Surgical management of intrathyroidal parathyroid adenoma with nodular goiter: a case report highlighting SPECT/CT localization

Introduction

Primary hyperparathyroidism (PHPT) most frequently results from parathyroid adenomas (80–85%), with ectopic locations accounting for 11–25% of cases (1). Intrathyroidal parathyroid adenomas (ITPAs) present diagnostic challenges as they closely resemble thyroid nodules on ultrasound (2). Although technetium-99m-methoxyisobutylisonitrile (^99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) remains the reference standard for locating ectopic glands (3), its diagnostic performance diminishes when ITPAs coexist with thyroid nodules (4). Here we describe a successful SPECT/CT-guided surgical intervention that resolved PHPT in a patient with complex thyroid pathology. We present this case in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-154/rc).

Case presentation

A 69-year-old woman presented for evaluation of longstanding thyroid nodules. Cervical ultrasonography performed ten years prior had incidentally detected a 46-mm left thyroid nodule with indistinct margins and calcifications, though the patient remained asymptomatic. Recent ultrasonography revealed a dominant 77 mm × 61 mm hypoechoic nodule with cystic components and well-circumscribed borders in the left thyroid lobe, demonstrating peripheral vascularity on Doppler imaging, alongside multiple smaller hypoechoic nodules (largest 18 mm × 10 mm) without significant vascularity in the right lobe. These bilateral cervical nodules were classified as TI-RADS 3 (Thyroid Imaging Reporting and Data System, Category 3), indicating low malignant potential (Figure 1).

Figure 1 Ultrasound (TI-RADS 3): bilateral thyroid hypoechoic nodules [left: 77 mm × 61 mm (A); right: 18 mm × 10 mm (B)] with cystic components, regular morphology, and well-defined margins. Peripheral blood flow (left, CDFI+) and no lymphadenopathy. CDFI, Color Doppler flow imaging; TI-RADS, Thyroid Imaging Reporting and Data System.

Physical examination identified a firm, 48-mm left thyroid mass that moved with swallowing. Contrast-enhanced CT confirmed multiple thyroid nodules, with the largest (58 mm × 46 mm × 37 mm) in the left lobe, consistent with nodular goiter (Figure 2).

Figure 2 Computed tomography features. Plain CT (A): marked left thyroid enlargement with hypodense nodules (largest: 58 mm × 46 mm × 37 mm). Contrast CT (B) heterogeneous enhancement, and non-enhancing areas (necrosis/cystic changes). Diagnosis: nodular goiter. CT, computed tomography.

Laboratory tests revealed severe hypercalcemia (3.04 mmol/L; reference range, 2.11–2.52 mmol/L), hypophosphatemia (0.57 mmol/L; reference range, 0.85–1.51 mmol/L), and markedly elevated parathyroid hormone (PTH) levels (1,656 ng/L; normal, 12–88 ng/L), accompanied by increased alkaline phosphatase (191 U/L). Thyroid function tests were normal, though thyroglobulin was elevated (465 µg/L). Bone densitometry demonstrated osteoporosis (T-scores: hip −4.5, lumbar spine −5.4).

Dual-phase ^99mTC-MIBI scintigraphy with SPECT/CT was performed to evaluate hyperparathyroidism, revealing early tracer uptake in the left thyroid upper pole with delayed retention, consistent with an ITPA (Figure 3).

Figure 3 ^99mTc-MIBI SPECT/CT. Early phase (A): enlarged left thyroid lobe with rightward displacement; heterogeneous bilateral uptake, focal nodular hyperconcentration (left upper pole). Delayed phase (B): enlarged left thyroid lobe with rightward displacement; heterogeneous bilateral uptake, the left thyroid with delayed retention, consistent with an intrathyroidal parathyroid adenoma (black arrow). Fusion SPECT/CT (C): poor washout in left lobe solid components (upper left); cystic photopenic defects (upper right). Co-registered CT (lower left): dominant cystic-solid nodule (57 mm × 73 mm, left lobe) with central hypodensity; bilateral thyroid nodules. The black arrow indicates a parathyroid adenoma (lower right). CT, computed tomography; SPECT/CT, single-photon emission computed tomography/computed tomography; ^99mTc-MIBI, technetium-99m-methoxyisobutylisonitrile.

The patient underwent total left thyroidectomy and partial right lobectomy. Histopathology confirmed a cystic parathyroid adenoma in the left thyroid (Figure 4A,4B) with adjacent follicular hyperplasia, while the right lobe exhibited nodular goiter (Figure 4C,4D). Although nuclear medicine findings supported an ITPA, distinguishing this from thyroid adenomas remains challenging, as both may show tracer uptake on parathyroid scintigraphy.

