Introduction: Nephrotic syndrome is a known cause of hypothyroidism; however, its effect on replacement doses of L-thyroxine in patients with primary hypothyroidism is not systematically studied. Aim: The aim of the present study was to evaluate the effect of newly diagnosed nephrotic syndrome on the dose of L-thyroxine replacement in previously diagnosed patients with primary hypothyroidism who were on full, stable dose of L-thyroxine replacement for at least one year. Materials and Methods: Patients with previously diagnosed primary hypothyroidism on stable and full (>= 1.6 mu g/day) replacement dose of L-thyroxine for at least one year who developed newly diagnosed nephrotic syndrome were included in the study. Patients were evaluated with thyroid function tests at diagnosis and every 2-3months. Replacement doses of L-thyroxine were titrated by a single endocrinologist based on serum Thyroid Stimulating Hormone (TSH) level. Results: The study included nine patients with mean age of 42.77 +/- 9.61years. There was significant increase in TSH at diagnosis of nephrotic syndrome (8.16 +/- 2.82 mu lU/ml) when compared to the immediate past visit (2.08 +/- 0.7 mu lU/ml) and needed 17.6% increase in the replacement dose of L-thyroxine. At last follow-up four patients had remission of nephrotic syndrome and in them thyroid function tests improved with reduction in replacement dose of L-thyroxine by 15% whereas patients who did not achieve remission had required further increase in L-thyroxine dose by 19.1%. Conclusion: Development of nephrotic syndrome significantly increases the need for L-thyroxine replacement dose in previously diagnosed primary hypothyroidism patients on full stable dose of L-thyroxine replacement.