IGF-1 levels in different stages of liver steatosis and its association with metabolic syndrome.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome related to insulin resistance. Insulin-like growth factor 1 (IGF-1) is mainly produced by hepatocytes and its secretion is stimulated by growth hormone. Our aim was to assess possible changes in IGF-1 levels in patients with different ultrasonography stages of NAFLD and its association with hyperlipidemia, impaired glucose tolerance, non-insulin dependant type 2 diabetes, waist circumference, obesity and arterial hypertension. METHODS: One hundred and ten consecutive patients were evaluated. RESULTS: IGF-1 levels decreased as liver steatosis worsened. There was a statistically significant difference between mild-moderate steatosis on one hand, and severe steatosis on the other (142 vs. 110, P < 0.05). Homeostasis model assessment of insulin resistance (HOMA) and insulin levels showed a tendency to inverse association with IGF-1, but it was not statistically significant. HOMA significantly increased in severe liver steatosis when compared with mild-moderate steatosis (6.20 vs. 3.99, P < 0.05). Insulin levels also showed a significant increase (3.01 +/- 0.61 vs. 2.59 +/- 0.56, P < 0.05). Body mass index showed a significant inverse correlation with IGF-1 level (r = -0.19, P < 0.05) and a tendency to increase as liver steatosis worsened. Waist circumference increased significantly as liver steatosis worsened (severe vs. mild-moderate: 114 vs. 100, P < 0.05). CONCLUSIONS: IGF-1 levels showed a decrease as liver steatosis worsened. This difference was statistically significant between mild-moderate and severe stetaosis. Inverse correlation between IGF-1 levels and BMI was also statistically significant. There was no statistically significant correlation between IGF-1 levels and HOMA and insulin levels.

A novel 1297-1304delGCCTGCCA mutation in the exon 10 of the thyroid hormone receptor ß gene causes resistance to thyroid hormone.

INTRODUCTION: Resistance to the thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to hormonal action caused by mutations located in the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor ß (TRß) gene. PATIENT: The patient in this study, a 42-year-old Caucasian male, came to medical attention because he experienced atrial fibrillation. Clinical evaluation showed a small and diffuse goiter and biochemical tests revealed markedly elevated concentrations of total T(4), total T(3), and free T(4), normal thyroid-stimulating hormone (TSH) values and slightly increased I(131) thyroid uptake at 24 hours. The thyroperoxidase, thyroglobulin, and TSH receptor antibodies were positive. He was treated with cabergoline plus methimazole. This treatment was stopped because of the inconsistent response, monotherapy with tri-iodothyroacetic acid (TRIAC) was then prescribed after molecular diagnosis confirmed RTH syndrome. METHODS: The exons 9 and 10 of the TRß gene, including splicing signals and the flanking intronic regions of each intron, were amplified with PCR. DNA sequences from each amplified fragment were performed with the Taq polymerase-based chain terminator method and using the specific TRß forward and reverse primers. RESULTS: Direct sequence analysis of the exons 9 and 10 of the TRß gene revealed an eight basepair deletion, 1297-1304delGCCTGCCA in exon 10. The mutation produces a frameshift at amino acid 433 and introduces a stop codon TGA at position 461, 85 nucleotides downstream from deletion. This alteration was not detected in either the father or mother of the patient, suggesting a de novo mutation that was confirmed by DNA fingerprint analysis. CONCLUSIONS: In the present study we have identified a novel sporadic mutation corresponding to 1297-1304delGCCTGCCA deletion in the activating function 2 (AF-2) region of TRß. To our knowledge, this is the first time that the presence of a partial deletion of eight nucleotides in the TRß has been reported.

A novel 1297-1304delGCCTGCCA mutation in the exon 10 of the thyroid hormone receptor beta gene causes resistance to thyroid hormone.

INTRODUCTION: Resistance to the thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to hormonal action caused by mutations located in the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor beta (TRbeta) gene. PATIENT: The patient in this study, a 42-year-old Caucasian male, came to medical attention because he experienced atrial fibrillation. Clinical evaluation showed a small and diffuse goiter and biochemical tests revealed markedly elevated concentrations of total T4, total T3, and free T4, normal thyroid-stimulating hormone (TSH) values and slightly increased I131 thyroid uptake at 24 hours. The thyroperoxidase, thyroglobulin, and TSH receptor antibodies were positive. He was treated with cabergoline plus methimazole. This treatment was stopped because of the inconsistent response, monotherapy with tri-iodothyroacetic acid (TRIAC) was then prescribed after molecular diagnosis confirmed RTH syndrome. METHODS: The exons 9 and 10 of the TRbeta gene, including splicing signals and the flanking intronic regions of each intron, were amplified with PCR. DNA sequences from each amplified fragment were performed with the Taq polymerase-based chain terminator method and using the specific TRbeta forward and reverse primers. RESULTS: Direct sequence analysis of the exons 9 and 10 of the TRbeta gene revealed an eight basepair deletion, 1297-1304delGCCTGCCA in exon 10. The mutation produces a frameshift at amino acid 433 and introduces a stop codon TGA at position 461, 85 nucleotides downstream from deletion. This alteration was not detected in either the father or mother of the patient, suggesting a de novo mutation that was confirmed by DNA fingerprint analysis. CONCLUSIONS: In the present study we have identified a novel sporadic mutation corresponding to 1297-1304delGCCTGCCA deletion in the activating function 2 (AF-2) region of TRbeta. To our knowledge, this is the first time that the presence of a partial deletion of eight nucleotides in the TRbeta has been reported.