Aug. 17, 2024
Secondary adrenal insufficiency (SAI) can be a challenging diagnosis to make, particularly in the setting of borderline baseline hormone testing. The cosyntropin stimulation test, the most widely used dynamic test to diagnose SAI, has a reported sensitivity as low as 64%. And although it's considered the gold standard, the insulin tolerance test is cumbersome and carries risk, including hypoglycemia.
The overnight metyrapone test (OMT) is reported to have high concordance with the insulin tolerance test but is not widely used due to lack of setup in many centers, the risk of adverse events when used in the outpatient setting and variable 11-deoxycortisol cutoffs for interpretation.
To address the need for a reliable, simple test to diagnose SAI, Irina Bancos, M.D., M.S., an endocrinologist at Mayo Clinic in Rochester, Minnesota, and her colleagues set out to retrospectively determine test characteristics of the overnight metyrapone test (OMT). They compared results to the cosyntropin stimulation test, where available, in a cohort of adults with suspected SAI. These findings were published in Clinical Endocrinology.
Dr. Bancos notes: "The OMT was performed as follows: Patients were advised to take a single dose of metyrapone at midnight with a snack and then go to the Endocrine Testing Center at 8 a.m. to draw blood for cortisol and 11-deoxycortisol. The administration of 20 mg hydrocortisone immediately after the blood draw was added later to the protocol. The 11-deoxycortisol concntration was measured by LC-MS/MS.
"We used an 11-deoxycortisol cutoff of < 7 mcg/dL to confirm SAI, while a cutoff of > 10 mcg/dL excluded the diagnosis. If 11-deoxycortiol after OMT was between 7 and 10 mcg/dL, the diagnosis of SAI was made on clinical judgment."
OMT was performed in 114 patients, with a range of etiologies for suspected SAI, including pituitary pathology and chronic glucocorticoid use. The pretest probability for SAI was low in 52 (46%), moderate in 48 (42%) and high in 14 (12%) patients. Mild adverse events were reported in seven (6%) patients, including nausea, vomiting, chills, fatigue, lightheadedness, warmth and drowsiness.
Dr. Bancos continues: "The prevalence of OMT-based SAI diagnosis was 26 (23%) and 47 (41%) using the 11-deoxycortisol cutoff of < 7 and < 10 mcg/dL, respectively. A higher pretest probability was associated with the OMT-based diagnosis of SAI. Compared with the OMT-based diagnosis of SAI using the 11-deoxcycortisol cutoff of 10 mcg/dL, the specificity of the cosyntropin stimulation test was 100%, but the sensitivity was only 52%."
Dr. Bancos concluded that the OMT is safe and well tolerated and can be useful in patients with low and moderate clinical probability of SAI. The OMT may be offered as a next step in select patients with normal cosyntropin test results where the diagnosis of SAI is being considered.
For more information
Saini J, et al. Use of overnight metyrapone test in suspected secondary adrenal insufficiency: A retrospective single centre-study. Clinical Endocrinology. 2024;100:203.
Refer a patient to Mayo Clinic.