Thyroid status in a large cohort of patients with mental retardation: the TOP-R (Thyroid Origin of Psychomotor Retardation) study

Visser, W. Edward; Rijke, Yolanda B. de; Toor, Hans van; Visser, Theo J.

doi:10.1111/j.1365-2265.2011.04089.x

Cited by 8 publications

(12 citation statements)

References 26 publications

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“…However, AEDs were strongly associated with decreased T 4 , free T 4 (FT 4 ), T 3 , and rT 3 levels which is in agreement with other studies (24,25,26). It has been speculated that the changed thyroid parameters in patients that use AEDs can be explained by an influence of AEDs on binding proteins (27), a stimulation of hepatic degradation or conjugation of TH (28) or an altered peripheral deiodinase activity (23). Interestingly, AEDs have been associated with changes in serum levels of Se and Cu (23,29,30,31,32,33).…”

Section: Introductionsupporting

confidence: 79%

“…Due to the observational nature of this study, it is very difficult to draw any conclusions on the causative or mechanistic features of these results. It is very well possible, although speculative, that AEDs interfere with the transport, metabolism, or excretion of trace elements, as is described for TH (23,24,25,26,27,28). Furthermore, although the generalizability of our findings may be limited, it is important to be aware of confounders if Se or Cu levels are analyzed in subjects on commonly prescribed AEDs.…”

Section: Figurementioning

confidence: 99%

“…In the Thyroid Origin of Psychomotor Retardation (TOP-R) study, thyroid parameters of subjects with intellectual disability (ID) were extensively profiled (23). In this cohort, it has been shown that TH profiles in subjects without anti-epileptic drugs (AEDs) were comparable with the general population.…”

Section: Introductionmentioning

confidence: 99%

“…It has been speculated that the changed thyroid parameters in patients that use AEDs can be explained by an influence of AEDs on binding proteins (27), a stimulation of hepatic degradation or conjugation of TH (28) or an altered peripheral deiodinase activity (23). Interestingly, AEDs have been associated with changes in serum levels of Se and Cu (23,29,30,31,32,33). However, the complex relationship between AEDs, THs, Se, and Cu has never been directly studied.…”

Section: Introductionmentioning

confidence: 99%

“…The study population has been described in detail before (23). In short, subjects were excluded if the aetiology of the ID was known.…”

Section: Top-r Studymentioning

confidence: 99%

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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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