Serum copper as a novel biomarker for resistance to thyroid hormone

Mittag, Jens; Behrends, Thomas; Nordström, Kristina; Anselmo, João; Vennström, Björn; Schomburg, Lutz

doi:10.1042/bj20111817

Cited by 45 publications

(41 citation statements)

References 38 publications

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“…Studies of Bastian et al (16,21,22) in mice showed that low levels of Cu were associated with a decreased TH state, which interfered with normal brain development. Similarly, serum ceruloplasmin and Cu levels have recently been proposed as direct biomarkers of TH signaling (54). In line with these studies, we observed strong positive associations between serum Cu and T 3 , rT 3 , and T 4 levels (Fig.…”

Section: Figuresupporting

confidence: 80%

Association of antiepileptic drug usage, trace elements and thyroid hormone status

Zevenbergen

Korevaar

Schuette

et al. 2016

European Journal of Endocrinology

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Background: Levels of thyroid hormone (TH) and trace elements (copper (Cu) and selenium (Se)) are important for development and function of the brain. Anti-epileptic drugs (AEDs) can influence serum TH and trace element levels. As the relationship between AEDs, THs, and trace elements has not yet been studied directly, we explored these interactions. Method: In total 898 participants, from the Thyroid Origin of Psychomotor Retardation study designed to investigate thyroid parameters in subjects with intellectual disability (ID), had data available on serum Se, Cu, thyroid stimulating hormone (TSH), free thyroxine (FT 4 ), tri-iodothyronine (T 3 ), reverse T 3 , T 4 , and thyroxine-binding globulin (TBG); 401 subjects were on AED treatment. Differences in trace elements according to medication usage was investigated using ANOVA, and associations between trace elements and thyroid parameters were analysed using (non-) linear regression models. Results: Study participants were not deficient in any of the trace elements analyzed. AED (carbamazepine, valproate and phenytoin) usage was negatively associated with serum Se and showed compound-specific associations with Cu levels. After correction for drug usage, Se was positively associated with TSH levels, negatively associated with FT 4 levels, and positively with T 3 levels. Cu was positively associated with T 4 , T 3 , and rT 3 , which was largely dependent on TBG levels. Conclusion: The subjects with ID did not display profound deficiencies in trace element levels. AEDs were associated with serum Se and Cu levels, while serum Se and Cu were also associated with thyroid parameters. Further studies on the underlying mechanisms and potential clinical importance are warranted.

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Section: Figuresupporting

confidence: 80%

Association of antiepileptic drug usage, trace elements and thyroid hormone status

Zevenbergen

Korevaar

Schuette

et al. 2016

European Journal of Endocrinology

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“…Mittag et al [18, 24] have shown that hepatic trace element metabolism (e.g., Se) is modulated by T 3 . Thus, we aimed to test whether these effects might at least be partially mediated via TAMs by the administration of T 0 AM and 3-T 1 AM.…”

Section: Discussionmentioning

confidence: 99%

In vivo Effects of Repeated Thyronamine Administration in Male C57BL/6J Mice

et al. 2017

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Objectives: Thyronamines are decarboxylated and deiodinated metabolites of thyroid hormones (THs). Of all possible thyronamine variants, only 3-iodothyronamine (3-T₁AM) and iodine-free thyronamine (T₀AM) have been detected in vivo. While intensive research has been done on the (patho-)physiological action of 3-T₁AM, the role of T₀AM has been studied less intensively. Study Design: We determined whether a single pharmacological dose (50 mg/kg, i.p.) or repeated administration (5 mg/kg/day, i.p., for 7 days) of T₀AM affects metabolism, cardiovascular function, or thermoregulation in male C57BL/6J mice. Since selenium (Se) is important for proper TH function and Se metabolism is affected by TH, we additionally analyzed Se concentrations in liver, serum, and kidney using total reflection X-ray analysis. Results: A single injection of T₀AM had no effect on heart rate, temperature, or activity as assessed by radio telemetry. Likewise, daily administration of T₀AM did not alter body weight, food or water intake, heart rate, blood pressure, brown adipose tissue thermogenesis, or body temperature, and no significant differences in hepatic glycogen content or mRNA expression of genes involved in cardiovascular function or metabolic control were determined. Also, the X-ray analysis of Se concentrations revealed no significant changes. However, hepatic T₀AM was significantly increased in the treated animals. Conclusions: In summary, our data demonstrate that T₀AM elicits no obvious metabolic, cardiovascular, or thermoregulatory activities in mice. As T₀AM does also not interfere with TH or Se metabolism, we conclude that the deiodination of 3-T₁AM to T₀AM constitutes an efficient inactivation mechanism, terminating the actions of the more powerful precursor.

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“…Furthermore, other important related tests involving Cu metabolism (i.e., zinc, iron, selenium) and urine copper concentrations [3], were not reported and are often performed in cases of suspected copper metabolism disorders in humans [3,4]. In fact, the case study by Karaca and co-workers is more difficult to interpret than their conclusions might suggest.…”

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confidence: 96%