Clinicopathological Outcomes of TENIS Syndrome in Differentiated Thyroid Carcinoma: A Study from a Tertiary Center in South India

Abstract

Background: Thyroglobulin Elevated Negative Iodine Scintigraphy (TENIS) syndrome is an uncommon but clinically significant entity in differentiated thyroid carcinoma (DTC). It is characterized by persistently elevated serum thyroglobulin (Tg) despite negative radioactive iodine (RAI) scans. The condition poses diagnostic and therapeutic challenges, with limited data available from South India.

Objective: This study aimed to evaluate the clinicopathological features, treatment patterns, and outcomes of patients with TENIS syndrome managed at a tertiary care center in South India, with emphasis on factors influencing disease persistence and progression.

Methods: A retrospective descriptive analysis was conducted on adult patients with papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma (FTC) who developed TENIS following total thyroidectomy and radioactive iodine (RAI) therapy. Data on demographics, histopathology, tumor stage, Tg levels, imaging, treatment modalities, and outcomes were extracted from medical records. Associations between clinicopathological variables and disease course were assessed using Chi-square and appropriate statistical tests, with significance defined at p<0.05.

Results: Thirty-three patients were included (12 males, 21 females; mean age 45.2±13.1 years). Classical PTC was the predominant subtype (60.6%). At diagnosis of TENIS, the median Tg was 8 ng/mL. Lymph node metastasis occurred in 36.4%and distant metastasis in 24.2%, most commonly involving lungs and bones. Empirical RAI was the most frequently used therapy (33.3%), while others underwent salvage surgery, combined therapy, or observation. Treatment responses varied; some patients achieved Tg decline, while others had persistent or progressive disease. Tumor stage (p=0.031) and nodal status (p=0.018) were significantly associated with persistence, whereas treatment modality showed no correlation (p=0.79). The mean follow-up duration was 6.5 years.

Conclusion: TENIS syndrome represents an aggressive subset of DTC with high rates of persistence and metastasis. Tumor stage and nodal involvement are important prognostic indicators, while treatment responses remain inconsistent. Individualized management, integration of advanced imaging, and long-term surveillance are essential. Further multicentric studies and novel targeted therapies are needed to improve patient outcomes.