Primary hyperparathyroidism and non-medullary thyroid cancer- A review

  • Nathalie El-Boueiz American University of Beirut
  • Ibrahim Salti American University of Beirut



The association of thyroid disease and primary hyperparathyroidism is well described, with thyroid carcinoma being reported in 2-15% of cases. The most commonly associated carcinoma is non-medullary thyroid cancer. While the association of PHPT and medullary thyroid cancer (MCT) is well known, that of NMTC, despite its increasing incidence, is still not established. Our study is a review of incidence and underlying mechanisms of non-medullary thyroid cancer associated with PHPT. Also, best imaging tools for concomitant diagnosis is reviewed to ensure an adequate plan of care.

Methods & findings:

A search was done using two databases: Medline & Embase. The search conducted from the period of 2008 until April 2018 yielded a total of 142 studies. After an adequate screening, 26 studies were reviewed. 

Incidence of DTC in association with PHPT in the literature ranged between 0.91% and 17.6%. The main histological thyroid malignancy found is micropapillary carcinoma. Despite its less aggressive presentation, these microcarcinomas may grow or develop nodal metastases on follow up. Although bilateral neck exploration with hemi/total thyroidectomy carries the risk of temporary recurrent laryngeal nerve injury or hypoparathyroidism, permanent complications are rare especially when compared to re-do neck surgery. Recently, parathyroid surgeries are going towards minimal invasive procedures, requiring an adequate imaging tool to ensure diagnosis of both diseases. Multiple risk factors for concomitant diseases were hypothesized, the more robust are the common embryologic origin and activation of angiogenic growth factors.


NMTC is frequently associated with PHPT especially in endemic goiter areas. With the high prevalence of micropapillary carcinoma and its risks, a partial/total thyroidectomy in addition to parathyroidectomy may be warranted. With the recent need of adequate diagnostic tools, combining both Technetium Sestamibi scintigraphy and thyroid ultrasound improved sensitivities and accuracy of diagnosis, but dual-isotope scintigraphy (I-123 sodium iodide/ 99mTc-sestamibi) seems an attractive modality in hyperparathyroid patients with concomitant suspicious thyroid nodules. However, further studies for validation may be needed.


