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Serological detection of relevant autoantibodies and hormones  

  • Reliable detection of thyroid-specific antibodies (against TSH receptor, TPO and TG), hormones (FT3, FT4, calcitonin) and antigens (TSH, TG)
  • Useful to support the diagnosis of autoimmune thyroid diseases and in suspected thy- roid carcinoma, as well as for therapy monitoring and postoperative tumour after-care
  • Comprehensive product portfolio with a large method spectrum (ELISA, RIA, IIFT)

 

Autoimmune thyroid diseases

The delicate balance of thyroid hormone regulation can be disturbed by the presence of various autoantibodies. Antibodies against thyroid microsomes, with their main antigen thyroperoxidase (TPO), and antibodies against thyroglobulin (TG) or thyrotropin receptor (also thyroid-stimulating hormone) are characteristic of autoimmune thyroid diseases. The most fre- quent autoimmune thyroid diseases are autoimmune thyroiditis (AIT) of the Hashimoto type and immune hyperthyroidism, which is also known as Graves’ disease.1 Whereas AIT can manifest in the form of thyroid overfunction (hyperthyroidism) or underfunction (hypothyroidism), Graves’ disease is always associated with hyperthyroidism.1

  

Hashimoto’s thyroiditis

Hashimoto’s thyroiditis is characterised by the destruc- tion of thyroid tissue due to autoimmune lymphocytic in- filtration, which mostly results in a long-term diminished thyroid hormone production.2 Initial hyperthyroidism is explained by the release of preformed thyroid hormones during organ destruction (hashitoxicosis). The symptoms can therefore vary significantly.1 However, they typically include fatigue, muscle weakness and weight gain.

Associated antibodies: Anti-TPO antibodies can be de- tected in 90 % of patients. They have the highest preva- lence in Hashimoto’s thyroiditis.3 Additionally, autoanti- bodies against TSH receptor (TRAb) can be found in 6 to 60 % of cases and anti-TG antibodies in 45 to 60 %. 

 

TSH: thyrotropin  TRH:  TSH-releasing hormone

TSHR: TSH receptor TPO:  thyroperoxidase

TG: thyroglobulin(precursor of T3 and T4) T3: triiodothyronine 

T4: thyroxine (tetraiodothyronine)

Graves’ disease

Graves’ disease is characterised by the continuous stimu- lation of the TSH receptor through the binding of autoanti- bodies. This results in the activation of signal cascades, leading to an increased uptake of iodine in the thyroid. Consequently, the production and release of the thyroid hormones triiodothyronine (T3) and thyroxine (T4) is in- creased.6 Typical symptoms include struma, exophthal- mos, and tachycardia (Merseburg triad). 

Associated antibodies: TRAb are the most important se- rological markers in Graves’ disease. They are detectable in over 90 % of patients. Increased antibody titers are as- sociated with a severe course of the disease.7 In addition, anti-TPO and anti-TG antibodies occur with a prevalence of around 80 % and 30 %, respectively.5,7

 

FT4: free, non-protein-bound, biologically active form of T3 / T4

 T4: protein-bound, biologically inactive form of T3 / T4

 increase or decrease in the concentration

 rT3: reverse T3, biologically inactive form of T3

                                                                            

 

 Further autoimmune thyroid diseases

A special form of AIT is postpartum thyroiditis, a temporary hypothyrotic functional disorder of the thyroid gland which is accompanied by high titers of anti-TPO antibodies. The disease affects around 5 to 9 % of women after giving birth. The risk is particularly high in women with diabetes mellitus.5 The measurement of anti-TPO antibodies is therefore advisable in all postpartum women as they require hormone substitution if they have the disease.

 

Moreover, AIT often occurs together with other autoimmune diseases, such as rheumatoid arthritis, Sjögren’s syndrome, Addison’s disease, coeliac disease, type 1 diabetes mellitus and vitiligo.8 For this reason, other autoantibodies directed against non-thyroid antigens are frequently found in the serum of AIT patients.

