A Case With Graves Ophthalmopathy With Onset Of Hypothyroidism Treated By Methylprednisolone Impaction Followed By Mycophenolate Mofetil And Literature Review

Objective:To discuss the pathogenesis,clinical characteristics,and therapeutic methods of Graves'Ophthalmopathy?GO?through analyzing the clinical process of a male GO patient with onset of hypothyroidism and to reviewe the relevant literature.Methods:We retrospectively analyzed the clinical features of this GO patient,and discuss the reason of hypothyroidism,the changing of clinical characteristcs,as well as the reaction to the treatments of glucocorticoids and immunosuppressants.We reviewed the relevant literature focusing on the pathogenetic process,the characteristics and clinical experiences,and the clinical trials of new treatment methods of GO.Results:In June 2016,a 61-year-old male patient complained the symptoms,such as binocular diplopia,blurred vision,and eyelid swelling?especially the left eye?.He felt the symptoms more serious and visited our clinic six months later.The results of the thyroid function showed that serum thyroid stimulating hormone?TSH?was 22.34?IU/ml,free triiodothyronine?FT₃?was 4.62 pmol/L,free thyroxine?FT₄?was 14.54pmol/L,thyrotropin receptor antibody?TRAb?was 33.35 IU/L,thyroglobulin antibody?Tg Ab?was 670.00 IU/ml,thyroid peroxidase antibody?TPOAb?was 528.00 IU/ml.The patient was given levothyroxine sodium orally with the dosage of 25?g/d for 6w,and then of 50?g/d for 6m.In March 2017,the symptoms of diplopia and blurred vision were aggravated,accompanied by eye pain,too much tears and temporary blindness,which result in his hospitalization in our ward.He had a history of gastric ulcer for 15 years,of smoking for more than 40 years,with 10-20 sticks per day.No family history of thyroid diseases,or autoimmune diseases.Physical examination showed that exophthalmos,of which the degree was 18>—100—<18mm,edema in the double eyelids,bulbar conjunctiva,and palpebral conjunctiva,adduction in the left eye,limited upper vision and abduction of the left eye,and limited under vision in right eye.Mobious sign and von Graefe sign were positive,but Joffroy sign and Stellwag sign were negative.No enlargement of the thyroid glands.The results of the thyroid function tests showed that serum TSH was 145.80?IU/ml,FT₃was 3.67 pmol/L,FT₄was 10.64 pmol/L,TRAb was 93.20 IU/L,Tg Ab was more than 500.00 IU/ml,TPOAb was more than 1300.00 IU/ml.Orbital CT scan showed obvious thickening in the upper,lower,inner,and external rectus muscles of both eyes.As a result,the diagnosis of hypothyroidism and GO was clear.The clinical activity score?CAS?was 5/7 points,and the GO classification was considered as extremely severe?threatening vision type?according to the European group on graves'orbitopathy?EUGOGO?.Let the patient give up smoking,wear sunglasses,take levothyroxine sodium 50?g/d orally.Due to gastroscope showed ulcer healing period and erosion of gastric mucosa,agents of acid inhibition and protection of gastric mucosa were given.Re-examination of gastroscope showed improvement two month later.From August to October in 2017,cumulative dose of 4.5 g of methylprednisolone,divided into 12 weekly infusions?6 weekly infusions of 0.5 g,followed by 6 weekly infusions of 0.25 g?was given.Selenious Yeast agents?200?g/d×6m?were orally taken to resist oxidation.In November 2017,no obvious improvement was gained.The patient still complained eye pain,edema,and diplopia with the appearance of paroxysmal transient blindness.CAS remained the same without any decrease.The thyroid testings showed as TSH 18.60?IU/ml,FT₃3.21 pmol/L,FT₄8.13 pmol/L,TRAb 130.90 IU/L,Tg Ab over than 500.00IU/ml,and TPOAb over than 1300.0IU/ml.In January 2018,there was no improvement in eye symptoms and signs,and there were relative contraindications for the application of glucocorticoids such as gastric ulcers and decreased bone mass density.Mycophenolate mofetil dispersible tablets?Seccopine?with the dosage of 0.75 g/d,lasted for 6m were taken orally.Meanwhile,levothyroxine sodium 50?g/d and methimazole 5 mg/d were taken orally.In August 2018,the symptoms were relieved.The CAS dropped to 2/7 points,and the results of the thyroid function tests showed that TSH was 59.162?IU/ml,FT₃was 3.26 pmol/L,FT₄was 10.21 pmol/L,TRAb was201.7 IU/L.Orbital CT scan indicated the thickening of the extraocular muscles was alleviated in the left eye,but the right eye was aggravated.The dose of levothyroxine sodium was adjusted to 75?g/d,and methimazole was stopped.In December 2018,the CAS was 2/7 points.The results of the thyroid function tests showed that TSH was0.02?IU/ml,FT₃was 8.18 pmol/L,FT₄was 25.01 pmol/L,TRAb was 145.0 IU/L,indicating mild hyperthyroidism.So methimidazole 2.5 mg/d and levothyroxine sodium 50??g/d?were given.Eye symptoms improved significantly in January 2020,and the CAS was 1/7 points,the severity classification was reduced to moderate.Serum TRAb level decreased to 37.55 IU/L,as well as Thyroid stimulating antibody?TSAb?,also called Thyroid stimulating immunoglobulin?TSI?,was 37.4 IU/L?reference range,0 to 0.55 IU/L?,orbital CT scan showed each extraocular muscle become thinner than before.Conclusions:1.This GO patient developed hypothyroidism at onset and during the course of disease,with transient hyperthyroidism.Although the activity and severity of GO is not related to thyroid functions in this patient,the testing of thyroid function still should be detected regularly throughout follow-up to reduce the risk of GO.2.To treat with the patient severe refractory GO,methylprednisolone infusion should be chosen as the first-line treatment.And immunosuppressive,such as mycophenolate mofetil,may be a better choice with good efficacy and safety.