OBJECTIVES: Adrenal insufficiency (AI) is a rare disease caused by a deficiency in hormone synthesis by adrenal glands, due to either the destruction of the glands (primary AI: PAI) or hypothalamic / pituitary causes (secondary AI: SAI). Patients are treated with hormone replacement therapy, mainly hydrocortisone. Our aim was to assess the cost of AI management in France METHODS: We used data from the French National Health Insurance (Social security) on patients who benefited from a long duration disease status N°31 for their AI in 2011 (primary and secondary combined) on the one hand, and the results of a Delphi Panel survey on the other hand. This survey, involving 15 endocrinologists from academic hospitals, was designed to better understand the patients’ pathway in the absence of guidelines.  An epidemiological approach on the prevalence of the disease has led to a cost study using a "top-down" method. Sensitivity analyses were conducted on the following cost parameters: medical and drugs costs in primary care, costs of public and private hospitalizations - chosen according to their weight in the pathway described by the Delphi Panel. RESULTS: The social security paid a total of € 5,612,842 for 1377 AI patients in 2011. The annual cost per patient is therefore € 4,076, including 62% for primary care expenses, 29% for public hospital expenses and 9% for private hospital. The total population with AI is estimated between 26,000 and 30,000 patients, leading to a total cost ranging from € 106M and € 122M. A 1% reduction in hospital spending would generate a gain of € 430,000 to € 500,000 per year. CONCLUSIONS: Despite AI concerns few patients, significant costs are borne by Social Security. An increased compliance and a better management of symptoms such as fatigue could help optimizing this cost.