Adrenal insufficiency usually develops as a chronic, progressive illness. It can also become acute as an adrenal crisis, which is chiefly a complication of the primary form but can also occur in the secondary and tertiary forms.
Chronic adrenal insufficiency
The clinical picture depends on two things: how much of the adrenal gland has been lost, and whether the zona glomerulosa, the outer layer that makes mineralocorticoids, is involved. Primary adrenal insufficiency is by its nature a chronic progressive condition; because it strips all three hormones — glucocorticoids, mineralocorticoids and androgens — it produces non-specific signs and symptoms that accumulate over time:
- malaise and fatigue
- weight loss
- nausea and vomiting
- hypotension
- diarrhea alternating with constipation
- electrolyte imbalance: hyponatremia, hyperkalemia, metabolic acidosis, and dehydration
- lack of libido and amenorrhea
- hyperpigmentation of the skin, due to the high ACTH level
- vitiligo
Acute adrenal insufficiency (adrenal crisis)
Primary adrenal insufficiency is chronic, but it can be complicated by an acute episode, adrenal crisis, in which glucocorticoid secretion falls abruptly. The major manifestation is shock, but patients may also have non-specific features such as nausea, anorexia, abdominal pain, confusion, weakness and fatigue.
The major precipitating factor for adrenal crisis in primary adrenal insufficiency is mineralocorticoid deficiency, which causes the loss of sodium and water that dominates the crisis. It is also thought that the low glucocorticoid level desensitizes the adrenergic receptors, so the patient responds less to adrenergic stimulation; the resulting fall in vasoconstriction can add to the shock.
Adrenal crisis may happen in response to a major stressor such as:
- infections
- hemorrhage or infarction of the adrenal glands
- sudden withdrawal of steroid replacement therapy
It mainly happens in patients who are not receiving their needed mineralocorticoid replacement.
Secondary and tertiary adrenal insufficiency
The signs and symptoms of secondary and tertiary adrenal insufficiency are very similar to those of the primary form, with two exceptions. There is no hyperpigmentation, because ACTH or CRH is deficient rather than high. And there is no hyperkalemia, metabolic acidosis or dehydration from mineralocorticoid loss, because aldosterone secretion is preserved, unlike in the primary form. Hyponatremia can nevertheless occur, because cortisol deficiency itself impairs the kidney’s ability to excrete free water, so sodium can fall even when aldosterone is normal.
In secondary and tertiary adrenal insufficiency, depending on the cause and its extent of progression, neurological and hormonal signs and symptoms appear that arise from mass effect or involvement of other anterior pituitary hormones; therefore, headache, hormonal insufficiency, and visual disturbances can also be seen.
Hypoglycemia is more common in secondary adrenal insufficiency, possibly due to a concomitant lack of growth hormone (GH) that can be seen in secondary adrenal insufficiency alongside the lack of glucocorticoids.
Adrenal crisis is also different in these forms. Because the zona glomerulosa is preserved, aldosterone secretion continues, so these forms are not complicated by the salt and water loss of primary adrenal insufficiency and their hypovolemic crisis is much less likely. A crisis can still occur when a major stressor such as an infection arrives, because the pituitary or hypothalamus cannot raise ACTH and the cortisol surge the body needs does not come.