An intronic SNP in the thyroid hormone receptor ß gene is associated with pituitary cell-specific over-expression of a mutant thyroid hormone receptor ß2 (R338W) in the index case of pituitary-selective resistance to thyroid hormone.

BACKGROUND: The syndrome of resistance to thyroid hormone (RTH) is caused by mutations in the thyroid hormone receptor ß gene (THRB). The syndrome varies from asymptomatic to diffuse hypothyroidism, to pituitary-selective resistance with predominance of hyperthyroid signs and symptoms. The wide spectrum of clinical presentation is not completely attributable to specific THRB mutations. The THRB gene encodes two main isoforms, TR ß1 which is widely distributed, and TR ß2, whose expression is limited to the cochlea, retina, hypothalamus, and pituitary. Recent data demonstrated that in mice an intron enhancer region plays a critical role in the pituitary expression of the ß2 isoform of the receptor. We thus hypothesized that polymorphisms in the human homologous region could modulate the pituitary expression of the mutated gene contributing to the clinical presentation of RTH. METHODS: Screening and in vitro characterization of polymorphisms of the intron enhancer region of the THRB gene in the index case of pituitary-selective RTH. RESULTS: The index case of pituitary-selective resistance is characterized by the missense R338W exon 9 mutation in cis with two common SNPs, rs2596623T and rs2596622C, located in the intron enhancer region of the THRB gene. Reporter gene assay experiments in GH3 pituitary-derived cells indicate that rs2596623T generates an increased pituitary cell-specific activity of the TR ß2 promoter suggesting that rs2596623T leads to pituitary over-expression of the mutant allele. CONCLUSIONS: The combined coding mutation and non-coding SNP therefore generate a tissue-specific dominant-negative condition recapitulating the patient's peculiar phenotype. This case illustrates the role of regulatory regions in modifying the clinical presentation of genetic diseases.

[The biopsychosocial model of adjustment of the rheumatoid arthritis as chronic illness]. / II modello biopsicosociale nell'adattamento all'artrite reumatoide come malattia cronica.

Through biopsychosocial model, empirical research about rheumatoid arthritis highlights the interdependence among psychological factors (cognitive, behavioural and emotional ones), psychopatological outcomes (measured as anxiety and depression), physical outcomes (showed by self-reported pain and disability) and physiological ones (measured by activation of immune and neuroendocrine system indexes) to originate psychological and physical adjustment to illness.

Thyroid disease in patients with McCune-Albright syndrome.

Involvement of the thyroid gland in the McCune-Albright Syndrome (MAS) is a common and sometimes overlooked feature of this disorder. The characteristics of the thyroid in MAS include isolated or combinations of generalized inhomogeneity, cystic and/or nodular features coupled with functional abnormalities. While most often the pathology is diffuse, it is rarely associated with compressive symptoms and signs. The functional abnormalities, which are seldom observed in the absence of underlying echographic structural changes, are characterized by autonomous function, frequently with a shifted T3/T4 ratio, suggesting an increase in intra-thyroidal conversion of the pro-hormone T4 into the active metabolite T3. While MAS-associated thyrotoxicosis is not always symptomatic, it is often linked with increased morbidity, especially in the presence of underlying conditions requiring surgical intervention. Although thyroid cancer has been described in two cases of MAS, the prevalence of malignancy does not appear to be high. The therapeutic options in MAS involvement of the thyroid gland include thionamides, 131Iodine and surgery.