Special Populations, Emerging Targets, and Biomarkers

Managing thyroid eye disease in special populations requires careful attention to both disease activity and treatment-related risks. In this segment, Andrea Kossler, MD, discusses the complexity of caring for pregnant patients, individuals with diabetes, and those with coexistent neuropathies or autoimmune conditions. She notes that pregnancy represents a state of immunologic fluctuation in which Graves disease and TED may flare during or after gestation. Teratogenic and safety considerations preclude the use of teprotumumab in pregnancy, and patients who receive this biologic therapy must avoid conception for a prolonged period after treatment.

For patients with diabetes mellitus, Andrea Kossler, MD, stresses strict glycemic control before and during therapy, given the potential for corticosteroids and IGF‑1R inhibitors to exacerbate hyperglycemia. She also highlights the need for baseline and ongoing assessment of comorbid conditions such as inflammatory bowel disease, hearing impairment, and other autoimmune disorders, which may influence the safety profile of newer agents. Close collaboration with ophthalmology is particularly important when coexistent optic neuropathy or myopathy is suspected.

The discussion then turns to emerging therapeutic targets and biomarkers. Dr Kossler describes a pipeline that includes additional IGF‑1R–directed agents and drugs targeting IL‑6 or the neonatal Fc receptor (FcRn). She suggests that combination or sequential approaches may ultimately be necessary to fully address the heterogeneity of TED, where some patients experience durable remission after a single biologic course while others manifest persistent or relapsing disease. She also anticipates a growing role for serologic markers, such as thyrotropin receptor antibodies (TRAb), thyroid‑stimulating immunoglobulins (TSI), and potentially IGF‑1R‑related antibodies, to help stratify relapse risk and guide duration of therapy.

In special populations, Andrea Kossler, MD, emphasizes the need to align thyroid eye disease therapy with broader systemic considerations. Pregnancy is associated with dynamic changes in immune function that can precipitate flares of Graves disease and TED in the antepartum or postpartum periods. Dr Kossler notes that teprotumumab is contraindicated during pregnancy and requires an extended washout period before conception, necessitating alternative strategies and careful preconception counseling. For patients with diabetes mellitus, she prioritizes aggressive glycemic control, recognizing that both systemic corticosteroids and IGF‑1R–targeted therapy can significantly worsen hyperglycemia.

Dr Kossler also highlights the importance of screening for coexisting conditions—such as inflammatory bowel disease, preexisting hearing deficits, and other autoimmune disorders—prior to initiating biologic therapy. These comorbidities may influence both drug selection and monitoring strategies. In patients with coexistent optic neuropathy or restrictive myopathy, she advocates particularly close coordination with ophthalmology and oculoplastic surgery to balance medical therapy and potential surgical interventions.

Regarding emerging therapies, Andrea Kossler, MD, describes an expanding field that includes next-generation IGF‑1R antibodies, IL‑6 inhibitors, and FcRn blockers. She envisions scenarios in which combinations of anti-inflammatory agents and disease-modifying biologics are used sequentially or concurrently, tailored to individual phenotypes (eg, inflammation-predominant vs proptosis-predominant disease). In parallel, she foresees increased reliance on biomarkers such as TRAb, TSI, and potentially IGF‑1R–specific assays, drawing analogies to how serologic profiles are already used in Graves disease to inform timing of antithyroid drug withdrawal. These tools may ultimately enable more precise prediction of treatment response and relapse risk in TED.