A case of postpartum thyroiditis following SARS-CoV-2 infection.

Postpartum thyroiditis (PPT) is characterized by mild thyrotoxicosis occurring within one year of parturition commonly followed by transient hypothyroidism. Having genetic background of autoimmune thyroid disorders is a risk factor for it because the immune reactivation during postpartum period is a trigger for PPT. Pandemic of COVID-19: caused by SARS-CoV-2 infection is a global health problem, and occurrence of Graves' disease and Hashimoto's thyroiditis after the viral infection have been reported but occurrence of PPT with COVID-19 has never been reported. A 29-year-old woman developed general fatigue four and a half months after parturition, and was diagnosed as having PPT: one month before, she had COVID-19. Hereafter, we define the date of delivery as Day 0 to make timeline clear. SARS-CoV-2 infection was diagnosed by PCR on Day 103, its disappearance from the upper airway confirmed on Day 124, and the thyroiditis diagnosed on Day 136. She had been euthyroid on Day 0 and 95, but thyrotoxic on Day 136. Serum thyroglobulin (Tg) concentration was normal in the presence of anti-Tg antibody, other thyroid-related autoantibodies were negative, and by ultrasonography, the thyroid gland was normal in size and no evidence of increased vascularity. Thyroid function returned to normal by Day 172 without any specific drug therapy. In conclusion, although a clear causal relationship could not be found, we documented the world's first case of PPT developed following COVID-19.

Targeted Antenatal Screening for Predicting Postpartum Thyroiditis and Its Evolution Into Permanent Hypothyroidism.

Postpartum thyroiditis (PPT) has a prevalence of 1-22%, with an ~50% rate of evolution into permanent hypothyroidism (PH). PPT risk is assessed by measuring serum thyroid antibodies during gestation, as 1/3-1/2 of Ab+ve pregnant women will develop PPT. Family and personal history positive for autoimmune non-thyroid diseases (AINTDT), and consumption of swordfish increases while consumption of small oily fish decreases the risk of PPT. Monitoring thyroid function in a very high-risk subgroup avoids the costs of the Ab-based universal screening. We aimed at identifying such subgroup in 412 women followed from week 7-11 of gestation to month 12 postpartum. At study entry, we measured serum TPOAb, TgAb, TSH, FT4, FT3, and evaluated seafood consumption, familial history for thyroid diseases and AINTD, and personal history for AINTD. We measured TSH, FT4, FT3 at 1.5, 3, 6, and 12 months postpartum. PPT occurred in 63 women (15.3%), and PH in 34/63 (54%). Based on positivity/negativity for the three histories, women were classified into 8 categories, with PPT rates of 3.8-100%. Seafood consumption allowed further separation of subgroups having different PPT risks. We considered 11 possible strategies, termed [a] through [k]. Strategy [a] consisted in omitting gestational screening, while performing universal postpartum monitoring with TSH and one thyroid hormone; strategy [k] consisted in selective gestational screening with TPOAb and TgAb, based on history and fish consumption, and selective postpartum monitoring in TPOAb and/or TgAb+ve women. The 100% sensitivity, specificity and diagnostic accuracy of strategy [a] were counterbalanced by the highest costs (Euro 32,960 or 523 per each PPT caught). The corresponding numbers for strategy [k] were 78, 95, 93%, and Euro 8,920 or 182/PPT caught. These savings stem from gestational screening being done in 186 women, and postpartum monitoring done in 65/186 women. One gestational screning-free strategy was the cheapest (Euro 2,080 or 83/PPT caught), because based on postpartum monitoring of only 26 women, but had the lowest sensitivity (40%). Identification of pregnant women having different risks for PPT is feasible, with the costless evaluation of history and seafood consumption driving gestational screening of thyroid antibody status and postpartum monitoring of thyroid function.

Impact of positive thyroid autoimmunity on pregnant women with subclinical hypothyroidism. / Impacto de la autoinmunidad antitiroidea positiva en gestantes con hipotiroidismo subclínico.

