Thyrotoxic Phase Research Articles

Postpartum thyroiditis: risk factors, differential diagnosis, clinical features

Postpartum thyroiditis (PT), one of the commonest causes of disturbed thyroid function (TF), is believed to occur in 5% of the women. The present study involving 57 patients with PT was designed to study risk factors and clinical features of this pathology as well as approaches to its diagnosis. Two control groups comprised female carriers of anti- thyroid peroxidase antibodies (TPO-AB) without PT and women having symptoms of Graves disease (GD) in the postpartum period, respectively. Patients with PT were shown to have significantly elevated TPO-AB levels during pregnancy compared with controls. Postpartum GD manifested itself later than PT, it was associated with a significantly higher freeT4 level and a greater thyroid volume. In twenty of the 57 women with PT, it was manifest in the thyrotoxic phase and in the remaining 37 in the hyperthyroid state. The TSH level in the first half of pregnancy was significantly higher in the women that eventually developed a monophasic hypothyroid variant of PT. In the same group, the TPO-AB level at the time of PT diagnosis was significantly higher than in the biphasic variant of PT. Forty (70%) of the 57 women with PT recovered to an euthyroid state by the end of the study whereas in 17 (30%) hypothyroidism persisted. The biphasic variant of PT was manifest starting from the thyrotoxic phase and more frequently ended in the recovery to the euthyroid state (90%) than the monophasic one, the difference being statistically significant. In contrast, the monophasic hypothyroid variant more frequently resulted in persistent hypothyroidism (40%).

Change in Thyroid Autoantibodies According to the Clinical Course of Painless Thyroiditis Excluding Postpartum Thyroiditis

Background: Painless thyroiditis is characterized by painless, destructive inflammation of the thyroid gland. Although thyroid autoantibodies are frequently detected in patients suffering from this condition, the clinical significance of these antibodies is not well understood. Therefore, this study was conducted to investigate the relationship between thyroid function and thyroid autoantibodies in painless thyroiditis according to clinical course. Methods: Patients proven to have painless thyroiditis were retrospectively included in this study. We analyzed their clinical features, thyroid function and titers of thyroid autoantibodies according to clinical course, which was divided into three phases; thyrotoxic, hypothyroid and recovery. Results: Of the 21 patients included in this study, 2 were male and 19 were female. During the thyrotoxic phase, the mean free T4 concentration was 4.03 (2~6.8) ng/mL and the mean concentration of thyroid stimulating hormone (TSH) was 0.02 (0.01~0.07) U/mL. In addition, the titer of antithyroglobulin antibody and antithyroid peroxidase antibody was 298 (4.8~995) U/mL and 3318 (0.1~25280) U/mL, respectively during this phase. During the hypothyroid phase, the mean TSH was 16.3 (4.3-49.5) U/mL and was found to be positively correlated with the level of free T4 observed during the thyrotoxic phase (r = 0.523, P = 0.031). During the recovery phase, the titer of antithyroglobulin antibody was significantly reduced to 180 (38~487) U/mL when compared with the titer taken during the thyrotoxic phase (P = 0.016). Additionally, during the hypothyroid phase, patients found to have antithyroid peroxidase antibody had a higher titer of TSH than those that did not (23.9 (6.5~49.5) vs. 11.2 (5.3~18.2) U/mL, P = 0.004). Conclusion: The titer of free T4 and the presence of antithyroid peroxidase observed during the thyrotoxic phase were related to the titer of TSH during hypothyroid phase. Additionally, the titer of antithyroglobulin antibody was significantly reduced during the recovery phase. (J Korean Endocr Soc 23:245~252, 2008)

Steroid-Responsive Recurrent Encephalopathy Associated with Subacute Thyroiditis

BackgroundSteroid-responsive encephalopathy associated with subacute thyroiditis has, to our knowledge, not been reported previously.Case ReportA 49-year-old woman was found collapsed and brought to our institution with decreased mentality, dysarthria, and gait disturbance. Brain magnetic resonance imaging and angiography were normal but blood tests revealed thyroid-autoantibody-negative thyrotoxicosis. Results of a 99mtechnetium-pertechnetate scan were compatible with the thyrotoxic phase of subacute thyroiditis. 14-3-3 proteins were detected in cerebrospinal fluid. Her mental status began to improve from the day following steroid administration. Recurrent encephalopathy was found 2 months after the initial admission, which was also effectively treated with steroid.ConclusionsWe speculate that steroid-responsive recurrent encephalopathy associated with subacute thyroiditis is a subtype of Hashimoto's encephalopathy, and consider that steroid treatment should not be delayed in suspected patients.

