Vitamin D Status Association with Thyroid Antibodies in Hypothyroidism Patients

Background: Deficiency in Vitamin D is a global health issue, in the recent decade, there has been substantial proof that low levels of Vitamin D can lead to thyroid disorders. The present study aims to analyze the relationship between hypothyroidism and the level of Vitamin D, as well as to analyze the relationship between Vitamin D level with thyroid antibodies (TPO-Abs and TG-Abs). Methods: Forty patients diagnosed as hypothyroidism which compared with twenty healthy control groups with matching in sex and age between studied groups. The blood sample was collected from both groups to estimate the level of vitamin D, T3, T4, TSH hormones and the existence of thyroid autoantibodies. Results: Patients with hypothyroidism showed a significantly lower mean of Vitamin D level compared with the healthy control group (p=0.0001). Half (20/40) of the hypothyroid group tested positive for TPO-Ab, (15/40) were positive for TG-Ab, and (14/40) of hypothyroidism patients have positive results for Anti-Thyroid Peroxidase and AntiThyroglobulin antibodies with highly statistical significant between hypothyroid group according to the presences of autoantibodies. As for the interaction of vitamin D levels with autoantibodies in patients with hypothyroidism, we observed that levels of Vitamin D were correlated with neither TPO antibodies (p=0.292) nor TG antibodies (p=0.108). Conclusion: The levels of vitamin D were significantly lower in patients with hypothyroidism relative to healthy control. Vitamin D does not have a strong association with the titers of thyroid antibodies.

Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility

Thyroid disorders are common, affecting more than 10% of people in the US, and laboratory tests are integral in the management of these conditions. The repertoire of thyroid tests includes blood tests for thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, thyroglobulin (Tg), thyroglobulin antibodies (Tg-Ab), thyroid peroxidase antibodies (TPO-Ab), TSH receptor antibodies (TRAb), and calcitonin. TSH and free thyroid hormone tests are frequently used to assess the functional status of the thyroid. TPO-Ab and TRAb tests are used to diagnose Hashimoto's thyroiditis and Graves' disease, respectively. Tg and calcitonin are important tumor markers used in the management of differentiated thyroid carcinoma and medullary thyroid carcinoma (MTC), respectively. Procalcitonin may replace calcitonin as a biomarker for MTC. Apart from understanding normal thyroid physiology, it is important to be familiar with the possible pitfalls and caveats in the use of these tests so that they can be interpreted properly and accurately. When results are discordant, clinicians and laboratorians should be mindful of possible assay interferences and/or the effects of concurrent medications. In addition, thyroid function may appear abnormal in the absence of actual thyroid dysfunction during pregnancy and in critical illness. Hence, it is important to consider the clinical context when interpreting results. This review aims to describe the above-mentioned blood tests used in the diagnosis and management of thyroid disorders, as well as the pitfalls in their interpretation. With due knowledge and care, clinicians and laboratorians will be able to fully appreciate the clinical utility of these important laboratory tests.

A study of prevalence of autoantibodies in patients with lichen planus from Mumbai, India

Background: Lichen planus is a common chronically relapsing autoimmune skin condition with poorly understood etiology. Apart from cellular immunity, presence of various antibodies has been hypothesized. Various studies have found the presence of serum anti-nuclear antibody, anti-mitochondrial antibody, anti-desmoglein 1 and 3 antibodies, anti-keratinocyte antibody and anti-thyroglobulin antibody in patients of cutaneous and oral lichen planus. Aim: To study the prevalence of autoantibodies and the clinical spectrum of disease in an Indian patient subpopulation with lichen planus. Methods: A cross-sectional epidemiological study comprising 100 lichen planus patients was conducted in the dermatology outpatient department of Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India. Serum concentrations of circulating anti-nuclear antibodies, anti-desmoglein 1 antibody, anti-desmoglein 3 antibody, anti-keratinocyte antibodies, anti-mitochondrial antibodies and anti-thyroglobulin antibodies were determined by indirect immunofluorescence. Pairs of groups were compared using “Student's t-test” for normally distributed continuous data. The “χ2-test” was used for the categorical variables as needed. Statistical significance was set at P < 0.05. Results: It was found that 65 (65%) patients showed the presence of at least one of the six autoantibodies that we studied, while 35 (35%) tested negative for all six of them. Positivity of anti-keratinocyte antibody in 26 (26%), anti-nuclear antibody in 22 (22%), anti-desmoglein 1 antibody in 19 (19%), anti-desmoglein 3 antibody in 16 (16%), anti-mitochondrial antibody in 9 (9%) and anti-thyroglobulin antibody in 6 (6%) patients was detected. It was observed that 55 (71.4%) patients of cutaneous lichen planus, 6 (46.1%) patients of mucosal lichen planus and 4 (40%) patients of cutaneous and mucosal lichen planus overlap showed presence of at least one autoantibody. Conclusion: This study provides the serological parameters of a population of lichen planus from western India. Presence of autoantibodies in lichen planus suggests the possible role of humoral immunity in lichen planus. Identifying antibodies linked to lichen planus may help in identifying suitable diagnostic tests and therapeutic targets. Well-controlled studies with larger sample size are the need of the hour to confirm the role of humoral immunity in lichen planus. Limitations: Studies with a larger number of patients as well as controls should be undertaken to further evaluate the role of autoantibodies in lichen planus.

