Pituitary response to thyrotropin releasing hormone in children with overweight and obesity

Jesse Rijks, Bas Penders, Elke Dorenbos, Saartje Straetemans, Willem-Jan Gerver, Anita Vreugdenhil, Jesse Rijks, Bas Penders, Elke Dorenbos, Saartje Straetemans, Willem-Jan Gerver, Anita Vreugdenhil

Abstract

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.

Trial registration: ClinicalTrials.gov NCT02091544.

Figures

Figure 1. TSH release of the pituitary…
Figure 1. TSH release of the pituitary in response to exogenous TRH stratified into baseline serum TSH concentrations quartiles.
Baseline serum TSH concentrations were stratified for quartiles: Q1 = n = 18); Q2 = 2.05–2.99 mU/L (n = 17); Q3 = 3.00–3.69 mU/L (n = 19); Q4 = > 3.69 mU/L (n = 19). The TSH iAUC during the TRH test was significantly different between the baseline serum TSH concentration quartiles (p < 0.001). Post-hoc analysis showed a significant difference between quartile 1 and quartile 3 (p = 0.002), and between quartile 1 and quartile 4 (p < 0.001). Baseline serum TSH concentrations were within the normal range in all children based on age specific references ranges. TSH = thyroid stimulating hormone; TRH = thyrotropin releasing hormone; Q1 = quartile 1; Q2 = quartile 2; Q3 = quartile 3; Q4 = quartile 4.
Figure 2. Baseline serum TSH concentrations in…
Figure 2. Baseline serum TSH concentrations in association with TSH concentrations at t20 and the TSH iAUC.
(A) Association of baseline TSH concentrations and the TSH concentrations at t20 (r2 = 0.484, p < 0.001), n = 73. (B) Association of baseline TSH concentrations and the TSH iAUC during the TRH stimulation test (r2 = 0.307, p < 0.001), n = 73. Baseline serum TSH concentrations were within the normal range in all children based on age specific references ranges. TSH = thyroid stimulating hormone; TRH = thyrotropin releasing hormone; t20 = 20 minutes after TRH administration; iAUC: incremental area under the curve.
Figure 3. Postulated mechanisms contributing to TSH…
Figure 3. Postulated mechanisms contributing to TSH concentrations in children with overweight and obesity.
TRH = thyrotropin releasing hormone; T3 = triiodothyronine; TSH = thyroid stimulating hormone.

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