BACKGROUND: The impact of subclinical hypothyroidism (SH) and thyroid autoimmunity on obstetric and perinatal complications continues to be a matter of interest and highly controversial. AIM: To assess the impact of SH and autoimmunity in early pregnancy on the obstetric and perinatal complications in our population. MATERIAL AND METHOD: A retrospective cohort study in 435 women with SH (TSH ranging from 3.86 and 10 µIU/mL and normal FT4 values) in the first trimester of pregnancy. Epidemiological and clinical parameters were analyzed and were related to obstetric and perinatal complications based on the presence of autoimmunity (thyroid peroxidase antibodies [TPO] > 34 IU/mL). RESULTS: Mean age was 31.3 years (SD 5.2). Seventeen percent of patients had positive TPO antibodies. Presence of positive autoimmunity was associated to a family history of hypothyroidism (P=.04) and a higher chance of miscarriage (P=.009). In the multivariate analysis, positive TPO antibodies were associated to a 10.25-fold higher risk of miscarriage. No statistically significant associations were found with all other obstetric and perinatal complications. CONCLUSIONS: In our region, pregnant women with SH and thyroid autoimmunity had a higher risk of miscarriage but not of other obstetric and perinatal complications.

The effect of vitamin D on thyroid autoimmunity in non-lactating women with postpartum thyroiditis.

The study included 38 non-lactating l-thyroxine-treated women with postpartum thyroiditis (PPT) and 21 matched healthy postpartum women. Women with vitamin D deficiency were treated with oral vitamin D (4000 IU daily), whereas women with vitamin D insufficiency and women with normal 25-hydroxy vitamin levels were either treated with vitamin D (2000 IU daily) or left untreated. Serum hormone levels and thyroid antibody titers were measured at the beginning of the study and 3 months later. 25-hydroxy vitamin D levels were lower in women with PPT than in healthy women. Thyroid peroxidase and thyroglobulin antibody titers inversely correlated with vitamin D status. Apart from increasing serum levels of 25-hydroxy vitamin D and decreasing serum levels of parathyroid hormone, vitamin D reduced titers of thyroid peroxidase antibodies and this effect was stronger in women with vitamin D deficiency. The study's results suggest that vitamin D supplementation may bring benefits to l-thyroxine-treated women with PPT.

Thyroid disorders during pregnancy and postpartum.

An awareness of the gestational changes to thyroid physiology and the impact of uncontrolled thyroid disease on pregnancy and infant outcome is essential for the successful management of hypothyroidism and hyperthyroidism. This review summarizes strategies for the management of thyroid disease in pregnancy and post partum, and it highlights areas where there is still a lack of consensus.

Increased thyroid autoimmunity among women with multiple sclerosis in the postpartum setting.

BACKGROUND: Multiple sclerosis (MS) patients are predisposed to thyroid abnormalities, but the risk for pregnancy-related thyroid pathology among MS patients has not been evaluated. OBJECTIVES: The objectives of this research are to prospectively evaluate the prevalence of thyroid autoimmunity among MS patients in relation to pregnancy, and to investigate its impact on pregnancy outcome, postpartum depression and fatigue. METHODS: Forty-six pregnant MS patients underwent repeat testing for serum thyroid antibodies (Abs), clinical evaluation and thyroid hormone measurement. Results were compared to 35 age-matched healthy mothers. RESULTS: At six months postpartum 35.3% of MS patients presented elevated levels of thyroid Abs compared to 5.7% of controls, p = 0.01. Mean thyroid Ab concentrations among MS patients were significantly reduced during pregnancy and returned to maximal levels at six months postpartum. The proportion of individuals with postpartum thyroid dysfunction did not differ significantly between MS patients and healthy controls (3.4% vs 2.9%, p = 1.00). Elevated thyroid Ab levels did not increase the risk for adverse pregnancy outcome, fatigue or postpartum depression. CONCLUSIONS: Considering the tendency of MS mothers to develop thyroid autoimmunity postpartum and in association to treatments, we recommend screening MS patients for thyroid dysfunction (TSH) during early pregnancy and after delivery.

Positive thyroid peroxidase antibody titer is associated with dysphoric moods during pregnancy and postpartum.

