Prevalence of thyroid antibodies in Nigerian patients.

BACKGROUND: Thyroid antibody testing is not routinely available in developing countries, and few studies have measured thyroid antibodies in Africans. The significance of thyroid autoimmunity in an African setting is thus unclear. AIM: To determine the prevalence of thyroid antibodies in patients attending a Nigerian teaching hospital. DESIGN: Prospective survey. METHODS: We measured antibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) using an ELISA technique in 104 patients with various thyroid pathologies attending an endocrine referral centre in Lagos, Nigeria. Patients were clinically grouped into Graves' disease (GD) (n = 69), simple non-toxic goitre (SNTG) (n = 21), toxic nodular goitre (TNG) (n = 8) and suspected Hashimoto's thyroiditis (HT) (n = 6). Blood donors without thyroid disease (n = 100) acted as controls. RESULTS: TgAb and TPOAb were found in 4% and 7%, respectively, of healthy adult controls, 11.6 and 76.8% of patients with GD, 25% and 12.5% of patients with TNG and 9.52% and 14.29% of patients with SNTG. TPOAb testing confirmed HT in six patients, and identified two further cases that would have been misdiagnosed without antibody testing. DISCUSSION: Thyroid autoimmunity appears more common in these Nigerian patients than in previous reports from Africa, and TPOAb was significantly associated with auto-immune thyroid disease. The clinical utility of these antibody measurements requires further evaluation in a wider African population.

Sequential studies on thyroid antibodies during pregnancy.

Thyroid antibodies were measured sequentially in 25 pregnant women from a Sri Lankan population. A high prevalence of antithyroid antibodies, particularly antithyroglobulin antibodies (TgAb) had previously been demonstrated in female schoolchildren drawn from this population. In the present study TgAb were detected in 36.8% of nonpregnant controls while thyroid peroxidase antibody (TPOAb) positivity was present in 26.3%. The prevalence of both antibodies in the pregnancy study group showed a progressive decline compared to nonpregnant controls throughout gestation becoming undetectable in the third trimester. The results are consistent with an immunosuppressive effect of pregnancy in a population in whom high thyroid autoantibody titers may have resulted from a recent salt iodization program.

Thyroglobulin autoantibodies in iodized subjects: relationship between epitope specificities and longitudinal antibody activity.

INTRODUCTION: We previously reported a high thyroglobulin autoantibodies (TgAb) prevalence in healthy Sri Lankans after iodine supplementation. In the present study 58 TgAb-positive schoolgirls were followed up after 5 years of continued iodination. The objectives were: (1) to observe the longitudinal profile of TgAb epitope specificities and (2) to examine the relationship between these specificities and the course of thyroid autoimmunity in this population. METHODS: Paired subjects' sera (at onset and at 5-year follow-up) were tested for TgAb, thyroid peroxidase antibody (TPOAb), and TgAb epitope-specificity. Epitope reactivity was determined by employing a panel of 10 murine monoclonal antibodies (Tg-mAbs) directed against 6 Tg antigenic clusters (I-VI) in competitive enzyme-linked immunosorbent assay (ELISA) reactions with test sera. RESULTS: The overall pattern of epitope recognition in individual subject's sera remained preserved over the time period. Nine subjects showed restricted specificities while majority of the subjects were broadly heterogeneous. At follow-up, median TgAb concentration in the restricted group was higher than in the unrestricted (1650 versus 110 kIU/L; p < 0.005). Epitope specificity was a stronger determinant of TgAb persistence than the height of the initial TgAb response or the TPOAb status of subjects. CONCLUSION: Tg epitope reactivity pattern in iodised populations may identify subjects at greater risk of developing autoimmune thyroid disease (AITD).

The role of complement in the pathogenesis of postpartum thyroiditis.

