AI: A Focus on Subtypes

Adrenal insufficiency (AI) broadly describes a disease where there is a lack of production of cortisol. To better understand what is going on in the body of a child with pediatric adrenal insufficiency, it’s helpful to focus on the subtypes of AI. The two main categories are primary (problems with adrenal glands) and central (problems with pituitary glands or hypothalamus).

Primary AI

Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia (CAH) is the most common cause of primary AI in children. There are three types of CAH, including:
Classic Salt-Wasting

  • 75% of classic CAH
  • Cortisol + aldosterone deficiency
  • Life-threatening (salt wasting); may develop salt wasting crisis without treatment
  • Usually detected by newborn screening or in early childhood
  • Can cause genital ambiguity in girls

Classic Simple Virilizing

  • 25% of classic CAH
  • Cortisol deficiency
  • Less severe
  • Can cause genital ambiguity in girls

Non-Classic (Late Onset) (NCAH)

  • Most prevalent form of CAH
  • Cortisol deficiency
  • Mild
  • Symptoms that mimic early puberty, such as pubic hair growth, increased body hair, body odor, and acne
  • Some children do not experience symptoms or need treatment

Addison’s Disease

The primary cause of AI in adolescence is an autoimmune disease, also called Addison’s disease, in which a person’s immune system produces antibodies that attack and slowly destroy the adrenal glands. Often the body is unable to produce both cortisol and aldosterone. Except for salt craving, signs and symptoms are often nonspecific, such as vomiting, weight loss, abdominal pain, weakness, tiredness, muscle or bone pain, and anxiety. Without treatment, Addison’s disease could result in an acute life-threatening adrenal crisis.

X-Linked Adrenoleukodystrophy

Adrenal insufficiency is also noted in many individuals with adrenoleukodystrophy (ALD) , a rare genetic disease that affects boys and men. It results from defects in breakdown of very long chain fatty acids which accumulate and damage the protective sheath of the nerves in the brain. Symptoms include seizures and hyperactivity, as well as progressive worsening of speech, listening, and understanding verbal instructions.


Central AI

In central adrenal insufficiency, the pituitary gland and/or the brain do not make the hormones that trigger the adrenal gland to make steroids. This can be due to long term use of steroids (for example for asthma or juvenile idiopathic arthritis) or conditions that affect the brain and pituitary gland. Steroid medications suppress the production of one’s own steroid hormone from the adrenal gland, ultimately leading to adrenal insufficiency. Symptoms are often nonspecific and may include weakness, tiredness, upset stomach, poor weight gain, and headaches. Left untreated, this condition could lead to a life-threatening adrenal crisis.

Central AI includes the following:

  • Check

    Secondary AI (pituitary gland doesn’t work properly)

    • Congenital Pituitary Dysfunction (ACTH Deficiency)
    • Acquired Pituitary Dysfunction (including that caused by external steroid intake)

  • Check

    Tertiary AI (hypothalamus doesn’t work properly)

    • Secondary to steroid intake (Iatrogenic)
    • Other

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