Endocrine Exophthalmos
Disease Details
Family Health Simplified
- Description
- Endocrine exophthalmos is characterized by the abnormal protrusion of the eyes, typically associated with thyroid disorders such as Graves' disease.
- Type
- Endocrine exophthalmos is typically associated with Graves' disease, which is an autoimmune disorder. The genetic transmission of Graves' disease is complex and involves multiple genes, with a polygenic mode of inheritance. It is not transmitted in a simple Mendelian fashion but rather involves a combination of genetic susceptibility and environmental factors.
- Signs And Symptoms
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In mild disease, patients present with eyelid retraction. In fact, upper eyelid retraction is the most common ocular sign of Graves' orbitopathy. This finding is associated with lid lag on infraduction (Von Graefe's sign), eye globe lag on supraduction (Kocher's sign), a widened palpebral fissure during fixation (Dalrymple's sign) and an incapacity of closing the eyelids completely (lagophthalmos, Stellwag's sign). Due to the proptosis, eyelid retraction and lagophthalmos, the cornea is more prone to dryness and may present with chemosis, punctate epithelial erosions and superior limbic keratoconjunctivitis. The patients also have a dysfunction of the lacrimal gland with a decrease of the quantity and composition of tears produced. Non-specific symptoms with these pathologies include irritation, grittiness, photophobia, tearing, and blurred vision. Pain is not typical, but patients often complain of pressure in the orbit. Periorbital swelling due to inflammation can also be observed.
Eye signsIn moderate active disease, the signs and symptoms are persistent and increasing and include myopathy. The inflammation and edema of the extraocular muscles lead to gaze abnormalities. The inferior rectus muscle is the most commonly affected muscle and patient may experience vertical diplopia on upgaze and limitation of elevation of the eyes due to fibrosis of the muscle. This may also increase the intraocular pressure of the eyes. The double vision is initially intermittent but can gradually become chronic. The medial rectus is the second-most-commonly-affected muscle, but multiple muscles may be affected, in an asymmetric fashion.In more severe and active disease, mass effects and cicatricial changes occur within the orbit. This is manifested by a progressive exophthalmos, a restrictive myopathy that restricts eye movements and an optic neuropathy. With enlargement of the extraocular muscle at the orbital apex, the optic nerve is at risk of compression. The orbital fat or the stretching of the nerve due to increased orbital volume may also lead to optic nerve damage. The patient experiences a loss of visual acuity, visual field defect, afferent pupillary defect, and loss of color vision. This is an emergency and requires immediate surgery to prevent permanent blindness. - Prognosis
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Risk factors of progressive and severe thyroid-associated orbitopathy are:
Age greater than 50 years
Rapid onset of symptoms under 3 months
Cigarette smoking
Diabetes
Severe or uncontrolled hyperthyroidism
Presence of pretibial myxedema
High cholesterol levels (hyperlipidemia)
Peripheral vascular disease - Onset
- Endocrine exophthalmos, commonly associated with Graves' disease, typically has an onset in adulthood, most frequently between the ages of 30 and 50. Onset can vary and might occur slowly over weeks to months. The exact timing can differ from person to person.
- Prevalence
- Prevalence data for endocrine exophthalmos, which is commonly associated with Graves' disease, can vary. Overall, thyroid eye disease occurs in approximately 25-50% of patients with Graves’ disease.
- Epidemiology
- The pathology mostly affects persons of 30 to 50 years of age. Females are four times more likely to develop Graves' than males. When males are affected, they tend to have a later onset and a poor prognosis. A study demonstrated that at the time of diagnosis, 90% of the patients with clinical orbitopathy were hyperthyroid according to thyroid function tests, while 3% had Hashimoto's thyroiditis, 1% were hypothyroid and 6% did not have any thyroid function tests abnormality. Of patients with Graves' hyperthyroidism, 20 to 25 percent have clinically obvious Graves' ophthalmopathy, while only 3–5% will develop severe ophthalmopathy.
- Intractability
- Endocrine exophthalmos, often associated with Graves' disease, involves the immune system attacking tissues around the eyes, leading to inflammation and swelling. It is not inherently intractable. With appropriate treatment, which may include medications, radiation therapy, or surgery, the symptoms can often be managed effectively. However, treatment success varies, and some cases may be more challenging to manage than others.
