What is the treatment for adrenal insufficiency using Adrenocorticotropic hormone (ACTH) or its analogs, such as cosyntropin?

From the Guidelines

Adrenocorticotropic hormone (ACTH) and its analogs, such as cosyntropin, are not typically used as treatments for adrenal insufficiency, but rather as diagnostic tools. The standard treatment for adrenal insufficiency involves glucocorticoid replacement therapy, usually with hydrocortisone (15-25 mg daily in divided doses), as recommended by the most recent guidelines 1. For patients with primary adrenal insufficiency (Addison's disease), mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) is also necessary. Some key points to consider in the treatment of adrenal insufficiency include:

• The use of hydrocortisone allows for 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
• Long-acting steroids such as prednisone can be used in special circumstances, but carry a risk of over-replacement 1
• All patients need education on stress dosing for sick days, use of emergency injectables, and when to seek medical attention for impending adrenal crisis 1
• Endocrine consultation should be part of planning before surgery or high-stress treatments 1 ACTH stimulation tests using cosyntropin (250 mcg IV or IM) are used diagnostically to assess adrenal function by measuring cortisol response before and after administration 1. ACTH therapy itself would be ineffective in primary adrenal insufficiency since the adrenal glands cannot respond to stimulation. In secondary adrenal insufficiency, while theoretically ACTH could stimulate cortisol production, long-term ACTH therapy has significant disadvantages, including cost, need for injection, and potential antibody development, making glucocorticoid replacement the preferred treatment approach.

From the FDA Drug Label

Cosyntropin for injection is an adrenocorticotropin hormone indicated, in combination with other diagnostic tests, for use as a diagnostic agent in the screening of adrenocortical insufficiency in adults and pediatric patients.

The recommended dose is 0.25 mg to be administered by intravenous or intramuscular injection for adults.

For pediatric patients, the recommended dose to be administered by intravenous or intramuscular injection is

o 0.125 mg for patients birth to less than 2 years of age

o 0.25 mg for patients 2 to 17 years of age

The treatment for adrenal insufficiency using Adrenocorticotropic hormone (ACTH) or its analogs, such as cosyntropin, is diagnostic. Cosyntropin is used as a diagnostic agent to screen for adrenocortical insufficiency in adults and pediatric patients. The dosage for adults is 0.25 mg administered by intravenous or intramuscular injection. For pediatric patients, the dosage is 0.125 mg for those under 2 years of age and 0.25 mg for those between 2 and 17 years of age 2.

From the Research

Treatment for Adrenal Insufficiency using Adrenocorticotropic Hormone (ACTH) or its Analogs

• The treatment for adrenal insufficiency involves life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises 3.
• Adrenocorticotropic hormone (ACTH) stimulation testing is the current standard for assessing primary and secondary adrenal insufficiency (AI) 4.
• Cosyntropin, an analog of ACTH, is used in stimulation testing to assess adrenal function 4, 5.
• The diagnosis of adrenal insufficiency can be confirmed by demonstrating inappropriately low cortisol secretion, and the condition is often delayed by months, with many patients presenting with acute adrenal crisis 6.

Diagnostic Accuracy of Basal Cortisol Level

• The basal cortisol level can be used to predict adrenal insufficiency, with a high diagnostic accuracy 4.
• A basal cortisol level of ≥450 nmol/L can rule out adrenal insufficiency with a negative predictive value of 98.7%, while a level of ≤100 nmol/L can rule in adrenal insufficiency with a positive predictive value of 93.2% 4.

Treatment Options for Adrenal Insufficiency

• Conventional hydrocortisone therapy cannot provide physiological replacement, and new approaches such as circadian hydrocortisone infusions are being explored 7.
• Circadian infusion of hydrocortisone can improve control of ACTH and androgen levels in patients with adrenal insufficiency and congenital adrenal hyperplasia 7.
• Novel modified-release hydrocortisone formulations and subcutaneous formulations are available, offering improved treatment options for adrenal insufficiency 3.

Diagnostic Cutoffs for Adrenal Insufficiency

• The accurate interpretation of the cosyntropin stimulation test requires method- and assay-specific cutoffs of the level of cortisol 5.
• New diagnostic cutoffs for adrenal insufficiency after cosyntropin stimulation using the Abbott Architect cortisol immunoassay have been established, with a recommended threshold of 14.6 μg/dL at 60 minutes after stimulation 5.