Abstract
BackgroundLevothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone.ObjectiveTo study if serum miRNA profiles are changed in different thyroid states.Design and methodsWe studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification.ResultsMean age of the subjects was 44.0 years (range 20–61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 μg/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment.ConclusionAlthough we previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state also affects serum miRNAs in humans.
Highlights
Hypothyroidism is one of the most common endocrine disorders [1]
Serum microRNA in different thyroid states analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment
We previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state affects serum miRNAs in humans
Summary
Hypothyroidism is one of the most common endocrine disorders [1]. In a subset (~10–15%) of patients, symptoms of hypothyroidism persist despite serum thyroid hormone concentrations within the laboratory reference range during levothyroxine (LT4) replacement therapy [2,3,4]. TSH typically reflects local T3 concentrations in the pituitary, it may not necessarily reflect local thyroid status in all tissues, especially when thyroid hormone production is not endogenously controlled, such as in athyreotic patients during LT4 therapy [8, 9]. For this reason, novel markers representing thyroid state of other tissues than the pituitary would be of great clinical relevance. Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone
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