Megestrol acetate-associated adrenal insufficiency

Background:Megestrol acetate (MA) is commonly used to promote weight gain in malnourished elderly patients. Although adrenal insufficiency has been reported as an adverse effect of MA, this association is not well recognized in clinical practice. Case summary: An 80-year-old woman with worsening dyspnea was transferred to our university-affiliated community medical center from an inpatient psychiatric facility, where she was being treated for major depressive disorder with psychotic features. She had undergone a general decline in physical function accompanied by some weight loss and anorexia consistent with failure to thrive and, 1 month earlier, had been started on MA 400 mg/d to stimulate her appetite and improve her nutrition. During hospitalization at our center, the patient's dyspnea worsened and she was transferred to the intensive care unit, where she was intubated. While in the intensive care unit, the patient developed hypotension. Infectious, cardiac, and neurologic causes of hypotension having been ruled out, a cosyntropin stimulation test was performed to rule out adrenal insufficiency. Cortisol levels before, 30 minutes after, and 60 minutes after administration of cosyntropin were 1.6, 7.1, and 9.8 μg/dL, respectively, indicating a suboptimal response. The adrenocorticotropic hormone level was 8 pg/mL (normal, 10-60 pg/mL). Based on these findings suggesting adrenal insufficiency, MA was discontinued and steroid replacement was initiated. The patient's blood pressure normalized and she improved slowly. She was weaned from the ventilator several weeks later and was discharged to a skilled nursing facility. At 2-month follow-up, the patient's strength and respiratory function were improved, and the results of a repeat cosyntropin stimulation test were normal (cortisol response before, 30 minutes after, and 60 minutes after cosyntropin administration: 15.4, 22.6, and 25.2 μg/dL, respectively). The Naranjo score for this case was 7, indicating a probable correlation between MA use and adrenal insufficiency. Conclusions: This case of adrenal insufficiency in an elderly woman was probably related to MA use. Clinicians should be alert to the possibility of this adverse effect when considering use of MA therapy.