Learning Outcome

1. Identify the range of adrenal insufficiency
2. Distinguish secondary adrenal insufficiency from tertiary adrenal insufficiency
3. Understand what system regulates mineralocorticoid levels
4. Differentiate between acute versus chronic adrenal insufficiency
5. Identify risk factors related to adrenal insufficiency
6. List presenting factors
7. Understand lab abnormalities related to adrenal insufficiency

Introduction

Adrenal insufficiency ranges from mild nonspecific symptoms to life-threatening shock condition. Adrenal insufficiency is a diagnosis that will not be made unless the clinician maintains a level of suspicion. The decreasing or suppressed adrenal function may be masked until stress or illness triggers an adrenal crisis.[1][2][3]

An important distinction in these patients is the presence of mineralocorticoid deficiency. Those with secondary or tertiary adrenal insufficiency will typically have preserved mineralocorticoid function due to the separate feedback systems. Mineralocorticoid levels are regulated by the renin-angiotensin system, independent of hypothalamic or pituitary signals.

Another important distinction is the acute versus chronic nature of the disease. Acute adrenal insufficiency patients often present in a critically ill state while chronic presentations can be insidious.

Nursing Diagnosis

• The risk for infection related to immunocompromise as evidence by fever
• The risk for volume depletion related to salt wasting as evidenced by low serum sodium
• Alteration in perfusion related to hypotension as evidenced by low blood pressure

Causes

Most cases of Addison disease are iatrogenic and caused by long-term administration of glucocorticoids, which suppress the feedback mechanisms. This suppression can be so severe that during a stress period, the brain and adrenal gland may not be able to respond adequately. Alternatively, if the exogenous glucocorticoids are discontinued without a taper, the patient may have an adrenal crisis.[4]

The most common cause of primary adrenal insufficiency relates to autoimmune damage to the adrenal cortex. Other insults to the adrenal gland that lead to primary insufficiency include adrenal hemorrhage, cancer, infections (HIV, syphilis, TB, bacterial), and certain drugs such as etomidate, ketoconazole, fluconazole, metyrapone. Phenytoin and rifampin increase the metabolism of cortisol and can, therefore, precipitate adrenal insufficiency in those predisposed.

Adrenal hemorrhage can occur in patients on anticoagulation medications or a bleeding diathesis, or in the postoperative setting. 

Primary adrenal insufficiency can also be congenital. Congenital adrenal hyperplasia has been extensively studied and described in the literature. Panhypopituitarism and many genetic conditions can cause adrenal insufficiency. Pituitary hemorrhage or infarction (Sheehan syndrome) can cause secondary adrenal insufficiency.

Risk Factors

As many as 144 million individuals in the developed world may have Addison disease. When treated properly, patients can have a roughly normal lifespan. Untreated patients have a high mortality rate.[5][6]

The autoimmune form of adrenal insufficiency and has male-female predisposition based on the type of autoimmune condition. Females are more likely to have a polyglandular form while isolated adrenal damage is more common in males in the first two decades. By the fourth decade, the isolated form is more common in women.

Due to the diverse causes of adrenal insufficiency, no distinct group of individuals is at increased risk of disease.

The epidemiology of adrenal insufficiency in children is not well-defined. Congenital adrenal hyperplasia (CAH) is the most common etiology of primary adrenal insufficiency in children, occurring once in 14,200 live births.

Assessment

Patients with adrenal insufficiency often present with hypotension, altered mental status, anorexia, vomiting, weight loss, fatigue, and recurrent abdominal pain. Reproductive complaints typically occur in women (amenorrhea, loss of libido, decreased axillary, and pubic hair). Salt craving and orthostatic hypotension are common in patients with primary adrenal insufficiency, due to the volume depletion from the reduced mineralocorticoid function. Obtaining a history of exogenous corticosteroid use is crucial in making the diagnosis, especially in cases of chronic adrenal insufficiency.

Patients may have poor skin turgor and increased skin pigmentation. Patients may also manifest neuropsychiatric signs and symptoms. One might notice signs of Cushing syndrome, such as skin atrophy, striae, edema, obesity, muscle wasting, and neuropsychiatric disturbance.

As many as half of the patients will develop shock with no preceding hypotension. Hypotension can be present in any form of adrenal insufficiency. Fever should lead to an investigation for infectious etiology, although it can be present in any form of adrenal insufficiency.

