Stan, Marius N.

AbstractBackgroundThe management of Graves' disease (GD) in the US is shifting towards increased use of anti‐thyroid drugs (ATD). If patients fail to achieve remission after a standard course of therapy of 12–18 months, long‐term treatment with ATD (≥24 months) may be chosen over definitive therapy with radioiodine (RAI) or surgery. Clinicians will need to contrast this strategy to ablative therapies as they help patients in decision making.SummaryReview of the literature illustrates that long‐term ATD delivers euthyroidism with minimal complications, low financial cost and with an advantageous profile regarding quality of life (QoL) and other biological outcomes.ConclusionsLong‐term ATD is a viable alternative to ablative therapies in the management of GD offering advantages across multiple patient centred outcomes. Decision making must factor differences in this approach compared to ablative therapies and ultimately be tailored to individualized patient situations.

Background: Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF). Due to the rarity of thyrotoxic HF, population-based studies are lacking, and data from smaller studies are widely variable. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. HF was defined according to Framingham criteria. GD-related HFrEF was defined by left ventricular ejection fraction of <50%, while HFpEF was defined according to the Heart Failure Association of the European Society of Cardiology. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were analyzed with adjustments for age, gender, and history of coronary artery disease (CAD). 1:1 matching with controls (age, gender, and CAD) was additionally done. Results: HF occurred in 74 patients (31 HFrEF; 43 HFpEF). Incidence of GD-related HF, HFrEF, and HFpEF was 5.4%, 2.3%, and 3.1%, respectively. In HFrEF, atrial fibrillation (AF) (RR 10.05, p <0.001) and thyrotropin receptor antibodies (TRAb) level (RR 1.05 per unit, p=0.005) were independent predisposing factors. In HFpEF, independent risk factors were COPD (RR 5.78, p < 0.001), older age (RR 1.48 per 10 years, p = 0.003), overt hyperthyroidism (RR 5.37, p = 0.021), higher BMI (1.06 per unit, p = 0.003), and HTN (RR 3.03, p = 0.011). Rates of cardiac hospitalizations were higher in HFrEF (41.9% vs 3.2%, p <0.001) and HFpEF (44.2% vs 4.7%, p < 0.001) compared to controls. Furthermore, while both increased risk of strokes (HFrEF: RR 4.12, p = 0.027; HFpEF: RR 4.64, p = 0.009), only HFrEF increased risk of all-cause mortality (RR 3.78, p = 0.045). Conclusion: De novo HF occurs in 5.4% of patients with GD and increases the rate of cardiovascular events. HF occurs more frequently in GD patients with AF, higher TRAb, higher BMI, and overt hyperthyroidism, suggesting that these may be targets for treatment to prevent cardiovascular complications, especially in older multimorbid patients.

Background: Hyperthyroidism is associated with atrial fibrillation (AF) with a reported prevalence of 16-60%. However, risk factors for onset of AF with hyperthyroidism are not well defined. We sought to identify patients with hyperthyroidism most likely to develop AF. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. GD-related AF was defined as AF diagnosed up to 30 days before or at any time after Grave’s disease (GD). Spontaneous recovery was defined as sinus rhythm after attainment of euthyroidism without the need for pharmacologic or electrical cardioversion. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were compared between cases and controls (GD without AF) matched 1:1 for age, gender, and history of coronary artery disease. Results: AF occurred in 140 patients with an incidence of 10.2%. Older age (RR 1.63 per 10 years, p <0.001), male gender (RR 2.06, p < 0.001), overt hyperthyroidism (RR 2.48, p = 0.002), COPD (RR 2.14, p =0.006), and higher BMI (RR 1.03 per unit, p=0.023) were independent risk factors for AF. Spontaneous AF recovery occurred in 44 of 128 (34.6%) patients with adequate follow up. The multivariate risk factor for failed recovery was the presence of heart failure (HF) (OR =3.52, p= 0.004). GD patients with AF had higher rates of cardiac hospitalizations (Figure) that persisted even after adjusting to HF presence (27.9% vs 2.9%, p < 0.001). Conclusion: Risk factors for AF in GD are similar to those in the general population, although overt hyperthyroidism conferred the highest risk. These data argue for careful monitoring of GD patients with multimorbidity who may be at high risk of developing AF.

Abstract Background Currently acceptable management options for patients with adult papillary thyroid microcarcinoma (APTM) range from immediate surgery, either unilateral lobectomy or bilateral lobar resection, to active surveillance (AS). An alternative minimally invasive approach, originally employed for eliminating neck nodal metastases, may be ultrasound-guided percutaneous ethanol ablation (EA). Here we present our experience of definitively treating with EA 15 patients with APTM. Patients and Methods During 2010 through 2017, the 15 cT1aN0M0 patients selected for EA were aged 36 to 86 years (median, 45 years). Tumor volumes (n = 17), assessed by sonography, ranged from 25 to 375 mm3 (median, 109 mm3). Fourteen of 15 patients had 2 ethanol injections on successive days; total volume injected ranged from 0.45 to 1.80 cc (median, 1.1 cc). All ablated patients were followed with sonography and underwent recalculation of tumor volume and reassessment of tumor perfusion at each follow-up visit. Results The ablated patients have now been followed for 10 to 100 months (median, 64 months). There were no complications and no ablated patient developed postprocedure recurrent laryngeal nerve dysfunction. All 17 ablated tumors shrank (median 93%) and Doppler flow eliminated. Median tumor volume reduction in 9 identifiable avascular foci was 82% (range, 26%-93%). After EA, 8 tumors (47%) disappeared on sonography after a median of 10 months. During follow-up no new PTM foci and no nodal metastases have been identified. Conclusions Definitive treatment of APTM by EA is effective, safe, and inexpensive. Our results suggest that, for APTM patients who do not wish neck surgery and are uncomfortable with AS, EA represents a well-tolerated and minimally invasive outpatient management option.

