Primary Adrenal Insufficiency Guidelines from the Endocrine Society: 5 Highlights

The Endocrine Society issued the first Clinical Practice Guideline on diagnosis and treatment of primary adrenal insufficiency.¹ These guidelines are designed to provide clinicians with best practices for diagnosing and treating patients during and after an adrenal crisis.

We spoke with Task Force member, Andreas Barthel, MD, MSc, to discuss highlights of the recommendations. Dr. Barthel is a professor at Endokrinologikum RUHR, in Bochum, Germany, and with the Department of Medicine at the University of Dresden, Germany.

Endocrine Society Panel Highlights Essential Points

• Blood test to measure adrenocorticotropic hormone (ACTH) is needed to confirm a diagnosis of primary adrenal insufficiency.

• Serum renin and aldosterone should be monitored to rule out hormone deficiencies.

• Treatment is: glucocorticoid replacement therapy--hydrocortisone (cortisol)

• Patients with aldosterone deficiency require fludrocortisone replacement therapy; and, ongoing blood monitoring of electrolytes.

A Closer Look at the Recommendations

Q: Who should be tested for primary adrenal insufficiency and how?
Dr. Barthel: The guidelines suggest diagnostic testing for the exclusion of primary adrenal insufficiency (PAI) in all patients with indicative clinical symptoms or signs. In particular, for acutely ill patients with otherwise unexplained symptoms or signs suggestive of PAI, such as volume depletion, hypotension, hyponatremia, hyperkalemia, fever, abdominal pain, hyperpigmentation or— especially in children, hypoglycemia.

The recommended diagnostic tests include:

• serum cortisol

• plasma adrenocorticotropic hormone (ACTH) for screening

• corticotropin stimulation test as a confirmatory test

For routine clinical practice, obtaining a sampling of serum cortisol and plasma ACTH is generally possible, whereas the corticotropin stimulation test is usually performed in specialized centers.

Q: How should physicians test for primary adrenal insufficiency?
Dr. Barthel: The short corticotropin stimulation test (250µg) is regarded as the “gold standard” diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels is recommended.

To determine the presence of mineralocorticoid deficiency, the simultaneous measurement of plasma renin and aldosterone is recommended. In patients with confirmed diagnosis of disease, the etiology of PAI should be ascertained.

Q: What are the treatment recommendations for adults with PAI?
Dr. Barthel: Glucocorticoid therapy is recommended in all patients with confirmed PAI. Usually, hydrocortisone or cortisone acetate in two or three divided oral doses per day is suggested, although prednisolone, administered orally once or twice daily, may also be used. Dexamethasone should not be used for the treatment of PAI because of the risk of Cushingoid side effects. Glucocorticoid replacement should be monitored based on clinical assessment including body weight, postural blood pressure, energy level, and signs of frank glucocorticoid excess. Individual circumstances like physical stress or advanced pregnancy may require an increase of the glucocorticoid dose.

Mineralocorticoid therapy with fludrocortisone is recommended in all patients with confirmed aldosterone deficiency. Mineralocorticoid replacement also should be monitored primarily based on clinical assessment (salt craving, postural hypotension, or edema), and blood electrolyte measurements.

Dehydroepiandrosterone (DHEA) replacement may be suggested in women with PAI and low libido, depressive symptoms, and/or low energy levels despite otherwise optimized glucocorticoid and mineralocorticoid replacement.

Q: What are the treatment recommendations for children with PAI?
Dr. Barthel: In children with PAI, it is suggested to treat with hydrocortisone; synthetic, long-acting glucocorticoids (eg, prednisolone, dexamethasone) should be avoided. Dosing should be based on body surface area. Glucocorticoid replacement should be monitored by clinical assessment, including growth velocity, body weight, blood pressure, and energy levels.

In children with PAI and confirmed aldosterone deficiency, treatment with fludrocortisone is recommended. For infants, sodium chloride supplements in the newborn period and up to the age of 12 months are recommended.

Q: What other aspects of the guidelines would you like to highlight to our readers?
Dr. Barthel: PAI is a rare condition and most physicians have little or no experience with the disease. Consequently, the level of suspicion is currently rather low.

The most pressing need for the treatment of PAI is the early diagnosis. In order to accomplish this, we need to increase our awareness for the disease and add PAI early to the list of differential diagnosis in severely ill patients with particular symptoms and signs like hypotension, hyponatremia, fever, abdominal pain, hyperpigmentation or hypoglycemia.

Another pressing need is patient education with regard to the necessity of self-management of the disease and care of equipment for those with a steroid emergency card or medical alert identification in order to improve management and prevention of adrenal crisis.

March 8, 2016