Disease relevance of MNG1

• A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary) [1].
• Mortality in patients with Graves' disease and with multinodular goitre appeared similar to that of other patients of comparable age [2].
• The hyperthyroidism seemed typical of the autoimmune subgroup of toxic multinodular goitre [3].
• No blocking or receptor binding activity was detectable in patients with primary myxoedema (n = 23), Hashimoto's disease (n = 11), multinodular goitre (n = 6), or rheumatoid arthritis (n = 10) [4].
• TRAb positivity in patients with other thyroid disorders such as silent thyroiditis, toxic multinodular goitre and subacute thyroiditis has been reported but the role of TRAb in these disorders is unclear [5].

Psychiatry related information on MNG1

• A variant of the Capgras syndrome is described in a 43-year-old woman who had vitiligo and multinodular goitre [6].

High impact information on MNG1

• In Graves' disease and toxic multinodular goitre the remission rate is about 40-50% after antithyroid drugs, but these drugs have little effect in toxic adenoma [7].
• Circulating autoantibodies against a human-eye-muscle soluble antigen were detected in 17 of 23 patients with Graves' ophthalmopathy but in only 1 of 14 patients with Hashimoto's thyroiditis, in 2 of 11 patients with subacute thyroiditis, in no patient with Graves' hyperthyroidism without eye disease, and in none with multinodular goitre [8].
• Thyroid-stimulating immunoglobulins (TSIs) were measured by radioreceptor assay in serum from 51 patients with a multinodular goitre, divided into four groups according to thyroid function, and in 30 normal people [9].
• We postulate that non-toxic multinodular goitre, like Graves' disease, may result from increased circulating T.S.I., which in some cases may be present in sufficient concentration to cause thyrotoxicosis [10].
• In the normal thyroid (n = 10) and in benign thyroid disorders (n = 21; toxic diffuse goitre; multinodular goitre; follicular adenomas), E-cadherin mRNA levels were equally high and the follicles were generally stained, mainly along the lateral surface of the epithelial cells, by the anti-E-cadherin monoclonal antibody [11].

Chemical compound and disease context of MNG1

• Antithyroid drugs were prescribed for Graves' disease (n=8), thyrotoxicosis related to amiodarone intake (n=6) and multinodular goitre (n=6) [12].
• SUBJECTS: Sixteen post-menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre, eight of whom were treated with methimazole [13].
• These data suggest that the mechanisms leading to loss of iodide uptake in nonfunctioning hyperplastic nodules of toxic multinodular goitre are different from those that act on solitary nonfunctioning follicular adenomas [14].
• METHODS: Galectin-3 protein expression was assessed by immunohistochemistry in formalin-fixed thyroid tissues from 124 patients with histological diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 19), follicular adenoma (n = 32) and dominant nodules of multinodular goitre (n = 35) [15].
• Scintiscans were obtained for 13 patients: 8 had toxic diffuse goitre, 2 toxic multinodular goitre, 1 toxic uninodular goitre, and 2 had a lack of visualization consistent with 'painless thyroiditis'. Nine patients received a course of carbimazole and 6 of these remain in remission [16].

Biological context of MNG1

• The only genes known to be directly involved in susceptibility to NMTC are MNG1 on chromosome 14q32 and TCO on chromosome 19q13.2, previously localized by us and others [17].
• Three loci have been identified through genetic linkage: MNG1 on 14q32, TCO1 on 19p13.2, and fPTC on 1p21 [18].
• In contrast only 4% of 79 control sera from individuals with Hashimoto's, non-thyroid autoimmunity or multinodular goitre produced R.L.U. >1 [19].
• The level of apoptosis has been investigated in thyroid tissue from eight patients with Graves's disease, one with Hashitoxicosis, three with Hashimoto's thyroiditis, and five patients with multinodular goitre, using flow cytometry and an in situ immunofluorescence technique [20].
• Linkage analysis of candidate genes in autoimmune thyroid disease. III. Detailed analysis of chromosome 14 localizes Graves' disease-1 (GD-1) close to multinodular goiter-1 (MNG-1). International Consortium for the Genetics of Autoimmune Thyroid Disease [21].

