Endocrine Abstracts

Introduction: Resistance to thyroid hormones (RTH) is a rare syndrome. This condition is caused by gene mutations of thyroid hormone receptors (THR). There are two types of genes that code THR: THR alpha (THRA) and THR beta (THRB). The RTH alpha is associated with mutations in the THRA gene and is less common than RTH beta [1]. It is challenging to identify patients with RTH alpha because usually they only have mildly abnormal (or even normal) thyroid hormone levels and the severity of clinical features may depend on localization of the particular mutation in THRA [1].

Clinical case: A 38 year-old female patient was admitted to our outpatient clinic with symptoms of mild hypothyroidism (obesity, weakness, constipations, lethargy). 10 years ago she was diagnosed with hypothyroidism (FT4 0.69 ng/dl (normal: 0.8-1.9 ng/dl), TSH 1.89 mlU/ml (normal: 0.4-4.0 mlU/ml)) and levothyroxine (L-T4) was prescribed. Currently the patient was using L-T4 75 mg per day. Phenotypic features of the patient showed short stature (height 161 cm), obesity (BMI 40.12 kg/m²), coarse facial features, skin tags and puffy hands. The laboratory tests showed low TSH, normal FT4 and high FT3. The ultrasound of the thyroid gland showed no changes. Autoimmune thyroid diseases were excluded. Simultaneously the patient was consulted by a geneticist due to neurological disorders (ataxia, speech disorders, epilepsy). For this, next generation sequencing was performed, incidental findings showed a heterozygous THRA mutation NM_199334.5:c.871G>A. The variant was interpreted as likely pathogenic (as there were no records in GnomAD and very few reports in literature with the same interpretation) [1]. The diagnosis of autosomal dominant hypothyroidism due to THRA mutation was confirmed and the treatment with L-T4 was continued. Subsequently, the same mutation variant was verified for the patients’ mother and brother.

Conclusion: Although the mutation of THRA gene causes hypothyroidism, the clinical features are mostly mild and the disease is often left undiagnosed or is diagnosed in adulthood as it was in our case. We recommend that RTH should be suspected for every patient that has unusual clinical and laboratory test changes of thyroid function.1. Al Shidhani, Azza et al. “Thyroid Hormone Resistance due to a Novel De Novo Mutation in Thyroid Hormone Receptor Alpha: First Case Report from the Middle East and North Africa.” Oman medical journal vol. 36,1 e226. 31 Jan. 2021, doi:10.5001/omj.2021.20.