Case description
A Caucasian female (age 25), smoker, was admitted to the emergency unit with symptoms of tachycardia and anxiety. Thyroid tests were ordered on suspicion of hyperthyroidism. The test results showed values characteristic of severe hyperthyroidism: TSH was below the detection limit of the assay (<0.001 mU/L), 40 pmol/L free T4 (ref. interval 10–18 pmol/L) and 6.4 nmol T3/L (ref. interval 1.2–2.8 nmol/L). Antibody levels against thyroid peroxidase (anti-TPO) and TSH receptor were increased as follows: 29 kIU anti-TPO/L (ref. interval <16) and 11 anti-TSH receptor U/L (ref. interval <0.6 U/L). The patient was diagnosed with Graves's disease showing disseminated thyroid enlargement. Initial treatment included a β-receptor blocker, propranolol and an inhibitor of thyroxin synthesis called timazol. Later, a thyroidectomy was performed.
Plasma levels of creatinine and cystatin C were analyzed as markers of kidney function. When the patient was in the hyperthyroid state, plasma creatinine was 36 μmol/L (ref. interval 50–90 μmol/L) and cystatin C was 1.36 mg/L. Calculated glomerular filtration rate (GFR) from creatinine was 145 mL/min/1.73 m
2 according to the bias-corrected MDRD equation [
13] and 51 mL/min/1.73 m
2 as calculated from cystatin C [
14]. A subsequent iohexol clearance was performed two days later due to the disproportion between the two GFR estimations. The GFR determined by iohexol clearance during the hyperthyroid period was 121 mL/min/1.73 m
2.
Six months later (after surgery), the patient was clinically euthyroid with a TSH value of 3.69 mIE/L and 15 pmol free T4/L. Creatinine and cystatin C levels were 65 μmol/L and 0.78 mg/L, respectively. GFR-calculated from the creatinine concentration was 73 mL/min/1.73 m2 compared to 114 mL/min/1.73 m2 using the cystatin C concentration.
GFR was determined by measuring the plasma clearance of iohexol, an x-ray contrast agent that is a reliable marker for GFR. The patient was given 5 mL iohexol solution (Omnipaque, Nycomed Amersham) intravenously in an antecubital vein. The GFR was calculated from the iohexol concentration after the injection. Serum iohexol levels were determined by high-pressure liquid chromatography. The total analytical imprecision of the method was 2.5% using a control sample with an assigned value of 33.5 mg/L and 2.4% for a control sample with an assigned value of 65.7 mg/L.
Plasma creatinine measurements were performed by means of the modified kinetic Jaffe reaction on an Architect ci8200 analyzer (Abbott Laboratories, Abbott Park, IL, USA) and reported using S.I. units (μmol/L). The total analytical imprecision of the creatinine method was 3.2% both at 94 and 337 μmol/L.
Cystatin C immunoparticles (code 1014), assay buffer (code 1007), calibrator (code 1012) and control set (code 1019) were all obtained from Gentian (Moss, Norway). The immunoparticles are coated with purified chicken antibodies to cystatin C on uniform polystyrene particles. Plasma cystatin C measurements on the Architect ci8200 was performed using the following instrument settings: primary wavelength 548 nm, secondary wavelength 700 nm, sample blank position 18, and spline calibration method. 220 μL reagent 1 and 3 μL sample were mixed with 45 μL reagent 2. The total analytical imprecision of the cystatin C method was 1.7% at 0.77 mg/L, 1.1% at 1.25 mg/L and 1.4% at 5.45 mg/L.
TSH, free T4 and T3 were also analyzed using the Architect ci8200. The measuring range of the TSH method was 0.001–100 mU/L. The total analytical imprecision of the TSH method was 2.4% at 0.52 mU/L and 2.4% at 5.07 mU/L. The total analytical imprecision was 7.7% at 0.81 nmol/L and 2.53% at 4.06 nmol/L for the T3 method, and 5.2% at 11.5 pmol/L and 4.4% at 16.8 pmol/L for the free T4 method.
Anti-TPO was analyzed on a Liaison instrument (DiaSorin Laboratories, Saluggia, Italy). The total analytical imprecision of the anti-TPO method was 5.8% at 17.7 kU/L and 8.1% at 161.8 kU/L. Anti-TSH receptor antibodies were analyzed with an ELISA kit from RSR Ltd. (Cardiff, United Kingdom).