Atrophic Autoimmune Thyroiditis Research Articles

Growth impairment in children with atrophic autoimmune thyroiditis and pituitary hyperplasia.

Atrophic autoimmune thyroiditis (AAT) is a rare phenotype of autoimmune thyroiditis (AT) in pediatric age. AAT occurs without thyroid enlargement leading to a delay in its diagnosis. Growth impairment is infrequent in autoimmune thyroiditis, if timely diagnosed. Prolonged severe hypothyroidism is a rare cause of pituitary hyperplasia (PH) in childhood. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients. Twelve patients were retrospectively evaluated at five Italian and Polish Centres of Pediatric Endocrinology for height growth impairment. In all Centres, patients underwent routine clinical, biochemical and radiological evaluations. At the time of first assessment, the 75% of patients presented height growth arrest, while the remaining ones showed growth impairment. The study of thyroid function documented a condition of hypothyroidism, due to AT, in the entire cohort, although all patients had no thyroid enlargement. Thyroid ultrasound showed frankly atrophic or normal gland without goiter. Cerebral MRI documented symmetrical enlargement of the adenohypophysis in all patients and a homogeneous enhancement of the gland after the administration of Gadolinium-DPTA. Replacement therapy with levothyroxine was started and patients underwent close follow-up every 3 months. During the 12 months of follow-up, an improvement in terms of height growth has been observed in 88% of patients who continued the follow-up. Laboratory findings showed normalization of thyroid function and the control brain MRI documented complete regression of PH to a volume within the normal range for age and sex. This is the largest pediatric cohort with severe autoimmune primary hypothyroidism without goiter, but with pituitary hyperplasia in which significant growth impairment was the most evident presenting sign. AAT phenotype might be correlated with this specific clinical presentation. In youths with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism.

БОЛЬШОЙ ПЕРИКАРДИАЛЬНЫЙ ВЫПОТ У ГРУДНОГО РЕБЕНКА С АУТОИММУННЫМ ТИРЕОИДИТОМ В ФАЗЕ ГИПОТИРЕОЗА И СИНДРОМОМ ДАУНА: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

The article describes the difficulties in diagnosing and treating a large pericardial effusion caused by the autoimmune atrophic thyroiditis with a debut in the form of a myxedema coma in a 7 months old child with Down syndrome. The clinical, laboratory and instrumental picture of a rare complication of a hypothyroidism - a hypothyroid (myxedematous) coma, the epidemiology and comorbidity of Down syndrome, autoimmune thyroiditis and hypothyroidism, manifestation of hypothyroidism with pericardial effusion prevailing in the pathological symptom complex are discussed in the article.

Investigation of TSH receptor blocking antibodies in childhood-onset atrophic autoimmune thyroiditis.

.Atrophic autoimmune thyroiditis (AAT) is a type of autoimmune hypothyroidism without goiter. TSH receptor-blocking antibodies (TSBAb) are involved in its etiology in adults. Reportedly, this disease is extremely rare in children. In this study, we aimed to investigate the prevalence of TSBAb during AAT onset in children using a commercially available cell-based bioassay TSAb kit. We conducted a multicenter retrospective observational study. We collected data of patients with AAT who were < 15 yr old, enrolled in a collaborative research group, and diagnosed since July 2003. AAT was defined as acquired autoimmune hypothyroidism without thyroid enlargement. Eighteen patients (including 15 females) whose TSH receptor antibody (TRAb) or TSBAb levels were measured within a year from the initial visit were included. The median age at diagnosis was 9.3 years, and the estimated time between onset and diagnosis was 2.6 yr. The positive rate for either TSBAb or TRAb was 38.8% (95% confidence interval: 18.3–59.5%). There were no significant differences in age, the estimated time between onset and diagnosis, and FT4 levels at diagnosis between the TSBAb-positive and -negative groups. Unlike previous reports, we showed that the prevalence of TSBAb-positivity in childhood-onset AATs is not rare, as in adults.

