Adrenal Crisis


Article Author:
Faysal Alghoula


Article Editor:
Jordan Jeong


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
11/14/2018 2:38:00 PM

Introduction

Adrenal crisis is an acute life-threatening condition precipitated by an internal or external process in the setting of known or unknown adrenal insufficiency and corticosteroid deficiency. It is important to note that there is a difference between adrenal insufficiency and adrenal crisis. Addison's disease, among other causes, is characterized by long-term adrenal insufficiency, whereas adrenal crisis is an acute process that can present with symptoms such as abdominal pain, vomiting, fever, weakness, among others. However, it is most notably accompanied by cardiovascular collapse with patients found to be in acute distress. While this disease is well described, it is often difficult to recognize, and treatment initiation may be delayed leading to notable morbidity and mortality.[1][2][3]

Etiology

Adrenal crisis can be precipitated by many things ranging from infections and trauma, to pregnancy, surgery, and medications, with a common direct etiology being a gastrointestinal (GI) illness. However, regardless of the etiology, the adrenal crisis is an acute complication of adrenal insufficiency. There are several causes of adrenal insufficiency which can be broken down into primary, secondary, tertiary as well as glucocorticoid-induced. While the most common cause of the adrenal crisis is a sudden withdrawal of long-term corticosteroid therapy (usually greater than 4 weeks), there are many other clinically important and often missed etiologies that can lead to significant mortality. Primary causes can be simplified to include etiologies that affect the adrenal gland directly, most notably Addison's disease, which can involve the autoimmune destruction of the adrenal gland. Other primary causes can include surgical removal, congenital adrenal disorders and in the setting of meningitis, Waterhouse-Friderichsen Syndrome. Secondary causes of adrenal insufficiency are due to a disruption of the regulation of cortisol usually from the compromise of the pituitary gland which produces ACTH, which stimulates cortisol release from the adrenal gland. This can occur from pituitary tumors, pituitary apoplexy, Sheehan syndrome in pregnancy, etc. Tertiary causes refer to disruption of the hypothalamus which in turn affects ACTH release.[4][5]

Epidemiology

It is difficult to determine the exact frequency of adrenal crisis in the general population as there is much variability in recognition and diagnosis, but studies focusing on known adrenal insufficiency report anywhere from 5 to 10 cases per 100 patient years. Some of these studies also showed an increased risk of adrenal crisis in the elderly (older than 60 years old) and patients with thyroid or other endocrine disorders. One study reported a higher incidence of the crisis in females (62.5%), but this varies with other studies which show a similar distribution between men and women.[6][7]

Pathophysiology

The adrenal glands produce both aldosterone and cortisol while ACTH from the pituitary stimulates cortisol release from the adrenal glands. Based on the underlying reason for insufficiency (primary vs. secondary) there will be deficiencies in either both mineralocorticoids (aldosterone) and glucocorticoids (cortisol) or simply a deficiency in glucocorticoids alone.  Aldosterone aids in sodium retention and potassium secretion and cortisol promotes gluconeogenesis, increases sensitivity to catecholamines, and regulates the immune system. If a patient with primary insufficiency has an adrenal crisis, they may be found to be hyponatremic and hyperkalemic in addition to having hypoglycemia and hypotension due to both aldosterone and cortisol deficiency, respectively. Patients with isolated cortisol deficiency may have only hypoglycemia due to impaired gluconeogenesis and hypotension due to decreased sensitivity to catecholamines. This is why hypotension is often refractory to vasopressors. Stressors that precipitate adrenal crisis also release inflammatory cytokines. Cortisol works to regulate these cytokines. One cytokine, tumor necrosis factor alpha, can promote cortisol resistance. Cortisol will work to suppress this in the acute phase, but when there is a deficiency of cortisol, then tumor necrosis factor (TNF)-alpha release and sensitivity increase leading to further cortisol resistance. This may explain mortality in the setting of adrenal crisis despite appropriate treatment, especially when treatment or recognition is delayed.[8][9]

Histopathology

The histology of the adrenal gland will depend on the cause of the crisis. in most cases, there is bilateral adrenal hemorrhage. 

