Renal impairment resulting from hypothyroidism-or impaired estimated glomerular filtration rate in a patient with hypothyroidsm.

Abstract

Sir, We read with interest the two cases described by Andrew Connor and Joanne E. Taylor [1]. They summarize the medical literature that the lower cardiac output and renal blood flow is likely to be the predominant mechanism of impaired renal function in hypothyroidism. In the discussion, they also list other possible mechanisms, so that hypothyroidism may increase creatinine release from muscle. This renders creatinine a poor marker of GFR. In case 1 the creatinine kinase (CK) was elevated, as a sign of rhabdomyolysis. We think that in cases with elevated endogenous creatinine, we do not know if there is an impaired renal function or not. Furthermore, we want to highlight some important points, which we have to consider in the treatment of patients with hypothyroidism and rhabdomyolysis. As often described in patients with hypothyroidism, they may suffer from a polymyositis-like syndrome and an elevated CK may be observed [2–7]. In these cases, there is a high amount of released creatine and therefore higher endogenous creatinine production. In all these cases, eGFR would be wrong and measuring the creatinine clearance rate does not improve the results. Cystatin C, an endogenous marker to estimate the GFR, independent from muscle mass, age and alimentation may be a better parameters in diagnosing impaired renal function in a patient with hypothyroidism. But there are also problems with this measurement in patients with thyroid dysfunction [8–11]. Cystatin C levels are lower in hypothyroidosis and higher in the hyperthyroid state as compared with the euthyroid state. Manetti et al. described decreased cystatin C concentrations in 24% of hypothyroid patients [11]. We saw a young patient with hypothyroidism and elevated serum creatinine, normal serum urea, reduced estimated GFR (47 ml/min/1.73 m2, estimated by MDRD-4; 30 ml/min/1.73 m2 estimated with a 24-h urine collection) and CK of 4438 U/l. Cystatin C was 0.72 mg/dl, which resulted in a normal GFR of 117 ml/min. We decided to start hormone replacement therapy and to watch closely the pathological parameters. The therapy led to normal laboratory findings for serum creatinine after 6 weeks. Later, we observed a difference in our patient between cystatin C levels in euthyroidism (0.98 mg/l) and in hypothyroidism (0.72 mg/l). One investigation with radioisotopic filtration markers in patients with hypothyroidism underlines the opinion of A. Connor and J. E. Taylor: Karanikas et al. [12] investigated isotopic renal function in severe hypothyroidism and after hormone replacement therapy. They did not find any influence of thyroid hormones on the outcome of 99m-Tc-MAG3-renography. The Cr-EDTA clearance was significantly lower in hypothyroidism. This reflects a normal tubular function and to these authors it seems that the renal haemodynamic changes mainly affect the GFR. If this is right, perhaps in cases of hypothyroidism and mild rhabdomyolysis we have a combination of both high amounts of creatinine and a change in renal haemodynamics. Only inulin clearance may give the answer, if there is really an impaired renal function. Unfortunately, we did not find any case report where the authors use the inulin clearance for estimation of the GFR in a patient with hypothyroidism. There may be risk factors in patients with hypothyroidism, which lead to renal damage with pathological urine sediment and any other sign for tubular failure, described by Sekine et al. [13]: they reported about a patient and cited three other cases with some precipitating factors such as hypotension with myxoedema coma, certain inflammatory reactions of the muscles or, and this is very important, vigorous exercise which may cause massive rhabdomyolysis. In these special cases, high urine and serum myoglobin levels and tubular necrosis can be observed and perhaps dialysis has to be started. We agree with A. Connor and J. E. Taylor that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation. Also, we have to look for signs of rhabdomyolysis. Taking these points into account, as described above, we can decide to start hormone replacement therapy and to watch closely the pathological parameters in patients with hypothyroidism, rhabdomyolysis and elevated serum creatinine as the only evidence for an impaired renal function. The hormonal therapy will lead to normal laboratory findings for serum creatinine after some weeks. In cases with hypothyroidism and myalgia, patients have to avoid muscle training or vigorous exercise. There is an increased risk to develop massive rhabdomyolysis and renal damage. If the renal haemodynamic changes mainly affect the GFR in patients with hypothyroidism, we have to take these into account in the therapy. For instance, COX-inhibitors to treat myalgia should be avoided. Inhibition of COX-mediated prostaglandin synthesis by NSAIDs can promote further reduction in renal haemodynamics and increase the risk for acute renal failure. Editorial Note: Dr Connor et al. had no further comments on this letter. Conflict of interest statement. None declared.