Uncategorized References
1. Scerrino G, Attard M, Lo Piccolo C, Attard A, Melfa GI, Raspanti C, et al. The coexistence of primary hyperparathyroidism and thyroid nodules: should the preoperative work-up of the parathyroid and the thyroid diseases be specifically adjusted? Giornale di Chirurgia. 2016;37(3):123-9.
2. Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nature reviews Endocrinology. 2018;14(2):115-25.
3. Xue Y, Ye ZQ, Zhou HW, Shi BM, Yi XH, Zhang KQ. Serum calcium and risk of nonmedullary thyroid cancer in patients with primary hyperparathyroidism. Medical Science Monitor. 2016;22:4482-9.
4. Guo R, Wang J, Zhang M, Zhang M, Meng H, Zhang Y, et al. Value of 99mTc-MIBI SPECT/CT parathyroid imaging and ultrasonography for concomitant thyroid carcinoma. Nuclear Medicine Communications. 2017;38(8):676-82.
5. Kwon JH, Kim EK, Lee HS, Moon HJ, Kwak JY. Neck ultrasonography as preoperative localization of primary hyperparathyroidism with an additional role of detecting thyroid malignancy. European Journal of Radiology. 2013;82(1):e17-e21.
6. Arciero CA, Shiue ZS, Gates JD, Peoples GE, Dackiw AP, Tufano RP, et al. Preoperative thyroid ultrasound is indicated in patients undergoing parathyroidectomy for primary hyperparathyroidism. Journal of Cancer. 2012;3:1-6.
7. Wright MC, Jensen K, Mohamed H, Drake C, Mohsin K, Monlezun D, et al. Concomitant thyroid disease and primary hyperparathyroidism in patients undergoing parathyroidectomy or thyroidectomy. Gland surgery. 2017;6(4):368-74.
8. Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS. The Diagnosis and Management of Thyroid Nodules: A Review. Jama. 2018;319(9):914-24.
9. Jovanovic M, Zivaljevic V, Diklic A, Zoric G, Tausanovic K, Slijepcevic N, et al. Incidental papillary thyroid cancer in patients who have undergone parathyroid surgery. Langenbeck's Archives of Surgery. 2017;402(2):374-5.
10. Beebeejaun M, Chinnasamy E, Wilson P, Sharma A, Beharry N, Bano G. Papillary carcinoma of the thyroid in patients with primary hyperparathyroidism: Is there a link? Medical Hypotheses. 2017;103:100-4.
11. Wells SA, Jr., Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567-610.
12. Wells SA, Jr., Pacini F, Robinson BG, Santoro M. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab. 2013;98(8):3149-64.
13. Jovanovic MD, Zivaljevic VR, Diklic AD, Rovcanin BR, G VZ, Paunovic IR. Surgical treatment of concomitant thyroid and parathyroid disorders: analysis of 4882 cases. European Archives of Oto-Rhino-Laryngology. 2017;274(2):997-1004.
14. Emirikci S, Ozcinar B, Oner G, Omarov N, Agcaoglu O, Soytas Y, et al. Thyroid cancer incidence in simultaneous thyroidectomy with parathyroid surgery. Turkish Journal of Surgery. 2015;31(4):214-7.
15. Morita SY, Somervell H, Umbricht CB, Dackiw AP, Zeiger MA. Evaluation for concomitant thyroid nodules and primary hyperparathyroidism in patients undergoing parathyroidectomy or thyroidectomy. Surgery. 2008;144(6):862-6; discussion 6-8.
16. Kutluturk K, Otan E, Yagci MA, Usta S, Aydin C, Unal B. Thyroid pathologies accompanying primary hyperparathyroidism: a high rate of papillary thyroid microcarcinoma. Turkish Journal of Surgery. 2014;30(3):125-8.
17. Ghorra C, Rizk H, Abi Hachem R, Tannoury J, Abboud B. Association of parathyroid pathology with well-differentiated thyroid carcinoma. Presse Medicale. 2012;41(6 PART 1):e265-e71.
18. Yazici P, Mihmanli M, Bozdag E, Aygun N, Uludag M. Location of parathyroid adenomas in primary hyperparathyroidism: Where to look? World Journal of Endocrine Surgery. 2015;7(1):1-5.
19. Riss P, Kammer M, Selberherr A, Scheuba C, Niederle B. Morbidity Associated with Concomitant Thyroid Surgery in Patients with Primary Hyperparathyroidism. Annals of Surgical Oncology. 2015;22(8):2707-13.
20. Heizmann O, Viehl CT, Schmid R, Müller-Brand J, Müller B, Oertli D. Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism. European Journal of Medical Research. 2009;14(1):37-41.
21. Kosem M, Algun E, Kotan C, Harman M, Ozturk M. Coexistent thyroid pathologies and high rate of papillary cancer in patients with primary hyperparathyroidism: controversies about minimal invasive parathyroid surgery. Acta Chir Belg. 2004;104(5):568-71.
22. Brito JP, Gionfriddo MR, Al Nofal A, Boehmer KR, Leppin AL, Reading C, et al. The accuracy of thyroid nodule ultrasound to predict thyroid cancer: systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(4):1253-63.
23. Yazici P, Mihmanli M, Bozdag E, Aygun N, Uludag M. Incidental Finding of Papillary Thyroid Carcinoma in the Patients with Primary Hyperparathyroidism. The Eurasian Journal of Medicine. 2015;47(3):194-8.
