Changing Concepts in Hyperthyroidism Management

CHICAGO — Endocrinologists may be shifting toward greater use of antithyroid drugs (ATDs) over radioactive iodine (RAI) for initial treatment of Graves’ disease. Severe thyrotoxicosis remains rare but is challenging to treat. And investigational agents like batoclimab and K1-70 hold promise for the future of hyperthyroidism management. These are a few takeaways from a clinical session at the American Thyroid Association (ATA) 2024 Meeting.

Trends in Initial Treatment of Graves’ Disease

US endocrinologists have increasingly shifted to ATDs as their preferred initial treatment for Graves’ disease over RAI therapy in recent decades, endocrinologist Brian W. Kim, MD, of the University of Chicago, Chicago, Illinois, told ATA attendees. Kim reviewed data from surveys of practice patterns published in 1990, 2011, 2013 and 2023. 

For example, a 2011 survey found that US practice patterns of initial use of I-131 initially decreased from 70% in 1990 to 60% in 2011. In that time, the initial use of ATDs increased from 30% to 39%.

A 2020 analysis of US insurance data from 2005 to 2013 found that 33% of patients had received initial I-131, while 60% had initially received ATDs.

Recently, a 2023 survey of North American endocrinologists found that only 11% chose I-131 as initial therapy for their patients with Graves’ disease. “Remember that about 60% had done so in 2011,” said Kim. “It’s quite apparent that by 2023, long-term antithyroid drug therapy had gained a lot of favor.”

Longer treatments with ADT (for over 18 months) have also become more common in the United States. These extended regimens are associated with higher rates of disease remission, though the potential cardiovascular risks of prolonged antithyroid drug use remain unclear, he said.

The fear of radiation-induced secondary cancers may lead to further declines in the use of RAI therapy in the future, said Kim.

How to Manage Severe Thyrotoxicosis

Patients with thyrotoxicosis resistant to usual treatments, while fortunately rare, are challenging to treat and may have a relatively high mortality rate, Carla Moran, MB BCh PhD, of University College Dublin in Dublin, Ireland, told attendees. 

Conventional treatment failure occurs most often in patients with amiodarone-induced thyrotoxicosis (AIT), said Moran. After evaluating the patient’s clinical stability, comorbidities and the severity of thyrotoxicosis, endocrinologists should consider a variety of therapies. These include iodine solutions, cholestyramine, lithium, perchlorate, iopanoic acid, plasma exchange, and RAI. “It’s helpful to have a favored option that is deliverable and practical for your practice,” she said, noting she may have one or two such patients per year.

These therapies should generally be considered a bridge to thyroidectomy, said Moran, noting that guidelines recommend salvage thyroidectomy for patients with AIT who have deteriorating cardiac function or whose thyrotoxicosis remains unresponsive to medical treatment. 

“While emergency thyroidectomy for thyroid storm has a 10% mortality rate, salvage thyroidectomy for AIT also carries a mortality rate of 6%-10%,” said Moran. “Thyroidectomy may be safer in acutely thyrotoxic patients in the modern era, but recommendations remain to render a patient euthyroid before surgery if possible.”

New Therapies, Approaches on the Horizon

Marius Stan, MD, of the Mayo Clinic in Rochester, Minnesota, closed the session by looking at potential improvements in managing hyperthyroidism. One such agent is the investigational monoclonal antibody batoclimab, which targets neonatal fragment crystallizable receptor inhibition and is designed to reduce immunoglobulin G levels. Stan noted that data from a proof-of-concept study with batoclimab had just been presented at the ATA meeting.

Another investigational agent, K1-70, a human monoclonal thyroid stimulating hormone (TSH) receptor-specific autoantibody, also shows promise in Graves’ disease and its accompanying orbitopathy, Stan said. He referred attendees to a paper that reported the findings of an open-label phase 1 safety and dose-finding study. “In 18 patients, K1-70 was safe and well tolerated, and six patients with thyroid eye disease showed improvement,” he said.

Many questions remain to be answered about K1-70, said Stan, including whether TSH receptor blockade can shrink large goiters or suppress TSH receptors on differentiated thyroid cancer cells. “We’ll also need to know whether patients on TSH receptor blockers will require bone health and other monitoring since thyroid-stimulating immunoglobulin and TSH will both increase,” he said. 

Stan also noted the variety of new management approaches in hyperthyroidism underway in early stages globally. These potential options include alterations to the gut microbiome, computer-based modeling of methimazole dosing, and new forms of ablation, perhaps with high-intensity focused ultrasound ablation and microwave ablation in addition to radiofrequency ablation.

In another new approach, improved wearable devices may offer guidance on when patients should receive testing and monitoring. “Wearable devices, like the iPhones that many of you already have, will tell you and will tell your physician when your heart rate has gone up,” Stan said. “That real-time information could be a trigger for testing, as opposed to the standard timeframe we discussed 4 weeks ago in the office.”

Kim and Moran disclosed no relevant financial relationships. Stan’s disclosures included relationships with Tourmaline, Genentech, Third Rock Ventures, Argenx, Septerna, Immunovant, Lassen Therapeutics,Viridian Therapeutics, Amgen, Lundbeck, MingHui Pharmaceutical, TshakaBio, Avilar Therapeutics, and Grifols.