Adrenal Crisis in Emergency Medicine

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Adrenal crisis and severe acute adrenocortical insufficiency are often elusive diagnoses that may result in severe morbidity and mortality when undiagnosed or ineffectively treated. ^{[1, 2]}

Although it is thought by experts that more than 50 steroids are produced within the adrenal cortex, ^[3] cortisol and aldosterone are by far the most abundant and physiologically active. Regulation of the adrenal cortex is illustrated in the image below.

In primary adrenocortical insufficiency, glucocorticoid and mineralocorticoid properties are lost; however, in secondary adrenocortical insufficiency (ie, secondary to disease or suppression of the hypothalamic-pituitary axis), mineralocorticoid function is preserved.

Although suppression of the hypothalamic-pituitary axis from chronic exogenous steroid use is the most common cause of secondary adrenal insufficiency, the possibility of hypopituitarism due to hypothalamic-pituitary disease must be considered. With acute hypopituitarism, other hormone deficiencies must be identified and treated in addition to treating adrenal insufficiency with corticosteroids. For instance, if a patient with panhypopituitarism due to Sheehan syndrome (postpartum pituitary infarction) is only treated for adrenal crisis, severe cardiovascular compromise from the untreated associated hypothyroidism likely occurs. Death can result if the hypothyroid state is not diagnosed.

Every emergency physician should be familiar with adrenocortical insufficiency, which is a potentially life-threatening entity. The initial diagnosis and decision to treat are presumptive and are based on history, physical examination, and, occasionally, laboratory findings. Delay in treatment while attempting to confirm this diagnosis can result in poor patient outcomes.

Adrenal medullae normally secrete 80% epinephrine and 20% norepinephrine. Sympathetic stimulation results in secretion.

The adrenal cortex produces cortisol, aldosterone, and androgens. Cortisol is produced from 2 hydroxylations of 17alpha-hydroxyprogesterone. Cortisol, also known as hydrocortisone, is 90-93% protein bound (primarily by corticosteroid-binding globulin).

Glucocorticoids are nonspecific cardiac stimulants that activate release of vasoactive substances. In the absence of corticosteroids, stress results in hypotension, shock, and death. Glucocorticoids act as follows to:

Stimulate gluconeogenesis and decrease cellular glucose use

Mobilize amino acids and fatty acids

Inhibit the effects of insulin

Give rise to ketone bodies in metabolism (ketogenesis)

Elevate RBC and platelet levels

Exhibit anti-inflammatory effects, including the following:

Maintenance of normal vascular response to vasoconstrictors

Opposition to increases in capillary permeability

Inhibition of interleukin-2 (IL-2) production by macrophages

Stimulation of polymorphonuclear neutrophil (PMN) leukocytosis

Reduction of adherence of macrophages to endothelium

Depletion of circulating eosinophils and lymphocytes

Reduction of circulating lymphocytes (primarily T cells)

Aldosterone is produced by multiple hydroxylations of deoxycorticosterone and is normally 60% protein bound. The renin-angiotensin system stimulates aldosterone release. Increased potassium stimulates aldosterone production, and decreased potassium inhibits production. Chronic adrenocorticotropic hormone (ACTH) deficiency may inhibit production.

The primary actions of aldosterone cause the kidneys, gut, and salivary/sweat glands to affect electrolyte balance. The primary targets are the kidneys; where it stimulates reabsorption of sodium and secretion of potassium and hydrogen ions. The kidneys’ effect on sodium and potassium depend on the intake of these cations (ie, increased sodium intake = increased potassium secretion). The effects on hydrogen probably can occur independently.

Persistent aldosterone excess results in atrial natriuretic factor release and renal hemodynamic changes for compensation. Congestive heart failure (CHF) and cirrhosis with ascites are exceptions that cause progressive sodium retention. Excess aldosterone results in sodium retention, hypokalemia, and alkalosis. Aldosterone deficiency results in sodium loss, hyperkalemia, and acidosis. Hyperkalemia stimulates aldosterone release to improve potassium excretion. Aldosterone is the first-line defense against hyperkalemia.

Primary adrenal insufficiency, which can be acute or chronic, may be caused by the anatomic destruction of the gland. This destruction can have various causes, including tuberculosis or fungal infection, other diseases infiltrating the adrenal glands, and hemorrhage. However, the most frequent cause is idiopathic atrophy, which is probably autoimmune in origin.

Primary adrenal insufficiency also may be caused by metabolic failure (eg, insufficient hormone production). This failure may be a result of congenital adrenal hyperplasia (CAH), enzyme inhibitors (eg, metyrapone), or cytotoxic agents (eg, mitotane).

