What are the causes of hypocortisolism (low cortisol)?

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Last updated: April 15, 2025View editorial policy

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From the Guidelines

Low cortisol, also known as adrenal insufficiency, requires immediate attention and treatment with hydrocortisone, typically starting with 100 mg intravenously at the start of surgery or during significant stress, followed by an infusion of 200 mg/24 h, as recommended by the most recent guidelines 1.

Causes and Risk Factors

Adrenal insufficiency can be primary, due to adrenal gland damage, or secondary, resulting from pituitary gland issues affecting ACTH production. Patients taking prescribed glucocorticoid therapy, including oral, inhaled, topical, intranasal, or intra-articular routes, are at risk of adrenal crisis due to suppression of the hypothalamo-pituitary-adrenal axis 1.

Diagnosis and Treatment

Diagnosis involves blood tests measuring cortisol levels, and treatment typically involves cortisol replacement therapy with hydrocortisone, prednisone, or cortisone acetate. Patients with adrenal insufficiency should carry a medical alert card and have emergency injectable hydrocortisone available for crisis situations. During illness, injury, or significant stress, cortisol doses may need to be doubled or tripled temporarily, and regular medical follow-up is essential to adjust medication dosing 1.

Management During Peri-Operative Period

The guidelines recommend hydrocortisone 100 mg intravenously at the start of surgery, followed by an infusion of 200 mg/24 h, and doubling the regular oral replacement dose of hydrocortisone for 48 h, or up to a week following major surgery, before resuming the maintenance dose 1.

Key Points

  • Adrenal insufficiency requires prompt treatment with hydrocortisone
  • Patients taking prescribed glucocorticoid therapy are at risk of adrenal crisis
  • Diagnosis involves blood tests measuring cortisol levels
  • Treatment involves cortisol replacement therapy and emergency injectable hydrocortisone
  • Regular medical follow-up is essential to adjust medication dosing
  • The guidelines provide recommendations for management during the peri-operative period, including hydrocortisone dosing and infusion rates 1.

From the FDA Drug Label

Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for corticosteroid insufficiency after withdrawal of treatment. Adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage

Low cortisol can be caused by the use of corticosteroids, such as prednisone, due to hypothalamic-pituitary adrenal (HPA) axis suppression. This suppression can lead to adrenocortical insufficiency after withdrawal of treatment. To minimize this risk, a gradual reduction of dosage is recommended when stopping corticosteroid therapy 2.

From the Research

Definition and Causes of Low Cortisol

  • Low cortisol, also known as adrenal insufficiency, occurs when the adrenal glands do not produce enough cortisol, a hormone that plays a vital role in the body's response to stress, regulating blood sugar, and aiding in metabolism 3, 4.
  • The causes of low cortisol can be primary, such as Addison's disease, or secondary, resulting from hypopituitarism or long-term use of corticosteroids 3, 5.

Diagnosis of Low Cortisol

  • A morning serum cortisol level greater than 13 mcg/dL can reliably rule out adrenal insufficiency, while levels less than or equal to 13 mcg/dL require further evaluation with the cosyntropin stimulation test (CST) 6.
  • The CST involves intravenous or intramuscular administration of cosyntropin and multiple blood draws to assess the adrenal glands' response to stimulation 6.

Consequences of Low Cortisol

  • Low cortisol levels have been observed in patients with stress-related disorders, such as chronic fatigue syndrome, fibromyalgia, and post-traumatic stress disorder, characterized by enhanced stress sensitivity, pain, and fatigue 7.
  • Prolonged periods of hyperactivity of the hypothalamic-pituitary-adrenal axis due to chronic stress can lead to hypocortisolism, which may have both detrimental and beneficial effects on the organism 7.

Treatment and Management of Low Cortisol

  • Glucocorticoid replacement therapy is the standard treatment for adrenal insufficiency, involving twice- or thrice-daily dosing with a glucocorticoid, most commonly oral hydrocortisone 3.
  • However, current treatment regimens may not adequately replicate the natural circadian rhythm of cortisol release, leading to increased morbidity and decreased life expectancy in patients with adrenal insufficiency 3.
  • The use of biologic therapies targeting inflammatory mediators may help reduce or eliminate the need for long-term corticosteroid use in conditions such as severe asthma, but further research is needed to define the optimal strategy for identifying and treating adrenal insufficiency in these patients 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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