The natural history of euthyroid multinodular goitre.

In this communication data on the natural history of euthyroid multinodular goitres are presented. From a total group of 140 patients (mean age 54.6 years, 14 men and 126 women; 88 with autonomous, 52 with non-autonomous function), follow-up data were available for 90 patients (mean age 54.0 years, 11 men and 79 women; 64 with autonomous, 26 with non-autonomous function). During follow-up (means: 5.0 years, maximum 12.2 years) transitions in function were seen 15 times; 8 autonomous patients became hyperthyroid after less than 1-7 years. There were 6 transitions from non-autonomy to autonomy and 1 from autonomy to non-autonomy. One patient who demonstrated the whole cycle from non-autonomy through autonomy up to hyperthyrodism is described in more detail. In one patient operated upon because of hyperparathyroidism a follicular carcinoma was found by chance. Mechanical problems were the reason for surgery in 6 patients only, 16 patients were operated upon because of cosmetic reasons (mostly in the early years of the study). Finally, results from 19 TRH tests in 16 autonomous patients suggest that TRH tests in patients with autonomously functioning euthyroid multinodular goitres are not yet redundant.

Changes in basal and stimulated TSH and other parameters of thyroid function in acromegaly after transsphenoidal surgery.

T1 and T3 levels, TSH response to TRH and somatomedin-C levels in 63 patients with acromegaly, were measured before transsphenoidal surgery and during a 4-year follow-up period. Criteria for cure were: mean GH level less than 5 mU/l, suppression of GH by oral glucose tolerance test below 2.5 mU/l and normalization of paradoxical GH reaction to TRH. Nine patients underwent radioiodine studies to assess the renal and thyroid clearance of iodide, plasma inorganic iodine level and absolute iodine uptake. Among the patients 40% had goitre, with a male preponderance. T1 and T3 levels were in the normal range both before and after surgery. A transient decrease in T3 levels was found in the immediate postoperative period. Before treatment a diminished or absent TSH response to TRH was exhibited by 64% of the goitre patients and 34% of the non-goitre groups (p less than 0.05). Despite normalization of GH and somatomedin-C levels and normal T4 and T3 levels no improvement of the TSH response was found during follow-up. No correlation between the incremental response of TSH to TRH and circulating T4 or T3 levels, basal TSH, GH or tumour size was found. There was, however, a negative correlation (r = -0.765, p less than 0.05) between the incremental TSH response to TRH and somatomedin-C levels for females with goitre. Somatomedin-C levels were higher in patients with goitre than in those without goitre (95 +/- 26 vs 75 +/- 30 nmol/l; mean +/- SD, p = 0.05). Radioiodine studies showed an increased renal clearance of iodide which was related to the increase in creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyrotropin (TSH) receptor modulation by specific TSH receptor antibodies in Graves' disease.

In Graves' disease (GD), an antireceptor autoantibody disease, individual variability in the pathogenic interaction between TSH receptors and autoantibodies has been reported. This variability can be due to allotypic (person to person) variability in the receptors or differences in autoantibody amount or specificity. This fundamental issue was investigated by evaluating immunoglobulin G (Ig)-induced TSH receptor modulation in thyroid tissue from 19 patients with GD. TSH receptor modulation by Graves' Ig was defined as the appearance of 1 class of high affinity binding sites, instead of the usual 2 classes of binding sites. Ig-induced modulation of receptors occurred in 9 of 19 (47%) experiments with autologous (patient's own) tissues and correlated with the presence of TSH receptor antibodies, measured as TSH binding inhibitor Igs. Of these 9 receptor-modulating Graves' Ig preparations, 7 (78%) also had a receptor-modulating effect in other patient's (homologous) thyroid tissue. Nine of the 10 Graves' Ig preparations that were negative for TSH receptor-modulating activity in autologous thyroid tissue were tested with other patients' thyroid tissues; 7 (78%) were negative, and all were TSH binding inhibitor Ig negative. We conclude that variability in the occurrence of TSH receptor modulation was associated with the presence or absence of TSH-binding inhibitor Ig. No evidence for allotypic differences in TSH receptors in GD was found.

Graves' disease: immunological and immunogenetic indicators of relapse.

