Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status.

Background: Despite being the most performed laboratory endocrine investigation, the optimum use of thyroid tests (thyrotropin [TSH] and thyroid hormone [TH] measurement) is open to question and the interpretation of the results from these tests can be ambiguous. The American Thyroid Association (ATA) with its expertise support the endeavor of the U.S. Centers for Disease Control (CDC) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) to improve and maintain standardization and harmonization of thyroid testing. ATA mandated an international interdisciplinary working group panel to survey the status of thyroid testing by reviewing the recent literature to revise or update the criteria as needed in mutual agreement and to inform clinical care. Summary: This review represents the conclusions on the clinical use of current routine TSH and TH (thyroxine [T4] and triiodothyronine [T3]) assays, taking into account geographic differences in disease prevalence and clinical and laboratory practice among writing members. The interaction between physiological, pathophysiological, and pharmacological factors and thyroid assays can affect their measurements and confound result interpretation. These factors need to be considered in the clinical context of the patient for appropriate test ordering and result interpretation. Despite significant advances in laboratory methods over the past 50 years, routine thyroid assays remain susceptible to idiosyncratic analytical interference that may produce spurious results. Improved standardization needs to be demonstrated through ongoing international efforts before results from different assays can be considered equivalent. Emerging technology (e.g., mass spectrometry) shows promise for improved analytical performance, but more evidence of its clinical utility and improved throughput is required before it can be considered for routine use. Close clinical-laboratory collaboration is encouraged to overcome and avoid the pitfalls in thyroid testing as well as resolve clinically discrepant results. The evidence base supporting the conclusions of this review is summarized in four detailed online technical supplements. Conclusions: Over the past five decades, testing for TSH, T4, and T3 has evolved from manual radioisotopic immunoassays to nonisotopic multiplexed immunometric assays using highly automated equipment. Despite these technical advances, physicians and laboratorians performing these analyses must understand limitations of these methods to properly order tests and interpret results.

Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP).

Antibodies are widely used biomarkers for the diagnosis of many diseases. Assays based on solid-phase immobilization of antigens comprise the majority of clinical platforms for antibody detection, but can be undermined by antigen denaturation and epitope masking. These technological hurdles are especially troublesome in detecting antibodies that bind nonlinear or conformational epitopes, such as anti-insulin antibodies in type 1 diabetes patients and anti-thyroglobulin antibodies associated with thyroid cancers. Radioimmunoassay remains the gold standard for these challenging antibody biomarkers, but the limited multiplexability and reliance on hazardous radioactive reagents have prevented their use outside specialized testing facilities. Here we present an ultrasensitive solution-phase method for detecting antibodies, termed antibody detection by agglutination-PCR (ADAP). Antibodies bind to and agglutinate synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. ADAP detects zepto- to attomoles of antibodies in 2 µL of sample with a dynamic range spanning 5-6 orders of magnitude. Using ADAP, we detected anti-thyroglobulin autoantibodies from human patient plasma with a 1000-fold increased sensitivity over an FDA-approved radioimmunoassay. Finally, we demonstrate the multiplexability of ADAP by simultaneously detecting multiple antibodies in one experiment. ADAP's combination of simplicity, sensitivity, broad dynamic range, multiplexability, and use of standard PCR protocols creates new opportunities for the discovery and detection of antibody biomarkers.

Evaluation of risk-factor-based screening for thyroid peroxidase antibody positivity in pregnancy.

OBJECTIVE: To determine whether risk-factor-based screening for thyroid dysfunction in pregnancy performs well for detecting thyroid peroxidase antibodies (TPOAb), a marker for autoimmune thyroid disease. STUDY DESIGN: We prospectively evaluated pregnant women for thyroid dysfunction using The Endocrine Society's eleven screening questions. Serum was analysed for TPOAb. RESULT: We enrolled 546 women. TPOAb positivity was higher in women with a personal (odds ratio (OR) = 8·0; 95% confidence interval (CI) = 1·7-37·4; P = 0·02) or family history of thyroid disease (OR = 2·7; 95% CI = 1·3-5·7; P = 0·02). There was no association between the number of positive responses and TPOAb positivity (P = 0·41). Risk-factor-based screening missed 18 women (33%) with TPOAb. CONCLUSION: One-third of women with TPOAb were missed by the case-finding method. A personal or family history of thyroid disease was most strongly associated with TPOAb positivity.

Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes.

CONTEXT: Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). OBJECTIVE: The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. METHODS: A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. RESULTS: The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. CONCLUSIONS: Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.

In search of an unstimulated thyroglobulin baseline value in low-risk papillary thyroid carcinoma patients not receiving radioactive iodine ablation.

BACKGROUND: The clinical use of serum thyroglobulin (Tg) as a tumor marker in papillary thyroid cancer (PTC) patients following total thyroidectomy continues to evolve, due in part to the introduction of more sensitive (second generation) Tg immunometric assays (Tg(2G)IMA, functional sensitivity ≤ 0.10 ng/mL), and the implementation of new recommendations against radioactive iodine ablation (RAIA) for patients at the lowest risk of recurrence. As a result, there is a need to establish the optimal timing and interpretation of serum Tg values while on levothyroxine-induced suppression of thyrotropin (TSH) in thyroidectomized PTC patients with a thyroid remnant. This study examines the pattern of decline and eventual baseline value of unstimulated Tg (uTg) concentrations following total thyroidectomy in patients with low-risk PTC who did not receive RAIA. METHODS: The medical records of consecutive patients with thyroid cancer seen at the Los Angeles County + USC Medical Center were retrospectively reviewed. Serial uTg and TSH values from Tg-antibody negative low-risk PTC patients treated with total thyroidectomy and no RAIA were analyzed. Patients were stratified by degree of TSH suppression to assess the effect on uTg. Serial postoperative uTg values were evaluated for the temporal pattern of decline and ultimate baseline. Patients with medullary thyroid cancer (MTC) were studied as a surgical reference group. RESULTS: Records from 577 consecutive thyroid cancer patients were reviewed, of which 36 met all criteria for inclusion. By 6 months, uTg fell to <0.5 ng/mL in 61% of patients and all patients demonstrated uTg < 0.5 ng/mL 2 years after surgery. During a median follow up of 5.7 years, uTg values remained below this level. The median uTg values in patients with papillary microcarcinoma, PTC, and MTC were similar at 0.11, 0.12, and 0.09 ng/mL, respectively. Further decline in uTg was not observed once the TSH was <0.5 mIU/L. CONCLUSIONS: The uTg values during TSH suppression in Tg antibody-negative, low-risk PTC patients who did not receive RAIA were below 0.5 ng/mL by 6 months postoperatively in most cases and remained stable over the duration of patient follow-up.

Clinical review: Clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC).

CONTEXT: Thyroglobulin autoantibodies (TgAb) are primarily measured in serum in conjunction with thyroglobulin (Tg)--the primary tumor marker used to monitor patients with differentiated thyroid cancers (DTC). Every specimen needs TgAb testing to authenticate that the Tg measurement is not compromised by TgAb interference. When present, TgAb concentrations per se can be monitored as a surrogate tumor marker. OBJECTIVES: The aims of the study were: 1) to review published reports concerning whether there are associations between DTC, thyroid autoimmunity (Hashimoto's thyroiditis), and the presence of TgAb; and 2) to evaluate the methodological factors that influence TgAb interference with serum Tg testing. DATA SOURCES: PubMed was used to identify studies published over the last 55 yr that focused on DTC relationships with thyroid autoimmunity and the presence of thyroid autoantibodies. RESULTS: Many studies have reported significant associations between papillary thyroid cancer and Hashimoto's thyroiditis that may have a favorable prognostic significance. TgAb is detected in approximately 20% of DTC patients and may be a more specific thyroid tumor marker than thyroid peroxidase antibodies. TgAb interferes with Tg immunometric assay (IMA) measurements, causing falsely low/undetectable Tg values, especially when TgAb concentrations are high and serum Tg concentrations (measured by RIA) are low. TgAb concentrations respond to changes in Tg-secreting thyroid tissue such that the TgAb trend can be used as a more reliable surrogate DTC tumor marker than Tg IMA. Current TgAb assays may not always detect interfering TgAb because of insensitivity and specificity differences. It is critical to retain the same method for long-term TgAb monitoring. CONCLUSIONS: Patients with Hashimoto's thyroiditis frequently have TgAb detected and may have a higher risk for papillary thyroid cancer. Although TgAb interferes with Tg IMA measurements, TgAb trends can be used as a surrogate DTC tumor marker in preference to Tg IMA, provided that the same method is used.

