Subclinical Autoimmune Thyroid Disease Research Articles

AB0719 ASSOCIATION BETWEEN FIBROMYALGIA AND CHRONIC AUTOIMMUNE THYROIDITIS. RETROSPECTIVE OBSERVATIONAL DATA FROM A MONOCENTRIC ENDOCRINOLOGIST-RHEUMATOLOGIST COLLABORATIVE ANALYSIS

Background:Endocrine and metabolic imbalance conditions can affect the development of subjective abnormal perceptions within fibromyalgia (FMR). In the case of autoimmune thyroid disease (ATD), prolonged, clinically active states of impaired glandular function may be associated with an FMR-type condition. Less clear is the association between subclinical or rapidly well-controlled states of thyroid disease and the presence of FMR, since this assessment, although analysed in some previous studies, was usually performed on cohorts of subjects where the absence of any other confusing factors was not well defined.Objectives:To evaluate the prevalence of subclinical autoimmune thyroid disease, or functionally controlled autoimmune thyroid disease, in a retrospective cohort of consecutively diagnosed patients suffering from fibromyalgia condition.Methods:Over a 2 years period of time (2018-2019) a monocentric joint evaluation was activated with the endocrinology section of our healthcare area in order to consecutively monitor the subjects belonging to both specialist clinics. Patients with ATD were not unfrequently firstly evaluated in the rheumatology ambulatory. Diagnosis of FMR was defined according to the American College of Rheumatology 2010/2011 criteria. At the same time, at the rheumatology clinics, all cases addressed with diagnosis of fatigue or chronic pain of no defined origin were analysed in order to carefully identify any associated, comorbidity problems. The diagnosis of ATD was confirmed according to recognized international criteria. The following results will focus on subjects with chronic Hashimoto type Thyroiditis (HT).Results:Among the HT patients, 98% were women, aged between 28 and 64. Over the 2 years considered period of time, 65 subjects suffering from HT, showing no active disease or unstable endocrine function were addressed to the rheumatology clinics owing to FMR related symptoms. Among them, 55 (84.6%) had a confirmed diagnosis of FMR. Within this time, we recognized 239 consecutive diagnoses of FMR in subjects aging 22-76 years, with a number of 114 found to be devoid of factors (other than ATD) able to be responsible for chronic pain, except for a modest component of situational anxiety, or mild mood depression, not requiring any specific drug intervention. Among the 114, so called “primary” FMR, 35.6% showed to suffer from TCH, under confirmed clinical/hormonal remission, or in a preclinical, early stage of onset. Within the 125 subjects, carrying a FMR condition related to previous or associated fostering pathology, 26.8% were positive for current or previous thyroid problems. The prevalence of TCH, in the “secondary” FMR conditions differed significantly (p<0.01) from that of other FMR promoting diseases (eg connective tissue diseases, such as Sjogren Syndrome), except for moderate-severe mood disorders and/or anxiety, and the most severe chronic osteoarthritis conditions, showing a confirmed secondary neuropathy.Conclusion:Although limited in number, the here reported data confirm the hypothesis of a significant association between ATD and FMR, even in subjects who were considered to be in a subclinical condition or in full clinical remission by the endocrinology colleagues. The physiopathology of this association needs further appropriate insights.Acknowledgements:We thank Dr Alberto Petterle for his previous helpful contributionDisclosure of Interests:None declared

Considerations for Use of Immune Checkpoint Inhibitors in Cancer Therapy for Patients with Co-Existing Thyroid Eye Disease.

Immune checkpoint inhibitors (ICIs) have revolutionised the field of oncology. While most ICIs are well-tolerated, severe and fatal immune-related adverse events (irAEs) have been documented, likely related to the strengthened immunity harnessed by ICIs against tumours. Endocrinopathies are some of the most common irAEs, with both hypothyroidism and hyperthyroidism encountered after ICI use. As such, patients with pre-existing autoimmune conditions, such as Graves’ disease (GD) with clinically active thyroid eye disease (TED), are excluded from most clinical trials studying ICIs due to concerns of exacerbating pre-existing autoimmune conditions or of increasing the potential for irAE development. The limited information currently available on the safety and efficacy of ICIs in this population poses a clinical challenge for oncologists. The objective of this commentary is to highlight these challenges and provide treatment recommendations pertaining to two specific cohorts of patients with GD, namely GD patients with minimal eye complications and GD patients with previous TED who underwent radiotherapy, surgery or pulse methylprednisolone and whose disease is now quiescent, and to patients with subclinical autoimmune thyroid disease.

