TSH-R antibody levels correlate directly with clinical features of Graves' ophthalmopathy. The results support the hypothesis of a pathogenetic role of TSH-R antibodies and the TSH-R in the orbit of Graves' ophthalmopathy patients.

Increased serum cytokine levels have been reported in patients with autoimmune thyroid disease, but less is known about their levels in patients with Graves' ophthalmopathy (GO). It is not known whether GO is a cell‐mediated or humoral autoimmune disease. We investigated whether serum cytokines are elevated in GO patients and whether the cytokines were Th1‐ or Th2‐derived. In addition, elevated cytokines might reflect the activity of GO, and thus we investigated whether cytokine levels could predict the clinical response to orbital radiotherapy. We studied 62 consecutive patients with moderately severe untreated GO and 62 healthy controls, matched for sex, age and smoking habits. Serum concentrations of IL‐1RA, sIL‐2R, IL‐6, sIL‐6R, tumour necrosis factor‐alpha (TNF‐α) RI and II and sCD30 were measured using highly sensitive ELISAs, in the patients before and 3 and 6 months after radiotherapy. All patients were euthyroid, with anti‐thyroid drugs, before and during the entire study period. All baseline cytokine and cytokine receptor levels were significantly elevated in GO patients compared with healthy controls, except for IL‐1RA. The levels did not correlate with parameters of the thyroid disease, nor with the duration, activity or severity of GO. However, backward logistic regression analysis showed that IL‐6, sCD30 and TNFαRI were able to predict a beneficial response to orbital radiotherapy. We therefore conclude that both Th1‐ and Th2‐derived cytokines are elevated in GO patients compared with its controls. IL‐6, sCD30 and TNFαRI had some value for predicting therapeutic outcome to orbital irradiation, and may thus reflect active eye disease.

We measured sweat production to direct gland stimulation with intradermal methacholine in patients with autonomic failure and in normal subjects. The sympathetic skin response (SSR) to electrical stimulation was assessed in some of the same subjects. Patients with pure autonomic failure (PAF) and multiple system atrophy (MSA) produced significantly less sweat than controls. None of the patients manifested greater than normal sweat production. Impaired sweat gland function does not differentiate MSA and PAF. The SSR did not correlate with sweat response to methacholine. An SSR can occur in the absence of normal sweat gland function. The diminished production of sweat in response to intradermal methacholine in PAF suggests that human sweat glands do not develop chronic denervation supersensitivity. Intradermal methacholine is a simple method to assess sweat gland function.

SUMMARY Adhesion molecules play a key role in autoimmune disorders, and serum concentrations of soluble adhesion molecules are increased in Graves’ ophthalmopathy (GO). Whether this is due to the strong association with smoking is unknown. It is also not known if the severity or activity of GO determine the serum levels of adhesion molecules. We measured serum concentrations of sICAM‐1, sVCAM‐1 and sELAM‐1 in 62 euthyroid Graves’ patients with untreated GO, in 62 healthy controls matched for sex, age and smoking habits, and in 26 euthyroid Graves’ patients without GO. GO severity was assessed by the Total Eye Score and the activity by the Clinical Activity Score. Adhesion molecules were measured by highly sensitive ELISAs. GO patients had higher levels than controls (median values in ng/ml with range): sICAM‐1 300 [171–575] versus 244 [119–674], P < 0·001; sVCAM‐1 457 [317–1060] versus 410 [238–562], P < 0·001; and sELAM‐1 61 [19–174] versus 53 [23–118], P = 0·021. Euthyroid Graves’ disease patients without GO had levels similar to controls: sICAM‐1 273 138–453), sVCAM‐1 386 [260–1041] and sELAM‐1 46 [22–118]. Smoking had an independent effect and was associated with higher levels of sICAM‐1 and lower levels of sVCAM‐1 in both GO patients and controls; sELAM‐1 levels were comparable. In the 62 GO patients, sICAM‐1 correlated significantly with severity of eye disease (r = 0·40, P = 0·002). No correlation was found with the duration of GO, the Clinical Activity Score or TBII levels. Multivariate analysis of all 150 subjects showed that the presence of GO and smoking are independent determinants of sICAM‐1 and sVCAM‐1 concentrations. In GO patients, the Total Eye Score was a stronger determinant than smoking. It is concluded that (i) smoking is associated with increased sICAM‐1 and decreased sVCAM‐1 levels; (ii) independent from smoking, euthyroid GO patients have higher levels of sICAM‐1, sVCAM‐1 and sELAM‐1 than patients with euthyroid Graves’ disease or healthy controls; (iii) the major determinant of sICAM‐1 in GO patients is the severity of their eye disease.