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Purpose: The influence of Hashimoto's thyroiditis (HT) on calcitonin (Ct) production is unresolved question. The aim of this study was to explore if basal Ct levels are influenced by the presence/severity of HT or correlated with clinical phenotypes of HT patients., Methods: We included 467 HT patients and 184 control participants, from Croatian Biobank of HT patients (CROHT), in this retrospective study. Calcitonin levels between HT patients and controls were compared using Mann-Whitney test. Ct levels between two subgroups of HT patients, divided by intake of levothyroxine (LT4) therapy, were additionally tested to take into account the illness severity. Spearman rank correlation test was used to analyze correlations between Ct levels and 14 relevant phenotypes., Results: We have not detected significant differences in median Ct levels between HT patients and controls (2.2 vs 2.35 pg/mL, respectively, P = 0.717) nor in-between two subgroups of HT patients (P = 0.347). We have not detected statistically significant correlations between Ct levels and clinical phenotypes, although we identified three weak nominal correlations: negative correlation of Ct with TgAb in all HT patients (r = - 0.1, P = 0.04); negative correlation of Ct with age in subgroup of HT patients without LT4 therapy (r = - 0.13, P = 0.04); positive correlation of Ct with BSA in subgroup of HT patients on LT4 therapy (r = 0.16, P = 0.042)., Conclusion: Our results suggest that HT patients of all disease stages preserve Ct production as healthy individuals and there is no need for Ct measurements in the absence of a nodule. Additional confirmation and clarification of observed nominal correlations are needed due to potential clinical relevance of TgAb and age-dependent Ct decrease in HT women., (© 2021. Italian Society of Endocrinology (SIE).)

Purpose: To describe a case of autosomal-dominant (AD)-chronic mucocutaneous candidiasis (CMC) with a signal transducer and activator of transcription (STAT) 1 gene mutation, and some of the important complications of this disease such as chronic hepatitis., Methods: We present a 23-year-old woman with CMC, chronic active hepatitis, and hypothyroidism. Her father also had CMC. We performed several immunological analyses of blood and liver samples, and searched for gene mutations for CMC in the patient and her father., Results: We identified the heterozygous substitution c.821 G > A (p.Arg274Gln) in the STAT1 gene of both the patient and her father. The level of β-glucan induced interferon (IFN)-γ in her blood cells was significantly low. Immunoblot analysis detected serum anti-interleukin (IL)-17 F autoantibody. She was found to have increased (low-titer) antibodies related to her hypothyroidism and hepatitis. Her serum IL-18 levels fluctuated with her AST and ALT levels. Liver biopsy revealed CD68-positive cell infiltration and IL-18 expression in the sinusoidal regions. These results suggest that the chronic active hepatitis in this patient may be exacerbated by the excessive IL-18 accumulation caused by recurrent mucocutaneous fungal infection, and decreased IFN-γ production., Conclusions: AD-CMC is known to be caused by a gain-of-function mutation of the STAT1 gene. Chronic active hepatitis is a rare complication of AD-CMC, with currently unknown pathogenesis. It seems that the clinical phenotype in this patient is modified by autoimmune mechanisms and cytokine dysregulation. AD-CMC can be complicated by various immune disorders including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

We previously implicated TG leakage from fine-needle aspiration biopsy (FNAB) as responsible for circulating thyroid hormone autoantibodies (THAb). However, THAb were not always associated with TGAb. In the literature these negative findings have been interpreted against a role of TG as the antigen for THAb. To evaluate the TGAb status more fully and to gain information on TG epitopes involved in THAb development, we measured: 1) TGAb with an independent hemagglutination assay (HA), and 2) epitope specificity in a competitive ELISA using 2 monoclonal Abs (mAb) against TG: mAb 42C3 and mAb 134C2. MAb 42C3 recognizes a cross-reactive iodinated epitope, whereas 134C2 is specific for human TG. We tested 12 Hashimoto's thyroiditis (HT) and 35 non-HT patients sampled prior to, 1 and 3 months after FNAB. We found that, irrespective of thyroid disease or post-FNAB THAb status, certain patients previously classified as TGAb negative by IRMA tested TGAb positive by HA or by competition ELISA and vice versa. A post FNAB positive response to the 42C3 iodinated epitope in only one THAb IgM-T4+ve HT and a few THAb negative non-HT patients was observed. Furthermore, we observed that the 3 non-HT patients who expressed IgM-T3 THAb failed to bind either TG-mAb epitope. We conclude that a single TGAb assay is not sufficient to define the TGAb status, which can be achieved reliably only by using multiple TGAb assays. In addition, the TG-iodinated epitope recognized by 42C3 is not a major epitope in post-FNAB THAb, and the T3-epitope involved in THAb remains distinct from the mAb epitopes. In light of recent data in the literature, we further suggest that the responsible epitopes are more likely to be expressed in leaked TG fragments, rather than leaked intact TG.

