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.     

THYROID STIMULATING ANTIBODIES (TSAb) IN PATIENTS WITH GRAVES' DISEASE UNDERGOING ANTITHYROID DRUG TREATMENT: INDICATORS OF ACTIVITY OF DISEASE

Thyroid-stimulating antibodies (TSAb) were studied in patients with Graves' disease using a method based on cAMP production in isolated human thyroid membranes. Stimulation was detected in forty-one (82%) of fifty patients with untreated Graves' disease. In these subjects, the TSAb levels were correlated with the thyroid hormone levels. Among twenty patients treated for 1–2 months with carbimazole, 16 (80%) had positive TSAb. During prolonged treatment TSAb gradually diminished and finally normalized. In fifteen patients, it was possible to compare TSAb levels after cessation of previous medical therapy with TSAb levels at relapse. In nine of these patients, an increase of the TSAb level within the normal range at the time of relapse was found, in four the litres were positive. The results indicate that positive TSAb litres are markers of active Graves' disease and suggest that in such patients antithyroid therapy should be continued. A normal TSAb titre after anti-thyroid therapy does not exclude the possibility of relapse.     

THE PREDICTION OF RELAPSE AFTER DRUG TREATMENT OF GRAVES' DISEASE BY ASSAY OF LONG ACTING THYROID STIMULATOR-PROTECTOR (LATS-P)

In a study of fifty-two patients with Graves' disease followed for 1 year after stopping antithyroid drugs, a strong relationship has been found between serum LATS-P and relapse. In those with serum LATS-P activity on stopping therapy, twenty-one (88%) out of twenty-four relapsed. In those with no LATS-P activity on stopping antithyroid drugs only eight (29%) out of twenty-eight relapsed and in five LATS-P was detectable at relapse. The overall prevalence of positive assays for LATS-P at relapse (90%) was similar to that seen in untreated Graves' disease.     

REDUCTION OF PLASMA TRIIODOTHYRONINE (T3) INDUCED BY PROPRANOLOL

The effect of propranolol on plasma triiodothyronine (T3), thyroxine (T4) and triiodothyronine uptake by Sephadex G-25 (RT3U%) was studied in fourteen thyrotoxic patients and eight normal volunteers. 40 mg of propranolol as a single oral dose caused significant reduction in total serum T3 which began 60 min after administration. No significant changes were observed in T4 and RT3U% values. Plasma T3 levels remained suppressed during a 5 day course of treatment with propranolol. These results suggest that propranolol has a direct effect on peripheral metabolism of T3 rather than on thyroid hormone secretion.     

A LONG-TERM FOLLOW UP OF PATIENTS WITH AUTOIMMUNE THYROID DISEASE

A survey in a general practice in the North-East of England in 1963 detected thyroglobulin antibodies in 16.2% of women and 4.3% of men. High titres of antibodies were found in 4.6% of women and 1.6% of men. Forty-six subjects with thyroglobulin antibodies (from an original total of fifty-two) were studied in 1972 and forty of these were studied further in 1975. These subjects were compared with a group of age- and sex-matched controls from the original survey. Three of the subjects had developed overt hypothyroidism by 1975 and a raised serum thyroid-stimulating hormone (TSH) concentration was found more frequently in euthyroid subjects previously found to be antibody positive. There was a striking difference in the antibody studies in that only 26% of the previously antibody positive subjects had thyroglobulin antibodies in 1972 and 30% in 1975. A raised serum TSH concentration was found to correlate with cytoplasmic antibodies and particularly with the combination of cytoplasmic and thyroglobulin antibodies.     

EFFECTS OF LONG-TERM TREATMENT WITH METERGOLINE IN PATIENTS WITH IDIOPATHIC OLIGOSPERMIA

The effect of metergoline, an ergoline derivative with antiserotonin as well as dopaminergic properties, was studied in forty-five male patients with idiopathic oligospermia. Metergoline treatment (6 mg daily for 5 months) had no demonstrable effect on spermatogenesis; moreover, it did not influence the serum levels of LH, FSH, testosterone and oestradiol although it significantly reduced prolactin levels. It is concluded that, in all likelihood, serotonin plays little or no part in the pathogenesis of idiopathic oligospermia and that pharmacological reduction of normal prolactin levels has no therapeutic effect on this disease.     