Evaluation

Diagnosis of primary adrenal insufficiency requires suspicion. Hyponatremia with hyperkalemia and hypoglycemia may be present. Serum cortisol, ACTH, renin, aldosterone, and chemistry panel should be obtained early. Serum cortisol levels can help make diagnoses in the presence of elevated ACTH and plasma renin activity. The ACTH test can be performed to determine if the cause is central or peripheral.[7]

Patients with secondary adrenal insufficiency are more likely to have hypoglycemia but will not have dehydration, hyperkalemia, or skin hyperpigmentation.

Consider testing for HIV and tuberculosis in patients with unclear etiology.

The most common laboratory findings in chronic primary adrenal insufficiency are anemia, hyponatremia, and hyperkalemia.

Medical Management

The treatment of Addison disease is glucocorticoid replacement. If the infection is the inciting event of a crisis or the cause of primary adrenal failure, it must be treated aggressively. Patients in shock will require intravenous hydration and often, dextrose.[8][9][10]

In patients with established adrenal insufficiency, hydrocortisone is the treatment of choice, with 100 mg IV every 8 hours being the standard dose. Hydrocortisone has some mineralocorticoid effect in case the patient has deficient aldosterone. In an undiagnosed patient, dexamethasone (4 mg initial bolus) should be used, as this does not interfere with cortisol assays. Mineralocorticoid replacement with fludrocortisone may be required but is not usually necessary in an acute adrenal crisis. 

If patients with adrenal insufficiency require surgery, a stress dose of glucocorticoids must be given and continued for 24 hours after the procedure.

Nursing Management

• Assess patient and check vital signs
• Gain intravenous access and start the normal saline infusion
• Monitor lab values that include complete blood count, lactate, basic metabolic panel, and arterial blood gases
• Draw blood cultures to investigate possible infection
• Monitor changes and report changes to provider
• Monitor intake and output
• Assess and maintain adequate hydration
• Administer medications as advised by the doctor
• Assess and monitor skin pigmentation

When To Seek Help

• Temperature higher than 101 F
• Weight increase >3 Ibs a day
• Persistent hypotension

Outcome Identification

• The patient does not have an infection 
• The patient does not have volume depletion or dehydration
• The patient does not have an adverse medication reaction
• The issue is resolved and the patient is restored to baseline

Monitoring

• Lab values
• Blood pressure
• Respiration
• Temperature
• Weight
• Signs and symptoms of infection
• Skin turgor and signs of dehydration
• Electrolyte imbalance
• Irregular heartbeat or dysrhythmia

Coordination of Care

Adrenal insufficiency is a life-threatening disorder that can lead to very high morbidity and mortality if not recognized. The varied presentation is best managed by a multidisciplinary team that consists of an endocrinologist, radiologist, an infectious disease specialist, intensivist, and a pharmacist. While the cause of adrenal insufficiency is being investigated, the patient should immediately be managed with corticosteroids and mineralocorticoids because even with treatment, mortality rates remain high. Once treatment is initiated, patients need close monitoring. Any type of infection or stress can precipitate adrenal crises leading to death. Hence patients should be educated about the symptoms and when to return immediately to the emergency department. Finally, all patients with a diagnosis of adrenal insufficiency should be urged to wear a medical ID bracelet.[11][12](Level V)

Health Teaching and Health Promotion

Educate the patient about illness, and how stress can alter the requirements of medications. Patients should be counseled to take medications as advised and keep an emergency contact card at all times on their mobile phones. Also, patients should be taught how to self-inject with glucocorticoids and to seek help if their blood pressure is low or if they catch any other illness.

Risk Management

• Medication - correct dose at the right time to prevent adverse effect
• Fall injury prevention
• Infection prevention
• Prevent dehydration

Discharge Planning

• Follow up visit
• Medications, when, and how to take it.
• Medication side effect and when to call the provider
• Monitor laboratory parameters as advised by the clinician
• Monitor for infection

Pearls and Other issues

As mentioned above, patients in adrenal crisis manifest nonspecific symptoms and therefore, can be difficult to diagnose. Those physicians who prescribe the glucocorticoids such as prednisone must also be aware of the need to limit the length of time the patient is on the medication and taper when discontinuing.