History and Physical

Patients with adrenal crisis usually present with an unexplained shock which is refractory to vasopressors and fluids. An extensive history should be obtained to determine the etiology of these findings. There are many causes of the acute adrenal crisis in patients with no underlying adrenal insufficiency, and an adequate history may reveal the diagnosis in these challenging patients. In regards to the physical exam, some of the more common findings may include altered mental status, nausea, vomiting, abdominal pain, diarrhea, fever, and fatigue, with hypotension being the most significant. Recognizing these symptoms will further clue you into a potential diagnosis. It is important to ascertain whether or not the patient in question has any history of long-term steroid use as abrupt cessation or an acute process such as trauma or infection may be the precipitating factor in these patients. Pregnant patients, patients with meningitis and patients with a headache and vision changes represent a small subset of patients that may present with occult adrenal crisis secondary to Sheehan syndrome, Waterhouse-Friedrichsen syndrome, and pituitary apoplexy respectively. Patients with pituitary apoplexy may present with a headache and bitemporal hemianopsia in addition to signs of adrenal crisis.

Evaluation

Classic lab features may reveal hyponatremia, hyperkalemia, and/or hypoglycemia. Other lab tests may also help to reveal the underlying cause of the concomitant adrenal crisis. In patients with known adrenal insufficiency, you may be able to use laboratory findings to distinguish between primary and secondary causes.  Patients with primary adrenal insufficiency may be hyponatremic, hyperkalemic, and hypoglycemic due to both aldosterone and cortisol deficiency. Patients with secondary adrenal insufficiency may only be hypoglycemic due to impaired gluconeogenesis, but there is some variability overall as this is rare. In patients where the diagnosis of adrenal crisis is not clear, there are confirmatory tests that may be done, but this should not take precedence over empiric treatment in suspected cases. An ACTH stimulation test would confirm the diagnosis but should not be done in the acute setting. Several labs such as ACTH, serum cortisol, and aldosterone can be drawn before the administration of hydrocortisone for review at a later time. In some cases a random cortisol level before administration may exclude or support the diagnosis of adrenal insufficiency and crisis; however, this should not prevent administration of glucocorticoids when the picture is not clear.[1][10][11]

Treatment / Management

The definitive treatment of adrenal crisis is the administration of glucocorticoids, specifically hydrocortisone. The dose is 100 mg intravenously or intramuscularly (IV/IM) as an initial bolus followed by 100 to 300 mg daily after that. At this dosage, hydrocortisone will also provide sufficient mineralocorticoid coverage as well. While hydrocortisone is the preferred treatment, administration of prednisolone or methylprednisolone, and dexamethasone has been described. In addition to medical therapy, these individuals also require aggressive fluid and vasopressor management. A thorough search should also be made for the cause, and empiric antibiotics are recommended. Close monitoring in the intensive care unit (ICU) is required.[12][13][14]

Differential Diagnosis

Because the adrenal crisis is rarely an independent process, the differential diagnosis may be very broad depending on the presentation and underlying etiology. While altered mental status, abdominal pain, nausea vomiting, fever, among others are all common presenting symptoms. Hypotension is usually the most significant. In a patient with these symptoms and known adrenal insufficiency, adrenal crisis should be the top differential. However, there should be further investigation to determine the precipitating cause of the adrenal crisis whether that is sepsis, infection, trauma, physical or emotional stress, myocardial infarction, and so forth. In a patient with no known adrenal pathology who presents with hypotension that is refractory to fluid administration, vasopressor support, and appropriate management otherwise, the diagnosis of adrenal crisis should be considered and adequately ruled out.

Prognosis

Adrenal crisis is not a common event, but when it does occur it can carry a high mortality. However, because of the variability in the precipitating events and underlying disease processes which can lead to misdiagnosis, rates of death are difficult to estimate accurately. One study focusing on patients with known adrenal insufficiency reported that as high as 25% of patients die from an adrenal crisis. Prompt recognition and treatment of both the underlying condition and adrenal crisis may lead to clinical improvement, but in many cases, mortality remains high. However, a Japanese study looking at an adrenal crisis in patients with known insufficiency found a mortality rate of closer to 3% while a German study was just over 6%. In the Japanese study older age, concomitant endocrine disorders and impaired level of consciousness was associated with increased mortality.

Complications

Even with proper recognition and treatment, adrenal crisis may result in death. Other complications may include seizures, arrhythmias, coma, etc. due to electrolyte abnormalities such as hyponatremia, hyperkalemia, and hypoglycemia. Hypotension may lead to hypoperfusion and organ failure as well. However, many other complications may arise secondary to the precipitating disease or event.

Consultations

A critical care evaluation and consultation is needed in these patients as many of them will present with hypotension, altered mental status, and cardiovascular collapse. The severity of their presentations will often necessitate a higher level of care and monitoring which may include vasopressors, fluids, antibiotics and further management depending on the precipitating etiology of the adrenal crisis. Once the diagnosis of adrenal crisis is suspected, an endocrinology consultation should be obtained to confirm the diagnosis or to tailor the proper administration of corticosteroids further as well as to manage any underlying endocrine disorders.

