A-052 The Importance of Thyroid-stimulating Immunoglobulin (TSI) in the Diagnosis and Follow-up of Marine-Lenhart Syndrome
Authors: Fontes R , Negri M M , Araujo P , Marui S , Gomes A , Schrank Y , Perozo A , Pinheiro M F , Gomes D M , Campana G , Tourinho E K , Vangelotti A , Pena J T 
Published: September 2023

Abstract

Introduction
Marine-Lenhart syndrome is a rare cause of hyperthyroidism, occurring in 0.8%–2.7% of patients with Graves’ disease (GD). In this syndrome, GD, which is an autoimmune disease, coexists with one or more hyperfunctioning nodules—Toxic nodular goiter (TNG), or toxic multinodular goiter (TMNG)—which are usually thyroid adenomas. Both induce clinical hyperthyroidism, with suppressed thyroid-stimulating hormone (TSH) and elevated thyroid hormones (TH). Radioactive iodine uptake and thyroid scintigraphy are indicated when there is a nodule on ultrasonography (US) with suppressed TSH, for the differential diagnosis between GD and toxic nodules. However, in this syndrome, scintigraphy does not always define the diagnosis, as the aspects observed do not show the usual pattern. In these cases, it is necessary that a reliable autoimmune thyroid disease marker be performed in order to prove the concomitant autoimmunity.

Objectives
The aim of this study was to demonstrate the usefulness of thyroid-stimulating immunoglobulin (TSI) for diagnosing hyperthyroidism due to Marine-Lenhart syndrome.

Methods
The authors prospectively followed 19 patients with suspected Marine-Lenhart syndrome between 2018 and 2020. TSH and TH were measured by Electrochemiluminescence, Roche Diagnostics, and TSI was measured by Chemiluminescence, Siemens Diagnostics.

Results
All patients had TSH ≤ 0.01 mIU/L, free thyroxine (FT4) was 3.1 ± 0.9 ng/dL, and triiodothyronine (TT3) 312 ± 42.1 ng/dL. All of them had increased radioactive iodine uptake, but the scintigraphy showed nodules sometimes with increased, normo, or low uptake in relation to the adjacent tissue, a finding that is explained by the fact that, both, the nodule and the rest of the thyroid tissue, uptake the radioidine in excess and the pattern varies according to the activity of the DG and nodules in the period in which the test was performed. TSI was 3.98 ± 0.9 IU/L (Negative if &lt;0.55). All patients had positive TSI, confirming concomitant GD with TNG/TMNG. During treatment monitoring, in 14 cases the hyperfunctioning nodules were treated by local sclerosis procedure, with percutaneous injection of ethanol. Despite complete nodular sclerosis, with normal TH but still suppressed TSH, the TSI still remained elevated. This demonstrated that, despite the successful treatment of the nodule, the underlying GD was still active, requiring complementary treatment with antithyroid drugs until TSI was negative, after 18 ± 4 months of treatment.

Conclusion
In atypical cases of hyperthyroidism, the TSI measurement is decisive for the diagnosis, as in the rare Marine-Lenhart syndrome. This contributes in a relevant way to the definition of the treatment, which can be different between the two causes that occur concomitantly. Likewise, during treatment follow-up, the TSI was essential in defining the need to maintain clinical treatment, even if the nodule had been already adequately treated.