Abstract
Purpose
Brain perfusion abnormalities have recently been demonstrated by single-photon emission computed tomography (SPECT) in rare cases of severe Hashimoto’s thyroiditis (HT) encephalopathy; moreover, some degree of subtle central nervous system (CNS) involvement has been hypothesised in HT, but no direct evidence has been provided so far. The aim of this study was to assess cortical brain perfusion in patients with euthyroid HT without any clinical evidence of CNS involvement by means of 99mTc-ECD brain SPECT. Sixteen adult patients with HT entered this study following informed consent.
Methods
The diagnosis was based on the coexistence of high titres of anti-thyroid auto-antibodies and diffuse hypoechogenicity of the thyroid on ultrasound in association with normal circulating thyroid hormone and TSH concentrations. Nine consecutive adult patients with non-toxic nodular goitre (NTNG) and ten healthy subjects matched for age and sex were included as control groups. All patients underwent 99mTc-ECD brain SPECT. Image assessment was both qualitative and semiquantitative. Semiquantitative analysis was performed by generation of four regions of interest (ROI) for each cerebral hemisphere—frontal, temporal, parietal and occipital—and one for each cerebellar hemisphere in order to evaluate cortical perfusion asymmetry. The Asymmetry Index (AI) was calculated to provide a measurement of both magnitude and direction of perfusion asymmetry.
Results
As assessed by visual examination, 99mTc-ECD cerebral distribution was irregular and patchy in HT patients, hypoperfusion being more frequently found in frontal lobes. AI revealed abnormalities in 12/16 HT patients, in three of the nine NTNG patients and in none of the normal controls. A significant difference in the mean AI was found between patients with HT and both patients with NTNG (p<0.003) and normal controls (p<0.001), when only frontal lobes were considered.
Conclusion
These results show the high prevalence of brain perfusion abnormalities in euthyroid HT. These abnormalities are similar to those observed in cases of severe Hashimoto’s encephalopathy and may suggest a higher than expected involvement of CNS in thyroid autoimmune disease.
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References
Mariotti S, Pinna G. Autoimmune thyroid disease. In: Bravermam L, editor. Diseases of the thyroid. Totowa: Humana; 2003. p. 107–60.
Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2646–55.
Kusalic M. Grade II and grade III hypothyroidism in rapid-cycling bipolar patients. Neuropsychobiology 1992;25:177–81.
Monzani F, Del Guerra P, Caraccio N, Pruneti CA, Pucci E, Luisi M, Baschieri L. Subclinical hypothyroidism: neurobehavioral features and beneficial effect of l-thyroxine treatment. Clin Invest 1993;71:367–71.
Joffe RT, Sokolov ST. Thyroid hormones, the brain, and affective disorders. Crit Rev Neurobiol 1994;8:45–63.
Monzani F, Caraccio N, Del Guerra P, Casolaro A, Ferrannini E. Neuromuscular symptoms and dysfunction in subclinical hypothyroid patients: beneficial effect of L-T4 replacement therapy. Clin Endocrinol (Oxf) 1999;51:237–42.
Bauer M, Whybrow PC. Thyroid hormone, neural tissue and mood modulation. World J Biol Psychiatry 2001;2:59–69.
Claussmann C, Offner C, Chevalier Y, Sellal F, Collard M. Encephalopathy and Hashimoto thyroiditis. Rev Neurol (Paris) 1994;150:166–8.
Kothbauer-Margreiter I, Sturzenegger M, Komor J, Baumgartner R, Hess CW. Encephalopathy associated with Hashimoto thyroiditis: diagnosis and treatment. J Neurol 1996;243:585–93.
Hartmann M, Schaner B, Scheglmann K, Bucking A, Pfister R. Hashimoto encephalopathy: steroid-sensitive encephalopathy in Hashimoto thyroiditis. Nervenarzt 2000;71:489–94.
Watemberg N, Willis D, Pellock JM. Encephalopathy as the presenting symptom of Hashimoto’s thyroiditis. J Child Neurol 2000;15:66–9.
Nolte KW, Unbehaun A, Sieker H, Kloss TM, Paulus W. Hashimoto encephalopathy: a brainstem vasculitis? Neurology 2000;54:769–70.
Garrard P, Hodges JR, De Vries PJ, Hunt N, Crawford A, Balan K. Hashimoto’s encephalopathy presenting as “myxodematous madness”. J Neurol Neurosurg Psychiatry 2000;68:102–3.
Chen HC, Marsharani U. Hashimoto’s encephalopathy. South Med J 2000;93:504–6.
Canton A, de Fabregas O, Tintore M, Mesa J, Codina A, Simo R. Encephalopathy associated to autoimmune thyroid disease: a more appropriate term for an underestimated condition? J Neurol Sci 2000;176:65–9.
Byrne OC, Zuberi SM, Madigan CA, King MD. Hashimoto’s thyroiditis—a rare but treatable cause of encephalopathy in children. Eur J Paediatr Neurol 2000;4:279–82.
Boers PM, Colebatch JG. Hashimoto’s encephalopathy responding to plasmapheresis. J Neurol Neurosurg Psychiatry 2001;70:132.
