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Biomedical subjects

A D Toft

Publications and source records attributed to A D Toft.

18 recordsLinked to original sources

Inter-relationships between selenium and thyroid hormone metabolism in the rat and man.

Labelling of rat kidney microsomes in vitro with [125I]-bromoacetyl T4 produced two bands on SDS/PAGE with Mr of 55 kDa and 27.5 kDa representing protein disulphide isomerase and type I iodothyronine deiodinase (ID-I) respectively. The amount of the 55 kDa band was unchanged by selenium (Se) deficiency but the 27.5 kDa protein was markedly decreased in kidney microsomal fraction obtained from Se-deficient rats. Concurrent Se and iodine deficiency produced a significant increase in thyroid weight, plasma thyrotrophin (TSH) and a decrease in thyroidal iodine when compared with either single Se or iodine deficiency. These results suggest that ID-I is a selenoprotein and that Se deficiency can exacerbate the hypothyroidism observed in iodine deficiency. In man, blood glutathione peroxidase and blood Se levels were decreased in hyperthyroidism due to Graves' disease whilst normal levels of these analytes were found in patients treated for Graves' disease. These results suggest that thyroid status can affect Se balance rather than Se deficiency predisposes to Graves' disease.

Animals

Occult thyrotoxicosis: a correctable cause of "idiopathic" atrial fibrillation.

Serum total thyroxine, triiodothyronine and thyrotropin response to thyrotropin-releasing hormone were measured in 75 consecutive patients presenting to a cardiology clinic with atrial fibrillation with no obvious cardiovascular cause. A lack of response of serum thyrotropin to thyrotropin-releasing hormone, indicative of thyrotoxicosis, was found in 10 patients (13 percent), not all whom had raised serum thyroid hormone levels. These 10 patients were predominantly male, had no clinical signs of thyrotoxicosis and a relative excess of nonpalpable autonomous thyroid nodules demonstrated with scintigraphy. Eight of the 10 patients had reversion to stable sinus rhythm after treatment with iodine-131 or carbimazole, either spontaneously or after direct current cardioversion. It would appear that clinically occult thyrotoxicosis can be identified consistently only with the thyrotropin-releasing hormone test and is the cause of "idiopathic" atrial fibrillation in a significant proportion of patients.

Aged

Failure of the TRH test to predict the clinical course of patients in remission after antithyroid drug therapy for Graves' disease.

In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean +/- SE intervals since the withdrawal of drug therapy were 23.2 +/- 1.6 and 20.4 +/- 0.7 months, respectively, at the outset of the study. Five patients (45%) from group I and 7 patients (30%) from group II relapsed during the period of observation. In addition, a change from a subnormal TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.

Adult

How often should patients be reviewed after treatment with iodine-131 for thyrotoxicosis?

Six to 18 years after treatment with iodine-131 for thyrotoxicosis 69 euthyroid patients with raised serum thyrotrophin (TSH) concentrations (mean 25.0 +/- SE 2.0 mU/l) and 61 with normal concentrations (mean 4.0 +/- 0.2 mU/l) were included in a prospective five-year follow-up study beginning in 1972. During this period 13 patients from the original group with raised serum TSH concentrations became hypothyroid. In contrast it was five years before hypothyroidism developed in a single patient from the group with normal serum TSH concentrations in 1972, although raised concentrations were recorded in 19 of these patients during the study.

Aged

Thyroid function after surgical treatment of thyrotoxicosis. A report of 100 cases treated with propranolol before operation.

We assessed thyroid function for 12 months after subtotal thyroidectomy in 100 tyrotoxic patients treated with propranolol alone before and immediately after operation. The operation proved safe, with low morbidity. Suppression of the hypothalamic-pituitary-thyroid axis, present in the majority one month after operation, was evidenced by normal or low levels of serum total tri-iodothyronine and thyroxine, but absent or subnormal serum thyrotropin response to thyrotropin-releasing hormone. Eighty patients were euthyroid at 12 months. Three patterns of thyroid function were observed in this group between the first and 12th months: normal serum total tri-iodothyronine, thyroxine and thyrotropin levels at all stages (20 patients); normal serum total tri-iodothyronine and thyroxine, but raised thyrotropin levels on one or more occasions (40 patients); and temporary hypothyroidism (20 patients). Of the remaining 20 patients, permanent hypothyroidism developed in 14, and six relapsed. Postoperative thyroid function was related to the estimated weight of the thyroid remnant.

Adult

Familial studies of type-I and type-II idiopathic diabetes mellitus.