Deterrence and Patient Education

Patient education is imperative in preventing an adrenal crisis in those patients with and without the underlying adrenal disease. Because one of the most common causes of the adrenal crisis is the withdrawal of exogenous corticosteroids, patients who are taking long-term steroids for other diseases (i.e., asthma, COPD, autoimmune disorders) should be properly counseled on the dangers of abrupt cessation. These patients should also be educated on the importance of tapering when coming off these medications as well as dose management during episodes of physical stress such as acute illness, surgeries, and trauma. The latter is also extremely important in patients with known adrenal insufficiency. These patients depend heavily on exogenous corticosteroids to maintain their baseline health and they must be extensively educated to monitor for any aberrations and adjust their doses appropriately. Patients will need to give themselves "stress doses" in these situations which usually involves an increase in their oral daily dose. This is most commonly done in the setting of acute trauma, surgery, infection, and stress. Doing so will decrease the risk of these patients progressing to adrenal crisis. In situations where the patient cannot adequately adjust their dose due to decreased oral tolerability or intestinal absorption (i.e. gastroenteritis), patients can be educated to self-administer injectable corticosteroids. Patients should also be well informed regarding the signs and symptoms of adrenal crisis so that they may self-administer injectable hydrocortisone as well. These emergency situations can be somewhat analogous to the self-administration of epinephrine in patients with anaphylaxis. Medical alert bracelets in certain cases may be beneficial as well.

Pearls and Other Issues

An adrenal crisis should be suspected in patients presenting with acute shock that that is refractory to adequate fluid resuscitation and vasopressors.

Adrenal crisis may be found more often in the elderly and those with other endocrine disorders. Patients with altered mental status and concomitant endocrine disorders may be at risk for higher mortality.

Hyponatremia, hyperkalemia, and/or hypoglycemia may be clues toward a possible diagnosis of adrenal crisis especially in the setting of hypotension.

Hydrocortisone 100 mg IV/IM is the mainstay of treatment and should be given immediately when suspecting adrenal crisis.

Pregnant patients, patients with meningitis and patients with a headache and vision changes represent a small subset of patients that may present with an occult adrenal crisis.

Enhancing Healthcare Team Outcomes

Adrenal crisis is a life-threatening condition that can affect many organ systems. Hence, the disorder is managed by a multidisciplinary team that includes an intensivist, endocrinologist, radiologist, ICU nurse, pharmacist, and the primary care provider. Once the condition is diagnosed, the patient must be educated about the disease and its potential complications. The patient should be instructed to drink ample fluids and avoid exposure to infectious disorders like chickenpox and measles. If the patient develops nausea, vomiting or fatigue, he or she must see a healthcare provider immediately. The pharmacist should educate the patient on the importance of compliance with the corticosteroids and what adverse effects to watch out for.  Finally, all patients diagnosed with an adrenal crisis should be encouraged to wear and ID bracelet indicating the disorder. [15][16](Level V)

Outcomes

Once an adrenal crisis occurs, data show that despite the replacement of the steroids, the majority of patients have a poor quality of life. Symptoms like fatigue, depression, anxiety and inability to cope are common. Many patients remain disabled and are no longer able to work. In addition, if the cause is due to secondary adrenal insufficiency, this is also associated with an increase in mortality. The cause of the mortality remains unclear, but it is most likely due to respiratory infections, adverse cardiovascular events, and stroke. [1][17](Level V)

 


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Adrenal Crisis - Questions

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In a patient with adrenal crisis post adrenalectomy, which of the following is least likely?



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An elderly diabetic with steroid-dependent asthma undergoes bowel surgery. She is admitted to the intensive care unit in critical condition and requires pressors and mechanical ventilation. On postoperative day three, she develops a fever of 39.2 C, hypotension, and lethargy. Her laboratory values indicate hypoglycemia and hyperkalemia. Which of the following explains her situation?



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Which statement regarding adrenal crisis is false?



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Which is part of management of acute adrenal insufficiency?



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Which is the least likely to cause adrenal crisis?



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Which of the following is not a stressor that can induce adrenal crisis?



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What action should be taken in the emergency room if a patient is suspected to be at risk for adrenal crisis?



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A patient is admitted for the treatment of an acute adrenal crisis. What finding would indicate the patient is responding to treatment?



