Abstract. Introduction. Thyroid Hormone Resistance (THR) is a rare syndrome with a variable and fluctuating clinical course depending on complex genetic and molecular

Introduction. Thyroid Hormone Resistance (THR) is a rare syndrome with a variable and fluctuating clinical course depending on complex genetic and molecular defects.

Case report. SCPR, a caucasian female patient aged 23, was referred to outpatient endocrine department because of increased T4 levels. There was no evidence of thyroid dysfunction or goiter. Past medical history was negative with normal growth and neurophysiological development and regular menstrual cycles. There was no family history of thyroid disease. Analytical evaluation revealed T4 – 17.9 µg/dL [Reference Value (RV): 4.5-12.5], T3 – 247 ng/mL (RV: 72-170), TSH – 4.9 µU/mL (RV: 0.4-4.0), FT3 – 7.8 pg/mL (RV: 1.8-4.2), FT4 – 2.6 ng/dL (RV: 0.8-1.9), TPOAb 11 U/mL (RV: < 35), TgAb < 20 U/mL (RV: < 40), TRAb < 1 (RV: < 2). The TRH test (200 µg, ev) revealed a normal but high TSH response up to 23 µU/mL (5-25) and a sellar NMR scan showed no abnormalities. No medical treatment was prescribed. Over the follow up period of 10 years thyroid function fluctuated with borderline high FT4 and TSH. Clinical course was marked by the development of obesity, depressive syndrome and the diagnosis of chronic fatigue syndrome with two uneventful pregnancies. Over that period, either Hyperthyroidism or Hypothyroidism were diagnosed and treated at other institutions. Recently genetic testing revealed a new mutation on exon 10 of the β thyroid hormone receptor form c790G> T (p.Val264Phe) with unknown significance.

Discussion. Several important points are illustrated by this case. 1) thyroid function tests may fluctuate over time, only sometimes with clear evidence of THR. 2) clinical manifestations of the syndrome are multiform and the relation to thyroid hormone levels is far from clear with abnormalities of growth and neurophysiological development, infertility, obesity, psychiatric disorders or subtle symptoms suggesting thyroid dysfunction variably reported; 3) interpretation of analytical abnormalities may be difficult with thyroid dysfunction commonly misdiagnosed; 4) medical treatment is controversial; 5) More than 100 mutations have been reported and the particular complexity of thyroid hormone effects – several isoforms of the receptor, homo- or heterodimerization of the receptor with the retinoid X receptor and dominant negative effects making the interpretation of the functional significance of new mutations difficult.

Keywords

Thyroid Hormone Resistance

Название

Резистентность к тиреоидным гормонам: новая мутация

Авторы

A.F. Martins¹, J.M. Martins¹, S. do Vale¹, G. Miltenberger-Miltenyi²