Overt Hypothyroidism and Severe Growth Retardation in a Preschool Girl with Poorly Controlled Nephrotic Syndrome: Case Report and Literature Review

Abstract

 Background. Nephrotic children may develop thyroid hormone dysfunction due to urinary excretion of thyroid hormones. In contrast to the subclinical hypothyroidism that affects around 30% of children with nephrotic syndrome (NS), the patient in this case had overt hypothyroidism and severe growth retardation.
Clinical case. A 5 years and 8 months old girl with steroid-dependent NS was referred from another center due to persistent edema and decreased diuresis, being treated with mycophenolate mofetil (MMF) 250 mg once a day and L-thyroxine 50 mcg daily since 4 months of NS onset because of hypothyroidism. Her albumin was 12.64 g/l, cholesterol 25.64 mmol/l and proteinuria 5 g/l. Severe growth retardation was observed: patient’s height was 93.5 cm (–13 cm <3 percentile), weighted 17.2 kg (15–25 percentile). Her disease vintage was over 3 years. Girl’s growth velocity has slowed down from 3.5 months. The patient received a high cumulative dose of prednisolone (approx. 7800 mg in 1 year and 8 months). Thyroid-stimulating hormone was higher (18.04 mU/L) with reduced FT4 11.43 pmol/l and IGF-1 < 15 µg/L. Kidney biopsy revealed minimal change disease, and genetic testing was negative. Intensive NS treatment with methylprednisolone pulse therapy, enlarged doses of MMF and albumin infusion were started and L-thyroxine dose was increased to 75 mcg. TPOAb was in normal range (12.65 IU/ml). After 3 weeks she was discharged with no edema and after stopping methylprednisolone treatment thyroid function normalized and L-thyroxin was discontinued. Two weeks later standard growth hormone stimulation test with clonidine showed partially insufficient growth hormone secretion. During NS remission with normalization of thyroid function (TSH 6.680 mU/l, FT4 13.85 pmol/l) and normalization of IGF-1 level (132 mcg/l) partial catch-up growth was observed (height velocity increased from 3.5 cm/year to 7.3 cm/year, based on 4-month calculation period).
Conclusions. Clinicians should be aware of a risk of developing hypothyroidism and consider thyroid function testing during the treatment of children with NS, as well as actively treat hypothyroidism and evaluate growth.