title: Thyroid volume in hypothyroidism due to autoimmune disease follows a unimodal distribution: evidence against primary thyroid atrophy and autoimmune thyroiditis being distinct diseases.
abstract: BACKGROUND
  Primary overt autoimmune hypothyroidism is often divided into primary idiopathic hypothyroidism with thyroid atrophy (Ord's disease) and hypothyroidism with goitre (Hashimoto's disease).
  
  
  OBJECTIVE
  The aim of the present study was to characterize the two subtypes of disease.
  
  
  METHODS
  This was a population-based study identifying patients newly diagnosed with overt autoimmune hypothyroidism.
  
  
  METHODS
  We prospectively identified all patients with incident overt autoimmune hypothyroidism in a Danish population cohort, and 247 patients were invited to join a comprehensive program including thyroid ultrasonography and measurements of thyroid autoantibodies. Of the 144 patients investigated (58% of all invited), 139 were compared with 556 sex-, age-, and region-matched controls from the cohort.
  
  
  RESULTS
  Patients had lower median (11.6 ml vs. 13.5 ml, P = 0.001) and a more dispersed distribution of thyroid volumes compared with controls (P < 0.001). Log thyroid volume showed a Gaussian distribution in both males and females with no bimodal pattern. Nearly all patients had measurable thyroid autoantibodies, but with increasing thyroid volume (quartile I, II, III, and IV), levels of circulating antibodies were higher (median thyroid peroxidase autoantibody 1540, 3122, 4686, and 7058 kU/liter; median thyroglobulin autoantibody 72, 143, 119, and 1195 kU/liter), and thyroid volume correlated negatively with echogenicity (r = -0.21, P = 0.011). Patients with the smallest volumes were biochemically more hypothyroid at diagnosis (median serum T(4) 21.0, 45.5, 45.0, and 36.7 nmol/liter; median serum TSH 81.0, 40.9, 45.4, and 55.6 mU/liter). No difference between groups was observed in prevalence of TSH receptor autoantibody (14.7, 5.6, 14.7, and 8.3%) or duration of symptoms before hypothyroidism was diagnosed.
  
  
  CONCLUSIONS
  In primary autoimmune hypothyroidism, thyroid volume follows a normal distribution. Cases with thyroid atrophy and goiter are only extremes within this distribution and do not represent separate disorders. However, patients with low vs. high thyroid volume differ with respects to several characteristics.
authors.affiliation: Department of Endocrinology and Medicine, Aalborg Hospital, Aarhus University Hospital, DK-9000 Aalborg, Denmark. carle@dadlnet.dk
authors.forename: Allan
authors.initials: A
authors.lastname: Carlé
authors.forename: Inge Bülow
authors.initials: IB
authors.lastname: Pedersen
authors.forename: Nils
authors.initials: N
authors.lastname: Knudsen
authors.forename: Hans
authors.initials: H
authors.lastname: Perrild
authors.forename: Lars
authors.initials: L
authors.lastname: Ovesen
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Peter
authors.initials: P
authors.lastname: Laurberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy; D001323:Autoantibodies / Q000097:blood; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000473:pathology*; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000473:pathology*; D013972:Thyrotropin / Q000097:blood
chemical_list: D001323:Autoantibodies; D013972:Thyrotropin; D013954:Thyroglobulin; D007453:Iodide Peroxidase