European Journal of Nuclear Medicine and Molecular Imaging, 2026 (SCI-Expanded, Scopus)
Purpose: This review examines Marine-Lenhart syndrome (MLS), an uncommon thyroid disorder that combines Graves’ disease with autonomously functioning thyroid nodules (AFTNs) and demonstrates why nuclear medicine imaging is essential for accurate diagnosis and treatment planning. Methods: We reviewed case reports and case series published over the past three decades and analyzed clinical presentation, diagnostic approaches, prevalence rates, disease mechanisms, and treatment outcomes of MLS. Results: This relatively rare syndrome occurs in approximately 0.8–4.3% of patients with Graves’ disease, though rates vary depending on the diagnostic criteria and imaging methods used. It presents a diagnostic challenge because AFTNs often remain suppressed and appear “cold” on initial scans, only becoming visible after treatment - the characteristic “unmasking effect”. Thyroid scintigraphy with either 99mTc-pertechnetate or 123I provides functional information that structural imaging cannot show. Treatment differs from standard Graves’ disease management as MLS requires higher radioiodine activities because nodules may escape radiation damage, and patients may need radioiodine re-ablation. Type 3 MLS, which includes cold nodules, requires careful cancer risk evaluation with ultrasound and fine-needle aspiration when appropriate. Conclusion: Nuclear medicine imaging is crucial for MLS diagnosis and treatment planning. Functional imaging identifies AFTNs, guides appropriate radioiodine treatment, and prevents treatment failure. Routine thyroid scintigraphy is recommended in all patients with hyperthyroidism and thyroid nodules before starting therapy.