Transient adrenal insufficiency following treatment of rheumatoid arthritis with intramuscular methylprednisolone acetate
Keywords:Addisonian crisis, Addison’s disease, Adrenal suppression, Adverse drug reaction, Depo-Medrone, Methylprednisolone
An 82-year-old woman presented with dizziness, a fall, and pubic fractures. She had resting severe hypertension, with marked orthostatic hypotension. She was recently diagnosed with cyclic citrullinated peptide (+) rheumatoid arthritis. She had received 120 mg intramuscular methylprednisolone (Depo-Medrone®) eight months prior, and a second dose a day preceding hospitalisation. Two days into the admission, her Glasgow coma scale (GCS) score dropped acutely from 15/15 (E4;V5;M6) to 3/15 (E1;V1;M1). The initial differential diagnoses were: an acute stroke (a total anterior circulation syndrome-TACS or brainstem stroke), opiate toxicity (fracture pains), and possible unwitnessed seizure (in a post-ictal state). Urgent computerised tomography (CT) brain was unremarkable. She had an acute-on-chronic hyponatraemia (nadir 121 mmol/L) while on long-term proton pump inhibitor therapy, and hyperkalaemia (peak 5.8 mmol/L). Initial management included intravenous (IV) naloxone, fluids and diazepam with poor clinical response. Due to persistent low GCS, the admitting team were concerned about a potentially guarded prognosis. However, based on the history of recent high dose steroid injections, plus the evolving clinical picture and abnormal biochemistry, empirical treatment was started (IV hydrocortisone 100 mg QDS and 0.9% saline infusion) for possible adrenal insufficiency. An ‘add-on’ request for random serum cortisol was made to her admission bloods, and returned low (33 nmol/L). With treatment, her GCS improved rapidly from 3/15 to 15/15. A subsequent planned short synacthen test was abnormal (cortisol level pre-synacthen 100; 30min post-synacthen 340), suggestive of adrenal insufficiency. Following consultation with endocrinology, she was maintained on oral hydrocortisone 10 mg (am)/5 mg(teatime) with sustained clinical improvement.
Hahner S, Ross RJ, Arlt W, Bancos I, Burger-Stritt S, Torpy DJ et al. Adrenal insufficiency. Nature Rev Dis Primers. 2021;7(1):19.
Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-89.
Saverino S, Falorni A. Autoimmune Addison's disease. Best Pract Res Clin Endocrinol Metab. 2020;34(1):101379.
Betterle C, Presotto F, Furmaniak J. Epidemiology, pathogenesis, and diagnosis of Addison's disease in adults. J Endocrinol Invest. 2019;42(12):1407-33.
Hellesen A, Bratland E, Husebye ES. Autoimmune Addison's disease-An update on pathogenesis. Ann d'endocrinologie. 2018;79(3):157-63.
Ogundipe OA, Neill MJ, Dherwani V. COVID-19 vaccination: a possible trigger for Addisonian crisis in a patient with Addison’s disease. Int J Basic Clin Pharmacol. 2022;11:336-43.
Ogundipe OA, Cross C. Hyponatraemia associated with the use of a proton pump inhibitor. Scottish Med J. 2009;54(1):58.
Glucocorticoid therapy. Available at: https://bnf.nice.org.uk/treatment-summaries/glucocorticoid-therapy/. Accessed on 7 July 2022.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-45.
Busto U, Naranjo CA, Sellers EM. Comparison of two recently published algorithms to assess the probability of adverse drug reactions. Br J Clin Pharmacol. 1982;13(2):223-7.
Kramer MS, Leventhal JM, Hutchinson TA, Feinstein AR: An algorithm for the operational assessment of adverse drug reactions. I. Background, description, and instructions for use. JAMA. 1979;242(7):623-32.
12. The use of the WHO-UMC system for standardised case causality assessment. Uppsala Monitoring Centre. Available at: https://www.who.int/publications/m/item/WHO-causality-assessment. Accessed on 7 July 2022.