Prediction of postpartum thyroid dysfunction: Can it be improved?

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. 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. 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 (fT4) and TPOAb testing was performed. Thyroid dysfunction (TD) was defined as abnormal TSH either in combination with abnormal fT4 (overt TD) or without abnormal fT4 (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. Data from 291 women were available for analysis. Serum fT4 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 (TPOAb+): 9 had thyrotoxicosis (4 TPOAb+), 5 hypothyroidism (5 TPOAb+) and 1 thyrotoxicosis followed by hypothyroidism (TPOAb+). Independent risk factors for PPTD were TPOAb (relative risk (RR) = 2 7.2), bottle feeding (RR = 11.1) and smoking habits (ever smoked: RR = 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 non-autoimmune form; women with the autoimmune form were at risk for developing permanent hypothyroidism. 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 substantiall

Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum

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 first year postpartum, particularly in relation to (overt or subclinical) thyroid dysfunction and other determinants of depression. This work was a prospective observational study. 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. 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. 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% confidence 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% confidence 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% confidence interval: 2.9 (1.8-4.3). 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 depressio

Cell-mediated immunity and postpartum thyroid dysfunction:A possibility for the prediction of disease

Postpartum (pp) thyroid dysfunction (PPTD) is thought to be caused by an autoimmune (AI) destruction of thyroid follicles during the pp period. The chronic thyroid AI process [already present in pregnancy, as shown by the positivity for thyroid peroxidase antibodies (TPO-Ab)] becomes overt disease in the pp period, and one assumes that this exacerbation represents a rebound phenomenon after a general immunosuppression during pregnancy. The presence of TPO-Ab in pregnancy has been suggested as a predictor for later PPTD development. Apart from B cells, e.g. production of autoantibodies, various functions of the cell-mediated immune (CMI) system, including those of peripheral T cells, monocytes, and dendritic cells (DC), are also disturbed in AI states. The objectives of the present study were: determining alterations in various CMI parameters in pregnancies followed by PPTD vs. those not followed by PPTD; and determining the usefulness of these parameters in the prediction of PPTD. In a prospective study (region: Kempenland, southeast Netherlands), a random sample of 291 women were tested at 12 and 32 weeks gestation and 4 weeks pp for TPO-Ab. Women were followed until 9 months pp, for developing PPTD. PPTD was defined as both: an abnormal TSH, and fT4 pp women developing PPTD and/or being positive for TPO-Ab (n = 26); and thyroidological uneventful control women of the same cohort, matched for age and parity (n = 21), were tested for thyroid-stimulating antibodies, percentages of peripheral blood lymphocyte subsets using fluorescence-activated cell sorter analysis (CD3, CD4, CD8, CD16, CD56, major histocompatibility complex-class II), for monocyte polarization, and for cluster capability of monocyte-derived DC. Results were: 1) 31 women (10.7%) were positive for TPO-Ab (TPO-Ab+) in gestation (12 and/or 32 weeks); 2) 15 women (5.2%) developed PPTD, of whom 10 were TPO-Ab+ in gestation; 3) pregnancy-related CMI alterations consisted of low percentages of CD16+CD56+ natural killer (NK), cells and a low DC cluster capability at 12 weeks gestation (these functions were normalized at 32 weeks gestation); 4) the TPO-Ab+ PPTD+ women (4 hyper, 5 hypo, and 1 hyper/hypo) were characterized by a persistently low percentage of NK cells, a lowered monocyte polarization, and a raised percentage of major histocompatibility complex-class II+CD3+ T cells; 5) the TPO-Ab- PPTD+ women (all 5 hyper) had neither thyroid-stimulating antibodies nor CMI alterations, apart from those normally seen in pregnancy; 6) 21 women were positive for TPO-Ab in pregnancy but did not develop PPTD (they had the same lowered NK cell percentages and monocyte polarization as the TPO-Ab+ PPTD+ cases, but they had normal percentages of activated peripheral T cells and a lower titer of TPO-Ab); 7) determination of the number of NK cells and monocyte polarization hardly contributed to the prediction of PPTD (as compared with TPO-Ab status), because of strong interindividual variation and close association with the presence of TPO-Ab; and 8) combining TPO-Ab assays with testing for activated T cells was the most optimal parameter for the prediction of TPO-Ab+ cases of PPTD in our small test set. We conclude that TPO-Ab+ pregnant women who develop PPTD show several CMI abnormalities other than those seen in normal pregnant women, such as persistently lower percentage of NK cells, a lowered monocyte polarization, and a raised percentage of activated T cells. The latter seems rather specific for the actual PPTD development and is not found in TPO-Ab+ (but PPTD) uncomplicated pregnancies. TPO-Ab- (but PPTD+) women had no signs of CMI abnormalities (apart from those specific for the pregnancy state). Although studied cases are low in number, our data are suggestive for the existence of two forms of PPTD: a TPO-Ab+ (AI) form (two-thirds of patients, classical PPTD pattern); and a TPO-Ab- (non-AI) form (one-third of patients, only hyper). Such assumption implies that, at best, tw