Painless thyroiditis occurring during post-menopausal period, following remission of Graves’ disease

Painless thyroiditis (also called “silent thyroiditis”) is a clinical entity that belongs to the spectrum of autoimmune thyroiditis (1). Patients usually experience an initial thyrotoxic phase, followed by a hypothyroid state and returning to a euthyroid state. This disorder often develops in patients with positive tests for anti-thyroid antibodies during the post-partum period (2). Thyrotoxicosis observed in painless thyroiditis differs from that in Graves’ disease. In the former, thyroid hormones leak into the circulation as a result of thyroid destruction, whereas in the latter anti-TSH receptor antibodies stimulate production and secretion of thyroid hormones. The therapeutic approaches for both disorders are completely different and thus differential diagnosis is important in clinical practice. Here, we describe a patient developing painless thyroiditis during menopausal pe

Graves' Disease after Interleukin-2 Therapy in a Patient with Human Immunodeficiency Virus Infection

Interleukin-2 (IL-2) is a cytokine that regulates the proliferation and differentiation of lymphocytes, and is currently used clinically in the treatment of assorted malignancies. Additionally, IL-2 is being actively investigated in clinical trials for treatment of human immunodeficiency virus (HIV) infection. Patients treated with IL-2 are susceptible to autoimmune thyroid disease (AITD), presenting as thyroiditis, which leads to either thyrotoxicosis or hypothyroidism, if not correctly and promptly identified and treated. IL-2-induced hypothyroidism can also sometimes follow a thyrotoxic phase. However, the development of Graves' disease (GD) in this clinical setting has not been reported to date. Here, we report the case of a 39-year-old HIV-infected man in whom GD developed after IL-2 therapy. We correlated the immunologic parameters pertinent to the patient's HIV infection status with clinical, hormonal, and serologic evidence of GD during its emergence. This revealed an association between peripheral blood cell numbers of specific lymphocyte subpopulations (CD4(+), CD3(+)CD25(+), and naïve T-cells) and serum levels of markers for AITD (free thyroxine [T(4)] and thyroid-stimulating immunoglobulin). Interestingly, no association was found between natural killer (NK) cell numbers and AITD markers. The immunopathogenesis of GD in this patient may be similar to that hypothesized for the GD that occurs in immune-reconstituted patients after combination antiretroviral therapy. From a practical standpoint, we propose that patients who have received or are receiving treatment with IL-2 who show signs of hyperthyroidism need to be carefully evaluated for GD.

Impaired health-related quality of life in Graves' disease. A prospective study

In the acute, thyrotoxic phase, patients with Graves' disease often have both thyrotoxic and neuropsychiatric symptoms. The purpose of this prospective study was to examine health-related quality of life (HRQOL) in newly diagnosed and untreated Graves' patients and the effect of antithyroid medical treatment on HRQOL. In addition, we examined the potential influence of thyroid hormones and psychiatric symptoms on the impairment of HRQOL in the thyrotoxic phase. A total of 30 consecutively referred patients with newly diagnosed and untreated Graves' disease and 34 age-, sex- and education-matched healthy volunteers were included in the study. HRQOL was assessed with the Medical Outcome Study 36-item Short-Form Health Status Survey (SF-36) before treatment, after reaching euthyroidism and 1 year after initiation of treatment. In the thyrotoxic phase of Graves' disease, HRQOL was significantly impaired, in physical, mental and social dimensions. After reaching euthyroidism, the patients reported much fewer limitations on the subscales of SF-36. One year after initiation of treatment, all SF-36 scores had normalized. However, in some patients, HRQOL continues to be impaired even 1 year after initiation of treatment, as reviewed by the individual analysis. The reduced HRQOL in the acute phase of Graves' disease was correlated to depressive and anxiety symptoms, but thyroid-associated orbitopathy also influenced HLQOL. Impaired HRQOL is common in the acute phase of Graves' disease. A significant proportion of the patients demonstrated persistent HRQOL impairment 1 year after initiation of treatment. Improvement of HRQOL in these patients remains a challenge for the clinician.

