Autoimmune thyroiditis after elimination of iodine deficiency in Sri Lanka.
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Adolescent↗
Biomedical subjects
J H Lazarus
Publications and source records attributed to J H Lazarus.
Unusual complications of thyroid carcinoma.
Thyroid carcinomas are the most frequent endocrine malignancies. Complications may arise from an established malignancy and these may lead to the initial clinical presentation or cause subsequent problems. In this case report two elderly patients with differentiated and undifferentiated thyroid carcinomas who suffered unusual medical complications are described. The incidence and treatment of thyroid carcinoma is discussed and the importance of fine needle aspiration of thyroid nodules and the recognition of iodine containing radiographic contrast media in the causation of iodine induced thyrotoxicosis is highlighted.
Aged↗
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.
Adolescent↗
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.
Adolescent↗
Thyroglobulin: current aspects of its role in autoimmune thyroid disease and thyroid cancer.
Thyroglobulin (Tg) is a large glycoprotein (molecular weight: 660000) with 2 polypeptide chains of approximately 2768 amino acids each. It functions both as a pro-hormone and storage hormone for thyroid hormones. The complete Tg gene sequence has been determined for human, rat and bovine species. Tg is one of the thyroid autoantigens recognised in patients with autoimmune thyroid disease (AITD). Antibodies to Tg (TgAb) are present in the serum of patients with AITD and are also sometimes present in healthy euthyroid subjects. Though at least 40 antigenic epitopes on human Tg have been identified, only 2 or 3 of these bind TgAb. Epitope mapping studies suggest that TgAb in AITD patients express a restricted binding pattern while TgAb in the serum of healthy individuals do not show such specific binding. There is evidence to suggest that iodination of Tg may alter these epitope binding patterns. TgAb IgG on the other hand, do not appear to be subclass restricted. Several Tg fragments capable of inducing a T-cell response have been described. Tg is routinely used in the postoperative monitoring of patients with differentiated thyroid cancer. Its use has been limited by problems with assay methods which include poor inter-laboratory standardisation, poor inter-assay variation, low functional sensitivity of the assays, hook effects, and interference from TgAb present in patients serum. The use of rh-TSH in stimulating Tg prior to testing has improved the sensitivity of Tg values in the suppressed state.
Autoantibodies↗
Subacute thyroiditis in an immunosuppressed patient.
Subacute thyroiditis is a well-recognized cause of transient thyrotoxicosis, resulting from a destruction injury to the thyroid. The pathogenesis of this condition is not completely understood and there is debate regarding the extent of the contribution of autoimmunity and external agents, such as infections, to this process. We present the first reported case of subacute thyroiditis in a patient who had been on chronic lithium therapy as well as long-term immunosuppression, with cyclosporin and prednisolone, following an allogeneic bone marrow transplant. We speculate that this case suggests a minimal role of autoimmunity in the development of subacute thyroiditis.
Adult↗
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.
Antibody Affinity↗
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.
Autoantibodies↗
Increased central arterial stiffness in hypothyroidism.
Hypothyroidism is associated with cardiovascular dysfunction. It is increasingly apparent that stiffening of central arteries may lead to increased afterload and cardiac dysfunction. We noninvasively studied the peripheral and central pressure waveforms in 12 untreated hypothyroid patients as well as in 12 age-, sex-, and body mass index-matched controls using the technique of pulse wave analysis from recordings at the radial artery. Indexes of arterial stiffness, augmentation index (AI) and augmentation of central arterial pressure (AG), were derived as well as time of travel of the reflected wave (TR), a direct estimate of aortic pulse wave velocity. At baseline, there were no significant differences between the 2 groups in brachial and aortic blood pressures. Hypothyroid patients had significantly higher AI than controls (mean +/- SEM[SCAP], 32.0 +/- 3.4% vs. 17.0 +/- 2.4%; P < 0.0005) even when corrected for heart rate (AI(C); 28.0 +/- 3.2% vs. 17.0 +/- 2.4%; P < 0.006) and AG (13.0 +/- 2.2 vs. 7.0 +/- 2.1 mm Hg; P < 0.03) together with a lower TR (132.0 +/- 4.1 vs. 142.0 +/- 1.5 msec; P < 0.03). After 6 months of therapy with T(4), all patients were euthyroid. AI(C) had decreased in the patient group (23.0 +/- 3.2% vs. 28.0 +/- 3.2%; P < 0.01) as had AG (9.0 +/- 1.5 vs. 13.0 +/- 2.2 mm Hg; P < 0.008), but TR was significantly higher (142.0 +/- 3.0 vs. 132.0 +/- 4.1 msec; P < 0.008). AI correlated with age in all groups (hypothyroid group: r = 0.937; P < 0.0005; control group: r = 0.804; P < 0.0005), but correlated with TSH level only among controls (r = 0.591; P < 0.05). This study confirms that hypothyroidism is associated with increased cardiovascular risk, as evidenced by increased augmentation of central aortic pressures and central arterial stiffness. Furthermore, these abnormalities are reversed after adequate T(4) replacement.