A study of 296 diabetics demonstrated an association between the type of diabetes in the propositi and their first-degree relatives (aged 40 to 89 yr), the type of diabetes being defined as insulin-dependent (type I) or insulin-independent (type II). This association was significant at the 1% level and was still maintained when only the propositi in whom the diabetes was diagnosed at the age of 30 years or later were considered. The findings also suggest that there is a greater genetic independence between these two types than was previously supposed and that the disease should be subdivided into type according to the treatment needed rather than by the age of onset.

Administration, Oral

Spectrum of thyroid function in patient's remaining in remission after antithyroid drug therapy for thyrotoxicosis.

Thyroid function was assessed in 110 patients who were in remission for a period of 7-6 +/- 0-6 years (mean +/- S.E.) (range 0-25--25 years) after the withdrawal of antithyroid drug therapy for thyrotoxicosis. On the basis of clinical examination and on the results of thyroid-function tests, the following group of patients were identified: (I) euthyroid with normal plasma-total thyroxine (T4) and triiodothyronine (T3) concentrations, but an absent or subnormal response of plasma-thyrotrophin (T.S.H.) to thyrotrophin-releasing hormone (T.R.H.) (16%); (II) euthyroid with normal concentrations of plasma total T4 and T3 and a normal plasma-T.S.H. response to T.R.H. (59%); (III) euthyroid with normal concentrations of circulating thyroid hormones and a normal basal plasma-T.S.H., but an exaggerated plasma-T.S.H. response to T.R.H. (13%); (IV) euthyroid with normal plasma total T4 and T3 concentrations, but a raised basal plasma-T.S.H. concentration and an exaggerated plasma-T.S.H. response to T.R.H. (6%); (V) hypothyroid (6%). Although the need for short-term follow-up to identify those patients treated with antithyroid drugs who will relapse is well recognised, 16% of all patients in remission for longer than 4 years (10-8 +/- 0-7 years) in the present study showed some degree of thyroid failure. Evidence of hypothyroidism was associated with an increased frequency of thyroid microsomal antibodies. If the morbidity of the late development of hypothyroidism is to be avoided, patients who have been treated with antithyroid drugs should have long-term follow-up, as do patients treated surgically or with radioiodine.

Antithyroid Agents

Temporary hypothyroidism after surgical treatment of thyrotoxicosis.

Mild clinical hypothyroidism associated with low levels of serum total thyroxine (T4) and tri-iodothyronine (T3) and raised levels of serum thyroid-stimulating hormone (T.S.H.) has been observed in 14 of 40 patients (35%) in the early months after a subtotal thyroidectomy for thyrotoxicosis under cover of propranolol. In 10 of the patients, however, the hypothyroidism was temporary and at 6 months after operation the thyroid hormone levels were normal and the serum T.S.H. levels had fallen. In 4 of the patients in whom clinical and biochemical evidence of hypothyroidism persisted 6 months postoperatively, long-term T4 replacement therapy was instituted. It is concluded that the diagnosis of permanent hypothyroidism should not be made with confidence before 6 months have elapsed after operation and that the incidence of hypothyroidism following the surgical treatment of thyrotoxicosis may have been overestimated in the past.

Adult

Simple solid-phase radioimmunoassays for total tri-iodothyronine and thyroxine in serum, and their clinical evaluation.

1. Simple solid-phase radioimmunoassay methods for total tri-iodothyronine and thyroxine in serum or plasma are described. By using antibodies that are covalently coupled to microcrystalline cellulose, virtually identical assay procedures can be used for the determination of both hormones. An alkaline sodium glycinate buffer provides better assay conditions than the buffers often recommended for thyroid hormone radioimmunoassay. 2. Assay results are unaffected by moderate sample haemolysis. Plasma samples stored at room temperature for more than nine days often show an apparent increase in concentration of both thyroid hormones. 3. Serum tri-iodothyronine and thyroxine concentrations in healthy euthyroid subjects, and in euthyroid pregnant women are reported. In a series of 100 consecutive patients referred to a thyroid clinic the tri-iodothyronine assay discriminated better than the thyroxine assay between hyperthyroid and euthyroid patients. The thyroxine assay was much better than the tri-iodothyronine assay in discriminating between hypothyroid and euthyroid patients.

Anilino Naphthalenesulfonates

Assessment by continuous cardiac monitoring of minimum duration of preoperative propranolol treatment in thyrotoxic patients.

