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1.  Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity 
Background & objectives:
Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus.
Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies.
A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody.
Interpretation & conclusions:
Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.
PMCID: PMC3657903  PMID: 23481055
Anti-GAD antibody; anti-TPO antibody; anti-TTG antibody; thyroid autoimmunity
2.  Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus 
Upsala Journal of Medical Sciences  2009;114(4):214-220.
Type 1 diabetes mellitus (T1DM) is associated with an autoimmune reaction to thyroid antigens including thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg).
We determined in children with T1DM the relationship of positive anti-thyroid antibodies to potential risk factors, including, age, gender, duration of diabetes, and glutamic acid decarboxylase antibodies (anti-GAD).
Materials and methods
We studied 144 children and adolescents with T1DM. Their age was 12.3 ± 4.6 (mean ± SD) years, and duration of diabetes was 4.6 ± 3.8 years. Anti-thyroid antibodies were determined using a luminescence method and anti-GAD using an enzyme-linked immunosorbent assay.
The prevalence rates of anti-thyroid antibodies among the children with T1DM in our study were: anti-TPO (17.4%), anti-Tg (11.1%), and of both anti-thyroid antibodies (10.4%). The presence of serum anti-thyroid antibodies was positively associated with age (16.6 years in those with positive tests versus 12.0 years in those with negative tests, P = 0.027), duration of diabetes (7.4 versus 4.3 years, P = 0.031), and serum TSH (Thyroid-stimulating hormone) levels (4.8 versus 2.3 μIU/mL, P = 0.002). The presence of both anti-thyroid antibodies was associated with female sex (boys: 4/75 (5.3%), girls: 11/69 (15.9%), chi-square = 6.44, P = 0.04). Subclinical autoimmune thyroiditis (SAIT) was present in 55.5% of the patients with thyroid antibody-positivity and was positively associated with age (16.6 versus 12.0 years, P = 0.001) and diabetes duration (7.6 versus 4.2 years, P = 0.001). Multiple logistic regression analysis revealed that the development of anti-thyroid antibodies was predicted by: 1) the presence of anti-GAD (odds ratio (OR) 1.45, 95% confidence interval (CI) 1.09–1.92), 2) the presence of a second anti-thyroid antibody (OR 134.4, 95% CI 7.7–2350.3), and 3) older age (OR 22.9, 95% CI 1.13–463.2).
Thyroid autoimmunity was associated with female gender, increasing age, long diabetes duration, the persistence of anti-GAD, and with TSH elevation, indicating subclinical hypothyroidism.
PMCID: PMC2852777  PMID: 19824863
Childhood; subclinical autoimmune thyroiditis; thyroid autoantibodies; type 1 diabetes
3.  L-thyroxine Stabilizes Autoimmune Inflammatory Process in Euthyroid Nongoitrous Children with Hashimoto’s Thyroiditis and Type 1 Diabetes Mellitus 
Objective: To investigate if L-thyroxine (T4) treatment may influence the clinical course of autoimmune thyroiditis (AIT) or prevent progression to subclinical or overt hypothyroidism in euthyroid nongoitrous pediatric patients with type 1 diabetes mellitus (T1DM) and AIT.
Methods: The study was performed in four Polish pediatric diabetes centers. Of 330 children with T1DM and AIT followed between 2008 and 2012, 101 received L-T4 and 160 underwent clinical observation for 24 months. Thyroid stimulating hormone (TSH), free T4 (fT4), anti thyroid peroxidase antibody (anti-TPO), anti thyroglobulin antibody (anti-TG), glycosylated hemoglobin (HbA1c) levels, and lipid profile were assessed in all patients. Ultrasonographic evaluation was also performed in all children at each examination.
Results: Patients treated with thyroid hormones had higher TSH levels (3.99; interquantile 3.5 to 4.52 vs. 2.09 mIU/L; interquantile 1.55 to 3.06; p<0.0001). A fall in TSH level (0.87 mIU/L 95% CI 0.43-1.30; p<0.0001) was documented after the first year of treatment. FT4 level did not differ between the groups at baseline (p=0.7434), but rose in the treatment group and fell in the control group [mean difference 0.78 95% CI
-0.22-1.53 pmol/L (p=0.02) after 12 months and 0.98 95% CI 0.04-1.76 (p=0.005) after 24 months]. Higher levels of anti-TPO were initially found in the treated patients (p<0.0001) and significantly decreased over the 24-month period (p<0.0001). Children in the treatment group had higher anti-TG levels (p<0.0001), which showed a borderline decrease (p=0.08) in time. In the control group, anti-TG levels rose marginally (p=0.06) during the study.
Conclusions: The data demonstrate that treatment with L-T4 in euthyroid pediatric patients with T1DM and AIT stabilizes autoimmune inflammation in the thyroid gland and is to be recommended as soon as the diagnosis is established.
Conflict of interest:None declared.
PMCID: PMC3890223  PMID: 24379033
autoimmune thyroiditis; type 1 diabetes mellitus; L-thyroxine treatment; lipid profile; glycemic control; thyroid volume SDS
4.  Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty 
Archives of Disease in Childhood  2005;90(4):411-414.
Aims: To investigate the natural history and incidence of autoimmune thyroiditis (AIT) in paediatric patients with type 1 diabetes (T1D).
Methods: Since 1990, annual screening for thyroid disease has been performed in children and adolescents with T1D. Antibodies against thyroperoxidase (anti-TPO) and thyroglobulin (anti-TG) as well as TSH were measured in 659 patients (54.3% boys). In 126 patients, anti-TPO and anti-TG levels were followed at yearly intervals from onset up to five years of T1D. Anti-TPO above 30 U/ml and anti-TG above 20 U/ml were considered positive, values above 100 U/ml as significantly raised and indicative of AIT. L-thyroxine treatment was started if TSH was higher than 4.5 µU/ml and/or thyroid gland enlargement on thyroid ultrasound was present.