Manifestations buccodentaires des maladies thyroïdiennes

Oral disorders were observed in children with congenital hypothyroidism, lately apparent because of difficulties of feeding, swallowing disorders, and macroglossia. Macroglossia was also a component of the severe acquired myxedema, particularly observed in hypothyroidism related to autoimmune atrophic thyroiditis beyond menopause. Lingual ectopy in children and adults could determine respiratory gene or swallowing difficulties, and were detectable by visual examination and the endobuccal touch. Expression of these events was completely minimized since the neonatal screening of congenital hypothyroidism, also by the common practice in adults of serum TSH determinations. Congenital and acquired hormonal deficits are now early detected and correct with suppletive doses of levothyroxine. Oral expression of hyperthyroidism is poor, even if thyrotoxicosis is sometimes revealed by increased thirst. Caution is required for dental care, mainly due to changes in the hemostatic functions. Finally, a genetic predisposition to the medullary thyroid cancer may be revealed by an oral and neuromatosis. Radioisotopic therapy of thyroid cancers is likely to alter the salivation.

Fine needle aspiration cytology of thyroid and its correlation with serological findings

Background: Thyroid autoimmunity can cause several forms of thyroid disorders i.e. Grave’s disease, Hashimoto’s thyroiditis, atrophic autoimmune thyroiditis, post-partum thyroidits etc. Cytological diagnosis may be sometimes difficult is some cases. In such conditions, cytology along with serological tests aid at reaching a correct diagnosis.Hence, this study was undertaken to evaluate the serum level of anti-TPO antibody with respect to serum concentrations of thyroid hormones and its importance in diagnosing autoimmune thyroiditis.Material and Methods: This study was carried out in the department of pathology from June 2013-May 2014. Patients coming to the department of pathology TUTH, Maharajgunj for FNA of thyroid were included. TFT level was noted and anti TPO antibody level was evaluated by CLIA.Results: Ninety-five thyroid FNAC was included in the study, which comprises of 16.8 % males and 83.2% females with a M: F 1: 4.9. Maximum number of cases was seen in the age range 21-30 years (25.3%), mean age being 40.4years. The cytological diagnosis comprised colloid goiter(43.2%), lymphocytic thyroiditis (25.3%), Hashimoto thyroiditis(18.9%). Out of 42 cases of autoimmune thyroiditis diagnosed cytologically, 16 (38%) were hypothyroid, 4 (9.5%) hyperthyroid, 8 (19%) sub-clinical hypothyroid and 14 (33.5%) were euthyroid. The sensitivity and specificity of positive anti TPO in correctly identifying autoimmune thyroiditis was 85.7% and 79.2% respectively. The positive and negative predictive value for the test was 76.5% and 87.5% respectively.Conclusion: Nodular goitre can harbour a certain per cent of autoimmune thyroiditis and in such cases anti TPO antibody level along with cytodiagnosis appears to be helpful.

Successful Combined Treatment for Atrophic Thyroiditis With Growth Hormone Deficiency.

Persons with untreated atrophic thyroiditis develop a permanent height deficit. Adequate thyroxine replacement therapy can improve growth and the probability of attaining normal adult height. However, height deficit is related to duration of thyroxine deficiency, regardless of the adequacy of thyroxine replacement therapy after diagnosis.1 Several studies reported that use of adjunctive therapy with growth hormone (GH) and gonadotropin-releasing hormone agonist (GnRHa) to improve the final height of patients.2-5 The rationale for this therapy is to prolong the growth period by inhibiting pubertal progression and delaying epiphyseal fusion,6 although GH deficiency in atrophic thyroiditis patients usually improves after L-thyroxine treatment. We report a case of autoimmune atrophic thyroiditis in a boy who presented with GH deficiency even after his enlarged pituitary gland had decreased in size. Combined treatment with GH, GnRHa, and L-thyroxine was successful in allowing the patient to attain normal adult height.

Advances in Graves' Disease

Advances in Graves' Disease

A 5-year-old boy with atrophic autoimmune thyroiditis caused by thyroid-stimulation blocking antibodies

A 5-year-old boy was presented for a growth disturbance, which was initially noted at 3 years of age. Endocrinological testing identified severe hypothyroidism, defined by the following levels: TSH 990.5 microU/mL, F-T3 0.26 pg/mL, and F-T4 0.09 ng/dL. Serum anti-thyroid peroxidase (TPO) antibodies were 158 IU/mL and serum thyroid-stimulation blocking antibodies (TSBab) levels were 82.1 IU/mL (normal range < 45.6). Thyroid scintigraphy with 99mTc showed markedly decreased uptake, and magnetic resonance imaging (MRI) revealed pituitary hyperplasia. He was diagnosed with atrophic autoimmune thyroiditis. His thyroid function and pituitary size normalized following thyroid hormone replacement therapy. We report a rare case of a young boy with atrophic thyroiditis caused by TSBab.

