[Long-term follow up after antithyroid drug treatment in Graves' disease]

In Europe antithyroid drug (ATD) therapy is the preferred initial treatment for patients with a first episode of Graves' disease. Results of long-term recurrence rates following ATD therapy are conflicting. The main goal was to assess long-term recurrence rate after ATD treatment. Secondarily we tried to verify chemical and clinical findings (thyrotropin receptor antibodies (TRAb), duration of primary treatment, age and goitre size) as predictive factors.

Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease

OBJECTIVES: Recently, a genome-wide association study showed that single-nucleotide polymorphisms (SNPs) in the chromosome 4q27 region containing IL2 and IL21 are associated with celiac disease. Given the increased prevalence of inflammatory bowel disease (IBD) among celiac disease patients, we investigated the possible involvement of these SNPs in IBD. METHODS: Five SNPs strongly associated with celiac disease within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block on chromosome 4q27 and one coding SNP within the IL21 gene were analyzed in a large German IBD cohort. The study population comprised a total of 2,948 Caucasian individuals, including 1,461 IBD patients (ulcerative colitis (UC): n=514, Crohn's disease (CD): n=947) and 1,487 healthy unrelated controls. RESULTS: Three of the five celiac disease risk markers had a protective effect on UC susceptibility, and this effect remained significant after correcting for multiple testing: rs6840978: P=0.0082, P(corr)=0.049, odds ratio (OR) 0.77, 95% confidence interval (CI) 0.63-0.93; rs6822844: P=0.0028, P(corr)=0.017, OR 0.73, 95% CI 0.59-0.90; rs13119723: P=0.0058, P(corr)=0.035, OR 0.75, 95% CI 0.61-0.92. A haplotype consisting of the six SNPs tested was markedly associated with UC susceptibility (P=0.0025, P(corr)=0.015, OR 0.72, 95% CI 0.58-0.89). Moreover, in UC, epistasis was observed between the IL23R SNP rs1004819 and three SNPs in the KIAA1109/TENR/IL2/IL21 block (rs13151961, rs13119723, and rs6822844). CONCLUSIONS: Similar to other autoimmune diseases such as celiac disease, rheumatoid arthritis, type 1 diabetes, Graves' disease, and psoriatic arthritis, genetic variation in the chromosome 4q27 region predisposes to UC, suggesting a common genetic background for these diseases.

[Diagnosis and therapy of hyperthyreosis]

Hyperthyreosis, diabetes and calcium disorders are frequent endocrine diseases that are often encountered by the primary care physician. The diagnosis of hyperthyreosis can be established by many different laboratory and analytical tests. However, the clinical context can often guide a specific diagnostic approach. Graves disease and toxic adenomas are the most frequent causes of hyperthyreosis. Diagnosis of Graves disease is most frequent between age 35 and 60 and about 10-20% of patients show already initially signs of endocrine orbithopathy. Measurement of thyroid stimulating immunoglobulins (TSI) is especially valuable in unclear cases. Toxic adenomas are always diagnosed by thyroid uptake studies. Rare causes of hyperthyreosis include thyreoiditis, which is characterized by transient hyperthyreosis (<2 months), and thyrotoxicosis factitia. Here, we discuss diagnosis and therapy of different causes of hyperthyreosis based on three clinical examples.

Expression of nitric oxide synthase III in human thyroid follicular cells: evidence for increased expression in hyperthyroidism

Nitric oxide mediates a wide array of cellular functions in many tissues. It is generated by three known isoforms of nitric oxide synthases (NOS). Recently, the endothelial isoform, NOSIII, was shown to be abundantly expressed in the rat thyroid gland and its expression increased in goitrous glands. In this study, we analyzed whether NOSIII is expressed in human thyroid tissue and whether levels of expression vary in different states of thyroid gland function. Semiquantitative RT-PCR was used to assess variations in NOSIII gene expression in seven patients with Graves' disease, one with a TSH-receptor germline mutation and six hypothyroid patients (Hashimoto's thyroiditis). Protein expression and subcellular localization were determined by immunohistochemistry (two normal thyroids, five multinodular goiters, ten hyperthyroid patients and two hypothyroid patients). NOSIII mRNA was detected in all samples: the levels were significantly higher in tissues from hyperthyroid patients compared with euthyroid and hypothyroid patients. NOSIII immunoreactivity was detected in vascular endothelial cells, but was also found in thyroid follicular cells. In patients with Graves' disease, the immunostaining was diffusely enhanced in all follicular cells. A more intense signal was observed in toxic adenomas and in samples obtained from a patient with severe hyperthyroidism due to an activating mutation in the TSH receptor. In multinodular goiters, large follicles displayed a weak signal whereas small proliferative follicles showed intense immunoreactivity near the apical plasma membrane. In hypothyroid patients, NOSIII immunoreactivity was barely detectable. In summary, NOSIII is expressed both in endothelial cells and thyroid follicular cells. The endothelial localization of NOSIII is consistent with a role for nitric oxide in the vascular control of the thyroid. NOSIII expression in thyroid follicular cells and the variations in its immunoreactivity suggest a possible role for nitric oxide in thyrocyte function and/or growth.

Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.

[ABC of thyroid diseases and their treatment]

Thyroid diseases are caused by a disturbance of thyroid hormone secretion, inflammations or tumors of the thyroid or combinations thereof. Most important causes for hyperthyroidism are Graves' disease and toxic nodular goiters (including toxic adenomas). Hypothyroidism is often caused by Hashimoto's chronic thyroiditis and can occur in patients after thyroidectomy. Chronic hashimoto's thyroiditis and subacute de Quervain's thyroiditis are the thyroid inflammations most frequently seen. Graves' disease and Hashimoto's thyroiditis are autoimmune thyroid diseases. Thyroid tumors encompass benign solitary nodules, diffuse and nodular goiters, papillary, follicular, medullary and anaplastic carcinomas.

Enhanced-depth optical coherence tomography for imaging horizontal rectus muscles in Graves' orbitopathy.

PURPOSE Graves' orbitopathy (GO) is an extraocular eye disease with symptoms ranging from minor discomfort from dry eyes to strabismus and visual loss. One of the hallmarks of active GO is visible hyperemia at the insertion of the extraocular muscles. The aim of the present study was to evaluate the use of enhanced-depth imaging spectral domain anterior segment optical coherence tomography (EDI SD AS-OCT) for detecting pathological changes in horizontal recti muscles of patients with GO. METHODS Prospective cross sectional study of 27 eyes. Only women were included. EDI AS-OCT was used to measure the thickness of the tendons of the horizontal recti muscles in a predefined area in patients with GO and healthy controls. RESULTS EDI AS-OCT was able to image the tendons of the horizontal recti muscles in both healthy controls and patients suffering from GO. The mean thickness of the medial rectus muscle (MR) tendon was 256.4 μm [±17.13 μm standard deviation (SD)] in the GO group and, therefore, significantly thicker (p = 0.046) than in the healthy group which had a mean thickness of 214.7 μm (±5.516 μm SD). There was no significant difference in the mean thickness of the tendon of the lateral recti muscles (LRs) between these groups. CONCLUSION This is the first report showing that EDI AS-OCT is suitable to detect swelling at the insertion site of the MR muscle in GO. MR tendon thickness may be a useful parameter to monitor activity in these patients.