63. Adrenal (cortex) insufficiency

From greek.doctor

Adrenal insufficiency refers to decreased production of adrenocortical hormones. It can be primary, where the problem lies in the adrenals, or secondary, where the problem lies in the ACTH-producing pituitary. Primary adrenal insufficiency is also known as Addison disease.

Etiology

Secondary adrenal insufficiency is more common than primary adrenal insufficiency.

Primary adrenal insufficiency

  • Autoimmune adrenalitis – 80% of cases of primary insufficiency
  • Tuberculosis
  • Infiltration of the adrenals
    • Tumors
    • Amyloidosis
    • Haemochromatosis
  • Iatrogenic (adrenalectomy)
  • Waterhouse-Friderichsen syndrome
  • 21-hydroxylase deficiency (congenital adrenal hyperplasia)

The only acute form of primary adrenal insufficiency is Waterhouse-Friderichsen syndrome.

Secondary adrenal insufficiency

  • Discontinuation of long-term glucocorticoid therapy
  • Hypopituitarism
    • Pituitary tumors

Pathomechanism

When the insufficiency is primary there will be hypoandrogenism (in females), hypoaldosteronism, hypocortisolism and increased ACTH.

In secondary insufficiency the conditions are similar, except that aldosterone level will be normal or almost normal as ACTH isn’t the major regulator of aldosterone secretion; angiotensin II is. ACTH is decreased rather than increased.

Many cases of adrenal insufficiency are subclinical and only become apparent as an adrenal crisis, which is discussed later.

Clinical features

In primary adrenal insufficiency:

  • Due to hypoaldosteronism
    • Hypotension
    • Hyponatraemia
    • Hyperkalaemia
    • Normal anion gap metabolic acidosis
  • Due to hypocortisolism
    • Weight loss
    • Depression
    • Nausea, vomiting
    • Diarrhoea
    • Hypotension
    • Increased susceptibility to hypoglycaemia
  • Due to hypoandrogenism (in females only)
    • Loss of libido
    • Loss of pubic hair
  • Due to elevated ACTH
    • Hyperpigmentation of skin, including areas not exposed to sunlight

In secondary adrenal insufficiency only the symptoms of hypocortisolism and hypoandrogenism are present.

Complications

An adrenal crisis is an acute deterioration of the patient’s condition due to a severe relative deficiency of adrenocortical hormones (especially cortisol). It is often triggered when the cortisol requirement increases, such as during surgery, trauma or infection. Stress can increase the body’s cortisol requirement by a factor of 10! It can also occur after sudden discontinuation of glucocorticoid therapy. Abdominal pain and vomiting is common.

Adrenal crisis is accompanied by circulatory shock. Acute deficiency of mineralocorticoids causes excessive fluid loss, hyponatraemia, metabolic acidosis and hyperkalaemia, while acute loss of glucocorticoids causes hypoglycaemia and hypotension.

Adrenal crisis is fatal if untreated and often fatal in treated (in 40% of cases).

Treatment

Treatment involves correcting the underlying cause (is present) and substituting the deficient hormones.

Waterhouse-Friderichsen syndrome

Waterhouse-Friderichsen syndrome is an acute adrenal insufficiency that occurs because of destructive bleeding into the adrenal glands. It usually follows a meningococcal sepsis, but can occur in sepsis with other bacteria as well. DIC occurs, in which the consumption coagulopathy phase causes bleeding into the adrenals and thereby loss of their function.

The pathophysiology is similar to that of an adrenal crisis. Deficiency of cortisol and aldosterone causes excessive volume loss and hypotension, resulting in circulatory shock. Loss of cortisol’s anti-inflammatory effect might contribute to the deadliness of the sepsis.

The mortality of Waterhouse-Friderichsen syndrome is high even if treated.