Incidence and clinical presentation of moderate to severe graves' orbitopathy in a Danish population before and after iodine fortification of salt

Abstract

Context: Population-based data on the incidence and clinical presentation of moderate to severe Graves' orbitopathy (GO) are scarce, and virtually nothing is known on the effect of an iodization program on the incidence and presentation of GO.

Objective: The objective of the study was to characterize incident moderate to severe GO in North Jutland County, Denmark, during the period 1992-2009, before and after the Danish salt iodization program.

Design and patients: The design of the study was a prospective register of patients with incident moderate to severe GO in a population during 8.9 million persons × years of observation.

Setting: The study was conducted at a thyroid-eye clinic of university hospital.

Main outcome measures: Clinical presentation and incidence before and after the year 2000 initiation of the mandatory Danish iodization of salt were measured. The incidence of GO was related to the incidence of Graves' hyperthyroidism (GH) in the same population.

Results: The incidence rate of moderate to severe GO was 16.1/million per year (women: 26.7; men: 5.4), with no change associated with iodization of salt. The moderate to severe GO incidence was 4.9% of the incidence of GH. The incidence rate ratio between women and men with GO (4.9) was not different from the ratio in GH. Compared with GH, only a few patients (<2%) suffered from moderate and severe GO below the age of 40 yr, whereas GO was relatively common in age groups 40-60 yr (∼8%).

Conclusions: Approximately 5% of the patients with Graves' disease develop moderate to severe GO, with a similar risk in women and men with Graves' disease. The risk of GO is much higher in patients aged 40-60 yr than in young patients with Graves' disease. Salt iodization was not associated with a change in the incidence of GO.

Fig. 1.

Schedule of the Danish mandatory iodization of salt in relation to the period of inclusion of patients with moderate to severe GO. The patients were included during 9-yr periods before and after salt iodization. Salt iodization increased the median urinary iodine concentration in the Danish population, as indicated elsewhere (34).

Fig. 2.

Ratio between incidence rates of moderate to severe Graves' orbitopathy and of Graves' hyperthyroidism according to patient age. The horizontal stippled line indicates the incidence rate ratio (4.87 × 10⁻²) at all ages combined and the shaded area around the line is the 95% CI (4.02–5.90) for this value. The incidence rate ratio (95% CI) for patients younger than 40 yr was 1.16 (0.63–2.15), and for patients 40+ yr of age, it was 6.50 (5.27–8.01).

Fig. 3.

Temporal relationship between diagnosis of thyroid dysfunction [hyperthyroidism (Hyper) or hypothyroidism (Hypo)] indicated by the 0-arrow and debut of Graves' orbitopathy in 133 patients with moderate to severe Graves' orbitopathy and with thyroid dysfunction. Note the change in time scale of abscissa indicated by stippled lines.

Fig. 4.

Upper panel, Frequency of uniocular restriction in field of fixation (worst eye) (percentage of expected field of motility). Lower panel, Reduction in binocular field of single vision. For evaluation of double vision, three patients with monocular vision were excluded.

Fig. 5.

Distribution of Hertel exophthalmometer readings (worst eye) in women and men with moderate to severe GO. One patient was excluded for technical reasons. Hertel readings in women were 22.6 ± 3.2 mm (mean ± sd), and they were 24.2 ± 3.1 mm in men. Assuming an upper normal value of 19 mm in women and 21 mm in men (34), 82.2% of women and 87.5% of men had elevated values.