Results: At initial screening, 15.4% of patients had raised anti-TPO and 14.4% anti-TG. Girls had more frequently raised antibodies than boys. Sixty two patients (9.4%, 61% girls) required treatment with L-thyroxine. The cumulative incidence (SE) of AIT after 10 years of diabetes was 0.14 (0.02), being significantly higher in females (0.18 (0.03)), particularly after the age of 12 years. At T1D onset, positive anti-TPO and anti-TG were present in 21 of 126 patients (16.7%), each. All patients with significantly increased values of anti-TPO (n = 17, 148–5340 U/ml) and anti-TG (n = 11, 140–2000 U/ml) at T1D onset remained positive during the following five years.
Conclusions: For early detection of autoimmune thyroiditis in children with T1D, measurement of anti-TPO and TSH at T1D onset and in yearly intervals after the age of 12 years is recommended.
PMCID: PMC1720371  PMID: 15781936
5.  Thyroid disorders in polycystic ovarian syndrome subjects: A tertiary hospital based cross-sectional study from Eastern India 
Polycystic ovarian syndrome (PCOS), the most common endocrinopathy of women in the reproductive age group seems to be adversely affected by associated thyroid dysfunction. Both pose independent risks of ovarian failure and pregnancy related complications.
The present study from Eastern India is, therefore, aimed to investigate the prevalence and etiology of different thyroid disorders in PCOS subjects.
Settings and Design:
Cross-sectional hospital based survey-single centre observational case-control study.
Materials and Methods:
This prospective single-center study recruited 106 female patients with hypertrichosis and menstrual abnormality among which 80 patients were defined as having PCOS according to the revised 2003 Rotterdam criteria and comprised the study population. Another 80 age-matched female subjects were studied as the control population. Thyroid function and morphology were evaluated by measurement of serum thyroid stimulating hormone (TSH), free thyroxine levels (free T3 and free T4), anti-thyroperoxidase antibody (anti-TPO Ab), clinical examination and ultrasound (USG) of thyroid gland.
Statistical Analysis Used:
It was done by Student's t-test and Chi-square test using appropriate software (SPSS version 19).
This case-control study revealed statistically significant higher prevalence of autoimmune thyroiditis, detected in 18 patients (22.5% vs. 1.25% of control) as evidenced by raised anti-TPO antibody levels (means 28.037 ± 9.138 and 25.72 ± 8.27 respectively; P = 0.035). PCOS patients were found to have higher mean TSH level than that of the control group (4.547 ± 2.66 and 2.67 ± 3.11 respectively; P value < 0.05). There was high prevalence of goiter among PCOS patients (27.5% vs. 7.5% of control, P value > 0.001). On thyroid USG a significantly higher percentage of PCOS patients (12.5%; controls 2.5%) had hypoechoic USG pattern also compatible with the diagnosis of autoimmune thyroiditis.
High prevalence of thyroid disorders in PCOS patients thus points towards the importance of early correction of hypothyroidism in the management of infertility associated with PCOS.
PMCID: PMC3683210  PMID: 23776908
Anti-thyroperoxidase antibody; autoimmune thyroiditis; hypothyroidism; polycystic ovarian syndrome
6.  Anti-thyroid peroxidase antibody and vitiligo: a controlled study 
BMC Dermatology  2006;6:3.
Vitiligo is an acquired depigmenting disorder due to destruction of melanocytes. Although many theories have been suggested for its pathogenesis, the role of autoimmunity is the most popular one. The association of vitiligo with autoimmune thyroid diseases and the increased prevalence of autoantibodies including thyroid autoantibodies in vitiligo favor this role. Our objective was to compare the frequency of thyroid peroxidase antibody (anti-TPO) in vitiligo patients with healthy subjects in Iran.
Ninety-four cases of vitiligo (46 female and 48 male) and 96 control subjects (49 female and 47 male) were enrolled in this controlled study. Patients with known thyroid disease, history of thyroid surgery and those receiving thyroid medications were not included. The two groups were matched regarding gender and age. The demographic data, symptoms related to thyroid diseases and results of skin and thyroid examinations were recorded in a questionnaire for each subject. Thyroid function tests including free T3, free T4 and TSH-IRMA were performed. Anti-TPO levels were assessed as well. The collected data were analyzed by SPSS version-11 in vitiligo patients and subgroups according to gender, age, extent, and duration of the disease compared with the control group.
Anti-TPO was detected in 17 (18.1%) of patients affected by vitiligo, while this figure was 7 (7.3%) in the control group; the difference was significant with p-value < 0.025 (Phi & Cramer's V = 0.162). When analyzing subgroups, the difference in the frequency of anti-TPO remained significant only in females (p-value < 0.044) (Phi & Cramer's V = 0.207) and in patients in the age ranges of 18–25 (p-value < 0.05) (Phi & Cramer's V = 0.28) and 26–35 year-old (p-value < 0.042) (Phi & Cramer's V = 0.304).
The difference of the frequency of anti-TPO was not significant regarding the duration and extent of vitiligo. In addition, there was no significant difference in the levels of free T3, free T4, and TSH in vitiligo patients compared with the control group.
According to our study, anti-TPO was shown to be significantly more common in vitiligo patients especially in young women, compared with control group. As this antibody is a relatively sensitive and specific marker of autoimmune thyroid disorders including Hashimoto thyroiditis and Graves' disease, and considering the fact that vitiligo usually precedes the onset of thyroid dysfunction, periodic follow-up of vitiligo patients for detecting thyroid diseases is further emphasized especially in young women with increased level of anti-TPO.
PMCID: PMC1431557  PMID: 16526964
7.  The Evaluation of Thyroid Diseases in Patients with Pemphigus Vulgaris 
The Scientific World Journal  2012;2012:146897.