Postpartum thyroiditis (PPT) affects half of the 10% of women who have elevated circulating thyroid autoantibodies during the postpartum year. Because of the similarities between PPT and Hashimoto's thyroiditis, the pathogenic role of complement in PPT has been investigated. Complement fixation by thyroid peroxidase antibodies (TPO Abs) (expressed as log reciprocal titer) in serum from euthyroid TPO Ab-positive women (n = 29) was 0.91 at 1 month postpartum and increased to 1.45 by 12 months postpartum; complement C3 activation, measured by enzyme-linked immunosorbent assay, in a similar group of women (n = 75) was 0.05 at delivery and increased to 0.33 by 6 months postpartum. In women with PPT, there was greater TPO Ab-related complement activation during the postpartum year; complement fixation increased from 1.00 at 1 month postpartum to 1.48 at 4 months postpartum (P < 0.005) (n = 25), and C3 activation increased from 0.11 at delivery to 0.63 at 6 months postpartum (P < 0.005) (n = 73). Bioactive TPO Ab (TPO Ab x C3 index) was significantly higher in PPT women (55 kilo international units of activity (kIU)/L at 6 months postpartum) (Hashimoto range, 30-108 kIU/L) compared with euthyroid TPO Ab-positive women (< 9 kIU/L at all time points; P < 0.005). Serum samples from TPO Ab-negative control women showed no interaction with complement in either assay at any time during the postpartum year (complement fixation < 0.7; complement C3 activation index < 0.01). This detailed examination of the role of complement in the pathogenesis of PPT shows that TPO Ab-driven complement fixation is a marker for thyroid dysfunction in TPO Ab-positive women. The levels of bioactive TPO Ab in PPT fall within the range seen in Hashimoto's thyroiditis, suggesting similarities in their pathology.

Association of postpartum thyroid dysfunction with antepartum hormonal and immunological changes.

Postpartum thyroid dysfunction (PPTD) develops during the first 9 months in up to 50% of women who have thyroid peroxidase antibodies (anti-TPOAb +ve). Humoral immunity in PPTD has been well documented, but the cellular immunological events accompanying the Th2 to Th1 state postpartum are less clear. Peripheral blood lymphocyte cytokine secretion was examined in 48 TPOAb +ve and 33 TPOAb -ve women at 36 wk gestation and at 6, 12, and 24 wk postpartum. Eighteen women with PPTD had significantly greater secretion of interferon gamma and IL-4 than euthyroid women at 36 wk gestation with no significant differences in cytokine secretion at other time points. Also, at 36 wk gestation, the median plasma cortisol concentration in the PPTD group was significantly lower than the euthyroid group (442 nmol/liter vs. 567 nmol/liter, P < 0.02). There were no differences between the groups in levels of prolactin, progesterone, or estradiol. These data suggest that there may be less immunological suppression at 36 wk in TPOAb +ve women destined to develop PPTD possibly because of lower levels of cortisol. Thus, the immunological determinants of PPTD may in part occur antenatally, although the mechanism(s) for this is still unclear.

Reversible adrenocorticotropin deficiency due to probable autoimmune hypophysitis in a woman with postpartum thyroiditis.

The natural history and pathogenesis of lymphocytic hypophysitis remain poorly understood. We describe a 34-yr-old woman with postpartum thyroiditis and ACTH deficiency, studied at monthly intervals for 18 months after pregnancy. A significant titer of thyroid peroxidase autoantibodies was detected at 16 weeks gestation, and she was recruited into a prospective study of postpartum thyroid function. Four months postpartum she developed mild hyperthyroidism [free T4 (fT4), 27 pmol/L; TSH, less than 0.2 mU/L] and showed a rise in thyroid peroxidase and thyroglobulin autoantibodies. At 9 months postpartum, serum fT4 and fT3 levels were low normal (8.0 and 1.7 pmol/L, respectively), but TSH was not raised (0.4 mU/L). Subsequent investigation showed a low basal plasma cortisol level (28 nmol/L) in association with undetectable ACTH, and subnormal cortisol responses to depot Synacthen (535 nmol/L at 6 h) and hypoglycemia (peak, 145 nmol/L). FSH, LH, GH, and PRL function and computerized tomography of the pituitary were normal. Retrospective analysis of serum samples taken throughout the postpartum year showed developing hypocortisolemia between 3-9 months postpartum. Each sample was also tested for pituitary autoantibodies using a specific indirect immunofluorescent assay; none was detected. The ACTH deficiency recovered spontaneously, with normal cortisol responses to depot Synacthen (greater than 1380 at 6 h) and hypoglycemia (peak, 590) 14 and 18 months postpartum, respectively. This case illustrates that postpartum pituitary deficiencies are potentially reversible. The pattern of pituitary deficit and postpartum thyroiditis supported a diagnosis of autoimmune hypophysitis.

