Thyroid scintigraphy: establishing a clinically useful normal range for ^99mTc pertechnetate uptake

Abstract

Purpose This study aims to establish a normal range for the thyroid uptake derived from ^99mTc pertechnetate scans. In particular, variations of uptake with TSH stimulation and other factors such as urinary iodine concentration are taken into account and compared with the calculation of a raw uptake value.

Methods Clinical multicentric (center A, B and C) prospective study on 125 consecutive healthy patients undergoing thyroid scans for thyroid nodules. Normal functional thyroid status was assured by normal TSH, normal thyroid size, no thyroid antibodies and no symptoms of thyroid functional disorders. Calculations of raw Tc-uptake (uptake) and modified uptake values regarding current TSH value (uptake_TSH1), urinary iodine concentration (uptake_TSH1&uic), gland volume, age, smoking status, weight and tissue thickness ventral to the thyroid were performed.

Results There is a positive correlation of thyroid uptake with TSH allowing for the calculation of a normalized uptake value (uptake_TSH1). The normal range for uptake_TSH1 compares favourable to that for raw uptake in that it yields a clear distinction from thyroid functional disorders. The additional normalization for urinary iodine concentration (uptake_TSH1&uic) may even improve the distinctive power whereas further normalizations such as for gland volume, age and others are not warranted by this study. The 95% CI of uptake_TSH1 for sites A, A&B, and A&B&C were 0.21%–2.06%, 0.22%–2.38% and 0.24%–2.40%.

Conclusion A normal range for the thyroid uptake can be established with respect to the current TSH stimulation. This normalization (uptake_TSH1) overcomes the drawback of raw uptake by yielding a clinically useful parameter with obviously high distinctive power against functional thyroid disorders.

Keywords

thyroid scintigraphy - TSH - urinary iodine concentration - 99mTc-pertechnetate uptake

