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. Author manuscript; available in PMC: 2026 Feb 19.
Published in final edited form as: Chemosphere. 2011 Jul 6;84(7):863–868. doi: 10.1016/j.chemosphere.2011.06.020

Incidence of Thyroid Disease Following Exposure to Polybrominated Biphenyls and Polychlorinated Biphenyls, Michigan, 1974–2006

Ellen E Yard a, Metrecia L Terrell b, Danielle Rentz Hunt a, Lorraine L Cameron c, Chanley M Small b, Michael A McGeehin a, Michele Marcus a,b,*
PMCID: PMC12915485  NIHMSID: NIHMS2142516  PMID: 21737118

Abstract

Thyroid hormones, which influence body metabolism and development, could be affected by persistent organic pollutants. We sought to examine the relationship between polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) and thyroid disease. We employed incidence density sampling to perform a nested case control analysis of the Michigan Long-Term PBB Cohort. Cohort members (n=3,333) were exposed to PBBs through contaminated cattle feed in 1973–1974 and to PCBs through daily life. Those with detectable serum PBB and PCB concentrations at enrollment were categorized into tertiles of PBB and PCB exposure. Case-patients were cohort members answering “Yes” to “Has a healthcare provider ever told you that you had a thyroid problem?” during follow-up interviews; control-patients were cohort members answering “No”. We used odds ratios (OR) with 95% confidence intervals (CI) to compare odds of thyroid disease by PBB and PCB exposure and by various risk factors. Total cumulative thyroid disease incidence after 33 years was 13.9% among women and 2.6% among men. After adjusting for body mass index, we found no statistically significant differences in odds of any type of thyroid disease among women or men with elevated PBB or PCB exposure. Compared to control-patients, women with thyroid disease had increased odds of being overweight/obese (OR=2.82, 95% CI: 1.94–4.11) and developing infertility (OR=1.71, 95% CI: 1.08–2.69), diabetes (OR=1.61, 95% CI: 1.04–2.51), or arthritis (OR=1.71, 95% CI: 1.18–2.50) during follow-up. Additional research should explore potential associations between PBBs/PCBs and thyroid disease among children exposed in utero.

Keywords: brominated flame retardant, polybrominated biphenyl, polychlorinated biphenyl, persistent organic pollutant, incidence density sampling

1. Introduction

Thyroid hormones influence body metabolism, growth, and development throughout life (Dussault and Ruel, 1987). Unfortunately, up to 12% of the U.S. population has a thyroid disease (Canaris et al., 2000). Although thyroid disease can negatively affect quality of life by causing conditions such as fatigue, depression, and weight gain (Ladenson et al., 2000), most thyroid diseases are treatable if detected. By identifying potential risk factors for thyroid disease, preventive strategies can be developed to identify at-risk persons so they can seek screening and, if warranted, receive treatment.

Exposure to persistent organic pollutants (POPs) could increase risk for thyroid disease (Li et al., 2006). POPs are resistant to degradation, they bioaccumulate (Longnecker et al., 1997; Lohmann et al., 2007), and they can be detected in the environment many years after their initial release (Matthews and Dedrick, 1984; Rosen et al., 1995; Blanck et al., 2000a). POPs include structurally related halogenated organics and brominated flame retardants such as polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). PBDE, which had a worldwide production of 67 metric tons in 2001 (Li et al., 2006), had a geometric mean of 20.5 parts per billion (ppb) in the U.S. population in 2003–2004 (Centers for Disease Control and Prevention, 2010). Although U.S. PBB and PCB production ceased in the 1970s, the U.S. population had detectable levels in 2003–2004, with geometric means of 2.3 ng/g lipid for PBB-153 and 5.0 ng/g lipid for PCB (Centers for Disease Control and Prevention, 2010).