Postpartum thyroiditis and long-term thyroid status: prognostic influence of thyroid peroxidase antibodies and ultrasound echogenicity.

Postpartum thyroid dysfunction (PPTD) occurs in 5% of women, with hypothyroidism developing in 23% of these after 3-5 yr. We have determined the prognostic significance of thyroid peroxidase antibody (TPOAb), thyroid ultrasound morphology (U/S), human leukocyte antigen haplotype, and postpartum thyroid status on the development of thyroid dysfunction 77-81 months after PPTD. Ninety-eight TPOAb-positive [48 who had developed PPTD (group 1) and 50 without PPTD (group 2)] and 70 TPOAb-negative (group 3) women (derived from 145 TPOAb-positive and 229 TPOAb-negative cohorts at the index pregnancy), with comparable ages, parity, pregnancies after index pregnancy, and follow-up duration, were studied. Thyroid dysfunction occurred in 46% of group 1 vs. 4% of group 2 (P<0.001) and 24.5% of groups 1 and 2 vs. 1.4% of group 3 (P<0.001). Factors predictive of thyroid dysfunction included a hypothyroid form of PPTD, TSH more than 20 mU/L, and higher TPOAb levels (213.8 kIU/L in group 1 vs. 131.8 kIU/L in group 2; P<0.002) during the postpartum period. Although TPOAb was higher in group 1 than in group 2 at follow-up (166 vs. 97.7 kIU/L; P<0.03), there was no significant fall in TPOAb levels within either group during the period of follow-up. The prevalence of ultrasound hypoechogenicity was higher in group 1 than in group 2 at follow-up (76% vs. 52%; P<0.006), but U/S improved in 62.5% of group 1 during the period of follow-up. Human leukocyte antigen DR10 was lower in those who developed late thyroid dysfunction. These data, representing the longest follow-up of PPTD women, clearly show that the hypothyroid form of PPTD, high TPOAb levels, and a hypoechogenic U/S pattern lead to a high risk (relative risk, 32) of long term thyroid dysfunction. This compares with a relative risk of 12.9 for TPOAb- and PPTD-positive women, who remained euthyroid at the end of the first postpartum year, and 2.8 for TPOAb-positive but PPTD-negative women, all compared to TPOAb-negative women. Therefore, long term surveillance of TPOAb- and PPTD-positive women (group 1) is indicated.

Thyroid peroxidase autoantibody fingerprints. II. A longitudinal study in postpartum thyroiditis.

It is not known whether epitopes recognized by autoantibodies in an individual remain constant or change over time, especially during perturbations of the humoral immune response. To address this question, we studied the epitopic profile ("fingerprint") of autoantibodies to thyroid peroxidase (TPO) in the sera of 19 women during the postpartum period. Fingerprints were determined in competition studies using 4 recombinant F(ab). At delivery and at 3 time intervals over the subsequent 9-12 months, the pool of F(ab) inhibited autoantibody binding to TPO by 80-100%, consistent with the definition by these F(ab) of a TPO immunodominant region (A1, A2, B1, and B2 domains). Despite a wide spectrum among individuals, the TPO epitopic fingerprints for all 19 women were relatively unchanged throughout the postpartum period. Fingerprint constancy occurred regardless of fluctuations in serum TPO autoantibody levels. When assessed numerically as a ratio of inhibition by the A domain F(ab) to inhibition by the B domain F(ab), the A/B domain ratios in individual women ranged from 0.2 (predominantly B domain) to more than 3.0 (predominantly A domain). However, for each individual woman, the A/B epitopic ratio was conserved throughout the study interval. Our TPO autoantibody epitopic fingerprint data have potential implications for understanding the humoral autoimmune response in man. First, the present study indicates a remarkable lack of spreading of B cell epitopes during a state of perturbation of the immune system over a period of 1 yr. Second, and perhaps more important, despite marked variations in TPO epitopic profiles among different individuals, their constancy over time suggests that TPO autoantibody fingerprints may be inherited.

Labelling and immunoprecipitation of thyroid microsomal antigen.

