Application of the data to the case
To effectively assess the patient for adrenal insufficiency, we need additional information. First and foremost, is a description of the patient’s current clinical status. If she is demonstrating evidence of adrenal crisis, treatment should not be delayed for additional testing. If she is stable, a thorough history including use of corticosteroids by any route, pregnancy, oral contraceptives, recent surgery, and liver and kidney disease is essential.
Additional evaluation reveals the patient has been using her fluticasone inhaler daily. No other source of hyponatremia or lightheadedness is identified. The patient’s risk factors of corticosteroid use and unexplained hyponatremia with associated lightheadedness increase her pretest probability of AI and a single morning cortisol of 10 mcg/dL is insufficient to exclude adrenal insufficiency. The appropriate follow-up test is a standard high-dose cosyntropin stimulation test at least 18 hours after her last dose of fluticasone. A cortisol level > 18 mcg/dL at 30 minutes in the absence of other conditions that impact cortisol testing would not be suggestive of AI. A serum cortisol level of < 18 mcg/dL at 30 minutes would raise concern for abnormal adrenal reserve due to chronic corticosteroid therapy and would warrant referral to an endocrinologist.
Bottom line
An isolated serum cortisol is often insufficient to exclude adrenal insufficiency. Hospitalists should be aware of the many factors that impact the interpretation of this test.
Dr. Gordon is assistant professor of medicine at Tufts University, Boston, and a hospitalist at Maine Medical Center, Portland. She is the subspecialty education coordinator of inpatient medicine for the Internal Medicine Residency Program. Dr. Herrle is assistant professor of medicine at Tufts University and a hospitalist at Maine Medical Center. She is the associate director of medical student education for the department of internal medicine at MMC and a medical director for clinical informatics at MaineHealth.
References
1. Bleicken B et al. Delayed diagnosis of adrenal insufficiency is common: A cross-sectional study in 216 patients. Am J Med Sci. 2010;339(6):525-31. doi: 10.1097/MAJ.0b013e3181db6b7a.
2. Bornstein SR et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89.
3. El-Farhan N et al. Measuring cortisol in serum, urine and saliva – Are our assays good enough? Ann Clin Biochem. 2017 May;54(3):308-22. doi: 10.1177/0004563216687335.
4. Kazlauskaite R et al. Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: A metaanalysis. J Clin Endocrinol Metab. 2008;93:4245-53.
5. Wood JB et al. A rapid test of adrenocortical function. Lancet. 1965;191:243-5.
6. Singh Ospina N et al. ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab. 2016;101(2):427-34.
7. Burgos N et al. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2019;26(3):139-45.
8. Odom DC et al. A Single, post-ACTH cortisol measurement to screen for adrenal insufficiency in the hospitalized patient. J Hosp Med. 2018;13(8):526-30. doi: 10.12788/jhm.2928.
9. Broersen LHA et al. Adrenal insufficiency in corticosteroids use: Systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(6): 2171-80.
Key points
• In general, random cortisol testing is of limited value and should be avoided.
• Serum cortisol testing in the hospitalized patient is impacted by a variety of patient and disease factors and should be interpreted carefully.
• For patients with low pretest probability of adrenal insufficiency, early morning serum cortisol testing may be sufficient to exclude the diagnosis.
• For patients with moderate to high pretest probability of adrenal insufficiency, standard high-dose (250 mcg) corticotropin stimulation testing is preferred.
Additional reading
Bornstein SR et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89.
Burgos N et al. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2019;26(3):139-45.
Quiz
An 82 y.o. woman with depression is admitted from her long-term care facility with worsening weakness and mild hypoglycemia. Her supine vital signs are stable, but she exhibits a drop in systolic blood pressure of 21 mm Hg upon standing. There is no evidence of infection by history, exam, or initial workup. She is not on chronic corticosteroids by any route.
What would be your initial workup for adrenal insufficiency?
A) Morning serum cortisol and ACTH
B) Insulin tolerance test
C) Corticotropin stimulation test
D) Would not test at this point
Answer: C. Although her symptom of weakness is nonspecific, her hypoglycemia and orthostatic hypotension are concerning enough that she would qualify as moderate to high pretest probability for AI. In this setting, one would acquire a basal serum total cortisol and ACTH then administer the standard high-dose corticotropin stimulation test (250 mcg) followed by repeat serum total cortisol at 30 or 60 minutes.
