Failure to identify a parathyroid gland during thyroidectomy or parathyroidectomy represents a well-recognized intraoperative challenge and is most commonly explained by ectopic gland location rather than true agenesis. A comprehensive understanding of parathyroid embryology, migration patterns, and cervical anatomy is therefore essential for safe endocrine neck surgery and for minimizing failed explorations, hypoparathyroidism, and recurrent disease. This review provides a practical and surgically oriented overview of the “missing” parathyroid gland, integrating embryologic development, anatomic variability, operative identification strategies, and contemporary nomenclature systems. The embryologic descent of the superior and inferior parathyroid glands from the fourth and third pharyngeal pouches, respectively, explains the predictable distribution of ectopic glands encountered during surgery. Superior glands typically maintain relatively constant locations near the posterior aspect of the upper thyroid pole, whereas inferior glands demonstrate greater positional variability because of their longer migratory course with the thymus. Common ectopic locations include the tracheoesophageal groove, retroesophageal space, thyrothymic ligament, cervical thymus, carotid sheath, retropharyngeal region, mediastinum, and intrathyroidal or subcapsular locations. This review emphasizes operative pearls for gland identification, including recognition of key landmarks such as the inferior thyroid artery, recurrent laryngeal nerve, prevertebral fascia, cervical thymus, and characteristic parathyroid fat pads. Strategies for systematic exploration are discussed in the context of both thyroidectomy and parathyroidectomy. Additionally, the manuscript reviews the Perrier classification system for ectopic parathyroid glands and proposes its practical application during cervical exploration to facilitate structured localization of missing glands. By combining embryologic principles with operative anatomy and contemporary surgical nomenclature, this review aims to provide endocrine surgeons, trainees, and head and neck surgeons with a clinically relevant framework for identifying orthotopic and ectopic parathyroid glands, reducing operative failure, and improving surgical outcomes in thyroid and parathyroid surgery.
References
[1]
Taterra, D., Wong, L.M., Vikse, J., Sanna, B., P？kala, P., Walocha, J., et al. (2019) The Prevalence and Anatomy of Parathyroid Glands: A Meta-Analysis with Implications for Parathyroid Surgery. Langenbeck’s Archives of Surgery, 404, 63-70. https://doi.org/10.1007/s00423-019-01751-8
[2]
Manatakis, D.K., Balalis, D., Soulou, V.N., Korkolis, D.P., Plataniotis, G. and Gontikakis, E. (2016) Incidental Parathyroidectomy during Total Thyroidectomy: Risk Factors and Consequences. International Journal of Endocrinology, 2016, 1-6. https://doi.org/10.1155/2016/7825305
[3]
Arrangoiz, R., Cordera, F., Caba, D., Mu？oz Juárez, M., Moreno, E. and Luque, E. (2017) Parathyroid Embryology, Anatomy, and Pathophysiology of Primary Hyperparathyroidism. International Journal of Otolaryngology and Head & Neck Surgery, 6, 39-58. https://doi.org/10.4236/ijohns.2017.64007
[4]
Akerstrom, G., Malmaeus, J. and Bergstrom, R. (1984) Surgical Anatomy of Human Parathyroid Glands. Surgery, 95, 14-21.
Rosen, R.D. and Bordoni, B. (2026) Embryology, Parathyroid. StatPearls Publishing.
[7]
Scharpf, J., Kyriazidis, N., Kamani, D. and Randolph, G. (2016) Anatomy and Embryology of the Parathyroid Gland. Operative Techniques in Otolaryngology-Head and Neck Surgery, 27, 117-121. https://doi.org/10.1016/j.otot.2016.06.003
[8]
Wang, C. (1976) The Anatomic Basis of Parathyroid Surgery. Annals of Surgery, 183, 271-275. https://doi.org/10.1097/00000658-197603000-00010
[9]
Roy, M., Mazeh, H., Chen, H. and Sippel, R.S. (2013) Incidence and Localization of Ectopic Parathyroid Adenomas in Previously Unexplored Patients. World Journal of Surgery, 37, 102-106. https://doi.org/10.1007/s00268-012-1773-z
[10]
Mansberger Jr, A.R. and Wei, J.P. (1993) Surgical Embryology and Anatomy of the Thyroid and Parathyroid Glands. SurgicalClinicsofNorthAmerica, 73, 727-746. https://doi.org/10.1016/s0039-6109(16)46082-2
[11]
Gray, S.W. (1994) Embryology for Surgeons. 2nd Edition, Williams & Wilkins.
[12]
Mohebati, A. and Shaha, A.R. (2012) Anatomy of Thyroid and Parathyroid Glands and Neurovascular Relations. Clinical Anatomy, 25, 19-31. https://doi.org/10.1002/ca.21220
[13]
Perrier, N.D., Ituarte, P.H.G., Morita, E., Hamill, T., Gielow, R., Duh, Q., et al. (2002) Parathyroid Surgery: Separating Promise from Reality. The Journal of Clinical Endocrinology & Metabolism, 87, 1024-1029. https://doi.org/10.1210/jcem.87.3.8310
[14]
Phitayakorn, R. and McHenry, C.R. (2006) Incidence and Location of Ectopic Abnormal Parathyroid Glands. The American Journal of Surgery, 191, 418-423. https://doi.org/10.1016/j.amjsurg.2005.10.049
[15]
Shen, W. (1996) Reoperation for Persistent or Recurrent Primary Hyperparathyroidism. Archives of Surgery, 131, 861-867. https://doi.org/10.1001/archsurg.1996.01430200071013
[16]
Randolph, G.W. (2021) Surgery of the Thyroid and Parathyroid Glands. 3rd Edition, Elsevier.
[17]
Perrier, N.D., Edeiken, B., Nunez, R., Gayed, I., Jimenez, C., Busaidy, N., et al. (2009) A Novel Nomenclature to Classify Parathyroid Adenomas. WorldJournalofSurgery, 33, 412-416. https://doi.org/10.1007/s00268-008-9894-0
[18]
Goodman, A., Politz, D., Lopez, J. and Norman, J. (2011) Intrathyroid Parathyroid Adenoma: Incidence and Location—The Case against Thyroid Lobectomy. Otolaryngology—HeadandNeckSurgery, 144, 867-871. https://doi.org/10.1177/0194599811400366
[19]
Ruda, J.M., Hollenbeak, C.S. and Stack, B.C. (2005) A Systematic Review of the Diagnosis and Treatment of Primary Hyperparathyroidism from 1995 to 2003. Otolaryngology–Head and Neck Surgery, 132, 359-372. https://doi.org/10.1016/j.otohns.2004.10.005
[20]
Parikh, A.M., Suliburk, J.W. and Morón, F.E. (2018) Imaging Localization and Surgical Approach in the Management of Ectopic Parathyroid Adenomas. Endocrine Practice, 24, 589-598. https://doi.org/10.4158/ep-2018-0003
[21]
Sayeed, S., Joseph, J., Stanisce, L., Ramirez, R., Khorsandi, A., Brandwein-Weber, M., et al. (2025) Undescended Ectopic Parathyroid Adenoma within Ectopic Cervical Thymus in the Carotid Sheath. Head & Neck, 47, E131-E133. https://doi.org/10.1002/hed.28176
[22]
Stack, B.C., Tolley, N.S., Bartel, T.B., Bilezikian, J.P., Bodenner, D., Camacho, P., etal. (2018) AHNS Series: Do You Know Your Guidelines? Optimizing Outcomes in Reoperative Parathyroid Surgery: Definitive Multidisciplinary Joint Consensus Guidelines of the American Head and Neck Society and the British Association of Endocrine and Thyroid Surgeons. Head & Neck, 40, 1617-1629. https://doi.org/10.1002/hed.25023
[23]
Johnson, S.J. (2010) Changing Clinicopathological Practice in Parathyroid Disease. Histopathology, 56, 835-851. https://doi.org/10.1111/j.1365-2559.2010.03515.x
[24]
Hannabass, K.R., Austerlitz, J., Noel, J.E. and Orloff, L.A. (2024) Parathyroid Adenoma Orientation for Gland Embryologic Origin on Ultrasonography. JAMA Otolaryngology–Head & Neck Surgery, 150, 756-762. https://doi.org/10.1001/jamaoto.2024.1571
[25]
Abts, T., Vu, T., Perrier, N.D., Wang, Y., Ning, J. and Debnam, J.M. (2025) Detection Rate and Concordance of 4D-MDCT, US, and Tc99m MIBI Imaging in the Detection of Ectopic and Intrathyroidal Parathyroid Adenomas. World Journal of Surgery, 49, 957-963. https://doi.org/10.1002/wjs.12512
[26]
Yeh, R., Tay, Y.D., Tabacco, G., Dercle, L., Kuo, J.H., Bandeira, L., et al. (2019) Diagnostic Performance of 4D CT and Sestamibi SPECT/CT in Localizing Parathyroid Adenomas in Primary Hyperparathyroidism. Radiology, 291, 469-476. https://doi.org/10.1148/radiol.2019182122
[27]
Aggarwal, P., Gunasekaran, V., Sood, A. and Mittal, B.R. (2025) Localization in Primary Hyperparathyroidism. Best Practice & Research Clinical Endocrinology & Metabolism, 39, Article 101967. https://doi.org/10.1016/j.beem.2024.101967
[28]
Alvarez, M.R., Arrangoiz, R., Olarte, M.á., Carreras, C., León S., M.M. and Cordera, F. (2020) 11C-Choline PET/CT in the Management of Primary Hyperparathyroidism. InternationalJournalofOtolaryngologyandHead&NeckSurgery, 9, 149-160. https://doi.org/10.4236/ijohns.2020.95019
[29]