24. Cinamon U, Levy D, Marom T. Is primary hyperparathyroidism a risk factor for papillary thyroid cancer? An exemplar study and literature review. International Archives of Otorhinolaryngology. 2013;19(1):42-5.
25. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133.
26. Weiss DM, Chen H. Role of cervical ultrasound in detecting thyroid pathology in primary hyperparathyroidism. Journal of Surgical Research. 2014;190(2):575-8.
27. Sun B, Guo B, Wu B, Kang J, Deng X, Zhang Z, et al. Characteristics, management, and outcome of primary hyperparathyroidism at a single clinical center from 2005 to 2016. 2018;29(3):635-42.
28. Bentrem DJ, Angelos P, Talamonti MS, Nayar R. Is preoperative investigation of the thyroid justified in patients undergoing parathyroidectomy for hyperparathyroidism? Thyroid. 2002;12(12):1109-12.
29. Ito Y, Miyauchi A, Inoue H, Fukushima M, Kihara M, Higashiyama T, et al. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg. 2010;34(1):28-35.
30. Hay ID, Grant CS, van Heerden JA, Goellner JR, Ebersold JR, Bergstralh EJ. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992;112(6):1139-46; discussion 46-7.
31. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 2003;13(4):381-7.
32. Ito Y, Miyauchi A. A therapeutic strategy for incidentally detected papillary microcarcinoma of the thyroid. Nature clinical practice Endocrinology & metabolism. 2007;3(3):240-8.
33. Lang BH, Wong CK. A cost-effectiveness comparison between early surgery and non-surgical approach for incidental papillary thyroid microcarcinoma. Eur J Endocrinol. 2015;173(3):367-75.
34. Wang TS, Roman SA, Cox H, Air M, Sosa JA. The Management of Thyroid Nodules in Patients With Primary Hyperparathyroidism. Journal of Surgical Research. 2009;154(2):317-23.
35. Panarese A, D’Andrea V, Pontone S, Favoriti P, Pironi D, Arcieri S, et al. Management of concomitant hyperparathyroidism and thyroid diseases in the elderly patients: a retrospective cohort study. Aging Clinical and Experimental Research. 2017;29(1):29-33.
36. Riss P, Kammer M, Selberherr A, Scheuba C, Niederle B. Morbidity Associated with Concomitant Thyroid Surgery in Patients with Primary Hyperparathyroidism. Annals of Surgical Oncology. 2015;22(8):2707-13.
37. Wagner B, Begic-Karup S, Raber W, Schneider B, Waldhausl W, Vierhapper H. Prevalence of primary hyperparathyroidism in 13387 patients with thyroid diseases, newly diagnosed by screening of serum calcium. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 1999;107(7):457-61.
38. Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ. Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype. J Clin Endocrinol Metab. 2007;92(8):3001-5.
39. Simpson RJ, Moss J, Jr. Parathyroid adenoma and nonmedullary thyroid carcinoma association. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 1989;101(5):584-7.
40. Wilson SD, Doffek KM, Wang TS, Krzywda EA, Evans DB, Yen TW. Primary hyperparathyroidism with a history of head and neck irradiation: the consequences of associated thyroid tumors. Surgery. 2011;150(4):869-77.
41. Prinz RA, Paloyan E, Lawrence AM, Barbato AL, Braithwaite SS, Brooks MH. Unexpected parathyroid disease discovered at thyroidectomy in irradiated patients. Am J Surg. 1981;142(3):355-7.
42. Pickard AL, Gridley G, Mellemkjae L, Johansen C, Kofoed-Enevoldsen A, Cantor KP, et al. Hyperparathyroidism and subsequent cancer risk in Denmark. Cancer. 2002;95(8):1611-7.
43. Michels KB, Xue F, Brandt L, Ekbom A. Hyperparathyroidism and subsequent incidence of breast cancer. International journal of cancer. 2004;110(3):449-51.
44. Nilsson IL, Zedenius J, Yin L, Ekbom A. The association between primary hyperparathyroidism and malignancy: nationwide cohort analysis on cancer incidence after parathyroidectomy. Endocr Relat Cancer. 2007;14(1):135-40.
45. Fuszek P, Lakatos P, Tabak A, Papp J, Nagy Z, Lakatos PL, et al. [Significance of serum calcium levels in colorectal cancer]. Orvosi hetilap. 2004;145(30):1561-5.
46. Gómez-Ramírez J, Sancho-Insenser JJ, Pereira JA, Jimeno J, Munné A, Sitges-Serra A. Impact of thyroid nodular disease on 99mTc-sestamibi scintigraphy in patients with primary hyperparathyroidism. Langenbeck's Archives of Surgery. 2010;395(7):929-33.
47. Onkendi EO, Richards ML, Thompson GB, Farley DR, Peller PJ, Grant CS. Thyroid cancer detection with dual-isotope parathyroid scintigraphy in primary hyperparathyroidism. Annals of Surgical Oncology. 2012;19(5):1446-52.
How to Cite
EL-BOUEIZ, Nathalie; SALTI, Ibrahim. Primary hyperparathyroidism and non-medullary thyroid cancer- A review. International Archives of Medicine, [S.l.], v. 11, nov. 2018. ISSN 1755-7682. Available at: <>. Date accessed: 20 jan. 2019. doi: