October 21, 2021
5 minute read
Haymart M. Year in Thyroidology. Presented at the American Thyroid Association Annual Meeting; Sept. 30-Oct. 3, 2021 (virtual meeting).
Disclosures: Haymart does not report any relevant financial information.
In an update on notable and recently conducted thyroid studies, a speaker reviewed the latest imaging treatments and modalities for children and adults that have the potential to change the practice of thyroidology.
Megan R. Haymart
“As a clinician-scientist, I focused on new and potentially practice-changing studies,” Megan R. Haymart, MDProfessor of Medicine, Metabolism, Endocrinology and Diabetes and Nancy Wigginton Professor of Endocrinology Research in Thyroid Cancer at the University of Michigan and endocrine today Member of the editorial board, says Healio. “There were many fantastic posts between November 2019 and August 2021, but these five stood out. Two of the publications focus on new or better treatment options for certain patients, and three of the publications challenge current practice paradigms and/or suggest a need for new research directions.
In a literature review presented at the annual meeting of the American Thyroid Association, Haymart highlighted clinical research on thyroid disease published between November 2019 and August 2021. The meta-analyses, reviews, statements of consensus and guidelines were excluded, as were manuscripts focusing on surgery and procedures. .
Selpercatinib for medullary thyroid cancer
As Healio reported, researchers reported in August 2020 that selpercatinib (Retevmo, Eli Lilly), an anti-RET kinase inhibitor, was effective and safe for adults RET– altered medullary thyroid cancer (MTC).
Selpercatinib was administered orally in 28-day cycles; participants in phase 2 received 160 mg twice daily. The cohort included participants with RET mutant MTC who had received prior treatment with (n=55) or without (n=88) the multikinase inhibitors vandetanib (Caprelsa, Sanofi Genzyme) and/or cabozantinib (Cometriq/ Cabometyx, Exelixis), as well as as in patients with previously treated RET fusion-positive thyroid cancer (n=19). The primary endpoint was complete or partial response; secondary endpoints were duration of response, progression-free survival (PFS), and safety.
Among the 55 participants with RET-mutant MTC, those previously treated with vandetanib and/or cabozantinib showed an objective response rate of 69% (95% CI, 55-81), with a 1-year PFS rate of 82% (CI 95%, 69-90) . Among those with RET– MTC mutants who had not received prior treatment, 73% (95% CI, 62-82) achieved an objective response, with a 1-year PFS rate of 92% (95% CI, 82-97 ).
Haymart noted that most associated adverse events were grade 1 or 2; the most common grade 3 or 4 adverse events were hypertension (21%), alanine transaminase increased (11%) and aspartate transaminase increased (9%). Discontinuation of treatment due to treatment-related adverse events occurred in only 2% of participants, she said.
Based on the results, published in The New England Journal of Medicine, the FDA has granted accelerated approval to selpercatinib for adults and children ages 12 and older with advanced or metastatic disease RET– Mutant MTC requiring systemic treatment and adults and children aged 12 years and older with advanced or metastatic disease RET fusion-positive thyroid cancer that requires systemic treatment and has stopped responding to or is unsuitable for radioactive iodine treatment.
“This is a clinically important study that suggests there may be treatment options with excellent risk-benefit ratios for some patients,” Haymart said.
Teprotumumab for thyroid eye disease
Adults with thyroid eye disease assigned the human monoclonal antibody teprotumumab-trbw (Tepezza, Horizon Therapeutics) were significantly more likely to experience a significant improvement in proptosis after 21 weeks of treatment compared to those who received a placebo, according to results of a randomized controlled trial published in the New England Journal of Medicine.
As Healio reported in January 2020 , adults with Graves’ disease and moderate to severe active thyroid eye disease received an IV infusion of teprotumumab (n=41) or placebo (n=42) once every 3 weeks for 21 weeks. The primary endpoint was reduction of proptosis by at least 2 mm at 24 weeks. Within the cohort, 82% of teprotumumab-treated participants achieved a proptosis response versus 10% in the placebo group (P .001).
