Citations

Abstract Disclosure: M. Dhanasekaran: None. A.A. Rajwani: None. M.R. Castro: None. J.C. Morris: None. J. Schmitz: None. R.A. Lee: None. M. Callstrom: None. M. Stan: None. Context: Autonomously functioning thyroid nodules (AFTNs) constitutes 5% of thyroid nodules and is the second most common cause of hyperthyroidism following Graves’ Disease. Untreated hyperthyroidism is associated with adverse cardiovascular and skeletal complications. Currently, radioactive iodine (RAI) and surgery are the standard treatment options for AFTNs, and both incur a risk of post-procedural hypothyroidism. To overcome this and other surgery/radiation-related complications, radiofrequency ablation (RFA) has been utilized in multiple countries (for both toxic and non-toxic thyroid nodules). It has been shown to induce significant nodule volume reduction along with restoration of normal thyroid function in many AFTNs. Methods: We present a single-center experience using RFA as an alternative treatment modality for AFTNs. The study's primary aim was to assess the efficacy of RFA in normalizing thyroid hormone concentration and restoring the euthyroid state. In addition, we analyzed the efficacy of RFA in nodule volume rate reduction (VRR) and its associated adverse events. Results: A total of 22 consecutive patients (17 F and 5 M) underwent RFA for a solitary AFTN (hot nodule in thyroid uptake and scan) under variable degrees of general anesthesia. 72% (n=16) had subclinical hyperthyroidism, 9% (n=2) had overt hyperthyroidism, and 18% (n=4) were biochemically euthyroid on anti-thyroid drugs (ATD). The mean age at the time of ablation was 52.09 years (SD= 14.6), with a mean BMI of 27.36 kg/m2 (SD= 4.67). Average pre-treatment TSH was 0.41 mIU/L (SD= 0.980) and free T4 1.29 ng/dl (SD= 0.33). The thyroid function was assessed after a single RFA session. TSH normalized in all patients within 3-6 months following the ablation. All four patients on ATD pre-treatment discontinued therapy within three months following the procedure. The average VRR (62.54%) was achieved within 3-6 months following the RFA, and importantly, none of the nodules grew back during the follow-up period (up to 24 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and two (9%) developed mild hypothyroidism requiring levothyroxine therapy. One patient, euthyroid post RFA, developed recurrent hyperthyroidism 45 months later and elected to undergo lobectomy. No serious adverse effects were noted in this cohort. Conclusions - RAI and/or surgery represent the standard of care for toxic adenomas but RFA shows excellent efficacy along with an excellent safety profile. Therefore at centers with RFA expertise it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications. Presentation Date: Saturday, June 17, 2023

Background: Corticosteroid therapy is often employed in thyroid eye disease (TED), but its efficacy is variable. Teprotumumab and tocilizumab have been considered as effective alternatives. This study aims to evaluate their clinical outcomes and safety in patients with steroid-resistant TED. Methods: A retrospective case–control study was conducted between 2018 and 2022 within a national multicenter health system. Thirty-seven patients with moderate to severe steroid-resistant TED treated with teprotumumab or tocilizumab (cases) were compared with steroid-naïve patients treated with similar therapy (controls). Due to lack of steroid-naïve patients treated with tocilizumab, a control subgroup for tocilizumab was not included in the analysis. Demographic and clinical characteristics were described. Proptosis, diplopia, clinical activity score (CAS), and disease severity (European Group on Graves' orbitopathy classification) were evaluated at weeks 0, 12, 24, and 52 after therapy initiation. Results: Thirty-one patients received teprotumumab (13 cases and 18 controls) and 6 received tocilizumab (cases). The mean age was 57 years (standard deviation ±14.3), median duration of TED was 11.5 months (interquartile range [IQR]: 7.2–17.7), and median excess proptosis was 4 mm (IQR: 2–8) above the upper limit of normal for sex and race. At week 24, in the teprotumumab cases, 81% had proptosis response (reduction of ≥2 mm), 45.5% resolution of diplopia, 85.7% disease inactivation (CAS <3), and 58.3% reverted to mild disease severity. There were comparable results in teprotumumab controls, with no significant differences between subgroups. In the tocilizumab cases, 50% had a proptosis response, 16.7% resolution of diplopia, 100% disease inactivation, and 75% returned to mild disease. In the teprotumumab cases, there was a trend toward worsening proptosis and diplopia between weeks 24 and 52. In the same time frame, the tocilizumab cases had a trend toward worsening diplopia, disease activity, and severity. In the teprotumumab subgroup, 46.2% experienced otic changes and 23.1% hyperglycemia. In the tocilizumab subgroup, there were no reported adverse events. Conclusions: Teprotumumab and tocilizumab improved inflammation in patients with moderate to severe TED who had failed previous steroid therapy. Additionally, the teprotumumab cases demonstrated similar improvement in proptosis and diplopia to the teprotumumab controls. Further evaluation, particularly regarding the long-term response and side effect profile, of these medications in steroid-resistant TED is needed.

AbstractContextInhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED).ObjectiveWe report the first clinical studies of an FcRn inhibitor, batoclimab, in TED.DesignProof-of-concept (POC) and randomized, double-blind placebo-controlled trials.SettingMulticenter.ParticipantsPatients with moderate-to-severe, active TED.InterventionIn the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks.Main OutcomeChange from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial).ResultsThe randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P &lt; .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P &lt; .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P &lt; .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.ConclusionsThese results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.