- Disease Severity
- Endocrine exophthalmos, also known as thyroid eye disease or Graves' orbitopathy, can range in severity from mild to severe. In mild cases, symptoms may include eye redness, irritation, and slight bulging. Moderate cases may involve significant bulging, double vision, and restricted eye movement. Severe cases can lead to vision-threatening complications due to optic nerve compression and severe corneal exposure.
- Healthcare Professionals
- Disease Ontology ID - DOID:12359
- Pathophysiology
- Graves' is an orbital autoimmune disease. The thyroid-stimulating hormone receptor (TSH-R) is an antigen found in orbital fat and connective tissue, and is a target for autoimmune assault.On histological examination, there is an infiltration of the orbital connective tissue by lymphocytes, plasmocytes, and mastocytes. The inflammation results in a deposition of collagen and glycosaminoglycans in the muscles, which leads to subsequent enlargement and fibrosis. There is also an induction of the lipogenesis by fibroblasts and preadipocytes, which causes enlargement of the orbital fat and extra-ocular muscle compartments. This increase in volume of the intraorbital contents within the confines of the bony orbit may lead to dysthyroid optic neuropathy (DON), increased intraocular pressures, proptosis, and venous congestion leading to chemosis and periorbital oedema. In addition, the expansion of the intraorbital soft tissue volume may also remodel the bony orbit and enlarge it, which may be a form of auto-decompression.
- Carrier Status
- Endocrine exophthalmos, often associated with Graves' disease, does not have a "carrier" status, as it is not an inherited disease in the traditional sense. It is an autoimmune condition where the immune system mistakenly attacks tissues around the eyes. Therefore, "nan" (not applicable) would be correct in this context for carrier status.
- Mechanism
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Endocrine exophthalmos, commonly associated with Graves' disease, involves the protrusion of the eyes and is primarily caused by autoimmune reactions targeting the tissues around the eyes.
**Mechanism:**
The mechanism involves the immune system mistakenly attacking the thyroid gland, leading to hyperthyroidism. The same autoimmune response also targets the orbital fibroblasts, causing inflammation and tissue expansion behind the eyes.
**Molecular Mechanisms:**
1. **Autoantibodies:** The presence of thyroid-stimulating immunoglobulins (TSI) and thyrotropin receptor antibodies (TRAb) stimulates the thyroid gland and also cross-reacts with orbital tissues.
2. **Cytokines and Chemokines:** These inflammatory mediators, such as Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α), are released, leading to inflammation and fibroblast activation.
3. **Orbital Fibroblasts:** These cells differentiate into adipocytes and myofibroblasts under the influence of cytokines, resulting in an increase in tissue volume and subsequent eye protrusion.
4. **Glycosaminoglycans (GAGs):** Accumulation of GAGs, such as hyaluronan, within the orbital tissues attracts water, leading to further swelling and edema.
Understanding these mechanisms provides insight into potential therapeutic targets for managing endocrine exophthalmos. - Treatment
- Even though some people undergo spontaneous remission of symptoms within a year, many need treatment. The first step is the regulation of thyroid hormone levels. Topical lubrication of the eye is used to avoid corneal damage caused by exposure. Corticosteroids are efficient in reducing orbital inflammation, but the benefits cease after discontinuation. Corticosteroids treatment is also limited because of their many side effects. Radiotherapy is an alternative option to reduce acute orbital inflammation. However, there is still controversy surrounding its efficacy. A simple way of reducing inflammation is to stop smoking, as pro-inflammatory substances are found in cigarettes. The medication teprotumumab-trbw may also be used. There is tentative evidence for selenium in mild disease. Tocilizumab, a drug used to suppress the immune system has also been studied as a treatment for TED. However, a Cochrane Review published in 2018 found no evidence (no relevant clinical studies were published) to show that tocilizumab works in people with TED.In January 2020, the US Food and Drug Administration approved teprotumumab-trbw for the treatment of Graves' ophthalmopathy.
- Compassionate Use Treatment
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Endocrine exophthalmos, also known as thyroid eye disease (TED) or Graves' orbitopathy, primarily affects individuals with thyroid disorders like Graves' disease. Various treatment options are sometimes considered under compassionate use, off-label, or experimental categories:
1. **Teprotumumab**: An FDA-approved medication for thyroid eye disease, Teprotumumab has shown efficacy in reducing proptosis (eye bulging). It might be considered under compassionate use in cases where standard treatments are not effective.
2. **Rituximab**: An off-label use of this monoclonal antibody, typically used in conditions like lymphoma and rheumatoid arthritis, is being explored due to its immunomodulatory effects.