Background. Thyroid disorders may affect all of the organ systems of the body and they are also highly associated with a wide variety of skin disorders. The aim of this study was to investigate the prevalence of thyroid function abnormalities and thyroid autoimmunity in patients with pemphigus vulgaris (PV) and to determine the association between thyroid disorders and clinical involvement and systemic corticosteroid treatment in patients with PV. Methods. The study consisted of eighty patients with PV and eighty healthy individuals. Thyroid functions (fT3, fT4, and TSH) and thyroid autoimmunity (anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibodies) were investigated in both groups. Primary thyroid disease (PTD) was diagnosed with one or more of the following diagnostic criteria: (i) positive antithyroid antibodies, (ii) primary thyroid function abnormalities. Results. Significant changes in the serum thyroid profile were found in 16% (13/80) of the PV group and 5% (4/80) of the control group. Positive titers of antithyroid antibodies (anti-TPO and anti-Tg) were observed in 7 patients (9%) with PV and one in the control group (1,2%). Hashimoto thyroiditis was diagnosed in 9% of PV patients and it was found to be more prevalent in the mucosal form of PV. PTD was found in 13 of (%16) PV patients which was significantly high compared to controls. PTD was not found to be associated with systemic corticosteroid use. Free T3 levels were significantly lower in PV group compared to the control group and free T4 levels were significantly higher in PV group compared to the controls. Conclusions. PV may exist together with autoimmune thyroid diseases especially Hashimoto thyroiditis and primer thyroid diseases. Laboratory work-up for thyroid function tests and thyroid autoantibodies should be performed to determine underlying thyroid diseases in patients with PV.
PMCID: PMC3478722  PMID: 23118611
8.  Prevalence, clinical and biochemical profile of subclinical hypothyroidism in normal population in Mumbai 
Subclinical Hypothyroidism (ScHt) affects 3–15% of the adult population. It's clinical and biochemical profile is not well defined, especially in Indian scenario. Our study aimed at screening normal population to define normative ranges of thyroid hormones and Serum thyroid stimulating hormone (S.TSH) and prevalence of ScHt and thyroid autoimmunity.
Materials and Methods:
Two-hundred thirty-seven normal subjects without family history of thyroid disease were evaluated for symptoms and laboratory tests for thyroid dysfunction and autoimmunity.
The thyroid function tests were as follows:
Euthyroid Group:
Mean values were: T3: 1.79 ± 0.42 ng/mL, T4: 10.23 ± 2.25 μg/dL, FT3: 1.88 ± 0.19 pg/mL, FT4: 1.12 ± 0.21 ng/dL, S.TSH: 2.22 ± 1.06 μlu/mL. 10.2% of euthyroid subjects had antimicrosomal antibodies (AMA) +ve (mean titer 1:918) and 23.6% were anti-thyroid peroxidase autoantibody (anti-TPO) +ve (mean titer 15.06 Au/mL). The euthyroid outlier range for S.TSH was 0.3–4.6 μlu/mL. The values were comparable in both the sexes. Those with S.TSH ≥ 5 μlu/mL were defined to have ScHt.
ScHt Group:
Prevalence of ScHt was 11.3% (M:F ratio 1:3.7). 74% belonged to 35–54 years age group and prevalence increased with age (post-menopausal females: prevalence 20%). S.TSH was 9.8 ± 7.22 μlu/mL, mean S.AMA was 1:5079 (40.7% positivity) and mean S.anti-TPO was 260 Au/mL (47.6% positivity). Majority were agoitrous (74%), and stage I goiter was seen in 26% of this population. Symptom score of 5–8 was seen in 55% ScHt subjects versus 35% normal subjects.
Mean S.TSH in our population was 2.22 μlu/mL (euthyroid outliers: 0.3–4.6 μlu/mL); hence, S.TSH above 4.6 μlu/mL should be considered as abnormal. The prevalence of thyroid autoimmunity increases after age of 35 years. ScHt presents mainly in agoitrous form and with positive antibodies, suggesting autoimmunity as the cause.
PMCID: PMC3712376  PMID: 23869302
Autoimmunity; normative ranges; prevalence; subclinical hypothyroidism
9.  Evaluation of thyroid dysfunction in pregnant women with gestational and pre-gestational diabetes 
Objective: The aim of this study was to investigate thyroid function tests in Gestational Diabetes Mellitus (GDM) and pre-gestational DM and control group.
Methodology : There were 61 pregnant diabetic women in study group and 35 pregnant women in control group. Serum T4, T3, T3RU, FTI, TSH and Anti TPO Ab were assessed in each person.
Results : About 36% of patients had GDM and 64% pre-gestational DM. Thyroid dysfunction was detected in 18% of study group compared with 8.6% of control group (P = 0.2). There was Thyroid dysfunction in 4.5% of GDM and 25.6% of pregestational DM (P = 0.045). There was no statistically significant difference between thyroid dysfunction in GDM group and control group (P=0.99).27% of GDM and 36% of pregestational DM and 23% of control group had positive titer of Anti TPO Ab without statistically significant differences among the three groups.
Conclusion : Thyroid dysfunction is prevalent in women with pre-gestational DM so, thyroid function should be evaluated in these patients during pregnancy. Rate of thyroid dysfunction in GDM patients is similar to normal pregnant control women. High prevalence of positive titer of TPO Ab was seen in diabetic and non-diabetic pregnant women.
PMCID: PMC3809223  PMID: 24353594
Thyroid dysfunction; GDM; Pregestational DM; Anti TPO Ab; Anti TgAb
10.  Protein-energy Malnutrition in Goitrous Schoolchildren of Isfahan, Iran 
Some studies have shown the possible role of protein-energy malnutrition (PEM) in persistence of endemic goiter in iodine replenished areas. The present study was conducted to assess the association between PEM and goiter in schoolchildren of Isfahan, Iran.
In a cross-sectional study using multistage cluster random-sampling, 2331 schoolchildren with age ranged from 6-13 years old with a female to male ratio of 1.60 were enrolled. Thyroid size was examined by two endocrinologists for goiter detection. Children were considered goitrous if they had palpable or visible goiters according to World Health Organization (WHO)/United Nations children's Fund/International Council for the Control of Iodine Deficiency criteria. Weight and standing height were measured using the standard tools and anthropometric indices were calculated using the WHO AnthroPlus software developed by the World Health Organization. Height-for-age Z-scores (HAZ), weight-for-age Z-scores (WAZ) and body mass index (BMI) for age were calculated for each child. Children with a HAZ, WAZ or BMI-for-age of Z-score < –2.0 were classified as stunted, underweight or thin, respectively. Blood samples were drowned to measure serum thyroid hormones.
