Safety of Aesthetic Medicine Procedures in Patients with Autoimmune Thyroid Disease: A Literature Review

Autoimmune thyroid diseases are the most common organ-specific autoimmune diseases, affecting 2–5% of the world’s population. Due to the autoimmune background of thyroid diseases, we analyzed a wide range of cosmetic procedures, from minimally invasive cosmetic injections (mesotherapy) to highly invasive procedures, such as lifting threads. Out of the seven categories of treatments in aesthetic medicine analyzed by us—hyaluronic acid, botulinum toxin, autologous platelet-rich plasma, autologous fat grafting, lifting threads, IPL and laser treatment and mesotherapy—only two, mesotherapy and lifting threads, are not recommended. This is due to the lack of safety studies and the potential possibility of a higher frequency of side effects in patients with autoimmune thyroid diseases.

Manifest hyperthyroidism in patient with autoimmune hepatitis (clinical observation)

Among patients with autoimmune hepatitis concomitant autoimmune diseases occur in 40 % of cases. The most commonly associated autoimmune hepatitis is primary biliary cholangitis, primary sclerosing cholangitis and thyroid disease. With regard to the association of autoimmune liver diseases with each other there is experience in management and this is reflected in the clinical guidelines. Information on the features of comorbidity in autoimmune hepatitis and autoimmune thyroid diseases is very limited. This article presents our own clinical observation of the manifestation of thyrotoxicosis against the background of autoimmune hepatitis.

Vitamin D and autoimmune thyroid diseases (part 1)

Autoimmune thyroiditis (AIT) and Graves’ disease (GD) are common autoimmune diseases, and their prevalence assessed as 5 % of general population. Currently, selective immunosuppressive agents for pathogenetic treatment of autoimmune pathology are being developed. Vitamin D with the known anti­inflammatory and immunoregulatory properties, is also of great interest. The first part of the article reviews the roles of various immune cells in the pathogenesis of autoimmune thyroid diseases, which is necessary to reveal the therapeutic potential of calcitriol in these disorders. Classically, AIT was considered to be mediated by T­helpers type 1 (Th1), and GD — by T­helpers type 2 (Th2). This misunderstanding was based on the idea that humoral immunity is controlled by Th2 cytokines, and cellular immunity — by Th1. In the past decades, the role of new subsets of immune cells in the pathogenesis of autoimmune thyroid diseases is being studied, displacing the traditional paradigm of Th1/Th2 dichotomy. It has been established that T­helpers type 17 (Th17) play an important role in the development of various inflammatory and autoimmune diseases, previously classified as Th1­dependent pathologies. The involvement of T­ and B­regulatory lymphocytes in the autoimmune process is also of particular interest. It was found that these cells accumulate in inflamed thyroid tissue in patients with thyroid pathology, but they are unable to suppress the immune response effectively. Further research will help to find out which immune cells can become targets for vitamin D agonists in the complex treatment of autoimmune diseases.

The effect of radioiodine treatment on the characteristics of TRAb in Graves’ disease

Background Graves’ disease (GD) is one of the most common autoimmune thyroid diseases (AITDs) in humans, and thyrotropin receptor antibody (TRAb) is a characterized autoantibody in GD. The use of radioactive iodine therapy (RAI) for GD treatment is increasing. Objectives We studied the biological properties of TRAb and evaluated the effect of RAI therapy on TRAb in GD patients. Methods In total, 225 patients (22 onset GD patients without 131I therapy, 203 GD patients treated with 131I therapy) and 20 healthy individuals as normal controls were included in this study. Clinical assessments were performed, and we examined in vitro the biological properties of TRAb in the 22 onset GD patients and 20 controls as well as 84 GD patients with 131I therapy. Results Serum TRAb and thyroid peroxidase antibody (TPOAb) levels increased in the initial year of RAI treatment, and both antibodies decreased gradually after one year. After 5 years from radioiodine treatment, TRAb and TPOAb levels decreased in 88% and 65% of GD patients, respectively. The proportion of patients positive for thyroid-stimulatory antibody (TSAb) was significantly higher in the 7–12-month group, and thyroid-blocking antibody (TBAb) levels were elevated after one year in half of the patients who received 131I treatment. Conclusions Treatment of GD patients with radioiodine increased TPOAb and TRAb (their main biological properties were TSAbs) within the first year after therapy, and the main biological properties of elevated TRAb were TBAbs after 1 year.