OBJECTIVE: To examine general dysphoric moods prospectively in women who tested positive for thyroid peroxidase autoantibodies (TPO) during pregnancy and postpartum. DESIGN: Longitudinal, correlational, two-group, observational study. SETTING: Perinatal clinics. PARTICIPANTS: Six-hundred thirty-one (631) pregnant women. METHODS: Participants were screened for TPO antibodies, and 63 were TPO euthyroid positive. All were asked to continue into a 6-month postpartum follow-up and 47 agreed. A comparison group of TPO negative women (n = 72) was randomly selected for follow-up. Women were visited monthly for 6 months and a blood sample was obtained to measure thyroid stimulating hormone (TSH), a targeted physical exam was conducted, and a thyroid symptom checklist (Perceived Stress Scale) and the Profile of Mood States (POMS) checklist were completed. RESULTS: Pregnant TPO-positive women had significantly higher depressive symptoms and were more likely to score higher than 20 on the POMS depression (POMS-D) scale than TPO-negative women. The TPO-positive women had significantly higher depression, anger, and total mood disturbance scores postpartum than TPO-negative women, regardless of development of postpartum thyroiditis (n = 25). CONCLUSIONS: Our results suggest that the presence of TPO autoantibodies alone in euthyroid pregnant and postpartum women increases the possibility of negative dysphoric moods, especially depressive symptoms that cannot be explained by stress or demographic factors.

[Concept and management of postpartum thyroid dysfunction].

Postpartum thyroid dysfunction is found in 5-10% of women within one year after delivery. Dysfunction is developed from subclinical autoimmune thyroiditis through immune rebound mechanism and divided into 5 types. Most frequent one is destructive thyrotoxicosis, named as postpartum thyroiditis, which occur in early postpartum period and usually followed by transient hypothyroidism. Some of them progress into permanent hypothyroidism. Graves' disease is also developed mainly after 4 months postpartum and found in one out of 200 postpartum women in general population. Treatment of this dysfunction is principally the same as ordinal thyroid disease except for transient hypothyroidism.

Thyroid physiology and autoimmunity in pregnancy and after delivery.

During pregnancy and after delivery, the maternal thyroid gland faces several metabolic, hemodynamic and immunologic changes. In this article we first summarize the current knowledge on the physiologic adaptation of the healthy thyroid to pregnancy, including variations of thyroid-stimulating hormone and free thyroid hormones, as well as variations of thyroid volume. Our second aim is to illustrate the background of thyroid autoimmunity in this period, which characteristically ameliorates during pregnancy and aggravates after delivery. Although rare during pregnancy, Graves' disease is the most frequent cause of hyperthyroidism, while Hashimoto's thyroiditis is the most frequent cause for hypothyroidism. Both types of thyroid dysfunction may lead to detrimental complications in mother and child and therefore timely recognition and treatment is essential. Postpartum autoimmunity most frequently exacerbates in the form of postpartum thyroiditis, which presents with diverse clinical presentations and may lead to permanent hypothyroidism.

Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study.

OBJECTIVE: To evaluate the progression in time from euthyroidism to overt autoimmune hypothyroidism or to overt autoimmune hyperthyroidism. SUBJECTS AND METHODS: The design is that of a nested case-control study within the prospective Amsterdam autoimmune thyroid disease (AITD) cohort study in which 790 healthy euthyroid women with at least one first or second degree relative with documented AITD were followed for 5 years. Thyroid function tests were assessed annually. Contrast between cases (overt hypothyroidism - TSH>5.7 mU/l and free thyroxine (FT(4))<9.3 pmol/l and overt hyperthyroidism - TSH<0.4 mU/l and FT(4)>20.1 pmol/l, also referred to as events) and controls (matched for age and duration of follow-up). RESULTS: At baseline, the 38 hypothyroid cases had already higher TSH and lower FT(4) concentrations than their 76 controls, and the difference between both the groups persisted 1 year before occurrence of the event. In contrast, neither TSH nor FT(4) values differed between the 13 hyperthyroid cases and their 26 controls at baseline or 1 year before the event. The prevalence of thyroid peroxidase-Ab was higher in both hypothyroid and hyperthyroid cases than in controls. At the time of event, hypothyroid cases were less common among current smokers (P=0.083) and more common in the postpartum period (P=0.006) than their controls, whereas hyperthyroid cases were pregnant more frequently (P=0.063). CONCLUSIONS: The data suggest that progression toward overt autoimmune hypothyroidism is a gradual process taking several years, but in contrast overt autoimmune hyperthyroidism develops faster in terms of months.