To verify the greater prevalence of circulating thyroid hormone autoantibodies (THAb) in primary Sjogren syndrome (SS) vs Hashimoto's thyroiditis (HT) and Graves' disease (GD), we measured THAb in the serum of patients with these 3 diseases who were sampled from 1998-1999 (no.=20, 88, 25) and 1990-1992 (no.=13, 75, 31). Patients with rheumatoid arthritis (RA) (no.=23 and 16) and other collagenoses (no.=20 and 16) were also studied. A third series of patients with these 5 diseases was studied from 1975-1982, and data have been taken into account. THAb were detected using a specific radioimmunoprecipitation method, and their presence was correlated with the presence of TG antibodies (TGAb). We found that IgG antibodies against T3, T4 or both were present with these prevalences in the 1975-1982, 1990-1992 and 1998-1999 series: HT=1, 4, 20%; GD=2, 6, 32%; SS=20, 31, 50%; RA=0, 12, 26%; other collagenoses=0, 0, 0%. The majority of the Sjogren or arthritis cases positive for THAb were negative for TGAb, while the opposite was true for the 2 autoimmune thyroid diseases. We conclude that prevalence of THAb in the 2 non-thyroid autoimmune diseases is greater than in the 2 thyroid autoimmune diseases. In addition, prevalence of THAb is increasing over time regardless of disease. Molecular similarity between extra-thyroid connective proteins (specifically associated to primary SS and RA) and iodinated regions of TG, and an increased preponderance of environmental factors as triggers of autoimmune diseases might account for our findings.

Unlabelled: In order to establish its usefulness for the diagnosis and follow-up of thyroid autoimmune diseases, thyroid ultrasonography together with free T4 (FT4), free T3 (FT3), TSH, antibodies (Tg Ab) and thyroperoxidase antibodies (TPO Ab) were performed and re-evaluated during a 3-yr follow-up in 482 apparently healthy subjects, living in a borderline iodine-sufficient urban area. Thyroid dysfunction was found in 7 out of 12 (58.3%) subjects with circulating thyroid autoantibodies, who also had thyroid hypoechogenicity (2 had overt and 3 subclinical hypothyroidism at booking; 2 developed subclinical hypothyroidism during the follow-up), and in none of the 12 subjects with normal thyroid echostructure (chi2=7.26, p=0.007). Thyroid dysfunction was found in 4 out of 29 (13.7%) subjects with negative Tg and/or TPO Ab who also had thyroid hypoechogenicity (1 had Graves' disease at booking, 1 developed Graves' disease and 2 subclinical hypothyroidism during the follow-up), and in none of the 429 with normal thyroid echostructure (chi2=82.03, p<0.0001). Although positive TPO and/or Tg Ab were more frequent (24/482, 5%) in subjects with thyroid dysfunction (7/11) than in those who remained euthyroid during the study (17/471, chi2=69.66, p<0.0001), thyroid hypoechogenicity had a higher sensitivity than the positivity of thyroid autoantibody tests (100 vs 63.3%) for diagnosing or predicting thyroid dysfunction., In Conclusion: 1) thyroid ultrasonography is a useful tool to detect thyroid autoimmune disease in apparently healthy subjects; 2) present and future thyroid dysfunction is more readily predicted by a hypoechogenic pattern at thyroid ultrasound than by the occurrence of serum thyroid autoantibodies.

Antithyroid hormone autoantibodies (THBA), described in both humans and animals, result in variable interference when thyroid hormone plasma levels are measured by immunoassays. We previously described a quick chromatographic method to detect circulating THBA in humans. In the present experience, we applied the method on canine sera (10 normal dogs and 3 dogs affected by hypothyroidism) to detect the THBA presence in a dog (no. 13) with clinical evidence of hypothyroidism, in spite of apparently extremely high values of thyroid hormone. After a short incubation of samples with 125I-T3 and 125I-T4 in presence of 8-anilino-1-naphtalenesulfonic acid, samples were eluted and radioactivity values counted. Eluate radioactivity values > 10% and > 30% were considered positive for THBA presence for antiT3 and antiT4 detection, respectively. High radioactivity values were detected in dog serum no. 13 and, therefore, it was considered positive for THBA presence. The Scatchard plot analysis revealed the presence of a monoclonal autoantibody with the highest affinity for T3 and an additional tenfold lower affinity for T4. In conclusion, our chromatographic method allows the detection and the characterization of THBA in species different from humans, with species specific differences in thyroid hormone metabolism; thus, taking into account the rarely availability of canine serum TSH and anti-thyroglobulin antibody immunoassay detection methods, it was possible to correctly diagnose the hypothyroidism in a dog with apparently extremely high values of thyroid hormones due to THBA interference.

