MIBI scintigraphy in hypofunctioning thyroid nodules

Summary

Aim: Several authors have investigated the value of technetium-MIBI scanning to predict the dignity of hypofunctioning, cold thyroid nodules (HTN) in regions with differing levels of iodine supply. They concluded that an MIBI scan can exclude thyroid malignancy, although comparisons between the studies are of limited value owing to differences in methodology and wide variations in patient selection criteria. The present study investigates whether the above claim is also valid in Germany, a country with a long-standing and persistent, mild iodine deficiency and a high incidence of nodules in large goiters with a low prevalence of malignancy. Patients, methods: The study compares the results of ^99mTc-MIBI scintigraphy (incl. SPECT and planar images) in HTN (MIBI) with those of fine-needle aspiration biopsy (FNAB) and histology. Of 154 consecutive patients (121 women, 33 men; mean age 56 ± 12 years), 73 underwent thyroid surgery from which the results of FNAB and MIBI were assessed. Selection criteria were risk estimation or conditions limiting the feasibility of FNAB. The mean thyroid volume was 42 ± 25 ml, with 2.1 ± 1.4 nodules per patient. Results: Histology revealed thyroid malignancies in 8 out of 73 patients (11.0%). The negative predictive value for MIBI was 97%, which is comparable to FNAB (94%). However, in 19.5% of patients FNAB was indeterminate. Lower specificity (54%) and low positive predictive value (19%) showed that MIBI accumulation cannot differentiate between malignant and benign thyroid nodules. However, comparison with cytological and/or histological findings indicated that it could distinguish between lesions with differing rates of mitochondrial metabolism. Conclusion: Even in areas of former or mild iodine deficiency MIBI forms a basis for choosing between wait-and-see and surgical strategies if FNAB is unfeasible or not representative. However, even for pathological MIBI results, the prevalence of malignancy is not very high.

Zusammenfassung

Einige Autoren untersuchten den Wert der Technetium-MIBI-Szintigraphie zur Dignitätbestimmung kalter Schilddrüsenknoten in Regionen mit unterschiedlicher Iodversorgung. Nach diesen Studien ermöglicht MIBI den Ausschluss eines Schilddrüsen malignoms, obwohl sie aufgrund unterschiedlicher Methodik und Patientenauswahl nur eingeschränkt vergleichbar sind. Ziel: Wir prüften, ob sich die Ergebnisse auf die Verhältnisse in Deutschland mit lange bestehendem, noch geringem Iodmangel und einer hohen Inzidenz von Knoten in großen Schilddrüsen übertragen lassen. Patienten, Methoden: Ergebnisse der ^99mTc-MIBISzintigraphie (inkl. SPECT und planaren Aufnahmen) bei kalten Knoten wurden mit denen der Feinnadelbiopsie (FNAB) und Histologie verglichen. Von einen Gesamtkollektiv aus 154 konsekutiven Patienten (121 Frauen, 33 Männer; Alter 56 ± 12 Jahre) ließen 73 eine Schilddrüsenoperation durchführen, wodurch die Ergebnisse von FNAB und MIBI überprüft werden konnten. Selektionskriterien für die MIBISzintigraphie waren auch eingeschränkte Voraussetzungen für die FNAB, z. B. bei mit einem Schilddrüsenvolumina bis 180 ml (im Mittel 42 ± 25 ml) mit mehrern Knoten (im Mittel 2,1 ± 1,4 pro Patient) und multiplen zystischen und regressiven Schilddrüsenveränderungen. Ergebnisse: Entsprechend der Selektionsktriterien erbrachte die Histologie eine relative niedrige Karzinomrate von 11%. Der negative prädiktive Wert der MIBI-Untersuchung war hoch (97%) und vergleichbar der FNAB (94%). Die FNAB aber war bei 19.5% der Patienten nicht be urteilbar. Die niedrige Spezifität (54%) und ein sehr niedriger positiver prädiktiver Wert (19%) zeigten, dass MIBI die Dignität von Schilddrüsenknoten nicht sicher bestimmen kann. Der Vergleich mit Zytologie bzw. Histologie ergab, dass die MIBI-Akkumulation vom mitochondrialen Stoffwechsel beeinflusst ist. Schlussfolgerung: MIBI-Szinti graphie sollte auch unter den deutschen Iodmangelbedingungen zur Strategiefestlegung (Abwarten oder Operation) beim kalten Knoten eingesetzt werden, wenn eine FNAB nicht möglich oder nicht repräsentativ ist. Bei pathologischem Ergebnis ist die Prävalenz eines Karzinoms aber nicht hoch.

