Thyroid function after subtotal thyroidectomy for hyperthyroidism.

Among 76 patients who had had a subtotal thyroidectomy for hyperthyroidism from one to seven years previously recurrent hyperthyroidism was found in three and hypothyroidism in 13. The remaining 60 subjects were clinically euthyroid but a raised level of serum thyroid-stimulating hormone (TSH; greater than 5-0 mu U/ml) was found in 39. Analysis of the data showed that their serum thyroxine was significantly lower than in the subjects with a normal TSH. The serum triiodothyronine (T-3) was similar in both groups. It is concluded that subjects with a raised TSH remain clinically euthyroid by maintaining a normal serum T-3 concentration. There was no evidence of any long-term progressive deterioration of thyroid function after subtotal thyroidectomy.

Treatment of hypothyroidism: a reappraisal of thyroxine therapy.

Twenty-two subjects with hypothyroidism have been studied in detail before and during replacement therapy with L-thyroxine (T-4). All subjects were stabilized on the minimum dose of T-4 which was necessary to suppress their serum thyroid-stimulating hormone (TSH) concentration to normal, and on this dose most subjects had a normal or impaired TSH response to thyrotrophin-releasing hormone (TRH). The daily dose of T-4 required to suppress TSH was 0.1 mg (13 subjects), 0.15 mg (six subjects), and 0.2 mg (three subjects). It was shown that all subjects were euthyroid on these doses and, using a range of thyroid function tests, that they were normal in all respects when compared with a group of euthyroid controls, with the exception of a small group who had a marginally raised serum triiodo-L-thyronine (T-3) concentration. It has been shown that those subjects who required the larger doses of T-4 had a more advanced degree of thyroid failure than those who were stabilized on 0.1 mg T-4 daily. It is concluded that conventional doses of T-4 (0.2-0.4 mg daily) are often associated with subclinical hyperthyroidism.

Grades of hypothyroidism.

Seventy-nine patients with hypothyroidism and autoimmune thyroid disease were studied, and allotted to one of four categories on the basis of clinical and biochemical features. Firstly, patients with overt hypothyroidism had obvious clinical features of hypothyroidism and abnormal results from routine tests of thyroid function. Secondly, those with mild hypothyroidism, however, had minor and non-specific symptoms, but the routine measurements of circulating thyroid hormone concentration generally lay within the normal range, although they were significantly lower than those seen in subclinical hypothyroidism or in normal subjects. The serum concentration of thyroid-stimulating hormone (TSH) was raised in this group and their symptoms resolve with treatment. Thirdly, patients with subclinical hypothyroidism were asymptomatic, had a raised serum TSH concentration, but all other measurements of thyroid function are indistinguishable from those recorded in people with autoimmune thyroid disease without disturbance of thyroid function and in normal subjects. Lastly, subjects with circulating thyroid antibodies, normal indices of thyroid function, and a normal serum TSH concentration were indistinguishable biochemically from normal subjects.Thus hypothyroidism is a graded phenomenon, the most valuable features for defining the individual grade being the clinical manifestations, the serum TSH concentration, and the presence of circulating antibodies to thyroid tissue.

Hormonal responses to synthetic luteinizing hormone and follicle stimulating hormone-releasing hormone in man.

The effects of the gonadotrophin-releasing hormone, synthetic decapeptide luteinizing hormone/follicle stimulating hormone-releasing hormone (LH/FSH-RH), have been studied in 18 normal men and five women in the follicular phase of their menstrual cycle. Rapid and dose-dependent (25 to 100 mug) increases in serum immunoreactive LH were seen, which reached a peak 20 to 30 minutes after a rapid intravenous injection. Similar but much smaller increases in serum immunoreactive FSH were seen. These conclusions have been validated by using two different immunoassay systems for each hormone. The LH/FSH-RH therefore causes both LH and FSH release in man as in animals but does not affect growth hormone, thyrotrophin, or ACTH. The gonadotrophin responses were the same in the women as in the men but were insufficient in the men to cause statistically significant changes in the serum levels of the gonadal steroid hormones, testosterone or oestradiol, or in their precursors 17 alpha-hydroxyprogesterone or progesterone. In the women, however, there was a rise in oestradiol after the 100-mug doses. The use of LH/FSH-RH will provide an important test to define the level of the lesion in hypogonadal patients and also should be valuable in the treatment of some types of male and female infertility. A simple and clinically useful LH/FSH-RH test of pituitary function is described (100 mug given intravenously), and the provisional normal responses of LH and FSH at 20 and 60 minutes are given.

Further observations on the effect of synthetic thyrotropin-releasing hormone in man.

Synthetic thyrotrophin-releasing hormone (TRH) given intravenously in doses of 50 mug or more causes a significant rise in serum thyroid-stimulating hormone (TSH) levels but has no effect on serum growth hormone, plasma luteinizing hormone, or plasma 11-hydroxycorticosteroids under carefully controlled basal conditions.The peak TSH response to intravenous TRH occurs at 20 minutes. The mild and transient side effects, which occur only after intravenous TRH, include nausea, a flushing sensation, a desire to micturate, a peculiar taste, and tightness in the chest. There is considerable variability in response to a given dose of TRH in the same subject on different occasions and in different subjects. Oral administration of TRH in doses of 1 mg and above causes a rise in serum TSH, maximal at two hours, a consistent response being obtained at doses of 20 mg and above. A rise in serum protein-bound iodine (P.B.I.) follows that of TSH, a consistent response being observed at 40-mg doses of TRH orally. Measurements of serum TSH after intravenous administration of TRH or of serum TSH or serum P.B.I. after oral TRH should prove useful tests of pituitary TSH reserve.

Radioimmunoassay of human serum thyrotrophin.

The double antibody radioimmunoassay of serum thyroid-stimulating hormone (TSH) allows measurement of circulating levels of the hormone in most normal subjects. The serum TSH level in normal subjects is 1.6 +/- 0.8muU/ml. Patients with non-toxic goitre and acromegaly have normal TSH levels. Values are always raised in hypothyroid patients (with primary thyroid disease) and are significantly lowered in those with hyperthyroidism. Of the many stimuli used in an attempt to raise TSH levels in normal adult subjects only three-synthetic thyrotrophin-releasing hormone, ethinyloestradiol, and carbimazole plus iodides-have been effective. The major clinical application of the TSH immunoassay lies in the diagnosis of minor degrees of hypothyroidism. An impaired response of serum TSH to synthetic thyrotrophin-releasing hormone should also help in the diagnosis of hypopituitarism affecting TSH production.

Diazepam and tests of thyroid function.

The effect of diazepam on thyroid function tests was examined in 12 euthyroid patients requiring the drug for psychiatric reasons and in six patients with thyrotoxicosis. Assessment was made before and after four weeks' therapy.There was no significant difference in results from tests of thyroid iodide trapping and binding (thyroid radioiodine uptake, thyroid clearance, and absolute iodine uptake) except in the one-hour thyroid uptake in the euthyroid group, which was increased after diazepam. This increase occurred without alteration in serum thyroid stimulating hormone levels. No change occurred in either group in tests of thyroid hormone release (protein-bound iodine, T-3 resin uptake, or Thyopac-3 and free thyroxine index).Patients with suspected thyroid disease who are taking diazepam do not need to stop therapy while their thyroid status is being determined.