Search Results

You are looking at 1 - 3 of 3 items for

  • Author: Anita Boelen x
Clear All Modify Search
Heleen I Jansen Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands

Search for other papers by Heleen I Jansen in
Google Scholar
PubMed
Close
,
Marijn M Bult Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands

Search for other papers by Marijn M Bult in
Google Scholar
PubMed
Close
,
Peter H Bisschop Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Endocrinology and Metabolism, Amsterdam, The Netherlands

Search for other papers by Peter H Bisschop in
Google Scholar
PubMed
Close
,
Anita Boelen Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

Search for other papers by Anita Boelen in
Google Scholar
PubMed
Close
,
Annemieke C Heijboer Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

Search for other papers by Annemieke C Heijboer in
Google Scholar
PubMed
Close
, and
Jacquelien J Hillebrand Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands

Search for other papers by Jacquelien J Hillebrand in
Google Scholar
PubMed
Close

Introduction

In our hospital, physicians noticed high free thyroxine (fT4) concentrations without complete suppression of thyroid-stimulating hormone (TSH) in blood samples of patients at the outpatient clinic, which appeared to occur more often following the introduction of a new fT4 immunoassay. This discordance may be explained by incorrect reference intervals, analytical issues, or patient-related factors. We aimed to establish the contribution of the possible factors involved.

Methods

Reference intervals of both fT4 immunoassays were re-evaluated using blood samples of healthy volunteers and the new immunoassay’s performance was assessed using internal quality controls and external quality rounds. The frequency of discordant fT4 and TSH pairings obtained from laboratory requests were retrospectively analysed using a Delfia (n = 3174) and Cobas cohort (n = 3408). Last, a literature search assessed whether the time of blood draw and the time of levothyroxine (L-T4) ingestion may contribute to higher fT4 concentrations in L-T4 users.

Results

The original reference intervals of both fT4 immunoassays were confirmed and no evidence for analytical problems was found. The Delfia (n = 176, 5.5%) and Cobas cohorts (n = 295, 8.7%) showed comparable frequencies of discordance. Interestingly, 72–81% of the discordant results belonged to L-T4 users. Literature indicated the time of blood withdrawal of L-T4 users and, therefore, the time of L-T4 intake as possible explanations.

Conclusions

High fT4 without suppressed TSH concentrations can mainly be explained by L-T4 intake. Physicians and laboratory specialists should be aware of this phenomenon to avoid questioning the assay’s performance or unnecessarily adapting the L-T4 dose in patients.

Open access
Emmely M de Vries Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Search for other papers by Emmely M de Vries in
Google Scholar
PubMed
Close
,
Hermina C van Beeren Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Search for other papers by Hermina C van Beeren in
Google Scholar
PubMed
Close
,
Albert C W A van Wijk Department of Experimental Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Albert C W A van Wijk in
Google Scholar
PubMed
Close
,
Andries Kalsbeek Department of Endocrinology and Metabolism, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

Search for other papers by Andries Kalsbeek in
Google Scholar
PubMed
Close
,
Johannes A Romijn Department of Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Johannes A Romijn in
Google Scholar
PubMed
Close
,
Eric Fliers Department of Endocrinology and Metabolism, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Eric Fliers in
Google Scholar
PubMed
Close
, and
Anita Boelen Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Search for other papers by Anita Boelen in
Google Scholar
PubMed
Close

Fasting induces profound changes in the hypothalamus-pituitary-thyroid axis and peripheral thyroid hormone (TH) metabolism, ultimately leading to lower serum thyroid hormone (TH) concentrations. In the present study, we aimed to investigate the regulation of type 3 deiodinase (D3) during fasting in two metabolic tissues: liver and white adipose tissue (WAT). To this end, we studied the effect of modulation of the mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1α (HIF1α) on D3 expression in primary rat hepatocytes and in 3T3-L1 adipocytes. In addition, we studied the role of the constitutive androstane receptor (CAR) on liver TH metabolism using primary hepatocytes and CAR-/- mice. Twenty-four-hour fasting increased liver Dio3 expression in mice. Inhibition of mTOR using mTOR inhibitors markedly induced Dio3 mRNA expression in primary hepatocytes; this increase was accompanied by a small increase in D3 activity. Stimulation of these cells with a CAR agonist induced both Dio3 mRNA expression and activity. Fasting increased hepatic D3 expression in WT but not in CAR-/- mice. In WAT, Dio3 mRNA expression increased five-fold after 48-h fasting. Treatment of 3T3-L1 adipocytes with mTOR inhibitors induced Dio3 mRNA expression, whereas stimulation of these cells with cobalt chloride, a compound that mimics hypoxia and stabilizes HIF1α, did not induce Dio3 mRNA expression. In conclusion, our results indicate an important role of mTOR in the upregulation of D3 in WAT and liver during fasting. Furthermore, CAR plays a role in the fasting induced D3 increase in the liver.

Open access
Anne H van der Spek Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by Anne H van der Spek in
Google Scholar
PubMed
Close
,
Olga V Surovtseva Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by Olga V Surovtseva in
Google Scholar
PubMed
Close
,
Saskia Aan Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by Saskia Aan in
Google Scholar
PubMed
Close
,
Anton T J Tool Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by Anton T J Tool in
Google Scholar
PubMed
Close
,
Annemarie van de Geer Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by Annemarie van de Geer in
Google Scholar
PubMed
Close
,
Korcan Demir Division of Pediatric Endocrinology, Dokuz Eylül University, Izmir, Turkey

Search for other papers by Korcan Demir in
Google Scholar
PubMed
Close
,
Anja L M van Gucht Department of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

Search for other papers by Anja L M van Gucht in
Google Scholar
PubMed
Close
,
A S Paul van Trotsenburg Department of Pediatric Endocrinology, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
Close
,
Timo K van den Berg Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by Timo K van den Berg in
Google Scholar
PubMed
Close
,
Eric Fliers Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by Eric Fliers in
Google Scholar
PubMed
Close
, and
Anita Boelen Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

Search for other papers by Anita Boelen in
Google Scholar
PubMed
Close

Innate immune cells have recently been identified as novel thyroid hormone (TH) target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα), which is the predominant TR in these cells, has not been studied to date. Studies in TRα0/0 mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα) and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHα patients (mutation D211G). Circulating interleukin-8 levels were elevated in 7 out of 8 RTHα patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTHα. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTHαD211G patient. RTHα macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T3 found in patients with RTHα.

Open access