Postpartum thyroiditis

Postpartum thyroiditis (PPT) is a syndrome of transient thyroid dysfunction occurring in the first postpartum year. A thyrotoxic phase may be brief and unnoticed before a more long-lasting hypothyroid phase occurs. The incidence is variably reported, ranging from 1.9% to 16.7%, perhaps reflecting racial or geographical differences in the distribution of genetic or environmental risk factors such as the titre of thyroid antibodies and the dietary intake of iodine. The syndrome is an autoimmune disorder, strongly associated with the presence of thyroid microsomal antibody in serum. The thyrotoxic phase may be distinguished from Graves' disease by the finding of low, rather than high, uptake of radioactive iodine or technetium in the thyroid. Screening may be valuable in women with other autoimmune disorders such as Type 1 diabetes mellitus. Treatment should be tailored to the symptoms. Significant thyrotoxic problems should be managed with beta-blocking agents, but severe hypothyroid symptoms should be treated with the short-term replacement thyroxine. A small proportion of affected women will remain permanently hypothyroid. There is also a significant risk of recurrent disease after a subsequent pregnancy.

Relationship between silent thyroiditis and recurrent Graves' disease in the postpartum period.

We carried out a close follow-up study of 96 episodes of postpartum hyperthyroidism, which developed in women with a history of Graves' disease. Hyperthyroidism had developed 1-6 months (mean +/- SD, 2.3 +/- 1.4) after delivery. Radioiodine uptake (RAIU) values during the thyrotoxic phase, determined after a 1-week restriction of iodine-rich diet, ranged from very low to very high (1-70%). The group with low RAIU values (group L: < 10%, n = 26) and the normal group (group N: 10-40%, n = 33) showed significantly higher urinary excretion of iodine (UI) than the high group (group H: > 40%, n = 37), and UI in group L was comparable to that in patients with silent thyroiditis. TSH binding inhibiting antibody (TBIAb) values were determined in 87 patients at the RAIU testing, and were above normal in most of them: all in group H, 68% in group N, and 52% in group L. The mean TBIAb value in group H was significantly higher than that in group N or L (P < 0.0001 for both). Fifty-one patients in group L and group N were observed without treatment. Of these, hyperthyroidism resolved spontaneously in 39 patients (76%), in whom transient hypothyroidism developed with substantial frequency. Hyperthyroidism subsequently resumed in 18 (46%) of these 39 between 4 and 9 months (mean +/- SD, 7.1 +/- 2.1) after delivery and did not resume in the other 21. RAIU values, determined again during this later phase of hyperthyroidism, were high enough to indicate Graves' hyperthyroidism in all but one patient. During the postpartum period, TBIAb values increased and then declined in the majority of the patients irrespective of the course of hyperthyroidism. Of the 21 patients who maintained euthyroidism after spontaneous resolution of hyperthyroidism, transient increase in TBIAb was observed in 14. These findings suggest that silent thyroiditis commonly develops concomitantly with the activation of Graves' disease and delays or masks the development of Graves' hyperthyroidism.

Circulating activated T lymphocyte subsets in patients with silent thyroiditis.

In order to investigate the immunological aspects of silent thyroiditis, T lymphocyte subsets were analyzed by two-color flow cytometry in 10 patients with silent thyroiditis in the thyrotoxic phase, 12 patients with silent thyroiditis in the recovery phase, and 11 healthy volunteers as a control. The percentages of CD3+, CD4+, and CD8+ cells were similar in all three groups. In contrast, activated matured T (HLA-DR+CD3+), activated helper/inducer T (HLA-DR+CD4+) and activated suppressor/cytotoxic T (HLA-DR+CD8+) cells were more numerous in both the thyrotoxic and the recovery phases of patients with silent thyroiditis when compared with healthy controls. In a serial study of 6 patients with silent thyroiditis, the percentage of activated helper/inducer T (HLA-DR+CD4+) cells was higher in the thyrotoxic phase than in the recovery phase. These data indicate that the activation of T cells, especially of helper/inducer T cells, might be important for the induction of silent thyroiditis.

