Occult Parathyroid Lesions on 99mTc-Sestamibi Scintigraphy: Morphometric, Histopathological and Anatomical Determinants of Detection

Background: Accurate preoperative localization of hyperfunctioning parathyroid glands remains challenging, particularly in secondary hyperparathyroidism where multiglandular disease may compromise scintigraphic performance. Methods: Our study evaluated biochemical, morphometric, and histopathological predictors of 99mTc-sestamibi scintigraphy detectability in both primary and secondary hyperparathyroidism. The study group included a total of 162 patients with primary and secondary hyperparathyroidism who underwent dual-phase 99mTc-sestamibi scintigraphy followed by parathyroidectomy. Demographics, biochemical parameters, histopathological features, lesion volume and scintigraphic findings were assessed at patient and lesion level. Results: In primary hyperparathyroidism, adenomas were larger and more frequently detected than hyperplastic glands. Lesion volume and solid growth pattern were found as positive predictors of sestamibi uptake. In secondary hyperparathyroidism, nodular hyperplasia was associated with larger volume, higher cellularity, and more frequent localizing studies. Upper quadrant position and diffusely hyperplastic lesions were associated with higher lesion miss rates, while lesion volume increased the likelihood of detection. Conclusions: Our findings highlight that 99mTc-sestamibi scintigraphy performance is strongly influenced by lesion volume, histopathological architecture and anatomical position, underscoring the needs for cautious interpretation of negative or incomplete scans, especially in secondary hyperparathyroidism.