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Introductory Chapter: A Brief Statement about Parathyroid Glands

Written By

Beyza Goncu and Robert Gensure

Published: 15 March 2023

DOI: 10.5772/intechopen.110125

From the Edited Volume

Parathyroid Glands - New Aspects

Edited by Beyza Goncu and Robert Gensure

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1. Introduction

1.1 Discovery

Almost two centuries have passed since the discovery of parathyroid glands. Many studies have been carried out on their function and effectiveness. Many known and reputable books and studies are already available by respected scientists worldwide, including information about its embryological, developmental, anatomical, functional, and clinical importance, diagnosis, related diseases, and treatment processes. During the discovery process, the naming of the parathyroid organ was determined entirely according to its location. Considering the given name, the importance of the function provided by the parathyroid gland seems relative to be less effective than the other endocrine organs. Furthermore, the public often exposes it to preliminary assumptions as an organ related to thyroid tissue. However, they have nothing in common except that they are two organs with very different functions.

Parathyroid glands release parathormone (PTH) to perform its function and regulate the metabolism of blood calcium, phosphorus, vitamin D, and magnesium in this way [1]. Common diseases of the parathyroid glands are defined as hyperparathyroidism when the organ overproduces PTH, and hypoparathyroidism, when the organ produces less PTH or lacks PTH [2]. In the absence of the organ or the case of insufficient blood supply, individuals become deprived of the PTH hormone and its regulation.


2. Related diseases

Hyperparathyroidism is observed in cases where the function of the parathyroid glands increases above the average level. Hyperparathyroidism can occur as a secondary disease as a result of another condition. The primary disease, in this case, is chronic renal failure that causes secondary hyperparathyroidism [3]. Primary disease treatment processes are the main reason for the development of hyperparathyroidism. As a palliative treatment approach, patients are advised to use calcimimetics to suppress the production of higher PTH. Individuals have to take dialysis in cases where chronic kidney disease treatment cannot be provided. Thus, years spent in dialysis lead to overproduced PTH and increased proliferating signals to the parathyroid glands [4]. Growing parathyroid glands will release more PTH and pressure the target organs, such as bones. The individuals are partially excised by surgical methods at a certain period of their lives. Partial surgery defines as subtotal parathyroidectomy, meaning three glands plus half of the fourth gland. Rarely there are supernumerary parathyroid glands in patients [5]. Nevertheless, the surgeon may control the decreased PTH level during surgery (subtotal parathyroidectomy) or, if observed by scintigraphy, then may remove the extra gland.

Further, among four parathyroid glands, hyperparathyroidism is also observed without primary reason and is called primary hyperparathyroidism. One or very rarely two of the glands may overproduce PTH. After the exact diagnosis, it is possible to treat by surgical intervention [6, 7, 8]. Another type of hyperparathyroidism is paraneoplastic hyperparathyroidism, which is very rare. Parathyroid hormone-related peptide (PTH-rp) production increases over average PTH levels due to hypercalcemia [9].

Hypoparathyroidism occurs for autoimmune or idiopathic or iatrogenic reasons. Autoimmune-related parathyroid gland diseases are observed due to genetic factors [10]. In addition, it should not be forgotten that genetic factors are considered “rare diseases” when looking at parathyroid-gland-related diseases. However, the most striking part here is that there is no known treatment option for parathyroid-gland-related genetic diseases, and developmental anomalies are observed in most diseases.

Moreover, idiopathic hypoparathyroidism refers to insufficient PTH secretion unrelated to secondary or acquired reasons. Idiopathic individuals constitute the relatively most unknown disease group for hypoparathyroidism. Iatrogenic hypoparathyroidism is observed when the surgeon unintentionally damages or removes the parathyroid gland in cases such as thyroid gland operations. Whether it is genetic, idiopathic, or iatrogenic reasons, one common problem occurs: the lack of parathyroid gland function [2, 11]. Besides, the majority of hypoparathyroidism patients are individuals who have the disease due to iatrogenic reasons. Considering the purpose and regulation mechanisms of parathyroid glands, it has a significant role in the human body. If a lack of function is observed, individuals must accept a complicated process that lasts their entire lives: permanent hypoparathyroidism [12, 13]. The regimens that should be used after that diagnosis are a part of palliative treatment that is far from improving the patient’s quality of life. Much information has already been shared about the number of medicines only aimed at symptomatic treatment. Side effects and secondary diseases that may develop are becoming more severe as time passes. Individuals experiencing many side effects related to medications have been reported. In cases where symptomatic treatment is insufficient, studies about the decrease in the medication’s efficiency, the time-dependent increase in the amount of medication, and the incidence of observed disorders such as anxiety and depression are rapidly taking place in the literature [14, 15, 16].