CLINICAL AND ENDOSCOPIC HEALING AFTER INFLIXIMAB TREATMENT IN PATIENTS WITH CROHN's DISEASE

Background: Intestinal mucosal lesions in Crohn's disease were endoscopically evaluated before and after giving infliximab, and the usefulness of this treatment was investigated. Patients and methods: The present study included 12 patients with active Crohn's disease who could undergo colonoscopy before and after giving infliximab. (i) The treatment assessment consisted of evaluations of short‐term and long‐term therapeutic effects. The clinical evaluation was conducted using the Crohn's disease activity index (CDAI). The results of the clinical evaluation were compared with those of the colonoscopic evaluation. (ii) The endoscopic evaluation findings were divided into polyposis, ulcer and stenosis, and the area ranging from the rectum to the terminal ileum. The scores for the findings at seven sites were totaled. In the short‐term therapeutic effect, characteristics of ulcer morphology and background factors were investigated endoscopically. Results: (i) The efficacy rate was 92% clinically and 67% endoscopically in the evaluation of short‐term therapeutic effects. The efficacy rate was 86% clinically and 86% endoscopically in the evaluation of long‐term therapeutic effects. (ii) On the endoscopic evaluation, the ulcer score was significantly (P = 0.03) improved after giving infliximab, while there was no remarkable change in the polyposis score and the stenosis score tended to worsen. On the evaluation of therapeutic effects based on ulcer morphology, infliximab was endoscopically effective in patients with longitudinal ulcers. On the evaluation of therapeutic effects based on background factors, the treatment was effective in patients given a combination of infliximab and immunosuppressants. Conclusion: The ulcerative lesions were found to be markedly improved, but the intestinal stenosis tended to worsen, after giving infliximab. It is necessary that the severity of intestinal stenosis be adequately understood before giving infliximab. Giving immunosuppressants should be used for combined treatment.     

TREATMENT OF REFRACTORY ASCITES IN PATIENTS WITH LIVER DISEASE

"When the liver is full of fluid and this overflows into the peritoneal cavity so that the belly becomes full of fluid, death occurs" - Hippocrates.     

THE VARIATION IN SERUM TRIIODOTHYRONINE (T3) ACHIEVED DURING SUPPRESSION TESTING IN THYROTOXICOSIS

Regular measurement of thyroidal radioiodine uptake has been widely used as a means of monitoring continued extrapituitary stimulation of the thyroid during the treatment of thyrotoxicosis with carbimazole and triiodothyronine (T3). However, it is unclear to what extent the serum T3 level may vary at the time of testing, nor what effect this might have on the uptake of radioiodine. Two studies have been undertaken. In the first, serum T3 levels in twenty-four thyrotoxic patients were measured at intervals during an 18-month course of carbimazole combined with T3, 20 μg qid. Considerable variations in the highest and lowest levels of serum T3 were found both between and within individuals. The second study was on twenty-three thyrotoxic patients thought to be entering remission because the iodine uptake after 5 months of drug treatment had fallen to less than 50% of the pretreatment value (suppressors). The changes in uptake of radioiodine after 5 and then 6 months of treatment were compared in seven patients, who received carbimazole and T3 throughout, with the corresponding changes in the remaining sixteen patients, whose T3 alone was withdrawn prior to the uptake test at month 6. The mean degree of suppression remained unchanged by month 6 in the first group. In the second group, however, the mean uptake rose significantly, and nine of the sixteen patients would have been classified as non-suppressors at the sixth month (i.e. uptake greater than 50% the pretreatment value) had their failure to maintain high serum levels of T3 gone undetected. The first study indicated this could well happen in routine circumstances, and it is suggested that the reliability of suppression tests be checked with simultaneous measurement of serum T3.     

T3 KINETICS IN EUTHYROID GRAVES'' DISEASE PATIENTS WHO EXHIBIT HYPER-RESPONSIVENESS TO TRH AFTER RADIOIODINE TREATMENT

A major reduction in T3 turnover has been demonstrated previously in clinically hypothyroid patients. We have used non-compartmental (NC) and monocompartmental (MC) analysis to study ten patients with Graves' disease who, following treatment with radioactive iodine (RAI), are now clinically euthyroid but who showed hyper-responsiveness to TRH although serum T3 and T4 concentrations are within the normal range. T3 production rate (PR), metabolic clearance rate (MRC) and fractional-turnover (K) were all significantly reduced in patients compared with seven controls (P less than 0.01). T3, MCR and PR were consistently higher, and T3 K lower, when calculated by MC, than values calculated by NC analysis. The difference in T3 production rates between patients (mean 16.6 nmol/day) and controls (mean 38.9 nmol/day) raises the question of replacement therapy in patients who are apparently euthyroid but TRH hyper-responsive.     

INFLUENCE OF TREATMENT WITH RADIOIODINE AND PROPYLTHIORACIL ON THYROID STIMULATING IMMUNOGLOBULINS IN GRAVES' DISEASE

Thyroid stimulating immunoglobulins (TSAb) were measured in fifty-four patients with Graves' disease before treatment with either radioiodine (seventeen patients) or propylthiouracil (PTU) (thirty-seven patients), and followed during treatment. After radioiodine TSAb increased to levels exceeding pre-treatment values, and became detectable in three of six originally TSAb negative patients.
In most patients TSAb decreased during treatment with PTU, and became undetectable after a mean of 12 months in patients above 40 years, and after a mean of 6 months in patients below 40 years. In order to eliminate the presumed causative agent in Graves' disease, antithyroid treatment should be at least 18 months in patients above 40 years, and at least 12 months in patients below 40 years of age. In twenty-nine patients TSAb were measured at cessation of 2 years antithyroid drug therapy. Ten patients were TSAb positive and all except one relapsed. Five of nineteen TSAb negative patients relapsed. Although TSAb positivity predict relapse, it is not an ideal index of prognosis after antithyroid therapy.     

