Endocrinologists' Role in Early Thyroid Eye Disease Recognition

Thyroid eye disease (TED), also known as Graves' ophthalmopathy, is an autoimmune inflammatory disorder affecting the orbit and periorbital tissues. It is strongly associated with Graves' disease, though it can occur in euthyroid or hypothyroid individuals. The pathogenesis involves autoantibodies, primarily against the TSH receptor, leading to fibroblast activation and subsequent inflammation, oedema, and adipogenesis within the orbit. This process can result in proptosis, diplopia, restrictive myopathy, and, in severe cases, optic neuropathy, which can lead to permanent vision loss. The natural history of TED typically involves an active inflammatory phase followed by a quiescent, fibrotic phase. Intervention during the active phase is crucial for disease modification and prevention of irreversible structural changes. However, early symptoms such as ocular irritation, tearing, or mild proptosis may be subtle and not immediately recognised as TED, leading to diagnostic delays. The average time from onset of ocular symptoms to diagnosis of TED can be substantial, impacting the efficacy of disease-modifying therapies.¹

The Endocrinologist's Vantage Point

Endocrinologists are frequently the first and often the primary clinicians managing patients with Graves' disease, the most common underlying cause of TED. This consistent patient contact provides a unique opportunity for early detection of ocular changes. Current guidelines emphasise the importance of a comprehensive assessment for TED in all patients with Graves' disease, irrespective of thyroid hormone status. This includes a detailed history regarding ocular symptoms and a focused physical examination. Key symptoms to inquire about include changes in vision, diplopia, ocular pain, redness, tearing, photophobia, and a sensation of grittiness or foreign body in the eye. Physical examination should include inspection for lid retraction, proptosis, periorbital oedema, and assessment of extraocular muscle motility. Subtle signs, such as mild lid lag or conjunctival injection, may be the earliest indicators of active disease.²

The clinical activity score (CAS) is a widely used tool to quantify inflammatory activity in TED. A CAS of 3 or more indicates active disease, warranting consideration for immunosuppressive therapy. Regular screening by endocrinologists can identify patients with a low CAS who are progressing, or those with early signs of active disease who may benefit from timely referral to an ophthalmologist with expertise in TED. For instance, a patient presenting with new onset diplopia or increasing proptosis, even without significant pain or redness, should trigger an immediate referral. Early referral to a specialist ophthalmologist, particularly within six months of symptom onset, has been shown to correlate with improved long-term outcomes, including reduced need for surgical intervention and better preservation of visual function. This is largely due to the ability to initiate immunomodulatory treatments, such as teprotumumab, during the active inflammatory phase, when they are most effective.³

The role extends beyond initial screening to ongoing monitoring. Patients with Graves' disease, even those without overt TED at diagnosis, remain at risk for developing ocular manifestations. Therefore, periodic re-evaluation for ocular symptoms and signs is essential during follow-up appointments. Education of patients about the potential for TED and encouragement to report any new or worsening ocular symptoms is also a critical component of comprehensive care. This proactive approach by endocrinologists can significantly shorten the diagnostic interval, allowing for earlier intervention and potentially preventing the progression to severe, sight-threatening forms of TED.⁴