[Autoimmune diseases of the thyroid gland]. / Autoimmune Schilddrüsenerkrankungen.

Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T­cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.

Clinical Evaluation of the First Automated Assay for the Detection of Stimulating TSH Receptor Autoantibodies.

Until recently, stimulating TSH receptor autoantibodies (sTRAbs) could only be measured by bioassays. A new assay system, which directly detects sTRAb in sera by applying bridge technology, has been established and is now available as automated chemiluminescence (bridge) immunoassay. We evaluated the automated bridge assay in clinical routine and compared it with a conventional automated TRAb assay (competition assay). Altogether, 226 Graves' disease (GD), 57 autoimmune thyroiditis, 74 non-autoimmune nodular goiter and 49 thyroid cancer patients, as well as 41 healthy controls were retrospectively evaluated. ROC plot analysis based on sera of newly diagnosed GD patients revealed an area under curve of 0.99 (95% CI: 0.99-1.0) indicating a high assay sensitivity and specificity. The highest sensitivity (100%) and specificity (99%) were seen at a cut-off level of 0.55 IU/l. The calculated positive predictive value was 94%, whereas the negative was 100%. Applying a ROC plot-derived cut-off of≥0.30 IU/l, derived from sera of GD patients already receiving antithyroid drug therapy for≤6 months, the sensitivity was 99% whereas the specificity was 98%. Detailed comparison of both assay systems used revealed a slightly different distribution of sTRAb and TRAb. Measurement of sTRAb during follow-up revealed a steady decline over one year of follow-up. In summary, our results demonstrate that the new automated bridge assay system for detecting sTRAb has a high sensitivity and specificity for diagnosing GD and to discriminate from other thyroid diseases, respectively. Our study, however, does not provide full evidence that the bridge assay is specific for sTRAb only.

Anti-Thyroperoxidase Antibody Levels >500 IU/ml Indicate a Moderately Increased Risk for Developing Hypothyroidism in Autoimmune Thyroiditis.

Autoimmune Thyroiditis (AIT) is the most common autoimmune disease, which is characterized by cellular and humoral immunity leading to thyroid destruction. The impact of the humoral immunity on the risk to develop hypothyroidism has not exactly been defined yet. The aim of the present study was to investigate the association between thyroid antibody levels and the risk for developing hypothyroidism. In this retrospective study, 335 untreated AIT patients were enrolled. Anti-thyroperoxidase (TPO) antibodies, anti-thyroglobulin (Tg) antibodies (Abs), and the TSH level were measured. Patients with TPO-Ab levels>500 IU/ml showed a moderately increased risk of having elevated TSH levels [p=0.0023; relative risk (95% confidence interval): 1.343 (1.108-1.627)] compared to those below this threshold. AIT patients with TPO- or Tg-Abs<100 IU/ml and between 100-500 IU/ml had no significantly different TSH levels. Presence of Tg-Abs alone or in combination with TPO-Abs did not help to increase the sensitivity to identify patients at risk. Long term follow-up of AIT patients with high TPO-Abs level (>500 IU/ml) showed an increase of TSH levels (mean: 0.5 mIU/l; range: 2.52±2.73 to 3.02±3.05 mIU/l; p=0.0420). Still, these patients remained euthyroid. Our data indicate largely elevated levels of TPO-Abs being associated with a moderately increased risk of developing hypothyroidism.

[Endocrinologic side effects of oncologic treatment with anti-CTLA-4-antibodies]. / Endokrinologische Nebenwirkungen einer onkologischen Therapie mit Anti-CTLA-4-Antikörpern.

New immune-modulating treatments like the anti-CTLA-4-antibodies-based therapies are increasingly used in medical oncology. The action of Ipilimumab, a monoclonal anti-CTLA-4-antibody used for the treatment of metastasized melanoma and other solid tumors, is well documented. Blocking the CTLA-4-receptors on lymphocytes leads to T-cell activation and hence reduction of the tumor-mediated immunotolerance. This mechanism constitutes the basis of the antiproliferative effects but is also responsible for a spectrum of specific adverse events (immune-related adverse events, IRAE). IRAE of the endocrine system comprise hypophysitis, thyroiditis and adrenalitis. Especially adrenal insufficiency can be fatal when not diagnosed and treated. Symptoms often are unspecific and early diagnosis and targeted treatment are crucial. We present a case report and summarize - based upon the current literature - the diagnosis and treatment of endocrinologic IRAEs.