Technetium-99m thyroid scan; does it have a diagnostic aid in sub-clinical auto-immune thyroid disease in systemic lupus erythematosus patients?

Technetium-99m (Tc-99m) thyroid scintigraphy is a well known diagnostic tool that shows the entire gland in a single image. We aimed to evaluate its additive diagnostic value in subclinical autoimmune thyroid disease (S-AITD) in systemic lupus erythematosus (SLE) patients. We investigated 100 systemic lupus erythematosus (SLE) patients without overt thyroid involvement (eight men and 92 women; mean age 40±6.5 years) and 50 age and sex matched controls. All were subjected to thyroid evaluation using anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) antibodies; hormones (FT3; FT4 and TSH) and Tc-99m thyroid scintigraphy. 14/100 (14%) and none (0%) were positive for S-AITD in SLE and control groups, respectively (P = 0.0001). They were classified by thyroid scintigraphy and hormonal profile into 2/14 Hashimoto; 10/14 atrophic thyroiditis and 2/14 Graves' disease. Anti-TPO was elevated in 12 SLE cases, while anti-TG was elevated in only 2/14 (P = 0.0001). Thyroid scintigraphy showed statistically significant associations with FT4, TSH and anti-TPO. Tc-99m thyroid scintigraphy may have an additional diagnostic role in S-AITD among SLE patients, with an impact on patient management. This potential needs to be further evaluated in a larger series on a multicenter basis.

Subclinical autoimmune thyroid disease and cardiovascular risk factors

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Turner's Syndrome and Subclinical Autoimmune Thyroid Disease: A Two-Year Follow-up Study

Although autoimmune thyroid disease (AITD) is frequent in Turner's syndrome (TS), followup studies are scant, and there are none regarding subclinical thyroiditis. We investigated thyroid function and morphology in 17 patients with TS (mean age 14.6 years) with transient and asymptomatic variations of TSH and/or thyroid hormones. Our 2-year follow-up included measurements of TSH, free T4, T3 and TPO and Tg antibodies, ultrasound (US) (first and last evaluations) and scintigraphy (first evaluation). Thyroid volume was evaluated relative to the patients' stature. Fourteen had abnormal hormones, including four with hypothyroidism and one with hyperthyroidism, ten had positive antibodies, and all had abnormalities on US; uptake was normal in 14/16. Abnormal hormones were independent of antibodies, number of US findings, age, time of disease and volume. At the end of the follow-up, antibodies were associated with a high number of abnormal US features, particularly heterogeneous texture. Our results indicate that recurring thyroid hormone variations in TS are due to chronic AITD.

Clinical and subclinical autoimmune thyroid disease in adult celiac disease.

Our aim was to investigate the occurrence of clinical and subclinical autoimmune thyroid disease in 79 patients with celiac disease as reflected in thyroid function, antibodies, and ultrasound. Since subclinical thyroid diseases are common in the population, 184 nonceliac controls were also studied. Normal thyroid function combined with positive antibodies and marked hypoechogenicity was considered subclinical disease. Autoimmune thyroid disease was observed in 13.9% of celiac patients and in 2.1% of controls (P = 0.0005); and subclinical disease in 10.1% and 3.3%, respectively (P = 0.048). The mean thyroid gland volume was 8.3 ml in celiac patients and 10.4 ml in controls (P = 0.007). Hypoechogenicity was found in 73% of celiac patients and in 42% of controls (P < 0.0001). Positive thyroid antibodies were associated with hypoechogenicity in celiac patients but not in controls. In conclusion, the occurrence of both clinical and subclinical autoimmune thyroid disease was increased in celiac disease; subclinical thyroid disease indicates regular surveillance.

Low birth weight is not associated with clinically overt thyroid disease: a population based twin case-control study.