Overall, 32.9% of subjects were classified as goitrous. Weight, height, BMI, WAZ and BMI-for-age Z-score were significantly lower in children with goiter than in children who did not have goiter (P < 0.05). The prevalence of goiter in thin children was higher than that in non-thin ones (48.4 vs. 31.6%, odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.52-2.69, P < 0.001). Although 33.4% of non-stunted children were goitrous, 31% of stunted ones had goiter (P = 0.5). According to the logistic regression model taking sex and age as covariates, the only significant parameter affecting palpable goiter detection was thinness (OR = 2.13, 95% CI: 1.22-3.69, P < 0.001).
In the present study, we found a high prevalence of goiter in children who were malnourished. It seems that PEM may play a role in the still high prevalence of goiter in this region.
PMCID: PMC4050673  PMID: 24932384
Body mass index-for-age Z-score; goiter; height-for-age Z-score; Iran; protein-energy malnutrition; weight-for-age Z-score
11.  The relationship between thyroiditis and polycystic ovary syndrome: a meta-analysis 
Background: The link between AIT and PCOS has been reported on several studies, but it’s true pathogenesis is far from being elucidated. In an attempt to provide evidence of the relationship between PCOS and AIT, relevant literature of AIT markers in women with PCOS was reviewed and analyzed. Methods: PubMed, Embase, Medline, Web of Knowledge and the Cochrane trial register were searched with English language restriction for only human beings. Data were collected and analyzed by Revman. Results: A total of 6 studies, involving 726 PCOS patients and 879 controls, were eligible for our meta-analysis. Conculsion: The prevalence of AIT, serum TSH, anti-TPO and anti-Tg positive rate in PCOS patients are all significantly higher than those in control groups, which suggests PCOS may be a kind of autoimmune disease and has close association with AIT. So, It will be helpful to assess thyroid function routinely in patients with PCOS and offer thyroid hormone replacement therapy if necessary.
PMCID: PMC3832324  PMID: 24260593
Polycystic ovary syndrome; thyroiditis; atuoimmune diseases; meta-analysis
12.  Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease 
Medici, Marco | Porcu, Eleonora | Pistis, Giorgio | Teumer, Alexander | Brown, Suzanne J. | Jensen, Richard A. | Rawal, Rajesh | Roef, Greet L. | Plantinga, Theo S. | Vermeulen, Sita H. | Lahti, Jari | Simmonds, Matthew J. | Husemoen, Lise Lotte N. | Freathy, Rachel M. | Shields, Beverley M. | Pietzner, Diana | Nagy, Rebecca | Broer, Linda | Chaker, Layal | Korevaar, Tim I. M. | Plia, Maria Grazia | Sala, Cinzia | Völker, Uwe | Richards, J. Brent | Sweep, Fred C. | Gieger, Christian | Corre, Tanguy | Kajantie, Eero | Thuesen, Betina | Taes, Youri E. | Visser, W. Edward | Hattersley, Andrew T. | Kratzsch, Jürgen | Hamilton, Alexander | Li, Wei | Homuth, Georg | Lobina, Monia | Mariotti, Stefano | Soranzo, Nicole | Cocca, Massimiliano | Nauck, Matthias | Spielhagen, Christin | Ross, Alec | Arnold, Alice | van de Bunt, Martijn | Liyanarachchi, Sandya | Heier, Margit | Grabe, Hans Jörgen | Masciullo, Corrado | Galesloot, Tessel E. | Lim, Ee M. | Reischl, Eva | Leedman, Peter J. | Lai, Sandra | Delitala, Alessandro | Bremner, Alexandra P. | Philips, David I. W. | Beilby, John P. | Mulas, Antonella | Vocale, Matteo | Abecasis, Goncalo | Forsen, Tom | James, Alan | Widen, Elisabeth | Hui, Jennie | Prokisch, Holger | Rietzschel, Ernst E. | Palotie, Aarno | Feddema, Peter | Fletcher, Stephen J. | Schramm, Katharina | Rotter, Jerome I. | Kluttig, Alexander | Radke, Dörte | Traglia, Michela | Surdulescu, Gabriela L. | He, Huiling | Franklyn, Jayne A. | Tiller, Daniel | Vaidya, Bijay | de Meyer, Tim | Jørgensen, Torben | Eriksson, Johan G. | O'Leary, Peter C. | Wichmann, Eric | Hermus, Ad R. | Psaty, Bruce M. | Ittermann, Till | Hofman, Albert | Bosi, Emanuele | Schlessinger, David | Wallaschofski, Henri | Pirastu, Nicola | Aulchenko, Yurii S. | de la Chapelle, Albert | Netea-Maier, Romana T. | Gough, Stephen C. L. | Meyer zu Schwabedissen, Henriette | Frayling, Timothy M. | Kaufman, Jean-Marc | Linneberg, Allan | Räikkönen, Katri | Smit, Johannes W. A. | Kiemeney, Lambertus A. | Rivadeneira, Fernando | Uitterlinden, André G. | Walsh, John P. | Meisinger, Christa | den Heijer, Martin | Visser, Theo J. | Spector, Timothy D. | Wilson, Scott G. | Völzke, Henry | Cappola, Anne | Toniolo, Daniela | Sanna, Serena | Naitza, Silvia | Peeters, Robin P.
PLoS Genetics  2014;10(2):e1004123.
Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10−8) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68–2.81, P = 8.1×10−8), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26–1.82, P = 2.9×10−6), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66–0.89, P = 6.5×10−4). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22–1.54, P = 1.2×10−7 and OR: 1.25, 95% CI 1.12–1.39, P = 6.2×10−5). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18–2.10, P = 1.9×10−3). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.
