Adrenal insufficiency: Clinical sciences

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Introduction0:00–0:49

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 HP 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 ABCD E assessment to determine if your patient is unstable or stable, if unstable, stabilize their airway breathing and circulation.

Unstable patient0:49–3:05

Additionally, obtain IV access, provide supplemental oxygen if needed and put them on continuous vital sign monitoring, including BP, 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 hypertension or even shock as well as altered mental status and significant abdominal tenderness.
Finally, labs can reveal hypoglycemia as well as hyponatremia and hyperkalaemia. Additionally, you might notice elevated B UN 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 H PA axis and the patient's serum cortisol level doesn't increase as it should. Ok.
Now, let's go back to the ABCD E assessment and take a look at stable patients. Your first step is to take a focused history and physical exam.

Stable patient3:05–3:48

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 a.m.
cortisol level. First, let's discuss patients with decreased morning cortisol, which is typically less than 3 mcg per deciliter.
With this result, you can confidently diagnose adrenal insufficiency to proceed with labs primarily ACTH and B MP. These labs will help you classify adrenal insufficiency into primary secondary or tertiary type and therefore help you identify the cause.

Decreased cortisol3:48–4:15

Now, let's take a look at primary adrenal insufficiency. If the AC is elevated and other labs reveal abnormalities like hyponatremia hyperkalemia and perhaps hypoglycemia, then the diagnosis is primary adrenal insufficiency also known as Addison disease.

Elevated ACTH4:15–6:34

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 VL CFA.
For short normal VLCFA values suggest the diagnosis of idiopathic primary adrenal insufficiency on the flip side, elevated VL CFA suggests primary adrenal insufficiency due to adrenal leukodystrophy, which is an excellent genetic condition that typically affects male Children.
Ok. 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 Friedrichs syndrome, which is caused by bacterial sepsis from seria meningitis. Now moving on to treatment 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's important to treat the underlying cause as indicated. All right, let's go back to the ACTH and B MP results and take a look at secondary adrenal insufficiency.
If the patient has decreased ACTH and a normal B MP, go back to your history and assess for any exogenous glucocorticoid use as well as chronic opioid use.
If the patient doesn't have a history of glucocorticoid or opioid use, think of secondary adrenal insufficiency and look for organic causes.

Decreased ACTH6:34–8:52

Remember, secondary etiologies come from outside of the adrenal gland but still within the HP axis. Secondary etiologies most commonly arise from the pituitary gland.
So your next step is to obtain a brain MRI and assess the anterior pituitary hormones which include FSH, LH GH prolactin and TSH.
Now, if either the brain MRI or the pituitary hormones are abnormal, this confirms secondary adrenal insufficiency due to pituitary disease.
And you can further diagnose the cause such as a tumor or apoplexy treatment consists of glucocorticoid replacement with hydrocortisone as well as pituitary hormone replacement and consider surgical consultation and radiation therapy.
Ok. Now, going back to Glucocorticoid or opioid use and take a look at tertiary adrenal insufficiency.
If the patient does report a history of recent usage of glucocorticoids or chronic opioid use, then you should diagnose tertiary adrenal insufficiency.
This commonly occurs when glucocorticoids are tapered too quickly or opioids are used chronically. In these cases, the exogenous glucocorticoid or opioid causes downregulation of the HP axis leading to a decrease in production of endogenous glucocorticoids.
If the exogenous glucocorticoid is stopped too abruptly, the body is unable to keep up with Glucocorticoid demand and the result is adrenal insufficiency treatment consists of replacing glucocorticoids again with hydrocortisone and counseling on slow, tapering off exogenous glucocorticoids.
If the patient is unable to wean off opioid use, they will need concurrent glucocorticoid replacement. Here's a clinical pearl.
Even taking as little as 5 mg of predniSONE daily for a minimum of two weeks, can put the patient at risk of glucocorticoid withdrawal and adrenal crisis.
So if they come in with a new problem causing stress to the body, they'll need a higher glucocorticoid dose because they're adrenally insufficient.
Now, let's go all the way back to our morning cortisol level and take a look at patients with indeterminate cortisol level, indeterminate result or a level of 3 to 17 mcg per deciliter are considered nondiagnostic.

Intermediate cortisol8:52–9:56

The next step is to perform a cosyntropin stimulation test. This is where synthetic ACTH is given to the patient to try to stimulate the cortisol to rise.
If the cortisol level stays below 18, that's an inadequate response to diagnose adrenal insufficiency, then proceed with the workup to determine the type and initiate the appropriate management.
On the flip side. If the cortisol does rise to a normal level of greater than 18 after cosyntropin stimulation, then that is a normal response.
So you should consider an alternative diagnosis. Finally, let's return one more time to the morning cortisol test.
If the result is greater than or equal to 18 mcg per deciliter, that is a normal morning cortisol. So you should consider an alternative diagnosis.
One last clinical pearl. All patients with adrenal insufficiency, regardless of type who require glucocorticoid replacement must be counseled on the prevention of adrenal crisis by increasing the steroid medications during periods of increased stress like infection or trauma.

Review9:56–11:10

All right, as a quick recap, if you suspect adrenal insufficiency, first perform the ABCD E assessment to determine if your patient is unstable or stable, unstable patients typically present with adrenal crisis.
So immediately proceed with acute management. On the other hand, if your patient is stable check morning cortisol levels, decreased cortisol confirms the diagnosis of adrenal insufficiency.
So you should order additional lab and imaging findings to determine the type primary adrenal insufficiency can be autoimmune idiopathic due to adrenal leukodystrophy or associated with conditions like infection hemorrhage or even malignancy.
On the other hand, secondary adrenal insufficiency is typically caused by pituitary conditions like tumors or apoplexy. While tertiary adrenal insufficiency is usually associated with use of exogenous glucocorticoids or opioids.
In all cases, the management primarily relies on hormone replacement
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