Hypothyroidism might be related to breast cancer in post-menopausal womenKuijpens, J.L.; Nyklicek, Ivan; Louwman, W.J.; Weetman, A.P.; Pop, Victor; Coebergh, J.W.W. Published in: Thyroid Document version:Publisher's PDF, also known as Version of record General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.-Users may download and print one copy of any publication from the public portal for the purpose of private study or research -You may not further distribute the material or use it for any profit-making activity or commercial gain -You may freely distribute the URL identifying the publication in the public portal Take down policyIf you believe that this document breaches copyright, please contact us providing details, and we will remove access to the work immediately and investigate your claim. An association between breast cancer and thyroid (autoimmune) diseases or the presence of thyroid peroxidase antibodies (TPOAb; a marker of thyroid autoimmune disease) has been suggested. However, little is known about whether women with thyroid (autoimmune) diseases are at increased risk for developing breast cancer. This cross-sectional and prospective cohort study investigated whether the presence of TPOAb or thyroid dysfunction is related to the presence or development of breast cancer. An unselected cohort of 2,775 women around menopause was screened for the thyroid parameters thyrotropin (TSH), free thyroxine (FT 4 ), and TPOAb during 1994. Detailed information on previous or actual thyroid disorders and breast cancer, and on putative factors related to breast cancer and thyroid disorders, was obtained. Clinical thyroid dysfunction was defined by both abnormal FT4 and TSH, and subclinical thyroid dysfunction by abnormal TSH (with normal FT4). A TPOAb concentration Ն 100 U/ml was defined as positive (TPOAb ϩ ). The study group was linked with the Eindhoven Cancer Registry to detect all women with (in situ) breast cancer (ICD-O code 174) diagnosed between 1958 and 1994. Subsequently, in the prospective study, all women who did not have breast cancer in 1994 (n ϭ 2,738) were followed up to July, 2003, and all new cases of (in situ) breast cancer and all cancer-related deaths were registered. Of the 2,775 women, 278 (10.0%) were TPOAb ϩ . At the 1994 screening, 37 women (1.3%) had breast cancer. TPOAbs were (independently) related to a current diagnosis of breast cancer (OR ϭ 3.3; 95% CI 1.3-8.5). Of the remaining women, 61 (2.2%) developed breast cancer. New breast cancer was related to: (1) an earlier diagnosis of hypothyroidism (OR ϭ 3.8; 95% CI 1.3-10.9); (2) the use of thyroid medication (OR ϭ 3.2; 95% CI 1.0-10.7); and (3) low FT4 (lowest tenth percentile: OR ϭ 2.3; 95% CI 1.2-4.6). In the first 3 years follow up, the relationship between FT4 and log-TSH was disturbed in women wi...

Background. Given the longevity of thyroid cancer patients, any impairment in health-related quality of life (HRQoL) during the follow-up period is of considerable concern. Therefore, the fi rst aim of this study was to assess (thyroid cancer specifi c) HRQoL among long-term thyroid cancer survivors and to compare this with the HRQoL of an age-and sex-matched normative population. Secondly, our aim was to investigate which clinical and socio-demographic characteristics and thyroid cancer specifi c problems were associated with HRQoL. Material and methods. All patients diagnosed with thyroid cancer between 1990 and 2008, as registered in the Eindhoven Cancer Registry, received a survey on HRQoL (EORTC QLQ-C30) and disease-specifi c symptoms (THYCA-QoL). The scores were compared with age-and sex-matched cancer free controls (n ϭ 800). A series of multiple linear regression analyses were conducted to investigate the independent associations between clinical, socio-demographic and thyroid cancer specifi c factors with HRQoL. Results. A total of 306 patients (86%) responded to the invitation. Thyroid cancer survivors had signifi cantly lower scores on physical, role, emotional, cognitive and social functioning (p Ͻ 0.001) compared to the normative population after adjusting for comorbidities. Sympathetic problems [feeling chilly (52%), hot fl ushes (40%)], neuromuscular problems [cramp legs (43%) and pain joints/muscles (64%)] and abrupt attacks of fatigue (50%) were the most often reported thyroid cancer specifi c complaints. Thyroid cancer specifi c neuromuscular, concentration, sympathetic and psychological problems explained 41-58% of the variance in HRQoL. Clinical and socio-demographic factors explained a small part of the variance in (thyroid cancer specifi c) HRQoL (1-27%). Conclusion. Long-term thyroid cancer survivors experience more symptoms and deteriorated HRQoL compared to the normative population. Thyroid cancer specifi c neuromuscular, sympathetic, concentration and psychological symptoms are stronger associated with HRQoL than clinical and socio-demographic factors alone. Awareness of these specifi c determinants of HRQoL could help health care practitioners to provide better supportive care.