Métodos de tiroglobulina de primera y segunda generación: su utilidad en pacientes con cáncer diferenciado de tiroides / First and second generation thyroglobulin measurement methods: Their usefulness in patients with thyroid cancer

El cáncer diferenciado de tiroides (CDT) es el cáncer endocrinológico más frecuente y en las últimas décadas su incidencia ha aumentado. El seguimiento de la enfermedad se efectúa con la medición de tiroglobulina (Tg) sérica, ecografía cervical y barrido corporal total diagnóstico. Los métodos de Tg han evolucionado a través del tiempo. Actualmente, los ensayos inmunométricos de Tg se clasifican en 1.ª y 2.ª generación (1.ª G y 2.ª G). Comprobamos que los ensayos de 2.ª G alcanzan una precisión adecuada para medir valores del orden de 0,1 ng/ml y los de 1.ª G de 1 ng/ml. La bibliografía señala que en el caso de los pacientes de bajo riesgo, una Tg bajo levotiroxina indetectable por un método de 2.ª G puede evitar la realización de Tg estimulada, sea por la suspensión de la terapia hormonal como por el empleo de la TSH recombinante humana, debido a su mayor sensibilidad. Sin embargo, por su menor especificidad, un valor detectable no asegura la presencia de enfermedad, y debería confirmarse. Para optimizar la utilidad clínica de dicha medición se podrían emplear valores de cortes de acuerdo con la población y el método en lugar de la sensibilidad funcional o límite de cuantificación del mismo. Se señalan también otros aspectos críticos en la medición de Tg como son la discordancia entre distintas metodologías y las interferencias en su medición, principalmente por anticuerpos antitiroglobulina. En presencia de interferencias pierden utilidad los ensayos de Tg de 1.ª y 2.ª G. El seguimiento de los pacientes con Tg interferida tiene limitaciones todavía no resueltas. Es importante consensuar entre médicos y bioquímicos las dificultades técnicas y los criterios de interpretación de los valores de Tg en el seguimiento de los pacientes con CDT.

Differentiated thyroid cancer (DTC) is the most common endocrine cancer (tumour) and its incidence has risen in the past decades. Its follow-up includes measuring serum thyroglobulin (Tg), performing neck ultrasound and a diagnostic whole-body scan. Tg assays have evolved with time. At present immunoassays for Tg are classified as 1 st and 2 nd generation assays (1 st G and 2 nd G). 2 nd G assays show an adequate (good) precision at levels close to 0.1 ng/ml and 1 st G assays at levels close to 1 ng/ml. The literature shows that for low risk patients on levothyroxine treatment, who undetectable levels by 2 aG assays can avoid the stimulation test performed by thyroid hormone withdrawal or after recombinant human TSH, due to better sensitivity. However, due to lower specificity, detectable levels do not confirm the presence of disease (tumour), and should be confirmed. To optimise the clinical usefulness of the test, cut-off values specific for population and method should be used, instead of functional sensitivity or quantification limit. Critical issues for measuring Tg are discussed, such as non-harmonisation of methods, and interferences, mainly by antithyroglobulin antibodies (ATg). 1 st and 2 nd G assays are less useful in presence of ATg, and follow up of such patients is limited. Consensus between physicians and the laboratory on technical issues and interpretation criteria of Tg values is of outmost importance in the follow-up of DTC patients.

