Biochemical Evidence Of Hypothyroidism Research Articles

The incidence of occult thyroid disease associated with thyroid antibodies identified on routine autoantibody screening.

The presence of thyroid microsomal and/or thyroglobulin antibodies has been recorded over a 2 year period of 15 000 consecutive autoimmune profile request. Where there had been no initial clinical suspicion of thyroid diseases, 332 requests showed positive thyroid antibodies, and of these 63 (19%) had abnormal in vitro thyroid function tests (TFT). No differences were observed between the abnormal and normal groups with respect to the presence of different autoantibodies or to the age and sex distributions. Of these subjects with clinically unsuspected hypothyroidism but with abnormal TFTs, 29% were commenced on thyroxine therapy and experienced a symptomatic improvement, 25% remain well on no therapy and 9% continue on no treatment but with symptoms possibly attributable to hypothyroidism. 3% became clinically hypothyroid during a follow-up period of 2 years. 5% died of unrelated causes and there was inadequate follow-up information on the remainder. This study provides further confirmation that when thyroid antibodies, and in particular thyroid microsomal antibody, are found unexpectedly, a significant proportion of patients will have biochemical evidence of hypothyroidism and may benefit from appropriate treatment.

Hypothyroid myopathy. A clinical and pathologaical study.

Ten patients with varying degrees of hypothroid myopathy were studied clinically and by serial percutaneous needle muscle biopsies before and during treatment with L-thyroxine. The biochemical evidence of hypothyroidism was related to the severity of the myopathic and signs before treatment. The severity of myopathic symptoms before and during treatment correlated with the biochemical evidence of hypothyrodism, a type II fibre atrophy and increased central nuclear counts. Likewise, the clinical evidence of a myopathy before and during treatment was correlated with both a type II fibre atrophy and loss and increased central nuclear counts but was not related to the biochemical parameters of hypothyroidism, except the level of thyroid stimulating hormone. In the muscle, before and during treatment, of the two most severely affected patients, intracellular glycogen inclusions were seen in scattered muscle fibres. On light microscopy and on electronmicroscopy, numerous mitochondria were seen responding to L-thyroxine with accumulations of subsarcolemmal honey-combing. Vesicular abnormalities, an electron dense matrix or occasional crystalline deposits were seen in muscle mitochondria from less severely azffected patients. Severely myopathic muscle contained excessive glycogen, membrane bound glycogen and excess lipid in a mainly perinuclear distribution. Occasional myelin and membranous bodies were seen and satellite cells during the recovery phase. A group of patients with hypothyroid myopathy who are likely to have a delayed recovery of full muscle strength on L-thyroxine may be recognised by the presence of severe proximal muscle weakness and characteristic changes on histochemical and electronmicroscopic examination of muscle. The spectrum of histochemical and electronmicroscopic abnormalities of muscle revealed with increasing degree of hypothyrodism, suggests that a generally reversible acquired glycogen storage and mictochondrial disorder is an important feature in the pathogenesis of this condition.

Transient hypothyroidism after iodine-131 treatment of thyrotoxicosis.

Thirty consecutive patients with thyrotoxicosis were followed up at monthly intervals for 6 months after treatment with iodine-131. Serum total T4, serum total T3, and serum TSH response to TRH were measured at each review. Biochemical evidence of hypothyroidism (low T4 raised basal TSH) developed in 18 patients 1-4 months after treatment. In 5 of these patients, symptoms and signs of hypothyroidism remained absent or minimal and spontaneous recovery of thyroid function occurred during the ensuing 2 months. If biochemical hypothyroidism occurs during the first 6 months after radioiodine therapy, it is recommended that T4 replacement be withheld for 2 months unless the severity of symptoms demands treatment.

THYROID REPLACEMENT THERAPY IN DOWN'S SYNDROME WITH HYPOTHYROIDISM

Three elderly subjects with Down's syndrome and biochemical evidence of hypothyroidism were investigated before and after four months of thyroid replacement treatment. The patients' appearance was demonstrated by photographs and the biochemical thyroid values and the intellectual performance were assessed. The appearance before treatment varied from a florid myxoedematous appearance to a state without features indicating myxoedema. Thyroid replacement therapy was given in usual dose and the biochemical response was similar to that seen in normal subjects. The intellectual performance improved little or not at all. The characteristic discomfort usually associated with hypothyroidism was very pronounced in one case and disappeared totally during treatment. It is concluded that the diagnosis of hypothyroidism in elderly subjects with Down's syndrome can be very difficult when based on appearance and history alone and biochemical thyroid tests are often necessary. The patients should be treated with replacement therapy just as other patients suffering from hypothyroidism.

Central nuclear counts in muscle fibres before and during treatment in hypothyroid myopathy

Serial percutaneous needle muscle biopsies of vastus lateralis were studied in 10 patients who had varying degrees of hypothyroid myopathy. The biopsies were taken before and during treatment with l-thyroxine. Before treatment the most severely clinically affected patients showed type II muscle fibre atrophy and loss, together with increased central nuclear counts preferentially affecting the type II muscle fibre. Both the type II muscle fibre atrophy and loss and the increased central nuclear counts tended to return towards normal values during treatment with l-thyroxine. The severity of myopathic symptoms before and during treatment correlated with the biochemical evidence of hypothyroidism, a type II fibre atrophy, and increased central nuclear counts. The severity of myopathic signs before and during treatment was correlated with both a type II fibre atrophy and loss and increased central nuclear counts. There was no evidence that the myopathic signs before and during treatment were related to the biochemical parameters of hypothyroidism, except the level of thyroid stimulating hormone. It is suggested that sequential studies of muscle fibre percentages, diameters, and central nuclear counts may provide an additional method of assessing the response to treatment in hypothyroid and possibly other types of myopathy. When increased central nuclear counts are confined to a specific muscle fibre type, this may suggest a hitherto unsuspected specificity of muscle fibre damage.