Abstract Introduction: Anti-thyroid Drugs (ATD) have become the most frequently used treatment for Graves’ disease (GD) in the United States. However, the response to this therapy is variable. Factors that predict biochemically responsive vs. biochemically persistent disease remain unknown. Identifying predictors of disease poorly responsive to ATD can help guide treatment decision making, follow up planning and prognosis. Methods: From a database of patients with GD treated with ATD and receiving care at an academic medical center between 2009–2019, we selected adults with incident GD treated with ≥14 days of ATD. Results: 172 patients (from a database of 730 patients with GD on ATD) were sampled for the purpose of this pilot and 97 of these met inclusion criteria. Patients had a median age of 50 (18–90); female, 70.1%; never smokers, 64.9%; median goiter size of 40 g (15–100); and median TRAb on presentation of 8.1 mIU/L (1.0- 60). Graves’ orbitopathy (GO) was present in 13.4% at baseline. Patients (100%) were started on methimazole at a median dose of 20 mg (2.5–60). The median time from presentation until biochemical improvement (defined as the first instance of FT4 ≤1.7 ng/dL) was 120.9 days (18–1525), and to biochemical euthyroidism (normal TSH & FT4) was 251 days (41–1259) including a median of 3 (0–17) dose adjustments. In a univariate analysis, response to ATD was divided into two groups; biochemically responsive and biochemically persistent disease (based on reaching biochemical improvement in ≤6 months, or &gt;6 months respectively). Biochemically persistent disease was more common in those with GO at presentation (38.5% vs.11.1%) (p .024). There was a trend towards greater prevalence of biochemically persistent disease in those with TRAb ≥ 8.0 mIU/L (46.2% vs. 27.8%) (p .204), and goiter estimated 30 grams or above by physical examination (30.8% vs. 19.4%) (p .460). Biochemically responsive disease was associated with higher frequency of hypothyroidism during treatment (p .047). Conclusion: Our preliminary results illustrate the spectrum of response to ATD and predictors of biochemically persistent disease. We aim to expand this analysis utilizing a large database. As use of ATD increases, clinicians and patients can apply this data to estimate response to therapy, and identify patients that may require more aggressive therapy, thereby tailoring management plans.

Abstract Introduction: Thyroid eye disease (TED) is an autoimmune condition that negatively impacts patient’s quality of life (QOL). The GO-QOL questionnaire was originally developed in the Netherlands to quantify how TED and treatments affect patient QOL. This questionnaire includes eight questions each on visual functioning and appearance related QOL; the items are answered on a 3-point Likert scale and transformed to a 0 (worst) to 100 (best) scale. Though widely used and validated outside the US, the questionnaire has not been validated in the United States (US). Here we examine the content validity. Methods: Patients with moderate or severe TED were identified using an existing market research patient database, clinician referrals, patient groups, and social media. Interested participants were screened for eligibility prior to completing the GO-QOL. Subjects were also questioned about TED-related signs, symptoms, and treatments and underwent a cognitive interview following GO-QOL completion. Results: Thirteen TED patients completed the assessments (mean age = 44.8 ± 11.5 years, range: 26-67); all were female. Mean TED duration was 4.6 ± 5.5 years (range: 0.4-20.7). Twelve patients (92.3%) had Graves’ disease and one had Hashimoto’s thyroiditis. Descriptions of how TED signs and symptoms impacted quality of life were consistent with GO-QOL items, and qualitative interviews indicated that patients found the GO-QOL content relevant and complete. Responses indicated that minor wording changes may be needed to account for US cultural and language conventions and prevent confusion (specifically related to a bicycling question [12/13 reported not regularly riding a bike before TED symptom onset]). Visual functioning impacts most commonly-reported during the interview were difficulty driving a motor vehicle (92% of participants), difficulty with electronic screens (e.g., televisions, smart phones, and computers; 77%), difficulty moving around outdoors (including issues with light sensitivity, uneven surfaces, and depth perception; 69%), and difficulty doing hobbies or pastimes (69%). Emotional/psychological impacts frequently reported by participants were change in appearance (92%), depression and anxiety (including fear and worry; 77%), and frustration and anger (including moodiness; 69%). Negative reactions from others (staring, asking questions), social impacts and isolation, and lack of self-confidence and embarrassment were also reported (each 62%). Conclusion: This analysis of US patient interviews offered strong support for GO-QOL content validity. Therefore, the GO-QOL is appropriate to quantify TED-related QOL impact in a US population. However, a few slight wording modifications may be needed for future optimal use in the US.Reference: Terwee CB. Br J Ophthalmol 1998;82:773-779