Noussios, G., Anagnostis, P. and Natsis, K. (2012) Ectopic Parathyroid Glands and Their Anatomical, Clinical and Surgical Implications. ExperimentalandClinicalEndocrinology&Diabetes, 120, 604-610. https://doi.org/10.1055/s-0032-1327628
[30]
Silberfein, E.J. (2010) Reoperative Parathyroidectomy: Location of Missed Glands Based on a Contemporary Nomenclature System. ArchivesofSurgery, 145, 1065-1068. https://doi.org/10.1001/archsurg.2010.230
[31]
Cope, O. (1966) The Story of Hyperparathyroidism at the Massachusetts General Hospital. New England Journal of Medicine, 274, 1174-1182. https://doi.org/10.1056/nejm196605262742105
[32]
Lorente-Poch, L., Sancho, J.J., Ruiz, S. and Sitges-Serra, A. (2015) Importance of in Situ Preservation of Parathyroid Glands during Total Thyroidectomy. British Journal of Surgery, 102, 359-367. https://doi.org/10.1002/bjs.9676
[33]
Delbridge, L. (2003) Minimally Invasive Parathyroidectomy: The Australian Experience. Asian Journal of Surgery, 26, 76-81. https://doi.org/10.1016/s1015-9584(09)60225-6
[34]
Rao, S.S., Rao, H., Moinuddin, Z., Rozario, A.P. and Augustine, T. (2023) Preservation of Parathyroid Glands during Thyroid and Neck Surgery. Frontiers in Endocrinology, 14, Article 1173950. https://doi.org/10.3389/fendo.2023.1173950
[35]
Vidal Fortuny, J., Sadowski, S.M., Belfontali, V., Guigard, S., Poncet, A., Ris, F., et al. (2018) Randomized Clinical Trial of Intraoperative Parathyroid Gland Angiography with Indocyanine Green Fluorescence Predicting Parathyroid Function after Thyroid Surgery. British Journal of Surgery, 105, 350-357. https://doi.org/10.1002/bjs.10783
[36]
Vidal Fortuny, J., Belfontali, V., Sadowski, S.M., Karenovics, W., Guigard, S. and Triponez, F. (2016) Parathyroid Gland Angiography with Indocyanine Green Fluorescence to Predict Parathyroid Function after Thyroid Surgery. British Journal of Surgery, 103, 537-543. https://doi.org/10.1002/bjs.10101
[37]
Vidal Fortuny, J., Karenovics, W., Triponez, F. and Sadowski, S.M. (2016) Intra-Operative Indocyanine Green Angiography of the Parathyroid Gland. World Journal of Surgery, 40, 2378-2381. https://doi.org/10.1007/s00268-016-3493-2
[38]
Fortuny, J.V., Sadowski, S.M., Belfontali, V., Karenovics, W., Guigard, S. and Triponez, F. (2016) Indocyanine Green Angiography in Subtotal Parathyroidectomy: Technique for the Function of the Parathyroid Remnant. Journal of the American College of Surgeons, 223, e43-e49. https://doi.org/10.1016/j.jamcollsurg.2016.08.540
[39]
Wells Jr, S.A., Gunnells, J.C., Shelburne, J.D., et al. (1975) Transplantation of the Parathyroid Glands in Man: Clinical Indications and Results. Surgery, 78, 34-44.
[40]
Orloff, L.A., Wiseman, S.M., Bernet, V.J., Fahey, T.J., Shaha, A.R., Shindo, M.L., et al. (2018) American Thyroid Association Statement on Postoperative Hypoparathyroidism: Diagnosis, Prevention, and Management in Adults. Thyroid, 28, 830-841. https://doi.org/10.1089/thy.2017.0309
[41]
Sitges-Serra, A., Lorente-Poch, L. and Sancho, J. (2018) Parathyroid Autotransplantation in Thyroid Surgery. Langenbeck’s Archives of Surgery, 403, 309-315. https://doi.org/10.1007/s00423-018-1654-5
[42]
Cousart, A.G., Kiernan, C.M., Willmon, P.A., Thomas, G., Wang, T.S., Gauger, P.G., et al. (2025) Near-Infrared Autofluorescence for Parathyroid Detection during Endocrine Neck Surgery: A Randomized Clinical Trial. JAMA Surgery, 160, 936-944. https://doi.org/10.1001/jamasurg.2025.2233
[43]
Norman, J. and Politz, D. (2009) 5,000 Parathyroid Operations without Frozen Section or PTH Assays: Measuring Individual Parathyroid Gland Hormone Production in Real Time. Annals of Surgical Oncology, 16, 656-666. https://doi.org/10.1245/s10434-008-0276-5
[44]
Norman, J., Lopez, J. and Politz, D. (2012) Abandoning Unilateral Parathyroidectomy: Why We Reversed Our Position after 15,000 Parathyroid Operations. Journal of the American College of Surgeons, 214, 260-269. https://doi.org/10.1016/j.jamcollsurg.2011.12.007
[45]
Cope, O. (1941) Surgery of Hyperparathyroidism: The Occurrence of Parathyroids in the Anterior Mediastinum and the Division of the Operation into Two Stages. Annals of Surgery, 114, 706-733. https://doi.org/10.1097/00000658-194110000-00016
