Use of Methotrexate to Treat Isolated Graves Ophthalmopathy Developing Years After Thyroidectomy and Iodine 131 Treatment of Papillary Thyroid Cancer

ObjectiveTo describe a case of Graves ophthalmopathy developing years after subtotal thyroidectomy and radioactive iodine treatment of papillary thyroid cancer.MethodsWe present a case report including clinical and laboratory data. Current relevant literature is reviewed and summarized with regard to Graves ophthalmopathy.ResultsIn 2001, a 51-year-old woman presented with an asymptomatic thyroid nodule. Fine-needle aspiration biopsy results showed Hürthle cells, and the patient had a subtotal thyroidectomy in 2002. Stage 2 follicular variant of papillary thyroid carcinoma was diagnosed. She received radioactive iodine (I 131) therapy (94.8 mCi and 147.2 mCi) in 2003. Thyrotropin was suppressed with levothyroxine. The patient remained asymptomatic and had undetectable thyroglobulin antibodies. In 2007, her eyes became irritated (ie, erythematous, pruritic, watery). Thyroperoxidase and thyroglobulin antibodies were undetectable, but thyrotropin receptor antibody was elevated to 44% (reference range, < 16%). On physical examination, moderate periorbital edema and conjunctival injection were present; orbital magnetic resonance imaging was normal. Computed tomography of her orbits showed symmetric bilateral exophthalmos and prominence of orbital fat. Other ophthalmologic etiologies were ruled out by 2 independent ophthalmologists. She had minimal improvement with oral and intravenous steroids. Subsequent treatment with methotrexate resulted in marked symptomatic improvement and lowered the thyrotropin receptor antibody level to 24%.ConclusionsIsolated Graves ophthalmopathy in a patient after treatment of thyroid cancer and radioactive iodine ablation has not been previously reported. Methotrexate therapy may be a useful therapeutic approach in this setting. (Endocr Pract. 2008;14:422-425)     

Serum Selenium Levels in Patients With Graves Disease With or Without Thyroid Ophthalmopathy

BackgroundGraves disease is one of the most common autoimmune thyroid diseases. Thyroid has the highest concentration of selenium (Se) in the body. Se plays a crucial role in the functioning of some thyroid enzymes; however, there are controversial results regarding the administration of serum Se levels in patients with Graves disease.MethodsIn this study, patients with Graves disease with orbitopathy (GO group) or without orbitopathy (GD group) were recruited. Healthy individuals without a history of any disease were enrolled as the control group. Serum Se and thyroid hormone levels, including T3, T4, and thyroid-stimulating hormone (TSH), were measured using atomic absorption and radioimmunoassay techniques, respectively.ResultsIn this cross-sectional study, 60 and 56 patients and 58 healthy subjects were included in the GO, GD, and control groups. Serum Se levels in the GO, GD, and control groups were 94.53 ± 25.36 μg/dL, 96.82 ± 30.3 μg/dL, and 102.55 ± 16.53 μg/dL, respectively (P = .193). There was a reverse association between the serum Se level and thyroid hormones, including T3, T4, and TSH, in the GO group. However, serum Se levels exhibited a significant reverse association with T4 and TSH hormones but not with T3 in the GD group.ConclusionOur results showed no significant differences in the serum Se levels in the GO and GD groups compared with that in the control group. In addition, we did not detect any significant difference in the serum Se levels between the GO and GD groups.     

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer

ObjectiveTo determine the frequency of levothyroxine (LT4) supplementation after therapeutic lobectomy for low-risk differentiated thyroid cancer (DTC).MethodsThis retrospective cohort study enrolled adult patients with low-risk DTC confirmed using surgical pathology who underwent therapeutic lobectomy at a single institution from January 2016 through May 2020. The outcome measures were postoperative serum thyroid-stimulating hormone (TSH) levels and the initiation of LT4. The predictors of a postoperative TSH level of >2 mU/L and initiation of LT4 were evaluated using Cox proportional hazards models.ResultsPostoperative TSH levels were available for 115 patients (91%), of whom 97 (84%) had TSH levels >2 mU/L after thyroid lobectomy. Over a median follow-up of 2.6 years, a postoperative TSH level of >2 mU/L was associated with older age (median 52 vs 37 years; P = .01), higher preoperative TSH level (1.7 vs 0.85 mU/L; P < .001), and primary tumor size of <1 cm (38% vs 11%, P = .03). Multivariate analysis revealed that only preoperative TSH level was an independent predictor of a postoperative TSH level of >2 mU/L (hazard ratio [HR] 1.53, P = .003). Among patients with a postoperative TSH level of >2 mU/L, 66 (68%) were started on LT4 at a median of 74 days (interquartile range 41-126) after lobectomy, with 51 (77%) undergoing at least 1 subsequent dose adjustment to maintain compliance with current guidelines.ConclusionMore than 80% of the patients who underwent therapeutic lobectomy for DTC developed TSH levels that were elevated beyond the recommended range, and most of these patients were prescribed LT4 soon after the surgery.     

