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
In This Article

Discussion

Many thyroid disorders are caused by inflammation. The goal of this study was to determine whether elevated serum CRP levels, a highly sensitive but nonspecific marker for inflammation, were present in various inflammatory and non-inflammatory thyroid diseases. Marked variations in serum CRP levels with different thyroid disease entities, if present, might provide a valuable diagnostic tool.

In this study, no significant differences were detected in the prevalence of elevated CRP levels (>10 mg/L) between euthyroid, nongoitrous controls and patients with toxic or nontoxic multinodular goiter, or those with toxic diffuse goiter (Graves' disease), either treated or untreated. Similarly, no significant increase in the prevalence of CRP level elevations was found in euthyroid patients with Hashimoto's thyroiditis, or in thyroid cancer patients who were transiently hypothyroid while not taking live thyroxine.

Inflammation is not a pronounced feature of any of these conditions, and the normal CRP levels were not unexpected. Similarly, it has recently been reported that serum CRP levels did not correlate with thyroid hormone levels in groups of overtly and subclinically hypothyroid subjects, and that treatment of subclinical hypothyroidism did not alter serum CRP values.[30]

Painful subacute thyroiditis is a self-limited inflammatory disorder, probably of viral etiology. In this study, most subjects (86%) with untreated subacute thyroiditis had elevated serum CRP levels, which differed significantly from the control group. This is not surprising because the hallmark of the laboratory evaluation of subacute thyroiditis is a markedly elevated erythrocyte sedimentation rate (ESR) and elevated serum IL-6 levels,[31] as well as other inflammatory markers. The serum CRP level has some theoretic advantages over other inflammatory markers for the diagnosis of subacute thyroiditis: the ESR is influenced by red blood cell count and morphology, and by immunoglobulins present in plasma, so it may be less precise than the CRP level. Additionally, normal values for the ESR, unlike CRP levels, vary with both age and gender.[3] Finally, serum IL-6 concentrations are not readily available in clinical laboratories and are expensive.

Postpartum thyroiditis is relatively common, occurring within a few months of delivery in up to 10% of U.S. women, although estimates have varied.[32,33] Although this is known to be an inflammatory disorder, elevated CRP levels were not significantly more prevalent in women with post-partum thyroiditis at any stage (thyrotoxic, euthyroid, or hypothyroid) than in normal controls. Additionally, elevated CRP levels were not more prevalent in the inflammatory thyrotoxic phase than in the hypothyroid and euthyroid phases of pospartum thyroiditis. These results were consistent with previously reported findings that IL-6 levels are not increased in women with postpartum thyroiditis.[34]

No significant difference in the prevalence of serum CRP elevations was noted in type I versus type II AIT, despite the fact that type II AIT is a destructive inflammatory process and type I AIT is caused by excess iodine and not by inflammation. The failure of CRP to differentiate between the two entities suggests the possibility that the inflammatory changes in type II AIT are not sufficiently extensive to result in elevations of CRP as seen in subacute thyroiditis. It is also possible that the two types of AIT may coexist in a single patient, although in the present study a single type was dominant as defined by the diagnostic criteria.

Although serum CRP levels are theoretically promising as a way to discriminate between inflammatory and noninflammatory thyroid conditions, there appears to be only a limited role for measurement of CRP levels in the diagnosis and management of most thyroid diseases. The exception is subacute thyroiditis, in which elevated CRP levels were markedly more prevalent than in controls: an elevated serum CRP level may be as useful for the diagnosis of subacute thyroiditis as an elevated ESR, the traditional hallmark of the disorder.

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