A Rare Case of Adrenal Insufficiency Induced by Inhaled Corticosteroids

Abstract

A 76-year-old man was admitted to the geriatric ward for pronounced asthenia, inability to walk, anorexia, and loss of 10% of his weight in 1 month. He also complained about recent memory loss. He had a history of severe chronic obstructive pulmonary disease, heavy smoking (60 pack-years), depression, prostatic hyperplasia, and gastroesophageal reflux disease. His medication consisted of darifenacin (15 mg/d); esomeprazole (20 mg/d); oxazepam (7.5 mg/d); calcium and vitamin D supplements; and inhaled fluticasone (500 μg/d), salmeterol (100 μg/d), and tiotropium (18 μg/d). Upon admission, he was extremely weak and cachectic (body mass index 16 kg/m2). He had difficulty focusing attention and was stuporous. Temperature and heart rate were normal. Blood pressure was low (95/60 mmHg). Physical examination showed slight diffuse abdominal tenderness. Initial blood tests showed slight anemia (hematocrit 34.8%) but normal white blood cell count and slightly low blood sodium (134 mmol/L), blood potassium (3.4 mmol/L), and glucose (3.6 mmol/L). Nutritional biomarkers were low (albumin 23 g/L, prealbumin 47 mg/L) in the absence of any inflammation. Given the above clinical and biological findings, adrenal insufficiency was suspected. His morning blood cortisol level was extremely low (21 nmol/L). Blood adrenocorticotropic hormone level was also below normal (<2 pmol/L). The rest of the pituitary hormonal levels were normal (thyroid-stimulating hormone 2.13 mIU/L, follicle-stimulating hormone 8.4 IU/L, luteinizing hormone 14.7 IU/L, prolactin 8.2 μg/L). A dynamic test consisting of measuring plasma cortisol levels before and 60 minutes after intravenous administration of 250 μg of tetracosactide acetate stimulated cortisol production (plasma cortisol before tetracosactide acetate 10 nmol/L; plasma cortisol after tetracosactide acetate 150 nmol/L) and was compatible with a secondary adrenal insufficiency. Anti-adrenal antibodies were negative, excluding autoimmune adrenal insufficiency. Thoracoabdominal computed tomography and brain magnetic resonance imaging were also normal. The man's treating physician and pharmacist confirmed the absence of systemic corticosteroid prescriptions for at least the last 18 months. A diagnosis of adrenal insufficiency caused by inhaled corticosteroids was finally suggested. A treatment with 10 mg of prednisone was initiated, with excellent clinical and biological response, and he was discharged 4 weeks later. He had gained 5 kg, was able to walk with a simple cane, and reported no asthenia or memory loss. We present a rare case of adrenal insufficiency related to chronic use of inhaled corticosteroids in an older man. Adrenal function suppression by inhaled corticosteroids is uncommon, and most frequently, concomitant use of oral corticosteroids is reported.1 Adrenal function suppression depends on the type of corticosteroid, dosage, treatment duration, method of inhalation and drug interactions.2 Our patient was under long-term treatment with 500 μg/d of fluticasone propionate. A meta-analysis showed that fluticasone propionate is more potent for adrenal suppression than other inhaled corticosteroids, probably because of higher affinity and longer receptor residency, longer elimination half-life (14.4 hours), and higher lipophilicity, resulting in greater tissue residency and systemic activity. When 8:00 a.m. plasma cortisol suppression potency was considered, 1 mg of inhaled fluticasone was equivalent to 10 mg of oral prednisolone.3 Concomitant administration of cytochrome CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir, amiodarone) may further increase the risk of adrenal insufficiency caused by inhaled corticosteroids.2, 4 No such interaction was noted in our patient. Diagnosis in this patient was particularly challenging because asthenia, weight loss, and memory impairment are frequent and unspecific in this age group. This case illustrates well the diagnostic difficulties encountered in older adults and the risk of overlooking life-threatening conditions if such symptoms are dismissed as “age related.” Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Samaras N.: physician who treated patient, coordinated and participated in manuscript preparation. Schneider A.: intern who treated patient, participated in writing paper. Frangos E.: bibliography search and preparation of manuscript. Forster A.: physician who treated patient, participated in writing the manuscript. Samaras D.: nutrition specialist, participated in treating patient and writing manuscript. Sponsor's Role: No sponsor participated in the design, data collection, analysis, or preparation of paper.