title: The phenotype of newly diagnosed Graves' disease in Italy in recent years is milder than in the past: results of a large observational longitudinal study.
abstract: OBJECTIVE
  The Merseburg triad (hyperthyroidism, goiter, and orbitopathy) characterizes classical description of Graves' disease (GD). Aim of this observational, longitudinal study was to evaluate the current clinical features of newly diagnosed GD in Italy.
  
  
  METHODS
  In two Northern Italy centers (Varese and Pavia), 283 consecutive patients (211 women, 72 men; mean age 47.4 years) with newly diagnosed GD were recruited in the years 2010-2014. Diagnosis was based on established criteria, and thyroid volume was assessed by ultrasonography. A clinical severity score (CSS) to assess the overall disease severity was developed by grading each component of the Merseburg triad.
  
  
  RESULTS
  At diagnosis, 45 % of patients had no goiter, and 30 % had a small goiter. The proportion of goitrous patients was much lower than in two Italian studies performed 20-30 years ago. Hyperthyroidism was subclinical in 16 % and mild in 29 % of patients, and Graves' orbitopathy was present in 20 %, usually mild, and active in only 2.5 % of patients. Using the CSS, less than half (44 %) of the patients had severe GD, while 22 % had mild and 34 % moderate disease. CSS was associated with a significantly higher risk of poorly controlled hyperthyroidism at 6 months.
  
  
  CONCLUSIONS
  In Italy, a relevant proportion of Graves' patients at diagnosis have mild to moderate GD; about half of them have no goiter, slightly less than one-fifth have subclinical hyperthyroidism, and only 20 % have GO. Thus, the clinical phenotype of GD is milder than in the past, possibly due to both earlier diagnosis and treatment, and improved iodine nutrition.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy. luigi.bartalena@uninsubria.it.
authors.forename: L
authors.initials: L
authors.lastname: Bartalena
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Masiello
authors.affiliation: Salvatore Maugeri Foundation and Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Magri
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.|Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, Varese, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Veronesi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bianconi
authors.affiliation: Salvatore Maugeri Foundation and Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Zerbini
authors.affiliation: Salvatore Maugeri Foundation and Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gaiti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Spreafico
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Gallo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Premoli
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Piantanida
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Tanda
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy.|Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, Varese, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ferrario
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Vitti
authors.affiliation: Salvatore Maugeri Foundation and Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Chiovato
mesh_terms: D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
keywords: Antithyroid drugs; Goiter; Graves’ disease; Graves’ orbitopathy; Hyperthyroidism; Thyrotropin receptor antibody