EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Adrenal crisis

Abstract

Adrenal crisis is a life-threatening emergency contributing to the excess mortality of patients with adrenal insufficiency. Studies in patients on chronic replacement therapy for adrenal insufficiency have revealed an incidence of 5-10 adrenal crises/100 patient years and suggested a mortality rate from adrenal crisis of 0.5/100 patient years. Patients with adrenal crisis typically present with profoundly impaired well-being, hypotension, nausea and vomiting, and fever responding well to parenteral hydrocortisone administration. Infections are the major precipitating causes of adrenal crisis. Lack of increased cortisol concentrations during infection enhances pro-inflammatory cytokine release and sensitivity to the toxic effects of these cytokines (e.g. tumour necrosis factor alpha). Furthermore, pro-inflammatory cytokines may impair glucocorticoid receptor function aggravating glucocorticoid deficiency. Treatment of adrenal crisis is simple and highly effective consisting of i.v. hydrocortisone (initial bolus of 100 mg followed by 200 mg over 24 h as continuous infusion) and 0.9% saline (1000 ml within the first hour). Prevention of adrenal crisis requires appropriate hydrocortisone dose adjustments to stressful medical procedures (e.g. major surgery) and other stressful events (e.g. infection). Patient education is a key for such dose adjustments but current education concepts are not sufficiently effective. Thus, improved education strategies are needed. Every patient should carry an emergency card and should be provided with an emergency kit for parenteral hydrocortisone self-administration. A hydrocortisone pen would hold a great potential to lower the current barriers to hydrocortisone self-injection. Improved patient education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are expected to significantly reduce morbidity and mortality from adrenal crisis.

Adrenal Crisis: Still a Deadly Event in the 21st Century

“…42 While absorption may be reduced in a patient with shock, if more patients are able to administer hydrocortisone at an earlier time, then this may prove to be beneficial. 43 …”

Conduct protocol in emergency: Acute adrenal insufficiency

“…Other causes are displayed in Chart 1. 3,7,8,11,[16][17][18] The physician should always be alert to any changes in the vital signs of a patient with known chronic AI. Being aware and knowing how to correlate certain signs and symptoms that suggest acute AI is also necessary, as over 25% of patients with Addison's disease are diagnosed at the time of an adrenal crisis, probably triggered by a stressful event (surgery, infection or trauma).…”

“…4,16,18 Adrenal crisis should be included in the differential diagnosis when a patient enters the emergency room with hypotension that does not respond to the administration of volume or vasopressors, worsening on standing position, sometimes leading to shock, associated with nonspecific symptoms such as anorexia, nausea, vomiting, pain unexplained abdominal bloating, constipation, fever secondary to an infectious process, apathy, confusion, and drowsiness, which may progress to coma. 3,9,13,14,17,18,20 A suggestive sign of past Addison's disease, which can help make the diagnosis, is hyperpigmentation of mucous membranes and skin by melanin due to the excessive production of alpha-MSH (melanocortin stimulating hormone) derived from the same precursor protein of ACTH called POMC (pro-opiomelanocortin). This change in skin mainly affects areas exposed to the sun or pressure areas like fingers, knees, and ankles, in addition to the lips and nipples.…”

“…Importantly, administration of hypotonic solutions is contraindicated, as this would lead to dilution of natremia. 5,17,18 In this patient, glucocorticoid administration should be started:…”

“…In addition, AI can be further divided into: primary AI, known as Addison's disease, a result of destruction of 90% or more of the adrenocortical gland or conditions that involve the decreased production of adrenal steroids, resulting in subnormal synthesis of aldosterone, cortisol, and androgens; and secondary and tertiary AI, which have their pathophysiology linked to deficient secretion of cor-ticotropin (ACTH) and corticotropin releasing hormone (CRH), respectively. 2,17 ACTH is a hormone secreted by corticotropic cells of pars distalis in the hypophysis. It is upregulated by CRH, which is produced in the paraventricular nucleus of the hypothalamus (Figure 1).…”