Thymoma Associated With Myasthenia Gravis and Minimal Lesion Nephrotic Syndrome Catherine Lasseur, MD, Christian Combe, MD, PhD, Colette Deminie ` re, MD, Jean-Luc Pellegrin, MD, and Michel Aparicio, MD ● A nephrotic syndrome has been observed rarely in association with thymoma. In most of the reported cases, it occurs when the thymoma is in remission; histological examination generally shows minimal change disease. We report a case of a 43-year-old man presenting with minimal lesion nephrotic syndrome at the time of the diagnosis of thymoma and myasthenia gravis, which persists despite remission of the thymoma. The role of a disorder of T-cell function and of circulating cytokines is discussed.  1999 by the National Kidney Foundation, Inc. INDEX WORDS: Myasthenia gravis; thymoma; nephrotic syndrome; minimal-change glomerulonephritis. T HYMOMA AND myasthenia gravis are fre- quently associated. Ten to fifteen percent of patients who have myasthenia gravis have an epithelial tumor of the thymus, and approximately half of the patients who have a thymoma have myasthenia gravis. 1 In contrast, the occurrence of minimal lesion nephrotic syndrome during the course of a thymoma is much more rare. We report a new case in which a patient who pre- sented with minimal lesion nephrotic syndrome was found to have a thymoma. The nephrotic syndrome persisted despite remission of the thy- moma. A disorder of T-cell function involved in both disorders might explain their association. CASE REPORT A 43-year-old man was admitted in November 1993 for systemic symptoms. Over the preceding year, he had experi- enced repeated episodes of ptosis, diplopia, dysphonia, and muscular fatigue of the hands and neck. At referral, he had edema of the eyelids and lower limbs, and blood pressure of 150/100 mm Hg. Laboratory testing indicated a nephrotic syndrome (serum protein, 46 g/L; proteinuria, 14 g/24h), hematuria (1,330,000 red cells/min), and renal insufficiency (creatinine, 1.44 mg/dL). Soon after admission, the patient developed oligoanuria. Chest films showed bilateral pleural effusion and calcifications in the middle of the anterior mediastinum. The diagnosis of myasthenia gravis was rap- idly confirmed by electromyography and by the finding of anti-acetylcholine receptor antibodies (8.3  10 -9 mol/L, considered positive for values higher than 2  10 -9 mol/L). Serum analysis showed a substantially decreased level of immunoglobulin G (IgG) (1.87 g/L; normal range, 7.94 to 15.04 g/L) and a polyclonal increase in IgM (1.94 g/L; normal range, 0.62 to 1.84 g/L). The level of IgA was normal, as was the rest of the immunologic workup. Computed tomographic and magnetic resonance imaging showed, in the thymus, a tumor with regular margins that was partially calcified and appeared to invade the left phrenic nerve. A percutaneous renal biopsy was performed. No signifi- cant glomerular, tubulointerstitial, or vascular lesions were observed on light microscopy, and no immunoglobulin or complement fragment deposits were observed by immuno- fluorescence. Staining for amyloid deposits (thioflavine and Congo red) was negative. Electron microscopy showed fusion of the epithelial foot cell processes. These findings were consistent with a diagnosis of minimal lesion nephrotic syndrome. Treatment with an anticholinesterase was followed by quick and sustained remission of the signs of neurological deficit. Muscular testing and the electromyographic findings normalized, and the level of anti-acetylcholine receptor antibodies decreased to 0.7  10 -9 mol/L. The nephrotic syndrome was unsuccessfully treated (December 1993) with a corticosteroid regimen consisting of intravenous pulses of methylprednisolone (1 g/d for 2 days, 750 mg/d for 2 days, 500 mg/d, 250 mg/d, and 125 mg/d for 1 day each) followed by oral prednisone at a dose of 80 mg/d. The resistance of the nephrotic syndrome to diuretic therapy necessitated the use of dialysis, first by hemofiltration (January 1994), then by hemodiafiltration (March 1994), and finally by peritoneal dialysis (November 1994) after failure of successive vascular accesses that were created. The thymic tumor was surgically removed (January 1994). The excision was complete, but the margins were extremely close because of the macroscopically invasive nature of the tumor (invasion of the lower edge of the brachiocephalic trunk, pericardium, mediastinal pleura, upper left pulmonary lobe, and the lateral aspect of the aortic arch). The pathology From the Service de Ne ´phrologie et d’He ´modialyse, Ho ˆpi- tal Saint-Andre ´, Bordeaux; the Laboratoire d’Anatomie Pathologique, Ho ˆpital Pellegrin, Bordeaux; the Service de Me ´de- cine Interne et Maladies Infectieuses, Ho ˆ pital Haut-Leve ˆque, Pessac; and the Service de Ne ´phrologie, Ho ˆpital Pellegrin, CHU Bordeaux. Received September 11, 1998; accepted in revised form January 8, 1999. Address reprint requests to Catherine Lasseur, MD, Ser- vice de Ne ´phrologie et d’He ´modialyse, Ho ˆpital Saint-Andre ´, 1 rue Jean Burguet, 33075 Bordeaux Cedex, France. E-mail: christian.combe@nephro.u-bordeaux2.fr  1999 by the National Kidney Foundation, Inc. 1523-6838/99/3305-0035$3.00/0 American Journal of Kidney Diseases, Vol 33, No 5 (May), 1999: E4 1