From the Guidelines
Low ACTH levels are indicative of secondary adrenal insufficiency, where the pituitary gland fails to produce adequate amounts of this hormone, resulting in decreased cortisol production by the adrenal glands. This condition can be distinguished from primary adrenal insufficiency by the relationship between ACTH and cortisol levels, as noted in the American Society of Clinical Oncology clinical practice guideline 1. Secondary adrenal insufficiency can be caused by various factors, including pituitary tumors, pituitary surgery, radiation to the pituitary, traumatic brain injury, or prolonged use of corticosteroid medications like prednisone, which suppress the pituitary-adrenal axis.
Key Considerations
- Symptoms of secondary adrenal insufficiency include fatigue, weakness, weight loss, low blood pressure, nausea, and dizziness.
- Treatment typically involves hormone replacement therapy with hydrocortisone (usually 15-25 mg daily divided into 2-3 doses) or other glucocorticoids to replace the missing cortisol, as suggested by the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy guideline 1.
- Patients on corticosteroids for management of other conditions will have low morning cortisol as a result of iatrogenic, secondary adrenal insufficiency, and ACTH will also be low in these patients, making diagnosis challenging 1.
- Emergent therapy for suspected adrenal insufficiency is best done with dexamethasone, and if the diagnosis is already confirmed, hydrocortisone 100 mg can be used 1.
Management and Education
- All patients need education on stress dosing and a medical alert bracelet for adrenal insufficiency to trigger stress-dose corticosteroids by EMS.
- Endocrine consultation prior to surgery or any procedure for stress-dose planning is essential, as emphasized in the guideline 1.
- Regular medical follow-up is crucial to monitor hormone levels and adjust medication as needed to prevent adrenal crisis and ensure optimal management of secondary adrenal insufficiency.
From the Research
Low ACTH Levels
- Low Adrenocorticotropic hormone (ACTH) levels can indicate secondary adrenal insufficiency, a condition where the adrenal glands do not produce enough cortisol due to a lack of stimulation from the pituitary gland 2, 3.
- In secondary adrenal insufficiency, the pituitary gland does not produce enough ACTH, leading to decreased cortisol production by the adrenal glands.
- Low ACTH levels can also be seen in patients with primary adrenal insufficiency who are being treated with glucocorticoids, as the exogenous steroids can suppress the production of ACTH 4, 5.
Diagnosis of Adrenal Insufficiency
- The diagnosis of adrenal insufficiency is typically made using the ACTH stimulation test, which measures the response of the adrenal glands to ACTH stimulation 2, 3.
- A low cortisol response to ACTH stimulation can indicate adrenal insufficiency, and the cutoff values for a normal response can vary depending on the assay used to measure cortisol 5, 6.
- Newer studies have proposed lower cutoff values for cortisol response to ACTH stimulation, ranging from 14 to 15 μg/dL, depending on the assay used 5, 6.
Clinical Implications
- Low ACTH levels can have significant clinical implications, including fatigue, weight loss, and increased risk of infection 3, 4.
- Accurate diagnosis and treatment of adrenal insufficiency are essential to prevent long-term complications and improve quality of life 2, 5.
- Clinicians should be aware of the new cutoff values for cortisol response to ACTH stimulation and use them to guide diagnosis and treatment of adrenal insufficiency 5, 6.