The aim of this study was to evaluate the feasibility of a chromatographic method to easily detect circulating anti-thyroid hormone autoantibodies (THBA), to calculate their affinity constant and the total thyroid hormone (TH) levels in presence of THBA. This method was applied to sera from 4 subject with suspected THBA and 20 controls (10 normal subjects and 10 patients with thyroid dysfunctions). After a short incubation with 125I-T3 or T4 tracer solution containing 8-anilino-1-naphthalenesulfonic acid as inhibitor of the binding of TH to plasma proteins without affecting THBA binding, the samples were chromatographied on prepacked Sephadex LH 20 columns and eluted with TRIS buffer to separate free TH from THBA-bound TH. Samples were considered THBA positive when radioactivity values in TRIS eluates were higher than in controls. THBA-bound TH were subsequently eluted with methanol and used to calculate the total TH present in patients with THBA. After a validation test using two standardized methods, we propose this method to quickly detect TH-BA in samples with suspected spuriously high values of free and total TH.

The diagnosis of premature ovarian failure (POF) was made in 45 women (aged 14 to 39 yr) with high concentrations of FSH and LH. Sera from these patients and a control group of 28 women were used to detect organ-specific autoantibodies. Eighteen patients with POF (40%) were positive for at least one autoantibody. In the control group only one woman (3.6%) showed autoimmunity. Antithyroid was the most representative autoimmunity (20%) in the POF group. By indirect immunofluorescence, only one patient was positive for antiovarian and antiadrenal antibodies. In summary, the results of this study are consistent with previous immunohistochemical data which indicate that autoimmune disorders are common in patients with POF. Furthermore, the detection of antiovarian antibodies in only one patient confirms that they are probably detectable in a short period of the disease.

In the present study, we report the uncommon case of a 9.6-yr-old girl with circulating anti-T3 autoantibodies (T3-Ab) and hyperthyroidism due to inappropriate secretion of TSH (IST). The diagnosis of IST was based on the findings of normal TSH levels (2.4 mU/L) in the presence of high free T4 (28.2 pmol/L) and free T3 (FT3) levels, as measured by direct measurement methods based on "one-step" analog tracer (28.0 pmol/L) and "two-step" Lisophase (13.3 pmol/L) techniques. The discrepancy between the two measurements suggested a methodological interference due to T3-Ab in "one-step" technique, being the "two-step" methodology unaffected by the presence of such autoantibodies. T3-Ab were documented by high nonspecific binding of serum to labeled T3 (38.0% vs 4.3 +/- 2.1% in controls). The clinical picture of hyperthyroidism, the qualitatively normal TSH responses to TRH and T3 suppression tests, the normal pituitary imaging and the values of some parameters of peripheral thyroid hormone action compatible with hyperthyroidism indicated that the patient was affected by pituitary resistance to thyroid hormones (PRTH). Chronic treatment with dopaminergic agent bromocriptine (7.5 mg/day) did not cause TSH secretion to be suppressed, while the administration of thyroid hormone analog TRIAC (1.4 mg/day) inhibited TSH release (from 2.4 to 0.2 mU/L). As a consequence, circulating thyroid hormone levels normalized and euthyroidism was restored. During TRIAC administration, FT3 levels, measured by "one-step" analog tracer technique, gave spuriously high values due to the methodological interference of T3-Ab (15.2 vs 4.3 pmol/L as measured by "two-step" Lisophase technique).(ABSTRACT TRUNCATED AT 250 WORDS)

Haplotypes of the human major histocompatibility complex (HLA) and immunoglobulin G heavy chain allotype (Gm) were determined in nine members of a family in which three sisters had thyroid hormone autoantibodies (THAA) in serum. Among three sisters with THAA, two of them were hypothyroid and treated with synthetic thyroid hormones (patients nos. 1 and 2). The other remaining sister (patient no. 3) was euthyroid. Light chain allotype (Km) in them was also examined. Three patients had the same two Gm haplotypes. Km (1) allotype was negative in these three patients. HLA haplotypes of patient no. 1 were the same as those of patient no. 2. However, HLA haplotypes of patient no. 3 were completely different from those of patients nos. 1 and 2. The same combination of Gm haplotypes and the absence of Km (1) allotype were not observed in the remaining members without THAA. These results suggest that genes linked to Gm and Km allotypes are associated with the production of THAA at least in our patients.

We have found three sisters who had thyroid hormone autoantibodies (THAA) in serum. Two of them were hypothyroid due to Hashimoto's thyroiditis. They were treated with synthetic thyroxine (T4) (Case 1) or T4 and triiodothyronine (T3) (Case 2). The other sister (Case 3) was euthyroid throughout the investigation period. Changes in the titers of THAA, antithyroglobulin (Tg) antibodies as well as in the concentrations of thyrotropin (TSH), and total and free thyroid hormones (T3, T4, FT3, and FT4) in sera from each patient were examined for four years. A significant positive correlation was observed between titers of THAA and anti-Tg antibodies in both Case 1 (anti-T3 and anti-T4) and 2 (anti-T4). On the other hand, a significant negative correlation between titers of anti-T3 and anti-Tg antibodies was observed in Case 3. These results suggest that antigen of THAA might be Tg in Case 1 and 2 and mechanism(s) of the production of THAA of Case 1 might be different from that of Case 1 and 2 in terms of their antigen or immune recognition of Tg.