Table 2.

Summary of clinical features and suggested investigations for resistance to thyroid hormone alpha.

System	Clinical feature/phenotype	Investigations and possible findings
Appearance	•Flattened nasal bridge •Broad face, thickened lipsa •Macroglossiaa •Coarse facies, skin tags and molesa	○Dysmorphology
Skeletal	•Disproportionate short staturea •Macrocephalya •Delayed tooth eruptiona	○Auxology: reduced total height, normal sitting height but reduced subischial leg length, increased head circumference for age (children) or height (adults). Weight or BMI may be increased. ○Skull radiograph: thickened calvarium, delayed fontanelle fusion,b excessively serpiginous lambdoid suture (Wormian bones)b ○Pelvic and long bone radiographs: Cortical hyperostosis, femoral epiphyseal dysgenesisb ○Spine radiograph: Scalloped vertebral bodies ○Dental radiograph: Delayed tooth eruption ○Bone age radiograph: Delayed carpal bone maturationb ○DXA scan or quantitative CT: increased bone mineral density at hip
Gastrointestinal	•Constipationa	○Abdominal radiograph: dilated bowel loops and impacted faecal matter ○Colonic manometry: reduced peristalsis
Cardiovascular	•Bradycardia •Low blood pressure for age and gender	○Cardiac telemetry: reduced average sleeping heart rate ○Spectral analysis of cardiac autonomic tone: increased parasympathetic (vagal) tone ○Echocardiography: hypothyroid indices of contractility
Metabolic	•Low metabolic ratea •Borderline abnormal thyroid function testsa	○Indirect calorimetry: reduced resting energy expenditure ○Creatine kinase- skeletal muscle isoenzyme (MM): raised ○Lipid profiles: raised total and LDL cholesterol ○SHBG: raised or normal ○ft4/fT3 ratio: low or low normal ○Reverse T3: low or normal ○IGF-1: low or normal
Haematological	•Mild anaemia	○Full blood count: low red cell mass or haematocrit with normal MCV and normal B12, folate, reticulocyte count
Neurological & cognitive	•Delayed developmental milestones •Slow, dysarthric speecha •Slow initiation of movement, ataxic gait •Dysdiadochokinesis •Fine and gross motor incoordination (dyspraxia)a •Seizures •? Autism spectrum disorder	○MRI brain: microcephaly and reduced cerebellar size ○Neuropsychological testing: reduced IQ, low visual, verbal and working memory scores, reduced motor coordination

^aIndicates features found in the majority of patients.

^bIndicates radiological features found in children only.