2.1 Concerns

Contemporary studies offered a specific disease-characteristic questionnaire to measure disease manifestations for hypoparathyroidism patients. In 2019, Wilde et al. used an analytical empirical approach based on retrospective analysis without involving non-disease-specific questionnaires. These testing revealed major complaints include pain and cramps, gastrointestinal symptoms, depression and anxiety, neurovegetative symptoms, and loss of vitality [17]. A recent study by Bilginer et al. performed a medication adherence questionnaire (MAQ) to hypoparathyroidism patients concerning motivation and knowledge about the palliative treatment option. Observed concerns mainly involved the side effects such as nephrotoxicity for using calcium, and kidney damage, polyuria for using active vitamin D supplementation [15]. Considering its psychological effects, hypoparathyroidism, which affects the quality of life, is evaluated from a broader perspective with current studies. In a pilot study, it was even shown that the cognitive functions of hypoparathyroidism patients were weakened [18]. More studies are urgently needed to prevent hypoparathyroidism from the very beginning. The iatrogenic causes after thyroid surgery must be reduced.

Parathyroid imaging is essential for the location and diagnosis of hyperfunctioning glands correctly. In 2021, the European Association of Nuclear Medicine (EANM) proposed a guideline about the imaging of parathyroid glands. Several approaches and techniques were presented for nuclear medicine physicians who perform parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI). Assessing the localization of hyperfunctioning parathyroid lesions will be more accessible by this guideline [19].


3. Treatment Options

Reckoning the diseases associated with the parathyroid tissue, the treatment options are somewhat more limited. In the development of biomedical technology, two promising treatment options come forward, particularly in the treatment of hypoparathyroidism patients: the first is hormone replacement therapy [20, 21], and the second is parathyroid transplantation [22].

3.1 Hormone replacement therapy

Hormone replacement therapy provides the chance to treat the disease in a targeted way, in this sense, Natpara®, whose Phase studies have continued success for many years [23]. However, the manufacturer has recently announced that it would not continue producing due to technical problems [24]. Transcon PTH™, a prodrug product developed for a new PTH hormone therapy, also announced that it has applied to the Food and Drug Administration (FDA) for a Phase 3 study this year [25].

3.2 Parathyroid transplantation

Parathyroid transplantation is another treatment option for hypoparathyroidism, which has a 110-year history. The first transplant belonged to Brown in 1911 [26]. In the process that started after this date in history, many researchers/physicians continued to contribute to the improvement and efficiency of parathyroid transplantation [27]. Parathyroid gland transplantation is a method still used in today's transplantation processes shared by the Cleveland Clinic [28]. Among all parathyroid transplantations, the most extensive clinical series in the literature belongs to the Warsaw group from the University of Warsaw in Poland [29]. In 2017, they reported the survival results of 316 allotransplantation data. Since the early 1990s, many research projects have been added to the literature about cell isolation, graft delivery location, and follow-up parameters from the same group [29, 30, 31, 32, 33]. During the last five years of the parathyroid transplantation, advanced immunological transplantation criteria, including pre-op and post-follow-up processes after parathyroid transplantation, were brought to the literature by the same group from Bezmialem Vakif University in Turkiye [22, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43]

Parathyroid transplantation is the most effective and targeted hypoparathyroidism treatment in the literature due to limited access to hormone replacement therapy and ongoing phase studies. Long-term studies on research and parathyroid transplantation outcomes are carried out in the literature at specific intervals. Treatment options for hypoparathyroidism have certain boundaries with more specific approaches than hyperparathyroidism. On the subject of hyperparathyroidism disorders, primary hyperparathyroidism is treated with surgical intervention and is rarely seen recurrently. Secondary hyperparathyroidism is due to another primary disease, and calcimimetics are recommended to reduce the pressure on the parathyroid glands. Considering the complaints we received from patients regarding the side effects of calcimimetics, the need for more research about the formulation of pharmaceuticals reveals that necessity.