Primary adrenocortical insufficiency is rare and occurs at any age. The male-to-female ratio is 1:1.

A retrospective study by Rushworth et al indicated that in pediatric patients with CAH, adrenal crises occur mostly in younger children. The study, which evaluated 573 admissions for medical problems in youngsters with CAH, found that 21 of 37 adrenal crises occurred in patients aged 1-5 years, with another six in children aged up to 1 year. ^[4]

A Japanese study reported that in children under age 7 years with 21-hydroxylase deficiency, a cause of CAH, the incidence of adrenal crisis was 10.9 cases per 100 person-years. ^[5]

Secondary adrenal insufficiency may be caused by hypopituitarism due to hypothalamic-pituitary disease or may result from suppression of the hypothalamic-pituitary axis by exogenous steroids or endogenous steroids (ie, tumor).

Secondary adrenocortical insufficiency is relatively common. Extensive therapeutic use of steroids has greatly contributed to increased incidence.

Adrenal crisis may result from an acute exacerbation of chronic insufficiency, ^[6] usually caused by sepsis or surgical stress. Acute adrenal insufficiency also can be caused by adrenal hemorrhage (eg, usually septicemia-induced Waterhouse-Friderichsen syndrome [fulminant meningococcemia]) and anticoagulation complications. Steroid withdrawal is the most common cause of acute adrenocortical insufficiency and almost exclusively causes a glucocorticoid deficiency.

United States

Primary adrenocortical insufficiency is an uncommon disorder with an incidence in Western populations near 50 cases per 1,000,000 persons. With the advent of widespread corticosteroid use, however, secondary adrenocortical insufficiency due to steroid withdrawal is much more common. Approximately 6,000,000 persons in the United States are considered to have undiagnosed adrenal insufficiency, which is clinically significant only during times of physiologic stress.

Primary adrenocortical insufficiency has multiple etiologies; however, 80% of cases in the United States are caused by autoimmune adrenal destruction. Glandular infiltration by tuberculosis is the second most frequent etiology.

In patients with primary adrenocortical insufficiency due to idiopathic autoimmune lymphocytic infiltration, the presence of other associated endocrine disorders must be entertained. Consider polyglandular autoimmune disorders (PGAs) such as Schmidt syndrome.

Schmidt syndrome (PGA type II) includes adrenal insufficiency, autoimmune thyroid disease, and, occasionally, insulin-dependent diabetes mellitus. Adrenal insufficiency usually occurs in these patients when they are older than 20 years. In approximately 40-50% of patients with PGA II, the first manifestation of the syndrome is adrenal insufficiency.

PGA type I includes hypoparathyroidism and mucocutaneous candidiasis in conjunction with adrenal insufficiency. The full triad may manifest in approximately 30% of patients with PGA type I.

International

In a study from the Netherlands, Smans et al found evidence that in primary and secondary adrenal insufficiency, the incidence rate of adrenal crisis per 100 person-years is 5.2 and 3.6, respectively. ^[7]

A study by Notter et al found that among Swiss patients with primary or secondary adrenal insufficiency, 4.4 adrenal crises per 100 disease-years occurred. ^[8]

Acute adrenocortical insufficiency is a difficult diagnosis to make. The disorder rarely occurs without concomitant injury or illness. Many of the presenting signs and symptoms are nonspecific. For instance, a postoperative fever may presumptively be treated as infection or systemic inflammatory response syndrome when it may be a subtle indicator of adrenal insufficiency.

Left untreated, a patient with acute adrenal insufficiency has a dismal prognosis for survival. Therefore, treatment upon clinical suspicion is mandatory. Any delay in management while waiting for diagnostic confirmation cannot be justified. ^[9]

A Japanese study, by Ono et al, indicated that among patients with adrenal crisis, the risk of death is relatively high in those who are older and have impaired consciousness and diabetes mellitus. In the study, of 799 patients with adrenal crisis and concomitant primary or secondary adrenal insufficiency at hospital admission, 2.4% (19) suffered in-hospital mortality, including 15 who were older than 60 years, 12 who had impaired consciousness at admission, and 13 who received insulin therapy. ^[10]

Although primary adrenocortical insufficiency affects men and women equally, women are affected 2-3 times more often by the idiopathic autoimmune form of adrenal insufficiency.

In idiopathic autoimmune adrenal insufficiency, the diagnosis is most often discovered in the third to fifth decades of life; however, it is particularly important to recognize that adrenocortical insufficiency is not limited to any specific age group.