AbstractContextPregnant women with mutations in the thyroid hormone receptor beta (THRB) gene expose their fetuses to high thyroid hormone (TH) levels shown to be detrimental to a normal fetus (NlFe) but not to an affected fetus (AfFe). However, no information is available about differences in placental TH regulators.ObjectiveTo investigate whether there are differences in placentas associated with a NlFe compared with an AfFe, we had the unique opportunity to study placentas from 2 pregnancies of the same woman with THRB mutation G307D. One placenta supported a NlFe while the other an AfFe.MethodsSections of placentas were collected and frozen at −80 °C after term delivery of a NlFe and an AfFe. Two placentas from healthy women of similar gestational age were also obtained. The fetal origin of the placental tissues was established by gDNA quantitation of genes on the X and Y chromosomes and THRB gene. Expression and enzymatic activity of deiodinases 2 and 3 were measured. Expression of following genes was also quantitated: MCT10, MCT8, LAT1, LAT2, THRB, THRA.ResultsThe placenta carrying the AfFe exhibited a significant reduction of deiodinase 2 and 3 activities as well as the expression of the TH transporters MCT10, LAT1 and LAT2, and THRA.ConclusionWe present the first study of the effect of the fetal THRB genotype on the placenta. Though limited by virtue of the rarity of THRB mutations and sample availability, we show that the fetal THRB genotype influences the levels of TH regulators in the placenta.

Abstract Context Teprotumumab therapy for thyroid eye disease (TED) patients represents a major step forward. It targets and inhibits the insulin-like growth factor-1 receptor (IGF-1R), and its effectiveness is based on its interconnectedness with the thyrotropin receptor. However, IGF-1R has a ubiquitous expression and several adverse effects have been reported with teprotumumab use. Objective Describing these adverse effects for better understanding is the purpose of this review. Methods We reviewed the oncological studies in which teprotumumab was initially used. Subsequently we reviewed the clinical trials for TED and then the case series and case reports associated with teprotumumab use since it is US Food and Drug Administration approval (January 2020). We focused on common and/or serious adverse effects reported with the use of teprotumumab. Results We described the common occurrence of hyperglycemia (10%-30% incidence), its risk factors and suggested management. Hearing changes are described, a broad spectrum from mild ear pressure to hearing loss (sensorineural mechanism). Risk factors, suggested monitoring, and possible upcoming therapies are reviewed. We also reviewed data on fatigue, muscle spasms, hair loss, weight loss, gastrointestinal disturbances, menstrual changes, and infusion reactions. We noted some discrepancies between adverse effects in oncological studies vs studies focused on TED, and we aimed to explain these differences. Conclusion The use of teprotumumab should consider patient's values and preferences in balancing the expected benefit with these potential risks. Future drugs targeting IGF-1R should investigate these adverse effects for a possible class effect. Combination therapies with different agents hopefully will be identified that maximize benefits and minimize risks.

Abstract Thyroid dysfunction in pregnancy has been associated with hypertensive disorders of pregnancy and poor maternal and fetal outcomes. In this article, we describe two cases of significant thyroid dysfunction leading to new diagnoses of chronic hypertension in pregnancy and review physiologic changes in the thyroid gland, placenta and maternal cardiovascular system during pregnancy.

Purpose: To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared with conventional thyroid eye disease (TED). Methods: A multi-institutional retrospective case series of patients with AI-TED was compiled. Chart review evaluated for clinical characteristics, imaging findings, and treatment for AI-TED. Additionally, a comprehensive review of the literature identified all previously published cases of AI-TED. Results: Five new patients with AI-TED were included in this series. The average clinical activity score on presentation was 2.8 (range 1–4) and reached an average peak of 5.0 during the active phase of the disease (4–7). Patients were treated medically with selenium (40%) or monoclonal antibodies including teprotumumab or tocilizumab (40%). Surgical treatment with orbital decompression for compressive optic neuropathy was performed on 2 (40%) patients. Combined with 11 previously reported cases, these 16 patients with AI-TED had an average clinical activity score on presentation of 3.3. The average length of the AI-TED phase was 14.0 months, and all patients were treated with medical and/or surgical interventions for their disease. Conclusions: Clinical and imaging findings in AI-TED mirror that of conventional TED, however, AI-TED may present with greater severity. AI-TED may develop many months after Graves’ disease; therefore, providers should be aware of this association and monitor patients for the development of severe TED.

Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders.

Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists. Endocrinologists, therefore, have a key role in diagnosis, initial management, and selection of patients who require referral to specialist care. Given that the need for guidance to endocrinologists charged with meeting the needs of patients with TED transcends national borders, and to maximize an international exchange of knowledge and practices, the American Thyroid Association and European Thyroid Association joined forces to produce this consensus statement.

Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists. Endocrinologists, therefore, have a key role in diagnosis, initial management, and selection of patients who require referral to specialist care. Given that the need for guidance to endocrinologists charged with meeting the needs of patients with TED transcends national borders, and to maximize an international exchange of knowledge and practices, the American Thyroid Association and European Thyroid Association joined forces to produce this Consensus Statement.