Anatomical context of MNG1

• At least three genes account for familial papillary thyroid carcinoma: TCO and MNG1 excluded as susceptibility loci from a large Tasmanian family [22].
• Multinodular goitre with giant cell vasculitis of thyroid arteries in a woman with temporal arteritis [23].
• There was no significant difference between the proportion of gamma delta T cells in the PBMC of Graves' and MNG patients, nor between the PBMC and ITL populations in either patient group [24].
• The pattern of usage was similar to that in peripheral blood lymphocytes derived from normal subjects (n = 3) and from patients with Graves' disease (n = 3), as well as that present in the thyroids of patients with non-autoimmune toxic multinodular goitre (n = 4) [25].
• Like the 12 toxic adenomas, all the 14 functioning hyperplastic nodules and two adenomas of toxic multinodular goitre showed a high level of hNIS protein expression with respect to the normal collateral parenchyma and, in all cases, the protein was confined to the cell membrane [14].

Associations of MNG1 with chemical compounds

• Four patients (0.84%) with nodular thyroid disease (2 with uninodular and 2 with multinodular goitre) had both elevated basal and pentagastrin stimulated CT levels [26].
• We report here a case of generalized resistance to thyroid hormone associated with a multinodular goitre, which became toxic [27].
• Levothyroxine was given as a part of TSH suppression therapy in multinodular goitre patients [28].
• Circulating thyroid autoantibodies could be found in all amiodarone iodine-induced hyperthyroid patients with toxic diffuse goitre and in one with toxic multinodular goitre, whilst they were absent in the other patients [29].
• Propranolol improves the impaired TSH response to TRH in patients with autonomously functioning euthyroid multinodular goitre [30].

Other interactions of MNG1

• In a further family with 12 members in whom we have previously demonstrated linkage to the MNG-1 locus we investigated the Xp22 locus and the PDS gene in addition to our initial study [31].
• Furthermore, TSH-receptor antibodies were present in some patients with toxic multinodular goitre (TBIAb in 12.7% and TSAb in 15.9%) [32].
• On the other hand, 9 of the 11 patients with toxic multinodular goitre who had positive TSH-receptor antibody tests, also had serum thyroglobulin and/or thyroid microsomal antibodies [32].
• Ten of 502 patients presenting with thyroid cancer were hyperthyroid due to Graves' disease (4 patients), multinodular goitre (3), an autonomous functioning nodule (1) and a large functioning tumour (2) [2].
• In Graves' and multinodular goitre thyrocytes, inhibition of IL-1 (100 U/ml)-stimulated IL-6 release by dexamethasone (100 nmol/l) was 62.51% +/- 10.43 (S.E.M.), and in HTori3 cells it was 78.35% +/- 3 [33].

Analytical, diagnostic and therapeutic context of MNG1

• Induction of stimulating thyrotropin receptor antibodies after radioiodine therapy for toxic multinodular goitre and Graves' disease measured with a novel bioassay [34].
• For instance, total thyroidectomy may be beneficial in patients with endemic multinodular goitre or young patients with Graves' disease and accompanying cold nodules or high levels of autoantibodies [35].
• The value of intraoperative frozen-section biopsy of thyroid nodules (solitary or dominant in a multinodular goitre) was examined in patients who underwent fine-needle aspiration cytology (FNAC) for diagnosis before operation [36].
• Ultrasonography disclosed a multinodular goitre with cystic lesions [27].
• NCAM expression in thyrocytes was assessed by immunofluorescence in 59 surgical specimens of thyroid glands, and was found increased in 11/17 (64%) of Graves', in 5/25 (20%) of multinodular goitre (MNG) and in occasional adenoma glands [37].

References