4. Conclusion

The existing literature on treatment options for parathyroid gland diseases provides promising results. Simultaneous cellular and molecular biology studies are undoubtedly necessary and have positive effects in providing diagnostic, therapeutic, and predictive options. The unique function of the parathyroid glands and the inability to adequately treat the cause of the disease illustrate the urgent need for large cohort studies to be established. Even though the collaboration between the researchers on this subject is a fading dream, the editors hope this book will inspire such cooperation among scientific circles.


Conflict of interest

The authors declare no conflict of interest.


  1. 1. Lemoine S, Figueres L, Bacchetta J, Frey S, Dubourg L. Calcium homeostasis and hyperparathyroidism: Nephrologic and endocrinologic points of view. Annales d’endocrinologie. 2022;83(4):237-243
  2. 2. Bilezikian JP. Hypoparathyroidism. The Journal of Clinical Endocrinology and Metabolism. 2020;105:6
  3. 3. Muppidi V, Meegada SR, Rehman A. Secondary Hyperparathyroidism. Treasure Island (FL): StatPearls; 2022
  4. 4. Ketteler M, Bover J, Mazzaferro S. ERA CKD-MBD Working Groups. Treatment of secondary hyperparathyroidism in non-dialysis CKD: An appraisal 2022s. Nephrology, Dialysis, Transplantation. 17 Aug 2022:gfac236. DOI: 10.1093/ndt/gfac236. [Epub ahead of print] PMID: 35977397
  5. 5. Pattou FN, Pellissier LC, Noel C, Wambergue F, Huglo DG, Proye CA. Supernumerary parathyroid glands: Frequency and surgical significance in treatment of renal hyperparathyroidism. World Journal of Surgery. 2000;24(11):1330-1334
  6. 6. Pal R, Jignesh SR, Sanyasi S, Lohani S, Dahiya D, Bhadada SK. Revisiting captain Charles Martell: Witnessing the true face of primary hyperparathyroidism even in the twenty-first century. Archives of Osteoporosis. 2022;17(1):148
  7. 7. Bandeira F, de Moura NJ, de Oliveira LB, Bilezikian J. Medical management of primary hyperparathyroidism. Archives in Endocrinology Metabolism. 2022;66(5):689-693
  8. 8. das Neves MC, Santos RO, Ohe MN. Surgery for primary hyperparathyroidism. Archives of Endocrinology and Metabolism. 2022;66(5):678-688
  9. 9. Nakajima K, Tamai M, Okaniwa S, Nakamura Y, Kobayashi M, Niwa T, et al. Humoral hypercalcemia associated with gastric carcinoma secreting parathyroid hormone: A case report and review of the literature. Endocrine Journal. 2013;60(5):557-562
  10. 10. Mannstadt M, Cianferotti L, Gafni RI, Giusti F, Kemp EH, Koch CA, et al. Hypoparathyroidism: Genetics and diagnosis. Journal of Bone and Mineral Research. Dec 2022;37(12):2615-2629. DOI: 10.1002/jbmr.4667. Epub: 2022 Nov 14. PMID: 36375809
  11. 11. Rubin MR. Recent advances in understanding and managing hypoparathyroidism. F1000Research. 2020;2020:9
  12. 12. Khan AA, Koch CA, Van Uum S, Baillargeon JP, Bollerslev J, Brandi ML, et al. Standards of care for hypoparathyroidism in adults: A Canadian and international consensus. European Journal of Endocrinology. 2019;180(3):P1-P22
  13. 13. Astor MC, Lovas K, Debowska A, Eriksen EF, Evang JA, Fossum C, et al. Epidemiology and health-related quality of life in hypoparathyroidism in Norway. The Journal of Clinical Endocrinology and Metabolism. 2016;101(8):3045-3053