Author Summary
Individuals with thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune thyroid diseases (AITD), which are common in the general population and associated with increased cardiovascular, metabolic and psychiatric morbidity and mortality. As the causative genes of TPOAbs and AITD remain largely unknown, we performed a genome-wide scan for TPOAbs in 18,297 individuals, with replication in 8,990 individuals. Significant associations were detected with variants at TPO, ATXN2, BACH2, MAGI3, and KALRN. Individuals carrying multiple risk variants also had a higher risk of increased thyroid-stimulating hormone levels (including subclinical and overt hypothyroidism), and a decreased risk of goiter. The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, and the MAGI3 variant was also associated with an increased risk of hypothyroidism. This first genome-wide scan for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. These results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which individuals are particularly at risk of developing clinical thyroid dysfunction.
PMCID: PMC3937134  PMID: 24586183
13.  Prevalence of thyroid dysfunction in patients with diabetes mellitus 
Diabetes mellitus (DM) and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. The unrecognized TD may adversely affect the metabolic control and add more risk to an already predisposing scenario for cardiovascular diseases. The objective of this study was to investigate the prevalence of TD in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM).
This is an observational cross-sectional study. Three hundred eighty-six (386) patients with T1DM or T2DM that regularly attended the outpatient clinic of the Diabetes unit, Hospital Universitário Pedro Ernesto, participated in the study. All patients underwent a clinical and laboratory evaluation. Thyroid dysfunction was classified as clinical hypothyroidism (C-Hypo) if TSH > 4.20 μUI/mL and FT4 < 0.93 ng/dL; Subclinical hypothyroidism (SC-Hypo) if TSH > 4.20 μUI/ml and FT4 ranged from 0.93 to 1.7 ng/dL; Subclinical hyperthyroidism (SC-Hyper) if TSH < 0.27 μUI/ml and FT4 in the normal range (0.93 and 1.7 ng/dL) and Clinical hyperthyroidism (C-Hyper) if TSH < 0.27 μUI/ml and FT4 > 1.7 μUI/mL. Autoimmunity were diagnosed when anti-TPO levels were greater than 34 IU/mL. The positive autoimmunity was not considered as a criterion of thyroid dysfunction.
The prevalence of TD in all diabetic patients was 14,7%. In patients who had not or denied prior TD the frequency of TD was 13%. The most frequently TD was subclinical hypothyroidism, in 13% of patients with T1DM and in 12% of patients with T2DM. The prevalence of anti-TPO antibodies was 10.8%. Forty-four (11.2%) new cases of TD were diagnosed during the clinical evaluation. The forty-nine patients with prior TD, 50% with T1DM and 76% with T2DM were with normal TSH levels.
We conclude that screening for thyroid disease among patients with diabetes mellitus should be routinely performed considering the prevalence of new cases diagnosed and the possible aggravation the classical risk factors such as hypertension and dyslipidemia, arising from an undiagnosed thyroid dysfunction.
PMCID: PMC3852595  PMID: 24499529
Thyroid dysfunction; Prevalence; Diabetes mellitus
14.  Measures of Thyroid Function among Belarusian Children and Adolescents Exposed to Iodine-131 from the Accident at the Chernobyl Nuclear Plant 
Environmental Health Perspectives  2013;121(7):865-871.
Background: Thyroid dysfunction after exposure to low or moderate doses of radioactive iodine-131 (131I) at a young age is a public health concern. However, quantitative data are sparse concerning 131I-related risk of these common diseases.
Objective: Our goal was to assess the prevalence of thyroid dysfunction in association with 131I exposure during childhood (≤ 18 years) due to fallout from the Chernobyl accident.
Methods: We conducted a cross-sectional analysis of hypothyroidism, hyperthyroidism, autoimmune thyroiditis (AIT), serum concentrations of thyroid-stimulating hormone (TSH), and autoantibodies to thyroperoxidase (ATPO) in relation to measurement-based 131I dose estimates in a Belarusian cohort of 10,827 individuals screened for various thyroid diseases.
Results: Mean age at exposure (± SD) was 8.2 ± 5.0 years. Mean (median) estimated 131I thyroid dose was 0.54 (0.23) Gy (range, 0.001–26.6 Gy). We found significant positive associations of 131I dose with hypothyroidism (mainly subclinical and antibody-negative) and serum TSH concentration. The excess odds ratio per 1 Gy for hypothyroidism was 0.34 (95% CI: 0.15, 0.62) and varied significantly by age at exposure and at examination, presence of goiter, and urban/rural residency. We found no evidence of positive associations with antibody-positive hypothyroidism, hyperthyroidism, AIT, or elevated ATPO.
Conclusions: The association between 131I dose and hypothyroidism in the Belarusian cohort is consistent with that previously reported for a Ukrainian cohort and strengthens evidence of the effect of environmental 131I exposure during childhood on hypothyroidism, but not other thyroid outcomes.
PMCID: PMC3701991  PMID: 23651658
antithyroid antibodies; autoimmune thyroiditis; Chernobyl; Chornobyl; dose response; hyperthyroidism; hypothyroidism; radioiodine; thyroid gland
15.  Thyroid heterogeneity, as indicated by the CV of ultrasonographic intensities, correlates with anti-thyroid peroxidase antibodies in euthyroid Hashimoto’s thyroiditis 
Thyroid Research  2013;6:5.
To prospectively evaluate the heterogeneous appearance of the thyroid gland, reflecting inflammation and destruction in euthyroid Hashimoto’s thyroiditis (HT), we investigated the clinical utilities of the heterogeneity index (HI) [the coefficient of variance (CV) of the ultrasonographic (US) intensities], focusing on anti-thyroid peroxidase antibodies (TPO-Ab), which represent not only disease activity but also subsequent thyroid destruction of HT.
Forty-four consecutive patients with euthyroid HT [60.5 ± 2.7 years old (mean ± SE)] and 30 age-matched normal controls were studied. HI was calculated as the CV (SD/mean) of US intensities of either four points per lobe of the thyroid gland along a horizontal line at the depth of the right common carotid artery. Evaluation included serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), anti-thyroid peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), thyroglobulin and thyroid volume.
