Adrenal insufficiency: Clinical sciences

Adrenal insufficiency is an uncommon, but potentially life-threatening condition, that occurs when hormones from the adrenal gland, like glucocorticoids and mineralocorticoids, are insufficient to meet the body’s demands. Common causes of adrenal insufficiency include autoimmunity, infections, malignancy, or exogenous use of glucocorticoids. And based on the location of the underlying cause, adrenal insufficiency can be classified as primary, which is when the adrenal gland cannot produce hormones; secondary, or when there are abnormalities in the hypothalamic-pituitary-adrenal axis or HPA axis for short; and tertiary, which is often due to exogenous glucocorticoid steroid use.

Now, if you suspect adrenal insufficiency, first, you should perform an ABCDE assessment to determine if the patient is unstable or stable.

If unstable, stabilize their airway, breathing, and circulation. Additionally, obtain IV access, provide supplemental oxygen, if needed, and put them on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry.

Next, proceed with a focused history and physical examination, and obtain labs like a BMP Typically, your patient will report fatigue, nausea and vomiting, and abdominal pain; as well as headaches, muscle pain, and cramping. Additionally, they will likely have a history of some sort of exacerbated stress on the body. This could come from a recent acute illness, a recent medical procedure, or being under significant psychological stress. Or the stressor may be recent abrupt withdrawal of glucocorticoid therapy.

On the other hand, physical exam findings usually include an acutely ill-appearing individual with hypotension or even shock, as well as altered mental status, and significant abdominal tenderness.

Finally, labs can reveal hypoglycemia, as well as hyponatremia and hyperkalemia. Additionally, you might notice elevated BUN and creatinine from significant dehydration.

At this point, you can clinically diagnose an adrenal crisis, also known as acute adrenal insufficiency, which is a medical emergency that requires prompt management. Immediately begin intravenous normal saline, intravenous glucocorticoid replacement with hydrocortisone, and intravenous glucose replacement with dextrose. Also, don’t forget to correct any electrolyte disturbances. Once the patient is stabilized, you should look for and treat the underlying cause.

Now, here’s a clinical pearl! A normal cortisol level in the setting of an acute adrenal crisis is abnormal. When the body is under stress the cortisol level should rise. In adrenal Insufficiency, there is some dysfunction in the HPA axis and the patient’s serum cortisol level doesn’t increase as it should.

Okay, now let’s go back to the ABCDE assessment and take a look at stable patients.

Your first step is to take a focused history and physical exam.

These individuals will likely report unintentional weight loss, decreased or absent appetite, nausea, fatigue, and pain in their muscles and abdomen. Additionally, some patients might describe intense cravings for salt or report a history of exogenous glucocorticoid use.

Next, the physical exam will likely reveal postural or orthostatic hypotension, and perhaps areas of hyperpigmented skin.

Now, with these findings you should suspect adrenal insufficiency, so your next step is to check a morning, or 8 AM, cortisol level.

First, let’s discuss patients with decreased morning cortisol, which is typically less than 3 micrograms per deciliter. With this result, you can confidently diagnose adrenal insufficiency, so proceed with labs, primarily ACTH and BMP. These labs will help you classify adrenal insufficiency into primary, secondary, or tertiary type, and therefore help you identify the cause.

Now, let’s take a look at primary adrenal insufficiency.

If the ACTH is elevated and the other labs reveal abnormalities like hyponatremia, hyperkalemia, and perhaps hypoglycemia, then the diagnosis is primary adrenal insufficiency, also known as Addison Disease.

Remember, primary means that the adrenal glands are dysfunctional, so first, check for antibodies to 21-hydroxylase, because autoimmunity is the most common cause of primary adrenal insufficiency. If 21-hydroxylase antibodies are present, diagnose Autoimmune Primary Adrenal Insufficiency.

On the other hand, if 21-hydroxylase antibodies are not present, order a CT scan of the adrenal glands.

If the adrenal glands are normal on imaging, then you should obtain serum very long chain fatty acids, or VLCFA for short. Normal VLCFA values suggest the diagnosis of Idiopathic Primary Adrenal Insufficiency.

On the flip side, elevated VLCFA suggests Primary Adrenal Insufficiency due to Adrenoleukodystrophy, which is an X-linked genetic condition that typically affects male children.

Okay, let’s go back to our adrenal CT scan one last time. If the CT reveals abnormal findings, then consider etiologies such as infection, like tuberculosis or AIDS; malignancy; or hemorrhage, for example Waterhouse-Friderichsen Syndrome, which is caused by bacterial sepsis from Neisseria meningitidis.

Treatment for all causes of primary adrenal insufficiency consists of glucocorticoid replacement, usually with hydrocortisone; as well as mineralocorticoid replacement, usually with fludrocortisone; and correcting any acute electrolyte disturbances. Keep in mind that these patients do not need dietary salt restrictions, even in the presence of hypertension, due to their mineralocorticoid deficiency. Lastly, it is important to treat the underlying cause as indicated.

Alright, let’s go back to the ACTH and BMP results and take a look at secondary adrenal insufficiency.