Effect of environmental perchlorate on thyroid function in pregnant women from Córdoba, Argentina, and Los Angeles, California.

OBJECTIVE: To determine whether environmental perchlorate exposure adversely affects thyroid function in women in the first trimester of pregnancy. METHODS: First-trimester pregnant women were recruited from prenatal clinics in the Los Angeles County Hospital, Los Angeles, California, and in the Hospital Universitario de Maternidad dependent Universidad Nacional de Córdoba, Córdoba, Argentina, between 2004 and 2007. Spot urine and blood specimens were obtained during the clinic visit. Urinary perchlorate, iodine, and creatinine were measured, and thyroid function tests were performed. RESULTS: The study included 134 pregnant women from Los Angeles, California (mean gestational age ± SD = 9.1 ± 2.2 weeks), and 107 pregnant women from Córdoba, Argentina (mean gestational age = 10.0 ± 2.0 weeks). Median urinary iodine values were 144 µg/L in California and 130 µg/L in Argentina. Urinary perchlorate levels were detectable in all women (California: median, 7.8 µg/L [range, 0.4-284 µg/L] and Argentina: median, 13.5 µg/L [range, 1.1-676 µg/L]). Serum thyroperoxidase antibodies were detectable in 21 women from California (16%) and in 17 women from Argentina (16%). Using Spearman rank correlation analyses, there was no association between urinary perchlorate concentrations and serum thyrotropin, free thyroxine index, or total triiodothyronine values, including within the subset of women with urinary iodine values less than 100 µg/L. In multivariate analyses using the combined Argentina and California data sets and adjusting for urinary iodine concentrations, urinary creatinine, gestational age, and thyroperoxidase antibody status, urinary perchlorate was not a significant predictor of thyroid function. CONCLUSIONS: Low-level perchlorate exposure is ubiquitous, but is not associated with altered thyroid function among women in the first trimester of pregnancy.

Serum TSH determinations in pregnancy: how, when and why?

Improvements in the sensitivity of the serum TSH assay have revolutionized our strategies for investigating thyroid function and firmly established TSH as the first-line thyroid function test for most clinical situations, including pregnancy. As a single hormone determination, serum TSH provides the most sensitive index to reliably detect thyroid function abnormalities. Normal thyroid function is important to ensure the best possible pregnancy outcome; in addition, disorders of the thyroid gland are relatively frequent in women of childbearing age. The aim of this article is, therefore, to present relevant information on analytical, as well as clinical, aspects regarding serum TSH determination and its usefulness to detect subtle thyroid function abnormalities associated with the pregnant state, namely overt and subclinical hypothyroidism and hyperthyroidism. As these disorders are associated with poor pregnancy outcome, the authors of the present article are in favor of serum TSH measurement for all pregnant women.

Mildly elevated TSH and cognition in middle-aged and older adults.

BACKGROUND: It is accepted that markedly elevated thyroid-stimulating hormone (TSH) levels are associated with impaired cognitive function. However, the findings regarding the association between mildly elevated TSH levels and cognition are equivocal. The objective of this study was to assess the relation between TSH levels in the normal to mildly elevated range (0.3-10.0 mIU/L) and several domains of cognitive function. METHODS: A healthy, community-based sample of 489 men and women (40-88 years old, mean = 60.5 years) enrolled in the B-Vitamin Atherosclerosis Intervention Trial were studied. A neuropsychological test battery was used to assess a broad array of cognitive functions. Four uncorrelated neuropsychological factors were extracted by principal component analysis. Using multivariable linear regression, performance on each factor was examined in relation to TSH levels, controlling for age, gender, race-ethnicity, education, homocysteine levels, low-density lipoprotein cholesterol levels, and smoking status. RESULTS: TSH levels were not associated with any of the four factor scores in the total sample or in younger (age < 60) or older (age >or= 60) subjects, although there was a trend for older subjects with higher levels of TSH to do more poorly on paragraph recall (p = 0.06). Gender-stratified analyses showed that TSH was positively associated with scores on word list learning for females only (p = 0.003). CONCLUSIONS: In this community-based sample of middle-aged to older individuals, increasing TSH levels were not associated with significantly reduced cognitive performance in any domain. Further exploration of the effects of gender on the association between TSH and cognition is warranted.

