Membranous nephropathy associated with thyroid-peroxidase antigen

Abstract

A 6-year-old previously healthy Japanese girl was found to have dipstick 2+ proteinuria and a goiter based on the results of a routine school medical examination. Her serum free-thyroxine level was 4.98 ng/dL (normal range 0.95-1.74 ng/dL), thyroid-stimulating hormone (TSH) was less than 0.003 microU/mL (0.34-3.88 microU/mL), anti-microsomal (anti-thyroid-peroxidase) antibody was 1600 T (up to 100), anti-thyroglobulin antibody was 400 T (up to 100), and TSH-receptor antibody was 84% (up to +/-10%). These results are consistent with a diagnosis of Graves' disease. Electron microscopy examination of a renal biopsy specimen revealed electron-dense deposits located in the subepithelial spaces, and immunofluorescence microscopy examination demonstrated bright granular stainings of immunoglobulin G along the glomerular capillary walls. These findings are characteristic of membranous nephropathy. To investigate the relationship between the membranous nephropathy and Graves' disease, we carried out a second immunofluorescence study, which revealed that the immunoglobulin G granular deposits corresponded to glomerular granular staining of thyroid-peroxidase, whereas staining for thyroglobulin was absent. It was therefore assumed that the deposition of immune complexes mediated by thyroid-peroxidase had caused the membranous nephropathy in this patient. This is the first report of membranous nephropathy associated with Graves' disease in which deposits of thyroid-peroxidase, rather than thyroglobulin, have been confirmed in the kidney.

Membranous nephropathy secondary to Graves’ disease with deposits of thyroid peroxidase in an adult

“…The cause of this deposition of only the TPO antigen is unclear. Serum thyroglobulin levels were low in the report of Shima et al [7] but high in our report, suggesting that the condition is not dependent on serum thyroglobulin levels. Further investigation with a greater number of patients is necessary.…”

“…Interestingly, thyroglobulin and TPO antigen deposition in the kidneys has been previously reported in Hashimoto's disease; in these reports, deposits of both thyroglobulin and TPO antigens were seen with the fluorescent antibody technique [9,10]. In contrast, both our group and Shima et al [7] found only TPO antigen deposits, with no deposits of the thyroglobulin antigen in Graves' disease. The cause of this deposition of only the TPO antigen is unclear.…”

“…The present case is the first report of TPO antigen-positive membranous nephropathy due to Graves' disease in an adult. To date, only thyroglobulin has been demonstrated to stain positively in membranous nephropathy due to Graves' disease [3][4][5][6], and our present case and that from Shima et al are the only two that report staining for both the TPO antigen and the thyroglobulin antigen [7]. Interestingly, thyroglobulin and TPO antigen deposition in the kidneys has been previously reported in Hashimoto's disease; in these reports, deposits of both thyroglobulin and TPO antigens were seen with the fluorescent antibody technique [9,10].…”

“…Two mechanisms, not mutually exclusive, have been thought to elicit thyroid disease-derived membranous nephropathy: adherence of immune complexes to glomeruli as a result of the antibody-antigen reaction of thyroglobulin and activation of the complement pathway [3,4]; and release of thyroglobulin or other antigens from the thyroid gland that bind to glomeruli, thus forming immune complexes [5,8]. Shima et al [7] reported the first case of TPO antigen-positive membranous nephropathy in a child, and considered that the same mechanisms could also occur with TPO. The present case is the first report of TPO antigen-positive membranous nephropathy due to Graves' disease in an adult.…”

“…Approximately 10-20 % of membranous nephropathy cases occur secondary to collagen disease, malignant tumors, drugs, infections, or other conditions [1,2]. However, reports of membranous nephropathy as a complication of Graves' disease are sparse, and thyroglobulin antigen deposition has been detected in only several adult cases [3][4][5][6], and thyroid peroxidase (TPO) deposition in only a single pediatric case [7].…”