Serum immunoglobulin G4 levels and Graves' disease phenotype.
OBJECTIVE
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.
Endocrinology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. sorina.martin@gmail.com.|Endocrinology Department, Elias Hospital, Marasti Avenue 17, 011461, Bucharest, Romania. sorina.martin@gmail.com.
Carmen Sorina
CS
Martin
Endocrinology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.|Endocrinology Department, Elias Hospital, Marasti Avenue 17, 011461, Bucharest, Romania.
Anca Elena
AE
Sirbu
Endocrinology Department, Elias Hospital, Marasti Avenue 17, 011461, Bucharest, Romania.
Minodora Andreea
MA
Betivoiu
Laboratory Department, Elias Hospital, Marasti Avenue 17, 011461, Bucharest, Romania.
Suzana
S
Florea
Endocrinology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.|Endocrinology Department, Elias Hospital, Marasti Avenue 17, 011461, Bucharest, Romania.
Carmen Gabriela
CG
Barbu
Endocrinology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.|Endocrinology Department, Elias Hospital, Marasti Avenue 17, 011461, Bucharest, Romania.
Simona Vasilica
SV
Fica
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006111:Graves Disease / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D011989:Receptors, Thyrotropin / Q000276:immunology; D013954:Thyroglobulin / Q000097:blood / Q000276:immunology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D001323:Autoantibodies; D007074:Immunoglobulin G; D011989:Receptors, Thyrotropin; D014284:Triiodothyronine; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine
ATA; Graves’ disease; IgG4; Ophthalmopathy; TPOAb