W. M. Wiersinga

On assessing responsiveness of health-related quality of life instruments: Guidelines for instrument evaluation

A lack of clarity exists about the definition and adequate approach for evaluating responsiveness. An overview is presented of different categories of definitions and methods used for calculating responsiveness identified through a literature search. Twenty-five definitions and 31 measures were found. When applied to a general and a disease-specific quality of life questionnaire large variation in results was observed, partly explained by different goals of existing methods. Four major issues are considered to claim the usefulness of an evaluative health-related quality of life (HRQL) instrument. Their relation with responsiveness is discussed. The confusion about responsiveness arises mostly from a lack of distinction between cross-sectional and longitudinal validity and from a lack of distinction between responsiveness defined as the effect of treatment and responsiveness defined as the correlation of changes in the instrument with changes in other measures. All measures of what is currently called responsiveness can be looked at as measures of longitudinal validity or as measures of treatment effect. The latter ones tell us little about how well the instrument serves its purpose and are only of use in interpreting score changes. We therefore argue that the concept of responsiveness can be rejected as a separate measurement property of an evaluative instrument.

TSH-R expression and cytokine profile in orbital tissue of active vs. inactive Graves' ophthalmopathy patients

objective From in vitro studies using cultures of orbital fibroblasts, it has become clear that cytokines play an important role in the orbital inflammation in Graves’ ophthalmopathy (GO). Orbital fibroblasts seem to be the key target cells of the autoimmune attack, and they are able to express the TSH receptor (TSH‐R). In vivo data on the presence of cytokines in orbital tissues are sparse, and mostly limited to samples obtained from patients with endstage, inactive GO; the same holds true for the presence of the TSH‐R. The aim of the present study was to determine whether the cytokine profile and TSH‐R expression differ in the active vs. the inactive stage of GO.

Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of sporadic non-toxic goitre

The efficacy of treatment with TSH-suppressive doses of L-thyroxine (T4, 2.5 micrograms/kg body weight daily) either alone or combined with carbimazole (CBZ, 40 mg daily) was studied in 78 patients with sporadic non-toxic goitre in a prospective placebo-controlled double-blind randomised clinical trial. Treatment was given for 9 months, with 9 months of follow-up. A response to treatment as measured by ultrasonography was found in 58% of the T4 group, in 35% of the T4/CBZ group, and in 5% of the placebo group. The mean (SEM) decrease of thyroid volume at 9 months in the responders was 25% (2). After discontinuation of treatment, thyroid volume increased in the responders and had returned to base-line values after 9 months of follow-up. In the placebo group mean thyroid volume had increased by 6% (4) at 4 months, 20% (7) at 9 months, and 27% (8) at 18 months. The findings show that untreated sporadic non-toxic goitre continues to increase in size; T4 is effective in the treatment of the disorder; and the addition of CBZ has no therapeutic advantage.

Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves’ ophthalmopathy? A randomized controlled trial

Objective  Only a small percentage of Graves’ ophthalmopathy (GO) patients develop optic neuropathy with impending loss of visual acuity. Therapy with methylprednisolone pulses is the treatment of first choice in severe and active GO patients. When the effect is insufficient, patients are usually treated with surgical decompression. We investigated whether surgery could become the first‐line treatment, thus preventing treatment with steroids.

Temporal relationship between onset of Graves’ ophthalmopathy and onset of thyroidal Graves’ disease

The temporal relationship between the onset of Graves’ ophthalmopathy and the onset of thyroidal Graves’ disease was evaluated in 125 consecutive patients with Graves’ ophthalmopathy. Thyroidal Graves’ disease — past or present — was clinically evident in 99 patients (79%): hyperthyroidism in 96 and hypothyroidism in 3 cases. Thyroid disease preceded the eye disease in 37 patients, it occurred simultaneously with the eye disease in 39 patients, and it developed after the eye disease in 23 patients (in 16 cases within one yr after the onset of eye disease). The age at the onset of thyroid disease (38.7 ± 12.9 yr) was lower than the age at the onset of ophthalmopathy (41.8 ± 12.5 yr; p< 0.001). Among the 26 clinically euthyroid patients (21%) laboratory evidence of thyroidal Graves’ disease was found in 14 cases (11%): abnormal TRH test, n = 9; normal TRH test but abnormal T3-suppression test, n = 4; normal TRH and T3-suppression tests but positive thyroid stimulating antibodies, n = 1). We conclude that Graves’ ophthalmopathy as a rule develops at a time when thyroid autoimmunity also exists. This strongly suggests a common factor in the pathogenesis of thyroidal and ocular expressions of Graves’ disease.

Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures

Aim: To compare the outcome of various surgical approaches of orbital decompression in patients with Graves’ orbitopathy (GO) receiving surgery for disfiguring proptosis. Method: Data forms and questionnaires from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed. Results: Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches. The average proptosis reduction for all decompressions was 5.0 (SD 2.1) mm. After three-wall decompression the proptosis reduction was significantly greater than after two-wall decompression. Additional fat removal resulted in greater proptosis reduction. Complications were rare, the most frequent being worsening of motility, occurring more frequently after coronal decompression. The average change in quality of life (QOL) in the appearance arm of the GO-QOL questionnaire was 20.5 (SD 24.8) points. Conclusions: In Europe, a wide range of surgical approaches is used to reduce disfiguring proptosis in patients with GO. The extent of proptosis reduction depends on the number of walls removed and whether or not fat is removed. Serious complications are infrequent. Worsening of ocular motility is still a major complication, but was rare in this series after the swinging eyelid approach.

