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A 67-year-old man was admitted with a 1-month history of spontaneous hematoma in his right back and severe anemia. He had suffered from rashes with blisters involving both legs for 10 years, which had shown worsening and extended to his entire body concurrently with the hematoma. APTT was markedly prolonged to 119 seconds, and Factor VIII:C and FVIII inhibitor levels were less than 1% and 153.1 BU/ml, respectively, confirming the diagnosis of acquired hemophilia A (AHA). Skin biopsy revealed his rashes to be caused by autoimmune bullous disease (ABD), and laboratory and physical findings showed that he also had autoimmune hypothyroidism (Hashimoto's disease). Recombinant FVIIa was effective for management of his bleeding; in addition, FVIII inhibitor reduction and FVIII:C recovery, in parallel with improvement of the skin lesions, were achieved by administering prednisolone and cyclophosphamide. To our knowledge, this is the first report of AHA associated with ABD and Hashimoto's disease.

Objective: To quantify clinical outcome in patients with steroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) after the acute phase and explore potential associations of initial serum thyroid peroxidase antibody titers (TPO-Abs) with outcome., Materials and Methods: Retrospective chart review of patients diagnosed with SREAT between 01/2005 and 05/2014 in a tertiary care center and followed in an affiliated autoimmune outpatient clinic. Outcome was quantified using the extended Glasgow Outcome Scale (GOS-E). We calculated Pearson's correlation coefficients to quantify associations with clinical outcome at follow-up., Results: Among 134 patients with encephalopathy of unknown etiology, we identified 13 patients diagnosed with SREAT. In two patients, the diagnosis was revised at subsequent hospitalization (NMDA-R encephalitis and adult-onset Still's disease). The median follow-up time was 11 months, and the median GOS-E was 6 (range 3-8). Higher serum TPO-Ab-titers correlated with more favorable outcomes (Pearson coefficient 0.65, P = 0.03)., Conclusion: A correlation between TPO-Ab-titers and outcome has not been reported previously and challenges the notion of a mere bystander role of TPO-Abs in SREAT., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Even though the presence of antithyroglobulin antibodies (TgAbs) represents a significant problem in the follow-up of patients with differentiated thyroid cancer (DTC), the current guidelines on the management of DTC that have been published in recent years contain no text concerning the methods to be used for detecting such antibody-related interference in thyroglobulin (Tg) measurement or how to manage TgAb-positive patients in whom Tg cannot be used reliably as a tumor marker., Aim: An international group of experts from the European Thyroid Association Cancer Research Network who are involved in the care of DTC patients met twice to form a consensus opinion on how to proceed with treatment and follow-up in TgAb-positive DTC patients based on the available evidence in the literature. Here we will report on the consensus opinions that were reached regarding technical and clinical issues., Results: This clinical opinion article provides an overview of the available evidence and the resulting consensus recommendations. The current literature does not provide sufficient data for giving evidence-based answers to many questions arising in the care of TgAb-positive DTC patients. Where insufficient evidence was available, a thorough discussion by a group of physician-scientists, all of whom have a distinguished track record in thyroid cancer care, was held to arrive at a consensus expert opinion. The questions and answers discussed were then summarized into an algorithm for the management of TgAb-positive patients., Conclusion: We were able to define 26 consensus expert recommendations and a resulting algorithm for the care of TgAb-positive DTC patients.

Thyrotropin receptor autoantibodies (TSHR-Abs) of the stimulating variety are the hallmark of Graves' disease. The presence of immune defects leading to synthesis of TSHR-Abs causes hyperthyroidism and is associated with other extrathyroidal manifestations. Further characterization of these antibodies has now been made possible by the generation of monoclonal antibodies with this unique stimulating capacity as well as similar TSHR-Abs not associated with hyperthyroidism. Their present classification divides TSHR-Abs into stimulating, blocking (competing with TSH binding) and neutral (no signaling). Recent studies using monoclonal TSHR-Abs has revealed that stimulating and blocking antibodies bind to the receptor using mostly conformational epitopes, whilst neutral antibodies utilize exclusively linear peptides. Subtle differences in epitopes for stimulating and blocking antibodies account for the diversity of their biological actions. Recently non-classical signaling elicited by neutral antibodies has also been described, raising the need for a new classification of TSHR-Abs.