Adult↗
The effects of thyrotoxicosis and its treatment on central arterial stiffness.
OBJECTIVE: To assess central arterial stiffness in thyrotoxicosis using the technique of pulse wave analysis. DESIGN: Case control study designed to determine the effect of thyrotoxicosis on central arterial stiffness and at 6 months after radioiodine treatment. PATIENTS: Twenty (18 women and 2 men) thyrotoxic patients and 20 age- and sex-matched controls were studied at baseline. Thyrotoxic patients were re-studied at 6 months following treatment of thyrotoxicosis with 555 MBq (131)I with no additional therapy for the six-month period. MEASUREMENTS: Using the sphygmocor apparatus, peripheral pressure waveforms were recorded non-invasively from the radial artery and central pressure waveforms were generated from these. Indices of arterial stiffness, central augmentation index (AI), augmentation of central arterial pressure (AG) and central blood pressures were derived. AI corrected for heart rate (AIc) was calculated. RESULTS: Thyrotoxic patients recorded a significantly lower AI (means+/-s.e.m.) compared with controls (15.0+/-2.1 vs 28.0+/-2.1%; P<0.0005) even when corrected for differences in heart rate AIc (20.0+/-2.1 vs 28.0+/-2.1%; P<0.005) as well as AG (6.0+/-0.8 vs 10.0+/-1.1 mmHg; P<0.002) but higher pulse pressure (58.0+/-3.5 vs 47.0+/-2.0 mmHg; P<0.02). At 6 months following treatment, a significant rise in AIc (27.0+/-1.8 vs 20.0+/-2.1%; P<0.005) and AG (11.0+/-1.0 vs 6.0+/-0.8 mmHg; P<0.005) was noted. Lipid profiles were comparable between the groups. CONCLUSIONS: These data suggested that subjects with untreated thyrotoxicosis have a decreased augmentation of central arterial pressure or lowered central arterial stiffness that would not appear to contribute to any excess cardiovascular risk in that condition.
Blood Pressure↗
An abnormal venous clot.
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Diagnosis, Differential↗
Paralysis after a diarrhoeal illness.
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Adult↗
McCune-Albright syndrome: growth hormone dynamics in pregnancy.
Excess GH secretion has a well recognized association with McCune-Albright syndrome. Although there have been a number of reported pregnancies in uncontrolled acromegaly, none has been described in the McCune-Albright syndrome. We have studied the GH and insulin-like growth factor I (IGF-I) profiles in a patient with confirmed McCune-Albright syndrome and GH hypersecretion throughout a successful pregnancy and postpartum period. Prepregnancy, IGF-I was 60.6 nmol/L (normal, 18.0--43.1), and the daytime GH profile measured using assay A was 9.6--14.0 mU/L. At 13 weeks gestation there was a decline of IGF-I to 33.9 nmol/L and in the daytime GH profile (assay A) to 5.4--6.8 mU/L. At 24 weeks, IGF-I had risen to 51.6 nmol/L. A simultaneous daytime GH profile at this time using assay A revealed levels between 21.3--22.1 mU/L, but only 2.1--3.0 mU/L with assay B. Assay A has significant cross-reactivity with human placental lactogen (HPL), unlike assay B. At 36 weeks, IGF-I was still elevated at 56.6 nmol/L, with a daytime GH profile of 16.6--17.7 mU/L using assay A and 1.5--3.9 mU/L with assay B. At 12 weeks postpartum, IGF-I was 71.4 nmol/L, and the daytime GH profile with assay B was 5.6--8.6 mU/L. These data support a picture of GH suppression during pregnancy in acromegaly associated with McCune-Albright syndrome, shown best with assay B, which discriminates between GH and HPL. These results contrast with previous reports of pregnancy in uncontrolled acromegalics, in whom pituitary GH levels were unaffected by pregnancy, and total GH and IGF-I levels were noted to be elevated. These data suggest that GH secretion in a pregnant acromegalic with the McCune-Albright syndrome may not be entirely autonomous, as seen in classic acromegaly, but may be associated with a degree of negative feedback control that could be exerted by a circulating factor of placental origin, probably HPL or placental GH.
