What is the primary treatment for secondary adrenal insufficiency?

From the Guidelines

The primary treatment for secondary adrenal insufficiency is glucocorticoid replacement therapy, typically with oral hydrocortisone, at a dose of 15-20 mg per day, divided into two or three doses, with the majority given in the morning to mimic the body's natural cortisol rhythm. This approach is supported by the most recent guidelines, including the 2021 ASCO guideline update 1. The dosing regimen may vary depending on the individual patient's needs, but the goal is to replicate the normal diurnal rhythm of cortisol production.

Key Considerations

• Hydrocortisone is preferred over other glucocorticoids because it allows for the recreation of the diurnal rhythm of cortisol, with 2/3 of the dose given in the morning and 1/3 in the early afternoon 1.
• Mineralocorticoid replacement with fludrocortisone is usually not necessary in secondary adrenal insufficiency, as aldosterone production remains intact 1.
• Patients should be educated on stress dosing for sick days, the use of emergency injectables, and when to seek medical attention for impending adrenal crisis, and should wear a medical alert bracelet or necklace for adrenal insufficiency 1.
• Dose adjustments are necessary during times of illness, surgery, or significant stress, typically doubling or tripling the usual dose temporarily, as outlined in the management guidelines for immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1.

Monitoring and Adjustment

• Treatment effectiveness is monitored through symptom improvement and clinical response rather than blood tests.
• Endocrine consultation is crucial for planning before surgery or high-stress treatments and for managing potential complications or comorbidities 1.
• The therapy is lifelong in most cases, as secondary adrenal insufficiency results from inadequate ACTH production by the pituitary gland, which fails to stimulate the adrenal glands to produce cortisol.

From the FDA Drug Label

Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance) The primary treatment for secondary adrenal insufficiency is hydrocortisone or cortisone, and in some cases, synthetic analogs may be used in conjunction with mineralocorticoids 2.

• Key points:
  • Hydrocortisone is the first choice for treatment
  • Mineralocorticoid supplementation is important, especially in infancy
  • Synthetic analogs may be used in certain situations It is essential to note that the treatment should be tailored to the individual case, and the dosage should be carefully managed to minimize potential complications 3.

From the Research

Treatment for Secondary Adrenal Insufficiency

The primary treatment for secondary adrenal insufficiency involves glucocorticoid replacement therapy. Key aspects of this treatment include:

• The use of glucocorticoids, most commonly oral hydrocortisone, administered in twice- or thrice-daily dosing regimens 4.
• The goal of therapy is to mimic the natural circadian rhythm of cortisol release as closely as possible, while also managing individualized cortisol exposure and adjusting doses during stress-related events 4, 5.
• Recent developments in treatment aim to improve upon conventional glucocorticoid replacement by using new modes of replacement that more closely mimic normal glucocorticoid physiology 5.
• Various glucocorticoid formulations are available, including short-acting, intermediate, long-acting, and novel modified-release hydrocortisone, as well as subcutaneous formulations 6.
• The daily glucocorticoid replacement dose is recommended to be between 15 to 25 mg of hydrocortisone (or 3 to 5 mg prednisolone) in divided doses for otherwise healthy individuals with adrenal insufficiency, although some studies suggest that lower doses may be more appropriate for some patients 7.

Management Considerations

Management of secondary adrenal insufficiency also involves:

• Stress adaptation to prevent adrenal crises, which can be life-threatening 6.
• Repeated education of patients and their partners on the correct use of glucocorticoids and early dose adjustments to cover increased glucocorticoid demand during stress 8.
• Potential need for additional structured information and training on adrenal insufficiency for physicians, even in specialized hospitals, due to the complexity and rarity of the condition 8.