One of the easiest ways to detect possible medication errors is to verify the reason for every medication a patient is taking. It sounds simple but often enough, patients will be taking a round white tablet daily and not know why. What is worse is when the physician doesn’t notice the medication and does not understand why it was prescribed. When this occurs, the pharmacist is in the best position to catch the oversight. This is especially important in nursing home patients, who are frequently transferring to and from hospitals. Medication reconciliation (review of medications upon arrival) reduces the risk of medication errors such as therapeutic duplication (for example, Prilosec and Prevacid), inappropriateness (for example, antibiotic for a resolved infection), and inadvertent medication omission. The continuity of care is better streamlined from facility to facility when this process is properly done.

In this case, the patient is taking prednisone which appears to have no indication based on the patient’s medical history. The admitting physician does not mention it in their notes. Read the case. What role does prednisone play in this patient?

MC is an 84-year old Asian female who presents to the emergency room (ER) after sustaining a fall at her nursing home. For the past two weeks, she complains of lightheadedness and weakness. There is no loss of consciousness or head trauma. Her past medical history include anemia, dementia, sick sinus syndrome with permanent pacemaker, hypertension, hyperlipidemia, obesity, headache, anemia, osteoarthritis, diabetes mellitus, and cataract surgery in both eyes. The computerized tomography (CT) scan of her head is negative. CT of her chest shows bilateral pleural effusions and a calcified granuloma in the right middle lobe.

On admission, her labs are unremarkable except for a sodium level of 120 mEq/liter (low) and a serum osmolality of 251.2 mOsm/liter (low). Thyroid stimulating hormone (TSH) is 2.10 (normal). She is afebrile with blood pressure of 135/79 and heart rate is 20.

Her routine medications from the nursing home include docusate 100 mg BID, furosemide 40 mg BID, and prednisone 5 mg every morning and 2.5 mg every night.

The doctor resumes all her medications and orders a cosyntropin or adrenocorticotropic hormone (ACTH) stimulation test. Do you recognize a problem with this order?

1. Conduct your research

The problem is that there is a drug-test interaction with cosyntropin and prednisone. Cosyntropin is adrenocorticotropic hormone (ACTH), used to test for adrenal insufficiency. A baseline cortisol level must be drawn before the test is given. Cosyntropin is administered as 0.25 mg IV slow push over 2 minutes. After 30 minutes, another cortisol level is drawn. If the cortisol level increases (level of 18 mcg/dl or more) after the test, then the body is showing a normal response to ACTH. There is no adrenal insufficiency. If there is minimal or no change from baseline, the test is positive for adrenal insufficiency which means that the patient is not producing enough cortisol.

If a baseline ACTH level is drawn, then it can be used to differentiate between primary and secondary adrenal insufficiency. Patients with primary adrenal insufficiency will have elevated levels of ACTH. However, patients with secondary adrenal insufficiency will have low levels of ACTH.   

Patients who are concurrently taking steroids, spironolactone, and estrogens need to hold their doses on the day before and on the day of the test. If your patient is taking prednisone, the cortisol levels may be extremely elevated giving you a false normal result.

Now, let’s go back to the original question: what is the role of prednisone in this patient?  The patient is taking low dose prednisone, probably for adrenal insufficiency. There are two clues: first, the doses are split during the day (5 mg in the AM and 2.5 mg in the PM) which is to mimic the body’s own diurnal rhythm and second, there is no other diagnosis such as asthma, rheumatoid arthritis, SLE, or any other autoimmune disease that may be the reason for why prednisone was prescribed.

If the patient is already taking a cortisol replacement, then why does the physician still suspect adrenal insufficiency? Replacing cortisol is difficult in regards to the steroid choice and dosing. Hydrocortisone, prednisone, and dexamethasone are well-studied for cortisol replacement. They have varying potencies as a glucocorticoid and mineralocorticoid. In addition, dosing is tricky. The dose needs to be low enough to replace the deficiency but not excessive enough to inhibit the hypothalamus-pituitary-adrenal (HPA) axis. The doses need to be split to mimic the body’s own diurnal rhythm. And higher doses are warranted when the patient is undergoing surgery, has a fever, upper respiratory infection, or a serious illness. In this case, a cosyntropin test is probably not necessary. This patient may have benefitted from a higher dose of prednisone or adding on fludrocortisone to increase salt and water reabsorption.  

2. Notify the physician

When you notify the physician, avoid the pitfall of “oversharing”. You want to list the facts; there is no need to explain the mechanism, pathophysiology, or research unless specifically asked to. An example would be, “Doctor, may I make a suggestion? Can we hold the cosyntropin test? The patient is already on low-dose prednisone which has the same dosing used for adrenal insufficiency. To increase mineralocorticoid activity, we can increase the dose of prednisone or add fludrocortisone 0.1 mg daily. What do you think?”

The physician agrees with you but wants the cosyntropin test to be done first. Regardless of your opinion, you need to honor the request and still provide the best patient care. Advise to hold the prednisone dose on the day before and on the test day. Remind the physician, lab, or nursing to order the post-test cortisol level and baseline ACTH level.

Outcome of the case

The physician agrees and the tests are ordered. The baseline cortisol level is 7.4 mcg/dl. After the cosyntropin stimulation test, the cortisol rises to only 9.8 mcg/dl. The baseline ACTH is 55 pg/ml, which is high normal. Most likely, this patient has primary adrenal insufficiency. Instead of resuming prednisone, the physician orders hydrocortisone 20 mg every morning and 10 mg at night. Hydrocortisone has twice more mineralocorticoid properties than prednisone which is responsible for salt and water retention.

References

Lovas K, Husebye ES. Replacement Therapy for Addison’s disease: Recent developments. Expert Opin Investig Drugs. 2008 Apr;17(4):497-509.

About the Author

Dr. Karine Wong has a 10 year history of working in hospital management and 2 years as a hospital pharmacist and outpatient pharmacist. She recently published a children's book called Don't Sit on Her.