Gifford’s sign refers to resistance to eversion of the upper eyelid, observed in patients with thyrotoxicosis. The resistance reflects orbital and eyelid tissue changes associated with hyperthyroid states.

Pathophysiology

• Thyrotoxicosis, particularly Graves’ disease, can cause thyroid-associated orbitopathy.

• Increased orbital fat, edema, and fibrosis of eyelid tissues lead to mechanical restriction.

• Resistance during eyelid eversion indicates soft tissue changes in the upper eyelid rather than primary ocular disease.

Examination Technique

1. Patient positioning: Have the patient sit comfortably with head supported.

2. Eyelid manipulation: Gently attempt to raise the upper eyelid and evert it over a blunt object (e.g., cotton-tipped applicator).

3. Observation: Note any resistance or difficulty in eyelid eversion.

4. Documentation: Record the presence, severity, and laterality of the resistance.

Clinical Features

Differential Diagnosis

Pediatric considerations

• Rarely assessed in children; pediatric thyrotoxicosis is uncommon.

• If present, evaluate for Graves’ disease or congenital hyperthyroidism.

Geriatric considerations

• Older adults may exhibit weaker lid tissues, making subtle resistance harder to detect.

• Evaluate for coexisting ocular conditions such as dermatochalasis or ptosis.

Limitations

• Mild cases may not produce noticeable resistance.

• Requires gentle technique to avoid patient discomfort or reflexive blinking.

• Should be interpreted alongside other ocular and systemic signs of thyrotoxicosis.

Patient counseling

• Explain that resistance of the eyelid is a sign of thyroid-related eye changes, not a primary eye disease.

• Emphasize the importance of thyroid evaluation and management.

• Advise on ocular care to prevent dryness or corneal exposure if lid retraction is present.

Conclusion

Gifford’s sign is a subtle but useful clinical indicator of thyrotoxicosis and thyroid-associated orbitopathy, reflecting resistance of the upper eyelid to eversion. Careful assessment can aid in early diagnosis, monitoring of ocular involvement, and planning appropriate systemic and ophthalmic management.

References

1. Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477–588.

2. Bahn RS. Graves’ ophthalmopathy. N Engl J Med. 2010;362:726–738.

3. Wiersinga WM, Kahaly GJ. Thyroid eye disease: Pathophysiology and management. Endocrinol Metab Clin North Am. 2020;49(2):355–375.

4. Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology. 11th ed. New York: McGraw-Hill; 2021.