Thyroid gene expression in familial nonautoimmune hyperthyroidism shows common characteristics with hyperfunctioning autonomous adenomas.

CONTEXT: Dominant activating mutations of the TSH receptor are the cause of familial nonautoimmune hyperthyroidism (FNAH) (inherited mutations affecting the whole gland since embryogenesis) and the majority of hyperfunctioning autonomous adenomas (AAs) (somatic mutations affecting only one cell later in the adulthood). OBJECTIVE: The objective of the study was defining the functional and molecular phenotypes of FNAH and comparing them with the ones of AA. DESIGN: Functional phenotypes were determined in vitro and molecular phenotypes by hybridization on microarray slides. PATIENTS: Nine patients with FNAH were investigated, six for functional in vitro study of the tissue and five for gene expression. RESULTS: Iodide metabolism, H(2)O(2), cAMP, and inositol phosphate generation in FNAH slices stimulated or not with TSH were normal. The mitogenic response of cultured FNAH thyrocytes to TSH was normal but more sensitive to the hormone. Gene expression profiles of FNAH and AAs showed that among 474 genes significantly regulated in FNAH, 93% were similarly regulated in AAs. Besides, 783 genes were regulated only in AAs. Bioinformatic analysis pointed out common down-regulations of genes involved in immune response, cell/cell and cell/matrix adhesions, and apoptosis. Pathways up-regulated only in AAs mainly involve diverse biosyntheses. These results are consonant with the larger growth of AAs than FNAH tissues. CONCLUSIONS: Whether hereditary or somatic after birth, activating mutations of the TSH receptor have the same qualitative consequences on the thyroid cell phenotype, but somatic mutations in AAs have a much stronger effect than FNAH mutations. Both are variants of one disease: genetic hyperthyroidism.

[Subclinical hypothyroidism and quality of life of women aged 50 or more with hypercholesterolemia: results of the HYOGA study]. / Hypothyroïdie fruste et qualité de vie chez des femmes hypercholestérolémiques de plus de 50 ans: résultats de l'étude HYOGA.

AIM: Subclinical hypothyroidism (SCHT) is defined by the combination of an increased TSH level and a normal free thyroxin concentration. The aim of this survey is the description of the prevalence, the symptoms and the quality of life in SCHT diagnosed in a group of hypercholesterolemic women. METHODS: A total of 1610 female patients aged 50 or more with hypercholesterolemia (total cholesterol between 240 and 400mg/dl, receiving or not a lipid-lowering treatment) were enrolled by 347 general practitioners (GPs). A clinical form including symptoms, clinical history, and treatments was completed by GPs while a SF-36 QOL form was filled up by the patients. Further GPs' prescriptions for tests and treatments were also recorded. RESULTS: Full data leading to subclinical hypothyroidism are available in 721 patients (44.8%) who were selected into the study. Among these patients, the prevalence of SCHT (SCHT+) is 16.6% (120 patients) and 76.3% of the patients have at least one symptom. Most frequent symptoms are physical and intellectual asthenia, muscular weakness, and sensitivity to cold but those symptoms are present in patients without SCHT (SCHT-) too and there is no significant difference between the two groups. TSH level was 4 to 10 mUI/l in 90% of SCHT+ patients. 38.6% of hypercholesterolemic SCHT+ patients never had any TSH measurement. QOL is affected in SCHT+ compared to SCHT- patients with a significantly decreased mental summary score of 36.21+/-9.4 versus 39.4+/-12.18 (p<0.006). QOL (mental health score) is significantly lower when TSH value raised from a 2.4-4 range up to a 4-10 mUI/L range. CONCLUSIONS: SCHT is frequent in a population of hypercholesterolemic female patients aged 50 or more. In the presence of suggestive symptoms, screening is important especially as QOL is affected even when TSH is < 10 mUI/L. It remains to show with controlled prospective studies whether thyroxin supplementation can improve symptoms and QOL.

[Multinodular goiters]. / Goitres multinodulaires.

The incidence of multinodular goiters (MNG) differs according to the countries, and seems to be widely dependent of the iodine status. In France, the SU.VI.MAX study indicates that 4.75% of the active population is suffering from MNG, this incidence is increased with gender and age. The role of genetic factors is estimated as being around 80%. The remaining 20% are related to environmental factors, some of them being still unknown. Admit these external factors, the iodine deficiency is predominant and should be theoretically easy to avoid. Most of MNG develop on diffuse goiters and could be prevented when these underlying lesions are treated early by the administration of thyroid hormone alone or associated with iodide potassium. Once the nodularity of the thyroid tissue is present, the medical treatment is of weak efficacy, it usually stabilises the goiter and prevents the occurrence of new nodules. The two main treatments are surgery and radioactive iodine, the latter is currently used not only when the former is contra-indicated. In some countries, radioactive iodine is considered as the best alternative in the majority of cases.