In recent years low birth weight has been proposed as a risk factor for the development of several chronic diseases in adult life, including diabetes and subclinical autoimmune thyroid disease. The association could, however, also be due to genetic or environmental factors affecting both birth weight and adverse health outcomes in adult life. Moreover, it is at present unknown whether or not low birth weight is associated with an increased risk of developing clinically overt thyroid disease. The aim of the present study was to investigate the impact of birth weight and several other birth characteristics on the development of clinically overt thyroid disease. A twin case-control study of same sex twin pairs. One hundred and thirty-one same sex twin pairs (262 twin individuals) discordant for clinically overt thyroid disease, ascertained from a population based nation-wide twin register. Information about birth weight, birth length, birth order (first vs. second born), and prematurity was obtained from the original midwife records. Forty-nine twin pairs were discordant for clinically overt autoimmune thyroid disease (Graves' disease = 35 and Hashimoto's thyroiditis = 14) and 82 pairs were discordant for overt nonautoimmune thyroid disease (Simple goitre = 79 and toxic nodular goitre = 3). Overall, there was no difference in birth weights between probands and the healthy co-twins in monozygotic (MZ, n = 39) or in dizygotic (DZ, n = 92) pairs (MZ: mean +/- SE: 2619 +/- 93 g vs. 2553 +/- 89 g, P = 0.40; DZ: 2576 +/- 45 g vs. 2585 +/- 49, P = 0.86). By means of logistic regression, the impact of other birth characteristics such as birth length, birth order (first vs. second born), and prematurity was tested. None of the variables reached statistical significance. Subdividing the twin pairs into those discordant for clinically overt Graves' disease, Hashimoto's thyroiditis, and nonautoimmune thyroid disease did not change the results. This is the first study of the effect of birth weight and other birth characteristics on the subsequent development of clinically overt thyroid disease in which maternal, socioeconomic, and to a high degree, genetic factors have been controlled for. Our study did not show any effect of birth weight or any of the other birth characteristics on the risk of developing clinically overt autoimmune or nonautoimmune thyroid disease.

Therapeutic controversy: Screening for postpartum thyroiditis.

Postpartum autoimmune thyroid dysfunction is briefly characterized as a postpartum exacerbation of subclinical autoimmune thyroid disease, wherein some immunological abnormalities are observed before the onset of thyroid dysfunction. Therefore, we can detect the high-risk group for postpartum thyroid dysfunction by screening, in early pregnancy, those with subclinical autoimmune thyroiditis. Among several methods for detecting thyroid autoimmunities, the measurement of anti-thyroid microsomal antibody (MCAb) or thyroid peroxidase (TPO) antibody is the most useful marker for detecting subclinical autoimmune thyroiditis and, therefore, for predicting the occurrence of postpartum thyroid dysfunction. When MCAb is positive, there is always lymphocytic infiltration into the thyroid, indicating subclinical autoimmune thyroiditis (15) that may be exacerbated after delivery. Sixty to seventy percent of women with positive MCAb in early pregnancy develop postpartum thyroid dysfunction (1). Other investigators have also reported that MCAb-positive subjects had approximately 20 –23 times the relative risk (over normal subjects) for developing postpartum thyroid dysfunction (16, 17). On the other hand, the prevalence of postpartum thyroid dysfunction in the MCAb-negative subjects in early pregnancy is estimated as 1/100 of that in MCAb-positive subjects (Fig. 1). So, when we screen 1000 early pregnant women in the general population, we can expect to find about 50 patients with postpartum thyroid dysfunction. Although MCAb is a good marker for the occurrence of postpartum thyroid dysfunction, it gives no information about the type of dysfunction that will occur. Among the various types of dysfunctions, postpartum Graves’ disease is clinically the most important and is predicted by the measurement of thyroid-stimulating antibodies (TSAb) with a sensitive bioassay (18). Our subsequent study (19) revealed that pregnant women with positive TSAb in early pregnancy had a much higher risk of developing postpartum Graves’ disease. We observed 71 pregnant women with positive MCAb from early pregnancy through the postpartum period. Among them, 7 showed positive TSAb, and 5 of those 7 (71%) developed postpartum Graves’ disease. Thyrotoxicosis in 3 of those 5 was transient and spontaneously improved within a year. Graves’ disease did not occur in the TSAb-negative subjects. AntiTSH receptor (TSHR) antibodies (TRAb) with conventional radio-receptor assay (thyrotropin binding inhibitory immunoglobulin; TBII) were not useful in predicting postpartum Graves’ disease. Figure 2 shows a protocol that we have tentatively employed to screen for postpartum thyroid dysfunction at the outpatient maternity clinic of the Osaka University Hospital for several years. In the protocol, MCAb-positive mothers are examined for thyroid status, measuring serum free thyroxine (FT4), serum free triiodothyronine (FT3), serum thyrotropin (TSH), anti-TSHR antibody (TRAb), and antithyroglobulin (TgAb), and are observed every Accepted March 8, 1999. Address correspondence and requests for reprints to: Alex StagnaroGreen, MD, Dean for Student Affairs and Medical Education, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1255, New York, New York 10029-6574. E-mail: stagnaro@smtplink.mssm.edu. Reprints of the Therapeutic Controversies will include all authors and all pages, as shown in the journal. 0021-972X/99/$03.00/0 Vol. 84, No. 6 The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 1999 by The Endocrine Society

