodium in diet; and importance of wearing a Medic-Alert bracelet |
hours after volume depletion. Close attention must be paid to the patient’s nutritional status in an effort to assess for and correct hypogly- cemia as well as to maintain adequate caloric intake. Psychologic support for the patient is vital during this time of overwhelming physi- cal, psychologic, and environmental stress.23 Nursing interventions aimed at providing a calm and controlled environment are essen- tial. Adrenal insufficiency may be a lifelong disease. Like the person with diabetes, the AI patient needs to be thoroughly knowledge- able about daily replacement medications as well as necessary dietary modifications. Most importantly, the patient must be acutely aware of the need for compliance to avoid a life-threatening adrenal crisis.
SUMMARY
Adrenal insufficiency is a disease that pre- sents a confounding clinical picture. The var- ied etiologies of the disease as well as the nonspecific nature of the signs and symptoms of AI often delay recognition of this poten- tially life-threatening disorder. Management of AI is equally challenging. A broad array of management techniques are necessary to ef- fectively treat adrenal dysfunction. The clini- cian must be prepared to provide the inten- sive and aggressive interventions that are cru- cial during an adrenal crisis as well as to provide comprehensive patient education about the lifelong management of chronic AI.
ACKNOWLEDGMENTS
The authors acknowledge Lillie Fairchild, Head Nurse, 10 West Adult Endocrine Unit, and Linda Coe, Clinical Nurse Specialist, Clinical Center Department of Nursing, Na- tional Institutes of Health, for their support and guidance throughout this project.
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AACN Advanced Critical Care
Adrenocortical Insufficiency: A Medical Emergency Laura M. Lee and Julle Gumowski
AACN Adv Crit Care 1992;3 319-330 10.4037/15597768-1992-2005 @1992 American Association of Critical-Care Nurses Published online http://acc.aacnjournals.org/
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