Association of CT60 cytotoxic T lymphocyte antigen-4 gene polymorphism with thyroid autoantibody production in patients with Hashimoto's and postpartum thyroiditis.

Strong genetic contribution has been demonstrated to influence the development of autoimmune thyroid disease (AITD) as well as thyroid autoantibody production. In order to assess the relation between CT60 cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism and thyroid autoantibody production, we investigated 180 consecutive newly diagnosed patients with two forms of AITD, 105 with Hashimoto's thyroiditis (HT) and 75 with postpartum thyroiditis (PPT). We evaluated thyroid function, measured antibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg), and determined CT60 CTLA-4 gene polymorphism. In HT, TPO antibody median value was significantly lower in the AA compared to the AG and GG genotypes (65, 122 and 319 U/ml, P<0.005), while the Tg antibody median value was lower in the AA compared to the AG genotype (91 and 189 U/ml, P<0.02). In PPT, the frequency of thyroid autoantibody-positive patients was higher among G-allele-carrying genotypes (P<0.04). Similar to HT, the TPO antibody median value was lower in the AA compared to the AG and GG genotypes (12, 130 and 423 U/ml, P<0.006). Hypothyroid PPT patients were more often thyroid autoantibody-positive (P<0.005) and the TPO antibody median value was higher compared to hyperthyroid PPT patients (500 and 32 U/ml, P<0.0001). The frequency of the G-allele was significantly higher among hypothyroid patients (P<0.05). Our data suggest that in both HT and PPT, the CT60 CTLA-4 gene polymorphism contributes importantly to thyroid autoantibody production. In PPT, the genotype also seems to influence thyroid function, as patients with the polymorphous allele are more prone to develop hypothyroid form of PPT.

Dynamic changes of IgG subtypes of thyroid peroxidase antibody in patients with postpartum thyroiditis.

AIM: To clarify dynamic changes of IgG subtypes of thyroid peroxidase antibody (TPOAb) during the first postpartum year in Chinese patients diagnosed with postpartum thyroiditis (PPT). METHODS: We retrospectively collected serum samples before and 3, 6, 9 and 12 months postpartum from 58 PPT patients. Levels of TPOAb and its IgG subtypes were examined by ELISA. RESULTS: Titers of total TPOAb and its IgG subtypes were lowest before delivery in PPT patients. Following delivery, titers of total TPOAb increased. Concentrations of IgG1 and IgG4 subtypes increased for 3 months postpartum, then became stable. Concentrations of the IgG2 subtype increased gradually until 9 months postpartum. Concentrations of the IgG3 subtype reached a peak at 6 months postpartum and remained at a high level thereafter. In PPT patients with an episode of hypothyroidism, levels of total TPOAb and of the IgG subtypes as well as the IgG1/IgG4 ratios were significantly higher than those in patients with an episode of hyperthyroidism and normal controls. Correlations between titers of TPOAb and thyroid-stimulating hormone levels (positive) and free T(4) levels (negative) were seen 6 months postpartum. CONCLUSION: TPOAb is related to thyroid injury and the IgG1 subtype of TPOAb may play a major role in the damage of the thyroid in PPT.

Postpartum thyroiditis and hypothalamo-hypophysial insufficiency in the same woman with successive pregnancies: a case report.

OBJECTIVE: Although the incidence of postpartum autoimmune disorders of endocrine glands are not rare, the presence of two different entities in the same patient with two different pregnancies is uncommon. METHODS: We present a 35-year-old woman whose story starts with her first pregnancy when she was 29 years old, she had the diagnosis of postpartum thyroiditis with hypothyroidism.We followed up the patient when she had her second pregnancy. RESULTS: When she was being followed up with levothyroxine replacement, 5 years later she had her second delivery after which she had complaints of polydipsia, polyuria, weight loss and had the diagnosis of central diabetes insipitus and she has started desmopressin treatment and 17 months later the delivery she again applied with amenorrhea, continuation of lactation later she noticed oligomenorrhea, and her gonadotropin levels were found to be low as well as her TSH levels, although the L-thyroxine treatment dose was not changed. Dynamic tests of hypophysis revealed hypophyseal insufficiency and repeated hypophyseal MRI was in concordance with lymphocytic hypophysitis which explains the pattern of endocrinological abnormalities after the second delivery. CONCLUSION: This case signals role of autoimmune mechanisms underlying the endocrinopathies seen after successive pregnancies of the same patient.