Human thyroid microsomes have been solubilized, labelled with 125I, immunoprecipitated with microsomal antibody and analysed by gel electrophoresis. The analysis indicated that two peptides of relative molecular masses 108 and 118 kDa, under reducing conditions, were specifically immunoprecipitated by microsomal antibody. Similar values were obtained under non-reducing conditions indicating that the two peptides were not linked by disulphide bridges to each other or to different peptides. These results suggest that the microsomal antigen contains two components which may be linked by non-covalent bonds to form a single protein of 230 kDa. Studies with lectin affinity columns suggested that the antigen was glycosylated.

Stress protein expression in primary and immortalized cultures of human thyroid cells: a model system for the study of stress proteins in the pathogenesis of autoimmune thyroid disease.

Stress has, for many years, been linked to the onset of autoimmune disease and, in particular, autoimmune thyroid disease (AITD). Whilst the exact mechanism of this association is unknown, it is clear that episodes of stress can induce profound changes in the immune system. More specifically, recent studies from several laboratories have shown an association between the expression of stress proteins and, particularly, the Hsp70 family with AITD. Our own studies describe a thyroid-specific Hsp70 which shares antigenicity with the key thyroid autoantigen, thyroid peroxidase. Further studies on the molecular basis for this observation are, however, hampered by the lack of a suitably validated thyroid cell model. In this paper we compare the response of primary cultures of human thyrocytes to hyperthermia with the response seen in the immortalized human thyroid cell line HTori3. Both cell types responded in a broadly similar manner, synthesizing proteins from two of the major stress protein families, Hsp70 and Hsp90. In the primary human thyrocyte cultures the 70 kDa proteins showed a 7.5-fold increase and the 90 kDa proteins a 2.7-fold increase with hyperthermia whilst in the HTori3 cells the increases in response to hyperthermia were 10- and 6.5-fold, respectively. We also show a dose-dependent stress response in HTori3 cells cultured in the presence of arsenite ions. We conclude that the response of this highly differentiated and stable thyroid cell line to stress is similar to that seen in primary cultures of human thyroid cells and that these immortalized cells will afford a convenient and effective model for the further study of the role of stress in the pathology of AITD.

Role of complement in the pathogenesis of postpartum thyroiditis: relationship between complement activation and disease presentation and progression.

The aim of this study was to assess whether the presentation and progression of autoimmune postpartum thyroiditis (PPT) was related to the degree of thyroid peroxidase autoantibody (TPO-ab)-mediated activation of the complement cascade. One hundred and forty-eight thyroid autoantibody-positive women have been followed during their postpartum year. Seventy-five women remained euthyroid during this time whilst the remaining 73 showed one or more episodes of thyroid dysfunction. Fourteen women showed hyperthyroid PPT, 23 showed a biphasic PPT and the remaining 36 showed hypothyroid PPT. Hyperthyroid PPT was always transient but 29 of the 59 women with hypothyroidism remained hypothyroid or still required thyroxine replacement therapy at the conclusion of the study. Thyroid autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), free triiodothyronine and free thyroxine by the Amerlex M methods and thyrotrophin by the Amerlite TSH (monoclonal) assay. Complement component C3b, immobilized as a result of classical complement pathway activation in the presence of TPO/TPO-ab complexes in vitro, was measured by ELISA. Bioactive TPO-ab were calculated as the product of the C3 index and TPO-ab level. Basal levels of complement C3 activation were seen in the euthyroid TPO-ab-positive women (C3 index 0.06 at delivery rising to 0.36 at 12 months postpartum; bioactive TPO-ab activity 0.4 kIU/l at delivery rising to 10.4 kIU/l at 12 months' postpartum (N = 75). These parameters were elevated progressively as the severity of the clinical syndrome increased. In 14 hyperthyroid PPT women the C3 index was 0.47 at 8 months' postpartum (bioactive TPO-ab activity = 20 kIU/I; p vs euthyroid group, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased prevalence of thyroglobulin antibodies in Sri Lankan schoolgirls--is iodine the cause?

