ESPE Abstracts

Background: Resistance to thyroid hormone alpha (RTH-α) is characterized by varying degrees of symptoms and findings related to hypothyroidism. However, diagnosis is difficult since thyroid-stimulating hormone (TSH) levels are normal. Free triiodothyronine (fT3) and free thyroxine (fT4) levels can also be normal, but normo- or macrocytic anemia is generally present in the reported cases. L-thyroxine can alleviate some symptoms; however, there is limited data regarding screening methods. Objective: To assess the efficiency of a screening strategy for RTH-α.

Methods: Among the 6540 children who were assessed in the pediatric neurology outpatient clinics during two years and underwent complete blood count and thyroid function test, 432 had anemia. We detected children (n=41) without a neurologic diagnosis who had normo- or macrocytic anemia along with normal TSH, free triiodothyronine (T3) levels in the upper half of the normal range or high, and free thyroxine (T4) levels low or in the lower half of the normal range. One known patient with RTH-α was excluded. Among remaining subjects, clinical evaluation, biochemical assessment, and THRA sequencing analysis were performed on 32 children.

Results: The median age of the patients was 5.7 (5.1–7.4) years, and 22 of them were males (69%). The main reasons for admission were autism spectrum disorder (n=12,38%), epilepsy (n=11,34%), and delay in developmental stages (n=8,25%). Constipation was present in five of the cases (16%), while closure of the anterior fontanelle and tooth eruption were delayed in two (6%) and one case (3%), respectively. The median length/height and weight SD scores were 0.3 [(-0.8)-(1.1)] and -0.1 [(-0.8)-(0.3)], respectively. The median fT3, fT4, and TSH levels were 4.6 (4.2–5.0) pg/mL, 0.9 (0.8–1.0) ng/dL, and 2.2 (1.8–3.1) uIU/mL, respectively. Thirteen of the patients (41%) had high fT3 levels, while none of them had low fT4 levels. The rate of normo- or macrocytic anemia was 47% (normocytic/macrocytic, n=8/7) at the time of reassessment. Creatine kinase was elevated in five of the patients (16%, one of them had anemia). None of the patients had a pathological variant in THRA. Conclusions: This strategy found one known patient with RTH-α but did not reveal a new patient. Normo- or macrocytic anemia did not persist in nearly half of the patients, and this indicates that presence of other suggestive clinical or biochemical features would be needed before genetic analysis of THRA among patients with neurological problems.