Precision Medicine in Autoimmune Thyroiditis and Hypothyroidism

Autoimmune thyroid diseases (AITD) are T-cell-mediated organ specific autoimmune disorders, deriving from an altered response of the immune system that leads to the immune attack to the thyroid. Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are the two principal AITD clinical presentations. Hypothyroidism and thyrotoxicosis are, respectively, the clinical hallmarks of HT and GD. Patients with autoimmune thyroiditis are treated daily with synthetic L-thyroxine (L-T4) at the dose of 1.5–1.7 μg/kg. Various L-T4 formulations are commercially available (tablet, liquid solution, or soft gel capsule). L-T4 in tablets is generally prescribed to treat hypothyroidism, whereas the liquid formulation, or soft gel capsules, can be administered in hypothyroid patients in case of malabsorption or in patients in therapy with drugs interfering with L-T4 absorption. Furthermore, myoinositol has a crucial role in thyroid autoimmunity and function. Clinical studies reported a significant decline in TSH and antithyroid autoantibodies levels after treatment with myoinositol + selenium in patients with subclinical hypothyroidism and autoimmune thyroiditis. Moreover, thyroidectomy can be rarely recommended in patients with autoimmune thyroiditis, with cosmetic reasons for a goiter, or with important signs or symptoms of local compression, or nodular disease with a “suspicious” cytology for malignancy. Furthermore, a recent randomized trial suggested that total thyroidectomy can improve quality of life and fatigue, while medical therapy did not. In this review, we overview currently available evidence in personalized medicine in patients with autoimmune thyroiditis and hypothyroidism. Further research is needed in larger population to investigate the effect of these new treatments on quality of life.

The Roles of Exosomes in Immunoregulation and Autoimmune Thyroid Diseases

Exosomes are extracellular microvesicles (30-150 nm) released from cells that contain proteins, lipids, RNA and DNA. They can deliver bioactive molecules and serve as carriers facilitating cell-cell communication, such as antigen presentation, inflammatory activation, autoimmune diseases (AIDs) and tumor metastasis. Recently, much attention has been attracted to the biology and functions of exosomes in immune regulation and AIDs, including autoimmune thyroid diseases (AITDs). Some studies have shown that exosomes are involved in the occurrence and development of AITDs, but they are still in the preliminary stage of exploration. This review mainly introduces the association of exosomes with immune regulation and emphasizes the potential role of exosomes in AITDs, aiming to provide new research strategies and directions for the pathogenesis and early diagnosis of AITDs.

Circulating Exosome Involves in the Pathogenesis of Autoimmune Thyroid Diseases Through Immunomodulatory Proteins

Autoimmune thyroid diseases (AITDs) are chronic organ-specific autoimmune diseases, mainly including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Exosomes, as extracellular vesicles, contain a variety of biologically active substances that play a role in information exchange, thereby affecting the occurrence and progression of diseases. However, it is unclear whether exosomes are involved in the pathogenesis of AITDs. In this study, the role of exosomes in AITDs was explored from a proteomics perspective. Plasma exosomes were isolated from 12 patients with GD, 10 patients with HT, and seven normal controls (NC). Protein profiles were detected using the data-independent acquisition (DIA) method and analyzed to investigate changes in plasma exosome proteins. In the setting of GD, 11 proteins were upregulated while 197 proteins were downregulated compared with healthy people. Among them, MAP1S (log2 FC = 4.669, p = 0.009) and VAMP8 (log2 FC = 3.216, p = 0.003) were the most significantly upregulated, and RSU1 (log2 FC = −6.797, p = 0.001), ACTB (log2 FC = −4.795, p < 0.001), and CXCL7 (log2 FC = −4.674, p < 0.001) were the most significantly downregulated. In the cases of HT, HGFL (log2 FC = 2.766, p = 0.001), FAK1 (log2 FC = 2.213, p < 0.001), and PTN12 (log2 FC = 1.624, p < 0.001) were significantly upregulated, while PSMF1 (log2 FC = −3.591, p < 0.001), PXL2B (log2 FC = −2.622, p = 0.001), and CYTM (log2 FC = −1.609, p < 0.001) were the most downregulated. These differential proteins were mainly enriched in the immune system and metabolic system, indicating that plasma exosomes may play an important role in systemic immune imbalance in AITDs.