LACK OF SUPPRESSION OF INSULIN SECRETION BY EXERCISE IN PATIENTS WITH INSULINOMA

Serum glucose, insulin and glucagon concentrations were measured in three patients with insulin-producing tumours of the pancreas while performing an exercise test. In contrast to the normal adrenergic inhibition of insulin release in response to exercise, plasma insulin concentration remained at a constant and high level during exercise in patients with insulinomas. Their plasma glucose concentrations fell during exercise and in the post-exercise period. No significant changes occurred in plasma glucagon concentration. An exercise test may be a useful new diagnostic tool in organic hyperinsulinism.     

ANTITHYROID DRUGS IN THE TREATMENT OF HYPERTHYROIDISM OF Graves'' DISEASE: LONG-TERM FOLLOW-UP OF 434 PATIENTS

A study of antithyroid drug (ATD) therapy with a mean follow-up period of 10 years (range 2-25) in 434 patients with Graves' disease has been made by linking hospital records with those of a central follow-up register. The majority (89%) were treated with carbimazole and 87% received combined therapy with triiodothyronine (T3) (73%) or thyroxine (T4) (14%). Sixty-one per cent were assessed for T3 suppression tests on completion of treatment, of whom 61% (95% CL, 55-67%) suppressed. The overall 5-year cumulative proportion developing recurrent hyperthyroidism was 54-62% with rates of 26-44% in suppressed patients and 65-79% in those not suppressed. In unsuppressed patients, most (72%) of the recurrences occurred within 1 year with only an additional 10% predicted up to 10 years. In suppressed patients 30% of recurrences occurred in the first year, 60% between 1 and 5 years and a further 10% between 5 and 10 years. Suppression with T3 is probably the best and cheapest predictor of outcome but has an accuracy of only 70% for both positive and negative tests which limits its usefulness in planning long-term follow-up and surveillance. A standard format should be adopted for the analysis and reporting of follow-up studies, based on actuarial methods of estimating the cumulative proportion with recurrences or other events, to facilitate comparisons between different centres.     

RESPONSE OF PITUITARY-ADRENAL AXIS TO CORTICOTROPHIN RELEASING HORMONE IN PATIENTS WITH CUSHING'S DISEASE BEFORE AND AFTER KETOCONAZOLE TREATMENT

Ketoconazole is an antimycotic agent and a potent inhibitor of gonadal and adrenal steroidogenesis. It has been used successfully as a palliative treatment of Cushing's syndrome due to its ability to lower Cortisol production. However, the effects of ketoconazole on ACTH and aldosterone secretion have not yet been clarified. We evaluated the effect of ovine corticotrophin releasing hormone (oCRH) (100 μg bolus) on plasma ACTH, Cortisol and aldosterone levels in six patients with Cushing's disease before and after 4 to 6 weeks of treatment with ketoconazole 600 mg/d. Before treatment, plasma Cortisol levels were high and significantly increased after oCRH stimulation in all cases, while various patterns of aldosterone secretion were observed. Patients with higher levels showed a greater response to oCRH, while two patients with very low aldosterone showed no response. ACTH showed a marked rise after oCRH administration in all patients with a maximum peak at 30-45 min. After ketoconazole treatment, both plasma Cortisol and aldosterone were lowered and their response to oCRH was impaired. Basal ACTH levels were increased in four patients and ACTH response to oCRH was enhanced in all, compared to pretreatment. These findings confirm the inhibitory action of ketoconazole on basal and stimulated Cortisol secretion. A similar inhibition affected aldosterone production, indicating that ketoconazole also interferes with the mineralocorti-coid pathway. The enhanced response of ACTH to oCRH after the administration of ketoconazole argues against an inhibitory effect of this agent at the pituitary level and might best be explained by reduced negative Cortisol feedback.     

皮肤科门诊足病调查

目的了解皮肤科门诊患者足病发病情况。方法采用统一调查表格,以问卷形式随机连续调查我科门诊患者500例,分析足病发病情况。结果发现301例足病患者,占60.2%。其中男性足病患者177例(35.4%),女性患者中发现足病124例(24.8%)。随着年龄增加,足病患者明显增加,在>70岁组足病患病率高达77.08%。结论足病在皮肤科门诊患者中有很高的比例,尤其是老年患者,应引起皮肤科医师及社会高度关注。