Adrenal crisis (also known as the acute Addisonian crisis) is the most important – and potentially fatal – complication of hypoadrenalism (i.e. decreased activity of the adrenal glands). This condition develops in situations when marginally adequate adrenal reserve suddenly becomes insufficient to combat the growing needs for adrenal hormone cortisol during stress.

Adrenal crisis is a known factor that contributes to excess mortality in patients with a diagnosis of chronic adrenal insufficiency. Furthermore, research on the epidemiology of this complication reveal a consistent picture with an incidence range between five and ten adrenal crises per 100 patient/years in individuals on standard replacement therapy.

Triggers of Adrenal Crisis

Adrenal crisis is basically always precipitated by some for stress, therefore physical, traumatic, anesthetic, or emotional stress should all be taken into account as potential triggers. Nevertheless, the most notorious factor that can precipitate an adrenal crisis is the infection – even apparently simple viral infection can be responsible for this condition.

Medications can also act as triggers in certain cases. For example, the use of antibiotic rifampicin accelerates the turnover of the cortisol hormone, which can in turn precipitate decompensation in marginally compromised situations. The sudden withdrawal of steroid therapy and thyroxine therapy initiation are other examples where compromised adrenals are not able to cope adequately.

Clinical Presentation

In cases where the background of adrenocortical failure is known, the clinical presentation of adrenal crisis is easy to recognize. For example, the development of this condition in the patient with Addison disease and steroid replacement therapy is often identified – even at the very early stages of its evolution.

The syndrome usually starts with nausea, vomiting, loss of appetite, and diarrhea with unspecific abdominal cramps. Such gastrointestinal manifestations of an acute Addisonian crisis can be accompanied by fever, chills, and profuse sweating. If it remains untreated, patients eventually develop volume depletion and dehydration, which is often so severe that everything culminates in shock.
 

Pathophysiologically, there is significant hyponatremia and hyperkalemia, often associated with metabolic acidosis, hypoglycemia, and (every so often) hypercalcemia. It is important to know that hyperkalemia can be masked by diarrhea and severe vomiting, which can result in missing the diagnosis of adrenal crisis (even by highly experienced physicians).

When Adrenal Crisis is of Diagnostic Concern?

Several conditions should raise suspicion of the potential adrenal crisis in the background. First and foremost concern should be dehydration and electrolyte irregularities in patients with a medical history of ill health characterized by weakness and weight loss, but also in cases of dehydration and diarrhea with normal/elevated potassium and low sodium levels in the blood.

In addition, the unusual mix of low blood sugar in association with low blood pressure (more commonly in children), shock in the background of tuberculosis or carcinomatosis, as well as the occurrence of hyperpigmentation should strongly point to adrenal disease (and subsequently adrenal crisis) as a root of illness.

Biochemical tests that are usually ordered in order to support the diagnosis of adrenal crisis include ACTH (corticotropin) stimulation test, cortisol levels, fasting blood sugar, serum pH, as well as levels of sodium and potassium in the serum.

Treatment and Management

Suspected adrenal crisis necessitates immediate therapeutic action, which (in cases of undiagnosed adrenal insufficiency) most often precedes the biochemical proof of diagnosis. It is well known that the outcome of adrenal crisis is heavily reliant on the physician’s clinical competence and swift initiation of specific treatment, but also on the recognition of any precipitating factors.

An early administration of glucocorticoids can really make the difference between life and death, with the beneficial effects becoming evident within 24 hours of implementing such therapy. Vigorous saline infusions in combination with stress doses of hydrocortisone (100 milligrams intravenously three times a day) can rapidly resolve dehydration, electrolyte imbalances, and cortisol deficiency of adrenal crisis.

Reducing morbidity and eliminating mortality from adrenal crisis is currently a number one priority for endocrinologists dealing with adrenal disorders. Better understanding of the physiopathology of adrenal crisis in order to define optimum treatment doses and patient education are pivotal steps towards a structured, quality-controlled approach for every patient.