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Reduced pituitary size in subjects with mutations in the THRB gene and thyroid hormone resistance
Marcus Heldmann1,2, Krishna Chatterjee3, Carla Moran3
1Department of Neurology, University of Lübeck, Lübeck, Germany.
Background:
Thyroid hormone action is mediated by two forms of thyroid hormone receptors (α, β) with differential tissue distribution. Thyroid hormone receptor β (TRβ) mutations lead to resistance to thyroid hormone action in tissues predominantly expressing the β form of the receptor (pituitary, liver). This study seeks to identify the effects of mutant TRβ on pituitary size.
Methods:
High-resolution 3D T1-weighted magnetic resonance images were acquired in 19 patients with RTHβ in comparison to 19 healthy matched controls. Volumetric measurements of the pituitary gland were performed independently and blinded by four different raters (two neuroradiologists, one neurologist, one neuroscientist).
Results:
Patients with mutant TRβ (resistance to thyroid hormone β, RTHβ) showed elevated free tri-iodothyronine/thyroxine levels with normal thyroid-stimulating hormone levels, whereas healthy controls showed normal thyroid hormone levels. Imaging revealed smaller pituitary size in RTHβ patients in comparison to healthy controls (F(1,35) = 7.05, P = 0.012, partial η2 = 0.17).
Conclusion:
RTHβ subjects have impaired sensitivity to thyroid hormones, along with decreased size of the pituitary gland.
Insights
Mutations in thyroid hormone receptor beta (TRβ) cause resistance to thyroid hormone action. This study found that patients with TRβ mutations have smaller pituitary gland size compared to healthy individuals.
Area of Science:
- Endocrinology
- Neuroimaging
- Genetics
Background:
- Thyroid hormone action is regulated by thyroid hormone receptors (TRα and TRβ).
- Mutations in TRβ disrupt thyroid hormone sensitivity, particularly in the pituitary and liver.
- The impact of TRβ mutations on pituitary size remains largely uncharacterized.
Purpose of the Study:
- To investigate the effect of mutant thyroid hormone receptor beta (TRβ) on pituitary gland volume.
- To compare pituitary size in patients with resistance to thyroid hormone beta (RTHβ) and healthy controls.
Main Methods:
- Acquisition of high-resolution 3D T1-weighted MRI scans in 19 RTHβ patients and 19 healthy controls.
- Independent, blinded volumetric measurements of the pituitary gland by four expert raters.
- Comparison of pituitary volumes between RTHβ patients and controls.
Main Results:
- RTHβ patients exhibited elevated free tri-iodothyronine/thyroxine levels with normal TSH.
- Imaging analysis revealed significantly smaller pituitary gland size in RTHβ patients compared to healthy controls (P=0.012).
- The observed difference in pituitary size was statistically significant, indicating a notable effect of mutant TRβ.
Conclusions:
- Individuals with resistance to thyroid hormone beta (RTHβ) demonstrate impaired thyroid hormone sensitivity.
- RTHβ is associated with a decreased pituitary gland size.
- These findings highlight a specific impact of TRβ mutations on pituitary morphology.
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