  14. 14. Stamm B, Blaschke M, Wilken L, Wilde D, Heppner C, Leha A, et al. The influence of conventional treatment on symptoms and complaints in patients with chronic postsurgical hypoparathyroidism. JBMR Plus. 2022;6(2):e10586
  15. 15. Bilginer MC, Aydin C, Polat B, Faki S, Topaloglu O, Ersoy R, et al. Assessment of calcium and vitamin D medications adherence in patients with hypoparathyroidism after thyroidectomy. Archives of Osteoporosis. 2022;17(1):22
  16. 16. Frey S, Figueres L, Pattou F, Le Bras M, Caillard C, Mathonnet M, et al. Impact of permanent post-thyroidectomy hypoparathyroidism on self-evaluation of quality of life and voice: Results from the national QoL-Hypopara study. Annals of Surgery. 2021;274(5):851-858
  17. 17. Wilde D, Wilken L, Stamm B, Blaschke M, Heppner C, Chavanon ML, et al. The HPQ-development and first Administration of a Questionnaire for Hypoparathyroid patients. JBMR Plus. 2020;4(1):e10245
  18. 18. Rubin MR, Tabacco G, Omeragic B, Majeed R, Hale C, Brickman AM. A pilot study of cognition among hypoparathyroid adults. Journal of Endocrinal Society. 2022;6(3):bvac002
  19. 19. Petranovic Ovcaricek P, Giovanella L, Carrio Gasset I, Hindie E, Huellner MW, Luster M, et al. The EANM practice guidelines for parathyroid imaging. European Journal of Nuclear Medicine and Molecular Imaging. 2021;48(9):2801-2822
  20. 20. Clarke BL, Vokes TJ, Bilezikian JP, Shoback DM, Lagast H, Mannstadt M. Effects of parathyroid hormone rhPTH(1-84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study. Endocrine. 2017;55(1):273-282
  21. 21. Vokes TJ, Mannstadt M, Levine MA, Clarke BL, Lakatos P, Chen K, et al. Recombinant human parathyroid hormone effect on health-related quality of life in adults with chronic hypoparathyroidism. The Journal of Clinical Endocrinology & Metabolism. 2017;103(2):722-731
  22. 22. Goncu B, Salepcioglu Kaya H, Yucesan E, Ersoy YE, Akcakaya A. Graft survival effect of HLA-A allele matching parathyroid allotransplantation. Journal of Investigative Medicine. 2021;69(3):785-788
  23. 23. Yao L, Li J, Li M, Lin C, Hui X, Tamilselvan D, et al. Parathyroid hormone therapy for managing chronic hypoparathyroidism: A systematic review and Meta-analysis. Journal of Bone and Mineral Research. Dec 2022;37(12):2654-2662. DOI: 10.1002/jbmr.4676. Epub: 2022 Nov 16. PMID: 36385517
  24. 24. Takeda to Discontinue Manufacturing of NATPAR®/NATPARA® for Patients with Hypoparathyroidism at the End of 2024 [Internet]. Takeda Pharmaceutical Company Limited. 2022 [cited December 5, 2022]. Available from:
  25. 25. TRANSCON PTH Designed to replace parathyroid hormone to physiologic levels in patients with hypoparathyroidism [Internet]. Ascendis Pharma. [cited December 5, 2022]. Available from:
  26. 26. Brown WH. Parathyroid implantation in the treatment of Tetania Parathyreopriva. Annals of Surgery. 1911;53(3):305-317
  27. 27. Zhang JLH, Appelman-Dijkstra NM, Schepers A. Parathyroid Allotransplantation: A systematic review. Medical Science (Basel). 2022;10(1):19-32
  28. 28. Agarwal A, Waghray A, Gupta S, Sharma R, Milas M. Cryopreservation of parathyroid tissue: An illustrated technique using the Cleveland clinic protocol. Journal of the American College of Surgeons. 2013;216(1):e1-e9
  29. 29. Barczynski M, Golkowski F, Nawrot I. Parathyroid transplantation in thyroid surgery. Gland Surgery. 2017;6(5):530-536