Free T4 immunoassays are flawed during pregnancy.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracies of 2 free thyroxine immunoassays during pregnancy. STUDY DESIGN: Serum was collected from healthy, thyroid peroxidase antibody-negative women during each trimester and nonpregnant controls. Thyrotropin, total T4 (TT4), free T4 index (FT4I), and 2 different FT4 immunoassays were studied. RESULTS: As expected, TT4 was elevated in all 3 trimesters compared to controls (P < .001). FT4I was elevated in the 1st trimester as compared with controls (P < .05) and returned to the nonpregnant range in the 2nd and 3rd trimesters. In contrast, 1st trimester FT4 immunoassay values were either comparable or lower than controls and by the 2nd and 3rd trimesters had decreased to approximately 65% of controls. CONCLUSION: Neither FT4 immunoassay accurately reflects established free T4 changes during pregnancy. TT4 and the FT4I retained an appropriate inverse relationship with TSH throughout pregnancy and appear to provide a more reliable free T4 estimate.

Effect of thyroid peroxidase antibodies on thyroid-stimulating hormone reference limits in a primarily Latina population.

The aim of the paper is to determine the prevalence of thyroid peroxidase antibodies (TPOAb) and assess its effect on the thyroid-stimulating hormone (TSH) reference range during pregnancy in a primarily Latina population. Serum samples were collected from healthy pregnant women and non-pregnant controls. TSH reference ranges were calculated when TPOAb-positive patients were either included or excluded. A total of 134 pregnant women and 107 non-pregnant controls were recruited. Positive TPOAb titres were found in 23 (17.2%) of the 134 pregnant women, and in 14 (13.1%) of the 107 non-pregnant controls. When the TPOAb-positive women were included in the TSH analysis, the upper reference limit using two different methods was consistently higher: 0-2.2 fold in the non-pregnant women, 2.01-2.78 fold in the first trimester, 3.18-4.7 fold in the second and 1.05-1.42 fold in the third. The lower TSH reference limit was not affected by the inclusion of TPOAb-positive subjects. In conclusion, inclusion of TPOAb-positive patients results in higher upper reference limits during pregnancy.

Measuring thyroglobulin and thyroglobulin autoantibody in patients with differentiated thyroid cancer.

Measurement of serum thyroglobulin is primarily used as a tumor marker in the postoperative management of patients with differentiated thyroid cancer. Unfortunately, the technical quality of current thyroglobulin assay methods varies and influences the clinical utility of this test. Two different methodologic approaches are used to measure serum thyroglobulin: the original competitive radioimmunoassay methodology and noncompetitive immunometric assay methods. Although the newer immunometric assays offer the technical benefits of eliminating the use of isotopes, using smaller specimen volumes, and having higher sensitivity potential, shorter turnaround times and the convenience of automation, immunometric assays also have a higher propensity for interference from both thyroglobulin autoantibodies and heterophilic antibodies, if present in the specimen. It is critical that physicians understand the technical limitations inherent in thyroglobulin measurement in order to effectively use this test for the postoperative management of patients with differentiated thyroid cancers.

Lifestyle still predicts mortality in older men with established vascular disease.

