What is the significance of low serum cortisol?

From the Guidelines

Low serum cortisol is a clinically significant indicator of adrenal insufficiency, requiring prompt diagnosis and treatment to prevent life-threatening complications, and should be managed with glucocorticoid replacement therapy, such as hydrocortisone (15-25 mg daily in divided doses), and mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) in primary adrenal insufficiency. The significance of low serum cortisol lies in its indication of adrenal insufficiency, a condition where the adrenal glands fail to produce adequate amounts of cortisol, which can be life-threatening if not properly diagnosed and treated 1. Primary adrenal insufficiency (Addison's disease) occurs when the adrenal glands themselves are damaged, while secondary insufficiency results from pituitary dysfunction. Symptoms of adrenal insufficiency include fatigue, weakness, weight loss, hypotension, salt cravings, and hyperpigmentation.

Diagnosis of adrenal insufficiency is confirmed through an ACTH stimulation test, which measures the response of the adrenal glands to adrenocorticotropic hormone (ACTH) 1. Treatment typically involves glucocorticoid replacement therapy with hydrocortisone (15-25 mg daily in divided doses) or prednisone (5-7.5 mg daily), and patients with primary adrenal insufficiency also require mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) 1. All patients should carry an emergency steroid card and injection kit, and know to double or triple their glucocorticoid dose during illness, surgery, or severe stress.

Key aspects of management include:

• Initiating replacement therapy with hydrocortisone (15-20 mg in divided doses) and titrating to a maximum of 30 mg daily total dose for residual symptoms of adrenal insufficiency 1
• Adding fludrocortisone (starting dose 0.05-0.1 mg/d) and adjusting based on volume status, sodium level, and renin response 1
• Educating patients on stress dosing for sick days, use of emergency injectables, and when to seek medical attention for impending adrenal crisis 1
• Considering endocrine consultation as part of planning before surgery or high-stress treatments 1.

Low cortisol is physiologically significant because cortisol regulates metabolism, immune response, stress adaptation, and blood pressure maintenance, so its deficiency disrupts these essential functions. Therefore, prompt recognition and treatment of low serum cortisol are crucial to prevent morbidity, mortality, and improve quality of life in patients with adrenal insufficiency.

From the Research

Significance of Low Serum Cortisol

Low serum cortisol can have significant implications for an individual's health, particularly in relation to adrenal insufficiency. Adrenal insufficiency occurs when the adrenal glands do not produce adequate amounts of cortisol and, in some cases, aldosterone [ 2 ].

Adrenal Insufficiency and Its Consequences

• Normal adrenocortical activity is necessary for electrolyte regulation and the maintenance of cardiovascular function [ 2 ].
• Chronic adrenal insufficiency generally presents with the gradual onset of a set of characteristic symptoms and signs [ 2 ].
• The more sudden loss of adrenal activity can present with acute, rapidly progressive cardiovascular dysfunction that can be fatal if not recognized and treated promptly [ 2 ].

Cortisol Replacement Therapy

• Cortisol replacement in patients with adrenal insufficiency usually consists of hydrocortisone given orally during the daytime [ 3 ].
• Due to the short half-life of hydrocortisone, cortisol levels between midnight and early morning are very low in contrast to the physiological rise of cortisol serum levels during this time [ 3 ].
• Mimicking the physiological rise in cortisol secretion during the night in patients with adrenal insufficiency did not significantly affect quality of life or cognitive performance and vegetative functions [ 3 ].

Relationship Between Cortisol Levels and Patient Outcomes

• Basal total and free plasma cortisol levels in patients with septic shock ranged from 203 to 2169 and from 17 to 372 nmol/l [ 4 ].
• Patients with "inadequate" steroid production could be weaned from vasopressor therapy significantly faster [ 4 ].
• Random serum cortisol levels correlated positively with illness severity in ICU patients [ 5 ].
• Those with the highest random serum cortisol levels had the greatest mortality [ 5 ].

Treatment Considerations

• Replacement doses of 10-15 mg/24 h of hydrocortisone seem sufficient in non-obese individuals [ 6 ].
• The day-night variation and in particular the fast oscillations in plasma cortisol concentration may be important for the patient's well-being [ 6 ].
• There is no documentation for the benefit of high doses (100-400 mg hydrocortisone) in patients with critical disease and adrenal insufficiency [ 6 ].