Influence of 4‐week or 12‐week glucocorticoid treatment on metabolic changes in patients with active moderate‐to‐severe thyroid‐associated ophthalmopathy

Abstract

Thyroid-associated ophthalmopathy (TAO) is a serious, progressive, vision-threatening and difficult-to-treat organ-specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High-dose intravenous glucocorticoid (IVGC) therapy is considered a first-line treatment for active moderate-to-severe TAO, but there is still insufficient evidence regarding the treatment duration. Long-term IVGC therapy can influence the metabolism of glucose, lipids and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 weeks and 12 weeks IVGC therapy. Forty-eight patients with active moderate-to-severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12-week group had increased fasting plasma glucose (P=0.004), glycated hemoglobin (P=0.028), total cholesterol (P<0.001) and low-density lipoprotein (P<0.001) after therapy. The patients in both groups had reduced bone metabolism markers after therapy. Thyroid peroxidase antibody and thyrotropin receptor antibody levels decreased after treatment in both groups (P<0.001). A significant decrease in thyroglobulin antibody levels was found in the 4-week group (P=0.006). The change in the ADC was higher in the 4-week group than in the 12-week group (P=0.014). However, there were no significant differences in CAS values between the two groups. Therefore, 4-week IVGC therapy was recommended for TAO patients with glucose and lipid disorders.

Decrease in Bone Formation and Bone Resorption during Intravenous Methylprednisolone Pulse Therapy in Patients with Graves’ Orbitopathy

“…However, the decrease of P1NP persistent after the full course of IVMP therapy in our study indicates that the cumulative effect of intravenous GCs on bone may be dose-dependent, similarly to the oral GCs [ 12 ]. Chen et al evaluated the effect of various IVMP therapy regimens in GO on BTM (using the same cumulative dose of 4.5 g over 12 weeks versus over 4 weeks), showing similar decrease in P1NP [ 25 ]. Hu et al showed the decrease in P1NP only after the second cycle of IVMP therapy with a cumulative dose of 4.5 g [ 15 ].…”

“…Previous studies suggest that excessive bone resorption occurs especially in the early phase during oral GCs therapy [ 14 , 29 ]. In reports assessing the impact of intravenous GCs, bone resorption was decreased [ 15 , 16 , 18 , 25 ] or increased [ 19 , 20 ], depending on the time of measurement and the parameter analyzed ( Table 3 ). However, it should be noted that in all studies involving GO patients treated with repeated IVMP pulses, a decrease of bone resorption markers was found [ 15 , 16 , 18 , 25 ].…”

“…In reports assessing the impact of intravenous GCs, bone resorption was decreased [ 15 , 16 , 18 , 25 ] or increased [ 19 , 20 ], depending on the time of measurement and the parameter analyzed ( Table 3 ). However, it should be noted that in all studies involving GO patients treated with repeated IVMP pulses, a decrease of bone resorption markers was found [ 15 , 16 , 18 , 25 ]. It seems that IVMP therapy in GO does not increase bone resorption but may result in its inhibition.…”

“…The number of reports assessing the effects of intravenous GCs on BTM is limited. There are studies demonstrating the suppression of bone formation (expressed by a decrease in different BTM) occurring immediately after very high doses of intravenous GCs [ 19 , 20 , 22 , 23 , 24 , 25 ]; however, none has done so after 0.5 g of IVMP. The impact on bone resorption remains to be elucidated.…”

Mechanisms of immune-related differentially expressed genes in thyroid-associated ophthalmopathy based on the GEO database

“…Glucocorticoids (GCs) have long been used in the treatment of various ocular diseases due to their powerful anti-inflammatory, anti-edema, and anti-neoangiogenic properties (38)(39)(40). In patients with TAO, a GC is the main treatment option, and the European group for GD orbitopathy recommends intravenous GC therapy as the 1st-line option for patients with moderately severe active TAO (41,42).…”