Introduction: The pathology of thyroid gland is Ukraine is quite common and in 2018y included 277,708 patients with diffuse goiter (36.47 per 1000 population), 2,311 patients (0.30:1000) with nodular goiter, 341 patients with diffuse toxic goiter (0.04:1000), 7,157 (0.94:1000) with autoimmune thyroid disease and 129 patients with thyroid cancer (1.7:100000). However the syndrome of resistance to thyroid hormone (RTH) or Familial Dysalbuminemic Hyperthyroxinemia (FDH) are relatively uncommon disorders and have not been previously diagnosed.
Case presentation 1: A 5.5 y.o. girl presented to endocrinologist with complaints on emotional lability symptoms and hyperactivity disorder. Diffuse euthyroid goiter was diagnosed, and she received iodine supplements within 6 months without improvement of her condition. Hereafter fT4 was measured, and raised level (5.7 ng/dl [normal range, 0.6-1.1]) was revealed on a background of normal TSH. Iodine supplements were cancelled and after 2 months repeated measurements of fT4 and fT3 showed their permanent increased levels (ranged 1.4-2.4 ng/dl and 5.1-6.2 pg/ml [normal range, 2.5-3.9], accordingly) on a background of normal TSH and negative TSH-receptor antibodies (TRAb), Ab-TPO and Ab-TTG levels. Detailed evaluation revealed similar changes of thyroid function tests in father (normal TSH level, increased fT4 and fT3 levels (2.9 ng/ml and 7.4 pg/ml accordingly), however no changes in mother's and sister's tests. Subsequent genetic analysis of the patient and family confirmed RTH with THRB p.Arg438Cys, c. 1312C>T variant in the proband and his father.
Case presentation 2: A 13.4 y.o. Caucasian boy presented to endocrinologist with complaints of growth retardation since 2 years of age. According to the results of examination his height was 140 cm (-2.4 SD), repeated hormonal test revealed a constantly elevated level of fT4 1.65-2.14 ng/ml [normal range, 0.7-1.46], T4 14.9 mcg/dl [normal range, 6.4-13.4], fT3 4.15-5.16 ng/ml [normal range, 2.4-3.9] on a background of normal TSH, Ab-TPO, Ab-TTG and TRAb. Detailed examination showed similar changes of thyroid function in his father (elevated fT4 [1.73 ng/ml], and normal TSH, fT3 and T4). Clonidin test and measurement of IGF-1 level didn't confirm GH-deficiency in the child. Subsequent genetic analysis of the patient and his parents confirmed FDH with ALB p.Arg218His, c.725 G>A variant in the proband and his father.
Conclusion: Patients with euthyroid hyperthyroxinemia should undergo genetic testing due to the similar clinical presentation of RTH and FDH syndromes.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology