Steroid-sensitive nephrotic syndrome, sarcoidosis and thyroiditis—a new syndrome?

Masateru Nishiki, Yoshio Murakami, Yuko Yamane and Yuzuru Kato

First Division, Department of Medicine, Shimane Medical University, Izumo, Japan

Correspondence and offprint requests to: Masateru Nishiki, MD, First Division, Department of Medicine, Shimane Medical University, 89-1 Enya-cho, Izumo 693-8501, Japan.

Keywords: chronic thyroiditis; IgA nephropathy; nephrotic syndrome; sarcoidosis



   Introduction
 Top
 Introduction
 Case
 Discussion
 References
 
It has been reported that several immune complex diseases are often complicated by a steroid-sensitive nephrotic syndrome [1]. Sarcoidosis is a systemic disease characterized by non-caseating granulomas. Although immune complex production is known to be increased in this disease, the aetiology has not been elucidated fully. There has been only one suggestive case report on the association between a steroid-sensitive nephrotic syndrome and sarcoidosis as well as Graves' disease [2].

Here, we report a case of steroid-sensitive nephrotic syndrome in association with sarcoidosis still developed in a patient with known immunoglobulin A (IgA) nephropathy and chronic thyroiditis. Oral administration of prednisolone relieved both the renal and pulmonary abnormalities.



   Case
 Top
 Introduction
 Case
 Discussion
 References
 
A 63-year-old male patient was referred to our hospital for further examination of massive proteinuria, hypertension and abnormal findings on chest X-ray. He had a past history of chronic thyroiditis diagnosed at the age of 49 years. Microscopic haematuria was first detected on an annual health check at age 57 years. For the past year, he had been suffering from violent cough attacks. He had noticed painless swelling of the lower extremities 2 months previously.

On physical examination, body temperature was 36.4°C, pulse rate was 96/min, respiratory rate was 22/min and blood pressure was 168/90 mmHg. Diffuse and elastic hard goitre was palpable. Heart sounds were normal. Fine inspiratory crackles were audible at the lower field of both lungs. The liver and kidneys were not palpable. Pitting oedema was present in his lower thighs. Superficial lymphadenopathy or visual disturbances were not noted. Circumferential pigmentation along the iridocorneal angle or on the frontal surface of the lens were not found either.

Urinalysis revealed massive proteinuria (6.3 g/day), microscopic haematuria (20–30 RBC/HPF), hyaline (10–29/HPF) and fatty casts (3/WF). Circulating blood count showed no remarkable abnormalities. Serum biochemistry showed hypoproteinaemia (total protein 7.0 g/dl and albumin 2.9 g/dl). Serum electrolyte levels were within the normal range. Serum blood urea nitrogen (10 mg/dl) and creatinine (0.9 mg/dl) were normal, but the creatinine clearance rate was decreased to 63 ml/min. Urinary N-acetyl-ß-D (24.1 IU/l) and ß2-microglobulin levels (667 µg/l) levels were elevated. Serum angiotensin-converting enzyme (ACE) (30.6 IU/l) and serum IgA (649 mg/dl) levels were elevated. Anti-thyroid peroxidase antibody (1.9 U/ml) was positive, but anti-thyroglobulin and anti-thyroid-stimulating hormone (TSH) receptor antibodies were not detected. T3 (178 ng/dl), free T4 (1.0 ng/dl) and TSH (3.51 µU/ml) were all within the normal range. Echography showed homologous low echoic swelling of the thyroid gland; a tuberculin test was negative. Bilateral hilar lymph node swelling and infiltrations in the lower lung fields were revealed by chest X-ray and computed tomography. Abnormal accumulations were found in the lungs but not in the kidneys on systemic gallium scintigraphy.

Microscopic examination of the right paratracheal lymph nodes biopsied by a transbronchial approach revealed non-caseating epitheloid cell granulomas consistent with sarcoidosis. Proliferation of mesangial cells and sclerotic changes of the glomeruli were shown by light microscopic examination of the renal specimen biopsied. Two of nine glomeruli had cellular or fibrous crescents. In the interstitial region, focal tubular atrophy with fibrosis was found, but neither sarcoid tubercles or granulomatous infiltration were detected. Immunohistochemistry revealed depositions of IgA and C3 in the mesangial region, which were demonstrated as electron-dense deposits by electron microscopic examination (Figure 1Go). These findings were consistent with IgA nephropathy.



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Fig. 1. Electron microscopic view of the renal specimen biopsied. Electron-dense deposits are shown in the mesangial region (x1800).

 
As shown in Figure 2Go, the patient was treated with oral administration of prednisolone. Clinical symptoms such as violent cough attacks and oedema subsided. Bilateral hilar lymph node swelling and pulmonary infiltration decreased in size and density. In addition to the respiratory symptoms, proteinuria gradually diminished. Serum angiotensin-converting enzyme and serum IgA levels were normalized completely by prednisolone, but anti-thyroid peroxidase antibody titres persisted (1.4 U/ml). The dose of prednisolone was tapered off without any sign of relapse to date. Thyroid hormone concentrations all remained within the normal range during and after therapy.



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Fig. 2. Clinical course. ACE; serum angiotensin-converting enzyme; IgA; immunoglobulin A; TP, total protein; Alb; albumin; U-pro, urinary protein excretion.

 


   Discussion
 Top
 Introduction
 Case
 Discussion
 References
 
Known renal disorders in patients with sarcoidosis are nephrocalcinosis secondary to hypercalcaemia, granulomatous interstitial nephritis and glomerulonephritis. The histological forms of sarcoidosis-associated glomerulonephritis include focal glomerulosclerosis, mesangiocapillary glomerulonephritis, crescentic glomerulonephritis and, rarely, IgA nephropathy [35]. In the present case, microscopic haematuria preceded by 5 years the appearance of lung abnormalities and upward range proteinuria. It is plausible, therefore, that the answer of the nephrotic syndrome and of sarcoidosis coincided. There have been a limited number of case reports of IgA nephropathy in patients with sarcoidosis [57], suggesting some immunological link between these two conditions [7]. Prednisolone relieved not only the nephrotic syndrome but also pulmonary manifestation of sarcoidosis in the on case.

Furthermore, the present case was complicated by chronic thyroiditis, as demonstrated by diffuse hard goitre and positive anti-thyroid peroxidase antibodies. Sarcoidosis is often complicated by autoimmune thyroid diseases. Nakamura et al. [8] recently reported on the high prevalence of autoantibodies against thyroid peroxidase and thyroglobulin in Japanese patients with sarcoidosis. Mündlein et al. [2] observed the simultaneous occurrence of Graves' disease and sarcoidosis in a patient with minimal-change glomerulonephritis which was steroid-sensitive, and speculated that a disruption of the immunoregulatory network provided a causal link between these disorders. Taken together, we propose that the simultaneous occurence steroid-sensitive nephrotic syndrome of sarcoidosis and of autoimmune thyroid disease constitutes a new syndrome.

In summary, we report the development of steroid-sensitive nephrotic syndrome and sarcoidosis in a patient with preceding IgA nephropathy and chronic thyroiditis. The nephrotic syndrome as well as the pulmonary manifestation of sarcoidosis responded to oral administration of prednisolone.



   Acknowledgments
 
We are indebted to Mrs Akiko Kanayama for technical assistance and to Mrs Akiko Kawakami for secretarial assistance. This work was supported in part by grants from the Ministry of Education, Science and Culture, Japan, the Ministry of Health and Welfare, Japan, and the Growth Foundation, Japan.



   References
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 Introduction
 Case
 Discussion
 References
 

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Received for publication: 22. 1.99
Accepted in revised form: 17. 4.99