OBJECTIVE: Iodine deficiency was the likely cause of a high prevalence of goitre previously in Sri Lankan schoolchildren. Salt iodination was made compulsory in 1993 but there has been no recent study, using modern techniques, of its benefits or harmful effects. METHODS: Three hundred and sixty-seven schoolgirls between the ages of 11 and 16 years had ultrasound thyroid volume, free thyroxine (T4), free tri-iodothyronine (T3), thyrotrophin (TSH), anti-thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) antibodies, and urine iodine concentrations measured. RESULTS: Median ultrasound thyroid volume ranged from 4.8 ml (11-year-old girls) to 8.6 ml (16-year-old girls) with an age-related increase. Median urine iodine concentrations ranged from 105 to 152 microg/l. Free T4 and free T3 were normal in all, but TSH was elevated in four subjects (5. 53-41.29 mU/l). However, the prevalence of TgAb was markedly raised, ranging between 14.3% (11-year-old girls) and 69.7% (16-year-old girls) (P<0.03). In contrast, the prevalence of TPOAb was 10% or less in all age groups. CONCLUSIONS: Normal median thyroid volumes, iodine concentrations and thyroid function would indicate that iodine deficiency is not a major problem in this group. The high prevalence of TgAb, hitherto unreported, most likely reflects excessive iodination of Tg resulting in increased immunogenicity. There is an urgent need to continuously monitor the adequacy and risks of iodination in this population.

Major histocompatibility complex class II and complement polymorphisms in postpartum thyroiditis.

The objective was to re-evaluate the association between class II HLA-DR and DQ MIIC antigens and postpartum thyroiditis (PPT) and to determine the prevalence of the class III complement allotypes of Properdin factor B (Bf), C4A and C4B in this condition. Two hundred and sixty-five (of 2897) pregnant women screened positive for thyroid autoantibody activity took part. Further blood samples were obtained for HLA class II (185) and complement (193) typing. The severity of the ensuing PPT was assessed by measuring thyroid function during the postpartum year. The HLA-DR and DQ phenotypes were assigned from restriction fragment length polymorphism analysis, and Bf, C4A and C4B allotypes were determined by immunofixation with anti-Bf or anti-C4 antibodies after electrophoresis. A weak association between the HLA class II antigens and PPT, as indicated by a reduced frequency of DR15 and DQ6 together with an increased frequency of-DR5 and DQ7, was confirmed. However, only the change in DR5 frequency remained significant after correction (corrected p < 0.05). Postpartum thyroiditis was also associated with frequency disturbances in BI and C4A allotypes but not C4B allotypes. Whilst this study has not provided evidence of a strong marker gene for PPT, it does not preclude the involvement of the MIIC in this condition. These data show disturbances in complement allotype frequencies, suggesting that the class III region may provide a useful focus for further study of this pathology.

Evolution of thyroid autoimmunity during iodine prophylaxis--the Sri Lankan experience.

OBJECTIVE: To study the evolution of thyroid autoimmunity, in relation to the change in goitre prevalence, during 3 Years of iodine prophylaxis in Sri Lanka. METHODS: Two groups of Sri Lankan schoolgirls between the ages of 10.8 and 17.5 Years were studied in 1998 (401 girls) and 2001 (282 girls). A prospective study was performed in 42 schoolgirls who were thyroid autoantibody (Ab)-positive (+ve) in 1998. Anthropometric measures, urinary iodine excretion (UIE), thyroid Volume, free thyroxine, free tri-iodothyronine, TSH, and thyroglobulin (Tg) and thyroid peroxidase (TPO) Ab were evaluated in all 683 girls. RESULTS: Goitre prevalence was significantly lower in 2001 compared with 1998 related to age (2.9% compared with 20.2%) and body surface area (11.6% compared with 40.8%), although UIE was unchanged. Prevalence of thyroid Ab in 2001 was also lower (23.4% compared with 49.9%); among those with the Ab, 34.8% had TgAb alone and 46.9% had a combination of TgAb+TPOAb, compared with 82.0% TgAb alone in 1998. In 2001, subclinical hypothyroidism was more frequent in Ab+ve (6.3%) than Ab-negative girls (1.0%). A cohort of 42 Ab+ve schoolgirls in 1998 (34 with TgAb alone, eight with TgAb+TPOAb) were evaluated again in 2001. Only 10 of them (23.8%) remained Ab+ve (mostly TPOAb+/-TgAb) in 2001. CONCLUSIONS: This study demonstrates that: (1) in 2001, goitre prevalence and thyroid autoimmunity rates were significantly lower than in 1998; (2) the pattern of thyroid Ab was different in the two surveys; (3) in 2001 alone, the occurrence of hypothyroidism was correlated with the presence of thyroid autoimmunity. These results indicate an evolution of thyroid autoimmune markers during the course of iodine prophylaxis, which has not been described before.