Figure 4 Pathological section. (A) Uniform proliferation of round-oval cells with eosinophilic cytoplasm and sinusoidal vasculature was observed on rapid section, suggestive of parathyroid neoplasm (H&E, ×200). (B) Comprehensive histopathological evaluation (including serial sectioning of the left thyroid lobe and isthmus) confirmed a parathyroid adenoma characterized by cystic degeneration and demarcation from the surrounding thyroid parenchyma (H&E, ×40). (C) The focal follicular hyperplasia with equivocal nuclear pseudostratification and chromatin clearing was most suggestive of NIFTP lesion (H&E, ×40). (D) Colloid-distended macrofollicles lined by flattened thyrocytes, interspersed with hemorrhagic foci containing hemosiderin-laden macrophages and fibrous septa. No nuclear atypia, pseudoinclusions, or papillary architecture is observed (H&E, ×40). H&E, hematoxylin & eosin; NIFTP, non-invasive follicular thyroid neoplasm with papillary-like nuclear features.

Postoperative PTH levels decreased from 32 ng/L (intraoperative) to 2.1 ng/L by postoperative day 3. Calcium and PTH levels normalized (2.21 mmol/L and 12 ng/L, respectively) at the 2-week follow-up. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval was waived by the Medical Ethics Committee of Ningbo Medical Center Lihuili Hospital. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Although ectopic parathyroid glands occur infrequently, ITPAs present diagnostic difficulties due to their scarcity. This challenge becomes particularly pronounced when, as in this case, the adenoma undergoes cystic degeneration, complicating both diagnosis and management. Accurate preoperative localization remains essential for surgical success, and experienced teams can typically identify ITPAs through standard localization techniques. While conventional CT demonstrates high resolution and reasonable sensitivity for ectopic parathyroid tissue, its specificity proves inadequate without clear clinical history or laboratory findings, frequently yielding false-positive results. Ultrasound and ^99mTc-MIBI SPECT/CT serve as the primary imaging modalities for locating PHPT (5). The latter technique, offering both high sensitivity and broad anatomical coverage, has become the gold standard for ectopic parathyroid lesion detection.

^99mTc-MIBI SPECT/CT dual-phase imaging operates on functional principles, with only hyperactive parathyroid glands retaining tracer in delayed phases. The radiopharmaceutical enters parathyroid cells through combined active transport and passive diffusion mechanisms, a process enhanced in hyperfunctional cells with elevated membrane potentials. Consequently, these cells accumulate more ^99mTc-MIBI than normal tissue during early phases, while normal thyroid tissue clears the tracer more rapidly. This differential uptake pattern produces abnormal radiotracer concentrations outside thyroid regions during early phases that persist in delayed imaging.

Despite these advantages, conventional ^99mTc-MIBI scintigraphy suffers from limited specificity for ITPAs due to its planar acquisition format and overlapping features with nodular goiter, restricting both diagnostic accuracy and anatomical delineation (4). Ultrasound, while cost-effective and capable of detailed neck anatomy visualization, shares similar limitations in distinguishing ITPAs from thyroid nodules. Its diagnostic performance varies significantly with operator experience (6), and ectopic lesions prove particularly challenging due to interference from thoracic structures, bony anatomy, cervical lymph nodes, and thyroid nodules. Studies vary in their assessments of ultrasound and MIBI-SPECT for preoperative localization of parathyroid adenomas within the thyroid gland (2,4,5,7). While ^99mTc-MIBI SPECT typically demonstrates marginally higher sensitivity than ultrasound, the comparative accuracy remains debated.

The dual-phase ^99mTc-MIBI SPECT/CT protocol overcomes the localization limitations of conventional planar scintigraphy, achieving 90% diagnostic sensitivity for PHPT and 86% sensitivity in cases with concurrent thyroid pathologies (8). Our standardized protocol employed early-phase (20-minute post-injection) and delayed-phase (2-hour post-injection) imaging, combining functional tracer kinetics from nuclear medicine with precise anatomical correlation through CT. Hybrid image fusion technology facilitated three-dimensional localization of the ITPA within the thyroid’s complex architecture, substantially improving both lesion detection and diagnostic accuracy. This integrated approach proved especially effective for distinguishing hypervascular parathyroid adenomas from adjacent nodular goiter components.

Preoperative ultrasound and physical examination suggested nodular goiter in this patient, revealing a large thyroid nodule with cystic degeneration, hemorrhage, and malignant potential that warranted surgical intervention. Laboratory tests demonstrated elevated PTH, abnormal calcium-phosphorus ratios, and increased alkaline phosphatase levels, consistent with hypercalcemia and indicative of parathyroid pathology. Ultrasound and contrast-enhanced cervical CT detected no parathyroid space-occupying lesions in typical or ectopic locations, though multiple hypoechoic thyroid nodules classified as TI-RADS 3 were observed. Parathyroid MIBI dual-phase SPECT-CT scintigraphy subsequently identified a persistent cystic-solid lesion in the left thyroid lobe during the delayed phase, suggesting ITPA. The patient underwent left total thyroidectomy with partial right parathyroid resection, which intraoperatively confirmed a cystic parathyroid adenoma in the left lobe alongside multifocal nodular goiter with fibrosis and calcification in both lobes. Postoperative PTH levels normalized immediately, followed by restoration of calcium-phosphorus balance and significant alkaline phosphatase reduction within two weeks.