While no differences were observed for TSH, FT4 and FT3, thyroglobulin and thyroid volume between the two groups, HI exhibited a tendency towards a significant difference (3.59 ± 0.20% in HT patients vs 3.23 ± 0.19% in normal group, p = 0.089). In HT patients, there was a significant and positive correlation of HI with TPO-Ab (r = 0.396, p = 0.034), whereas such a correlation was absent in normal controls. In both groups, there were no significant correlations of HI with Tg-Ab, FT3, FT4 or TSH.
This is the first report of the close relation between heterogeneity of US of the thyroid gland and TPO-Ab in euthyroid HT patients before the heterogeneity becomes distinguishable from normal thyroid glands. Furthermore, at this stage, subsequent thyroid destruction in HT might be already be predicted through the heterogeniety of the thyroid tissue.
PMCID: PMC3610302  PMID: 23522401
Hashimoto’s thyroiditis; Heterogeneity; Ultrasonography; Anti-thyroid peroxidase antibodies
16.  Autoimmune Thyroiditis in Childhood 
Autoimmune thyroiditis (AIT) is the most common thyroid disorder in the pediatric age range. The disease results from an as yet poorly characterized defect or defects in immunoregulation and a cascade of events progressing from lymphocyte infiltration of the thyroid, to T-cell- and cytokine-mediated thyroid follicular cell injury, and apoptotic cell death. Approximately 70% of disease risk has been attributed to genetic background with environmental factors being important in triggering disease in susceptible individuals. The contribution of individual genes is small and probably polymorphisms in multiple genes play a role. Some immunosusceptibility genes affect immune recognition or response in general, while others are thyroid-specific. Environmental agents may act through an epigenetic mechanism. Antibodies (Abs) to a variety of thyroid-specific antigens are detectable in a majority of patients, but the role of Abs in mediating cell injury and death is unclear and only thyrotropin (TSH) receptor Abs significantly affect thyroid function by interfering with (or stimulating) the action of TSH. Nonetheless, thyroid peroxidase (TPO) Abs and thyroglobulin (Tg) Abs, present in a majority of patients, are valuable diagnostically as markers of underlying autoimmune thyroid destruction. TSH receptor blocking Abs are found in ˜18% of children and adolescents with severe hypothyroidism and, when persistent, may identify an adolescent likely to have a baby with TSH receptor blocking Ab-induced congenital hypothyroidism. AIT may coexist with other organ-specific autoimmune diseases. Although the most common age at presentation is adolescence, the disease may occur rarely in children <1 year of life.
Conflict of interest:None declared.
PMCID: PMC3608006  PMID: 23154164
Thyroiditis; hypothyroidism; children; Autoimmunity
17.  Thyroid peroxidase antibodies in children with autoimmune thyroiditis. 
Journal of Clinical Pathology  1992;45(2):106-109.
AIMS: To compare the prevalence of thyroid peroxidase antibodies in 25 children with autoimmune thyroid disorders and in 41 children and young adults with type 1 diabetes, and to test the prevalence of thyrotropin receptor antibodies. METHODS: Two commercially available radioimmunoassays for antibodies to thyroid peroxidase, a commercially available agglutination test of particles coated with thyroid microsomal antigens, and a radioimmunoassay for thyrotropin receptor antibodies were used. Patients and controls were studied. RESULTS: One of the radioimmunoassays detected thyroid peroxidase antibodies not only in all children with autoimmune thyroid disorders and children and young adults with type 1 diabetes and thyroid microsomal antibodies, but also in 20% of healthy control children without microsomal antibodies. With this thyroid peroxidase assay and with microsomal agglutination, 94% of the children with autoimmune thyroiditis, 71% of those with Graves' disease, and over 90% of those with type 1 diabetes and thyroid dysfunction tested positive. In the other radioimmunoassay for thyroid peroxidase antibodies thyroid peroxidase antibody titres in half or more of the children with microsomal antibodies failed to reach the level of positivity given by the producers. Eighty five percent of children with Graves' disease and 71% of those with autoimmune thyroiditis had thyrotropin receptor antibodies but so did 35% of children studied for other endocrinological disorders such as delayed growth or puberty. CONCLUSIONS: Testing patients with well characterised disorders of thyroid function and with other endocrine disorders is important in evaluating the efficacy of new diagnostic tests for thyroid autoantibodies.
PMCID: PMC495646  PMID: 1541688
18.  351 Prevalence of Thyroid Peroxidase Autoantibodies (ANTI-TPO) in Women with Autoimmune Connective Tissue Diseases (ACTD) 
Chronic autoimmune thyroiditis, manifested by positive test for antithyroid antibodies, is common in the general population, occurring in 10 to 20 percent of women. The aim of the study was to determine whether Anti-TPO is more prevalent in women with ACTD, compared to the general population.
Anti-TPO was determined in 290 women diagnosed with ACTD based on ACR (American College of Rheumatology) criteria and in 50 healthy women (control group). Among ACTD patients, 121 were diagnosed with Rheumatoid Arthritis (RA), 44 Systemic Lupus Erythematosus (SLE), 43 Sjοgren's Syndrome (SS), 42 Systemic Scleroderma (SScl) and 40 Psoriatic Arthritis (PsA). Anti-TPO was measured by Chemiluminescent Microparticle Immunoassay (CMIA) on Architect i2000SR (ABBOT Laboratories).
The prevalence of Anti-TPO in separate groups of patients had as follow: RA 28.93%, SLE 29.55%, SS 27.91%, SScl 23.81%, PsA 30% and control group 12%.
ACTD and thyroid autoimmune diseases often overlap with each other. Increased Anti-TPO may be most common among women patients with ACTD. On the other hand, these systemic diseases are often present in Hasimoto's thyroiditis subjects. Therefore it is clinically important to screen women patients with ACTD for the co-existence of thyroid disorders.
