Thyroid hormone resistance syndrome(THRS) occurs in 1:40000 live births and can be diagnosed after a period of enigmatic changes in thyroid hormones(TH). Patients may be clinically euthyroid, have clinical hypo or hyperthyroidism. Mostly, it is an autosomal dominant disease due to germline mutations in THRβ-gene(exons 7-10). Resistance to peripheral action of TH leads to absence of TSH suppression (which can be normal/elevated) despite elevated fT4 and fT3.
Case 1: A 38-year-old-man was referred because of persistent elevations of TH (TSH 43 µUI/ml (0.4-4.0), fT4 2.7 ng/dl (0.7-1.5), fT3 3.4 pg/ml (1.8-4.2)) together with depression, a palpabre goitre and hyperlipidemia; his sister had hypothyroidism. The pituitary-MRI excluded a thyrotropinoma; the remaining pituitary function was normal. Autoimmune thyroid disease was excluded. Genetic analysis confirmed a heterozygous G344R mutation(exon 9) in THRβ-gene: his sister had the same mutation; his 11-year-old daughter had normal TH. He begun treatment with levotyroxine(L-T4) up to 200 µg/daily: TSH reduced to 27 µUI/ml, fT4 1,8 ng/dl, fT3 4,1 pg/ml. The patient improved substantially, but lost follow-up until 15 years later, when he presented with TSH 112 µUI/ml, fT4 1,9 ng/dl, fT3 4,1 pg/ml under L-T4 125 µg/daily. He had gained weight, attempted suicide, and had elevation of CK and liver enzymes. He resumed the 200 µg/daily L-T4 dose: TSH decreased to 73 µUI/ml and he clinical and biochemical improved.
Case 2: A 20-year-old-woman with short stature(148 cm), sensorineural deafness and attention deficit disorder, with TSH 5,4 µUI/ml, fT4 4,1 ng/dl, fT3 4,3 pg/ml was diagnosed with THRS after a confirmed heterozygous G344R mutation in THRβ-gene. Her brother had the same mutation. She underwent hemithyroidectomy due to a follicular adenoma and TSH slightly increased to 6,9 µUI/ml. She was under liothyronine, with maximum doses of 25 µg/bid: TSH 5,0 µUI/ml, fT4 1,8 ng/d, fT3 4,2 pg/ml. At 47-years-old, she is not under any thyroid replacement hormone but begun atenolol due to palpitations and insomnia: TSH 4,2 µUI/ml, fT4 2,29 ng/dl and fT3 7,0 pg/ml (1,8-4,2).
Discussion: Frequently, THRS treatment is not necessary unless signs of decompensation appear (great elevation of TSH together with elevated fT3 and fT4 levels), common if concomitant thyroiditis or previous ablative therapy. The woman from case 2 underwent thyroid surgery, however TSH remained minimally elevated, and years later she developed hyperthyroidism. In case 1, despite the absence of apparent causes for the decompensation, high doses of L-T4 were needed to resolve clinical hypothyroidism. More case reports are needed to better understand the course of this widely variable clinical presentation disease.
13 May 2023 - 16 May 2023