What causes low serum cortisol in a normal individual?

From the Guidelines

Low serum cortisol in a normal individual can be caused by various factors, including normal diurnal variation, recent food intake, stress reduction techniques, certain medications, and exogenous steroid use, as well as potential early adrenal insufficiency. The most common reason for low serum cortisol is the normal diurnal variation of cortisol, with levels being highest in the early morning and lowest in the evening and during early sleep 1. Other physiological causes include recent food intake, particularly carbohydrates, which can temporarily suppress cortisol levels. Stress reduction techniques like meditation or deep breathing can also lower cortisol. Certain medications can decrease cortisol production, including etomidate, ketoconazole, metyrapone, and high-dose opioids. Exogenous steroid use can suppress the hypothalamic-pituitary-adrenal axis, leading to decreased endogenous cortisol production. Some key points to consider when evaluating low serum cortisol include:

• The timing of blood sampling is crucial for accurate interpretation, as cortisol levels naturally fluctuate throughout the day 1.
• If low cortisol is found without symptoms of adrenal insufficiency, repeat testing at the appropriate time of day (morning) is often recommended before further investigation.
• In some cases, low cortisol may reflect early adrenal insufficiency, which can be primary (affecting the adrenal glands directly) or secondary (due to pituitary dysfunction) 1.
• The use of inhaled corticosteroids, even at recommended doses, can cause suppression of the adrenal response to ACTH and increase the risk of adrenal crisis 1. It is essential to consider these factors when evaluating low serum cortisol in a normal individual to determine the underlying cause and provide appropriate management.

From the FDA Drug Label

Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted

The cause of low serum cortisol in a normal individual is not directly addressed in the provided drug labels. However, secondary adrenocortical insufficiency can be caused by sudden discontinuation of corticosteroid therapy, which may lead to low serum cortisol levels 2.

• Key points:
  • Gradual reduction of corticosteroid dosage can minimize secondary adrenocortical insufficiency
  • Relative insufficiency may persist for months after discontinuation of therapy
  • Hormone therapy should be reinstituted in situations of stress during this period However, the provided information does not directly answer the question of what causes low serum cortisol in a normal individual.

From the Research

Causes of Low Serum Cortisol in Normal Individuals

• Adrenal insufficiency (AI) is a condition characterized by an absolute or relative deficiency of adrenal cortisol production, which can be primary, secondary, or tertiary 3.
• Low serum cortisol can also be caused by factors such as inflammation, which can lead to decreased glucocorticoid signaling and/or levels, as seen in stress-related disorders like post-traumatic stress disorder (PTSD) 4.
• Other factors that can influence cortisol levels include body composition, oral contraceptive agents, and contemporary cortisol assays 5.
• In hospitalized patients, relative adrenal insufficiency (AI) is the most common cause of low cortisol levels and failed adrenocorticotropic hormone (ACTH) challenge 6.
• Daily glucocorticoid replacement dose can also affect cortisol levels, and a titration method for determination of the individual patient's daily glucocorticoid replacement dose is recommended to avoid overtreatment 7.

Factors Influencing Cortisol Levels

• Body composition, particularly central adiposity, can predict 30-min total cortisol levels in men 5.
• Oral contraceptive agents can affect cortisol levels, with women taking oral contraception having 2-fold elevated 30-min cortisol levels 5.
• Inflammation can lead to decreased glucocorticoid signaling and/or levels, as seen in stress-related disorders like PTSD 4.
• Contemporary cortisol assays can also influence cortisol levels, with different assays giving different results 5.