SAT-335 - Marine-Lenhart Syndrome with A Coexisting Cold Thyroid Nodule: A Diagnostic and Therapeutic Challenge

Background
Marine–Lenhart syndrome (MLS) is a rare cause of hyperthyroidism characterized by the coexistence of Graves’ disease and one or more autonomously functioning thyroid nodules. It is reported in fewer than 3% of patients with Graves’ disease. The presence of an additional hypofunctioning (“cold”) thyroid nodule further complicates diagnostic evaluation and management because of the associated increased risk of malignancy.

Case Presentation
A 36-year-old man with a history of migraines, who had recently completed a course of doxycycline for a suspected upper respiratory infection, presented to the emergency department for evaluation of elevated blood pressure and palpitations. On presentation, his heart rate was 112 BPM, with otherwise normal vital signs. Physical examination, including evaluation of the thyroid, was unremarkable.

Laboratory evaluation demonstrated biochemical hyperthyroidism, with a TSH < 0.005 mIU/L, free T4 of 1.78 ng/dL, and total T3 of 178 ng/dL. Liver function tests and white blood cell count were within normal limits.

Thyroid scintigraphy using Tc-99m pertechnetate revealed a hyperfunctioning (“hot”) nodule in the right thyroid lobe. Thyroid-stimulating immunoglobulin (TSI) and thyrotropin receptor antibodies (TRAb) were positive, confirming the diagnosis of Graves’ disease. The patient was started on methimazole 10 mg daily and propranolol 20 mg twice daily, resulting in improvement of palpitations and fatigue.

At follow-up, the patient reported persistent mild fatigue and intermittent dyspnea. Repeat thyroid function tests one month later demonstrated partial biochemical improvement, with a TSH of 0.01 mIU/L, free T4 of 1.5 ng/dL, and total T3 of 108 ng/dL. Thyroid ultrasound revealed a 4.0 × 2.0 × 3.6 cm right midpole nodule corresponding to the hyperfunctioning nodule on scintigraphy, as well as a 1.2 × 0.8 × 1.0 cm hypofunctioning (“cold”) nodule in the left lower pole.

Discussion
This case illustrates Marine–Lenhart syndrome with the additional complexity of a contralateral cold thyroid nodule. The presence of a cold nodule in a hyperthyroid patient is clinically significant, as such nodules carry a reported malignancy risk of 14–22% and warrant further evaluation.

The pathophysiology of MLS involves two distinct mechanisms: diffuse thyroid stimulation mediated by TSH-receptor antibodies, characteristic of Graves’ disease, and autonomous nodular hormone production due to somatic activating mutations in the TSH receptor (TSHR) or GNAS genes. The coexistence of these processes presents unique diagnostic and therapeutic challenges.

Conclusion
The concurrence of Graves’ disease, an autonomously functioning thyroid nodule, and a cold thyroid nodule represents a rare and complex clinical presentation. Thyroid scintigraphy and ultrasound are essential diagnostic tools and play a critical role in guiding management decisions.

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