Objectives: The impact of dental amalgam removal on the levels of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies was studied in patients with autoimmune thyroiditis (AT) with and without mercury allergy., Methods: Thirty-nine patients with AT were tested by an optimized lymphocyte proliferation test MELISA for allergy (hypersensitivity) to inorganic mercury. Patients were divided into two groups: Group I (n = 12) with no hypersensitivity to mercury and Group II (n = 27) with hypersensitivity to mercury. Amalgam fillings were removed from the oral cavities of 15 patients with hypersensitivity to mercury (Group IIA) and left in place in the remaining 12 patients (Group IIB). The laboratory markers of AT, anti-TPO and anti-Tg autoantibodies, were determined in all groups at the beginning of the study and six months later., Results: Compared to levels at the beginning of the study, only patients with mercury hypersensitivity who underwent amalgam replacement (Group IIA) showed a significant decrease in the levels of both anti-Tg (p=0.001) and anti-TPO (p=0.0007) autoantibodies. The levels of autoantibodies in patients with or without mercury hypersensitivity (Group I and Group IIB) who did not replace amalgam did not change., Conclusion: Removal of mercury-containing dental amalgam in patients with mercury hypersensitivity may contribute to successful treatment of autoimmune thyroiditis.

Epitopes for > 95% stimulating thyrotropin receptor autoantibodies (TSHRAbs) causally implicated in Graves' disease (Basedow's disease or primary hyperthyroidism) have been identified on on the N-terminal portion of the TSHR extracellular domain, residues 8-165. If the stimulating TSHRAb activity is solely dependent on this region, it is termed homogeneous; if its activity is only largely related to this region, it is termed heterogeneous. The presence of a heterogeneous stimulating TSHRAb in a patient is associated with rapid responses to propylthiouracil or methimazole and may be predictive of long term remission with these oral immunosuppressives. Epitopes for two different Graves' autoantibodies that inhibit TSH binding, TSH binding inhibition immunoglobulins or TBIIs, have also been identified on this region of the TSHR. They do not increase cAMP levels, although one may activate the inositol phosphate, Ca++, arachidonate release signal system. The epitope of blocking TSHRAbs with the ability to inhibit TSH binding (TBII activity), TSH activity, and stimulating TSHRAb activity, and that are causally implicated in the primary hypothyroidism of patients with idiopathic myxedema or some patients with Hashimoto's disease have, in contrast, been largely identified largely on the C-terminal portion of the TSHR extracellular domain, residues 270-395. They have been implicated as important in pregnancy where they attenuate the signs and symptoms of Graves' hyperthyroidism. The appearance of these blocking TSHRAbs during pregnancy in Graves' patients might cause overt or occult hypothyroidism, with resultant effects on fetal development and postnatal intelligence levels. The different TSHRAbs can exist in the same patient at any moment in time, potentially making disease expression a sum of their activities. Assays taking advantage of the epitope mapping findings enable us to detect individual TSHRAbs within a single patient and to better understand their clinical significance.