Postpartum thyroiditis.

Post partum thyroiditis occurs in 50% of TPO AB+ve women and is characterised by transient hyperthyroidism followed by transient hypothyroidism during the first six months, post partum. A third of the latter group develop permanent hypothyroidism. The syndrome is seen in 5-9% of women and post partum thyroid dysfunction (PPTD) reoccurs in 75% of women in a subsequent pregnancy. An increase in depressive symptomatology is seen in women with PPTD as well as in ante TPO Ab+ve women without PPTD. The immunology of PPT is associated with the presence of TPO antiboides with those IgG subclasses best able to activate the complement cascade. The HLA-DR frequencies seen in PPT suggest that PPT may be related to Hashimoto's thyroiditis. TPO Ab driven complement fixation is seen in PPT and complement activation relates to the extent and progression of thyroid damage. Recent studies have shown an increase in both Th2 and Th1 cytokine release from lymphocytes in ante partum women destined to develop PPTD. More data are required on the cellular immune changes both ante partum and post partum in PPT.

Postpartum thyroiditis: an organ specific syndrome which is not associated with a postpartum polyclonal B-cell activation.

Recent reports have detailed the presence of autoantibodies characteristic of non-organ specific autoimmune diseases in the serum of patients with autoimmune postpartum thyroiditis (PPT). These observations suggest that PPT could be part of a polyclonal B-cell activation postpartum. We have measured 4 non-organ specific autoantibodies (anti-DNA, anti-cardiolipin, anti-nuclear factor (ANF) and antibodies against extractable nuclear antigens (ENA)) together with autoantibodies against thyroglobulin and thyroid peroxidase in a group of PPT women at 4 time points during the first year postpartum (early, time of hyperthyroidism, time of hypothyroidism, late). Whilst 18/18 patients showed thyroid specific autoantibody changes there was only a low frequency of occurrence of the non-organ specific autoantibodies (ENA 2/18; ANF 1/18; anti-DNA 2/18; anti-dsDNA 0/18; anti-cardiolipin 0/18) and, when positive, the response was poor. We conclude that PPT is not associated with a polyclonal b-cell activation but is a postpartum rebound of a thyroid specific autoimmune phenomenon.

The clinical spectrum of postpartum thyroid disease.

The clinical and biochemical features of postpartum thyroid disease were analysed in 152 antithyroid peroxidase antibody-positive (anti-TPO+ve) women and compared with 239 anti-TPO-ve age-matched control postpartum women. All were assessed monthly for up to 12 months postpartum. Seventy three anti-TPO+ve women developed postpartum thyroiditis (PPT): 19.2% hyperthyroid alone, 49.3% hypothyroid alone, and 31.5% characterized by hyper- followed by hypothyroidism. None of the antibody-negative women developed any thyroid dysfunction. A significant increase in many of eleven symptoms of hypothyroidism and some of eight symptoms of hyperthyroidism compared to control women was observed in all anti-TPO+ve women, independent of thyroid status. This was particularly seen in women who later developed PPT when they were euthyroid, but was also observed in euthyroid anti-TPO+ve women who showed no decline of thyroid function during the postpartum period. Although PPT is usually transient, this condition, and the euthyroid antibody-positive state, may be associated with significant symptomatology, including an increased incidence of minor to moderate depression. Early recognition of this syndrome by antenatal screening of thyroid antibodies may contribute to improved management of women during the postpartum period.

Complement activation in postpartum thyroiditis.