Geographical distribution of subclinical autoimmune thyroid disease in Britain: A study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase

In order to determine whether the geographical distribution of autoimmune thyroid disease in Britain is influenced by the pattern of iodine intake, the prevalence of subclinical disease (detectable antithyroid antibodies in biochemically euthyroid individuals) has been measured in female blood donors from seven towns in England and Wales previously characterised in terms of past and present iodine intake. Thyroglobulin antibody and thyroid peroxidase antibody were measured by highly sensitive assays which are based on the direct interaction between antibody and radiolabelled antigen. Excluding cases of overt thyroid disease (biochemically hypo- or hyperthyroid with thyroid antibodies), the overall prevalences of the antibodies in sera from the 698 female blood donors were 17.8% for thyroglobulin antibody and 17.8% for thyroid peroxidase antibody. Both antibodies were found in 12.3% of the female blood donors. In contrast, the prevalences of thyroglobulin antibody and thyroid peroxidase antibody were 41 and 43%, respectively, in the 117 female relatives of 18 probands with autoimmune thyroid disease, but the highest prevalences were observed in groups of women patients with Graves' disease (N = 39) or Hashimoto's disease (N = 39) (51, and 97% for thyroglobulin antibody, respectively, and 72 and 97% for thyroid peroxidase antibody, respectively). Antibody prevalence increased with age in the female blood donors rising from 10.6% at age 18-24 to 30.3% at age 55-64 for thyroglobulin antibody and from 14.9% at age 18-24 to 24.2% at age 55-64 for thyroid peroxidase antibody. Geographical differences in the prevalences of both antibodies were not significant and did not correlate with either the previous goitre prevalence or with current differences in iodine intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Natural killer cell activity and serum autoantibodies in women with postpartum thyroiditis.

Postpartum thyroiditis (PPT) is a form of painless lymphocytic thyroiditis which is thought to be caused by an exacerbation of underlying subclinical autoimmune thyroid disease during a postpartum period of immune rebound. The purposes of this study were to analyze natural killer cell (NK) functional activity and antibody-dependent cell-mediated cytotoxicity (ADCC) of peripheral blood mononuclear cells in patients with PPT compared to those in normal nonpostpartum and postpartum women. NK activity and ADCC were determined by specific lysis of 51Cr-labeled K562 human erythroleukemia tumor cells at varying effector (mononuclear cell) to target cell ratios. Nineteen PPT patients between 4-9 months [mean, 6.5 +/- 0.4 (+/- SE)] postpartum were compared to 20 nonpostpartum women, 31 healthy women between 4-9 months (6.7 +/- 0.3) postpartum, and 14 women 2 days after delivery. There were significant differences in the NK functional activities of the 4 groups (F = 7.95; P = 0.0002). The mean NK activities, as measured by percent specific lysis at an effector to target cell ratio of 10:1, were 31.1 +/- 3.3%, 20.9 +/- 2.3%, 22.5 +/- 2.8%, and 11.5 +/- 2.0% in the nonpostpartum, PPT, postpartum, and 2-day postpartum groups, respectively. Specific lysis by ADCC was not significantly different from lysis by NK activity in any group. The PPT, postpartum, and 2-day postpartum groups had significantly lower NK activity compared to that in nonpostpartum women (P less than 0.05). Both the PPT and postpartum women had higher NK activities than the 2-day postpartum women (P less than 0.05). However, there were no significant differences in the NK activities of the PPT patients compared to those of the healthy postpartum women. Patients with PPT were also found to have associated autoimmune dysfunction. The PPT group had significantly higher serum antinuclear antibody titers; 8 of 24 patients (33%) had titers of 1:160 or greater compared to only 2 of 29 healthy postpartum women (7.4%; P less than 0.05). Seven of the PPT patients had serum immune complexes, and 3 had TSH receptor antibodies. We conclude that functional NK activity and ADCC in peripheral lymphocytes of PPT patients are not different from those in healthy postpartum women; however, the postpartum women had significantly decreased activity compared to that in nonpostpartum women. These data emphasize the importance of studying healthy postpartum women in investigations of PPT, since the immunological changes in pregnancy and the postpartum period remain largely undefined.