Previous research found associations between POPs and human endocrine conditions, including diabetes (Vasiliu et al., 2006; Lim et al., 2008), low infant birth weight (Givens et al., 2007), and adverse reproductive effects (Lilienthal et al., 2006; Roy et al., 2009). These adverse reproductive effects include male genitourinary problems (Small et al., 2009a; Small et al., 2009b) and female early menarche (Blanck et al., 2000b; Den Hond et al., 2002; Roy et al., 2009). Despite these known risks, research investigating links between POPs and thyroid disease is lacking (Brucker-Davis, 1998). Numerous animal studies reported that brominated flame retardants altered thyroid gland structure in exposed rodents and their offspring (Byrne et al., 1987; Meserve et al., 1992; Hallgren et al., 2001; Branchi et al., 2005; Ellis-Hutchings et al., 2006; Lilienthal et al., 2006). Most human research has been limited to identifying associations between PCBs and thyroid hormone levels (Kreiss et al., 1982; Osius et al., 1999; Hagmar et al., 2001; Persky et al., 2001; Bloom et al., 2003). One notable exception was a small study documenting elevated hypothyroidism among male PBB factory workers (Bahn et al., 1980). To date, no study has examined the relationship between serum PBB concentration and thyroid disease in a large cohort.

Conducting POP research is challenging. U.S. residents have detectable levels of most POPs, thus identifying non-exposed persons for comparisons is difficult. The Michigan Long-Term PBB Study provides a unique opportunity to study POPs through PBB exposure. Detailed information of this study cohort is published elsewhere (Anderson et al., 1979; Landrigan et al., 1979; Fries, 1985). A fire-retardant (FireMaster FF-1, Michigan Chemical Corporation, St. Louis, MI) was unintentionally added to animal feed in Michigan briefly during 1973 and 1974, causing widespread PBB contamination of Michigan livestock. Thousands of Michigan residents unknowingly ingested PBBs when consuming poultry, beef, and dairy products from contaminated animals. Subsequently, the Michigan Department of Community Health (MDCH) established the Michigan Long-Term PBB Study to monitor community members over time and assess long-term and trans-generational health effects.

This cohort can assess the relationship between both serum PBB and PCB exposure and thyroid disease. Compared to the U.S. population, this cohort has much higher PBB exposure (Meester, 1979), but similar PCB exposure (Kreiss, 1985). Thus, this cohort can investigate implications of high exposure to PBBs, a situation that is becoming more relevant because of the increasing environmental prevalence of brominated flame retardants. At the same time, this cohort can demonstrate the implications of current PCB exposure.

Our objective was to examine the relationship between serum PBB and PCB concentrations and thyroid disease in the Michigan PBB cohort. Specifically, our aims were to 1) describe thyroid disease incidence among cohort members, 2) determine whether thyroid disease incidence was related to serum PBB or PCB concentration and other risk factors, and 3) assess potential confounding and effect modification of this relationship by BMI and smoking.

2. Materials and methods

2.1. Subjects

Approximately 4,000 residents enrolled in the Michigan Long-Term PBB Study during the initial enrollment period (1976–1978). At enrollment, subjects completed detailed questionnaires that included demographics and various health outcomes. Following enrollment, investigators updated health outcome information through questionnaires (1991–1993 and 2000–2001) and comprehensive telephone interviews (1997–1998 and 2003–2006). This paper focuses primarily on women because they have a higher incidence of thyroid disease (Canaris et al., 2000; Ladenson et al., 2000); however, we also performed a descriptive analysis among men. We limited analyses to cohort members born on or before July 1, 1973, and who were directly exposed to PBBs through contaminated animal products.

2.2. PBB and PCB assessment

Blood serum PBB and PCB concentrations were assessed during the initial enrollment period by MDCH via capillary gas chromatography with electron capture detection (Kuwahara et al., 1980; Needham et al., 1981). PBB quantification was based on the main FireMaster FF-1 congener, 2,2’, 4,4’, 5,5’ hexa-bromobiphenyl (PBB-153), which was approximately 61% of the fire-retardant chemical mixture (Hass et al., 1978). PCB quantification was based on Aroclor 1254. The total PBB and PCB limits of detection (LOD) were 1.0 and 5.0 parts per billion (ppb), respectively. The PBB-153 detection method had a 7.1%–14.0% coefficient of variation and 80%–90% recovery ranges (Needham et al., 1981). The PCB-Aroclor 1254 detection method had a 12%–30% coefficient of variation and an 82% average recovery (Burse et al., 1980; Needham et al., 1981). Serum lipids were not measured.