JThe FDA approved teprotumumab for the treatment of adults with thyroid eye disease in January 2020, marking the first drug approved for the disease.
“Again, when you think about the risks versus the benefits, there was an excellent response, and most of the adverse events were grade 1 or 2,” Haymart said. “It’s another treatment option, and it may change clinical practice.”
Risks of overtreatment during pregnancy
A cohort of pregnant women in Canada who were overtreated for hypothyroidism with levothyroxine were more likely to have preterm labor than women with normal thyroid-stimulating hormone, according to a study published in Thyroid.
As reported by Healio, the objective of the retrospective study was to determine test and treatment regimens and the relationships between overtreatment and undertreatment with adverse pregnancy outcomes in women who were given prescribed thyroid hormone replacement. The researchers used multiple logistic regression analysis to determine whether a TSH level of less than 0.1 mIU/L (overtreatment) or at least 10 mIU/L (undertreatment) was associated with pregnancy or adverse neonatal outcomes.
Researchers found that pregnant women with at least one TSH measurement below 0.1 mIU/L (n=351 pregnancies) were more than twice as likely to have a preterm birth as controls (OR=2, 14; 95% CI, 1.51-2.78) . Undertreatment was not associated with adverse pregnancy or neonatal outcomes.
“It was a manuscript that resonated with me because it made me question some of my practices,” Haymart said. “It could change practice or at least spur further study.”
Thyroid imaging in children
The thyroid imaging data and reporting system (TI-RADS) for ultrasound scoring has not been previously validated in pediatric patients, Haymart said. A retrospective analysis published in Radiology in 2020, assessed data from 314 children (mean age, 15 years; 82.8% female) from a single center who underwent fine-needle aspiration biopsy between 2004 and 2017; the number of nodules that would be biopsied based on TI-RADS was compared to the number of nodules biopsied in the clinic. Researchers observed that 19.1% of nodules were malignant, and using TI-RADS alone would have missed 22% of cancers (17 out of 77), Haymart said.
“A limitation of this was the retrospective design; TI-RADS was doomed,” Haymart said. “But there is a signal of this [study] this suggests that further work is needed. Maybe we should think about modifications of the TI-RADS for children.
Racial Disparities in the Treatment of Hypothyroidism
A study published in the Journal of the Endocrine Society in March, analyzed data from adults who had thyroid function tests in the 2007-2012 waves of the National Health and Nutrition Survey and had hypothyroidism (n=698). Within the cohort, 536 adults were treated, 115 were untreated with subclinical hypothyroidism, and 47 were untreated with clinical hypothyroidism. Researchers stratified participants as undertreated (TSH > 5.6 mIU/L), overtreated (TSH < 0.3 mIU/L), and adequately treated. Within the cohort, 10.4% were undertreated and 12.7% were overtreated.
“I chose this because most disparity research done today focuses on thyroid cancer and thyroid surgery, and much of it has been conducted by our fellow surgeons,” Haymart said. . “There’s more work that can be done in thyroid function, in thyroid and pregnancy, and in other areas of the thyroid.”
The researchers found that male gender, age below 45, and lack of access to routine health care were associated with not receiving thyroid hormone treatment; race, income level and education level were not associated with treatment, Haymart said. However, in multivariate regression analyzes combining overtreated and undertreated adults, Hispanic race was associated with an increased risk of inadequate treatment compared to non-Hispanic white adults (OR = 2.42; 95% CI, 1. 14-5,14).
“Why is this clinically important?” Haymart said. “First, more work is needed to understand whether downstream Hispanic adults experience adverse outcomes or events because of this; no more osteoporosis or arrhythmia. Do young pregnant women experience worse pregnancy outcomes related to undertreatment or overtreatment? Are there systemic barriers that we are unaware of? Are there any patient-physician communication issues? This suggests an area for future research.