Autoimmune thyroid diseases: genetic susceptibility of thyroid-specific genes and thyroid autoantigens contributions

Autoimmune thyroid diseases are common polygenic multifactorial disorders with the environment contributing importantly to the emergence of the disease phenotype. Some of the disease manifestations, such as severe thyroid-associated ophthalmopathy, pretibial myxedema and thyroid antigen/antibody immune complex nephritis are unusual to rare. The spectrum of autoimmune thyroid diseases includes: Graves' disease (GD), Hashimoto's thyroiditis (HT), atrophic autoimmune thyroiditis, postpartum thyroiditis, painless thyroiditis unrelated to pregnancy and thyroid-associated ophthalmopathy. This spectrum present contrasts in terms of thyroid function, disease duration and spread to other anatomic location. The genetic basis of autoimmune thyroid disease (AITD) is complex and likely to be due to genes of both large and small effects. In GD the autoimmune process results in the production of thyroid-stimulating antibodies and lead to hyperthyroidism, whereas in HT the end result is destruction of thyroid cells and hypothyroidism. Recent studies in the field of autoimmune thyroid diseases have largely focused on (i) the genes involved in immune response and/or thyroid physiology with could influence susceptibility to disease, (ii) the delineation of B-cell autoepitopes recognized by the main autoantigens, thyroglobulin, thyroperoxidase and TSH receptor, to improve our understanding of how these molecules are seen by the immune system and (iii) the regulatory network controlling the synthesis of thyroid hormones and its dysfunction in AITD. The aim of the present review is to summarize the current knowledge regarding the relation existing between some susceptibility genes, autoantigens and dysfunction of thyroid function during AITD.

Severe hyperlipidemia, secondary to hypothyroidism due to atrophic thyroiditis in a girl

We present a 5 years 8 months old girl with severe hyperlipidemia (high total cholesterol, and low density lipoprotein values, and also, ectopic fat pericardial deposit). She was treated with diet and cholestyramine, without diagnosis of her disease etiology. Growth detention, weight loss, retarded bone age and clinical signs of hypometabolism were recorded. Thyroid profile confirms hypothyroidism diagnosis. Based on positive anti-thyroid antibodies and clearly reduced thyroid volume, a diagnosis of autoimmune atrophic thyroiditis was made, a very unusual pathology in early infancy. Linear growth was affected by late diagnosis.

A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure

Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism. A population study including 4649 randomly selected subjects. Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO-Ab), thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4. Thyroid volume was categorized as small (< 6.6 ml) in 4.7%, normal (6.6-14.9 ml) in 60.4% and large (> 14.9 ml) in 34.9% of participants. Thyroid nodules were found in 29.7%. Serum TSH was low (< 0.4 mIU/l) in 4.7%, normal (0.4-3.6) in 91.0% and high (> 3.6) in 4.3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0.62% and of subclinical autoimmune atrophic thyroiditis 0.24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0.001). An association between thyroid nodules and TPO-Ab in univariate analyses (P < 0.001) was due to confounding by sex and age (multivariate model, P = 0.23). We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short.

The long-term effect of replacement therapy in a short girl with autoimmune atrophic thyroiditis of prepubertal onset.

A 9 yr 11 mo old girl was admitted to our hospital because of short stature. Her growth rate gradually decreased and her height was 120 cm (–2.5 SD) on admission. The mother’s and father’s heights were 157 cm (–0.2 SD) and 163 cm (–1.3 SD), respectively. Her bone age was retarded (6 yr 10 mo). An MRI indicated pituitary enlargement, which mimicked adenoma. Evaluation of the pituitary-thyroid axis and thyroid function proved she had primary hypothyroidism (T3 0.5 ng/ml, T4 1.0 μg/dl, TSH 1,030 μU/ml). These findings, thyroid autoantibody (anti-microsome antibody 400 xs) and histopathology (moderate fibrosis and mild lymphocytic infiltration) suggested acquired hypothyroidism due to autoimmune atrophic thyroiditis of prepubertal onset. Since the evaluation, she has been treated with levothyroxine. The pituitary enlargement disappeared within 3 mo after levothyroxine replacement. The growth rate increased and her height reached 153.2 cm (–1.0 SD) during 10 yr replacement (at 19 yr 11 mo of age). An improvement in her final height was obtained by long-term thyroid hormone replacement therapy. Enough endocrinological study and repeated MRI evaluation are necessary in cases of pituitary enlargement which mimics adenoma before considering surgery.

Epidemiology and prevention of clinical and subclinical hypothyroidism.