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A 17-year-old female is brought to the emergency department by emergency medical services. She is too delirious to give a history but alert enough to complain of stomach pain. She is noted to be hypotensive and tachycardic. She is afebrile. Her exam is unremarkable except for dry mucous membranes. Intravenous fluids are started. Serum chemistry shows that the potassium is elevated and sodium is decreased. Blood glucose is borderline decreased. The electrolytes are otherwise within normal limits. A CBC is unremarkable. After 3 liters of fluids, the patient is still hypotensive. What is the definitive treatment for this patient's condition?



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A patient with Addison disease may experience an acute adrenal crisis. What signs and symptoms listed may appear in a patient in acute adrenal crisis? Select all that apply.



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A patient with rheumatoid arthritis undergoes an emergency appendectomy. Postoperatively, the patient's blood pressure is 86/58 mmHg with a respiratory rate of 6 breaths per minute. What could have been given preoperatively to prevent this presentation?



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Adrenal Crisis - References

References

Rushworth RL,Torpy DJ,Stratakis CA,Falhammar H, Adrenal Crises in Children: Perspectives and Research Directions. Hormone research in paediatrics. 2018     [PubMed]
Fischli S, [CME: Adrenal Insufficiency]. Praxis. 2018 Jun     [PubMed]
Hahner S, Acute adrenal crisis and mortality in adrenal insufficiency: Still a concern in 2018! Annales d'endocrinologie. 2018 Jun     [PubMed]
Ishii T,Adachi M,Takasawa K,Okada S,Kamasaki H,Kubota T,Kobayashi H,Sawada H,Nagasaki K,Numakura C,Harada S,Minamitani K,Sugihara S,Tajima T, Incidence and Characteristics of Adrenal Crisis in Children Younger than 7 Years with 21-Hydroxylase Deficiency: A Nationwide Survey in Japan. Hormone research in paediatrics. 2018     [PubMed]
Anand G,Beuschlein F, MANAGEMENT OF ENDOCRINE DISEASE: Fertility, pregnancy and lactation in women with adrenal insufficiency. European journal of endocrinology. 2018 Feb     [PubMed]
Meyer G,Badenhoop K, [Addisonian Crisis - Risk Assessment and Appropriate Treatment]. Deutsche medizinische Wochenschrift (1946). 2018 Mar     [PubMed]
Chabre O,Goichot B,Zenaty D,Bertherat J, Group 1. Epidemiology of primary and secondary adrenal insufficiency: Prevalence and incidence, acute adrenal insufficiency, long-term morbidity and mortality. Annales d'endocrinologie. 2017 Dec     [PubMed]
Cutright A,Ducey S,Barthold CL,Kim J, Recognizing and managing adrenal disorders in the emergency department [digest]. Emergency medicine practice. 2017 Sep 22     [PubMed]
Burger-Stritt S,Hahner S, [Adrenal crisis]. Der Internist. 2017 Oct     [PubMed]
Notter A,Jenni S,Christ E, Evaluation of the frequency of adrenal crises and preventive measures in patients with primary and secondary adrenal insufficiency in Switzerland. Swiss medical weekly. 2018     [PubMed]
Cutright A,Ducey S,Barthold CL, Recognizing and managing adrenal disorders in the emergency department Emergency medicine practice. 2017 Sep     [PubMed]
Yamamoto T, LATENT ADRENAL INSUFFICIENCY: CONCEPT, CLUES TO DETECTION, AND DIAGNOSIS. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2018 Aug     [PubMed]
Reznik Y,Barat P,Bertherat J,Bouvattier C,Castinetti F,Chabre O,Chanson P,Cortet C,Delemer B,Goichot B,Gruson D,Guignat L,Proust-Lemoine E,Sanson MR,Reynaud R,Boustani DS,Simon D,Tabarin A,Zenaty D, SFE/SFEDP adrenal insufficiency French consensus: Introduction and handbook. Annales d'endocrinologie. 2018 Feb     [PubMed]
Husebye ES,Allolio B,Arlt W,Badenhoop K,Bensing S,Betterle C,Falorni A,Gan EH,Hulting AL,Kasperlik-Zaluska A,Kämpe O,Løvås K,Meyer G,Pearce SH, Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. Journal of internal medicine. 2014 Feb     [PubMed]
Guignat L, Therapeutic patient education in adrenal insufficiency. Annales d'endocrinologie. 2018 Jun     [PubMed]
Burger-Stritt S,Kardonski P,Pulzer A,Meyer G,Quinkler M,Hahner S, Management of adrenal emergencies in educated patients with adrenal insufficiency-A prospective study. Clinical endocrinology. 2018 Jul     [PubMed]
Johannsson G,Falorni A,Skrtic S,Lennernäs H,Quinkler M,Monson JP,Stewart PM, Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy. Clinical endocrinology. 2015 Jan     [PubMed]

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