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Thyroid Volume in Hypothyroidism due to Autoimmune Disease Follows a Unimodal Distribution: Evidence against Primary Thyroid Atrophy and Autoimmune Thyroiditis Being Distinct Diseases

Department of Endocrinology and Medicine (A.C., I.B.P., P.L.), Aalborg Hospital, Aarhus University Hospital, DK-9000 Aalborg, Denmark; Endocrine Unit (N.K., H.P.), Department of Internal Medicine I, Bispebjerg Hospital, DK-2400 Copenhagen V, Denmark; National Heart Foundation (L.O.), DK-1127 Copenhagen K, Denmark; and Research Centre for Disease Prevention and Health (T.J.), DK-2600 Glostrup, Copenhagen, Denmark

Address all correspondence and requests for reprints to: Allan Carlé, M.D., Ph.D., Department of Endocrinology and Medicine, Aalborg Hospital, Aarhus University Hospital, DK-9000 Aalborg, Denmark. E-mail: carle{at}dadlnet.dk.

Context: 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.

Design and Setting: This was a population-based study identifying patients newly diagnosed with overt autoimmune hypothyroidism.

Patients: 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 T₄ 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.