Modulation of Sodium/iodide Symporter Expression in the Salivary Gland

Overview

Journal Thyroid

Date 2013 Feb 28

PMID 23441638

Citations 34

Authors

Krista M D La Perle

Dong Chul Kim

Nathan C Hall

Adam Bobbey

Daniel H Shen

Rebecca S Nagy

Paul E Wakely Jr

Amy Lehman

David Jarjoura

Sissy M Jhiang

Affiliations

Soon will be listed here.

Abstract

Background: Physiologic iodide-uptake, mediated by the sodium/iodide symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine-induced damage following (131)I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland.

Methods: NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative (123)I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after (123)I administration in 50 thyroid cancer patients.

Results: NIS is highly expressed in the basolateral membranes of the majority of striated ducts, yet weakly expressed in few intercalated and excretory duct cells. The ratio of (123)I accumulation between parotid and submandibular glands is 2.38±0.19. However, the corresponding ratio of (123)I accumulation normalized by volume of interest is 1.19±0.06. The percentage of NIS-positive striated duct cells in submandibular salivary glands was statistically greater than in parotid salivary glands, suggesting a higher clearance rate of saliva secretion in submandibular salivary glands. NIS expression in striated ducts was heterogeneously decreased or absent in sialoadenitis. Most ductal salivary gland tumors did not express NIS. However, Warthin's tumors of striated duct origin exhibited consistent and intense NIS staining, corresponding with radioactive iodine uptake.

Conclusions: NIS expression is tightly modulated during the transition of intercalated to striated ducts and striated to excretory ducts in salivary ductal cells. NIS expression in salivary glands is decreased during inflammation and tumor formation. Further investigation may identify molecular targets and/or pharmacologic agents that allow selective inhibition of NIS expression/activity in salivary glands during radioactive iodine treatment.

Citing Articles

Characteristics of Salivary Iodine Concentration in Elderly Residents of High-iodine Areas.

Liu M, Li J, Zhang H, Liu Y, Wang Z, Ren Z Biol Trace Elem Res. 2024; .

PMID: 39607587 DOI: 10.1007/s12011-024-04453-5.

Salivary, lacrimal and nasal (SALANS) measure to assess side effects following radioactive iodine treatment: development, psychometric properties, and factor structure.

Jonklaas J, Carr A, Luta G, Yu C, Jensen R, Reasner E Qual Life Res. 2024; 33(7):2011-2023.

PMID: 38769210 DOI: 10.1007/s11136-024-03684-2.

Salivary iodide status as a measure of whole body iodine homoeostasis?.

Alsaeedi E, Rose P, Welham S Br J Nutr. 2024; 131(10):1740-1753.

PMID: 38287697 PMC: 11063662. DOI: 10.1017/S000711452400031X.

Changes in Serum Alkaline Phosphatase, Calcium, and Parathyroid Hormone with Different Doses of Iodine Therapy:.

Movahedi M, Karimaghaei G, Noori A, Atefi M, Mahmoudi T, Gheisari F Galen Med J. 2023; 11:e2397.

PMID: 36698694 PMC: 9838107. DOI: 10.31661/gmj.v11i.2397.

Quantitative Scintigraphy Evaluated the Relationship between 131I Therapy and Salivary Glands Function in DTC Patients: A Retrospective Analysis.

Lv X, Yin L, Wu W, Li N, Zhang R, Li X J Healthc Eng. 2022; 2022:7640405.

PMID: 35463665 PMC: 9023193. DOI: 10.1155/2022/7640405.

References

Dodds M, Johnson D, Yeh C . Health benefits of saliva: a review. J Dent. 2005; 33(3):223-33. DOI: 10.1016/j.jdent.2004.10.009. View

Cotroneo E, Proctor G, Carpenter G . Regeneration of acinar cells following ligation of rat submandibular gland retraces the embryonic-perinatal pathway of cytodifferentiation. Differentiation. 2010; 79(2):120-30. PMC: 2841285. DOI: 10.1016/j.diff.2009.11.005. View

Jhiang S, Cho J, Ryu K, DeYoung B, Smanik P, McGaughy V . An immunohistochemical study of Na+/I- symporter in human thyroid tissues and salivary gland tissues. Endocrinology. 1998; 139(10):4416-9. DOI: 10.1210/endo.139.10.6329. View

Spitzweg C, Joba W, SCHRIEVER K, Goellner J, Morris J, Heufelder A . Analysis of human sodium iodide symporter immunoreactivity in human exocrine glands. J Clin Endocrinol Metab. 1999; 84(11):4178-84. DOI: 10.1210/jcem.84.11.6117. View

Bruno R, Giannasio P, Ronga G, Baudin E, Travagli J, Russo D . Sodium iodide symporter expression and radioiodine distribution in extrathyroidal tissues. J Endocrinol Invest. 2005; 27(11):1010-4. DOI: 10.1007/BF03345302. View

Van Nostrand D . Sialoadenitis secondary to ¹³¹I therapy for well-differentiated thyroid cancer. Oral Dis. 2010; 17(2):154-61. DOI: 10.1111/j.1601-0825.2010.01726.x. View

Konings A, Coppes R, Vissink A . On the mechanism of salivary gland radiosensitivity. Int J Radiat Oncol Biol Phys. 2005; 62(4):1187-94. DOI: 10.1016/j.ijrobp.2004.12.051. View

Yeh C, Johnson D, Dodds M . Impact of aging on human salivary gland function: a community-based study. Aging (Milano). 1999; 10(5):421-8. DOI: 10.1007/BF03339889. View

Vayre L, Sabourin J, Caillou B, Ducreux M, Schlumberger M, Bidart J . Immunohistochemical analysis of Na+/I- symporter distribution in human extra-thyroidal tissues. Eur J Endocrinol. 1999; 141(4):382-6. DOI: 10.1530/eje.0.1410382. View

10.

Liu B, Huang R, Kuang A, Zhao Z, Zeng Y, Wang J . Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer. Med Phys. 2011; 38(10):5412-9. DOI: 10.1118/1.3602459. View

11.

Malpani B, Samuel A, Ray S . Differential kinetics of parotid and submandibular gland function as demonstrated by scintigraphic means and its possible implications. Nucl Med Commun. 1995; 16(8):706-9. DOI: 10.1097/00006231-199508000-00015. View

12.

Mandel S, Mandel L . Radioactive iodine and the salivary glands. Thyroid. 2003; 13(3):265-71. DOI: 10.1089/105072503321582060. View

13.

Newkirk K, Ringel M, Wartofsky L, Burman K . The role of radioactive iodine in salivary gland dysfunction. Ear Nose Throat J. 2000; 79(6):460-8. View

14.

Venturi S, Venturi M . Iodine in evolution of salivary glands and in oral health. Nutr Health. 2009; 20(2):119-34. DOI: 10.1177/026010600902000204. View

15.

Murata Y, Yamada I, Umehara I, Okada N, Shibuya H . Diagnostic accuracy of technetium-99m-pertechnetate scintigraphy with lemon juice stimulation to evaluate Warthin's tumor. J Nucl Med. 1998; 39(1):43-6. View

16.

Weinstein G, Harvey R, Zimmer W, Ter S, Alavi A . Technetium-99m pertechnetate salivary gland imaging: its role in the diagnosis of Warthin's tumor. J Nucl Med. 1994; 35(1):179-83. View