激素冲击治疗联合放疗对中重度Graves 眼病临床疗效分析

目的:探讨激素冲击治疗联合放疗用于中重度Graves眼病的临床疗效。方法:将2014年2月~2015年6月之间我院收治的109例中重度Graves眼病患者随机分为A组(n=37)、B组(n=35)、C组(n=37)。A组患者单纯采用抗甲状腺药物治疗,B组患者则在A组的基础上进行激素冲击治疗,C组患者则采用B组基础上联合球后放疗方案治疗,所有患者治疗后保持随访至少6个月,对比三组疗效,记录三组患者治疗前、治疗6个月时的临床活动评分(CAS)及眼球突出度,及随访期间不良反应情况。结果:三组有效率比较,C组B组A组,差异有统计学意义(P0.05)。治疗后三组CAS评分均显著优于治疗前(P0.05),且C组显著低于A、B组(P0.05),A、B组间比较无显著差异(P0.05)。治疗后B、C组眼球突出度显著低于治疗前(P0.05),且C组显著低于A、B组(P0.05)。A、B、C三组不良反应发生率分别为0、14.29%、5.41%,A、C组比较无显著差异(P0.05),B组不良反应发生率明显高于A、C组(P0.05)。结论:激素冲击联合放疗治疗中重度Graves眼病具有显著的疗效,能够有效降低患者的CAS评分及眼球突出度,效果明显优于单纯抗甲状腺治疗或激素冲击治疗,且安全性较好,值得在临床上推广和应用。     

Preoperative Radiation in the Treatment of Cancer

In the treatment of advanced cancer of the hypopharynx, preoperative radiation therapy has proven to be of value for the prevention of recurrences in the operative area following radical neck dissection for cancer of the head and neck. Also it has been of value in the planned combined therapy of certain patients with lung, bladder, breast, esophagus, bone, endometrial and rectal cancers.Preoperative radiation therapy should be advantageous in patients who have malignant disease where the possibility exists for the cancer cells to be disseminated during the surgical procedure.     

Altered Retinal Perfusion in Patients with Inactive Graves Ophthalmopathy Using Optical Coherence Tomography Angiography

Objective: The aim of this study was to evaluate retinal and optic nerve head (ONH) perfusion in patients with inactive Graves ophthalmopathy (GO) and compare it to healthy controls using optical coherence tomography angiography (OCTA).Methods: Twenty-nine eyes of 29 patients with inactive GO (study group) and 29 eyes of 29 healthy subjects (control group) were included in this study. The vessel density (VD) data in the superficial and deep retinal OCT angiogram of the macula and the radial peripapillary capillary network (RPC) were extracted and analyzed. OCTA was performed using RTVue XR Avanti with AngioVue (Optovue Inc, Fremont, CA). Clinical activity was evaluated using the clinical activity score, the severity assessment using the NOSPECS classification.Results: The VD in the superficial OCT angiogram and in the OCT angiogram of the ONH was significantly lower in the GO group when compared to the control group (whole en face, P = .016; parafovea, P = .026; RPC peripapillary, P = .027). There was no significant correlation between VD and functional parameters or the NOSPECS classification.Conclusion: Macular VD and ONH capillary density measured using OCTA were significantly lower in the study group compared to healthy controls. Noninvasive quantitative analysis of retinal perfusion using OCTA could be useful in monitoring patients with GO.Abbreviations: CAS = clinical activity score; GO = Graves ophthalmopathy; OCTA = optical coherence tomography angiography; ONH = optic nerve head; RPC = radial peripapillary capillary; rSp = Spearman's correlation coefficient; VD = vessel density     

Application of Magnetic Resonance Imaging in the Evaluation of Disease Activity in Graves’ Ophthalmopathy

ObjectiveTo evaluate magnetic resonance imaging parameters, T2 signal intensity ratios (SIRs), and normalized apparent diffusion coefficients (n-ADC) of the extraocular muscles (EOMs) in the identification of different stages of Graves’ ophthalmopathy (GO) and to find out the correlation of T2-SIRs and n-ADC values with disease changes after anti-inflammatory treatment.MethodsAltogether, 43 patients (86 orbits) were enrolled and classified into “active” or “inactive” stages by clinical activity score (CAS). Twenty-three (53.5%) patients received anti-inflammatory treatment and underwent a follow-up evaluation. Fifteen age- and gender-matched control participants (30 orbits) were included. T2-SIRs and n-ADC values of EOMs were calculated among GO and healthy controls and were correlated with CAS. Changes in these parameters were also evaluated before and after anti-inflammatory treatment.ResultsMean T2-SIRs and n-ADC values were both significantly higher in GO patients than in controls and higher in active GO than in inactive GO. In the inactive stage, n-ADC values of inferior rectus muscles were still higher than those in healthy controls. Both T2-SIRs and n-ADC values decreased after intravenous steroid pulse therapy. The cutoff value of pretreatment n-ADC was 1.780 to detect stages with specificity of 93.7% and sensitivity of 48.3% (P = .035).ConclusionT2-SIRs and n-ADC values are valuable magnetic resonance imaging indicators of the inflammatory activity in GO by detecting involvement of EOMs. They are also ideal tools to monitor the efficacy of anti-inflammatory treatment in patients with active stage GO. n-ADC values, when combined with CAS, can be promising predictive factors in the detection of stages of diseases.     

Effect of Orbital Decompression on Corneal Topography in Patients with Thyroid Ophthalmopathy

Objective

To evaluate changes in corneal astigmatism in patients undergoing orbital decompression surgery.

Methods

This retrospective, non randomized comparative study involved 42 eyes from 21 patients with thyroid ophthalmopathy who underwent orbital decompression surgery between September 2011 and September 2014. The 42 eyes were divided into three groups: control (9 eyes), two-wall decompression (25 eyes), and three-wall decompression (8 eyes). The control group was defined as the contralateral eyes of nine patients who underwent orbital decompression surgery in only one eye. Corneal topography (Orbscan II), Hertel exophthalmometry, and intraocular pressure were measured at 1 month before and 3 months after surgery. Corneal topographic parameters analyzed were total astigmatism (TA), steepest axis (SA), central corneal thickness (CCT), and anterior chamber depth (ACD).

Results

Exophthalmometry values and intraocular pressure decreased significantly after the decompression surgery. The change (absolute value (|x|) of the difference) in astigmatism at the 3 mm zone was significantly different between the decompression group and the controls (p = 0.025). There was also a significant change in the steepest axis at the 3 mm zone between the decompression group and the controls (p = 0.033). An analysis of relevant changes in astigmatism showed that there was a dominant tendency for incyclotorsion of the steepest axis in eyes that underwent decompression surgery. Using Astig PLOT, the mean surgically induced astigmatism (SIA) was 0.21±0.88 D with an axis of 46±22°, suggesting that decompression surgery did change the corneal shape and induced incyclotorsion of the steepest axis.

Conclusions

There was a significant change in corneal astigmatism after orbital decompression surgery and this change was sufficient to affect the optical function of the cornea. Surgeons and patients should be aware of these changes.     

Development of a Novel Thyroid Function Fluctuated Animal Model for Thyroid-Associated Ophthalmopathy

Background

The establishment of a suitable and stable animal model is critical for research on thyroid-associated ophthalmopathy (TAO). In clinical practice, we found that patients treated with I-131 often exhibit TAO; therefore, we aimed to establish a novel thyroid function fluctuated animal model of TAO by simulating the clinical treatment process.

Methods

We treated SD rats with I-131 to damage the thyroid and then used sodium levothyroxine (L-T4) to supplement the thyroid hormone (TH) levels every seven days, leading to a fluctuating level of thyroid hormones that simulated the status of clinical TAO patients. Rats administered normal saline were considered as a control. The weight, intraocular pressure, and serum T3, T4, TSH and TRAb levels of the rats were measured, and the pathological changes were analyzed by H&E staining and transmission electron microscopy (TEM).

Results

The experimental rats (TAO group) exhibited significantly reduced weight and elevated intraocular pressure compared with the control rats. Meanwhile, the serum levels of T3 and T4 were up-regulated in the TAO group, but the TSH level decreased during the 10-week study. Moreover, increased numbers of blood vessels and inflammatory cell infiltrations were observed in the orbital tissues of the TAO rats, while no abnormal changes occurred in the control rats. The orbital myofibrils in the TAO rats appeared fractured and dissolved, with twisted structures. Mitochondrial swelling and vacuoles within the endoplasmic reticulum, swelling nerve fibers, shedding nerve myelin, and macrophages were found in the TAO group.

