Subclinical hypothyroidism in children with idiopathic childhood nephrotic syndrome at a tertiary institution in South-West Nigeria

Background: Hypothyroidism in children with nephrotic syndrome (NS) is often attributed to prolonged loss of thyroxine binding globulin and thyroid hormones alongside protein in the urine. It has been historically associated with steroid-resistant NS alone. However, recent evidence supports the fact that subclinical hypothyroidism (SCH) does occur even in children with steroid responsive NS. Complications such as weight gain, hypercholesterolemia, delayed growth, delayed puberty, and depression could result from hypothyroidism and be erroneously attributed to NS, or the effect of steroid used in treatment. Incidentally salt intake, the major form of dietary iodine is often restricted in children with NS, possibly exacerbating any underlying hypothyroid state.

Aim: The study aimed to determine the burden of SCH among our cohort of NS patients.

Patients and methods: A comparative cross-sectional study was designed to assess SCH [defined by high TSH (>6.0 mU/L and normal free T4 (0.8-2.0 ng/dl)] in hundred children with NS aged between one and fifteen years compared with hundred age and gender matched comparison group without NS. Blood and urine samples were collected to analyze thyroid function, serum albumin, serum protein and urinary protein.

Results: The prevalence of SCH was significantly higher in subjects with NS than their age, sex matched comparison group (12% vs. 2%, P = 0.006). The highest proportion (24.1%) of the children with NS who had SCH was found in the age range of 11-15 years and majority were females (19.4% vs. 7.8%, respectively, P = 0.086). The proportion of children with SCH were higher in those with steroid-resistant NS than those responsive to steroids (26.3% vs. 8.6% P = 0.033). The average values of serum albumin and protein were also significantly lower in children with SCH than those without (2.91 mg/dl ± 0.8 vs. 3.78 mg/dl ± 0.9 and 3.99 mg/dl ± 1.3 vs. 5.02 mg/dl ± 1.3, respectively, P < 0.005). Also, the average value of urinary protein was significantly higher in those with SCH than those without [94.29 mg/dl (42.3-101.0) vs. 69.19 mg/dL (31.2-108.2), respectively, P = 0.023]. Participants with steroid-resistant NS have almost three-folds odd of developing SCH compared to steroid sensitive subjects (AOR 2.901; 95% CI 1.831-4.012; P = 0.038).

Conclusion: Screening of children for SCH with NS especially steroid-resistant NS and frequent relapsing steroid sensitive NS for hypothyroidism before complications arise is pertinent to their holistic management. This becomes even more imperative in our environment as iodine deficiency hypothyroidism is still prevalent in some parts of the country.