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PubMed This is a summary of 19 peer-reviewed journal articles Updated
Ophthalmology · Thyroid Eye Disease

The Biology and Risk Factors Behind TED

At a Glance

Thyroid Eye Disease is driven by autoantibodies that cause swelling and extra fat production behind the eyes, leading to bulging. Smoking and Radioactive Iodine therapy are major risk factors that can worsen symptoms. Quitting smoking is the most important step to protect your eye health.

To understand Thyroid Eye Disease (TED), it helps to imagine the space behind your eye as a crowded room. Your eye sits in a “bony orbit”—a socket made of bone that cannot expand [1]. When the immune system mistakenly attacks this space, the room becomes overfilled, leading to the pressure and bulging you may be experiencing.

The “Master Switch”: TSHR and IGF-1R

The biological “engine” of TED is located on specialized cells called orbital fibroblasts [2]. These cells have two specific receptors on their surface: the TSH receptor (TSHR) and the IGF-1 receptor (IGF-1R) [3].

In TED, the same autoantibodies that cause your thyroid to be overactive also act like a “key” that fits into these receptors [4]. Instead of just turning on one receptor, these antibodies cause the TSHR and IGF-1R to “talk” to each other in a process called crosstalk [5][6]. This synergistic connection sends a powerful signal to the fibroblasts to start changing and growing in ways they normally shouldn’t [7].

Why the Eyes Swell: Hyaluronan and Fat

Once that “master switch” is flipped, the fibroblasts begin two major processes that take up space in the eye socket:

  1. Hyaluronan Production: Fibroblasts start churning out hyaluronan (or hyaluronic acid), a sugar molecule that acts like a molecular sponge [8]. It can hold up to 1,000 times its weight in water [9]. This causes the muscles and tissues behind the eye to swell significantly with fluid [8].
  2. Adipogenesis (Fat Creation): The fibroblasts are also triggered to differentiate, or transform, into new fat cells (adipocytes) [10]. This new fat physically pushes the eye forward, causing proptosis (bulging eyes), because there is nowhere else for the extra volume to go [11].

Major Triggers and Risk Factors

1. Smoking (The Most Critical Risk Factor)

Smoking is the single most important factor you can control. It makes TED significantly more likely to develop and much harder to treat [12]. Biologically, smoking acts like “fuel on the fire”:

  • Oxidative Stress: Cigarette smoke creates harmful molecules that damage cells and increase inflammation in the eye socket [13][14].
  • Venous Congestion: Smoking causes the veins in the orbit to become congested, meaning blood cannot flow out easily [15]. This increases the pressure behind the eye and makes swelling much worse [16].

2. Radioactive Iodine (RAI) Therapy

If your endocrinologist recommends treating your overactive thyroid with Radioactive Iodine (RAI), you must discuss your eyes first. RAI is a well-documented trigger for developing TED or causing a severe flare in existing TED [17]. To prevent this, doctors will often prescribe a short course of protective oral steroids alongside the RAI treatment [17].

3. Biological Sex and Age

While TED is an autoimmune disease that is significantly more common in females (like most autoimmune conditions), the disease behaves differently across demographics:

  • Biological Sex: Women are much more likely to develop TED overall. However, when men develop TED, they are at a higher risk for aggressive, severe, or “muscle-dominant” forms of the disease [12].
  • Age: Older patients (typically those over 50) are more likely to have significant eye muscle swelling, increasing the risk of double vision and optic nerve compression [12][18]. Younger and pediatric patients generally have milder symptoms [19].

Common questions in this guide

Why do my eyes bulge with Thyroid Eye Disease?
In Thyroid Eye Disease, the immune system mistakenly attacks the tissues behind the eye. This causes specialized cells to produce extra fat and a fluid-holding molecule called hyaluronan. Because the eye socket is made of solid bone, this extra tissue has nowhere to go and pushes the eyes outward.
How does smoking affect Thyroid Eye Disease?
Smoking is the most critical risk factor you can control for this condition. It creates harmful inflammation and causes congestion in the veins, preventing blood from flowing out of the eye area easily, which makes swelling significantly worse.
Can treating my overactive thyroid worsen my eye symptoms?
Yes, certain treatments like Radioactive Iodine therapy can trigger or worsen eye symptoms. Because of this, endocrinologists will often prescribe a short course of protective oral steroids alongside the therapy to help prevent an eye flare-up.
Who is at the highest risk for severe Thyroid Eye Disease?
While the condition is more common in women, men who develop the disease are at a higher risk for aggressive, muscle-dominant symptoms. Additionally, patients over the age of 50 are more likely to experience significant eye muscle swelling and double vision.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Am I at a higher risk for a more severe or 'muscle-dominant' form of TED based on my specific demographics?
  2. 2.How do the newer medications specifically interrupt the 'cross-talk' between the TSH and IGF-1 receptors in my case?
  3. 3.Is my eye bulging (proptosis) primarily caused by new fat growth or by hyaluronan-related swelling?
  4. 4.Since I need to manage my overactive thyroid, what is your perspective on using Radioactive Iodine (RAI) given my eye symptoms?
  5. 5.What resources can you provide to help me quit smoking immediately, given how critical it is for my eye health?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (19)
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    Interleukin-27 is a multitarget regulator of fibroblast remodeling in thyroid-associated ophthalmopathy.

    Zhang P, Wang X, Lu N, et al.

    iScience 2025; (28(12)):113982 doi:10.1016/j.isci.2025.113982.

    PMID: 41362621
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    Current and promising therapies based on the pathogenesis of Graves' ophthalmopathy.

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    Frontiers in pharmacology 2023; (14()):1217253 doi:10.3389/fphar.2023.1217253.

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    The therapeutic revolution in thyroid eye disease: from orbital radiotherapy to teprotumumab and AI.

    Yuan X, Li H, Wang F

    Frontiers in medicine 2026; (13()):1758015 doi:10.3389/fmed.2026.1758015.

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    Dual TSHR/IGF-1Rα electroporation induces progressive orbital remodeling and retinochoroidal alterations in a murine model of thyroid eye disease.

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    Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease.

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This page provides educational information about the biology and risk factors of Thyroid Eye Disease. Always consult your ophthalmologist or endocrinologist before making changes to your thyroid treatment plan or managing eye symptoms.

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