The use of measurements of antibody to the thyroid stimulating hormone receptor and HLA-DR3 phenotype for predicting relapse of hyperthyroidism in patients with Graves' disease receiving medical treatment is controversial. Fifty eight new patients with Graves' disease were followed up prospectively for up to 96 months after treatment with antithyroid drugs for 12 months. The presence of antibody to the thyroid stimulating hormone receptor before the start of treatment, measured as immunoglobulins inhibiting binding of thyroid stimulating hormone, was not associated with relapse. Patients who remained positive for antibodies after treatment tended to relapse within six months, but no relation with long term relapse was found. HLA-Cw7 but not HLA-DR3 was significantly associated with relapse. The presence of HLA-DR4 was significantly associated with remission and with absence of antibodies to thyroid stimulating hormone receptor. HLA-DR4 may therefore protect against relapse of thyrotoxicosis by immunomodulation triggered by antithyroid drugs, which results in the synthesis of antibodies to the thyroid stimulating hormone receptor being inhibited.

Radioiodine in the treatment of hereditary medullary carcinoma of the thyroid.

The effect of 131I therapy as an adjunct to surgery in the management of patients with hereditary medullary carcinoma of the thyroid (MCT) was studied in 20 patients from 3 kindreds. Plasma calcitonin levels were measured before and after a dose of 131I sufficient to ablate postoperative thyroid remnants. In patients with residual biochemical MCT no significant reduction of the calcitonin levels was found after administration of radioiodine. In patients with normal postoperative calcitonin levels no (biochemical) recurrence developed 3 months to 2 yr subsequent to radioiodine therapy. It is concluded that 131I therapy as an adjunct to surgery is not indicated in the management of patients with residual hereditary MCT, although 131I may be of value in the prevention of tumor recurrence in patients with normal postoperative calcitonin values.

Iodine kinetics in patients with euthyroid multinodular goitre compared with normal subjects.

In order to investigate whether patients with euthyroid multinodular goitre (EMG) lose more iodine through urinary excretion than is to be expected due to an elevated renal clearance of iodine and/or whether the iodine is handled differently in the thyroid of these patients than in that of normal subjects, the following data were obtained for 33 patients with EMG and 30 normal subjects: thyroid clearance (TC), absolute iodine uptake (AIU), renal 123I clearance (RC) and plasma inorganic iodine (PII). A significantly lower PII and a higher TC was found in the goitre patients. In the control group PII appeared to be higher and TC and RC lower in the older age group (greater than 50 years). The difference in PII and TC is most easily explained by a higher iodine uptake in the subgroup of normal subjects over 50 years of age. AIU did not differ in any of the groups. Thus, it may be concluded that an endogenous iodine deficiency due to elevated renal clearance of 123I is not a factor in sporadic goitre, at least in our patients. At the observed plasma iodine levels a significantly higher AIU was not found for goitrous patients.

Circulating immune complexes and thyroid-stimulating immunoglobulins before, during, and after antithyroid drug therapy in patients with Graves' disease.

Sera from patients with Graves' disease were assayed for thyroid-stimulating immunoglobulins (TSI) and circulating immune complexes (CIC) before, during, and after antithyroid drug treatment. 41 (72%) of 57 untreated patients had a positive TSI index and 17 (30%) had CIC. In untreated patients CIC were significantly more common in patients with a negative TSI index than in those with a positive one. It is suggested that because CIC prevent TSI from being detected the TSI index may be negative in Graves' disease. Early in the course of the treatment CIC developed in 85% of the patients; in all of these patients TSI disappeared. Later in the course of treatment when CIC could no longer be detected TSI did not reappear. These findings indicate that the development CIC could be the manifestation of the re-establishment of a natural tolerance to thyroid-stimulating hormone receptors in patients with Graves' disease.

Thyroid-stimulating immunoglobulins do not cause non-autonomous, autonomous, or toxic multinodular goitres.

Thyroid-stimulating immunoglobulins (TSIs) were measured by radioreceptor assay in serum from 51 patients with a multinodular goitre, divided into four groups according to thyroid function, and in 30 normal people. In 9 patients who were euthyroid and had non-autonomous thyroid function and in 6 patients who were hyperthyroid, TSI index was normal . Of 21 euthyroid patients with autonomous function only 2 had a slightly abnormal TSI index (66 in both, normal greater than or equal to 68). Another series of 15 clinically euthyroid patients also had a normal TSI index. These results suggest that TSIs do not contribute to the pathogenesis of multinodular goitre, as has been suggested by others.