Ishii M. Endocrine Emergencies With Neurologic Manifestations. Continuum (Minneap Minn). 2017 Jun. 23 (3, Neurology of Systemic Disease):778-801. [Medline]. [Full Text].

Alghoula F, Jeong JM. Adrenal Crisis. 2018 Jan. [Medline]. [Full Text].

Wyngaarden JB, Smith LH, Bennett JC. Adrenocortical hypofunction. Cecil Textbook of Medicine. 19th ed. WB Saunders; 1992. 1271-1288.

Rushworth RL, Falhammar H, Munns CF, Maguire AM, Torpy DJ. Hospital Admission Patterns in Children with CAH: Admission Rates and Adrenal Crises Decline with Age. Int J Endocrinol. 2016. 2016:5748264. [Medline]. [Full Text].

Ishii T, Adachi M, Takasawa K, et al. Incidence and Characteristics of Adrenal Crisis in Children Younger than 7 Years with 21-Hydroxylase Deficiency: A Nationwide Survey in Japan. Horm Res Paediatr. 2018. 89 (3):166-71. [Medline].

Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency – the need for new prevention strategies. Eur J Endocrinol. 2009 Dec 2. [Medline].

Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan. 84 (1):17-22. [Medline].

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 Med Wkly. 2018. 148:w14586. [Medline]. [Full Text].

Quinkler M, Ekman B, Zhang P, Isidori AM, Murray RD, EU-AIR Investigators. Mortality data from the European Adrenal Insufficiency Registry-Patient characterization and associations. Clin Endocrinol (Oxf). 2018 Jul. 89 (1):30-5. [Medline].

Ono Y, Ono S, Yasunaga H, Matsui H, Fushimi K, Tanaka Y. Clinical features and practice patterns of treatment for adrenal crisis: a nationwide cross-sectional study in Japan. Eur J Endocrinol. 2017 Mar. 176 (3):329-37. [Medline].

Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 Mar. 162(3):597-602. [Medline].

Ahi S, Esmaeilzadeh M, Kayvanpour E, Sedaghat-Hamedani F, Samadanifard SH. A bulking agent may lead to adrenal insufficiency crisis: a case report. Acta Med Iran. 2011. 49(10):688-9. [Medline].

Lundy JB, Slane ML, Frizzi JD. Acute adrenal insufficiency after a single dose of etomidate. J Intensive Care Med. 2007 Mar-Apr. 22(2):111-7. [Medline].

[Guideline] Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008 Jun. 36(6):1937-49. [Medline].

[Guideline] Arlt W, Society for Endocrinology Clinical Committee. SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients. Endocr Connect. 2016 Sep. 5 (5):G1-G3. [Medline]. [Full Text].

[Guideline] Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Crit Care Med. 2017 Sep 21. [Medline].

Hahner S, Allolio B. Therapeutic management of adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2009 Apr. 23(2):167-79. [Medline].

Duclos M, Guinot M, Colsy M, Merle F, Baudot C, Corcuff JB, et al. High risk of adrenal insufficiency after a single articular steroid injection in athletes. Med Sci Sports Exerc. 2007 Jul. 39(7):1036-43. [Medline].

Lelubre C, Lheureux PE. Epigastric pain as presentation of an addisonian crisis in a patient with Schmidt syndrome. Am J Emerg Med. 2008 Feb. 26(2):251.e3-4. [Medline].

Puar TH, Stikkelbroeck NM, Smans LC, Zelissen PM, Hermus AR. Adrenal crisis: still a deadly event in the 21st century. Am J Med. 2015 Sep 9. [Medline].

Hahner S, Hemmelmann N, Quinkler M, Beuschlein F, Spinnler C, Allolio B. Timelines in the management of adrenal crisis – targets, limits and reality. Clin Endocrinol (Oxf). 2015 Apr. 82 (4):497-502. [Medline].

Kevin M Klauer, DO, EJD, FACEP Assistant Clinical Professor, Michigan State University College of Osteopathic Medicine; Chief Medical Officer, Emergency Medicine Physicians, Ltd; Director, Center for Emergency Medical Education; Medical Editor-in-Chief, ACEP Now; Former Editor-in-Chief, Emergency Physicians Monthly

Kevin M Klauer, DO, EJD, FACEP is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Howard A Bessen, MD Professor of Medicine, Department of Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Program Director, Harbor-UCLA Medical Center

Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.

Adrenal Crisis in Emergency Medicine

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