BACKGROUND: Postpartum thyroid dysfunction (PPTD) develops in 50% of pregnant women who have raised levels of circulating thyroid peroxidase autoantibodies (TPOAb) at booking. Although these antibodies are able to activate the complement cascade in vitro, it is not known whether complement activation plays any role in the pathogenesis of this disease. AIM: To investigate potential and actual activation of the complement system in women with postpartum thyroiditis. DESIGN: Complement activation was monitored on a weekly basis in 24 postpartum women who had raised TPOAb at 16 weeks gestation, attending an antenatal clinic in Mid-Glamorgan, Wales. METHODS: ELISA procedures were used to measure both in-vitro complement C3 activation by TPOAb and circulating terminal complement complexes (TCC) in serum. RESULTS: Higher levels of bioactive TPOAb activity were seen in women who developed PPTD when compared to those who did not. However, TCC remained undetectable in serum throughout the period of study. CONCLUSIONS: In PPTD, despite the presence of circulating bioactive TPOAbs, the extent of complement activation is inadequate to cause detectable increases in peripheral blood TCC, suggesting that the complement system may not play a major role in PPTD pathogenesis.

Iodine metabolism in postpartum thyroiditis.

To investigate the etiologic role of iodine intake in postpartum thyroiditis (PPT), we have measured postpartum urinary iodine excretion serially in a large prospective study of PPT. A total of 1996 women were screened for thyroid microsomal antibody during the second trimester of pregnancy. One hundred fifty-two of the 235 antibody-positive women and an equal number of age-matched antibody-negative controls were followed postpartum with measurements of urinary iodine and thyroid function at monthly intervals for 12 months. Iodine excretion in the immediate postpartum period did not differ between the 73 women who developed PPT and the antibody-negative controls. In women with PPT with hyperthyroidism, hypothyroidism, or hyperthyroidism followed by hypothyroidism, increased urinary iodine excretion was observed between 8 and 16 weeks postpartum, which preceded the hormonal disturbances among the women with hypothyroidism. The height of the rise in urinary iodine excretion during the first 20 weeks postpartum correlated with the serum free thyroxine levels (r = 0.61, p less than 0.001). Iodine intake is unlikely to affect the prevalence of PPT. However, these data show that the hyperthyroid phase of PPT is associated with a significant release of intrathyroidal iodine due to thyroid destruction and that the same process also occurs to a lesser extent before the hormonal disturbances associated with hypothyroid PPT.

Thyroid peroxidase antibodies in early pregnancy: utility for prediction of postpartum thyroid dysfunction and implications for screening.

Thyroid peroxidase antibodies (TPOAb) in pregnancy are a marker for postpartum (PPTD) and long-term thyroid dysfunction, with variable sensitivity and specificity in PPTD prediction. To test its utility in prediction, we recruited 308 TPOAb-positive (147 developed PPTD (PPTD group) and 161 remained euthyroid [PPTE group]) and 102 TPOAb-negative women (none developed PPTD), in early pregnancy (median, 18; range, 9-19 weeks' gestation). TPOAb levels were higher in the PPTD group (median) (125.2 kIU/L; p < 0.001), and in its hypothyroid (162.4 kIU.; p < 0.0001), hyperthyroid (114.2 kIU/L; p < 0.007), and biphasic (105.1 kIU/L; p < 0.02) variants, compared to the PPTE group (66.7 kIU/L) The incidence of PPTD was significantly higher with TPOAb levels above 58.2 kIU/L (early pregnancy versus postpartum; relative risk, 1.37 [95% confidence interval [CI] 1.17-1.61] versus 0.78 [95% CI 0.5-1.2]) compared to levels below. The integrated postpartum TPOAb response was higher in the PPTD group (median) (159 kIU/L per week) and its variants (hypothyroid; 199 kIU/L per week; biphasic, 180 kIU/L per week; hyperthyroid, 120 kIU/L per week), compared to the PPTE group (86 kIU/L per week p < 0.004). Median early pregnancy TPOAb levels in the PPTD and PPTE groups correlated well with the postpartum antibody response (r = 0.58, p < 0.001). The sensitivity of TPOAb in PPTD prediction was 100% (early pregnancy and postpartum), specificity 62% (early pregnancy) versus 41% (postpartum) and positive predictive value 48% (early pregnancy and postpartum). The timing of TPOAb testing, the sensitive assay used and the absence of PPTD in TPOAb-negative subjects contributed to this high sensitivity. We recommend TPOAb in early pregnancy as a useful predictor of PPTD, particularly in populations where PPTD does not occur in TPOAb-negative women.