Coxsackie Virus Induced Graves’ Disease in an Immunocompetent Patient

Enteroviruses, such as Coxsackie virus, have been implicated in the past as a pathogen associated with subacute thyroiditis, also known as de Quervain’s thyroiditis. Less commonly are viruses associated with autoimmune thyroid diseases such as Hashimoto’s thyroiditis and Graves’ disease. We present a case of a healthy 43 year old female who presented to the emergency department complaining of several months of weakness, nausea, loose bowel movements, anxiousness, and shortness of breath. Physical exam revealed tachycardia, tremors, and a non-tender thyroid gland to palpation. Skin exam showed a rash on the palms of her hands and soles of her feet bilaterally with dark papules, suggestive of Hand, foot, and mouth disease. Laboratory workup would reveal an undetectable thyroid stimulating hormone (TSH), and levels of T3 & T4 too high to quantify. Thyroid receptor antibodies would return as positive, diagnostic of Graves’ disease. Coxsackie virus (the causative agent of Hand, foot, and mouth disease) IgM titers also returned positive suggesting recent infection. Although the etiology of Graves’ disease is still not clear, this case report provides evidence that environmental triggers such as Coxsackie viral infection may be involved in its pathogenesis.

Co-occurrence of Relapsing Polychondoritis and Autoimmune Thyroid Diseases

Background: Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilageous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves’ disease (GD) and Hashimoto thyroiditis (HT). However there have been no detailed studies on the co-occurrence of RP and AITD. In this study, we aimed to determine whether patients with RP tend to be complicated with AITD. We also analyzed clinical and genetic profiles of patients in whom these diseases co-occur.Methods: We recruited 117 patients with RP and reviewed their medical records. Furthermore, we genotyped Human Leucocyte Antigen (HLA)-A, B Cw, DRB1, DQB1 and DPB1 alleles for 93 of the 117 patients. The prevalence of AITD among the patients with RP was compared with that among the general Japanese population. We also analyzed the clinical and genetic features of the patients with both RP and AITD.Results: The prevalence of GD among the patients with RP was 4.3% (5 among 117 patients), significantly higher than that among Japanese (0.11%) (p=2.44×10-7, binomial test). RP patients with GD tended to have nasal involvement (p=0.023) (odds ratio (OR) 2.58) and HLA-DPB1*02:02 (p=0.035, OR 10.41). We did not find significant enrichment of HT in patients with RP.Conclusions: Patients with RP appear to be at elevated risk of GD. Nasal involvement and HLA-DPB1*02:02 may characterize the subset of RP patients with GD, which may guide attempts to characterize distinct subtype of RP for precision medicine.

Parvovirus B19 Infection Is Associated with Autoimmune Thyroid Disease in Adults

Background: Autoimmune thyroid diseases are the most frequent autoimmune disorders, with a global prevalence of about 10%. Several mechanisms have been proposed to induce autoimmune thyroid responses by infectious agents. In this study, we aimed to evaluate the association between parvovirus B19 infection and autoimmune thyroid disorders. Methods: Adult patients with newly diagnosed Graves’ disorder (GD) and Hashimoto’s thyroiditis (HT) and healthy euthyroid controls were recruited. Various clinical and biochemical parameters, including thyroid function tests and serum parvovirus B19 antibody level (IgG), were assessed and compared between the groups. Results: In this study, data from 404 cases with HT, 248 cases with GD, and 480 healthy individuals as a control group were analyzed. The prevalence of parvovirus B19 infection in patients with HT and GD and controls was 61.1%, 58.9%, and 47.1%, respectively. In the group of patients with HT, there was a significant positive correlation between the B19 IgG and TPOAb (r = 0.764, P < 0.001) and TgAb (r = 0.533, P < 0.001). Also, in patients with GD, the B19 IgG had a significant positive correlation with TPOAb (r = 0.779, P < 0.001) and TgAb (r = 0.467, P < 0.001). Conclusions: Parvovirus B19 infection is commonly seen in patients with autoimmune thyroid disorders.