Methylprednisolone Pulse Treatment of Graves' Ophthalmopathy Is Not Associated with Secondary Adrenocortical Insufficiency

Abstract

Objective: Graves' ophthalmopathy (GO) is an inflammatory disease in the orbital region. The first-line medical treatment is glucocorticoids. An important potential side effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal (HPA) axis with impairment of endogenous cortisol production, implicating symptoms of adrenocortical insufficiency, especially in the period after cessation of therapy with possible risks in cases of intercurrent illness. The aim of this study was to evaluate HPA axis function before and after methylprednisolone pulse treatment of GO. Study Design: HPA axis function was evaluated by measurements of plasma ACTH and an ACTH stimulation test with plasma cortisol measurements at 0 and 30 min after an intravenous bolus of synthetic ACTH (Synacthen® 250 µg). This was done in 12 patients with GO before and at cessation of methylprednisolone pulse treatment (500 mg i.v. per week for 6 weeks followed by 250 mg i.v. per week for an additional 6 weeks). Results: All patients included fulfilled the criteria of intact HPA axis function before and at cessation of methylprednisolone pulse treatment. Data are given as medians (with ranges). Before glucocorticoid treatment basal plasma cortisol was 290 n<smlcap>M</smlcap> (196-579) and 786 n<smlcap>M </smlcap>(612-1,050) after ACTH stimulation. At cessation of therapy the corresponding values were 309 n<smlcap>M</smlcap> (88-718) and 852 n<smlcap>M</smlcap> (524-1,011), respectively. Thus, all patients passed a 30-min stimulated plasma cortisol of 500 n<smlcap>M</smlcap>. Before treatment plasma ACTH was 4.2 pmol/l (4-16) and at cessation of therapy the corresponding value was 4.8 pmol/l (2-9; p = 0.27). Conclusion: Transient suppression of the HPA axis with secondary adrenocortical insufficiency does not seem to be a common phenomenon after intravenous methylprednisolone pulse therapy for GO. Therefore, routine precautions are not necessary. However, our results do not exclude that transient secondary adrenocortical insufficiency might occur occasionally.

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

“…Data about the influence of intravenous glucocorticoids used in the treatment of GO on the HPA-axis are scarce. Greek and Danish studies showed no association between ivGCS treatment and AI development [9,10]. In our study the same conclusion was drawn.…”

Management of Graves’ hyperthyroidism and orbitopathy in time of COVID-19 pandemic

“…It is essential to strongly recommend following general measures of social confinement and distancing, hands and surfaces hygiene, shielding if and when going outside. Although intravenous glucocorticoid therapy for GO does not seem to be associated with secondary adrenal insufficiency [16], patients who recently finished the intravenous glucocorticoid treatment, and more obviously, those who completed a long-term course of oral glucocorticoids for GO, should be considered at risk of potentially having an acute adrenal crisis if they get infected by Coronavirus. Accordingly, they should receive instructions on how to recognize symptoms of incipient adrenal insufficiency, inform immediately their family doctor, and adjust the daily dose of hydrocortisone as indicated for sick days.…”

Treatment with Intravenous Methylprednisolone in Patients with Graves’ Orbitopathy Significantly Affects Adrenal Function: Assessment of Serum, Salivary Cortisol and Serum Dehydroepiandrosterone Sulfate

“…In our research, we did not find a statistically significant decrease of serum and salivary cortisol before administration of the 12th IVMP pulse in comparison to evaluation before treatment, while one study showed a statistically significant decrease of serum cortisol concentration before administration of the 12th IVMP pulse [ 11 ]. The results of our study show that none of the patients developed secondary AI at the cessation of IVMP treatment in a cumulative dose of 4.5 g. Previous studies did not prove secondary AI after therapy with standard EUGOGO protocol (cumulative dose of 4.5 g IVMP) as well [ 11 , 12 , 13 ]. However, dynamic testing with synthetic ACTH has low sensitivity in ruling out secondary AI, especially when considering short-lasting (less than 4–6 weeks) AI [ 14 ].…”