Pregnancy, postpartum autoimmune thyroiditis, and autoimmune hypophysitis: intimate relationships.

Autoimmune diseases comprise a group of about 85 heterogeneous conditions that can affect virtually any organ and tissue in the body. Many autoimmune diseases change significantly during pregnancy: some ameliorate, some worsen, and others are unaffected. Two autoimmune diseases present prominently in relation to pregnancy: postpartum autoimmune thyroiditis and autoimmune hypophysitis. This article will review the current state of knowledge of the immunological changes that occur during normal pregnancy, and will explore the striking temporal association with pregnancy observed in thyroiditis and hypophysitis.

Circulating lymphocyte subsets and regulatory T cells in patients with postpartum thyroiditis during the first postpartum year.

The lymphocyte subsets and the percentages of activated T cells or regulatory T cells were observed during the course of postpartum thyroiditis (PPT). Heparin anticoagulant vein bloods were collected at 3, 6, 9 and 12 months postpartum consequently from 27 PPT patients and 23 normal postpartum subjects. Lymphocyte surface antigen CD3, CD4, CD8, HLA-DR and CD25 were stained in appropriate combination and detected with fluorescence-activated cell sorter analysis. The percentage of CD4 was significantly lower in both PPT groups with biphasic diseases and isolated hypothyroidism at 3 months postpartum as compared to control postpartum women separately (both P < 0.05). Then, decreased CD4/CD8 ratios were also appeared in these groups. Patients with both positive TPOAb and TgAb had higher percentage of activated T (HLA-DR(+)CD3(+)) cells compared to control postpartum women at 3 months postpartum (P < 0.05). The percentage of activated T cells correlated with a raised percentage of CD8(+) T cell subset (P < 0.001) and a decreased percentage of regulatory T (CD25(+)CD4(+)) cells (P < 0.01). The percentages of regulatory T cells were significantly higher in control postpartum women at 3, 6 and 9 months postpartum compared with non-postpartum women (P < 0.05). However, it was lower in PPT patients at 3 months compared to itself at 6 and 9 months postpartum (P < 0.05). In the early postpartum period of PPT patients, a reduced helper/inducer T cell subset, an increased percentage of activated T cells and a reduced percentage of regulatory T cells were reported, indicating that T cells may play a key role in the pathogenesis of PPT.

Serum pituitary antibodies in normal pregnancy and in patients with postpartum thyroiditis: a nested case-control study.

OBJECTIVES: The aim of this study was to evaluate antipituitary antibody (APA) prevalence in a series of patients with postpartum thyroiditis (PPT) during pregnancy and in the postpartum. DESIGN: We conducted a nested case-control study on consecutive PPT and normal pregnant women at the Centre for Endocrine and Diabetes Sciences in Cardiff and at the Department of Endocrinology in Pisa. METHODS: We enrolled 30 women with PPT: 17 were hypothyroid (Hypo), 7 with hyperthyroidism (Hyper) and 6 with a transient hyperthyroidism followed by hypothyroidism (Biphasic). Twenty-one healthy pregnant women served as controls. APA (measured using indirect immunofluorescence), free thyroxine, free triiodothyronine, TSH, antithyroid autoantibodies, and thyroid ultrasound were performed during pregnancy and postpartum. The stored sera have been sent to Pisa, where serum APA, IGF1, and cortisol were measured. RESULTS: APA were found in 8 out of the 30 PPT patients (26.7%) and in one normal pregnancy (4.7%, P=0.063). Three out of the seventeen Hypo with PPT (17.6%), three out of the seven Hyper PPT (42.8%), and two out of the six Biphasic PPT (33.3%) were positive for APA. APA prevalence was not significantly different in the PPT subgroups (P=0.453). With one exception, APA all increased in the postpartum period (87.5%, P<0.016). Basal serum IGF1 and cortisol were in the normal range with the exception of two patients with positive APA who presented low serum IGF1 levels (36 and 45 ng/ml). CONCLUSIONS: APA are frequently present in the postpartum period in patients affected by PPT. Further studies are necessary to evaluate whether APA in PPT patients are associated with pituitary function impairment.

