Endocrine Abstracts

Introduction: Congenital nephrotic syndrome (CNS) is defined as heavy proteinuria starting within three months after birth. It affects approximately 1 to 3 per 100 000 children worldwide. The classical form is the Finnish type, caused by mutations in the nephrin gene. Approximately 50 percent of all nephrotic patients have low total thyroxine (T4) concentrations resulting from urinary losses of T4-binding globulin (TBG) and other thyroid hormone-binding proteins (transthyretin and albumin) and the T4 bound to them. We present a case of CNS (Finnish type) and the difficulties in managing the associated hypothyroidism.

The case: This infant was born at 34 weeks gestation and noted on day ten of life to be oedematous, with proteinuria and hypoalbuminaemia. She was transferred to a tertiary neonatal unit at two weeks of age and found to have abnormal thyroid function tests (TFTs). (T4 11.0 pmol/L (11.5–28.3), TSH: 20.6 mIU/L (0.72–11.0). Her Guthrie was negative for congenital hypothyroidism. An ultrasound of her thyroid showed no structural abnormalities and her MRI brain showed no abnormalities of her pituitary gland. She was commenced on levothyroxine 25 μg once a day on day 15 of life. During her admission her thyroid function proved difficult to maintain. Over a period of two months she was titrated to 100 μg of levothyroxine. Issues encountered included timing of the administration of levothyroxine and of blood sampling in relation to her albumin infusions, timing of her levothyroxine in relation to her multiple other medications, intolerance of the high volume of liquid preparation levothyroxine and the high dose of levothyroxine required to maintain her T4. Her most recent bloods, performed at a corrected gestational age of 18.5 months, demonstrate a T4 14.6 pmol/L and TSH <0.01 mIU/L on 150 μg levothyroxine, given as a crushed tablet dissolved in water (17.5 μg/kg) and she is clinically euthyroid.

Conclusion and learning: Managing hypothyroidism in CNS offers unique challenges. Children with CNS often require higher than anticipated doses of levothyroxine and thought needs to be given to the preparation used and to the timing of doses. These children should have their thyroid function checked early in their clinical course.