Cortisol, serum

Clinical background:

Cortisol is the primary glucocorticoid hormone synthesised and secreted by the adrenal cortex. It is essential for life regulating carbohydrate, protein and lipid metabolism, maintaining blood pressure and inhibiting allergic and inflammatory reactions. Cortisol is synthesised and secreted by the cortex of the adrenal gland under the direction of adrenocorticotropic hormone (ACTH). ACTH is secreted in a circadian pattern by the anterior lobe of the pituitary gland in response to corticotropin releasing hormone (CRH) secretion by the hypothalamus. Increased ACTH levels stimulate cortisol secretion. As levels of cortisol increase they inhibit CRH secretion which subsequently inhibits ACTH secretion and the production of cortisol decreases. This is known as a negative feedback mechanism. Circulating cortisol levels follow a diurnal pattern in healthy individuals; the highest levels are seen in the morning after waking and the lowest in the evening. Disorders of the hypothalamic-pituitary-adrenal axis override this diurnal pattern.

Decreased cortisol levels are seen in both primary and secondary adrenal insufficiency. Addison’s disease is primary adrenal insufficiency due to destruction of the adrenal cortex, often autoimmune, after glucocorticoid treatment withdrawal or less commonly adrenalectomy, amyloidosis, haemachromatosis and adrenal haemorrhage. Secondary adrenal insufficiency is caused by pituitary destruction or failure, resulting in loss of ACTH stimulation of the adrenal gland.

Cushing’s syndrome is caused by increased levels of cortisol due to either primary or secondary adrenal hyperfunction. Causes of primary adrenal hyperfunction are adrenal tumours and nodular adrenal hyperplasia. Secondary adrenal hyperfunction is caused by pituitary overproduction of ACTH or ectopic production of ACTH by a tumour. Increased cortisol levels are induced by pregnancy and by stress due to depression, trauma, surgery, hypoglycaemia, alcoholism, uncontrolled diabetes and starvation.

Specimen container paediatric:

Serum (SST or plain tube)

Specimen container adult:

Serum (SST or plain tube)

Minimum volume paediatric:

0.5 mL blood

Minimum volume adult:

1 mL blood

Special requirements:

Sample timing is important and will affect interpretation.

9am samples preferred

Sample stability:

Unseparated: 7 days

Separated: 7 days at 4- to °C, 12 months at -20°C

Transport requirements:

Ambient

Interpretation:

Due to the diurnal pattern of secretion, single cortisol estimations may be of little diagnostic value. Cortisol is often measured during dynamic function tests, which are used to determine glucocorticoid insufficiency or excess. The short synacthen test (SST) is used to investigate Addison’s disease, and the dexamethasone suppression test used to diagnose Cushing’s syndrome or depression due to neuroendocrine disorders. 24-hour urinary cortisol measurement is also a useful test in the initial screening for Cushing’s as it is not subject to diurnal variation.

Reference ranges:

6am – 10am: 133 – 537 nmol/L

Factors affecting result:

Samples should not be taken from patients receiving therapy with high biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin administration.
In samples from patients who have been treated with prednisolone, 6-α-Methylprednisolone or prednisone, falsely elevated concentrations of cortisol may be determined.

During metyrapon tests, 11 deoxycortisol levels are elevated. Falsely elevated cortisol values may be determined due to cross reactions.

Patients suffering from 21 hydroxylase deficiency exhibit elevated 21 deoxycortisol levels and this can also give rise to falsely elevated cortisol results.

Other info:

Lithium heparin plasma samples also acceptable