Anti-thyroid hormone autoantibodies are occasionally found in Hashimoto's disease. They can interfere with thyroid hormone assays. The authors report the case of a 35-year-old hypothyroid (TSH between 29 and 46 microIU/ml) female patient with Hashimoto's disease and surprisingly high free and total levels of plasma T4 and T3 assayed with different solid phase radio-immunologic kits. Two immunoenzymologic assay kits gave a T4 level close to the one expected. The presence of circulating anti-T4, T3 and reverse T3 autoantibodies was demonstrated by precipitating the corresponding tracers with the patient's serum in the presence of polyethylene glycol without heterologous antibodies. The replacement treatment of 150 micrograms l-thyroxine allowed normalization of TSH at 3.4 microIU/ml, but the patient remained tired and anxious, with headaches and tachycardia. After discontinuing treatment for one month a series of four plasma exchanges was carried out in six days. After the first exchange the binding percentages were already much lower and went even lower after the other exchanges. After the fourth one, the free T4 and T3 levels were closer to the expected levels:7.3 pmol/l (N:10-30 pmol/l) and 4.3 pmol/l (N:3-9 pmol/l). Treatment by prednisone made it possible to maintain the percentages of binding to the three tracers for two weeks at the levels reached after the fourth plasma exchange. Two months after discontinuing corticosteroid treatment they returned to the initial levels and were again interfering with the free T4 and T3 assays. This finding suggests that usefulness of the thyroid hormone immuno-enzymologic assay, which apparently is not affected by the anti-thyroid hormone autoantibody interference.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Postpartum thyroiditis is a common but frequently unrecognized disorder, affecting approximately 5% of women during the first 12 months after delivery. We investigated whether the antimicrosomal antibody titer could be used to determine which women with positive titers postpartum (1) might develop symptomatic or biochemical abnormalities within the first postpartum year (early disease), (2) might require therapy with thyroid hormone, and (3) might have persistent abnormalities (late disease)., Methods: Women (n = 55) who had positive antimicrosomal antibody titers at delivery were prospectively followed for 11 to 45 months. Titers were evaluated again at 6 to 10 weeks postpartum and approximately every 8 weeks for the first year., Results: Early disease occurred in 40 of 55 (73%) women, late disease occurred in 29 of 55 (53%) women, and treatment was required by 21 of 55 (38%) women. The occurrence of early disease was associated with the occurrence of late disease (P < .05). The chances of developing early disease were 6 to 1 (P = .01) when serum titers of antimicrosomal antibodies were > or = 400 at delivery, and 5 to 1 (P = .02) when titers were > or = 1600 at 6 to 10 weeks postpartum. The chances of being given thyroid hormone therapy were 23 to 1 (P = .006) when titers at delivery were > or = 6400, and 6 to 1 when titers at 6 to 10 weeks postpartum were > or = 6400 (P = .004). Titers were not useful in estimating who would have late disease., Conclusions: Screening for postpartum thyroid dysfunction after delivery using antimicrosomal antibody titers is highly useful. The titer value can help guide the physician in the care of patients with postpartum thyroiditis whose disease may not be self-limiting and who will probably require thyroid hormone therapy.

We have evaluated the variations of thyroid function, of thyroid autoantibodies titer, of non-organ specific autoantibodies and of other autoimmunity indices in 3 patients affected with Hashimoto's thyroiditis treated with "high dose intravenous gammaglobulin" (IVIG) (400 mg/Kg/day for 3 cycles of 5 days and subsequently 9-12 cycles of 1 day every 21 days). Before the starting of IVIG treatment patient 1 presented clinically evident hypothyroidism while patients 2 and 3 presented a preclinical form of hypothyroidism. At the end of IVIG treatment patients presented no variation of thyroid function, while patients 2 and 3 presented a normalization of T3, T4 and TSH circulating levels. Before the starting of IVIG treatment thyroglobulin antibodies (TgAb) were positive in 3/3 patients, microsomal antibodies (MAb) were positive in 3/3 patients adt TRAb were positive in 2/3 patients and MAb titre was decreased or negative in 0/3 patients. At the end of IVIG treatment Tg Ab titre was decreased or negative in 2/3 patients and MAb titre was decreased or negative in 2/3 patients. Anti-nuclear antibodies (ANA) 1/3 patients before the titre and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA), anti-mitochondrial antibodies (AMA), C3, C4, CH50 and rheumatoid factors were negative or in the normal range in all the patients. In conclusion these data suggest that IVIG is effective in the treatment of preclinical hypothyroidism in patients with Hashimoto's thyroiditis and determine a stable immunosuppressive action on circulating thyroid and non organ specific autoantibodies.

The autoantigen thyroglobulin has been conjugated with the A chain of the toxin ricin. In vitro this conjugated "immunotoxin" specifically suppressed the thyroglobulin autoantibody response of lymphocytes from patients with Hashimoto's thyroiditis. Neither total immunoglobulin synthesis nor the synthesis of autoantibody to thyroid microsomes by these lymphocytes was affected by the immunotoxin. The demonstration that an autoantigen coupled to a toxin can induce specific immunological unresponsiveness suggests that such immunotoxins could provide a novel and highly selective means for deleting autoantibody-secreting lymphocyte clones in patients with autoimmune disease.