Enrollment serum PBB-153 concentration was categorized as at or below the LOD (≤1.0 ppb), with the remainder split into tertiles: low (1.1–2.5 ppb), moderate (2.6–6.0 ppb), and high (≥6.1 ppb) exposure. Similarly, enrollment serum PCB-Aroclor 1254 concentration was at or below the LOD (≤5.0 ppb), with the remainder split into tertiles: low (6.0–7.0 ppb), moderate (8.0–10.0 ppb), and high (≥11.0 ppb) exposure. For both PBB and PCB, participants with serum concentrations at or below the LOD were the referent group.

2.3. Thyroid assessment

Cohort members who reported “Yes” to the question “Has a doctor/health care provider ever told you that you had a thyroid problem?” during a follow-up interview were case patients. This could include underactive/hypothyroidism, overactive/hyperthyroidism, goiter, and thyroid cancer. Persons who reported thyroid disease upon enrollment were asked when their symptoms began; if their symptoms began before 1974, they were excluded. We requested medical records from women who reported thyroid disease during the 1997 telephone interview to verify their diagnosis. Although this medical record confirmation was not part of the case definition, we conducted an additional analysis on the subset of women with medical record-confirmed thyroid disease.

2.4. Statistical analysis

We used SAS (version 9.2; SAS Institute, Cary, NC) for statistical analyses. Cumulative thyroid disease incidence was the proportion of cohort members who developed thyroid disease during follow up. For women, we performed a nested case-control study using all case patients and matching control patients in a 1:4 ratio using incidence density sampling (Richardson, 2004). We employed the following matching criteria: 1) case and control patients were age-matched in 5-year strata to control for potential age effects at initial PBB and PCB exposure (Sweeney et al., 2001), as well as potential changes in thyroid disease diagnostic capabilities over time; and 2) a control patient had to remain in the study and survive to at least the same year when the case patient was diagnosed with thyroid disease (i.e., the index year) without reporting thyroid disease.

We then used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CIs) to assess the relationship between thyroid disease and serum PBB and PCB concentrations. Other covariates assessed were BMI at enrollment, history of smoking prior to the index year, history of pregnancy prior to the index year, history of infertility (defined as seeing a doctor about difficulty in becoming pregnant), history of diabetes, history of arthritis, history of other autoimmune disorders, and history of radiation exposure. BMI was calculated from enrollment height and weight for participants ≥16 years of age at enrollment and categorized as underweight (<18.5), normal weight (18.5–24.9), overweight/obese (>24.9), and unknown. BMI and smoking were left in the final multivariate model if they were statistically associated with reporting thyroid disease (P<0.05) or if they exhibited substantial confounding (>15% change in the odds ratio) or effect modification (P<0.05) with serum PBB or PCB concentrations. For men, we compared all case to all control patients while adjusting for BMI.