Iodine deficiency is the most common cause of hypothyroidism worldwide. In persons living in iodine-replete areas, causes are congenital, spontaneous because of chronic autoimmune disease (atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis [Hashimoto's thyroiditis]), or iatrogenic because of goitrogens, drugs, or destructive treatment for thyrotoxicosis. Screening for congenital hypothyroidism exists and its use prevents mental retardation. The prevalence of spontaneous hypothyroidism is between 1% and 2% and is more common in older women and 10 times more common in women than in men. A significant proportion of subjects have asymptomatic chronic autoimmune thyroiditis and 8% of women (10% of women over 55 years of age) and 3% of men have subclinical hypothyroidism. Approximately one third of patients with newly diagnosed overt hypothyroidism have received destructive therapy for hyperthyroidism and indefinite surveillance is required. There is not much that can be done to prevent the occurrence of spontaneous autoimmune hypothyroidism, but if identified early, something can be done to prevent progression to overt disease. Controversy exists as to whether healthy adults would benefit from screening for autoimmune thyroid disease because a significant proportion of subjects tested will have evidence of mild thyroid failure. Case finding in women at menopause or visiting a primary care physician with nonspecific symptoms appears justified.

Atrophic Autoimmune Thyroiditis with Positive Thyroid Stimulation Blocking Antibody in a Prepubertal Boy

Atrophic Autoimmune Thyroiditis with Positive Thyroid Stimulation Blocking Antibody in a Prepubertal Boy

Calcitonin reserve in different stages of atrophic autoimmune thyroiditis.

The objective of this study was to determine the calcitonin (CT) hormone reserve in different severity of atrophic autoimmune thyroiditis (AAT). Forty-eight female patients with AAT were divided into four groups based on basal and peak thyrotropin (TSH) values (after oral thyrotropin-releasing hormone [TRH], free triiodothyronine (FT3) and free thyroxine (FT4) ranging from normal in group 1 to overt hypothyroidism in group 4. All had thyroid antibodies. The control group comprised euthyroid females of comparable age, without thyroid antibodies. Basal CT and CT response to calcium infusion (area under the curve) were investigated as parameters of CT reserve. Basal CT was lower in groups 2 to 4 of patients with AAT (compared to controls), but the difference was not significant. Stimulated CT levels were lower (p < 0.05) in all groups of patients compared to controls, with markedly reduced CT-secretory reserve in group 4. Thyroid antibody concentrations and, basal and postinfusion calcium levels were not significantly different among the various groups. In conclusion CT deficiency (especially stimulated values) occurs in AAT and is more severe in hypothyroid patients than in earlier stages of AAT.

Helicobacter pylori infection is markedly increased in patients with autoimmune atrophic thyroiditis.

Infection by viral or bacterial pathogens has been suspected in playing a role in the development of autoimmune thyroid disease. Because Helicobacter pylori might be involved in the development of nongastrointestinal conditions such as rosacea, ischemic heart disease, and diabetes mellitus, we evaluated the prevalence of H. pylori infection in patients with autoimmune thyroid disease. Fifty-nine patients with autoimmune thyroid disease were included: autoimmune atrophic thyroiditis (n=21), Hashimoto's thyroiditis (n=18), and Graves' disease (n=20). Twenty patients with nontoxic multinodular goiter served as controls for nonautoimmune thyroid disease, and 11 patients with Addison's disease served as controls for nonthyroid endocrine autoimmune disease. The levels of anti-H. pylori immunoglobulin G (IgG) were determined, and a radiolabeled urea breath test were performed. The prevalence of H. pylori infection was markedly increased in the patients with autoimmune atrophic thyroiditis (85.7%), compared with the controls with nontoxic multinodular goiter (40%) and Addison's disease (45.4%). Infection by H. pylori resulted in increased levels of gastrin, pepsinogen I, and pepsinogen II in the H. pylori-positive groups, compared with the H. pylori-negative groups. A positive linear regression was found between the levels of microsomal autoantibodies and those of anti-H. pylori IgG in patients with autoimmune atrophic thyroiditis (n=21; r=0.79; p < 0.01). Finally, and although the overall prevalence of H. pylori infection was not increased, the anti-H. pylori IgG levels and the results from the breath test were higher in the patients with Graves' disease and Hashimoto's thyroiditis patients than in the controls. Clearly, the prevalence of H. pylori infection is increased in autoimmune atrophic thyroiditis and results in abnormalities of gastric secretory function. The strong relation between the levels of anti-H. pylori IgG and the levels of microsomal antibodies suggests that H. pylori antigens might be involved in the development of autoimmune atrophic thyroiditis or that autoimmune function in autoimmune atrophic thyroiditis may increase the likelihood of H. pylori infection.

