Acute adrenal insufficiency (ORPHA:95409)
A primary adrenal insufficiency caused by a sudden defective production of adrenal steroids (cortisol and aldosterone). It represents an emergency, thus the rapid recognition and prompt therapy are critical for survival even before the diagnosis is made.
Epidemiology
Acute adrenal insufficiency (AAI) exact prevalence is unknown.
Clinical description
The disease may occur at any age. The onset is often sudden. The initial presentation may be non specific and may be limited to abdominal pain, nausea, vomiting, weight loss, tachycardia, and fever. Asymptomatic hypoglycemia, Hypoglycemic seizures or symptoms of dehydration are common manifestations seen in children. If untreated, shock and bilateral adrenal hemorrhage can rapidly lead to death.
Etiology
Steroid withdrawal is the most common cause of AAI in patients with chronic adrenal insufficiency. A precipitating illness (severe infection, acute myocardial infarction, stroke), surgery without adrenal support, pregnancy, any acute or chronic disease, or acute trauma are other potential causes of an acute adrenal crisis. AAI may result from an acute exacerbation of chronic primary adrenal insufficiency (CPAI). Adrenal destruction may be associated with autoimmune adrenalitis (Addison disease), isolated or in the context of autoimmune polyendocrinopathy type 1, 2 or 4. It can also be caused by medications that reduce steroid metabolism for patients with tuberculosis, opportunistic mycoses and viral infections in immunocompromised patients and adrenal metastases. Adrenal destruction may occur in the absence of CPAI history and may be due to bilateral massive adrenal hemorrhage (BMAH) as seen in Waterhouse-Friderichsen syndrome. AAI may also result from corticotroph insufficiency, either isolated or more often resulting from complete anterior pituitary insufficiency. Chronic glucocorticoid therapy (exogenous steroid such oral prednisolone or inhaled steroid) is also a cause of adrenal insufficiency (secondary adrenal insufficiency). Abrupt withdrawal of treatment may result in acute adrenal insufficiency.
Diagnostic methods
The clinical signs are nonspecific but the diagnosis of AAI is suspected if a patient presents with hypotonia or shock that responds poorly to catecholamines. Laboratory exams show signs of adrenal insufficiency (hypoglycemia, hyponatremia and elevated natriuresis, hyperkaliemia, hemoconcentration, metabolic acidosis and functional renal failure) confirmed by hypocortisolemia, increased ACTH (Adreno CorticoTropic Hormone), and an insufficient response to rapid ACTH stimulation testing that leads to the diagnosis of absolute and peripheral AAI. The mineralocorticoid insufficiency, when present, can be confirmed by low aldosterone levels and high plasma renin activity (PRA). The etiological diagnosis is based on various imaging exams (CT-scan, ultrasound, or MRI). In case of anterior pituitary insufficiency, ACTH is low.
Differential diagnosis
Secondary adrenal insufficiency needs to be eliminated. Peritonitis is often a differential diagnosis as well as other causes of adrenal destruction such as bilateral adrenalectomy, Waterhouse-Friderichsen syndrome, autoimmune adrenalitis, infectious adrenalitis.
Management and treatment
Immediate treatment in an intensive care unit is necessary. Administration of 100 mg hydrocortisone i.v. (followed by 100-200 mg over 24 hours) combined with fluid resuscitation (1L saline solution during first hour, 500ml during second hour) is the standard treatment for an adrenal crisis. In children the dosage is based on 2 mg/kg/every 6 hours and hydroelectrolytic re-equilibration based on 3l/m2/d. During this time cardiac monitoring is essential. Antibiotics, vasopressors, heparin, packed red blood cells, platelets, cryoprecipitates and fresh frozen plasma are also administered if needed. Preventive strategies include dosage increase of oral steroid hormones during times of stress in those with CPIA or intramuscular, intraveinous or sub cutaneous injection. Patients and their families should also be educated on what to do during an adrenal crisis.
Prognosis
Prognosis varies depending on the etiologies, but is generally correlated with the rapidity of diagnosis and medical assistance. Death is rare when the patients receive appropriate medical assistance.

                            Last update: 
                            December 2019


                            - Expert reviewer(s): 
                            Pr Juliane LEGER