Thyrotoxicosis Followed by Hypothyroidism in Patients Treated With Amiodarone

Amiodarone is an iodine-rich drug used in the treatment of resistant cardiac arrhythmias. Amiodarone-induced thyrotoxicosis (AIT) is well recognized and is generally believed to be due to the excess iodine released from the metabolism of the drug, although amiodarone-associated thyroiditis has occasionally been observed. We report the clinical, laboratory, and therapeutic course of nine patients with AIT. The thyrotoxic phase was often followed by mild hypothyroidism during and after antithyroid drug or corticosteroid therapy. The thyroid was tender to palpation in two patients and a fine-needle aspiration biopsy of the thyroid revealed changes consistent with thyroiditis in three patients who underwent biopsy. These findings strongly suggest that the etiology of AIT, at least in some patients, is due, in part, to drug-induced inflammatory changes in the thyroid, as has been reported to occur in lung, bone marrow, and testes. Thus, the AIT may be due to excess iodine, drug-induced thyroiditis, or a combination of the two. The favorable response of AIT to corticosteroids in occasional patients previously reported also suggests that acute thyroiditis was probably present.

Circulating activated T cell subsets in autoimmune thyroid diseases: Differences between untreated and treated patients

To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy.

Serum ferritin concentration in subacute thyroiditis

Serum concentration of ferritin was measured in 20 patients (19 women, one man) with untreated (thyrotoxic phase) subacute thyroiditis, 32 patients (21 women, 11 men) with untreated Graves' disease, 17 patients (all women) with euthyroid Hashimoto's thyroiditis, 12 patients (all women) with hepatitis A (HAV), eight patients (all women) with pneumonia, and 59 normal controls (30 women, 29 men). In female patients with subacute thyroiditis, the serum concentration of ferritin was 163.6 ± 116.3 μg/L (after log transformation, 2.12 ± 0.31 μg/L, mean ± SD), which was significantly higher than values in female Graves' disease ( P < .05), Hashimoto's thyroiditis ( P < .001), pneumonia ( P < .05), and healthy subjects ( P < .001), being 97.9 ± 71.9 μg/L (after log transformation, 1.85 ± 0.42 μg/L), 51.6 ± 53.0 μg/L (after log transformation, 1.48 ± 0.50 μg/L), 88.2 ± 56.3 μg/L (after log transformation, 1.86 ± 0.30 μg/L), and 25.2 ± 7.4 μg/L (after log transformation; 1.16 ± 0.10 μg/L), respectively, but was not significantly different with HAV, being 368.3 ± 514.0 μg/L (after log transformation, 2.32 ± 0.47 μg/L). In a male with subacute thyroiditis, the serum concentration of ferritin was 521.8 μg/L (after log transformation, 2.72 μg/L), which was higher than ±3 SD and ±1 SD of the levels in healthy males (93.0 ± 55.9 μg/L; after log transformation, 1.89 ± 0.27 μg/L) and male Graves' disease patients (257.0 ± 195.5 μg/L; after log transformation, 2.28 ± 0.38 μg/L), respectively. Elevated serum ferritin concentration significantly declined with treatment by either aspirin or prednisolone (paired t test, P < .001). Despite the higher ferritin levels in subacute thyroiditis, serum free thyroxine (FT 4) levels in patients with subacute thyroiditis were significantly lower than those of Graves' disease patients ( P < .01). In addition, patients with untreated Graves' disease had a positive correlation between serum concentrations of ferritin and thyroxine (T 4) ( r = .65, P < .01) or FT 4 ( r = .60, P < .01), but no such significant correlation was observed in patients with untreated subacute thyroiditis. Serial examination of sera from five patients with subacute thyroiditis showed no significant changes in liver function tests. It was speculated that the elevated ferritin levels in patients with subacute thyroiditis was caused not only by thyrotoxicosis per se, but also by other factors such as the inflammation of the thyroid gland.

Increase in antideoxyribonucleic acid antibody titer in postpartum aggravation of autoimmune thyroid disease.

Serum antidouble stranded DNA antibody levels were measured during pregnancy and after delivery in women who had postpartum exacerbations of Graves' and Hashimoto's diseases. The changes in serum anti-DNA antibody levels closely paralleled those in the serum free T4 index, significantly increasing in the thyrotoxic phase 3-8 months postpartum in women with postpartum exacerbations of thyrotoxicosis due to Graves' disease and 1-3 months postpartum in women with postpartum destructive thyrotoxicosis of Graves' and Hashimoto's diseases. No change in anti-DNA antibody level was found in women with no postpartum exacerbations of thyroid diseases, nor could we demonstrate significant increases in serum anti-DNA antibody titers in patients with thyrotoxicosis due to subacute thyroiditis or in normal pregnant and postpartum women. The changes in serum anti-DNA antibody titers may reflect some generalized immunological abnormality in women who have postpartum exacerbations of Graves' or Hashimoto's diseases.

