It could be a long time before we see the necessary genetic testing available from our GPs. In the meantime, at the very least, acknowledge that the results described in the conclusion can be indicative of deep issues which require appropriate treatment. Not just ignore them, sweep them under the carpet, fail even to realise they are significant.
As for the hallmark symptoms...
Curr Top Dev Biol. 2017;125:337-355. doi: 10.1016/bs.ctdb.2017.02.001. Epub 2017 Mar 21.
Resistance to Thyroid Hormone due to Heterozygous Mutations in Thyroid Hormone Receptor Alpha.
van Gucht ALM1, Moran C2, Meima ME1, Visser WE1, Chatterjee K2, Visser TJ3, Peeters RP1.
1 Erasmus University Medical Center, Rotterdam, The Netherlands.
2 Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
3 Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: firstname.lastname@example.org.
Thyroid hormone (TH) acts via nuclear thyroid hormone receptors (TRs). TR isoforms (TRα1, TRα2, TRβ1, TRβ2) are encoded by distinct genes (THRA and THRB) and show differing tissue distributions. Patients with mutations in THRB, exhibiting resistance within the hypothalamic-pituitary-thyroid axis with elevated TH and nonsuppressed thyroid-stimulating hormone (TSH) levels, were first described decades ago. In 2012, the first patients with mutations in THRA were identified. Scope of this review: This review describes the clinical and biochemical characteristics of patients with resistance to thyroid hormone alpha (RTHα) due to heterozygous mutations in THRA. The genetic basis and molecular pathogenesis of the disorder together with effects of levothyroxine treatment are discussed.
The severity of the clinical phenotype of RTHα patients seems to be associated with the location and type of mutation in THRA. The most frequent abnormalities observed include anemia, constipation, and growth and developmental delay. In addition, serum (F)T3 levels can be high-normal to high, (F)T4 and rT3 levels normal to low, while TSH is normal or mildly raised. Despite heterogeneous consequences of mutations in THRA, RTHα should be suspected in subjects with even mild clinical features of hypothyroidism together with high/high-normal (F)T3, low/low-normal (F)T4, and normal TSH.
© 2017 Elsevier Inc. All rights reserved.
Development; Genotype–phenotype correlation; Growth retardation; LT4 therapy; Resistance to thyroid hormone; Thyroid hormone action; Thyroid hormone receptor alpha