Adrenal scintigraphy with 75Se selenonorcholestenol: a review.

We have reviewed 58 patients on whom adrenal scintigraphy has been performed using 75Se selenonorcholestenol. For 15 patients whose adrenal function was biochemically normal, the upper limit of normal of the 7 day adrenal uptake test was 0.45%, considerably higher than the generally accepted value of 0.3%. There is evidence from this group of patients that stress and obesity might account for uptakes in the range 0.3-0.45%. The sensitivity of the uptake test is poor, with 7 out of 23 patients with Cushing's syndrome having uptakes within the normal range. Scintigraphy of such patients may still be useful in differentiating between unilateral and bilateral adrenal involvement.

The pathogenesis of Graves' disease.

The abnormally increased thyroid activity that is characteristic of Graves' disease is caused by immunoglobulins which specifically interact with the thyroid cell and stimulate it. Increases and decreases in thyroid activity in Graves' disease can be clearly related to rise and fall of these immunoglobulin-mediated activities. The level of immunoglobulin stimulatory activity can be used for prediction of the likelihood of neonatal Graves' disease and of recurrence of disease after cessation of treatment with antithyroid drugs. Investigation of patients with Graves' disease and their families has led to identification of particular human leukocyte antigens and genetically linked markers on immunoglobulins which both appear to incur increased susceptibility to certain autoimmune diseases. Differences in immune function, when compared with control populations, have been found in patients with these genetically linked markers. Protection against autoimmune disease is maintained by purposeful inhibition of any self-directed activity within each function of the immune system and by the controlling interaction of other immune functions. No single deficiency of immune function can be selected as giving the major risk of autoimmune disease, but rather a sum of relative defects resulting in an increased risk. In some patients with Graves' disease the self-protection mechanisms regain sufficient control of the immune functions to reduce the activity of the autoimmune disease, and the patient may achieve clinical remission. Often, however, there is evidence that abnormal immune activity directed against thyroid tissue has persisted with liability to recurrence of the Graves' disease.

Thyroid function and immunological activity during and after medical treatment of Graves' disease.

The variable clinical course of Graves' disease has been followed in 27 patients each studied for 2 years from the time of diagnosis. Thyroid hormone synthesis was blocked with large doses of antithyroid drugs for the first 12 months while euthyroidism was maintained with triiodothyronine. The latter was given alone from 12 to 18 months, and for the last 6 months the patients received no treatment. The activity of the disease was determined by repeated measurements of thyroid uptake of pertechnetate and by assay of thyrotrophin receptor antibodies (TSH binding inhibitory immunoglobulins). Retrospectively there were no features on presentation which singly or in combination indicated the clinical outcome: 16 patients remained in remission (Group 1) whilst in 11 hyperthyroidism had recurred before the end of the study (Group 2). Both measures of disease activity (thyroid uptake and antibody levels) fell during the first 12 months in patients of both groups. Recurrence of Graves' disease could be predicted in some but not all patients of Group 2 at 12 months by higher thyroid uptakes and levels of thyrotrophin receptor antibodies. There was, however, evidence of abnormal thyroid function, from which we infer continuing activity of the disease, 12 to 18 months after diagnosis in all patients of Group 1, even though these patients had normal TRH tests during the last phase of the study. The difference in the course of Graves' disease 12 to 24 months after diagnosis between those patients who remained in remission and those who did not was relative: in no patient was completely normal physiological control of thyroid function re-established. Clinical remission from hyperthyroidism at this time is a level of disease activity at which the normal physiological output of thyroid hormones is not exceeded.

Consistency and variability in the character of thyrotrophin receptor antibodies in Graves' disease.

At diagnosis there was no correlation between the uptake of pertechnetate by the thyroid and thyrotrophin receptor antibodies (TRAb) measured as TSH binding inhibitory immunoglobulins in a series of 27 patients with Graves' disease. TRAb were detectable initially in 19 patients, in 11 of these there was a significant positive correlation (P less than 0.05) between serial measurements of pertechnetate uptake and TRAb made during 2 years following diagnosis. In five patients pertechnetate uptake fell with time whilst TRAb levels were maintained or fluctuated. In the remaining three of the 19 patients both measurements were low and did not change during treatment. We conclude that TRAb in any individual patient are a mixture of immunoglobulins of variable effectiveness as thyroid stimulators. In a majority of patients the composition of this mixture remains constant during the course of the illness and the clinical state reflects the levels of TRAb in the blood. In a minority, however, the character of these antibodies may alter with time or there is a change in the responsiveness of the thyroid gland. The general lack of correlation between measurements of thyroid stimulating activity and TSH binding inhibitory immunoglobulins in groups of patients is due to differences between patients in the composition of TRAb.

Graves' disease: thyroid function and immunologic activity.

Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of [99mTc]pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.

A comparative study of the binding of Graves' immunoglobulins by the patients own and other thyroid membranes.

Thyroid membrane preparations from six patients with active Graves' disease were tested in an assay which detects the thyroid interactive immunoglobulins of Graves' disease by their inhibition of binding of [125I]-thyroid stimulating hormone (TSH). With all preparations inhibition of binding of 125I-TSH by excess TSH could be demonstrated (specific binding). The patients' own immunoglobulins were assayed against their own thyroid membranes and against each other's under exactly comparable conditions. Inhibition of binding by IgGs from the patients varied between membrane preparations: with one preparation 5/6 IgGs were inhibitory but with another none were effective. Of the six patients, their own IgG inhibited binding of 125I-TSH to their own thyroid membrane preparation in only four instances, and when interaction did occur this did not reliably predict that the membrane preparation would interact with IgGs from other patients with Graves' disease. The selection of a membrane preparation for this assay cannot be made solely on ability to specifically bind TSH but the measure of the specific interaction with a Graves' IgG of proven potency must also be considered. Moreover, because of the variability between different membrane preparations, sequential clinical studies on individual patients, of the changes in concentration of Graves' IgG, must be performed using the same selected thyroid membrane preparation. We infer from these observations that the membrane structure in the vicinity of the TSH binding site is an important determinant of the interaction of Graves' IgGs with the TSH receptor, and that the configuration of this area is variable between individuals of the same species. The distinction between 'human-specific' and 'non-species-specific' thyroid stimulating antibodies is therefore probably not valid. The observation that the patient's own IgG was not often the most potent IgG inhibitor of binding of TSH also suggests that the Graves' IgG binding site is not identical or restricted to the TSH binding site; alternative explanations are discussed.

Spontaneous pneumopericardium.

Spontaneous pneumopericardium is a relatively rare event, although cases have been recorded over the past 130 years. Many were associated with malignancy, trauma, infection or as a complication of recent surgery. Attempts at surgical resolution have been infrequent and survival extremely rare. We describe a patient in whom pneumopericardium developed spontaneously and insidiously, probably being present for some weeks before hospital investigation. Surgical exploration revealed the cause to be a benign gastric ulcer without an hiatus hernia or other diaphragmatic defect. Repair was attempted but the patient died in the early postoperative period. From an extensive review of the literature it is clear that spontaneous perforation of a gastric ulcer into the pericardium must be less rare than some authors have suggested.

Oesophageal dilatation in Parkinson's disease.

In an unselected group of 37 patients with Parkinsonism the mean diameter of the oesophagus at the level of the 9th dorsal vertebra was 3·11 cm, which was significantly higher than the mean of 2·24 cm in a group of control patients. Six of the patients with Parkinsonism had gross oesophageal dilatation.