Outcomes After Lumbar Disk Herniation Surgery in the Dutch Population.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: There is only limited data on the outcome of primary surgery of lumbar disk herniation (LDH) in Dutch patients. The objective of this study is to describe undesirable outcomes after primary LDH. METHODS: The National Claims Database (Vektis) was searched for primary LDH operations performed from July 2015 until June 2016, for reoperations within 18 months, prescription of opioids between 6 to 12 months and nerve root block within 1 year. A combined outcome measure was also made. Group comparisons were analyzed with the Student's t-test. RESULTS: Primary LDH surgery was performed in 6895 patients in 70 hospitals. Weighted mean of reoperations was 7.3%, nerve root block 6.7% and opioid use 15.6%. In total, 23.0% of patients had one or more undesirable outcomes after surgery. The 95% CI interval exceeded the 50% incidence line for 14 out of 26 hospitals with less than 50 surgical interventions per year. Although the data suggested a volume effect on undesired outcomes, the t-tests between hospitals with volume thresholds of 100, 150 and 200 interventions per year did not support this (P values 0.078, 0.129, 0.114). CONCLUSION: This unique nationwide claims-based study provides insight into patient-relevant undesirable outcomes such as reoperation, nerve root block and opioid use after LDH surgery. About a quarter of the patients had a serious complication in the first follow up year that prompted further medical treatment. There is a wide variation in complication rates between hospitals with a trend that supports concentration of LDH care

Health-related quality of life and disease specific symptoms in long-term thyroid cancer survivors: A study from the population-based PROFILES registry

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 first aim of this study was to assess (thyroid cancer specific) 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 specific 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-specific symptoms (THYCA-QoL). The scores were compared with age- and sex-matched cancer free controls (n = 800). A series of multiple linear regression analyses were conducted to investigate the independent associations between clinical, socio-demographic and thyroid cancer specific factors with HRQoL. Results. A total of 306 patients (86%) responded to the invitation. Thyroid cancer survivors had significantly lower scores on physical, role, emotional, cognitive and social functioning (p < 0.001) compared to the normative population after adjusting for comorbidities. Sympathetic problems [feeling chilly (52%), hot flushes (40%)], neuromuscular problems [cramp legs (43%) and pain joints/muscles (64%)] and abrupt attacks of fatigue (50%) were the most often reported thyroid cancer specific complaints. Thyroid cancer specific 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 specific) HRQoL (1–27%). Conclusion. Long-term thyroid cancer survivors experience more symptoms and deteriorated HRQoL compared to the normative population. Thyroid cancer specific neuromuscular, sympathetic, concentration and psychological symptoms are stronger associated with HRQoL than clinical and socio-demographic factors alone. Awareness of these specific determinants of HRQoL could help health care practitioners to provide better supportive care

Rising incidence, no change in survival and decreasing mortality from thyroid cancer in The Netherlands since 1989

The incidence of thyroid cancer (TC) is increasing worldwide, partly due to increased detection. We therefore assessed combined trends in incidence, survival and mortality of the various types of TC in The Netherlands between 1989 and 2009. We included all patients ≥15 years with TC, diagnosed in the period 1989–2009 and recorded in The Netherlands Cancer Registry (n=8021). Information on age, gender, date of diagnosis, histological type of tumour and tumour–node–metastasis classification was recorded. Mortality data (up to 1st January 2010) were derived from Statistics Netherlands. Annual percentages of change in incidence, mortality and relative survival were calculated. Since 1989 the incidence of TC increased significantly in The Netherlands (estimated annual percentage change (EAPC)=+1.7%). The incidence rates increased for all age groups (except for females >60 years), papillary tumours (EAPC=+3.5%), T1 and T3 TC (EAPC=+7.9 and +5.8% respectively). Incidence rates decreased for T4 TC (−2.3%) and remained stable for follicular, medullary anaplastic and T2 TC. Five-year relative survival rates remained stable for papillary (88%) and follicular (77%) TC, all age groups and T1–T3 TC (96, 94 and 80% respectively) and somewhat lower for T4 (53%), medullary (65%) and anaplastic TC (5%) in the 2004–2009 period compared with earlier periods. Mortality due to TC decreased (EAPC=−1.9%). TC detection and incidence has been rising in The Netherlands, while mortality rates are decreasing and survival rates remained stable or slightly decreasing