WATER AND CREATININE CLEARANCE IN THYROTOXICOSIS

B. Aminian MD, M. Zaree MD, Gh. R. Omrani MD

Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

  • Abstract

    Background and objective-In thyrotoxicosis, changes in urine output and serum creatinine (Cr) concentration has been related to increased glomerular filtration rate (GFR). The aim of this study is to clarify the mechanism of these changes.
    Methods-Forty-one thyrotoxic patients, 9 male and 32 female with the age range of 16-62 years were selected and body weight, 24-h urine output, serum and urine Cr concentration, and GFR were measured in the thyrotoxic state and two months after treatment. The data was analyzed by student ‘t’ test and paired ‘t’ test.
    Results-The following parameters were measured and are compared in thyrotoxic and euthyroid states respectively. Body weight: 58.4±10.6 Kg and 61.6±10.4 Kg after receiving anti-thyroid therapy (p<0.001). 24-h urine output: 1430±420 ml, and 1165±450 ml (p <0.001). Serum creatinine concentration: 0.7±0.11 mg/dl, and 0.84±0.13 mg/dl (p<0.001). 24-h urine creatinine concentration: 906±225 mg/l and 1081±285 mg/l (p<0.001). The change in GFR was not statistically significant, being 90.1 ml/min before therapy and 89.5 ml/min in the euthyroid state.
    Conclusion-Increased urine output and decreased serum creatinine concentration in thyrotoxicosis is not GFR related.

    Keywords • Thyrotoxicosis • GFR • ANP • creatinine • creatinine clearance

    •

    Introduction

    The effect of thyroid hormone on renal function has been studied for long and different and controversial results were obtained. In an animal study on thyrotoxic rats, increased serum atrial natriuretic peptide (ANP) concentration was proved and was described as a possible mechanism for increased water excretion in thyrotoxic patients1. Ford evaluated renal function in thyrotoxic patients and related the low serum creatinine concentration, the high serum urea concentration and the low serum Cr/Urea ratio to increased GFR2. Aizaw studied 132 hyperthyroid patients and concluded that increased serum Urea/Cr concentration is due to increased urea production, decreased Cr production and increased urinary Cr excretion. Their thyrotoxic patients had high cardiac output state, so the low serum creatinine concentration was related to increased GFR3. Shirota studied 53 thyrotoxic patients (secondary to Grave’s disease) and showed that compared to euhtyroid patients, serum Cr concentration was lower and serum urea concentration was higher. The lower serum Cr concentration was related to its lower production and higher urinary excretion rate. Creatinine clearance in thyrotoxic patients was higher than euthyroids. When Inuline clearance was used for more accurate GFR measurement, it was shown that there was no change in GFR between thyrotoxic and euthyroid patients concluding that increased urinary Cr excretion was not GFR dependant, but related to renal tubular Cr excretion4. So in thyrotoxicosis, increased urine output and decreased serum creatinine concentration, which were claimed to be GFR related is not a proven fact and the aim of our study was to clarify the mechanism of these changes.

    Materials and Methods

    In this prospective study, seventy hyperthyroid patients, who were referred to the Endocrine OPD clinics of Shiraz University Hospital, thyrotoxicosis was diagnosed on clinical bases and thyroid function tests (T4, T3, and TSH were measured by Radioimmunoassay). In these patients, body weight, 24-h urine output, serum and urine Cr concentrations and GFR were measured (GFR measured by Urinary Cr concentration multiplied by Urine Volume per minute, divided by Plasma Cr concentration). Twelve patients who did not properly collect their 24-h urine were excluded and the remaining fifty-eight patients were then treated with Methimazole.™ After two months, forty-one patients who had become euthyroid were selected. They were 9 male and 32 female patients in the age range of 16-62 years. In these patients, body weight, 24-h urine output, serum and urine Cr concentration and Cr clearance were measured and the data was analyzed by student’s t-test and paired t-test. Urine output and serum and urine Cr concentrations as dependant parameters were compared to the level of thyroid hormones.

    Results

    The mean body weight before therapy was 58.4±10.6 Kg, which increased to 61.6 ±10.4 Kg in the euthyroid state. All patients had increased body weight after treatment and the change was statistically significant (p<0.001).

    The twenty-four-hour urine output before therapy was 1430±420 ml and it decreased to 1165 ±450 ml in the euthyroid state. This parameter decreased in 36, increased in four and remained unchanged in one patient. With paired t-test, the change in 24-h urine output between two groups was statistically significant (p<0.001). Serum Cr concentration before starting the therapy was 0.7±0.11 mg/dl which increased to 0.84±0.13 mg/dl after therapy. Serum Cr concentration increased in 38 euthyroid patients, and it was unchanged in 3 patients. This change also was statistically significant (p<0.001). Twenty-four

    hour urine creatinine concentration before therapy patients. The mean Cr clearance before therapy was 90.1 ml/min and after therapy it was 89.5 ml/min, which shows that the change was not statistically significant. After therapy and while euthyroid, Cr clearance decreased in 18, increased in 20 and remained unchanged in 3 patients. Results are shown in Table 1.

    No corelation was found between 24-h urine output, serum and urine Cr concentration and Cr clearance and the thyroid hormone level. There was a linear correlation between changes in body weight and 24-h urinary creatinine excretion in thyrotoxic and euthyroid state (Fig. 1) and between body weight and 24-h urine output in these two thyroid states (Fig. 2).

    Discussion

    Our study shows that as compared to the euthyroid state the urine output in thyrotoxic patients is higher and serum Cr concentration and 24-h urine Cr is significantly lower. The change in creatinine clearance is negligible between the two groups and is not statistically significant.

    In accordance with previous research works, it is clear that urine output is increased and serum Cr is decreased in thyrotoxicosis while these two parameters show reverse changes after patients become euthyroid. The important point is that the decreased serum Cr concentration is not related to increased GFR. In Ford’s study, without measuring GFR, changes in serum Cr concentration in their thyrotoxic patients were related to changes in GFR2. Aizwa claimed that decreased serum Cr concentration in thyrotoxic patients is related to high cardiac output state3, and concluded that this change is GFR-dependant. A study conducted by Shirota and coworkers showed that the GFR that was measured by Inuline clearance was unchanged in thyrotoxic and euthyroid patients4. In contrast to their findings, urinary Cr excretion was low in our thyrotoxic patients. In Rodier’s research work in nine thyrotoxic patients, urinry Cr output was measured and it was low.5

    So our findings indicate that decreased serum Cr concentration in thyrotoxicosis is not due to increased GFR and even not due to increased Cr excretion, because 24-h urine Cr is lower in thyrotoxic patients. These findings are more in favor of decreased body mass, as shown by linear correlation between body weight and serum creatinine, and also to less creatinine mobilization from muscle due to cell membrane stabilization6,7. In our thyrotoxic patients, the 24-h urine output was definitely increased while GFR was unchanged, so we can conclude that in these patients increased water clearance is not GFR

    dependant and other triggering factors such as increased serum ANP 8-11 and direct stimulatory effect of T4 on thirst center might have a contributory role12,13.

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