Predictive value of serum midkine for metastatic lesions in thyroid cancer patients with positive thyroglobulin antibody / 天津医药

Objective To investigate the predicative value of midkine (MK) as a cancer biomarker for metastatic lesions in differentiated thyroid cancer (DTC) patients with positive thyroglobulin antibodies (TgAb) before the first 131Ⅰ therapy.Methods MK levels were measured by enzyme-linked immunosorbent assay in 151 recruited DTC patients included in this study according to strict inclusion and exclusion criteria.There were 28 TgAb positive DTC patients with metastases and 123 DTC patients without metastases.The value of pre-131Ⅰ-ablative MK to predict metastasis was assessed by receiver operating characteristic (ROC) curves in these two groups of patients.Results MK levels were significantly higher in TgAb positive DTC patients than those in DTC patients without metastases.MK levels showed good diagnostic value,with an area under the curve of 0.856 (P＜0.001),and a diagnostic accuracy of 83％ at the optimal cut-off value of 550 ng/L.Conclusion Results show that MK can potentially be used as a surrogate biomarker for predicting DTC metastases when thyroglobulin is not suitable due to TgAb positivity.

Interferencia de la tiroglobulina en la determinación de anticuerpos antitiroglobulina en el líquido de lavado de aguja de punción ganglionar / Thyroglobulin Interference in the Determination of Thiroglobulin Antibody in Wash-Out Fluid from Fine Needle Aspiration Biopsy of Lymph Node

La interferencia producida por los anticuerpos antitiroglobulina (aTg) en la determinación de Tiroglobulina (Tg) ha sido bien estudiada, sin embargo la interferencia que puede producir esta última sobre la determinación de los anticuerpos no está clara. Objetivo: Investigar la interferencia que la Tg puede producir sobre la determinación de los aTg en el líquido de lavado de aguja de punción ganglionar. Material y Métodos: Se estudiaron retrospectivamente las muestras provenientes de la punción de adenopatías cervicales sospechosas de 19 pacientes tiroidectomizados por Cáncer Diferenciado de Tiroides (CDT). La punción se realizó con aguja 22 G bajo guía ecográfica y luego de la preparación del extendido para el estudio citológico se procedió al lavado de la aguja con 500 µl de solución fisiológica para determinar Tg y aTg. La medición de Tg se hizo por ensayo quimioluminiscente. Los aTg se midieron utilizando dos ensayos uno no competitivo quimioluminiscente (Q) y otro competitivo electroquimioluminiscente (Eq). Se consideraron aTg negativos valores < 20 UI/ml. Se realizaron diluciones de la muestra de uno de los pacientes para el estudio de interferencia. Resultados: En todas las muestras las concentraciones de Tg mostraron valores muy elevados (rango: 15.185 -1.141.275 ng/ml). Los resultados de los aTg fueron negativos en el 100 % de las muestras cuando se midieron por el método no competitivo (Q) y francamente positivos en un rango de 106 a > 4.000 UI/ml cuando se midieron por el método competitivo (Eq), siendo estos valores proporcionales a la concentración de Tg en la muestra. Se observó una falta de linealidad cuando se realizó ensayo de dilución a muestras de concentración elevada de aTg medidas por Eq. Los aTg por Eq se negativizaron a concentraciones de Tg inferiores a 3.000 ng/ml. Los aTg medidos por Q arrojaron valores negativos en todas las diluciones. Todos estos pacientes presentaban aTg negativos en suero por Q y Eq. Conclusión: Las altas concentraciones de Tg interfieren en la medición de aTg cuando los mismos son medidos por un método competitivo. La interferencia es proporcional a las concentraciones de Tg presentes en la muestra. Se recomienda que en los líquidos de lavado de aguja de punción ganglionar los aTg sean medidos por un método no competitivo ya que no parece estar interferido por las altas concentraciones de Tg característica de los ganglios metastásicos. La detección de esta interferencia no modificó el diagnóstico ni la conducta clínica en ningún caso, sin embargo es importante conocerla con el fin de no concluir erróneamente sobre la positividad de los anticuerpos en los ganglios cuando estos son medidos por un ensayo competitivo. Rev Argent Endocrinol Metab 51:1-7, 2014 Los autores declaran no poseer conflictos de interés.