PMCID: PMC3512836
19.  Thyroid dysfunction in major psychiatric disorders in a hospital based sample 
Background & objectives:
Abnormalities in thyroid hormonal status is common in major psychiatric disorders. Although the relevance of thyroid dysfunction to bipolar disorder is well-recognized, yet the association between thyroid dysfunction and schizophrenia-spectrum disorders is under-emphasized. The aim of this study was to examine and compare the rates of abnormal thyroid hormonal status in patients with schizophrenia-spectrum disorders and mood disorders in an inpatient tertiary care general hospital psychiatry unit.
This was a retrospective hospital-based study on 468 inpatient samples. Data on serum thyroid stimulating hormone (TSH), T3 (triiodothyroxine), T4 (L-thyroxine), free unbound fractions of T3 and T4 (FT3 and FT4) were obtained from records of 343 patients, 18 patients were anti-TPO (anti thyroid peroxidase antibody) positive. The rates of abnormal thyroid hormonal status were compared using the chi square test.
Abnormal thyroid hormonal status in general, and presence of hypothyroidism and hyperthyroidism, in particular were seen in 29.3, 25.17 and 4.08 per cent patients with schizophrenia spectrum disorders, respectively. These were comparable to the rates in patients with mood disorders (23.24, 21.62 and 1.62%, respectively). Eleven of the 18 patients with antiTPO positivity had a schizophrenia-spectrum disorder. There were no gender differences.
Interpretation & conclusions:
Thyroid dysfunction was present in patients with schizophrenia-spectrum disorder as well as mood disorders. Autoimmune thyroid disease was more commonly seen in patients with schizophrenia-spectrum disorders compared to mood disorders. The findings reiterate the relevance of screening patients with schizophrenia-spectrum disorders for abnormal thyroid hormonal status.
PMCID: PMC3978977  PMID: 24521631
Autoimmune thyroiditis; hyperthyroidism; hypothyroidism; mood disorder; schizophrenia
20.  Thyroid Disorders Associated with Alopecia Areata in Egyptian Patients 
Indian Journal of Dermatology  2014;59(1):49-55.
Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The etiopathogenesis of the disease is still unclear, but the role of autoimmunity is strongly suggested. AA is commonly associated with various autoimmune disorders; the most frequent among them is autoimmune thyroid disorders.
To determine whether AA is associated with thyroid autoimmunity or thyroid function abnormalities in Egyptian patients.
Materials and Methods:
Fifty subjects with AA (37 males and 13 females) without clinical evidence of thyroid disorders were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital, Menoufiya Governorate, Egypt, during the period from June 2009 to February 2010. They were divided into 3 groups according to severity of AA. Fifty age and sex-matched healthy volunteers (35 males and 15 females) were selected as a control group. Every case and control were subjected to history taking, complete general and dermatological examination. Venous blood samples were taken from cases and controls after taking their consents for measurement of thyroid stimulating hormone (TSH), free T3, freeT4 and detection of Anti-thyroglobulin Antibody (Tg-Ab) and Anti-thyroid Peroxidase Antibody (TPO-Ab).
Subclinical hypothyroidism was detected in 16% of cases. There were statistically significant differences between cases and controls regarding levels of TSH, free T3 and free T4. There were significant differences between cases and controls regarding the presence of Tg-Ab and TPO-Ab.
Every patient with AA should be screened for thyroid functions and presence of thyroid autoantibodies even in absence of clinical manifestations suggestive of thyroid affection.
PMCID: PMC3884928  PMID: 24470660
Alopecia; autoimmunity; thyroid gland
21.  Ultrasonographic evaluation of the thyroid gland volume among 8-15-year-old children in Isfahan, Iran 
Local reference data are needed in the screening of children for thyroid enlargement. We determined the thyroid gland volume using the ultrasonography (US) in schoolchildren of Isfahan, Iran.
Materials and Methods:
A total of 360 schoolchildren (59% girls) aged 8-15 years who met the study criteria were entered the study. Clinical grading of goiter was performed by an endocrinologist according to the World Health Organization (WHO) classification. Then, a single expert radiologist performed thyroid volume measurement using a portable ultrasound device. Urinary iodine (UI) concentration was checked in 36 randomly selected cases.
On physical examination, 327 (91%), 32 (8.8%) and 1 (0.2%) subjects were classified as normal, borderline and goiter Grade 2. Mean thyroid volume measured by US was 1.46 ± 0.70 ml. Thyroid volume in boys was significantly higher than girls (1.58 ± 0.67 ml vs. 1.38 ± 0.71 ml; P = 0.009). Thyroid volume was positively correlated with the clinical grade of the goiter (r = 0.30, P < 0.001) and with age (r = 0.25, P < 0.001). Both median and 95th percentile of thyroid volume of our subjects was lower than the reference values reported by WHO. Median of UI was 16.90 μg/dl. UI was not correlated with thyroid volume (r = 0.12, P = 0.46).
The thyroid size in Isfahanian schoolchildren is lower than the reference values reported by WHO. These data could be used in determining local reference in the screening of children for thyroid enlargement.
PMCID: PMC3929009  PMID: 24600596
Goiter; Isfahan; thyroid; thyroid volume; ultrasound
22.  Spectrum of lithium induced thyroid abnormalities: a current perspective 
Thyroid Research  2013;6:3.
Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. Thyroid abnormalities associated with treatment with lithium have been widely reported in medical literature to date. These include goitre, hypothyroidism, hyperthyroidism and autoimmune thyroiditis. This current review explores the varied thyroid abnormalities frequently encountered among patients on lithium therapy and their management, since lithium is still a fundamental and widely drug used in psychiatry and Internal Medicine.
PubMed database and Google scholar were used to search for relevant English language articles relating to lithium therapy and thyroid abnormalities up to December 2012. The search terms used were lithium treatment, thyroid abnormalities, thyroid dysfunction, goitre, hypothyroidism, hyperthyroidism, thyrotoxicosis, autoimmune thyroiditis, lithium toxicity, treatment of affective disorders and depression and side effects of antipsychotic drugs. Reference lists of the identified articles were further used to identify other studies.
