History

The following are important elements in the history of patients with adrenal crisis or adrenal insufficiency^{[5, 6]}:

Weakness (99%)
Pigmentation of skin (98%)
Weight loss (97%)
Abdominal pain (34%)
Salt craving (22%)
Diarrhea (20%)
Constipation (19%)
Syncope (16%)
Vitiligo (9%)

A cross-sectional study by Kawahara et al found that in adult patients presenting to a Japanese hospital’s emergency department with hypoglycemia, adrenal insufficiency was the cause in 6.1% of them. Adrenal insufficiency was the third most prominent etiology for hypoglycemia among hypoglycemic people aged 18 years or older who visited the emergency department, with antidiabetes medications (73.7%) and alcohol abuse (6.6%) being the first and second most frequent causes, respectively. The investigators also reported that hyponatremia, hypotension, and eosinophilia were found more often in association with adrenal insufficiency than with other causes of hypoglycemia. They recommended that in patients with protracted hypoglycemia of unknown etiology who also have hyponatremia, hypotension, and/or eosinophilia, a rapid adrenocorticotropic hormone (ACTH) loading test be used to evaluate adrenal function.^[15]

Physical

Physical findings in patients with adrenal insufficiency are subtle and nonspecific.

Patients with mineralocorticoid insufficiency may show signs of sodium and volume depletion (eg, orthostatic hypotension, tachycardia).
Evidence of hyperpigmentation is observed, particularly in areas exposed to the sun or areas subject to friction or pressure.

Causes

Causes and related conditions include the following:

Surgery
Anesthesia (eg, etomidate)
Volume loss (unmasks, unless there is bleeding in the adrenals)
Trauma
Asthma (steroid withdrawal)
Hypothermia (a consequence, not cause)
Alcohol (not well substantiated)
Myocardial infarction (unmasks but does not cause)
Fever/infection: In the aforementioned study from the Netherlands, Smans et al found that among patients with adrenal insufficiency, the existence of comorbidity is the most important risk factor for adrenal crisis, with infections being the most common precipitating factors^[11]
Hypoglycemia (more likely a consequence rather than cause)
Pain (unmasks, but does not cause)
Psychoses or depression (associated with, but not causative)
Exogenous steroid withdrawal

Differential Diagnoses

Ishii M. Endocrine Emergencies With Neurologic Manifestations. Continuum (Minneap Minn). 2017 Jun. 23 (3, Neurology of Systemic Disease):778-801. [QxMD MEDLINE Link]. [Full Text].
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Wyngaarden JB, Smith LH, Bennett JC. Adrenocortical hypofunction. Cecil Textbook of Medicine. 19th ed. WB Saunders; 1992. 1271-1288.
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Kawahara T, Tsuji M, Tominaga N, Toyama N, Toda M. Frequency of Adrenal Insufficiency in Patients With Hypoglycemia in an Emergency Department: A Cross-sectional Study. J Endocr Soc. 2022 Oct 1. 6 (10):bvac119. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
[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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link].
[Guideline] Simpson H, Tomlinson J, Wass J, Dean J, Arlt W. Guidance for the prevention and emergency management of adult patients with adrenal insufficiency. Clin Med (Lond). 2020 Jul. 20 (4):371-8. [QxMD MEDLINE Link]. [Full Text].
Hahner S, Allolio B. Therapeutic management of adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2009 Apr. 23(2):167-79. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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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. [QxMD MEDLINE Link].