Subclinical Hypothyroidism as the Most Common Thyroid Dysfunction Status in Children With Down’s Syndrome

IntroductionThyroid dysfunctions are one of the most common abnormalities coexisting in children with Down’s syndrome (DS) and have been reported in up to 54% of cases.Aim of the StudyThe purposes of this retrospective study were to investigate the course of subclinical hypothyroidism in children with DS, to evaluate the thyroid function of these subjects in relation to the risk of developing overt thyroid disease and autoimmunity, and to identify clinical and biochemical characteristics of patients prescribed L-T4 therapy in children and adolescents with DS and SH.Material and MethodsThe records of DS patients referred to the Endocrinology Outpatient Clinic between 2010 and 2015 for screening of thyroid function were observed till the end of 2019 June and analyzed retrospectively. The children diagnosed with congenital hypothyroidism, acute lymphoblastic leukemia, and seizures and treated with drugs that may have interfered with thyroid function like lithium, antiepileptic, or iodinated drugs and glucocorticoids were excluded from the study.ResultsThe data of 77 DS patients were collected, evaluated, and analyzed. The study group consisted of 73 patients (32 girls and 41 boys with the mean age at baseline of 3.0 ± 4.5 years). A total of 63/73 (87%) children were diagnosed with SH. The 16/63 (25.4%) patients were followed-up without the treatment (group SH-T0), and therapy with levothyroxine (L-T4) was introduced in 47/63 (74.6%) SH children with a mean dosage of 1.8 ± 1.0 μg/kg/day (group SH-T1). Thyroxine supplementation did not improve growth expressed as ΔhSDS (0.1 ± 1.3, ranged −2.1 to 3.8 in SH-T0 vs. 0.0 ± 0.7, ranged −1.7 to 1.4 in SH-T1, p = 0.96) and ΔBMI Z-score (0.3 ± 0.9, ranged −0.9 to 2.6 in SH-T0 vs. 0.3 ± 1.1, ranged −2.1 to 2.9 in SH-T1, p = 0.65). Positive anti-TPO and anti-TG antibodies were detected in 7/63 (11.1%) DS cases.ConclusionsSH is the most frequent presentation of thyroid gland dysfunction in DS children. A small percentage of patients develop an overt hypothyroidism, particularly in females with mostly positive titer of antithyroid autoantibodies.

Antithyroid autoantibodies in extrathyroid autoimmune diseases

This review summarizes data on the incidence of autoimmune diseases and examines the prevalence of antithyroid antibodies in extrathyroid autoimmune diseases. In the world, about 5–7 % of the population suffers from one or another type of autoimmune diseases. Among the six most common autoimmune diseases, thyroid and associated diseases predominate. The high prevalence of autoimmune thyroid diseases raises questions about the potential role of antithyroid antibodies in the course of extrathyroid autoimmune diseases. It is believed that autoimmune di­seases are the result of interactions between triggers, autoantigens, genetic predisposition, impaired tolerance of autoantigens and mechanisms of apoptosis. Among the currently known antithyroid autoantibodies, antibodies to thyroglobulin (TgAb), thyroid peroxi­dase (TPO), as well as bispecific autoantibodies to thyroglobulin and thyroid peroxidase are of particular importance. Categories of functionally significant autoantibodies that mimic hormone function and provoke the development of autoimmune pathology as a result of binding to the receptor and subsequent stimulation of thyrocytes include antibodies to thyroid-stimulating hormone receptor (rTSH-Ab). Circulating antibodies against thyroid antigens are not limited to autoimmune diseases of the thyroid gland, but are also found in other autoimmune diseases, most often in rheumatoid arthritis, type 1 diabetes mellitus and celiac disease. The association with other immune pathologies further confirms that TPO antibodies were also detected in 15 % of patients with asthma, in 10–29 % of those with idiopathic purpura and vitiligo. The prevalence of TPO antibodies is slightly higher than TgAb, and rTSH-Ab are rarely registered in non-thyroid immunological diseases.

The association of neuropsychiatric disorders and endocrine parameters in hashimoto thyroiditis

Hashimoto thyroiditis is the most common thyroid disease. This form of pathology has a diverse clinical picture, including neuropsychiatric disorders. There are frequent cases of comorbidity of autoimmune thyroiditis and psychiatric forms of pathology, along with such a nosological entity as Hashimotos encephalopathy (aka: Steroid-responsive encephalopathy of autoimmune thyroiditis), characterized by an increased level of antithyroid autoantibodies and various mental disorders, with still unclear pathogenesis. The question arises, how to regard patients with psychiatric disorders and Hashimoto thyroiditis either as patients having autoimmune thyroiditis, comorbid with psychiatric forms of pathology, or as patients with Hashimotos encephalopathy? We studied groups of patients with autoimmune thyroiditis free from any psychiatric disorders, autoimmune thyroiditis comorbid with psychiatric forms of pathology, and a group of healthy donors similar as regards to their age and sex. We also studied medical history, clinical manifestations of the disease, instrumental data and the serum levels of thyrotropin, thyroid hormones, various antithyroid autoantibodies, and prolactin. We analyzed the correlation of laboratory and instrumental parameters and clinical data in all groups of patients. Therewas a significant relationship (p 0,05) between various psychiatric symptoms and a decreased level of free thyroxine, an increased level of thyroid stimulating hormone (TSH), an increased level of prolactin and an increased volume of a thyroid gland. Asignificant relationship (p 0,05) was also found between various symptoms of hypothyroidism and a decreased level of free triiodothyronine (FT3), an increased level of antibodies to thyroglobulin (anti-TG Ab), and an increased level of antibodies to thyroid peroxidase (anti-TPO Ab).

