International Journal of Clinical Science and Medical Research

Graves’ disease (GD) is the leading cause of hyperthyroidism, with ophthalmic involvement occurring in up to 50% of cases (Graves’ orbitopathy, GO). Classical GO features include bilateral proptosis, lid retraction, and restrictive strabismus. Unilateral ptosis is an exceedingly uncommon presenting sign of Graves’ disease and poses a significant diagnostic challenge, frequently leading clinicians to prioritize neurological etiologies before the underlying thyroid autoimmune process is identified. 

We present a 34-year-old woman referred for progressive right-sided ptosis over six months, initially investigated for neurological causes. Ophthalmological assessment revealed mild right-sided proptosis and inferior scleral show contralateral to the ptotic lid, consistent with unilateral lid retraction masking asymmetric GO. Biochemical evaluation confirmed hyperthyroidism with a suppressed TSH, markedly elevated free T4 and T3, and positive thyroid-stimulating immunoglobulins (TSI) and thyrotropin receptor antibodies (TRAb). Thyroid ultrasound identified a diffusely enlarged gland with a 1.8 cm right lobe nodule. Tc-99m scintigraphy demonstrated diffusely increased uptake with a superimposed focus of relatively autonomous activity corresponding to the nodule, establishing the diagnosis of Marine–Lenhart syndrome the rare coexistence of Graves’ disease with an autonomously functioning thyroid nodule. Orbital MRI revealed asymmetric extraocular muscle enlargement bilaterally, right greater than left, confirming Graves’ orbitopathy as the cause of apparent unilateral ptosis. 

This case highlights two converging diagnostic challenges: the misclassification of contralateral lid retraction as unilateral ptosis, and the recognition of Marine–Lenhart syndrome a rare overlap of Graves’ hyperthyroidism with a coexisting autonomously functioning thyroid nodule (AFTN) found in fewer than 3% of Graves’ patients. The presence of Marine–Lenhart syndrome critically modifies the management strategy, particularly regarding radioiodine dosing, surgical planning, and the assessment of post-treatment euthyroidism. 

Marine–Lenhart syndrome; thyroid eye disease; unilateral ptosis; hyperthyroidism; TRAb; thyrotropin receptor antibodies; thyrotoxicosis.

1. Krohn K, Paschke R. Marine-Lenhart syndrome: an underdiagnosed cause of hyperthyroidism. Thyroid. 2001;11(6):539–541. 
2. Klobusnikova S, et al. Marine-Lenhart syndrome: clinical features, diagnosis, and therapeutic options. Endocr Pract. 2019;25(3):287–293.
3. Parma J, Duprez L, Van Sande J, et al. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature. 1993;365(6447):649–651. 
4. Kahaly GJ, Diana T. TSH receptor antibody functionality and nomenclature. Front Endocrinol (Lausanne). 2017;8:28. 
5. Niedziela M. Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer. 2006;13(2):427–453. 
6. Dietlein M, Dressler J, Grünwald F, et al. Guideline for radioiodine therapy for benign thyroid diseases (version 4). Nuklearmedizin. 2007;46(5):220–223. 
7. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133. 
8. Bhatt AA, Lopez MJ, Bhatt R. Graves' ophthalmopathy and lid retraction: pathogenesis and management. Semin Ophthalmol. 2021;36(4):222–228. 
9. Rootman J, Dolman PJ. Orbital Disease: Present Status and Future Challenges. Taylor & Francis; 2005. 
10. Kerty E, Elsais A, Argov Z, Evoli A, Gilhus NE. EFNS/ENS Guidelines for the treatment of ocular myasthenia. Eur J Neurol. 2014;21(5):687–693. 
11. Boelaert K, Newby PR, Simmonds MJ, et al. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med. 2010;123(2):183.e1–9. 
12. Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016;5(1):9–26. 
13. Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' Orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur Thyroid J. 2021;10(4):343–350. 
14. Mourits MP, Prummel MF, Wiersinga WM, Koornneef L. Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy. Clin Endocrinol (Oxf). 1997;47(1):9–14. 
15. Tallstedt L, Lundell G, Tørring O, et al. Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. N Engl J Med. 1992;326(26):1733–1738. 
16. Acharya SH, Avenell A, Philip S, Burr J, Bevan JS, Abraham P. Radioiodine therapy (RAI) for Graves' disease (GD) and the effect on ophthalmopathy: a systematic review. Clin Endocrinol (Oxf)2008;69(6):943–950. 
17. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343– 1421. 
18. Perros P, Wiersinga WM. Thyroidectomy for GO: when and how? Eur Thyroid J. 2020;9(Suppl 1):62–65. 
19. Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352(9):905–917.
20. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382(4):341–352. 
21. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748–1761. 
22. Ugradar S, Kang J, Goldberg RA. Teprotumumab for the treatment of chronic (inactive) thyroid eye disease. Eye (Lond). 2022;36(3):548–553.