Primary adrenal insufficiency

The physiology of cortisol can be altered in two ways: it can be either abnormally increased or abnormally reduced. 

Abnormally low levels of cortisol – or hypocortisolism – are the hallmark of adrenal insufficiency, causing symptoms such as fatigue, weight loss and muscle weakness. The first line of screening for adrenal insufficiency involves assessing cortisol levels in the blood. 

Suppressed levels of cortisol indicate that adrenal insufficiency is likely. Subsequent assessment of ACTH concentrations enables to differentiate whether the hypocortisolism is due to a dysfunction of the adrenal glands (primary adrenal insufficiency – or Addison’s disease) or to insufficient levels of ACTH (secondary adrenal insufficiency). 

In the most common form of primary adrenal insufficiency, Addison’s disease, the hormone-producing cells of the adrenal cortex are destroyed and thus, synthesis of multiple hormones is impacted. Consequently, the measurement of aldosterone is recommended as an aid in the diagnosis and to assess the presence of a mineralocorticoid deficiency. 

A less common form of primary adrenal insufficiency is caused by a congenital enzyme deficiency impairing cortisol production. This condition is referred to as congenital adrenal hyperplasia (CAH) and characterised by an accumulation of the cortisol precursor 17-OH progesterone.