3. Results

3.1. Females

The participants in the enrollment interview were 1,930 women born before July 1, 1973. Of these, 405 were excluded (Figure) for the following reasons: 213 (11.0%) had thyroid disease diagnosed before 1974, 181 (9.4%) had no serum PBB sample taken upon enrollment, 6 (0.3%) had unknown thyroid disease diagnosis year, and 5 (0.3%) had unknown thyroid disease status during the enrollment interview. Thus, 1,525 women were eligible for inclusion. On average, they were 25 years of age at PBB exposure (range=1 month–85 years, standard deviation [SD]=17.8 years), and they were monitored for an average of 23 years post-exposure (range=3–33 years, SD=9.45 years). Upon enrollment, participants had a mean serum PBB-153 concentration of 15.0 ppb (range=0.5–1745 ppb, SD=83.3 ppb, median=2.0 ppb). Categorizations were: ≤LOD (n=363, 34.4%), 1.1–2.5 ppb (n=224, 21.2%), 2.6–6.0 (n=241, 22.8%), ≥6.1 (n=228, 21.6%). Mean serum PCB-Aroclor 1254 concentration was 6.7 ppb (range=2.5–100 ppb, SD=6.6 ppb, median=6.0 ppb), with the following categorizations: ≤LOD (n=408, 38.6%), 6.0–7.0 (n=242, 22.9%), 8.0–10.0 (n=165, 15.6%), ≥11.0 (n=158, 15.0%), Unknown (n = 83, 7.9%).

Figure.

Figure.

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Women Participants (Born before July 1, 1973) in the Michigan Long-Term PBB Study, 1973–2006

aWe found 4 case patients who could be matched to only 3 control patients.

bOf the 102 case patients with unknown thyroid disease type, 95 did not participate in an interview where disease type was asked, 4 said no to a thyroid disease in the interview where disease type was asked, and 3 were asked but did not know disease type.

Cumulative thyroid disease incidence among women was 13.9% (n=212) (Figure), with an incidence rate of 6.43 thyroid diseases per 1,000 person-years during follow-up. Mean age at diagnosis was 42 years (range=11–85 years, SD = 15.6 years). Thyroid disease type was ascertained if the woman reported the disease during a telephone interview (n=129 of 212 cases). Of these women, 77 (59.7%) reported an underactive thyroid/hypothyroidism, 8 (6.2%) reported an overactive thyroid/hyperthyroidism, 25 (19.4%) reported another thyroid disease, 17 (13.2%) did not know their thyroid disease type, and 2 (1.6%) had missing responses.

The nested case-control analysis included 212 cases and 844 controls (4 cases could be matched to only 3 controls). Enrollment serum PBB concentration was ≤1.0 ppb (≤LOD) for 38.2% of case- and 33.4% of control-patients, and serum PCB concentration was ≤5.0 ppb (≤LOD) for 42.4% of case- and 37.7% of control-patients (Table 1). Compared to control-patients, a greater proportion of case-patients were overweight/obese at enrollment (52.5% vs. 32.4%, P<0.001) or had a history of infertility (21.3% vs. 14.1%, P<0.001), diabetes (15.1% vs. 10.0%, P<0.05), or arthritis (54.2% vs. 45.3%, P<0.05). Prior to the index year, similar proportions of case- and control-patients smoked or had been pregnant.

Table 1.

Characteristics of Women (Born before July 1, 1973): Age-Matched Case and Control Participants in the Michigan Long-Term PBB Study, 1973–2006

Risk Factor Cases (n = 212) Controls (n = 844)
n % n %
PBB (ppb)
 ≤1.0 (at or below LOD) 81 38.2 282 33.4
 1.1–2.5 39 18.4 185 21.9
 2.6–6.0 56 26.4 185 21.9
 ≥6.1 36 17.0 192 22.8
PCB (ppb)
 ≤5.0 (at or below LOD) 90 42.4 318 37.7
 6.0–7.0 47 22.2 195 23.1
 8.0–10.0 27 12.7 138 16.4
 ≥11.0 30 14.2 128 15.2
 Unknown 18 8.5 65 7.7
Body mass index at enrollmenta,b
 Underweight 7 3.9 27 3.9
 Normal weight 78 43.6 440 63.7
 Overweight/obese 94 52.5 224 32.4
Ever smoked regularlyb,c
 No 169 79.7 659 78.7
 Yes 43 20.3 178 21.3
Ever been pregnantb,c
 No 97 48.3 369 46.2
 Yes 104 51.7 429 53.8
History of infertilityb
 No 133 78.7 523 85.9
 Yes 36 21.3 86 14.1
History of diabetes
 No 180 84.9 760 90.1
 Yes 32 15.1 84 10.0
History of arthritisb
 No 137 68.5 600 76.8
 Yes 63 31.5 181 23.2
History of other autoimmune disorder
 No 206 97.2 827 98.0
 Yes 6 2.8 17 2.0
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Abbreviations: PBB, polybrominated biphenyl; PCB, polychlorinated biphenyl.

a

Calculated for women ≥16 years of age at enrollment.

b

Because of unknown responses, totals do not equal total number of cases and controls.

c

Prior to the index year.