Humoral thyroid autoimmunity is not involved in the pathogenesis of myxedematous endemic cretinism.

A role of thyroid autoimmunity in the pathogenesis of myxedematous endemic cretinism was suggested by reports indicating the presence of thyroid growth-blocking antibodies in the sera of these patients. To check this hypothesis, we searched for TSH receptor antibodies with thyroid growth-blocking or adenylate cyclase (AC)-inhibiting (TSH-blocking) activity in immunoglobulin G (IgG) from 18 euthyroid and 21 hypothyroid endemic cretins living in Italy and Peru. Among hypothyroid cretins, 12 had no palpable goiter. Stages I-III goiters were present in 12 of 18 euthyroid cretins. Controls included 25 euthyroid nongoitrous subjects living in the same endemic regions as cretins, and 10 normal subjects from an iodine-sufficient area. IgG from 4 selected patients with autoimmune atrophic thyroiditis and from 2 neonates with sporadic transient congenital hypothyroidism due to maternal TSH-blocking antibodies were included in the study. The blocking effect of the IgG was assessed in FRTL-5 cells by measuring TSH-stimulated [3H]thymidine incorporation, DNA accumulation, and AC activation. A radioreceptor assay was used to detect TSH-binding inhibiting antibodies (TBIAb). No IgG from hypothyroid endemic cretins without goiter contained TBIAb or inhibited TSH-stimulated cell growth or AC activation. The effect of IgG from hypothyroid nongoitrous cretins did not differ from that produced by IgG from hypothyroid cretins with goiter, euthyroid cretins with or without goiter, or normal controls. In contrast to these results, IgG from patients with autoimmune atrophic thyroiditis and from neonates with sporadic transient congenital hypothyroidism contained TBIAb that inhibited both TSH-stimulated cell growth and AC activation. In conclusion, our results indicate that, similar to other types of endemic cretinism, hypothyroid endemic cretins without goiter do not have TSH receptor antibodies able to inhibit TSH-stimulated thyroid cell growth or function. These observations argue against a role of humoral thyroid autoimmunity in the development of myxedematous endemic cretinism.

Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis

Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis

A strong association between thyrotropin receptor-blocking antibody-positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1*0302 in Koreans.

We investigated whether the associations between HLA alleles of patients with autoimmune hypothyroidism varied according to the presence or absence of TSH receptor-blocking antibody (TRBab). We analyzed the HLA-A, -B, -C, and -DR antigens by serotyping and the DQA1 and DQB1 genes using both enzymatic DNA amplification and sequence-specific oligonucleotide hybridizations. The patient population consisted of 47 Korean patients with atrophic autoimmune thyroiditis and 62 patients with goitrous autoimmune thyroiditis. The antigen frequency of HLA-DR8 was significantly increased in 23 atrophic autoimmune thyroiditis patients that were positive for TSH binding inhibitor immunoglobulin (TBII) compared to 136 controls [52% vs. 16%; chi 2 = 13.1; Pc (corrected P value) = 0.003]. This relative risk was 5.7; the etiological fraction was 0.43. HLA-DQB1*0302 was also increased in patients with TBII-positive atrophic autoimmune thyroiditis (24% vs. 7%; chi 2 = 11.2; Pc = 0.012; relative risk = 4.4; etiological fraction = 0.19). No specific DR antigens or DQB1 alleles were increased in either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. A significant decrease in the frequency of HLA-DR6 antigen was observed in both TBII-positive atrophic autoimmune thyroiditis (0% vs. 32%; chi 2 = 8.4; Pc = 0.03) and goitrous autoimmune thyroiditis (0% vs. 32%; chi 2 = 23.2; Pc < 0.001) patients. The frequency of the HLA-Cw1 antigen was significantly increased in all patient groups. We conclude that TRBab-positive atrophic autoimmune thyroiditis is immunogenetically different from both goitrous autoimmune thyroiditis and TRBab-negative atrophic autoimmune thyroiditis. It is possible that HLA-DR8 and/or DQB1*0302 may be related to the susceptibility genes involved in the production of TRBab in Koreans.

A strong association between thyrotropin receptor-blocking antibody- positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1*0302 in Koreans

A strong association between thyrotropin receptor-blocking antibody- positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1*0302 in Koreans