Objective: Depression is not adequately diagnosed in many cases. Therefore, the question arises as to whether markers exist for depression. We investigated whether the presence of thyroperoxidase antibodies (TPOAbs) during pregnancy can be regarded as a marker for depression in the ®rst year postpartum, particularly in relation to (overt or subclinical) thyroid dysfunction and other determinants of depression. Design: This work was a prospective observational study. Patients: A cohort of 310 unselected women (residing in the Kempen Region, southeastern Netherlands) were visited at 12 and 32 weeks gestation and at 4, 12, 20, 28 and 36 weeks postpartum. Methods: At each visit, TSH, free thyroxine and TPOAb testing was performed, determinants associated with depression were asked for, and depression was assessed (according to the Research Diagnostic Criteria). Multiple logistic regression was performed to determine independent risk factors (odds ratios, ORs) for depression in gestation and/or postpartum depression. Results: Data for 291 women were available for analysis; 41 women (14.1%) had TPOAbs at one or more time points, and 117 women (40.1%) had depression at one or more time points postpartum. The multiple logistic regression analysis showed that TPOAbs were independently associated with depression at 12 weeks gestation and at 4 and 12 weeks postpartum (OR, 95% con®dence interval: 2.4 (1.1±6.0), 3.8 (1.3±7.3) and 3.6 (1.2±7.1) respectively). After the exclusion of women who were depressed at 12 weeks gestation n 70, the presence of TPOAbs during early pregnancy was still found to be associated with the development of postpartum depression (OR, 95% con®dence interval: 2.8 (1.7±4.5); after exclusion of women who had had depression in earlier life n 51, TPOAb during early gestation was still associated with postpartum depression (OR, 95% con®dence interval: 2.9 (1.8±4.3). Conclusions: The presence of TPOAbs during gestation is associated with the occurrence of subsequent depression during the postpartum period and as such can be regarded as a marker for depression.

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Background: Screening pregnant women for thyroid peroxidase antibodies (TPOAb) to identify those at risk for post partum thyroid dysfunction (PPTD) is controversial, mainly because of the low positive predictive value (ppv) of TPOAb. Objectives: To evaluate if the ppv of TPOAb can be enhanced, either by taking into account the time of TPOAb testing, or by combining this parameter with other putative determinants of PPTD such as smoking, family history or other autoimmune diseases. Methods: A prospective study was performed in the Kempenland region (southeastern Netherlands). Three hundred and ten unselected women were visited at 12 and 32 weeks gestation and 4, 12, 20, 28 and 36 weeks post partum. Serial thyroid stimulating hormone (TSH), free thyroxine (fT 4 ) and TPOAb testing was performed. Thyroid dysfunction (TD) was defined as abnormal TSH either in combination with abnormal fT 4 (overt TD) or without abnormal fT 4 (subclinical TD). PPTD was defined as overt TD post partum. Multivariate regression analysis was performed for determining independent risk factors for PPTD. The sensitivity and specificity of TPOAb at different time points and at different concentrations were calculated and presented in receiver operating characteristic (ROC) curves. Women who had experienced PPTD were followed for 2.5-3 years. Results: Data from 291 women were available for analysis. Serum fT 4 declined during pregnancy and returned to baseline values post partum. TD in gestation was present in 23 women (7.9%): serum TSH was transiently decreased in 13 (6 had overt gestational thyrotoxicosis (2.1%)) and increased in 10 (2 had TPOAb). Both point prevalence and concentration of TPOAb decreased during gestation and returned to baseline levels within 12 weeks post partum. TD in post partum was present in 36 women (12.4%): 21 had subclinical and 15 overt TD. Out of the 15 women with overt TD (incidence of PPTD: 5.2%) 10 were positive for TPOAb (TPOAbþ); 9 had thyrotoxicosis (4 TPOAbþ), 5 hypothyroidism (5 TPOAbþ) and 1 thyrotoxicosis followed by hypothyroidism (TPOAbþ). Independent risk factors for PPTD were TPOAb (relative risk (RR) ¼ 27.2), bottle feeding (RR ¼ 11.1) and smoking habits (ever smoked: RR ¼ 3.1; women with PPTD had smoked more cigarettes for a longer period of time). The sensitivity of TPOAb testing was highest at 12 weeks gestation (0.67). The ppv of TPOAb was 0.31-0.75 (depending on time of testing and concentration), increasing slightly to 0.38-0.80 when combined with bottle feeding or smoking habits. There appeared to be an autoimmune form of PPTD in 2/3 of cases and a nonautoimmune form; women with the autoimmune form were at risk for developing permanent hypothyroidism. Conclusions: A maximum of 2/3 of PPTD cases can be predicted from the presence of TPOAb because 1/3 remained negative for TPOAb. The most appropriate time for TPOAb testing is in the first trimester of pregnancy. The combination of TPOAb testing with anamnestic determinants of PPTD does not increase ppv substantially.