Table 2 presents univariate odds ratios for thyroid disease. Compared to control-patients, case-patients had greater odds of being overweight/obese (OR=2.82, 95% CI: 1.94–4.11, P<0.001) or having a history of infertility (OR=1.71, 95% CI: 1.08–2.69, P<0.05), diabetes (OR=1.61, 95% CI: 1.04–2.51, P<0.05), or arthritis (OR=1.71, 95% CI: 1.18–2.50, P<0.05). Also, compared to control-patients, case-patients had a decreased odds of high PBB exposure (serum PBB concentration ≥6.1 ppb compared to PBB ≤1.0), although this finding was not statistically significant (Table 3).

Table 2.

Univariate Odds Ratios for Incidence of Thyroid Disease among First Generation (Born before July 1, 1973) Age-Matched Women in the Michigan Long-Term PBB Study, 1973–2006

Risk Factor OR 95% CI
Body mass index at enrollment
 Underweight 1.13 0.47, 2.74
 Normal weight 1.00
 Overweight/obese 2.82** 1.94, 4.11
Ever smoked regularlya
 No 1.00
 Yes 0.93 0.64, 1.35
Ever been pregnanta
 No 1.00
 Yes 0.87 0.55, 1.37
History of infertility
 No 1.00
 Yes 1.71* 1.08, 2.69
History of diabetes
 No 1.00
 Yes 1.61* 1.04, 2.51
History of arthritisb
 No 1.00
 Yes 1.71* 1.18, 2.50
History of other autoimmune disorder
 No 1.00
 Yes 1.42 0.55, 3.66
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*

P<0.05

**

P<0.001

a

Prior to the index year

b

In the 2000–2001 questionnaire, diagnosis of arthritis was limited to rheumatoid arthritis.

Table 3.

Multivariate Odds Ratios for Incidence of Thyroid Disease among First Generation (Born before July 1, 1973) Age-Matched Women in the Michigan Long-Term PBB Study, 1973–2006

Unadjusted Adjusteda
OR 95% CI OR 95% CI
PBB (ppb)
≤1.0 (at or below LOD) 1.00 1.00
1.1–2.5 0.74 0.49, 1.13 0.79 0.49, 1.27
2.6–6.0 1.07 0.73, 1.56 1.29 0.84, 1.99
≥6.1 0.67 0.44, 1.02 0.76 0.47, 1.24
PCB (ppb)
≤5.0 (at or below LOD) 1.00 1.00
6.0–7.0 0.83 0.56, 1.24 0.93 0.59, 1.45
8.0–10.0 0.68 0.42, 1.10 0.72 0.43, 1.22
≥11.0 0.81 0.50, 1.29 0.84 0.50, 1.42
Unknown 0.98 0.55, 1.76 1.03 0.50, 2.10
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Abbreviations: PBB, polybrominated biphenyl; PCB, polychlorinated biphenyl

a

Adjusted for BMI at enrollment.

The final models for PBB and PCB were both adjusted for BMI at enrollment (Table 3). Although women with thyroid disease appeared to have increased odds of serum PBB concentration 2.6–6.0 ppb and decreased odds of PBB ≥6.1 ppb and PCB 8.0–10.0 ppb, the odds ratios did not reach statistical significance.

The analyses were repeated while restricting the outcome to hypothyroidism, the most commonly reported thyroid disease (n = 77 of 212 cases). The odds ratios remained unchanged.