The patient presented with bilateral multiple thyroid nodules and requested thyroidectomy, fulfilling the standard surgical criteria for thyroid intervention. This clinical scenario facilitates the surgical treatment of intrathyroidal ectopic hyperparathyroidism by enabling concurrent excision of thyroid tissue and ectopic hyperfunctioning parathyroid glands. When patients lack thyroid nodules or surgical indications for thyroidectomy, surgeons must achieve complete resection of ectopic hyperfunctioning parathyroid tissue within the thyroid. Intraoperative PTH monitoring with frozen section analysis proves especially critical in these cases. Despite these techniques, identifying ectopic hyperfunctioning parathyroid glands within thyroid tissue continues to present significant diagnostic challenges. Some studies have found that four-dimensional computed tomography (4D-CT) (9) and 18F-fluorocholine PET/CT (10) may offer promising prospects in identifying parathyroid adenomas, especially ectopic parathyroid adenomas.

Conclusions

Intrathyroidal ectopic hyperparathyroidism remains diagnostically challenging due to its rarity and frequent coexistence with thyroid nodules. Although ultrasound often fails to localize these lesions, dual-phase radionuclide imaging and neck contrast-enhanced CT provide more reliable localization. The integration of ^99mTc-MIBI dual-phase SPECT-CT improves diagnostic accuracy beyond conventional radionuclide imaging alone.

Acknowledgments

The authors thank Dr. Xiaochun Ji and Dr. Lei Wang (Department of Thyroid Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, China) for providing clinical opinions and descriptions of the surgical procedures.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-154/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-154/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-154/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval was waived by the Medical Ethics Committee of Ningbo Medical Center Lihuili Hospital. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Gawrychowski J, Kowalski GJ, Buła G, et al. Surgical Management of Primary Hyperparathyroidism-Clinicopathologic Study of 1019 Cases from a Single Institution. J Clin Med 2020;9:3540. [Crossref] [PubMed]
2. Ye T, Huang X, Xia Y, et al. Usefulness of preoperative ultrasonographic localization for diagnosis of a rare disease: Intrathyroid parathyroid lesions. Medicine (Baltimore) 2018;97:e10999. [Crossref] [PubMed]
3. López-Mora DA, Sizova M, Estorch M, et al. Superior performance of 18F-fluorocholine digital PET/CT in the detection of parathyroid adenomas. Eur J Nucl Med Mol Imaging 2020;47:572-8. [Crossref] [PubMed]
4. Dream S, Lindeman B, Chen H. Preventing blind thyroid lobectomy in patients with intrathyroidal hyperfunctioning parathyroid glands with radioguided enucleation. Int J Endocr Oncol 2020;7:IJE28.
5. Ye T, Huang X, Xia Y, et al. Usefulness of preoperative ultrasonographic localization for diagnosis of a rare disease: Intrathyroid parathyroid lesions. Medicine (Baltimore) 2018;97:e10999. [Crossref] [PubMed]
6. El Hammoumi M, Kamdem M, Amraoui M, et al. Mediastinal ectopic parathyroid adenomas: diagnostic and therapeutic challenge. Kardiochir Torakochirurgia Pol 2021;18:227-30. [Crossref] [PubMed]
7. Zhao W, Lu R, Yin L, et al. The Value of Preoperative and Intraoperative Ultrasound in the Localization of Intrathyroidal Parathyroid Adenomas. J Invest Surg 2022;35:752-7. [Crossref] [PubMed]
8. Gouveia S, Rodrigues D, Barros L, et al. Persistent primary hyperparathyroidism: an uncommon location for an ectopic gland--case report and review. Arq Bras Endocrinol Metabol 2012;56:393-403. [Crossref] [PubMed]
9. Woisetschläger M, Gimm O, Johansson K, et al. Dual energy 4D-CT of parathyroid adenomas not clearly localized by sestamibi scintigraphy and ultrasonography - a retrospective study. Eur J Radiol 2020;124:108821. [Crossref] [PubMed]
10. Badier JR, Suthar PP, Singh JS, et al. Role of 18F-Fluorocholine Positron Emission Tomography (PET)/Computed Tomography (CT) in Diagnosis of Elusive Parathyroid Adenoma. Cureus 2023;15:e48892. [Crossref] [PubMed]