The influence of Graves' orbitopathy treatment with intravenous glucocorticoids on adrenal function

Graves' orbitopathy (GO) is the commonest extrathyroidal feature of Graves' disease. For active, moderate to severe GO intravenous glucocorticoid pulse therapy (ivGCS) is the first-line treatment, which might be followed by oral glucocorticoid therapy. Glucocorticoid treatment, especially in the time of withdrawal, carries a risk of adrenal insufficiency. The aim of this study was to assess the pituitary-adrenal axis function in patients with GO before and at the cessation of ivGCS, and after further oral glucocorticoid therapy.

Twenty patients received treatment in accordance with the EUGOGO protocol (500 mg methylprednisolone once a week for six weeks, then 250 mg once a week for another six weeks) followed by oral prednisone at a gradually decreasing dose from 30 mg/day over a three-month period. Adrenal function was evaluated directly before the ivGCS, before the last pulse, and after oral glucocorticoid intake. The assessment consisted of clinical evaluation, and measurements of morning total serum cortisol (TSC) and plasma adrenocorticotropic hormone (ACTH). Patients with decreased cortisol level underwent ACTH stimulation test with TSC measurements before, and 30 minutes and 60 minutes after the administration of synthetic ACTH.

All patients before and at the cessation of ivGCS treatment demonstrated intact adrenal function. One patient after prednisone therapy presented decreased adrenal reserve. TSC concentration was significantly lower after the ivGCS (p = 0.025) and oral glucocorticoid therapy (p = 0.0006) in comparison to evaluation before therapy.

Therapy with ivGCS for GO does not lead to secondary adrenocortical insufficiency. Further low-dose oral glucocorticoid therapy may result in secondary adrenocortical insufficiency in some patients.