Publication History

Received: 28 March 2024

Accepted after revision: 12 July 2024

Article published online:
31 July 2024

• Literature

• 1 Giovanella L, Avram AM, Iakovou I. et al. EANM practice guideline/SNMMI procedure standard for RAIU and thyroid scintigraphy. Eur J Nucl Med Mol Imaging 2019; 46: 2514-2525 DOI: 10.1007/s00259-019-04472-8. (PMID: 31392371)
• 2 Fricke E, Fricke H, Esdorn E. et al. Scintigraphy for risk stratification of iodine-induced thyrotoxicosis in patients receiving contrast agent for coronary angiography: a prospective study of patients with low thyrotropin. J Clin Endocrinol Metab 2004; 89: 6092-6096 DOI: 10.1210/jc.2004-0728.
• 3 Stanley MM, Astwood EB. The response of the thyroid gland in normal human subjects to the administration of thyrotropin, as shown by studies with I131. Endocrinology 1949; 44: 49-60 DOI: 10.1210/endo-44-1-49.
• 4 Knopp J, Stolc V, Tong W. Evidence for the induction of iodide transport in bovine thyroid cells treated with thyroid-stimulating hormone or dibutyryl cyclic adenosine 3’,5’-monophosphate. J Biol Chem 1970; 245: 4403-4408 (PMID: 4322436)
• 5 Mariani G, Tonacchera M, Grosso M. et al. The Role of Nuclear Medicine in the Clinical Management of Benign Thyroid Disorders, Part 1: Hyperthyroidism. Journal of Nuclear Medicine 2021; 62: 304-312 DOI: 10.2967/jnumed.120.243170. (PMID: 33008929)
• 6 Giovanella L, Avram AM, Ovčariček PP. et al. Thyroid functional and molecular imaging. La Presse Médicale 2022; 51: 104116 DOI: 10.1016/j.lpm.2022.104116. (PMID: 35124101)
• 7 Atkins HL. Technetium-99m pertechnetate uptake and scanning in the evaluation of thyroid function. Semin Nucl Med 1971; 1: 345-355 DOI: 10.1016/s0001-2998(71)80007-7. (PMID: 4329842)
• 8 Macauley M, Shawgi M, Ali T. et al. Assessment of normal reference values for thyroid uptake of technetium-99m pertechnetate in a single centre UK population. Nucl Med Commun 2018; 39: 834-838 DOI: 10.1097/mnm.0000000000000876. (PMID: 29877994)
• 9 Dietlein M, Eschner W, Lassmann M. et al. DGN-Handlungsempfehlung (S1-Leitlinie) Schilddrüsenszintigraphie (Version 4) Stand: 10/2014–AWMF-Registernummer: 031–011. Deutsche Gesellschaft für Nuklearmedizin. 2019
• 10 Sherwin JR, Tong W. The actions of iodide and TSH on thyroid cells showing a dual control system for the iodide pump. Endocrinology 1974; 94: 1465-1474 DOI: 10.1210/endo-94-5-1465. (PMID: 4823522)
• 11 Bähre M, Hilgers R, Lindemann C. et al. Physiological aspects of the thyroid trapping function and its suppression in iodine deficiency using ^99mTc pertechnetate. Acta Endocrinol (Copenh) 1987; 115: 175-182 DOI: 10.1530/acta.0.1150175. (PMID: 3037834)
• 12 Deutsche Gesellschaft für Ernährung e.V. Referenzwerte Iod. Accessed February 11, 2024 at: https://www.dge.de/wissenschaft/referenzwerte/jod
• 13 Deutsche Gesellschaft für Ernährung e.V. Nutritional Report 2016 of the German Society for Nutrition. Accessed February 11, 2024 at: https://www.dge.de
• 14 Ross DS, Burch HB, Cooper DS. et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016; 26: 1343-1421 DOI: 10.1089/thy.2016.0229. (PMID: 27521067)
• 15 Jonklaas J, Bianco AC, Cappola AR. et al. Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document. Eur Thyroid J 2021; 10: 10-38 DOI: 10.1159/000512970. (PMID: 33276704)
• 16 Baumgartner C, da Costa BR, Collet TH. et al. Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation. Circulation 2017; 136: 2100-2116 DOI: 10.1161/circulationaha.117.028753.
• 17 Esfandiari NH, Papaleontiou M. Biochemical Testing in Thyroid Disorders. Endocrinol Metab Clin North Am 2017; 46: 631-648 DOI: 10.1016/j.ecl.2017.04.002. (PMID: 28760230)
• 18 Caron PJ, Nieman LK, Rose SR. et al. Deficient nocturnal surge of thyrotropin in central hypothyroidism. J Clin Endocrinol Metab 1986; 62: 960-964 DOI: 10.1210/jcem-62-5-960. (PMID: 3958131)
• 19 Karmisholt J, Andersen S, Laurberg P. Variation in thyroid function tests in patients with stable untreated subclinical hypothyroidism. Thyroid 2008; 18: 303-308 DOI: 10.1089/thy.2007.0241. (PMID: 18303960)
• 20 Lewandowski KC, Garnysz K, Horzelski W. et al. Subclinical thyroid dysfunction in the first trimester of pregnancy: ‘Disease’ versus physiological (pulsatile) variation in TSH concentrations. Clin Endocrinol (Oxf) 2020; 93: 739-745 DOI: 10.1111/cen.14256. (PMID: 32430942)
