Endocrine Abstracts

Cretinism and neurological impairment are related to primary hypothyroidism (PHT) while children with central hypothyroidism (CHT) are usually diagnosed during the investigation process for short stature.

Objective: To describe two children with unusual presentation of CHT.

Case 1: Baby girl, born after 38 weeks of gestation, weighing 3000 g, and measuring 49.5 cm long was admitted when 3 months old. The parents reported stunted neurological development and difficulty in gaining weight. Neonatal screening: TSH<0.1 mU/ml. A typical cretinism face was observed, with depressed nasal base, pig nose and infiltrated eyelids associated with umbilical hernia, reduced muscle tone, short length (<P10) and low weight (<P10). Biochemical analysis: Free T₄<0.1 ng/ml, Total T₄=0.9 ng/ml, TSH<0.1 mU/ml and IGF-I: undetectable. Following thyroxin replacement, there was an improvement in the neurological development, height velocity and weight gain. IGF-I concentration increased to 70 ng/ml(P50). At the age 4.5 years, she was readmitted to the clinic after the treatment had been discontinued for 1.5 year. Her features were typical of severe cretinism with slow movements, difficulty in walking and height velocity close to 0 cm/yr and serum IGF-I level: undetectable. A low thyroxin treatment (1.5 ug/Kg per day) was initiated with full recovery of the cretinism features and neurological impairment.

Case 2: Baby girl, born after 38 weeks of twin pregnancy, weighing 2680 g and measuring 47 cm long. Neonatal screening: TSH=0.4 mIU/ml. She was admitted to the clinic when 1.7 years referring language delay. Initial investigation: TSH=1.3 mIU/ml and total T₄=5.4 mg/dl. Significant improvement in language development occurred after thyroxin replacement. Serum TSH and total T₄ during treatment were 0.6 mIU/ml and 7.6 mg/dl and change to 1.5 mUI/ml and 5.7 mg/dl, respectively thyroxin was discontinued for investigation purposes. Molecular analysis of the deceased twin brother revealed c.826G>A p.G276R mutation of MCT8 in the X chromosome (Xq13.2), in heterozygosis. MCT8 encodes the monocarboxylate transporter-8 (MCT8), responsible for the transmembrane transport of T₃ into the neuron.

Conclusion: Although rare, neurological and developmental related symptoms can be the leading finding to the diagnosis of CHT. Depending on its aetiology, CHT can be associated with cretinism and extremely low TSH and thyroxin levels. Thyroxin determination should be considered in cases of undetectable/extremely low TSH in order to prevent adverse outcomes. Regarding the MCT8 mutation, the severity of clinical findings is variable and changes in neurodevelopment and mental retardation are more frequently observed in male patients.