Postpartum thyroiditis

The special characteristics of postpartum thyroid syndromes are summarized in Table 8. Many of the cases will pass unnoticed, although a higher detection rate is to be expected if postpartum thyroid disease becomes better known among physicians and the general public. Screening in early pregnancy of women with a previous or family history of thyroid disease and in women with other autoimmune disorders (such as diabetes mellitus type 1) may be worthwhile. The initial manifestation of postpartum thyroiditis, often appearing during the first three months postpartum, is a thyrotoxic phase characterized by a low RAIU ('painless thyroiditis' or 'destruction-induced thyrotoxicosis'). Subsequently, a transient hypothyroid phase supervenes. In a small proportion of women hypothyroidism becomes permanent. After a subsequent pregnancy recurrence is the rule. Women who are genetically disposed to Graves' disease may experience thyrotoxicosis with a high RAIU usually appearing later than three months postpartum. As the thyroid function abnormalities are usually mild and transient it is often appropriate to withhold treatment. However, in women with pronounced symptoms treatment should be started. When the postpartum period has passed gradual withdrawal of treatment should be attempted. In women who have experienced postpartum thyroid dysfunction, the risk of developing permanent thyroid disease in later life seems important and therefore long-term follow-up is recommended.

Silent thyroiditis: a histologic and immunohistochemical study.

Twenty-six specimens obtained from 23 patients with clinically and laboratory-proven silent thyroiditis were examined histologically; 11 specimens were obtained during the thyrotoxic phase, and 15 specimens during the early or late recovery phase. All specimens showed chronic thyroiditis, focal or diffuse type; and lymphoid follicles were present in about half of the specimens. Most specimens showed neither stromal fibrosis nor oxyphilic cell changes. The follicular disruptions, which varied from moderate to severe and involved nearly all the visible follicles, were characteristic and common histologic features of this disorder. Giant cells were present in about two thirds of specimens. Six of the 7 specimens taken during the late recovery phase showed no follicular disruption. In 3 patients who had follow-up biopsies, the histologic involvement in the initial biopsy specimens clearly had disappeared in the second biopsy specimens. These histologic features indicate that silent thyroiditis may be a form of chronic thyroiditis, i.e., "chronic thyroiditis with marked follicular destruction." Thyroid biopsy is recommended as a useful tool in differentiating this disease from other thyroid diseases causing hyperthyroidism. In addition to the histologic analysis, intrathyroidal lymphocyte subsets were examined immunohistochemically and compared to those in chronic thyroiditis (Hashimoto's thyroiditis). In both silent and chronic thyroiditis, a great majority of lymphocytes infiltrating between thyroid follicles showed a T-cell phenotype, and no significant differences in T-cell and B-cell distribution between the diseases were observed.

Elevation of Anti-DNA Antibody Titer During Thyrotoxic Phase of Silent Thyroiditis

The elevation of anti-DNA antibody titers was observed in two cases of silent thyroiditis; the levels reverted to normal as thyrotoxicosis improved. Biopsy specimens of the thyroid gland revealed chronic lymphocytic thyroiditis. The elevation of anti-DNA antibody titers during the thyrotoxic phase of silent thyroiditis, to our knowledge, has not been reported. In one case, antinuclear antibody testing was also positive during the thyrotoxic phase and became negative in the euthyroid state. These observations provide further support for autoimmunity in silent thyroiditis.

