From the Guidelines
Diagnosing adrenal insufficiency requires a stepwise approach, starting with clinical suspicion based on symptoms, followed by initial testing with morning cortisol levels, and confirmed by the ACTH stimulation test, as recommended by the most recent guidelines 1. The diagnostic steps for adrenal insufficiency include:
- Clinical suspicion based on symptoms like fatigue, weight loss, hyperpigmentation, and hypotension
- Initial testing with morning cortisol levels, with values below 5 μg/dL suggesting insufficiency and above 15 μg/dL typically ruling it out
- ACTH stimulation test, where synthetic ACTH (cosyntropin, 250 μg) is administered and cortisol levels are measured at 0,30, and 60 minutes; failure to reach 18-20 μg/dL confirms the diagnosis
- Additional testing includes ACTH levels to differentiate primary (high ACTH) from secondary (low/normal ACTH) insufficiency, along with electrolytes, renin, and aldosterone measurements Treatment options for adrenal insufficiency include:
- Hormone replacement therapy, with glucocorticoids as the cornerstone
- For primary insufficiency, hydrocortisone (15-25 mg daily divided into 2-3 doses) is preferred, with prednisone (3-5 mg daily) as an alternative
- Mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) is needed for primary insufficiency
- Patients must carry emergency supplies and wear medical identification, with stress dosing (typically tripling the usual dose) during illness, surgery, or severe stress
- Regular monitoring of symptoms, blood pressure, electrolytes, and plasma renin activity guides dose adjustments
- Patient education about medication adherence, stress dosing, and recognizing adrenal crisis is essential for successful management of this chronic condition, as emphasized in the latest guidelines 1. Key considerations in managing adrenal insufficiency include:
- Starting corticosteroids first when planning hormone replacement therapy for multiple deficiencies
- Being aware of the potential for isolated central adrenal insufficiency with a low ACTH in patients on corticosteroids for other conditions
- Educating patients on stress dosing, emergency steroid injectables, and when to seek medical attention for impending adrenal crisis
- Consulting endocrinology for recovery and weaning protocols using hydrocortisone in patients with symptoms of adrenal insufficiency after weaning off corticosteroids, as recommended in the latest update 1.
From the FDA Drug Label
Cosyntropin for injection is indicated, in combination with other diagnostic tests, for use as a diagnostic agent in the screening of adrenocortical insufficiency in adults and pediatric patients.
2.5 Administration Information • Obtain blood sample for baseline serum cortisol. Obtain blood samples again for assessment of cortisol levels exactly 30 minutes and 60 minutes after administration of cosyntropin for injection.
2.6 Interpretation of Plasma Cortisol Levels after Cosyntropin for Injection • Stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin for injection are suggestive of adrenocortical insufficiency.
The diagnostic steps for adrenal insufficiency include:
- Baseline serum cortisol measurement: Obtain a blood sample for baseline serum cortisol level.
- Cosyntropin stimulation test: Administer cosyntropin for injection and obtain blood samples again for assessment of cortisol levels exactly 30 minutes and 60 minutes after administration.
- Interpretation of plasma cortisol levels: Stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin for injection are suggestive of adrenocortical insufficiency.
Treatment options are not explicitly mentioned in the provided drug labels for the diagnosis of adrenal insufficiency. 2 2 2
From the Research
Diagnostic Steps for Adrenal Insufficiency
- The diagnosis of adrenal insufficiency (AI) is based on clinical assessment and biochemical tests, including basal hormone level measurements and stimulation tests 3.
- Measurements of the basal serum cortisol at 8 am (<140 nmol/L or 5 mcg/dL) coupled with adrenocorticotrophin (ACTH) remain the initial tests of choice 4.
- The cosyntropin stimulation (short synacthen) test is used for the confirmation of the diagnosis 4, 5.
- Newer highly specific cortisol assays have reduced the cut-off points for cortisol in the diagnosis of AI 4.
- The salivary cortisol test is increasingly being used in conditions associated with abnormal cortisol binding globulin (CBG) levels such as pregnancy 4.
Treatment Options for Adrenal Insufficiency
- Severe chronic adrenal insufficiency (primary or secondary) is a potentially lethal disorder, unless the patient is regularly substituted with glucocorticoids, usually with hydrocortisone (15-25 mg/day) and with 9 alpha-fluor-hydrocortisone (0.05-0.2 mg/day) in addition in patients with the primary adrenal disorder (Addison's disease) 6.
- In stressful situations and in febrile disorders, the glucocorticoid dosage must be increased prophylactically in order to prevent an "adrenal crisis" 6.
- Most women with adrenal insufficiency will profit from the additional substitution of dehydroepiandrosterone (DHEA) with regard to well-being and sexual function 6.
- Adrenal crisis is a life-threatening medical emergency which must be treated immediately if there is strong clinical suspicion with fluids and corticosteroids otherwise can be fatal 7.
Special Considerations
- Children and infants require lower doses of cosyntropin for testing 4.
- 21-hydoxylase antibodies are routinely evaluated to rule out autoimmunity, the absence of which would require secondary causes of adrenal insufficiency to be ruled out 4.
- Cancer treatment with immune checkpoint inhibitors (ICI) is an emerging cause of both primary AI and SAI and requires close follow up 4.
- Patients must be educated and empowered to take control of their own medical management 7.