BACKGROUND: It is uncertain whether accepted associations between health behaviors and mortality are pertinent to elderly people. No previous studies have examined the patterns of lifestyle in elderly men with and without clinically evident vascular disease by using a lifestyle score to predict survival. METHODS: We measured prevalence of a healthy lifestyle (four or more healthy behaviors out of eight) and examined survival in 11,745 men aged 65-83 years participating in a randomized population-based trial of screening for abdominal aortic aneurysm in Perth, Western Australia. After stratifying participants into five groups according to history and symptoms of vascular disease, we compared survival of men in each subgroup with that of 'healthy' men with no history or symptoms of vascular disease. RESULTS: Invitations to screening produced a corrected response of 70.5%. After adjusting for age and place of birth, having an unhealthy lifestyle was associated with an increase of 20% in the likelihood of death from any cause within 5 years (95% CI: 10-30%). This pattern was consistently evident across subgroups defined by history of vascular disease, but was less evident for deaths from vascular disease. CONCLUSIONS: Our results highlight the importance of maintaining a healthy lifestyle through to old age, regardless of history of vascular disease.

A simple lifestyle score predicts survival in healthy elderly men.

BACKGROUND: Although improvements in life expectancy have been attributed in part to the adoption of a more prudent lifestyle, few studies have examined the association of lifestyle with survival, using several lifestyle factors simultaneously, in a healthy elderly population. METHODS: We investigated the association of health related behaviors with mortality in 7989 men aged 65 to 83 years participating in a population-based trial in Perth, Western Australia, by calculating a lifestyle score as a simple tally of how many of eight prudent behaviors each individual followed. RESULTS: Invitations to screening produced a corrected response of 70.5%. Out of a possible score of 8, 46% of men had a score of less than 5. Within 5 years, a total of 703 men (9%) had died from any cause. The hazard ratio in men with a low lifestyle score was 1.3 [95% confidence interval (CI): 1.1-1.5] compared with men with a score of 5 or more. CONCLUSIONS: Lifestyle remains an important predictor of mortality even in old age. Survival in older men without a history of cardiovascular disease can potentially be enhanced by promoting a healthy lifestyle.

Are detection and treatment of thyroid insufficiency in pregnancy feasible?

A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13, 2004. The workshop was sponsored jointly by The National Center on Birth Defects and Developmental Disabilities of The Centers for Disease Control and Prevention (CDC) and The American Thyroid Association. This paper reports on the individual session that examined the ability to detect and treat thyroid dysfunction during pregnancy. For this session, presented papers included: "Laboratory Reference Values in Pregnancy" and "Criteria for Diagnosis and Treatment of Hypothyroidism in Pregnancy." These presentations were formally discussed by invited respondents and by others in attendance. Salient points from this session about which there was agreement include the following: thyrotropin (TSH) can be used as marker for hypothyroidism in pregnancy, except when there is iodine deficiency usually evidenced by elevated serum thyroglobulin (Tg). We need more longitudinal studies of TSH during pregnancy in iodine-sufficient populations without evidence of autoimmune thyroid disease to develop trimester-specific TSH reference ranges. Current free thyroxine (FT4) estimate methods are sensitive to abnormal binding-protein states such as pregnancy. There is no absolute FT4 value that will define hypothyroxinemia across methods. Total thyroxine (TT4) changes in pregnancy are predictable and not method-specific. TT4 below 100 nmol/L (7.8 microg/dL) is a reasonable indicator of hypothyroxinemia in pregnancy. Women with known hypothyroidism and receiving levothyroxine (LT4) before pregnancy should plan to increase their dosage by 30% to 60% early in pregnancy. Women with autoimmune thyroid disease prior to pregnancy are at increased risk for thyroid insufficiency during pregnancy and postpartum thyroiditis and should be monitored with TSH during pregnancy.

Is screening for abdominal aortic aneurysm bad for your health and well-being?

