American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation.

Treatment of active, moderate-to-severe Graves’ orbitopathy (GO) is the administration of intravenous methylprednisolone (IVMP). IVMP may be followed by additional therapy with oral prednisone. The aim of this study was to analyze the impact of IVMP on adrenal function by evaluation of serum, salivary cortisol and serum dehydroepiandrosterone sulfate (DHEA-S). Fourteen patients received IVMP treatment (cumulative dose of 4.5 g in 12 weekly infusions) followed by oral prednisone (for three months). All patients showed normal adrenal function before the 12th IVMP pulse and one patient was diagnosed with secondary adrenal insufficiency (AI) after prednisone treatment. DHEA-S was significantly lower before the 12th IVMP pulse and after oral prednisone (p = 0.015 and p = 0.00002, respectively) in comparison to evaluation before therapy. DHEA-S levels were below the reference range in one and three patients before the 12th IVMP pulse and after prednisone therapy, respectively. We observed decreased serum (p = 0.05) and salivary (p = 0.011) cortisol levels after oral prednisone therapy in comparison to evaluation before therapy. Treatment with IVMP in a cumulative dose of 4.5 g affects adrenal function, causing more severe impairment of DHEA-S secretion than that of cortisol but does not cause secondary AI. Additional therapy with oral glucocorticoids after IVMP can cause secondary AI.

ABSTRACT Background: Intravenous glucocorticoids pulses administration is the main therapeutic option in the treatment of Graves’ orbitopathy. Such therapy could relate to the multiple adverse effects. The aim of the study is evaluation the influence of intravenous methylprednisolone (IVMP) pulse therapy on the heart rhythm (HR) changes in patients with active, moderate-to-severe Graves’ Orbitopathy (GO). Methods: We studied 20 patients with moderate-to-severe GO. All patients received 12 IVMP pulses (6x500 mg plus 6x250mg) at equal time intervals in a weekly schedule. We performed Holter ECG monitoring for 3 consecutive days (the day before, the day of IVMP and day after IVMP) to monitor HR and arrhythmias. We compared changes in HR between these 3 days and set time interval when the alteration was significant. This evaluation was performed during the 1st, 6th and 12th IVMP pulse. Results: Increased HR, in comparison with the day before, was registered on the day of IVMP administration. The most significant increase in HR started 5 hours (h) after a pulse administration and lasted 12 h. There were no significant differences in HR between the day before and the day after IVMP. We did not notice any major adverse cardiac events including severe arrhythmias. Conclusions: IVMP therapy is associated with increased HR, that occurs a few hours after infusion, lasts several hours and is transient.  Keywords: Graves’ ophthalmopathy; Graves’ disease; glucocorticoids; heart rate

Introduction. Systemic steroid therapy leads to disturbances in carbohydrate metabolism. The effect of immunosuppression with intravenous methylprednisolone (IVMP) pulses on glycaemia is not conclusive. Aim. This study aimed to assess the short-term effect of IVMP therapy in moderate-to-severe Graves' orbitopathy (GO) on glycaemic control in normoglycaemic patients with and without pre-diabetes. Material and Methods. Twenty-five GO patients treated with IVMP pulses (at initial dose of 6 x 0.5 g once a week, followed by0.25 g given for 6 consecutive weeksweekly) were recruited and divided into a normoglycaemic group (n = 15, patients without pre-diabetes) and a pre-diabetic group (n = 10, patients with impaired fasting glycaemia (IFG) and/or impaired glucose tolerance (IGT)). Six daily capillary blood glucose measurements were performed at fixed times the day before and on the day of the first pulse administration. Results. There was a significant increase in the glucose concentration on the day of IVMP administration in both groups of patients compared to the day before drug administration, with 50% of patients showing an increase in blood glucose above 200 mg/dl. There were no statistically significant differences between the two groups. Conclusions. Methylprednisolone in a high intravenous dose has a tremendous impact on the blood glucose level in normoglycaemic and pre-diabetic patients on the day of drug administration.