Giant cell arteritis and thyroid dysfunction: multicentre case-control study

The association between giant cell arteritis and thyroid dysfunction remains controversial, but as giant cells are a possible feature of Graves’ disease, a common pathway has been suggested. In two series of 101 and 98 patients, the prevalence of hyperthyroidism was reported to be six times higher in cases of giant cell arteritis than in controls.¹,² This was not confirmed on smaller series,³,⁴ but 15 cases of hypothyroidism were reported in 31 patients with giant cell arteritis.⁵

We conducted a multicentre case-control study on cases of giant cell arteritis to investigate this relation.

Subjects, methods, and results

Assuming a prevalence of thyroid dysfunction of 1% in the general population and an odds ratio of 6 for hyperthyroidism in the patient group, the sample size requested, with α=0.05 and β=0.2, had been estimated to be 269 cases and controls.²

We prospectively studied 285 cases of giant cell arteritis (205 women, mean age 74.7 ± 8.2 years; 80 men, 72.7 ± 8.2) newly diagnosed during 1991-96. An experienced pathologist reviewed 262 (92%) of the biopsies: temporal arteritis was confirmed in 145—68 were classed as negative (eight did not have a biopsy), and 72 were classed as having polymyalgia rheumatica alone (22 did not have a biopsy). Blood samples taken up to 48 hours after diagnosis were sent to a reference laboratory.

Controls, randomly selected by computer from residents of Saint-Etienne affiliated to a health insurance company, were matched to cases for age and sex. Of the 222 controls participating, 208 (94%) agreed to have a blood sample taken (140 women, mean age 74.9 ± 8.7 years; 68 men, 71.7 ± 8.0) (table). Neither cases nor controls had clinical signs or symptoms of thyroid dysfunction.

We measured concentrations of free thyroxine, thyroid stimulating hormone, and antithyroid peroxidase antibodies by standard radioimmunoassays. Antithyroglobulin antibodies were measured as follows: sera were incubated at room temperature with thyroglobulin labelled with 125-iodine, and the immune complexes were precipitated in fetal veal buffer with polyethylene glycol. A positivity threshhold of 50 U/l for a population free of thyroid disease was determined.

We performed multiple logistic regression. Dependent variables were high and low concentrations of thyroid stimulating hormone, high and low concentrations of free thyroxine, and concentrations of positive or negative antiperoxidase antibodies, positive or negative antithyroglobulin antibodies, and positive or negative antithyroid antibodies (antiperoxidase or antithyroglobulin). Independent variables were case or control, geographical origin (north or south), age, sex, and clinical subgroup of patients.

When we took potential confounders into account, we found no difference between cases and controls. Antithyroid antibodies occurred more frequently in women than in men, and prevalence increased with age.

We found no difference between cases and controls when thyroxine or thyroid stimulating hormone titres were outside the normal range, or when antithyroglobulin or antiperoxidase antibody titres were positive (Wilcoxon sum rank test) (table on website).

Comment

The prevalence of high concentrations of thyroid stimulating hormone and antithyroid antibody was similar in cases and controls at the onset of the disease. After adjustment for potential confounders, we found a threefold but non-significant increase in the risk of hyperthyroidism in cases when thyroid stimulating hormone concentrations were measured. If the risk was to be significant a sample size of 641 patients and 2564 controls would be needed; such a sample size with incident cases of giant cell arteritis seems unrealistic. However, a common pathway for Graves’ disease or hypothyroidism and giant cell arteritis seems unlikely. Determination of free thyroxine concentrations is probably less reliable in inflammatory syndromes, as thyroxine is bound to sera proteins.

The high prevalence of antithyroid antibodies in the controls should make researchers cautious when describing an association between autoimmune or inflammatory diseases and thyroid dysfunction in elderly patients.

Table.

Thyroid status of cases of giant cell arteritis and controls. ^*Values are numbers (percentages) unless stated otherwise

Variable	Cases (n=285)	Controls (n=208)	P value	Odds ratio (95% CI)
Thyroid stimulating hormone†
Low concentration	13 (4.6)	5 (2.4)	0.171	3.06 (0.62 to 15.20)
High concentration	12 (4.2)	16 (7.7)	0.227	0.38 (0.11 to 1.82)
Thyroxine‡
High concentration	2 (0.7)	1 (0.5)	0.546	0.34 (0.01 to 89.62)
Low concentration	7 (2.46)	0	0.324	NA
Antibodies
Antiperoxidase	42 (14.7)	29 (14.0)	0.327	1.57 (0.63 to 3.89)
Antithyroglobulin	71 (24.9)	47 (22.6)	0.574	1.26 (0.59 to 2.66)
Positive antiperoxidase and antithyroglobulin	89 (31.2)	59 (28.4)	0.3145	1.42 (0.71 to 2.84)

^*Independent variables: case or control, sex, age, geographical origin (north or south), and clinical subgroup of patient (positive or negative biopsy for temporal arteritis or polymyalgia rheumatica). 

^†Normal range 0.2-4 mIU/l. ^‡Normal range 10-26 pmoles/l.