 

 Serological diagnostics of autoimmune thyroid diseases

In suspected autoimmune thyroid disease, the concentra- tion of TSH in serum should be measured. An increased TSH level indicates hypothyroidism, while a decreased level is indicative of hyperthyroidism. Additionally, the serum FT3 and FT4 values should be determined. For differentiation of autoimmune thyroid disease from acute (bacterial) or subacute (non-infectious) thyroiditis or a non-autoimmune disorder of the thyroid hormone regulation, the determina- tion of antibodies against thyroid antigens is helpful.1 For the detection of thyroid-specific antibodies, hormones and antigens, EUROIMMUN offers a variety of different test sys- tems such as enzyme-coupled immunoadsorption assays (ELISA), radioimmunoassay (RIA) or indirect immunofluo- rescence tests (IIFT). Reliable differential diagnostics must be based on the overall picture obtained from the analysis of different parameters. Besides serological methods, clini- cal examinations (e.g. ultrasound, scintigraphy) and symp- toms must also be considered. The patient’s sex may also be relevant.9

 

Malignant tumour diseases of the thyroid gland

The incidence of thyroid carcinoma in Germany is 5 to 11 cases per 100,000 inhabitants (as of 2016). Distinction is mainly made between well-differentiated (papillary, follicular and oncocytic forms) and medullary carcinoma. The most important tumour treatment is surgery, which often involves complete removal of the thyroid gland (thyroidectomy).10 This results in the loss of the body’s own production of thyroid hormones T3 and T4 and their precursor TG.

 

After total thyroidectomy due to differentiated thyroid carcinoma and successful radiotherapy, regular examinations should be performed, including serological determination of TG. The presence of TG indicates an incomplete resection of the thy- roid gland or a relapse (TG-producing tumour cells).10 In parallel with the direct determination of TG, antibodies against TG should be investigated. Due to the binding of the antibodies to TG, it is possible that the latter is not correctly detected by direct tests. The investigation of endogenous antibodies against TG helps to limit false-negative TG results.11

 

In suspected cases of medullary thyroid carcinoma, the patient serum should be investigated for calcitonin. Malignant C cells of this type of tumour produce high amounts of calcitonin. Determination of this protein in serum is the method of choice for early diagnostics as well as postoperative after-care.10 The following serological results can be useful:

   

In a nutshell

  • The balance of thyroid hormone regulation can be disturbed by various
  • The detection of anti-TPO and anti-TG antibodies as well as TRAb can support the diagnosis of autoimmune thyroid diseases such as Hashimoto’s thyroiditis or Graves’ disease. Measurement of the TSH, FT3 and FT4 levels can be helpful in therapy
  • The investigation of anti-TG antibodies in parallel with TG is useful for early identification of relapses and metasta- ses after surgical removal of well-differentiated thyroid
  • The determination of the serum calcitonin level is recommended in the diagnostics of medullary thyroid carcinoma and for monitoring after total
  • EUROIMMUN offers various test systems for the detection of thyroid-specific autoantibodies (TRAb, anti-TPO, anti-TG), the autoantigen TG, thyroid hormones (FT3, FT4, calcitonin) and TSH

  

Order information

 