Thyroglobulin antibodies (TgAb) interference with thyroglobulin (Tg) measurements has been well studied; however, Tg interference with TgAb is unclear. Objective: To investigate how TgAb may interfere with Tg measurement in the washout fluid from lymph node fine-needle aspiration biopsy. Materials and Methods: We retrospectively studied the samples obtained by aspiration of suspicious cervical lymph nodes from 19 patients post thyroidectomy for Differentiated Thyroid Cancer (DTC). The puncture was performed with a 22 G needle under ultrasound guidance. After preparation of cytological specimens, the needle was washed with 500 ul of saline solution to determine Tg and TgAb. Tg was measured by chemilumi­nescent assay and TgAb was measured using two assays: a non-competitive chemiluminescent assay (Q) and a competitive electrochemiluminescence assay (Eq). Values of TgAb below 20 UI/ml were considered negative. Appropriate dilutions of the sample of one of the patients were performed in order to study interference. Results: In all samples tested, concentrations showed very high Tg values (range: 15.185 - 1.141.275 ng/ml). TgAb results were negative in all the samples measured by the non-competitive method. Results were clearly positive in a range of 106 to > 4.000 IU/ml when the competitive assay (Eq) was used, being proportional to Tg concentrations in the samples. A lack of linearity was observed when a dilution assay was performed in samples of high TgAb concentrations measured by Eq. When Tg concentrations were below 3.000 ng / ml, TgAb became negative when measured by Eq. TgAbs measured by Q were negative in all dilutions. TgAbs in serum were negative in all patients by the two methodologies (Q and Eq). Conclusion: High levels of Tg interfere with TgAb measurement when a competitive method is used. The interference is proportional to the concentrations of Tg. It is recommended that in the wash-out fluid from fine needle aspiration, TgAbs should be measured by a non-competitive method since there appears to be no interference from the high concentrations of Tg characteristic of metastatic nodes. The detection of this interference did not change the diagnosis or clinical management in any case; however, it is important to be aware of such interference so as not to make erroneous conclusions about the positivity of TgAbs in lymph nodes when a competitive method is used. Rev Argent Endocrinol Metab 51:1-7, 2014 No financial conflicts of interest exist.

Analysis of the factors affecting A-TG increased after the DTC operation and 131 I treatment / 国际检验医学杂志

Objective To analyze influence factors of serum A-TG level after DTC 131 I treatment ,to explore whether A-TG can be used as an indicator of follow-up ,recurrence and metastasis of DTC .Methods From 2008 January to 2013 February ,a total of 106 DTC patients underwent operation excisions of thyroid radioiodine were treated with 131 I .Before and 1 month after treatment , the levels of A-TG ,TG ,THS were measured .The relationship of A-TG and thyroid operation range operation times ,thyroid gland residual volume and time ,the levels of TSH and TG ,thyroid cancer metastasis and recurrence were examined .Results Serum A-TG concentration associated with operation scope ,frequency(P<0 .05) .It was showed that the A-TG concentration was positively correlated with the metastasis of thyroid cancer .Conclusion The serum TG level detection combined with A-TG and 131 I-WBS can improve the diagnostic sensitivity and accuracy of DTC recurrence and metastasis .

Limitaciones técnicas de los métodos para cuantificar tiroglobulina sérica y su repercusión clínica: [revisión] / Technical limitations of methods to quantify the serum thyroglobulin and its clinical repercussion: [review]

La determinación de tiroglobulina sérica se emplea, sobre todo, como marcador tumoral en el seguimiento posoperatorio de pacientes con cáncer diferenciado del tiroides. Lamentablemente, los métodos de tiroglobulina sérica presentan gran variabilidad en sus cualidades analíticas y padecen problemas técnicos que repercuten sobre la utilidad clínica de esta prueba. Para cuantificar tiroglobulina sérica se emplean 2 tecnologías diferentes: los iniciales radioinmunoensayos competitivos y los mßs recientes métodos inmunométricos no competitivos. Estos últimos son más propensos a sufrir las interferencias provocadas por la presencia de autoanticuerpos tiroglobulina y anticuerpos heterofílicos, a pesar de brindar los beneficios técnicos relativos al uso de reactivos no isotópicos, menor volumen de muestra, tiempos de incubación más cortos, así como mejor sensibilidad y facilidad de automatización. Resulta esencial que los clínicos conozcan y comprendan las limitaciones técnicas inherentes a la determinación de tiroglobulina sérica y su repercusión sobre la utilidad clínica de esta, con la finalidad de hacer un uso efectivo y eficiente de esta prueba en el seguimiento posoperatorio de pacientes con cáncer diferenciado del tiroides(AU)