3. **Tocilizumab**: This IL-6 receptor inhibitor is also used off-label for TED, leveraging its anti-inflammatory properties.
4. **Selenium Supplements**: Although not strictly experimental, the use of high-dose selenium has been explored as a supplemental treatment due to its potential benefits in mild TED cases by reducing inflammation and oxidative stress.
5. **Orbital Radiotherapy**: Used in some centers, this approach involves targeted radiation to reduce inflammation and immune response in the eye tissues.
6. **Biologics and Immunotherapies**: Other biologic agents and immune-modulating therapies are under investigation in clinical trials for their potential to treat TED by targeting specific pathways involved in the disease's pathogenesis.
These treatments are typically considered when patients do not respond to standard therapies such as corticosteroids, surgical intervention, or orbital decompression, and require careful evaluation by specialists. - Lifestyle Recommendations
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For endocrine exophthalmos, often associated with Graves' disease, lifestyle recommendations include:
1. **Regular Eye Care:**
- Use lubricating eye drops to alleviate dryness and irritation.
- Wear sunglasses to protect from sunlight and wind.
2. **Healthy Diet:**
- Maintain a balanced diet rich in vitamins and minerals.
- Reduce the intake of iodized salt and caffeine, which can exacerbate symptoms.
3. **Quit Smoking:**
- Smoking can worsen thyroid eye disease; quitting is crucial.
4. **Elevate Sleeping Position:**
- Use extra pillows to keep the head elevated, reducing eye swelling.
5. **Manage Stress:**
- Engage in stress-reducing activities like yoga, meditation, or gentle exercises.
6. **Regular Exercise:**
- Regular physical activity can help improve overall well-being and thyroid function.
7. **Regular Medical Check-Ups:**
- Consistently monitor thyroid levels and adjust treatments as necessary under medical supervision. - Medication
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Endocrine exophthalmos, often associated with Graves' disease, can be treated with several medications. The primary goal is to manage the underlying hyperthyroidism and reduce inflammation:
1. **Antithyroid medications** (e.g., methimazole, propylthiouracil) to control thyroid hormone production.
2. **Corticosteroids** (e.g., prednisone) to reduce inflammation and swelling in the eye muscles and tissues.
3. **Immunosuppressive drugs** (e.g., rituximab) in certain cases to modulate the immune response.
It's essential for patients to consult with a healthcare provider to determine the most appropriate treatment plan. - Repurposable Drugs
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Endocrine exophthalmos, commonly associated with Graves' disease, involves inflammation and swelling of the eye tissues. Potential repurposable drugs for managing symptoms include:
1. **Corticosteroids (e.g., prednisone)**: To reduce inflammation.
2. **Beta-blockers (e.g., propranolol)**: To manage symptoms like rapid heart rate.
3. **Anti-thyroid medications (e.g., methimazole or propylthiouracil)**: To control hyperthyroidism, indirectly benefiting the eye condition.
4. **Rituximab**: A monoclonal antibody used in autoimmune diseases.
5. **Teprotumumab**: Originally developed for cancer, now approved by the FDA for thyroid eye disease.
It's essential to consult a healthcare provider for an accurate diagnosis and appropriate treatment plan. - Metabolites
- Endocrine exophthalmos, also known as thyroid eye disease, is primarily associated with Graves' disease. The condition does not have specific "metabolites." Instead, it is characterized by an immune-mediated process affecting the eye muscles and connective tissue. While the key factors relating to pathophysiology involve immune responses and cytokines, there are no distinct metabolites being measured or tracked in the context of this disease. Therefore, it appears "nan" (not applicable) to discuss metabolites directly related to endocrine exophthalmos.
- Nutraceuticals
- For endocrine exophthalmos, also known as thyroid eye disease or Graves' orbitopathy, nutraceuticals might provide supportive benefits, though they are not a primary treatment. Selenium supplementation has shown promise in clinical studies for reducing inflammation and improving quality of life in mild cases. Vitamin D and omega-3 fatty acids may also help support immune and overall health. Always consult a healthcare professional before starting any new supplements.
- Peptides
- Endocrine exophthalmos, also known as thyroid eye disease or Graves' orbitopathy, is associated with hyperthyroidism, often due to Graves' disease. The condition can lead to inflammation and tissue expansion in the eye. While peptide-based treatments are not the standard, recent research is exploring the use of biologic agents and peptides to modulate the immune response involved in the disease. However, these are not yet widely adopted in clinical practice. Consultation with a healthcare professional for the latest treatment options is advised.