BACKGROUND: The purpose of the present paper was to investigate whether screening for abdominal aortic aneurysm (AAA) causes health-related quality of life to change in men or their partners. METHODS: A cross-sectional case-control comparison was undertaken of men aged 65-83 years living in Perth, Western Australia, using questionnaires incorporating three validated instruments (Medical Outcomes Study Short Form-36, EuroQol EQ-5D and Hospital Anxiety and Depression Scale) as well as several independent questions about quality of life. The 2009 men who attended for ultrasound scans of the abdominal aorta completed a short prescreening questionnaire about their perception of their general health. Four hundred and ninety-eight men (157 with an AAA and 341 with a normal aorta) were sent two questionnaires for completion 12 months after screening, one for themselves and one for their partner, each being about the quality of life of the respondent. RESULTS: Men with an AAA were more limited in performing physical activities than those with a normal aorta (t-test of means P = 0.04). After screening, men with an AAA were significantly less likely to have current pain or discomfort than those with a normal aorta (multivariate odds ratio: 0.5; 95% confidence interval (CI): 0.3-0.9) and reported fewer visits to their doctor. The mean level of self-perceived general health increased for all men from before to after screening (from 63.4 to 65.4). CONCLUSIONS: Apart from physical functioning, screening was not associated with decreases in health and well-being. A high proportion of men rated their health over the year after screening as being either the same or improved, regardless of whether or not they were found to have an AAA.

Population based randomised controlled trial on impact of screening on mortality from abdominal aortic aneurysm.

OBJECTIVE: To assess whether screening for abdominal aortic aneurysms in men reduces mortality. DESIGN: Population based randomised controlled trial of ultrasound screening, with intention to treat analysis of age standardised mortality. SETTING: Community based screening programme in Western Australia. PARTICIPANTS: 41,000 men aged 65-83 years randomised to intervention and control groups. INTERVENTION: Invitation to ultrasound screening. MAIN OUTCOME MEASURE: Deaths from abdominal aortic aneurysm in the five years after the start of screening. RESULTS: The corrected response to invitation to screening was 70%. The crude prevalence was 7.2% for aortic diameter > or = 30 mm and 0.5% for diameter > or = 55 mm. Twice as many men in the intervention group than in the control group underwent elective surgery for abdominal aortic aneurysm (107 v 54, P = 0.002, chi2 test). Between scheduled screening and the end of follow up 18 men in the intervention group and 25 in the control group died from abdominal aortic aneurysm, yielding a mortality ratio of 0.61 (95% confidence interval 0.33 to 1.11). Any benefit was almost entirely in men aged between 65 and 75 years, where the ratio was reduced to 0.19 (0.04 to 0.89). CONCLUSIONS: At a whole population level screening for abdominal aortic aneurysms was not effective in men aged 65-83 years and did not reduce overall death rates. The success of screening depends on choice of target age group and the exclusion of ineligible men. It is also important to assess the current rate of elective surgery for abdominal aortic aneurysm as in some communities this may already approach a level that reduces the potential benefit of population based screening.

C-reactive protein levels and the expansion of screen-detected abdominal aortic aneurysms in men.

BACKGROUND: C-reactive protein (CRP) levels have been shown to predict a number of cardiovascular outcomes. CRP levels have also been found to be elevated in patients with abdominal aortic aneurysms (AAAs). The aim of this study was to assess the relation between CRP levels and rates of expansion of small AAAs. METHODS AND RESULTS: A cohort of men with small aneurysms was identified in a trial of screening with ultrasound scanning. After initial screening, men were rescanned at 6- to 12-month intervals. CRP levels were measured at the first follow-up visit. Rates of expansion and risk factors for expansion were assessed with the use of data from 545 men who attended for at least 1 scan after CRP levels were measured. These men were followed for a median of 48 (range, 5 to 69) months. The mean annual rate of expansion was 1.6 mm. The median CRP level was 2.6 mg/L in men with the smaller AAAs (30 to 39 mm, n=433) compared with 3.5 mg/L in men with larger AAAs (40 to 54 mm, n=112) (P=0.007). The multivariate age-adjusted logistic model confirmed initial aortic diameter to be the only factor associated with rapid expansion with an odds ratio of 7.2 (95% CI, 4.3,12.2) for an initial diameter of 40 to 54 mm relative to one of 30 to 39 mm. CONCLUSIONS: Most small aneurysms expand slowly. CRP levels are elevated in larger aneurysms but do not appear to be associated with rapid expansion. The most useful predictor of aneurysmal expansion in men is aortic diameter.