• 21 Fu J, Zhang G, Xu P. et al. Seasonal Changes of Thyroid Function Parameters in Women of Reproductive Age Between 2012 and 2018: A Retrospective, Observational, Single-Center Study. Front Endocrinol (Lausanne) 2021; 12: 719225 DOI: 10.3389/fendo.2021.719225.
• 22 Seifert P, Schenke S, Zimny M. et al. Diagnostic Performance of Kwak, EU, ACR, and Korean TIRADS as Well as ATA Guidelines for the Ultrasound Risk Stratification of Non-Autonomously Functioning Thyroid Nodules in a Region with Long History of Iodine Deficiency: A German Multicenter Trial. Cancers 2021; 13: 4467
• 23 Petersen M, Schenke SA, Seifert P. et al. Correct and Incorrect Recommendations for or against Fine Needle Biopsies of Hypofunctioning Thyroid Nodules: Performance of Different Ultrasound-based Risk Stratification Systems. Nuklearmedizin 2023; DOI: 10.1055/a-2178-6739. (PMID: 37871628)
• 24 Giovanella L, Avram AM, Iakovou I. et al. EANM practice guideline/SNMMI procedure standard for RAIU and thyroid scintigraphy. European Journal of Nuclear Medicine and Molecular Imaging 2019; 46: 2514-2525 DOI: 10.1007/s00259-019-04472-8. (PMID: 31392371)
• 25 Paudel J, Bhattarai B. Standardizing Normal Reference Value for Thyroid Uptake of Technetium-99m Pertechnetate in Nepalese Population. World Journal of Nuclear Medicine 2024; DOI: 10.1055/s-0044-1779283. (PMID: 38595834)
• 26 Gotthardt M, Stübinger M, Pansegrau J. et al. Decrease of (99m)Tc-uptake in autonomous thyroid tissue in Germany since the 1970s. Clinical implications for radioiodine therapy. Nuklearmedizin 2006; 45: 122-125
• 27 Reinhardt MJ, Högerle S, Trupkovic T. et al. Influence of urinary iodine excretion on thyroid technetium-99m pertechnetate uptake with and without TSH suppression: what happens when iodine supply increases?. European Journal of Nuclear Medicine 1998; 25: 1475-1481 DOI: 10.1007/s002590050324.
• 28 Milakovic M, Berg G, Eggertsen R. et al. Effect of lifelong iodine supplementation on thyroid 131-I uptake: a decrease in uptake in euthyroid but not hyperthyroid individuals compared to observations 50 years ago. European Journal of Clinical Nutrition 2006; 60: 210-213 DOI: 10.1038/sj.ejcn.1602290. (PMID: 16251883)
• 29 Vassart G, Pardo L, Costagliola S. A molecular dissection of the glycoprotein hormone receptors. Trends Biochem Sci 2004; 29: 119-126 DOI: 10.1016/j.tibs.2004.01.006. (PMID: 15003269)
• 30 Taylor PN, Lansdown A, Witczak J. et al. Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice. Thyroid Res 2023; 16: 7 DOI: 10.1186/s13044-023-00149-5. (PMID: 37009883)
• 31 Fu J, Wang Y, Liu Y. et al. Reference intervals for thyroid hormones for the elderly population and their influence on the diagnosis of subclinical hypothyroidism. J Med Biochem 2023; 42: 258-264 DOI: 10.5937/jomb0-39570.
• 32 Yeap BB, Manning L, Chubb SA. et al. Reference Ranges for Thyroid-Stimulating Hormone and Free Thyroxine in Older Men: Results From the Health In Men Study. J Gerontol A Biol Sci Med Sci 2017; 72: 444-449 DOI: 10.1093/gerona/glw132.
• 33 Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol 2015; 3: 286-295 DOI: 10.1016/s2213-8587(14)70225-6. (PMID: 25591468)
• 34 Ahad F, Ganie SA. Iodine, Iodine metabolism and Iodine deficiency disorders revisited. Indian J Endocrinol Metab 2010; 14: 13-17 (PMID: 21448409)
• 35 Winder M, Kosztyła Z, Boral A. et al. The Impact of Iodine Concentration Disorders on Health and Cancer. Nutrients 2022; 14: 2209 DOI: 10.3390/nu14112209. (PMID: 35684009)
• 36 Du FM, Kuang HY, Duan BH. et al. Effects of thyroid hormone and depression on common components of central obesity. J Int Med Res 2019; 47: 3040-3049 DOI: 10.1177/0300060519851624. (PMID: 31144547)
• 37 Mele C, Mai S, Cena T. et al. The pattern of TSH and fT4 levels across different BMI ranges in a large cohort of euthyroid patients with obesity. Front Endocrinol (Lausanne) 2022; 13: 1029376 DOI: 10.3389/fendo.2022.1029376.
• 38 Mettler FA, Guiberteau MJ. 1 – Radioactivity, Radionuclides, and Radiopharmaceuticals. In: Mettler FA, Guiberteau MJ. Essentials of Nuclear Medicine Imaging (Sixth Edition). Philadelphia: W.B. Saunders; 2012: 1-21 DOI: 10.1016/B978-1-4557-0104-9.00001-9
• 39 Zhang Y, Shi L, Zhang Q. et al. The association between cigarette smoking and serum thyroid stimulating hormone, thyroid peroxidase antibodies and thyroglobulin antibodies levels in Chinese residents: A cross-sectional study in 10 cities. PLoS One 2019; 14: e0225435 DOI: 10.1371/journal.pone.0225435.