Effects of Graves’ ophthalmopathy on quality of life

General health-related quality of life is markedly impaired in patients with Graves’ ophthalmopathy (GO), and even worse than in patients with other chronic conditions like diabetes, emphysema or heart failure. A disease-specific quality-oflife questionnaire for GO has been developed, the so-called GO-QOL, consisting of two subscales: one for visual functioning (8 questions referring to limitations due to decreased visual acuity and/or diplopia) and one for appearance (8 questions referring to limitations in psychosocial functioning due to changes in appearance). The GO-QOL was found to be a valid and reliable instrument. A minimal clinically important difference (MCID) in the GO-QOL score was derived from data obtained before and after specific eye treatments. Based on the patient’s opinions, changes of ≥ 6 points (minor surgery) or ≥ 10 points (surgical decompression, immunosuppression) are recommended as MCID. It is concluded that the GO-QOL is an useful instrument for measuring changes over time in visual functioning and appearance of GO patients. The GO-QOL is available in six languages, and can be used as a separate outcome measure in clinical studies.

THE VALUE OF THYROID VOLUME MEASURED BY ULTRASONOGRAPHY IN THE DIAGNOSIS OF GOITRE

Thyroid volume was measured by ultrasonography in 80 euthyroid patients with sporadic nontoxic goitre and in 50 healthy adults, all residing in non‐iodine deficient areas. All patients were referred because of complaints of goitre and had been diagnosed as cases of goitre by inspection and palpation. The thyroid volume in 15 patients with goitre (19%) was within the normal reference range (4.9–19.1 ml). Fourteen of the 15 patients had thyroid nodules larger (mean diameter 2.9 ± 1.1 cm) than those detected in nine of the healthy adults (mean diameter 0.8 ± 0.6 cm; P < 0.001). Thyroid size as estimated by inspection and palpation (grade OA to III according to Stanbury et al, 1974) was poorly related to thyroid volume measured by ultrasonography. In conclusion: (1) a thyroid volume within the normal reference range does not rule out the presence of nodular goitre; and (2) application of thyroid volume measurement by ultrasonography may prevent overestimation of goitre prevalence in epidemiological surveys.

Cushing's syndrome complicated by multiple opportunistic infections.

The case history of a 56-year-old man is described who suffered from severe adrenocorticotrophic hormone (ACTH)-dependent Cushing’s syndrome. The clinical course was complicated by simultaneous infections with Pneumocystis carinii, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and Herpes simplex, which proved to be fatal. A study of the literature shows that opportunistic infections in endogenous Cushing’s syndrome are associated with severe cortisol excess and carry a high mortality. Opportunistic infections are most prevalent in the ectopic ACTH syndrome, explained by the very high plasma cortisol concentrations in this condition. Infections with Aspergillus species, Cryptoccus neoformans, Pneumocystis carinii and Nocardia asteroides predominated. Cushing’s syndrome with a very high plasma cortisol concentration causes a severe immunocompromized state. Prompt evaluation of the cause of the hypercortisolism, initiation of cortisol lowering therapy, primary prophylaxis for Pneumocystis carinii infection when plasma cortisol exceeds 2500 nmol L−1 and a search for concomitant infectious disease is recommended.

THE LONG‐TERM OUTCOME OF THYROIDECTOMY FOR SPORADIC NON‐TOXIC GOITRE

To study the long‐term outcome after thyroidectomy, 113 sporadic non‐toxic goitre patients who underwent thyroidectomy in our hospital in the period 1974–1983, were studied. Five patients complained of recurrent goitre; a goitre was found on inspection and palpation in these five and in 15 others. There were no differences between the 20 patients with goitre and the 93 patients without goitre with regard to sex, age, duration of goitre, indication and type of thyroidectomy, postoperative thyroid hormone medication, period of follow‐up, and T4, T3, or TSH plasma values at the time of follow‐up examination. Twenty‐three patients complained of voice changes since thyroidectomy. In a case control study, included in this follow‐up study, 19 patients with goitre, i.e. thyroid size I and II as estimated by inspection and palpation (cases), and 16 patients without goitre, i.e. thyroid size OA and OB (controls), were studied in more detail. No difference between cases and controls was found in any of the above mentioned parameters that could explain the recurrence of goitre. Thyroid volume (median) was greater in the cases (34–1 ml, range 7.9–83.4) than in the controls (10.3 ml, range 2.5–48.7) (P < 0.001), although a considerable overlap between the two groups was observed. One or more thyroid nodules were found in 89.5% of the cases and in 62–5% of the controls (NS). Serum thyroid growth stimulating immunoglobulin (TGI) was present both in cases (68%) and controls (50%). TGI was present in high titres in all five patients who complained about recurrent goitre. Thyroid volume was negatively related to the plasma level of TSH (r =−0.36, P < 0.05), and positively but not significant to serum TGI. In conclusion: (1) a goitre is found in 17.7% of sporadic non‐toxic patients at long‐term follow‐up after thyroidectomy, not related to age, sex, duration of goitre, indication or type of operation, postoperative thyroid hormone medication, period of follow‐up, or plasma T3, T4, or TSH; (2) TGI is more prevalent in patients who complain of recurrent goitre after thyroidectomy; (3) thyroidal nodular disease persists in the majority of patients after thyroidectomy.