Chong JY, Rowland LP, Utiger RD. Hashimoto encephalopathy: syndrome or myth? Arch Neurol 2003;60:164–71.
Sanna G, Piga M, Terryberry JW, Peltz MT, Giagheddu S, Satta L, et al. Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations. Lupus 2000;9:573–83.
Kao CH, Lan JL, Hsieh JF, Ho YJ, ChangLai SP, Lee JK, Ding HJ. Evaluation of regional cerebral blood flow with 99mTc-HMPAO in primary antiphospholipid antibody syndrome. J Nucl Med 1999;40:1446–50.
Lass P, Krajka-Lauer J, Homziuk M, Iwaszkiewicz-Bilikiewicz B, Koseda M, Hebanowski M, Lyczak P. Cerebral blood flow in Sjögren’s syndrome using 99Tcm-HMPAO brain SPET. Nucl Med Commun 2000;21:31–5.
Latinville D, Bernardi O, Cougoule JP, Bioulac B, Henry P, Loiseau P, Mauriac L. Hashimoto’s thyroiditis and myoclonic encephalopathy. Pathogenic hypothesis. Rev Neurol (Paris) 1985;141:55–8.
Forchetti CM, Katsamakis G, Garron DC. Autoimmune thyroiditis and a rapidly progressive dementia: global hypoperfusion on SPECT scanning suggests a possible mechanism. Neurology 1997;49:623–6.
Kinuya S, Michigishi T, Tonami N, Aburano T, Tsuji S, Hashimoto T. Reversible cerebral hypoperfusion observed with Tc-99m HMPAO SPECT in reversible dementia caused by hypothyroidism. Clin Nucl Med 1999;24:666–8.
Kalita J, Misra UK, Rathore C, Pradhan PK, Das BK. Hashimoto’s encephalopathy: clinical, SPECT and neurophysiological data. Q J Med 2003;96:455–7.
Colamussi P, Giganti M, Cittanti C, Dovigo L, Trotta F, Tola MR, et al. Brain single-photon emission tomography with 99mTc-HMPAO in neuropsychiatric systemic lupus erythematosus: relations with EEG and MRI findings and clinical manifestations. Eur J Nucl Med 1995;22:17–24.
Tanaka F, Vines D, Tsuchida T, Freedman M, Ichise M. Normal patterns on 99mTc-ECD brain SPECT scans in adults. J Nucl Med 2000;41:1456–64.
Leveille J, Demonceau G, De Roo M, Rigo P, Taillefer R, Morgan RA, et al. Characterization of technetium-99m-l,l-ECD for brain perfusion imaging. Part 2. Biodistribution and brain imaging in humans. J Nucl Med 1989;30:1902–10.
Walovitch RC, Franceschi M, Picard M, Cheesman EH, Hall KM, Makuch J, et al. Metabolism of 99mTc-l,l-ethyl cysteinate dimer in healthy volunteers. Neuropharmacology 1991;30:283–92.
Jacquier-Sarlin MR, Polla BS, Slosman DO. Cellular basis of ECD brain retention. J Nucl Med 1996;37:1694–97.
Zettinig G, Asenbaum S, Fueger BJ, Hofmann A, Diemling M, Mittlboeck M, Dudczak R. Increased prevalence of subclinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto’s encephalitis? Clin Endocrinol 2003;59:637–43.
Seo SW, Lee BI, Lee JD, Park SA, Kim KS, Kim SH, Yun MJ. Thyrotoxic autoimmune encephalopathy: a repeat positron emission tomography study. J Neurol Neurosurg Psychiatry 2003;74:504–6.
Shaw PJ, Walls TJ, Newman PK, Cleland PG, Cartlidge NE. Hashimoto’s encephalopathy: a steroid-responsive disorder associated with high anti-thyroid antibody titers—report of 5 cases. Neurology 1991;41:228–33.
Schauble B, Castillo PR, Boeve BF, Westmoreland BF. EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis. Clin Neurophysiol 2003;114:32–7.
Baxter LR Jr, Schwartz JM, Phelps ME, Mazziotta JC, Guze BH, Selin CE, et al. Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch Gen Psychiatry 1989;46:243–50.
Martinot JL, Hardy P, Feline A, Huret JD, Mazoyer B, Attar-Levy D, et al. Left prefrontal glucose hypometabolism in the depressed state: a confirmation. Am J Psychiatry 1990;147:1313–17.
Woods SW. Regional cerebral blood flow imaging with SPECT in psychiatric disease: focus on schizophrenia, anxiety disorders, and substance abuse. J Clin Psychiatry 1992;53:20–5.
Davidson RJ, Abercrombie H, Nitschke JB, Putnam K. Regional brain function, emotion and disorders of emotion. Curr Opin Neurobiol 1999;9:228–34.
Acknowledgements
This work was partially supported by M.I.U.R. (Rome, Italy) and by funds of Regione Autonoma Sardegna.
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Piga, M., Serra, A., Deiana, L. et al. Brain perfusion abnormalities in patients with euthyroid autoimmune thyroiditis. Eur J Nucl Med Mol Imaging 31, 1639–1644 (2004). https://doi.org/10.1007/s00259-004-1625-7
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DOI: https://doi.org/10.1007/s00259-004-1625-7