Experimentally induced thyrotoxicosis leads to increased connectivity in temporal lobe structures: A resting state fMRI study

Göttlich, Martin; Heldmann, Marcus; Göbel, Anna; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F.

doi:10.1016/j.psyneuen.2015.03.009

Cited by 34 publications

(36 citation statements)

References 35 publications

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“…Interestingly, as described in a previous study analyzing the same volunteer sample, subjectively the volunteers did not notice any thyrotoxic symptoms, which was supported by the negative results of a standardized questionnaire for thyrotoxicosis and a battery of behavioral and cognitive tests [24]. A 24-h blood pressure profile before and at the end of 8 weeks of thyroxine application was not significantly different, neither when analyzed over 24 h or during sleep between 01:00 and 06:00 am [24].…”

Section: Resultssupporting

confidence: 70%

“…As previously described [24], treatment with 250 μg/day L-T 4 for 8 weeks resulted in the expected suppression of mean TSH concentrations from 2.10 mU/L (standard deviation (SD): ±1.01) at baseline to 0.017 mU/L (SD: ±0.029) at 4 weeks and 0.007 mU/L (SD: ±0.007) at 8 weeks, respectively. Mean concentrations of FT 4 and FT 3 exhibited the opposite profile with peak concentrations of 28.6 pmol/L (SD: 5.7) and 9.19 pmol/L (SD: ±2.01) after 4 weeks of L-T 4 intake, respectively, consistent with a biochemical condition of overt hyperthyroidism (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…A 24-h blood pressure profile before and at the end of 8 weeks of thyroxine application was not significantly different, neither when analyzed over 24 h or during sleep between 01:00 and 06:00 am [24]. In contrast, comparison of the mean 24-h pulse rates revealed a moderate increase of about 8.9 beats/minute (from 66.7 to 75.6 beats/minute), which was not recognized by the volunteers [24]. …”

Section: Resultsmentioning

confidence: 99%

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Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Pietzner

Engelmann

Kacprowski

et al. 2017

BMC Med

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BackgroundDeterminations of thyrotropin (TSH) and free thyroxine (FT4) represent the gold standard in evaluation of thyroid function. To screen for novel peripheral biomarkers of thyroid function and to characterize FT4-associated physiological signatures in human plasma we used an untargeted OMICS approach in a thyrotoxicosis model.MethodsA sample of 16 healthy young men were treated with levothyroxine for 8 weeks and plasma was sampled before the intake was started as well as at two points during treatment and after its completion, respectively. Mass spectrometry-derived metabolite and protein levels were related to FT4 serum concentrations using mixed-effect linear regression models in a robust setting. To compile a molecular signature discriminating between thyrotoxicosis and euthyroidism, a random forest was trained and validated in a two-stage cross-validation procedure.ResultsDespite the absence of obvious clinical symptoms, mass spectrometry analyses detected 65 metabolites and 63 proteins exhibiting significant associations with serum FT4. A subset of 15 molecules allowed a robust and good prediction of thyroid hormone function (AUC = 0.86) without prior information on TSH or FT4. Main FT4-associated signatures indicated increased resting energy expenditure, augmented defense against systemic oxidative stress, decreased lipoprotein particle levels, and increased levels of complement system proteins and coagulation factors. Further association findings question the reliability of kidney function assessment under hyperthyroid conditions and suggest a link between hyperthyroidism and cardiovascular diseases via increased dimethylarginine levels.ConclusionOur results emphasize the power of untargeted OMICs approaches to detect novel pathways of thyroid hormone action. Furthermore, beyond TSH and FT4, we demonstrated the potential of such analyses to identify new molecular signatures for diagnosis and treatment of thyroid disorders. This study was registered at the German Clinical Trials Register (DRKS) [DRKS00011275] on the 16th of November 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0770-8) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Pietzner

Engelmann

Kacprowski

et al. 2017

BMC Med

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“…Abnormal functional connectivity of DMN was reported to contribute to disrupted working memory [40, 41] and emotional processing [42–44]. Previous studies of hyperthyroidism have revealed impaired metabolism and FC in brain regions anchored in DMN [7–9, 12, 13]. The related brain regions of DMN in hyperthyroidism primarily included PCC [8, 9, 12], inferior frontal gyrus [13] and superior frontal gyrus [7].…”

Section: Discussionmentioning

confidence: 99%

“…And the strength of functional connectivity was correlated with both the disease duration and depression level of hyperthyroidism. Furthermore, Gottlich et al [13] recruited twenty-nine healthy men and gave them 8 weeks of oral administration of 250 μg levothyroxine per day to induce short-term hyperthyroidism. The study showed that short-term hyperthyroidism resulted in increased FC between temporal lobes and cognitive control network, indicating a key role of thyroid hormones in regulating paralimbic structures.…”

Section: Introductionmentioning

confidence: 99%

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

et al. 2016

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Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed.

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Dysregulation within the salience network and default mode network in hyperthyroid patients: a follow-up resting-state functional MRI study

Liu

Ran

et al. 2018

Brain Imaging and Behavior

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Experimentally induced thyrotoxicosis leads to increased connectivity in temporal lobe structures: A resting state fMRI study

Cited by 34 publications

References 35 publications

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

Dysregulation within the salience network and default mode network in hyperthyroid patients: a follow-up resting-state functional MRI study

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