Adrenocortical insufficiency

Learning objectives

The adrenal glands of patients with adrenocortical insufficiency do not produce adequate levels of steroid hormones (i.e., glucocorticoids [cortisol), mineralocorticoids [aldosterone], and androgens)
These hormones play an important role in blood pressure homeostasis, electrolyte and fluid balance, and metabolism

Type	Mechanism
Primary adrenal insufficiency (Addison’s disease)	Deficient glucocorticoid secretion by the adrenal glands. The adrenal glands are directly affected, thus mineralocorticoid production is also reduced.
Secondary adrenal insufficiency	Deficient adrenocorticotropin hormone (ACTH) secretion by the pituitary gland and subsequent decreased adrenal stimulation. The adrenal glands are not directly affected, thus mineralocorticoid production is minimally impacted.
Tertiary adrenal insufficiency	Deficient corticotropin-releasing hormone (CRH) secretion by the hypothalamus, causing a downstream reduction in ACTH production and subsequently decreased adrenal stimulation. The adrenal glands are not directly affected, thus mineralocorticoid production is minimally impacted.

Acute condition (Addisonian crisis): Abdominal pain, vomiting, dehydration, and hypotension (particularly postural)
Chronic condition: Insidious onset with fatigue, anorexia, weight loss, and postural hypotension (salt and water loss)
Increased pigmentation
Hypoglycemia
Hyponatremia
Hyperkalemia
Raised serum urea
Disorientation
Weakness
Dizziness
Cardiovascular collapse
Muscle and joint pain
Nausea, vomiting, diarrhea

Addisonian crisis: Life-threatening situation resulting in hypotension, hypoglycemia, and hyperkalemia requiring emergency treatment (i.e., IV hydrocortisone and fluid support). It may result from undiagnosed or untreated Addison’s disease combined with sudden stress on the body (i.e., injury, infection, or illness).
Autoimmune Addison’s disease may be associated with other autoimmune diseases (e.g., pernicious anemia and Grave’s disease)

Physiological replacement doses of corticosteroids for all types of adrenocortical insufficiency
Adrenal crisis (acute) treatment
- IV fluids
- IV glucocorticoids (i.e., hydrocortisone) and mineralocorticoids (i.e., fludrocortisone)
- Supportive measures and correction of any additional issues (e.g., electrolyte abnormalities)
Chronic adrenal insufficiency treatment
- Oral glucocorticoids (i.e., hydrocortisone, prednisone, methylprednisolone, or dexamethasone) to replace cortisol
- Oral mineralocorticoids (i.e., fludrocortisone) to replace aldosterone, if primary adrenocortical insufficiency
- Oral androgens (i.e., dehydroepiandrosterone) to replace androgens, if necessary

Symptoms of long-term steroid therapy

Potential life-threatening situation: Shock, dehydration, hypotension
Physiological considerations
- Cardiovascular: Impaired myocardial contractility, arrhythmias secondary to hyperkalemia
- Volume status: Dehydration (2-3 L)
- Electrolyte imbalance: Hyperkalemia, hyponatremia (decreased level of consciousness, seizures), and hypoglycemia (decreased level of consciousness, seizures)
Pharmacologic considerations
- Reduced circulating catecholamines (consider vasopressin for hypotension)
- Succinylcholine-induced hyperkalemia

Stress of surgery, infection, or trauma can cause adrenocortical insufficiency to decompensate and lead to an Addisonian crisis
Prolonged steroid therapy can suppress the HPA axis without causing symptoms → symptoms manifest if the steroids are withheld or the dose is not adapted to increased requirements
Patients on corticosteroid substitution therapy require a perioperative increase of the dose to compensate for the increased requirements posed by the trauma of surgery
Patients with untreated adrenocortical insufficiency should not be scheduled for elective surgery until corticosteroid therapy has been given for a sufficient length of time
Patients with untreated manifest adrenocortical insufficiency or Addisonian crisis presenting for emergency surgery are high-risk patients and require invasive intraoperative monitoring