Thyroid function in lung cancer.

Thyroid function was assessed at the time of initial diagnosis in 204 patients with lung cancer and compared with that of age and sex-matched patients with non-malignant lung disease. Abnormalities in thyroid function were found in 67 patients (33%). The most prevalent abnormality was a low T3 concentration; this was not associated with other clinical or biochemical evidence of hypothyroidism, but the short-term prognosis of these patients was worse than that of matched patients with lung cancer having normal T3 concentrations. Primary hypothyroidism occurred in three patients, low T4 concentrations and free thyroxine index (FTI) with normal thyrotrophin (TSH) concentrations in four patients, and moderately raised TSH with normal thyroid hormone concentrations in six patients; nine patients had a raised FTI with or without raised T4 concentration as the sole abnormality.Overall, the pattern of thyroid hormone metabolism in lung cancer was a tendency towards reduced T3 concentrations with significantly increased T4/T3 ratios and modestly increased 3,3',5'-triiodothyronine (rT3) concentrations. The altered T4/T3 ratio was particularly noticeable in patients with anaplastic tumours of small ("oat cell") and large cell types, but was not apparently related to detectable extrathoracic metastases.These data suggest that thyroid hormone metabolism is altered in patients with lung cancer by decreased 5'-monodeiodination of T4. The resulting low T3 concentrations and altered T4/T3 ratio may be partly responsible for the reduced ratio of androsterone to aetiocholanolone observed in lung cancer, which is known to be a poor prognostic sign.

Thyroid function in term newborn infants with congenital goiter

Eighty-four term newborn infants without goiter and 45 newborn infants with congenital goiter were studied with regard to thyroid function. The radiologic development of the femoral and tibial epiphyses was evaluated in those with goiter. Fifty-eight percent of the patients had retarded bone age, markedly elevated TSH levels, elevated TBI, decreased total T4I, and decreased PBI values. Forty-two percent of newborn infants with congenital goiter had a normal bone age, normal values for TSH, PBI, and total T4I, and elevated values for TBI. It is concluded that the 58% of the newborn infants with congenital goiter had subtle hypothyroidism. They require substitution therapy with thyroid hormones in order to avoid possible retardation of normal brain development. Patients with congenital goiter who have no biochemical evidence of hypothyroidism should also be treated with thyroid hormones to achieve rapid regression of goiter.

TRF test in patients with hypothalamic-pituitary disorders.

TRF test with 50-100μg of synthetic TRF was performed in 57 patients with hypothalamic-pituitary disorders. According to the degree and the pattern of TSH response, they were classified as an absent, subnormal, normal or supernormal response and/or delayed pattern of TSH response. 9 of 21 patients with pituitary chromophobe adenoma showed an absent or a subnormal response. Six of them were hypothyroid. 21 of 23 patients with hypothalamic lesions had normal or supernormal TSH response. 5 with a normal response and all of the six with a supernormal response showed clinical or biochemical evidence of hypothyroidism. Since the pituitary of these cases remained intact from tumor invasion, they should be postulated as hypothalamic hypothyroidism. A delayed pattern of TSH response to TRF, where the peak TSH response occurred after 20min, was observed in 17 of 23 in hypothalamic lesions. 6 of 7 patients with diabetes insipidus showed just the same pattern of TSH response as observed in the patients with determined hypothalamic lesions. This delayed pattern of response and normal or supernormal response to a small dose of TRF, such as 50-100μg, could be used to distinguish hypothalamic lesions from pituitary diseases.

THE THYROTROPHIN-RELEASING HORMONE TEST IN DISEASES OF THE PITUITARY AND HYPOTHALAMUS

The increase in serum-thyroid-stimulating hormone (T.S.H.) levels measured twenty and sixty minutes after intravenous injection of 200 μg. of synthetic thyrotrophin-releasing hormone (T.R.H.) has been used as a test of pituitary-hypothalamic function. 77 patients with diseases of the pituitary or hypothalamus had T.R.H. tests and routine clinical and biochemical assessment of pituitary and thyroid function. Of 35 patients with acromegaly, 9 of whom had not received treatment directed to the pituitary, only 7 showed a normal response to T.R.H., and 4 of these were in the untreated group. No patient in whom growth hormone (G.H.) levels had returned to normal showed a normal T.S.H. reserve. In the acromegalic patients the T.S.H. reserve was impaired twice as frequently as the corticotrophin reserve (A.C.T.H.). Of 27 patients with various other pituitary lesions, 14 had an impaired or absent T.S.H. response, and 8 of these had other clinical or biochemical evidence of hypothyroidism. Unlike the acromegalic patients, T.S.H. and A.C.T.H. reserve were impaired with equal frequency in this group. Of 15 patients with various hypothalamic lesions, 8 had an impaired or absent response to T.R.H.; 3 patients who responded normally to T.R.H. had other evidence of hypothyroidism. A delayed response to T.R.H., where the twenty-minute T.S.H. level was less than the sixty-minute value, occurred in 13 of 15 in this group. This delayed pattern of response can be used to recognise hypothalamic disease. In patients with pituitary disease, but not in those with hypothalamic disease, a normal T.S.H. response to T.R.H. excludes the diagnosis of hypothyroidism. All patients with non-hormone-secreting pituitary lesions who had no response to T.R.H. were hypothyroid; this was not true in acromegaly or in a patient with active Cushing's disease. Since only 7 of the 26 patients with pituitary disease who showed impaired responses were hypothyroid by other criteria, it is suggested that impaired responses merely indicate a risk of the development of thyroid deficiency.