[Postpartum thyroiditis: current views on unappreciated disease]. / Poporodowe zapalenie tarczycy - wspólczesne spojrzenie na niedoceniana chorobe.

Postpartum thyroiditis is a form of autoimmune thyroiditis developing during the first 12 months postpartum as a consequence of the immunologic flare following the immune suppression of pregnancy. This disease, found in 5-10% of women in a general population and even more frequently in patients suffering from other autoimmune disorders, may re-occur in about 70% of women after a subsequent pregnancy. Postpartum thyroiditis is strongly associated with antithyroid peroxidase antibodies. Patients may present with symptoms of either thyrotoxicosis or hypothyroidism which may be transient or, in some (20-30%) cases of hypothyroidism, permanent in nature. A thyrotoxic phase of postpartum thyroiditis is usually brief and often unnoticed before a more long-lasting hypothyroid phase occurs. The diagnosis of postpartum thyroiditis is based on the observation of abnormal thyroid function tests in a postpartum antithyroid peroxidase- positive woman. In this paper, we discuss the etiopathogenesis, clinical picture, diagnosis, prognosis and treatment of postpartum thyroiditis and provide the reader with some practical guidance concerning dealing with a patient suffering from this disorder.

Smoking and environmental iodine as risk factors for thyroiditis among parous women.

OBJECTIVE: To elucidate whether exposure to some environmental factors, i.e. cigarette smoking and iodine deficiency influence the risk of thyroiditis. METHODS: We identified a cohort of 874, 507 parous women with self-reported information on smoking during pregnancy registered in the Swedish Medical Birth Registry from September 1983 through December 1997. Hospital diagnoses of thyroiditis (n = 286) and hypothyroidism (n = 690) following entry into the cohort were identified by record-linkage with the national Inpatient Registry. The hazard ratio (HR) of smokers compared to non-smokers and the corresponding 95% confidence limits (CL) were estimated by Cox regression. RESULTS: Smoking was inversely associated with risk of overt thyroiditis (adjusted HR = 0.72; CL = 0.54-0.95), even when diagnoses of primary hypothyroidism were included. However, a diagnosis of thyroiditis within 6 months from a childbirth was positively associated with smoking (adjusted HR = 1.88; CL = 0.94-3.76). Being born in areas of endemic goiter was not associated to hospital admission for thyroiditis. Thyroiditis patients who were smokers had more often than non-smokers a co-morbidity with other autoimmune disorders. CONCLUSIONS: Smoking may increase the risk of thyroiditis occurring in the post-partum period and influence the clinical expression of other thyroiditis, especially when occurring as part of a polymorphic autoimmune disease.

Follow up of patients with postpartum thyroiditis: a population-based study.

In this survey we studied the prevalence of permanent hypothyroidism and prognostic factors for its occurrence 3-5 yr after postpartum thyroiditis (PPT); 54 of 120 women with PPT and 50 of 920 healthy women from among 1,040 women followed 4-5 yr earlier for PPT were recalled. Demographic information, signs, and symptoms of thyroid disorders and results of physical exams were documented. Serum T3, T4, RT3U, TSH, and anti-thyroperoxidase (anti-TPO ab) and anti-thyro-gluboline (anti-Tg ab) antibodies were measured. Twenty-two percent of the cases and four percent of the control group had permanent hypothyroidism, p<0.01. Based on the TSH level we divided the case group into two subgroups: PPT-Hypothyroidism (PPT-Hypo) and PPT-Eutyhroidism (PPT-EU); PPT-Hypo had greater titer of anti-TPO ab than PPT-Eu (437+/-283 vs 126+/-221 IU/mL, p<0.001). Comparison of mean peak serum TSH level and anti-TPO ab during the postpartum thyroiditis phase between PPT-Hypo and PPT-Eu in the case group was significant (56+/- 24 vs 23+/- 28 mU/L, p<0.001, and 1960+/-1270 vs 640+/-959 IU/L, p<0.001, respectively). Results of this survey show a high prevalence of permanent hypothyroidism following PPT in Tehran. High titers of anti-TPOAb and TSH levels at postpartum period are prognostic factors for occurrence of permanent hypothyroidism.