Test system Test name Detected parameter Antigen / tracer / substrate Order number
SAELI Anti-TSH Receptor (TRAb) ELISA (IgG) Ab against TSH receptor (thyrotropin receptor) Ag-coated microplate wells EA 1015-9601 G
Anti-TSH Receptor (TRAb) Fast ELISA (IgG) EA 1015-9601-1 G
Anti-Thyroglobulin ELISA (IgG) Ab against thyroglobulin (TG) EA 1013-9601 G
Anti-TPO ELISA (IgG) Ab against thyroperoxidase (TPO) EA 1012-9601 G
Calcitonin ELISA Calcitonin Antibody-coated microplate wells EQ 6431-9601
Thyrotropin (TSH) ELISA Thyrotropin (TSH) EQ 1018-9601*
Free Triiodothyronine (FT3) ELISA Free triiodothyronine (FT3) EQ 1016-9601*
Free Thyroxine (FT4) ELISA Free thyroxine (FT4) EQ 1017-9601*
Reverse Triiodothyronine (rT3) ELISA Reverse triiodothyronine (FT3) EQ 1016-9601-9
RIA Anti-TSH Receptor (TRAb) RIA (CT) Ab against TSH receptor (thyrotropin receptor) Iodine-125 TSH RA 1015-10001-1
Anti-Thyroglobulin (TG) RIA (CT / Magnetic) Ab against thyroglobulin (TG) Iodine-125 TG RA 1013-10001-1
RA 1013-10001-3
Anti-Thyroperoxidase (TPO) RIA (CT / Precipitation / Magnetic) Ab against thyroperoxidase (TPO) Iodine-125 TPO RA 1012-10001-1
RA 1012-10001-2
RA 1012-10001-3
RA 1012-20001-3
Turbo-Thyrotropin (TSH) IRMA (CT) Thyrotropin (TSH) Iodine-125 anti-TSH RD 1018-10001-1
Thyroglobulin (TG) IRMA (CT) Thyroglobulin (TG) Iodine-125 anti-TG RD 1013-10001
Free Triiodothyronine (FT3) RIA (CT) Free triiodothyronine (FT3) Iodine-125 anti-T3 RD 1016-10001-1
Free Thyroxine (FT4) RIA (CT) Free thyroxine (FT4) Iodine-125 anti-T4 RD 1017-10001-1
Positive control: FT3 / FT4 RIA (5 ml)     CR 1010-0108-1
Calcitonin IRMA (CT) Calcitonin Iodine-125 anti-calcitonin RD 1019-10001-1
IIFT IIFT: Thyroid gland (Monkey) Ab against thyroid antigens Thyroid gland (monkey) FA 1010-1005
IIFT Mosaic: Thyroid Gland (Monkey) / Kidney (Rat) Ab against thyroid antigens and mitochondria (AMA) Thyroid gland (monkey, kidney (rat) FA 1010-1005-1
EUROPLUS Thyroid Gland (Monkey) /
Thyroglobulin
Ab against thyroid antigens and thyroglobulin (TG) Thyroid gland (monkey), Thyroglobulin EUROPLUS FA 1010-1005-3
FA 1010-1010-3

* in development

References

  1. Schott M, et Autoimmune Schilddrüsenerkrankungen. Dtsch Arztebl 103(45):A3023–32 (2006). [in German]
  2. Wiersinga WM. Hashimoto’s Thyroiditis. In: Vitti P., Hegedus L. (eds) Thyroid Diseases. Endocrinology. Springer, Cham, retrieved on 4 Aug 2020.
  3. Dawe K, et Autoantigens in thyroid diseases. Springer Semin Immunpathol 14(3):285-307 (1993).
  4. Slahor L, et Hypothyreose bei Autoimmunthyreopathie. Schweiz Med Forum 9(18):342-343 (2009). [in German]
  5. Saravanan P, et Thyroid Autoantibodies. Endocrinol Metab Clin North Am 30(2):315-337 (2001).
  6. Napier C, et Graves’ Disease. 2016. In: Vitti P., Hegedus L. (eds) Thyroid Diseases. Endocrinology. Springer, Cham, retrieved on 4 Aug 2020.
  7. Meng Diagnostik der Hyperthyreose. ZaeFQ 95:51-60 (2001). [in German]
  8. Ruggeri RM, et Autoimmune comorbidities in Hashimoto‘s thyroiditis: different patterns of association in adulthood and childhood/adolescence.

Eur J Endocrinol 176(2):133-141 (2017).

  1. Cui Z, et Establishment of clinical diagnosis model of Graves’ disease and Hashimoto’s thyroiditis. J Transl Med 17:11 (2019).
  2. Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). Operative Therapie maligner Schilddrüsenerkrankungen. S2k guideline, version 11/2012. [in German]
  3. Görges R, et Der Schilddrüsenknoten und der Stellenwert der Tumormarkerbestimmung. Der Nuklearmediziner 31(03):228-236. [in German]
 

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