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The Prevalence of Elevated Serum C-Reactive Protein Levels in
Inflammatory and Noninflammatory Thyroid Disease
Posted 09/29/2003
Elizabeth N. Pearce, Fausto Bogazzi, Enio Martino, Sandra Brogioni, Enia
Pardini, Giovanni Pellegrini, Arthur B. Parkes, John H. Lazarus, Aldo
Pinchera, Lewis E. Braverman
Abstract and Introduction
Abstract

C-reactive protein (CRP) levels have not been routinely used to diagnose
thyroid disease, although many thyroid conditions involve inflammation.
This study was intended to determine whether CRP levels could
differentiate between inflammatory and noninflammatory thyroid
conditions, especially between type II inflammatory amiodarone-induced
thyrotoxicosis (AIT) and type I iodine-induced AIT. Serum
high-sensitivity CRP levels were measured in 100 euthyroid controls (7
taking amiodarone) and 353 patients with one of the following thyroid
conditions: AIT, subacute thyroiditis, toxic diffuse goiter, nodular
goiter, Hashimoto's thyroiditis, short-term hypothyroidism, or
postpartum thyroiditis. No patients with nontoxic multinodular goiter (n
= 34), toxic nodular goiter (n = 23), or toxic diffuse goiter, either
untreated (n = 49) or euthyroid while taking methimazole (n = 33), had
positive CRP levels (>10 mg/L). The occurrence of positive CRP levels
among patients with Hashimoto's thyroiditis (n = 35), short-term
hypothyroidism (n = 38), and postpartum thyroiditis (n = 70) did not
differ significantly from controls. The occurrence of positive CRP
values did not differ significantly between patients with type I and
type II AIT and controls. Six of 7 patients (86%) with untreated
subacute thyroiditis had positive CRP levels (p < 0.00001). These
results indicate that there is only a limited role for measurement of
CRP levels in the diagnosis of thyroid diseases other than subacute
thyroiditis.
Introduction

C-reactive protein (CRP) was first discovered in the 1930s in the plasma
of patients with pneumococcal pneumonia.[1] It is one of the
constituents of the acute-phase reaction and tends to be elevated in
acute and chronic inflammatory conditions. Its secretion is increased in
response to a complex network of cytokines, especially interleukin-6
(IL-6) and either IL-1 or tumor necrosis factor-.[2] The function of CRP
is not fully understood, but may involve proinflammatory and
anti-inflammatory effects.[3]

Because serum CRP levels are elevated in inflammatory conditions, its
presence can aid in the diagnosis of multiple disease states. CRP is
markedly increased early in bacterial infections; therefore, it has been
shown to be a useful marker for sepsis in neonates.[4] CRP levels have
prognostic value in systemic inflammatory diseases such as rheumatoid
arthritis[5] or active systemic vasculitis.[6] They can also help in the
clinical management of more local inflammatory disorders such as Crohn's
disease.[7] Elevated serum CRP levels have been used as a marker for
renal transplant rejection.[8,9] In addition, elevated serum CRP has
been shown to be an important risk factor for diseases not traditionally
thought of as inflammatory conditions. A growing body of evidence
suggests that elevated CRP levels may be a predictor of atherosclerotic
cardiovascular disease,[10-13] and increased CRP levels may even be
linked to the development of insulin resistance and type 2
diabetes.[14-16]

To date, CRP levels have not been routinely used as a diagnostic tool
for thyroid disease, although a number of thyroid conditions involve
inflammatory processes. One goal of this study was to determine whether
CRP levels could be used to help distinguish between entities such as
postpartum thyroiditis, subacute thyroiditis, and type II
amiodarone-induced thyrotoxicosis (AIT), which are inflammatory
disorders, and toxic multinodular goiter, Graves' disease, type I AIT,
and Hashimoto's thyroiditis, which are not primarily inflammatory. It
has previously been determined that CRP levels do not help to
distinguish nonthyroidal illness from true thyroid dysfunction.[17]

AIT is a condition that can be difficult to diagnose definitively.
Amiodarone is an iodinated benzofuranic drug. Approximately 37% of
amiodarone by weight consists of iodine and the iodine is released at a
rate of 7-21 mg of iodide per day.[18] Amiodarone is widely used for the
management of recurrent ventricular arrhythmias and paroxysmal atrial
fibrillation and flutter.[19,20] However, amiodarone is associated with
multiple toxicities, including various effects on the thyroid and the
peripheral metabolism of the thyroid hormones, recently reviewed
elsewhere.[21] Amiodaroneinduced hypothyroidism occurs in up to 20% of
patients in areas with sufficient dietary iodine, and is therefore
relatively common in the United States. AIT occurs in 1%-23% of patients
taking amiodarone, and is more prevalent in iodine-deficient
regions.[22] Type I AIT is defined as iodine-induced excessive thyroid
hormone synthesis and release, and is more likely to occur in patients
with preexisting subclinical thyroid disorders, especially nodular
goiter. Type II AIT is a destructive thyroiditis that causes release of
preformed thyroid hormone from the damaged thyroid gland. It is likely
that both types of AIT may coexist in some patients.

It is important to distinguish between the two forms of AIT, because the
therapies for the two differ. Type I AIT is best treated by high doses
of antithyroid drugs, with the possible addition of potassium
perchlorate to prevent further uptake of iodine by the thyroid, while
type II disease generally responds to high-dose corticosteroids and less
so to iopanoic acid.[23] Color-flow Doppler sonography may show
hypervascularity in type I disease but reduced blood flow in type II
disease.[24,25] Radioactive iodine uptake values are typically low in
type II AIT, and usually so in type I disease in the United States, but
may be normal or elevated in Europe, where ambient iodine intake is
lower. Serum IL-6 has been found to be markedly elevated in most
patients with type II disease, but only slightly elevated in some
patients with type I AIT,[26] although this observation has not been
confirmed in other studies.[24] However, a single non-invasive,
inexpensive, readily available, and reliable method for distinguishing
between these two entities is not currently available.

The aim of this study was to determine whether CRP levels could help to
differentiate between various inflammatory and noninflammatory thyroid
conditions, and especially to explore the possibility of using elevated
CRP levels as a marker for type II AIT.

Section 1 of 4

Next Page: Materials and Methods
Elizabeth N. Pearce,1 Fausto Bogazzi,2 Enio Martino,2 Sandra Brogioni,2
Enia Pardini,2 Giovanni Pellegrini,2 Arthur B. Parkes,3 John H.
Lazarus,3 Aldo Pinchera,2 and Lewis E. Braverman1

1Section of Endocrinology, Diabetes, and Nutrition, Boston Medical
Center, Boston University School of Medicine, Boston, Massachusetts,
2Department of Endocrinology and Metabolism, University of Pisa, Pisa,
Italy, 3Department of Medicine, University College of Wales, College of
Medicine, Cardiff, Wales
Thyroid 13(7):643-648, 2003. © 2003 Mary Ann Liebert, Inc.

http://www.medscape.com/viewarticle/461146?mpid=19265