Thyroid eye disease (TED) is a complex autoimmune condition that primarily affects individuals with Graves’ disease and hyperthyroidism. However, a lesser-known but clinically significant group includes patients who are hypothyroid or euthyroid at the time of TED diagnosis. These cases often present diagnostic challenges, and until recently, treatment options were limited and nonspecific.
The emergence of teprotumumab, a targeted monoclonal antibody therapy, has reshaped the treatment landscape for TED. While most early clinical trials focused on hyperthyroid patients, new data, notably a case series published by Dr. Raymond Douglas and colleagues, suggest that teprotumumab is also highly effective in hypothyroid and euthyroid populations. This article explores that data, offering insight into how this breakthrough treatment can benefit a broader spectrum of TED patients.
Understanding Thyroid Eye Disease in Non-Hyperthyroid Patients
TED is most commonly associated with autoimmune hyperthyroidism, but about 10-15% of patients present with normal (euthyroid) or low (hypothyroid) thyroid function. These cases can stem from Hashimoto’s thyroiditis or result from treatment for hyperthyroidism, such as radioactive iodine therapy. Despite differences in thyroid status, the orbital pathology is strikingly similar across patient groups, marked by inflammation, fat and muscle expansion, and eventual fibrosis.
Clinically, hypothyroid and euthyroid TED may be underrecognized or misattributed to other ocular conditions, delaying appropriate treatment. The severity of TED in these groups can mirror or even exceed that in hyperthyroid patients, highlighting the need for effective and timely intervention.
Teprotumumab: A Targeted Approach
Teprotumumab is a fully human monoclonal antibody that inhibits the insulin-like growth factor-1 receptor (IGF-1R), a key driver of TED’s inflammatory and fibrotic changes. By blocking IGF-1R activation, teprotumumab prevents the stimulation of orbital fibroblasts, cells responsible for producing hyaluronan and promoting tissue remodeling in the orbit.
This mechanism directly addresses the root cause of TED, regardless of a patient’s thyroid hormone levels. In contrast to steroids or radiation, which provide general immunosuppression, teprotumumab offers a disease-modifying treatment targeting TED’s pathophysiology.
Key Study: Teprotumumab in Hypothyroid and Euthyroid Patients
In the multicenter case series led by Dr. Raymond Douglas, researchers evaluated the use of teprotumumab in 23 patients with TED who were either hypothyroid or euthyroid at the time of treatment. The study included individuals with varying disease durations and levels of disease activity.
Findings from the study include:
- Proptosis Reduction: A significant decrease in eye bulging (≥2mm) was observed in most patients (90%), consistent with results seen in hyperthyroid TED studies.
- Improved Clinical Activity Scores (CAS): Most patients (90%) experienced reduced inflammation and orbital congestion.
- Diplopia Relief: Several patients (67%) noted improvements or (47%) resolution in double vision, an outcome linked to reduced extraocular muscle involvement.
- Response Across Disease Durations: Patients with both recent-onset and longer-standing TED responded to treatment, broadening the potential application of teprotumumab beyond the traditional 9-month “active phase” window.
The study concluded that thyroid functional status does not limit the efficacy of teprotumumab—a finding that supports expanding treatment access to all TED patients, not just those with Graves’ hyperthyroidism.
Safety and Tolerability
Teprotumumab’s safety profile in hypothyroid and euthyroid patients mirrored that of other populations. Common side effects included:
- Muscle spasms
- Nausea and gastrointestinal discomfort
- Hyperglycemia, particularly in patients with preexisting glucose intolerance
- Hearing-related side effects, such as tinnitus or mild hearing loss
These adverse events were typically mild to moderate and resolved spontaneously or with supportive treatment. Importantly, no new safety concerns emerged specific to hypothyroid or euthyroid patients in the case series. Nonetheless, regular monitoring—especially of glucose levels and hearing—is recommended during the 8-infusion course of treatment.
Comparisons to Traditional Therapies
Historically, TED treatment has relied on systemic corticosteroids, orbital radiation, and surgery. These options remain helpful in some instances but have several limitations:
- Corticosteroids offer quick inflammation relief but carry long-term risks and do not reverse structural changes like proptosis.
- Radiotherapy has modest effectiveness and can pose ocular toxicity risks.
- Orbital decompression and eye muscle surgery can improve disfigurement and function but are invasive and usually reserved for stable, inactive disease.
Teprotumumab offers a non-surgical alternative with the potential to reverse structural damage and restore quality of life without the side effects of steroids or the recovery time of surgery.
Clinical Implications and Changing Practice Guidelines
The results of Dr. Douglas’s study have influenced clinical thinking and are beginning to inform TED treatment guidelines. In patients with moderate-to-severe TED who are hypothyroid or euthyroid:
- Teprotumumab should be considered first-line therapy, especially if proptosis or diplopia is present.
- It is suitable even in longstanding or recurrent disease, and not limited to new-onset cases.
- Patients with stable thyroid function (regardless of TSH or T4 levels) can safely receive treatment, provided they are otherwise healthy and meet eligibility criteria.
This broadens the potential candidate pool and supports earlier, proactive intervention in patients who might otherwise be left with “watchful waiting” or limited options.
Patient Access and Cost Considerations
As with many specialty biologics, cost and insurance coverage remain essential considerations. Teprotumumab is covered under Medicare Part B and by most commercial plans, including TED, when prescribed for FDA-approved indications. The manufacturer, Amgen, also offers patient assistance programs to help reduce financial barriers.
Given the high price of the entire treatment course—estimated at over $300,000—clinicians and insurers are increasingly weighing cost-effectiveness. However, early data suggest that reducing the need for surgery, hospitalization, and long-term care may make teprotumumab a cost-saving option in the long term.
Final Thoughts
The data from Dr. Raymond Douglas and colleagues offer compelling evidence that teprotumumab is effective in treating thyroid eye disease across all thyroid states, including hypothyroid and euthyroid patients. By directly targeting the IGF-1R pathway, teprotumumab not only relieves symptoms but may also halt or reverse disease progression.
As clinical practice continues to evolve, this treatment provides a safe, effective, and targeted option for a wider patient population than previously thought possible. For individuals living with TED—regardless of their thyroid lab results—teprotumumab represents a new standard of care and a real source of hope.