Keywords

Methylisobutyisonitrile - scintigraphy - SPECT - hypofunctioning thyroid nodule - goiter

Schlüsselwörter

MIBI - Technetium-Methylisobutyisonitril - kalter Schilddrüsenknoten - Struma

• References

• 1 Alonso O, Lago G, Mut F. et al. Thyroid imaging with Tc-99m MIBI in patients with solitary cold single nodules on pertechnetate imaging. Clin Nucl Med 1996; 21: 363-367.
• 2 Andermann P, Schlogl S, Mader U. et al. Intra- and interobserver variability of thyroid volume measurements in healthy adults by 2D versus 3D ultrasound. Nuklearmedizin 2007; 46: 1-7.
• 3 Ansquer C, Mirallie E, Carlier T. et al. Preoperative localization of parathyroid lesions. Value of ^99mTc-MIBI tomography and factors influencing detection. Nuklearmedizin 2008; 47: 158-162.
• 4 Baloch ZW, Livolsi VA. Follicular-patterned lesions of the thyroid: the bane of the pathologist. Am J Clin Pathol 2002; 117: 143-150.
• 5 Belfiore A, La Rosa GL, La Porta GA. et al. Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity. Am J Med 1992; 93: 363-369.
• 6 Boi F, Lai ML, Deias C. et al. The usefulness of ^99mTc-SestaMIBI scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology. Eur J Endocrinol 2003; 149: 493-498.
• 7 Boyd LA, Earnhardt RC, Dunn JT. et al. Preoperative evaluation and predictive value of fine-needle aspiration and frozen section of thyroid nodules. J Am Coll Surg 1998; 187: 494-502.
• 8 Cooper DS, Doherty GM, Haugen BR. et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006; 16: 109-142.
• 9 Demirel K, Kapucu O, Yucel C. et al. A comparison of radionuclide thyroid angiography, ^99mTc-MIBI scintigraphy and power Doppler ultrasonography in the differential diagnosis of solitary cold thyroid nodules. Eur J Nucl Med Mol Imaging 2003; 30: 642-650.
• 10 Dietlein M, Dressler J, Eschner W. et al. Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 3). Nuklearmedizin 2007; 46: 213-219.
• 11 Dietlein M, Dressler J, Eschner W. et al. Procedure guideline for iodine-131 whole-body scintigraphy for differentiated thyroid cancer (version 3). Nuklearmedizin 2007; 46: 206-212.
• 12 Dietlein M, Dressler J, Eschner W. et al. Procedure guideline for thyroid scintigraphy (version 3). Nuklearmedizin 2007; 46: 203-205.
• 13 Dietlein M, Kobe C, Schmidt M. et al. The incidentaloma of the thyroid. Over- or underuse of diagnostic procedure for an epidemiologic finding?. Nuklearmedizin 2005; 44: 213-124.
• 14 Dietlein M, Wegscheider K, Vaupel R. et al. Survey of management of solitary thyroid nodules in Germany. Nuklearmedizin 2008; 47: 87-96.
• 15 Dietlein M, Wieler H, Schmidt M. et al. Routine measurement of serum calcitonin in patients with nodular thyroid disorders?. Nuklearmedizin 2008; 47: 65-72.
• 16 Erdil TY, Ozker K, Kabasakal L. et al. Correlation of technetium-99m MIBI and thallium-201 retention in solitary cold thyroid nodules with postoperative histopathology. Eur J Nucl Med 2000; 27: 713-720.
• 17 Eschner W, Bahre M, Luig H. Iterative reconstruction of thyroidal SPECT images. Eur J Nucl Med 1987; 13: 100-102.
• 18 Foldes I, Levay A, Stotz G. Comparative scanning of thyroid nodules with technetium-99m pertechnetate and technetium-99m methoxyisobutyl-isonitrile. Eur J Nucl Med 1993; 20: 330-333.
• 19 Hagag P, Strauss S, Weiss M. Role of ultrasound-guided fine-needle aspiration biopsy in evaluation of nonpalpable thyroid nodules. Thyroid 1998; 8: 989-995.
• 20 Hurtado-Lopez LM, Arellano-Montano S, Torres Acosta EM. et al. Combined use of fine-needle aspiration biopsy, MIBI scans and frozen section biopsy offers the best diagnostic accuracy in the assessment of the hypofunctioning solitary thyroid nodule. Eur J Nucl Med Mol Imaging 2004; 31: 1273-1279.
• 21 Hurtado-Lopez LM, Martinez-Duncker C. Negative MIBI thyroid scans exclude differentiated and medullary thyroid cancer in 100% of patients with hypofunctioning thyroid nodules. Eur J Nucl Med Mol Imaging 2007; 34: 1701-1703.
• 22 Kassirer JP, Pauker SG. The toss-up. N Engl J Med 1981; 305: 1467-1469.