Conclusion

Rats treated with I-131 and sodium levothyroxine exhibited characteristics similar to those of TAO patients in the clinic, providing an effective and simple method for the establishment of a stable animal model for research on the pathogenesis and treatment of TAO.     

Thyroid Peroxidase Antibody Positivity is Associated With Relapse-Free Survival Following Antithyroid Drug Treatment for Graves Disease

Objective: Graves’ disease is an autoimmune disease characterized by production of autoantibodies directed against the thyroid gland. Thyrotropin-receptor antibodies (TRAbs) are clearly pathogenic, but the role of thyroidperoxidase antibodies (TPOAbs) in Graves disease is unknown.Methods: We retrospectively studied whether TPOAb positivity reduced risk of relapse following antithyroid drug (ATD) treatment in newly diagnosed Graves disease.Results: During follow-up of 204 patients with TRAb-positive Graves disease, 107 (52%) relapsed following withdrawal of ATD. Mean age was 40.0 years, and 82% were female. The average duration of ATD treatment was 23.5 months and was not different between patients who relapsed and those with sustained remission. Absence of TPOAbs significantly increased risk of Graves relapse (odds ratio, 2.21). Male sex and younger age were other factors significantly associated with increased risk of relapse.Conclusion: TPOAb positivity significantly improves the odds of remission following ATD treatment in newly diagnosed Graves’ disease.     

Thyroid Nodules and Thyroid Cancer

A review of clinical and laboratory features of thyroid cancer, designed to help in a more precise selection of patients for operation, showed that factors contributing to a high index of suspicion of cancer include previous exposure to low doses of radiation, the presence of a firm, solitary thyroid nodule clearly different from the rest of the gland, a young patient, nodules that are “cold” on scan with radioiodine, and nodules that fail to regress after an adequate trial of thyroxine therapy. Factors contributing to a low index of suspicion of thyroid cancer include soft or cystic lesions, multinodular goiters, nodules that are “hot” on ¹³¹ I scan, and those that regress during thyroxine treatment.When these factors are used to select patients for surgical operation, about 30 percent are found to have thyroid cancer.Until more precise methods for preoperative diagnosis are established, it is suggested that this type of clinical selection may be very helpful in the management of patients with thyroid nodules or nontoxic goiter.     

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine

ObjectiveThe aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism.MethodsA total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment.ResultsThe rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up.ConclusionProgression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.     

Predictors of Prolonged Euthyroidism After Radioactive Iodine Treatment for Graves’ Disease: A Pilot Study

ObjectivePatients with Graves’ disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI.MethodsDemographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models.ResultsAmong the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932.ConclusionPatients with Graves’ disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.     

Thyroglobulin Antibodies Disappeared After Stopping Immunoglobulin Therapy in a Patient with Thyroid Cancer

Abbreviations:Ig = immunoglobulinsTg = thyroglobulinTg Abs = anti-Tg antibodies     

The Impact of Thyroid Cancer and Post-Surgical Radioactive Iodine Treatment on the Lives of Thyroid Cancer Survivors: A Qualitative Study

Background

Adjuvant treatment with radioactive iodine (RAI) is often considered in the treatment of well-differentiated thyroid carcinoma (WDTC). We explored the recollections of thyroid cancer survivors on the diagnosis of WDTC, adjuvant radioactive iodine (RAI) treatment, and decision-making related to RAI treatment. Participants provided recommendations for healthcare providers on counseling future patients on adjuvant RAI treatment.

Methods

We conducted three focus group sessions, including WDTC survivors recruited from two Canadian academic hospitals. Participants had a prior history of WDTC that was completely resected at primary surgery and had been offered adjuvant RAI treatment. Open-ended questions were used to generate discussion in the groups. Saturation of major themes was achieved among the groups.

Findings

There were 16 participants in the study, twelve of whom were women (75%). All but one participant had received RAI treatment (94%). Participants reported that a thyroid cancer diagnosis was life-changing, resulting in feelings of fear and uncertainty. Some participants felt dismissed as not having a serious disease. Some participants reported receiving conflicting messages from healthcare providers on the appropriateness of adjuvant RAI treatment or insufficient information. If RAI-related side effects occurred, their presence was not legitimized by some healthcare providers.

Conclusions

The diagnosis and treatment of thyroid cancer significantly impacts the lives of survivors. Fear and uncertainty related to a cancer diagnosis, feelings of the diagnosis being dismissed as not serious, conflicting messages about adjuvant RAI treatment, and treatment-related side effects, have been raised as important concerns by thyroid cancer survivors.