Marco Medici

Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism

OBJECTIVEnResearch on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and fatigue-related symptoms. Furthermore, the relationship between fatigue and the TSH receptor (TSHR)-Asp727Glu polymorphism, a common genetic variant of the TSHR, was analyzed.nnnDESIGNnA cross-sectional study was performed in 278 patients (140 patients treated for differentiated thyroid carcinoma (DTC) and 138 with autoimmune hypothyroidism (AIH)) genotyped for the TSHR-Asp727Glu polymorphism.nnnMETHODSnThe multidimensional fatigue inventory (MFI-20) was used to assess fatigue, with higher MFI-20 scores indicating more fatigue-related complaints. MFI-20 scores were related to disease status and Asp727Glu polymorphism status.nnnRESULTSnAIH patients scored significantly higher than DTC patients on all five MFI-20 subscales (P<0.001), independent of clinical and thyroid hormone parameters. The frequency of the TSHR-Glu727 allele was 7.2%. Heterozygous DTC patients had more favorable MFI-20 scores than wild-type DTC patients on four of five subscales. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue was found in DTC patients only.nnnCONCLUSIONSnAIH patients had significantly higher levels of fatigue compared with DTC patients, which could not be attributed to clinical or thyroid hormone parameters. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue in DTC patients should be confirmed in other cohorts.

Genetic Influences on Thyroid Function Tests

In this review we will discuss the possible effects of polymorphic variation in the genes important for thyroid hormone synthesis, metabolism, and action, on the interindividual variation in thyroid functions tests. The genes involved are summarized in the following outline of thyroid hormone production and action, but their role is discussed in detail in other sections (Chaps. 1 and 4). In addition to these genes, we will also briefly discuss the possible contribution of genetic variation in the thyroid-specific transcription factors which are known to be important for thyroid development and regulation: TTF1, TTF2, and Pax8.