The Prevalence of Elevated Serum C-Reactive Protein Levels in Inflammatory and Noninflammatory Thyroid Disease

Elizabeth N. Pearce, Fausto Bogazzi, Enio Martino, Sandra Brogioni, Enia Pardini, Giovanni Pellegrini, Arthur B. Parkes, John H. Lazarus, Aldo Pinchera, Lewis E. Braverman

Disclosures
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Materials and Methods

The study included several groups of subjects ( Table 1 ). All subjects were residents of Pisa, Italy (where mean urinary iodine excretion is 110 µg/L), except for the women with postpartum lymphocytic thyroiditis, who resided near Cardiff, Wales (where mean urinary iodine excretion is 140 µg/L). The institutional review boards at each participating center approved the study protocol. Patients or their guardians provided written informed consent to participate in the study.

Diagnosis of each subjects' thyroid condition was made according to clinical and laboratory features as summarized in Table 1 . In particular, diagnosis of AIT was based on the combined results of color-flow Doppler sonography, 24-hour radioactive iodine uptake (RAIU), and follow-up. Patients with type I AIT had high thyroid volumes (mean 58 ± 32 mL), often normal-to-high 24-hour RAIU values (mean 20% ± 12%), and increased thyroid vascularity, while patients with type II AIT had normal thyroid volumes (mean 16 ± 5 mL), low or undetectable 24-hour RAIU values (mean 1.6% ± 1.0%), and absent thyroid hypervascularity. IL-6 levels were not obtained. Moreover, all patients with type II AIT responded to prednisone and remained euthyroid after steroid withdrawal. Patients with type I AIT required prolonged therapy with methimazole (MMI) and potassium perchlorate before restoration of euthyroidism; additionally, most underwent total thyroidectomy or radioiodine therapy later.

Thyroid function was assessed by measuring serum free thyroxine (FT4) and free triiodothyronine (FT3) (Lisophase kits, Laboratory Bouty, Sesto S. Giovanni, Italy) and serum thyroid-stimulating hormone (TSH) (Auto-Delfia Wallac, Gaithersburg, MD). The normal ranges were: serum FT4, 0.6-1.8 ng/dL (8.4-23.2 pmol/L); FT3, 0.25-0.55 ng/dL (3.8-8.4 pmol/L); and TSH, 0.4-3.7 mU/L. Serum antithyroid peroxidase (anti-TPO) antibody (Serodia, Tokyo, Japan; undetectable in normal controls) was also determined by a commercial kit. Thyroid volume was determined by ellipsoid method, as previously described.[27]

Twenty-four hour RAIU was determined after administration of a tracer dose (5 µCi) of 131I. Normal 24-hour RAIU values in the Pisa area range from 20%-44%.

Serum CRP was assessed by means of particle-enhanced immunonephelometry using a commercial kit (Dade Behring, Marburg, Germany). Briefly, polystyrene particles coated with monoclonal antibodies to CRP were used to form an agglutinated complex in the presence of CRP-containing sera. The intensity of the scattered light in the nephelometry was dependent on the CRP content of the sample; the concentration (mg/L) was determined versus dilutions of a standard of a known concentration. The intraassay coefficient of variability was 4.5%; the interassay coefficient of variability was 3.8%. Minimum detectable value was 0.175 mg/L. Serum CRP values in normal subjects were <5 mg/L, according to the test brochure. However, based on previous population studies in Italy and elsewhere, we considered CRP levels greater than 10 mg/L to be positive.[28,29]

Statistical analysis was carried out using SAS (SAS Institute, Cary, NC) and Excel (Microsoft) software. The analysis of differences between CRP positivity in different groups was performed using a two-tailed Fisher's exact test.

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