Referrals for Elevated Thyroid Stimulating Hormone to Pediatric Endocrinologists

Objective We aimed to determine the reproducibility of TSH testing in pediatric patients referred to pediatric endocrinologists and to identify the threshold TSH levels that would predict the presence of antithyroid autoantibodies and inform decisions by pediatric endocrinologists to initiate or continue treatment with levothyroxine. Study Design We analyzed a retrospective case series of 325 children aged 1 to 18 years referred for hypothyroidism to the endocrinology clinic at a tertiary care children’s hospital. The receiver operating characteristic area under curve (AUC) determined the ability of the initial TSH level to predict pediatric endocrinologists’ treatment decisions, presence of thyroid autoantibodies, and reproducibility of elevated TSH on repeat testing. Results Of 325 patients, 191 were treated. The treated patients were more likely to have had a higher referral TSH, positive autoantibodies, and abnormal thyroid gland examination findings. An initial TSH of 5 had a specificity of only 14% for a repeat TSH of ≥5. An initial TSH level of 11 had a specificity of 90% for a repeat TSH of ≥11, with sensitivity of 90%. TSH was a relatively poor predictor (AUC, 0.711) of the presence of autoantibodies with optimal classification at TSH >8.8 mIU/L. It was better (AUC, 0.878) at predicting whether endocrinologists started or continued treatment with levothyroxine, with optimal classification at 8.2 mIU/L. TSH levels combined with antibody status and thyroid examination findings had the best ability to predict treatment (AUC, 0.930). Conclusions TSH levels slightly above the reference range should not prompt referral to pediatric endocrinologists unless another basis for clinical concern is present.

Epidemiology, risk factors and prognosis of Interferon alpha induced thyroid disorders. A Prospective Clinical Study

Introduction: Hepatitis C virus (HCV) infection is a worldwide problem and hepatitis, which is its natural unfavourable course, is still a challenge for hepatologist. At present, standards of treatment are changing from combined therapy with interferon alpha (IFN-α) and ribavirin to new antiviral drugs. The current classification divides interferon induced thyroid diseases (IITD) into two groups: autoimmune (Hashimoto disease, Graves disease, positive antithyroid autoantibodies in euthyroid patients) and non-autoimmune (destructive thyroiditis, non-autoimmune hypothyroidism). A common complication of cytokine therapy is the induction of antithyroid autoantibodies de novo without thyroid dysfunction. During therapeutic regimens combined with ribavirin, destructive thyroiditis with typical biphasic course is more common than in IFN-α monotherapy. Clinically, overt pathologies often have discrete symptoms, which cause diagnostic and therapeutic dilemmas. Aims: The aim of this study was to estimate IITD occurrence, to find risk factors for IITD development. Material and methods: The study group consisted of 66 patients treated for HCV infection. Before and during antiviral therapy, hormonal (TSH, fT4, fT3), immunological (thyroid autoantibodies), ultrasonographic and genetic (HLA-A2) parameters were evaluated. Results: Hormonal disturbances were detected in 24.2% of patients; however, 43.9% of patients had positive thyroid autoantibodies (de novo) without hormonal imbalance. Multivariate analysis revealed the following: female sex, elevated TSH level, occurrence of anti-TPO autoantibodies (TPO-Ab), and increased blood velocity in thyroid arteries are risk factors for IITD development. In conclusion: Thyroid disorders are common during IFN-α therapy. Previous epidemiological data seem to be underestimated. Important risk factors for IITD development are: female sex, elevated serum TSH concentration (≥2.5 μU/mL), positive TPO-Ab and increased blood velocity in thyroid arteries.

The effect of long-term exposure to low doses of endocrine disruptor ddt on serum levels of thyroid protein autoantigenes and antithyroid autoantibodies

Changes in secretion of thyroid autoantigenes and production of antithyroid autoantibodies after long-term exposure to low doses of DDT were studied. Changes in serum levels of antithyroid peroxidase antibodies and thyroid peroxidase, attributed to disruption of thyroxine production by DDT were found. Long-term exposure of rats to low doses of DDT revealed no specific impact on serum autoantibodies to all thyroid autoantigenes studied. The increase of the ratio of autoantibody/autoantigen for thyroid peroxidase and thyroglobulin was rather small and thus could not be considered as a significant symptom of thyroid autoimmunity.