Lithium affects normal thyroid functioning through multiple mechanisms. At the cellular level, it decreases thyroid hormone synthesis and release. It also decreases peripheral deiodination of tetraiodothyronine (T4) or thyroxine by decreasing the activity of type I 5’ de-iodinase enzyme. Hypothyroidism and goitre (clinically and/ultrasonographically detected) are the most prevalent thyroid abnormalities among patients on long term lithium therapy. Lithium induced hyperthyroidism is very infrequent. Lithium increases the propensity to thyroid autoimmunity in susceptible individuals due to its effect of augmenting the activity of B lymphocytes and reducing the ratio of circulating suppressor to cytotoxic T cells.
Thyroid function tests (serum thyroid stimulating hormone, free thyroid hormones-T4 and triiodothyronine [T3] concentrations and thyroid auto-antibodies) and assessment of thyroid size clinically and by thyroid ultrasonography ought to be performed among patients initiating lithium therapy at baseline and later annually. More frequent assessment of thyroid function status and size during the course of therapy is recommended among middle aged females (≥50 years), patients with a family history of thyroid disease and those positive for thyroid auto-antibodies (anti-thyroid peroxidase and TSH receptor antibodies).
PMCID: PMC3568739  PMID: 23391071
Lithium therapy; Thyroid abnormalities; Goitre; Hypothyroidism; Hyperthyroidism; Thyroid autoimmunity
23.  Selenium supplementation in thyroid associated ophthalmopathy: an update 
The therapeutic effect of selenium (Se) has already been proven in thyroid disease and thyroid associated ophthalmopathy (TAO). In spite of clear scientific proof of its benefits in TAO, there appears to be no clear agreement among the clinicians regarding its optimum dose, duration of the treatment, efficacy and safety to date. In this review, the author summarises the findings of 135 English language articles published on this subject over the past four decades from 1973 to 2013. The regulation and metabolism of thyroid hormones require a steady supply of Se and recent studies have revealed several possible mechanisms by which Se improves the severity of thyroid disease and TAO. These mechanisms include 1) inhibitory effect of HLA-DR molecule expression on thyrocytes; 2) profound reductions of thyroid stimulating hormone (TSH) receptor antibodies (TSHR-Ab) and TPO antibodies (TPO-Ab); 3) prevention of dysregulation of cell-mediated immunity and B cell function; 4) neutralising reactive oxygen species (ROS) and inhibition of redox control processes required for the activation, differentiation and action of lymphocytes, macrophages, neutrophils, natural killer cells involved in both acute and chronic orbital inflammation in TAO; 5) inhibition of expression of pro-inflammatory cytokines and 6) inhibition of prostaglandin and leukotriene synthesis. An increased oxidative stress has been observed in both acute and chronic phases of thyroid disease with raised tissue concentrations of ROS. The benefits of Se supplementation in individuals with TAO appear to be proportionate to the degree of systemic activity of the thyroid disease. The maximal benefit of Se supplementation is therefore seen in the subjects who are hyperthyroid. Restoration of euthyroidism is one of the main goals in the management of TAO and when anti-thyroid drugs are combined with Se, the patients with Graves' disease (GD) and autoimmune thyroiditis (AIT) achieved euthyroidism faster than those treated with anti-thyroid drugs alone. Se status of normal adult humans can vary widely and Se supplementation may confer benefit only if serum Se levels are insufficient. The author recommends that serum Se levels of patients with TAO to be assessed prior to and during Se supplementation at regular intervals to avoid potential iatrogenic chronic Se overdose.
PMCID: PMC4003098  PMID: 24790886
selenium; selenoproteins; thyroid associated ophthalmopathy; Graves' orbitopathy
24.  Micronucleus frequency among Iraqi thyroid disorder patients 
Micronucleus (MN) assay has been extensively used in detection of DNA damage, instability in cancer, and genetic disorders. In the current study, MN, binucleated cells, and nuclear division index (NDI) were investigated in Iraqi patients with thyroid disorders. The results indicated significantly (p < 0.05) increased binucleated cells with micronucleus (BNMN) frequencies in thyroid cancer group (37.58 ± 3.07) versus other thyroid disorder groups (6.60 ± 1.29, 14.90 ± 1.69, 15.56 ± 1.76). On the other hand, the frequency of micronucleus per 1,000 and the NDI were significantly (p < 0.05) decreased in hypothyroidism (MN 1.55 ± 0.36) (NDI 0.009 ± 0.001) versus other thyroid disorder groups (MN: 6.05 ± 0.97, 6.09 ± 0.53, 5.34 ± 0.56) (NDI: 0.049 ± 0.003, 0.032 ± 0.002, 0.025 ± 0.002), with no difference versus healthy group (0.0 ± 0.0). The number of BNMN and MN are parallel to the severity of thyroid disorders which were 6.60 ± 1.29, 14.90 ± 1.69, 15.56 ± 1.76, and 37.58 ± 3.07 for hypothyroidism, thyroid toxic goiter, thyroid nontoxic goiter, and thyroid cancer, respectively. The number of BNMN and MN are parallel to the severity of thyroid disorders which were 6.60 ± 1.29, 14.90 ± 1.69, 15.56 ± 1.76, and 37.58 ± 3.07 for hypothyroidism, thyroid toxic goiter, thyroid nontoxic goiter, and thyroid cancer, respectively. The results also indicate that there were no significant differences among age and sex groups as related with BNMN formation within each thyroid disorder groups and healthy control group.
PMCID: PMC4016807  PMID: 24829552
Thyroid disorders; Micronucleus; NDI; BN
25.  Prospective Observation of 5-Year Clinical Course of Subclinical Hypothyroidism in Korean Population 
Journal of Korean Medical Science  2013;28(11):1622-1626.
Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 µIU/mL, free T4 < 1.09 ng/dL and Anti-TPO Ab > 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH.
PMCID: PMC3835504  PMID: 24265525
Subclinical Hypothyroidism; Natural History; Hypothyroidism

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