We asked women reporting thyroid disease during the 1997–1998 telephone interview (n=97 of 212 case-patients) to provide medical records. Most of these women (n=69, 71.1%) consented to releasing their medical records, and 56 (57.7%) medical records were received. Of these 56 records, 53 (94.6%) confirmed the thyroid disease diagnosis, and 3 (5.4%) did not contain enough information to confirm or refute the self–reported thyroid disease.

3.2. Males

The participants in the enrollment interview were 2,017 men born after July 1, 1973. Of these, 209 were excluded as follows: 178 (8.8%) had no serum PBB measurement taken upon enrollment, 26 (1.3%) had thyroid disease diagnosed prior to 1974, 3 (0.1%) had inadequate follow–up, and 2 (0.0%) had unknown thyroid disease status during follow–up interviews. Thus, 1,808 men were included. On average, men were 27 years of age at PBB exposure (range=1 month–84 years, SD=18.5 years). Participating men were monitored an average of 21 years post-exposure (range=3–29 years, SD=9.5 years). Upon enrollment, the men had a mean serum PBB-153 concentration of 27.5 ppb (range=0.5–1,900 ppb, SD=130.1 ppb, median = 5.0 ppb). Categorizations were: ≤LOD (n=239, 13.2%), 1.1–2.5 ppb (n=272, 15.0%), 2.6–6.0 (n=626, 34.6%), ≥6.1 (n=671, 37.1%). Mean serum PCB-Aroclor 1254 concentration was 8.5 ppb (range=2.0–88 ppb, SD=7.8 ppb, median=7.0 ppb), with the following categorizations: ≤LOD (n=560, 31.0%), 6.0–7.0 (n=346, 19.1%), 8.0–10.0 (n=307, 17.0%), ≥11.0 (n=341, 18.9%), Unknown (n=254, 14.0%).

During follow-up, 47 (2.6%) of the men reported a thyroid disease, with an incidence rate of 1.24 thyroid diseases per 1,000 person-years. The mean age at time of diagnosis was 51 years (range=7–86 years, SD=21.3 years). The men were not asked for their specific thyroid disease type, and medical records were not requested.

At enrollment, 8.5% of case and 13.3% of control-patients had a serum PBB concentration ≤1.0 ppb (≤LOD) (Table 1). For PCB, 19.1% of case- and 31.3% of control-patients had a serum concentration ≤5.0 ppb (≤LOD). Compared to control-patients, a greater proportion of case-patients had a history of smoking (66.7% vs. 48.0%, P<0.05). Similar proportions of case- and control-patients were overweight or obese at enrollment (51.4% and 57.4%, respectively) and developed diabetes (12.8% vs. 9.2%, respectively) or arthritis (61.7% vs. 43.2%, respectively) during follow–up.

Compared to control-patients, case-patients had similar odds of serum PBB concentration 1.1–2.5 ppb (OR=1.70, 95% CI=0.42–6.91), PBB 2.6–6.0 ppb (OR=1.38, 95% CI: 0.38–5.02) and PBB ≥6.1 ppb (OR=1.75, 95% CI: 0.50–6.15) after adjusting for BMI. Additionally, compared to control patients, case patients had similar odds of serum PCB concentration 6.0–7.0 ppb (OR=1.51, 95% CI: 0.52–4.43) and PCB 8.0–10.0 ppb (OR=1.55, 95% CI: 0.54–4.43) after adjusting for BMI.

4. Discussion

In this first large cohort study to examine the association between thyroid disease and serum PBB-153 and PCB-Aroclor 1254 concentrations, we found that thyroid disease incidence is not related to serum PBB or PCB concentrations.

We found that cumulative thyroid disease incidence in the Michigan PBB Long-Term Study was approximately 5 times greater among women (13.9%) than men (2.6%), a finding which is similar to previous reports (Canaris et al., 2000; Aoki et al., 2007). Furthermore, we found women were an average of 9 years younger than men when thyroid disease developed. Because most thyroid diseases can be managed with proper medication, this discovery highlights the importance of monitoring thyroid functioning throughout life to detect thyroid disease early, particularly among women.