Adult↗
Thyroid disease in relation to pregnancy: a decade of change.
Inspection of the references cited in this review indicates that much work has occurred in the area of thyroid and pregnancy during the last decade. Significant advances in our understanding of the immunology of pregnancy and the effect of thyroid disease on this process have taken place. The role of hCG in the physiology of pregnancy and its relevance to thyroid function has been an emerging theme. There is still no clear explanation for the association between thyroid antibodies and infertility or miscarriage. During the last decade a general concensus has developed in relation to the management of hyperthyroidism in pregnancy although there are still variations in antithyroid drug use at this time. The aetiological classification of congenital hyper- and hypothyroidism utilizing new technologies has opened up a new perspective on these disorders. Attention has been drawn to the importance of treating maternal hypothyroidism with adequate thyroid replacement therapy and to the possibility of impaired child neuropsychological development consequent on low maternal thyroid hormone concentration in early gestation in non iodine deficient areas. Significant advances have been made during the last decade in the description of the clinical features and in our understanding of the pathogenesis of postpartum thyroid disease. The importance of long-term follow up of selected patient groups has also been emphasized.
Abortion, Spontaneous↗
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.
Adult↗
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.
Adolescent↗
The quantitative measurement of autoantibodies to thyroglobulin and thyroid peroxidase by automated microparticle based immunoassays in Hashimoto's disease, Graves' disease and a follow-up study on postpartum thyroid disease.
The aim of this study was to investigate the association between various autoimmune thyroid diseases and the presence of anti-TPO and anti-Tg antibodies using two novel automated microparticle based immunoassays developed for the AxSYM analyzer. Serum samples from 65 individuals with Hashimoto's Disease, 38 with Graves' Disease and 80 UK blood donors were assayed. In addition, samples were taken from 50 women known to be positive for TPO antibodies, for up to 24 weeks following delivery. Precision for both assays ranges from 5.7-9.1% CV, while analytical sensitivity was determined to be 1.0 IU/ml for Anti-Tg and 0.3 IU/ml for Anti-TPO. The Anti-TPO test showed positive results in 86% of Hashimoto's Disease and 87% of Graves' Disease. The figures obtained for Anti-Tg were 58% and 73% respectively. Specificity was 94% with Anti-TPO and 99% with Anti-Tg. The postpartum women were divided into 2 groups, group A remained symptomless while group B developed thyroid dysfunction. Within the 2 groups, medians calculated at each time point were compared between and within groups using the Mann-Whitney Rank Sum Test or the Kruskal-Wallis One Way ANOVA on Ranks. Anti-TPO baseline levels (week 6) were statistically different between both groups (median 36 vs. 167 IU/ml, p = 0.002). In group A, the median values increased from 36 to 87 IU/ml within the observation period, although the difference was not statistically significant. In group B, antibody titres showed a statistically significant increase from 168 IU/ml (week 6) up to 676 IU/ml after 20 weeks (p < 0.001). Anti-Tg baseline levels were not statistically different between the two groups. In group A, the median values did not change significantly over time (range: 47-86 IU/ml) whereas antibody titres in group B showed a statistically significant increase from 79 IU/ml (week 6) to 276 IU/ml after 24 weeks (p = 0.002). Results obtained indicate that these assays provide useful tools for the quantitative determination of autoantibodies in both primary diagnosis as shown with the Hashimoto's disease and Graves' disease samples and patient follow-up as demonstrated with the postpartum samples. The automation and high precision of the assays make them perfectly suited to routine diagnostic use.
Autoanalysis↗