• 23 Kresnik E, Gallowitsch HJ, Mikosch P. et al. Technetium-99m-MIBI scintigraphy of thyroid nodules in an endemic goiter area. J Nucl Med 1997; 38: 62-65.
• 24 Ledley RS, Lusted LB. Reasoning foundations of medical diagnosis; symbolic logic, probability, and value theory aid our understanding of how physicians reason. Science 1959; 130: 9-21.
• 25 Leenhardt L, Hejblum G, Franc B. et al. Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules. J Clin Endocrinol Metab 1999; 84: 24-28.
• 26 Lindner O, Burchert W, Bengel FM. et al. Myocardial perfusion scintigraphy 2006 in Germany. Results of the query and current status. Nuklearmedizin 2008; 47: 139-145.
• 27 Luster M, Stinzing A, Reiners C. Inzidentalome der Schilddrüse beim Ultraschall-Screening: Initiative Papillon. Der Nuklearmediziner 2005; 28: 92-95.
• 28 Lyshchik A, Drozd V, Demidchik Y. et al. Diagnosis of thyroid cancer in children: value of gray-scale and power doppler US. Radiology 2005; 235: 604-613.
• 29 Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993; 328: 553-559.
• 30 Mezosi E, Bajnok L, Gyory F. et al. The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the differential diagnosis of cold thyroid nodules. Eur J Nucl Med 1999; 26: 798-803.
• 31 Nakahara H, Noguchi S, Murakami N. et al. Technetium-99m-sestamibi scintigraphy compared with thallium-201 in evaluation of thyroid tumors. J Nucl Med 1996; 37: 901-904.
• 32 Nam-Goong IS, Kim HY, Gong G. et al. Ultrasonography-guided fine-needle aspiration of thyroid incidentaloma: correlation with pathological findings. Clin Endocrinol (Oxf) 2004; 60: 21-28.
• 33 Pacini F, Schlumberger M, Dralle H. et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006; 154: 787-803.
• 34 Papini E, Guglielmi R, Bianchini A. et al. Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab 2002; 87: 1941-1946.
• 35 Piwnica-Worms D, Kronauge JF, Chiu ML. Uptake and retention of hexakis (2-methoxyisobutyl isonitrile) technetium(I) in cultured chick myocardial cells. Mitochondrial and plasma membrane potential dependence. Circulation 1990; 82: 1826-1838.
• 36 Reiners C. Scintigraphy or fine-needle aspiration biopsy to exclude thyroid malignancy: what should be done first in iodine deficiency?. Eur J Nucl Med Mol Imaging 2008; 35: 1171-1172.
• 37 Reiners C, Wegscheider K, Schicha H. et al. Prevalence of thyroid disorders in the working population of Germany: ultrasonography screening in 96,278 unselected employees. Thyroid 2004; 14: 926-932.
• 38 Rubaltelli L, Corradin S, Dorigo A. et al. Differential diagnosis of benign and malignant thyroid nodules at elastosonography. Ultraschall Med 2009; 30: 175-179.
• 39 Sathekge MM, Mageza RB, Muthuphei MN. et al. Evaluation of thyroid nodules with technetium-99m MIBI and technetium-99m pertechnetate. Head Neck 2001; 23: 305-310.
• 40 Schneider A, Dinant GJ, Szecsenyi J. Stepwise diagnostic workup in general practice as a consequence of the Bayesian reasoning. Z Arztl Fortbild Qualitatssich 2006; 100: 121-127.
• 41 Schroder S, Marthaler B. Autonomy and malignancy of thyroid glad tumors. A critical analysis of the literature on the existence of hyperfunctioning fol- licular and papillary thyroid gland carcinomas. Pathologe 1996; 17: 349-357.
• 42 Sundram FX, Mack P. Evaluation of thyroid nodules for malignancy using ^99mTc-sestamibi. Nucl Med Commun 1995; 16: 687-693.
• 43 Theissen P, Jockenhövel F, Lind T. et al. Ergebnisse des Schilddrüsen-Screenings Papillon I in Köln: Morphologie und Funktion. In: Dietlein M, Schicha H. (eds) Schilddrüse 2003. Berlin: Walter de Gruyter; 2004: 5-10.
• 44 Vattimo A, Bertelli P, Burroni L. Effective visualization of suppressed thyroid tissue by means of baseline ^99mTc-methoxy isobutyl isonitrile in comparison with ^99mTc-pertechnetate scintigraphy after TSH stimulation. J Nucl Biol Med 1992; 36: 315-318.
• 45 Wackers FJ, Berman DS, Maddahi J. et al. Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myo- cardial perfusion imaging. J Nucl Med 1989; 30: 301-311.
• 46 Wang HH. Reporting thyroid fine-needle aspiration: literature review and a proposal. Diagn Cyto- pathol 2006; 34: 67-76.