The effect of the beta-blocker, propranolol (40 mg 6-hourly orally) has been studied on the tachycardia of six patients with untreated thyrotoxicosis. Heart rate was monitored continuously using a light portable ECG recorder which allowed the patients to undertake normal activities during the recording periods. The most marked reduction in heart rate was evident at 24 h after starting propranolol treatment. In three of the patients there was only a minor further fall in heart rate despite continued propranolol administration, but in the remaining patients the reduction in heart rate with each successive day of treatment was more marked. These results suggest that if propranolol were to be used alone in the preparation of patients before partial thyroidectomy for thyrotoxicosis, a dose of 40 mg 6-hourly for 3-4 days might be sufficient.

Adult

A comparison of plasma TSH levels in patients with diffuse and nodular non-toxic goiter.

Plasma TSH levels were measured in 115 euthyroid patients with simple goiter, of whom 52 had diffuse and 63 nodular enlargement of the thyroid gland, and in 191 euthyroid patients without goiter. There was no significant difference between the plasma TSH levels in the patients with diffuse goiter and the non-goitrous controls, implying that the maintenance of diffuse hyperplasia is not dependent upon a raised level of plasma TSH. On the other hand, plasma TSH levels in the patients with nodular goiter were significantly lower than those recorded in either the patients with diffuse goiter (P less than 0.01) or in the patients without goiter (P less than 0.0001), supporting the view that thyroid function may be autonomous in nodular goiters.

Adenoma

Propranolol in the treatment of thyrotoxicosis by subtotal thyroidectomy.

Subtotal thyroidectomy was performed in 40 patients with thyrotoxicosis in whom propranolol alone was used as preparation for surgery. Propranolol was given orally in a dose of 40 mg every 6 h for a mean preoperative period of 17 days (range 4-60 days) and continued for seven days after operation. The mean +/- SE blood loss at operation was only 160 +/- 20 ml. The period of follow-up was from three to nine months. Recurrent thyrotoxicosis has not occurred in any patient. Low levels of total serum triiodothyronine (T3) and total serum thyroxine (T4) were observed in the early postoperative weeks in some patients and were associated with symptoms of mild hypothyroidism, but by six months in the presence of a raised serum thyrotropin (TSH) the thyroid hormone levels returned to normal. Permanent hypothyroidism developed in only two patients. Despite normal or low total serum T3 and T4 levels, the TSH response to thyrotropin-releasing hormone (TRH) was absent in all patients one week after operation. At four weeks and at eight weeks, the response was absent or sub-normal in 70% and 20% of the patients respectively, indicating a delay in the recovery of the hypothalamo-pituitary axis previously exposed to high levels of T3 and T4. It is considered that subtotal thyroidectomy for thyrotoxicosis in patients prepared with propranolol is an acceptable procedure which has some advantages over the conventional preparation with carbimazole and potassium iodide, not the least of which are the potential reduction in preparation time, the more flexible timing of operation, and the reduced operative blood loss.

Female

Thyroid function in the long-term follow-up of patients treated with iodine-131 for thyrotoxicosis.

In February, 1972, 58% of patients euthyroid after iodine-131 therapy for thyrotoxicosis between 1954 and 1966 had a raised plasma thyroid-stimulating-hormone (T.S.H.) (greater than 7-4 mU/l) and 42% a normal T.S.H. level. A group of 69 of the euthyroid patients with a raised plasma T.S.H. (25-0 +/- 2-0 mU/l) in 1972 was re-examined annually for three years. There was no apparent change in the mean plasma T.S.H. level between 1972 and 1975 in the patients remaining euthyroid, but overt hypothyroidism developed in 3 patients in 1973, in a further 3 patients in 1974, and in 1 patient in 1975. In contrast, none of a group of 61 patients, euthyroid with a normal plasma T.S.H. (4-0 +/- 0-2 mU/l) in 1972, developed overt hypothyroidism over the next three years, although slightly raised T.S.H. levels were recorded in 3 patients in 1974 and in a further 6 patients in 1975. Both the mean serum T-4 and T-3 in the euthyroid patients with a raised plasma T.S.H. were significantly lower, but still in the respective normal ranges, than those in the euthyroid patients with a normal plasma T.S.H. No significant difference in the fasting serum-cholesterol or triglyceride levels could be demonstrated between the two groups. Since no patient with a normal plasma T.S.H. after iodine-131 treatment for thyrotoxicosis six to eighteen years earlier developed overt hypothyroidism over a three-year period, the follow-up of such patients need not be so frequent as that of similarly treated euthyroid patients with a raised plasma T.S.H. in whom overt hypothyroidism develops at the rate of 2-5% per year.

Cholesterol