  30. 30. Nawrot I, Wozniewicz B, Szmidt J, Sladowski D, Zajac K, Chudzinski W. Xenotransplantation of human cultured parathyroid progenitor cells into mouse peritoneum does not induce rejection reaction. Central European Journal of Immunology. 2014;39(3):279-284
  31. 31. Nawrot I, Woźniewicz B, Tołłoczko T, Sawicki A, Górski A, Chudziński W, et al. Allotransplantation of cultured parathyroid progenitor cells without immunosuppression: Clinical results. Transplantation. 2007;83(6):734-740
  32. 32. Tolloczko T, Wozniewicz B, Gorski A, Sawicki A, Nawrot I, Migaj M, et al. Cultured parathyroid cells allotransplantation without immunosuppression for treatment of intractable hypoparathyroidism. Annals of Transplantation. 1996;1(1):51-53
  33. 33. Wozniewicz B, Migaj M, Giera B, Prokurat A, Tolloczko T, Sawicki A, et al. Cell culture preparation of human parathyroid cells for allotransplantation without immunosuppression. Transplantation Proceedings. 1996;28(6):3542-3544
  34. 34. Goncu B, Yucesan E, Basoglu H, Gul B, Aysan E, Ersoy YE. Xenotransplantation of microencapsulated parathyroid cells as a potential treatment for autoimmune-related hypoparathyroidism. Experimental and Clinical Transplantation. 9 Aug 2021. DOI: 10.6002/ect.2020.0403. Epub ahead of print. PMID: 34387152
  35. 35. Goncu B, Yucesan E, Ersoy YE, Aysan ME, Ozten KN. HLA-DR, -DP, -DQ expression status of parathyroid tissue as a potential parathyroid donor selection criteria and review of literature. Human Immunology. 2021;83(2):113-118
  36. 36. Aysan E, Yucesan E, Goncu B, Idiz UO. Fresh tissue parathyroid Allotransplantation from a cadaveric donor without immunosuppression: A 3-year follow-up. The American Surgeon. 2020;86(4):e180-e1e2
  37. 37. Yucesan EGB, Idiz O, Ucak R, Ozdemir B, Kanimdan E, Ersoy YE, et al. The effect of intravenously paratyroid cell xenotransplantation in sheep: As an animal model. Kafkas Universitesi Veteriner Fakultesi Dergisi. 2020;26(6):765-770
  38. 38. Aysan E, Yucesan E, Idiz UO, Goncu B. Discharging a patient treated with parathyroid allotransplantation after having been hospitalized for 3.5 years with permanent hypoparathyroidism: A case report. Transplantation Proceedings. 2019;51(9):3186-3188
  39. 39. Yucesan E, Goncu B, Ozdemir B, Idiz O, Ersoy YE, Aysan E. Importance of HLA typing, PRA and DSA tests for successful parathyroid allotransplantation. Immunobiology. 2019;224(4):485-489
  40. 40. Yucesan E, Basoglu H, Goncu B, Akbas F, Ersoy YE, Aysan E. Microencapsulated parathyroid allotransplantation in the omental tissue. Artificial Organs. 2019;43(10):1022-1027
  41. 41. Goncu B, Yucesan E, Aysan E, Kandas NO. HLA class I expression changes in different types of cultured parathyroid cells. Experimental and Clinical Transplantation. 2019
  42. 42. Goncu B, Yucesan E, Ozdemir B, Basoglu H, Kandas NO, Akbas F, et al. A new transport solution for parathyroid allotransplantation: Effects on cell viability and calcium-sensing receptors. Biopreservation and Biobanking. 2018;16(4):278-284
  43. 43. Yucesan E, Goncu B, Basoglu H, Ozten Kandas N, Ersoy YE, Akbas F, et al. Fresh tissue parathyroid allotransplantation with short-term immunosuppression: 1-year follow-up. Clinical Transplantation. 2017;31(11):10-14

Written By

Beyza Goncu and Robert Gensure

Published: 15 March 2023