Elevation of anti-DNA antibody titer during thyrotoxic phase of silent thyroiditis

Elevation of anti-DNA antibody titer during thyrotoxic phase of silent thyroiditis

Postpartum Thyroid Dysfunction

Until recently, postpartum thyroid dysfunction generally referred to secondary hypothyroidism due to pituitary failure (Sheehan's syndrome). Although cases of postpartum primary hypothyroidism have been previously reported, 1 the pioneering work of Amino and colleagues 2-4 in Osaka, Japan, followed by three series from Canada, 5 England, 6 and the United States, 7 has led to recognition of the syndrome of postpartum thyroid dysfunction. What is postpartum thyroid dysfunction? This usually refers to postpartum silent (painless) thyroiditis, a syndrome of transient low radioactive iodine uptake thyrotoxicosis followed by hypothyroidism, usually followed by a return to a euthyroid state. The thyrotoxic phase usually occurs between one to three months post partum and lasts for one to two months, while the hypothyroid phase usually occurs between three to six months post partum and lasts for three to five months. This syndrome appears to be the same as the syndrome of silent (painless) thyroiditis,

6 Post-partum hyperthyroidism

The importance of recognizing the frequent occurrence of the destructive (i.e. PPT) and stimulatory (i.e. PGD) causes of PH have been discussed. The estimated prevalence of PH in several geographical regions of Japan, North America and Europe ranges from 2.0-5%. Although the autoimmune basis for GD has been well-established, the clinical and laboratory features of PPT as well as the alterations of humoral and cellular thyroidal immune parameters, the typical needle biopsy evidence of lymphocytic infiltration, and the association with HLA and Gm allotypes associated with the PPT syndrome, favour the view that it is also likely a variant form of subclinical ATD which becomes transiently more active post-partum. Post-partum transient hyperthyroidism with or without transient or permanent hypothyroidism and relapse of GD thyrotoxicosis have been observed in patients with or without a previous history of GD. Hence, an RAIU test is the preferred diagnostic test in differentiating between these two entities, especially in the absence of associated stigmata of GD. When the RAIU test is suppressed, other causes such as thyrotoxicosis factitia and iodine exposure should be excluded. Without an RAIU test, only a rapid and spontaneous resolution of post-partum hyperthyroidism, accompanied by laboratory confirmation of a subsequent hypothyroid phase, can indirectly facilitate the differentiation between PGD and PPT. In the first trimester of pregnancy, an increased FT4I has been proposed as a risk factor for PGD and an increased AMA titre for PPT. Depending upon clinical manifestations, severity, patient and physician preferences, PGD can be treated by one of several choices of conventional therapy. The transient thyrotoxic phase of PPT when relatively asymptomatic may require no therapy, but when symptomatic, only conservative therapy with beta-adrenergic blockers, sedatives and/or tranquilizers is indicated. Close follow-up and long-term surveillance of mothers with PH due to PPT is essential for early detection and management of a possible subsequent hypothyroid phase, which may be symptomatic, but is seldom permanent. Treatment of recurrent episodes of PPT is controversial. Thyrotoxic symptoms are usually mild and transient and can best be managed by symptomatic therapy as indicated. In a few exceptional patients with recurrent episodes, prophylactic treatment with corticosteroid may be warranted but thyroidectomy and ablative radioactive iodine therapy is seldom justified.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of the HLA-DR4 antigen and iodine status on the development of autoimmune postpartum thyroiditis.

HLA-A, -B, and -DR antigens were determined in all 50 women with a serum thyroid microsomal hemagglutination antibody (MsAb) titer equal to or greater than 1:100 in the first trimester of pregnancy in a population of 733 pregnant women. The DR4 antigen was found in 58.0% of the women compared to 33.7% in control subjects, which corresponds to a relative risk of 2.71 (P less than 0.01 by X2 test). The MsAb-positive women were examined regularly during the year after delivery for the development of thyroid dysfunction. The DR4 antigen frequency was found to be even higher, 69.0% (relative risk = 4.36; P less than 0.001), among the 29 women who developed hypothyroidism in the postpartum period. No other HLA antigen deviations were found among those 15 hypothyroid women in whom an initial thyrotoxic phase occurred before hypothyroidism. The B8, DR3 haplotype was found in 3 of 5 women who developed Graves' thyrotoxicosis alone. Urinary iodine excretion measured in some MsAb-positive women 3 (n = 19) or 6 months (n = 29) postpartum, respectively, was compatible with leakage of thyroid iodine during the initial destruction-induced thyrotoxic phase of postpartum thyroiditis, followed by low iodine excretion during the subsequent hypothyroid phase. We conclude that genes coding for the DR4 antigen may have a regulatory influence on MsAb production, which in turn affects the development of postpartum hypothyroidism. Thyroid iodine content and iodine intake also may have an impact on the severity of the thyrotoxic and the hypothyroid phases of autoimmune postpartum thyroiditis.