The serum thyroglobulin assessment is used mainly as tumor marker during the postoperative follow-up of patients presenting with thyroid differentiated cancer. Progressively, the serum thyroglobulin methods have much variability in its analytical qualities and also have technical problems affecting on the technical usefulness of this test. To quantify the serum thyroglobulin we used two different technologies: the initial competitive radioimmunoassays and the most recent non competitive inmunometrical methods. These latter are more prone to have interferences provoked by presence of thyroglobulin antibodies and heterophilic antibodies despite to offer technical beneficial relative to use of non-isotopic reagents, a lower sample volume, shorter incubation times, as well as a better sensitivity and feasibility of automation. It is essential that clinicians know and understand the technical limitations inherent of serum thyroglobulin assessment and its repercussion on its clinical usefulness to an effective and efficient use of this test during the postoperative follow-up of patients presenting thyroid differential cancer(AU)

Effect of selenium on the Hashimoto thyroiditis / 中华内分泌代谢杂志

A total of 115 patients with Hoshimoto thyroiditis were classified under 2 groups: one group being treated with selenium and L-throxine (L-T4) and other group with L-T4 alone.All patients were followed up for 3 months.In the selenium treated group thyroid peroxidase antibody level was decreased in 33 patients (56%) and thyroglobulin antibody level was decreased in cases.

Prevalencia de hipotiroidismo y anticuerpos antitiroglobulina en pacientes mexicanos con esclerosis sistémica / Systemic sclerosis and hypothyroidism

Objetivo: Investigar la prevalencia de hipotiroidismo y anticuerpos antitiroglobulina (AATg) en pacientes mexicanos con esclerosis sistémica (ES). Material y métodos: Se estudió la función tiroidea en pacientes con ES y controles. Se les determinaron los niveles séricos de triyodotironina, tiroxina, hormona estimulante de la tiroides (TSH) y AATg. Resultados: Fueron 110 pacientes (106 mujeres y 4 hombres), edad promedio de 48.1 ± 28.5 años, versus 80 controles (76 mujeres y 4 hombres), edad promedio 47.5 ± 28.8 años. El hipotiroidismo clínico se encontró en 19% de pacientes con ES y en 1.3% de los controles (p < 0.01). Las medianas respectivamente de triyodotironina en ES y controles fueron: 82 versus 160 ng/dl, p < 0.01; tiroxina 5.4 versus 7 ng/dl, p < 0.01; TSH 8.2 versus 1.1 μUI/ml, p < 0.001. El hipotiroidismo subclínico se observó en 35% de los pacientes con ES y en 0% de los controles. Los valores de TSH en ES y en controles fueron 7.2 versus 1.2 μUI/ml, p < 0.01; triyodotironina 116 versus 160 ng/dl, p ns; tiroxina 7 versus 7 ng/dl, p ns, respectivamente. Los AATg estuvieron presentes en 54% de los pacientes y 2.5% en el grupo control, p < 0.01. Conclusiones: Los pacientes con ES presentan elevada prevalencia de hipotiroidismo, especialmente subclínico, por lo que debe investigarse la función tiroidea para iniciar tratamiento oportuno.

OBJECTIVE: Assess the prevalence of hypothyroidism and anti-thyroglobuline antibodies (AbATg) among Mexican patients with systemic sclerosis (SSc). MATERIAL AND METHODS: Thyroid function was studied in SSs patients and controls. Triiodothyronine, thyroxine, thyroid stimulant hormone (TSH) and AbATg were measured. RESULTS: 110 SSc patients (106 women and 4 men), mean age 48.1 +/- 28.5 yrs versus 80 healthy controls (76 women and 4 men) with mean age 47.5 +/- 28.8 yrs were included. Hypothyroidism was diagnosed in 19% patients compared with 1.3% in the control group. The following results were found; triyodotironina: 82 ng/dl versus 160 ng/dl, p < 0.000; tiroxina: 5.4 ng/dl versus 7ng/dl, p < 0.01; TSH: 8.2 uUl/ mL versus 1.1 +/- 2 uUl/mL, p < 0.000. Subclinical hypothyroidism was observed in 35% patients versus 0% controls, TSH: 7.2 uUl/ml versus 1.2 +/- 1.4 uUl/ml, p < 0. 000; triyodotironina: 116 ng/dl compared with 160 ng/dl, p = ns; tiroxina: 7.0 ng/dl vs. 7.0 ng/dl, p ns; AbATg were positive in patients 54% and 2.5%, p < 0.001 in the control group. CONCLUSIONS: Our study reports a high prevalence of hypothyroidism among SSc Mexican patients, especially of the subclinical type. We need to consider hypothyroidism as a clinical entity often found among SSc patients, and start hormone replacment treatment accordingly.