Women with thyroid disease, compared with control-patients, had increased odds of being overweight or obese or of having a history of diabetes, infertility, or arthritis. Previous research has found the inverse relationship, finding that untreated thyroid disease can lead to obesity, diabetes, infertility, and arthritis (Knudsen et al., 2005; Trokoudes et al., 2006; Staykova, 2007; Crunkhorn and Patti, 2008). This suggests that some women in our study may have had thyroid disease for some time before it was diagnosed. Because thyroid disease is manageable, this finding suggests that women who are overweight or obese or who have diabetes, infertility, or arthritis could benefit from regular thyroid screening.

We found no relationship between thyroid disease and serum PBB or PCB concentration in the Michigan Long-Term PBB Cohort. One previous study documented increased hypothyroidism incidence among men working in a PBB factory (Bahn et al., 1980; Kreiss et al., 1982). Because PBB exposure was not measured in this previous factory cohort, whether these workers had elevated PBB exposure compared to our men’s study population is unknown. Most of the factory workers were occupationally exposed to PBB through dermal and respiratory routes for several years; in contrast, men in our study were exposed only from 1973–1974 (no men in our study population had worked in a PBB factory). Thus, the factory cohort likely had higher PBB exposure compared to our population, which may be one reason for the contrasting findings. Although the population in the Michigan Long-Term PBB Cohort had higher PBB levels than non-Michigan residents (Meester, 1979), PBB exposure likely does not increase risk of thyroid disease for the general U.S. population.

In contrast to our results, a few previous studies found decreased thyroid hormone levels in animals and humans who had elevated serum PCB concentrations (Kreiss et al., 1982; Hagmar et al., 2001; Persky et al., 2001). The serum PCB concentrations in this cohort were possibly below the threshold needed to produce noticeable, clinical effects. Because we did not measure thyroid hormone levels, any subclinical effects would have gone undocumented.

Because we relied on self–reported thyroid diseases, disease misclassification could have occurred. Study staff did not request medical records from control patients to make sure that thyroid disease was absent. Of the 212 women case-patients in this study, 68 reported a thyroid disease during an earlier follow-up interview but reported no thyroid disease during a subsequent interview (i.e., a discrepant case). To investigate whether these discrepant case-patients could have affected the results, we ran a separate multivariate model that excluded discrepant case- and their matched control-patients; however, the results remained unchanged. Medical records were available for 12 of the 68 discrepant case-patients. Upon review, 11 of these 12 case-patients had confirmed thyroid disease, suggesting that most discrepant case-patients were true case-patients. One possible reason for discrepancy between interviews could be that these case-patients were being treated for their thyroid disease and that when reporting no thyroid disease, they actually reporting that their thyroid hormone levels were in normal range.

This study had several strengths. All cohort members were exposed during a specific time period to a specific PBB congener. In addition, because we measured PBB and PCB concentrations in serum, there was little chance for exposure misclassification.

The Michigan Long-Term PBB Cohort is and will continue to be valuable in assessing the public health effects of PBB and PCB exposures. Future research should determine whether any association exists between PBB and PCB concentration and thyroid disease among children exposed in utero, or any association between other POPs and thyroid disease.

Acknowledgments

This work was supported by NIEHS (grants RO1-ES08341 and RO1-ES012014), the US EPA (grant R825300) and supported by the Centers for Disease Control and Prevention cooperative agreement U37/CCU500392. We thank the staff of the Michigan Department of Community Health, participants of the Michigan Long-Term PBB Study, Jessica Spencer for her medical expertise and advice, and Alden Henderson for his early work on these analyses and the medical records verification.

Abbreviations:

POP

persistent organic pollutant

PBB

polybrominated biphenyl

PCB

polychlorinated biphenyl

MDCH

Michigan Department of Community Health

LOD

limit of detection

ppb

parts per billion

BMI

body mass index

OR

odds ratio

CI

confidence interval

SD

standard deviation

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