Primary adrenal insufficiency

Clinical information  

The function of the adrenal cortex is to synthesise numerous steroid hormones which play important roles in the metabolism, water balance and stress response. These are divided into glucocorticoids (e.g. cortisol), mineralocorticoids (e.g. aldosterone) and sex hormones (e.g. androgens).

Cortisol is the main glucocorticoid. The amount and timing of cortisol production is primarily regulated by the adrenocorticotropic hormone (ACTH) which is produced by the pituitary gland. ACTH release, in turn, is controlled by the corticotropin-releasing hormone (CRH). Under the control of ACTH stimulation, cortisol secretion follows a diurnal rhythm so that the blood levels of the hormone are highest is the early morning and then decrease during the day.  

Cortisol regulates glucose metabolism by enhancing the gluconeogenesis (synthesis of glucose) and by increasing the blood glucose levels. Further, it favours mobilization of fats and modulates the immune response with an anti-inflammatory action. 

Synthesis of aldosterone, the main regulator of salt and water in the body, is mainly controlled by the amount of sodium and potassium in the blood and by the renin-angiotensin-aldosterone system (RAAS).  

Hormone production in the adrenal cortex can be impaired by different conditions, resulting in a hormone over- or underproduction. 

Diagnostics  

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. 

Files

Chemiluminescence assays by IDS for adrenal function.