Serum immunoglobulin G4 levels and Graves' disease phenotype.

PURPOSE: We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. METHODS: This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. RESULTS: In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p < 0.001), had higher antithyroid peroxidase antibody (p = 0.01), and anti-thyroglobulin antibody levels (p = 0.006) and required shorter duration of the first methimazole treatment cycle (p = 0.041) than patients with immunoglobulin G4 below the 75th percentile. At diagnosis, patients with immunoglobulin G4 levels above the 90th percentile (>286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. CONCLUSIONS: Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

IGF1 deficiency in newly diagnosed Graves' disease patients.

OBJECTIVE: Thyroid hormones influence the GH/IGF1 axis, but previous studies have reported discrepant results regarding serum IGF1 levels in hyperthyroidism. We have therefore investigated, at diagnosis, the relationship between serum IGF1 levels and the main characteristics of Graves' disease (GD): severity of hyperthyroidism, goiter size, presence of active Graves' ophthalmopathy (GO), antythyroid antibodies status and titer. DESIGN AND METHODS: This cross-sectional study included 98 newly diagnosed hyperthyroid patients with GD who presented consecutively at our clinic. The main measured parameters were: TSH, FT4, FT3, TT3, thyroglobulin,anti-thyroid peroxidase antibodies (TPOAb), anti-thyroglobulin antibodies (ATA), thyrotropin receptor antibodies (TRAb), IGF1. Patients were considered IGF deficient if IGF1 z score was ≤-2SD from mean for age. RESULTS: In GD patients, men had higher IGF1 levels (p=0.023) and IGF1 z scores (p=0.013) than women. 18.4% of GD patients were, at diagnosis, IGF1 deficient. Compared to patients without IGF1 deficiency, these patients presented higher thyroglobulin (median=72.55, IQR=116.02 vs median=11.40, IQR=80.74 ng/ml, p=0.002) and FT3 (median=11.30, IQR=7.64 vs median=7.33, IQR=5.72 pg/ml, p=0.027), and lower ATA (median=20, IQR=0 vs median=34.05, IQR=161 iu/ml, p<0.001) levels. Thyroglobulin was independently associated with IGF1 deficiency (AUROC=0.732, 95% CI: 0.620-0.844, p=0.002; cut-off for thyroglobulin=50.40 ng/ml, Se=77.8%, Sp=70%). IGF1 status was not influenced by gender (p=0.084), current smoking (p=0.558), goiter size (p=0.533), active ophthalmopathy (p=0.334), TRAb (p=0.239) or TPOAb status (p=0.367). CONCLUSIONS: Nearly one fifth of newly diagnosed GD patients had IGF1 deficiency. IGF1 deficiency was associated with lower ATA titers, higher thyroglobulin levels and more severe FT3 hyperthyroidism at diagnosis.