Primary adrenal insufficiency (Addison's disease) is due to adrenocortical disease, while secondary and tertiary adrenal insufficiency are due to disorders of the pituitary gland (corticotropin [ACTH] secretion) or the hypothalamus (corticotropic-releasing hormone secretion), respectively. Primary adrenal insufficiency is associated with both cortisol and mineralocorticoid deficiency. In contrast, secondary and tertiary adrenal insufficiency are associated with cortisol, but not mineralocorticoid deficiency, because aldosterone is regulated primarily by the renin-angiotensin system, which is independent of the hypothalamus and pituitary. This distinction accounts for the different clinical presentation and management of these disorders.
The management of all forms of adrenal insufficiency is reviewed here. The causes, clinical manifestations, and diagnosis of adrenal insufficiency in adults are reviewed separately. (See "Causes of primary adrenal insufficiency (Addison's disease)" and "Clinical manifestations of adrenal insufficiency in adults" and "Diagnosis of adrenal insufficiency in adults".)
Adrenal crisis refers to acute adrenal insufficiency; it is most common in patients with primary adrenal insufficiency, but may also occur in those with secondary or tertiary adrenal insufficiency. It is a life-threatening emergency that requires immediate treatment (table 1).
In patients with primary adrenal insufficiency, the major clinical features of adrenal crisis are volume depletion and hypotension, resulting mainly from mineralocorticoid deficiency.
While secondary or tertiary adrenal insufficiency (isolated glucocorticoid deficiency) does not lead to volume depletion, it decreases vascular tone, which leads to hypotension. Thus, adrenal crisis occurs less frequently in patients with secondary or tertiary adrenal insufficiency. When they do have adrenal crisis, it tends to be during acute stress, or with acute cortisol deficiency due to pituitary infarction or after surgical cure of Cushing's syndrome. (See "Clinical manifestations of adrenal insufficiency in adults", section on 'Pituitary apoplexy'.)