Suppressed TSH Levels Research Articles

Serum thyroglobulin measurements in thyroid cancer: evaluation of‘false’ positive results

Serum thyroglobulin (Tg) should be undetectable in patients successfully treated for thyroid carcinoma. We have examined the course of disease in 19 patients with raised serum Tg (greater than 5 micrograms/l) on initial measurement but no other evidence of residual, recurrent or metastatic cancer. 416 patients from several centres were followed for periods between 1 and 9 years. Serum Tg was measured at 6-12-month intervals. All had differentiated thyroid cancer, treated by partial or total thyroidectomy and/or 131I ablation, and were receiving suppressive thyroxine therapy. Serum Tg was measured and clinical, X-ray and scan assessment made of presence or absence of residual, recurrent or metastatic cancer. Of 416 patients initially assessed, only 19 had Tg greater than 5 micrograms/l but no clinical or radiological evidence of disease. At follow-up, 11 patients had developed overt signs of malignancy; one had been treated with 131I with a subsequent fall in Tg; five had Tg between 5 and 20 micrograms/l with incompletely suppressed TSH levels; two subjects remained with slightly elevated Tg and undetectable TSH. Patients with elevated Tg require careful follow-up even in the apparent absence of disease. Moderate elevation of serum Tg may be due to inadequate thyroxine suppression therapy, assessed by detectable TSH values measured in a sensitive assay.

Thyroid Abnormalities in the McCune-Albright Syndrome: Ultrasonography and Hormonal Studies

Hyperthyroidism and goiter have been reported frequently in association with the McCune-Albright syndrome (MAS). To assess the prevalence and extent of thyroid abnormalities in girls with MAS, we studied 19 patients [mean age, 6.6 +/- 1 (+/- SE) yr; mean bone age, 9.5 +/- 1 yr] and 18 normal control girls (mean age, 10.3 +/- 0.5 yr). All patients appeared euthyroid when examined; 1 was taking antithyroid medication. Ultrasonography revealed thyroid abnormalities in 7 patients, including generalized inhomogeneity, small (2-4 mm) and large (greater than 10 mm) hypoechoic regions, and echogenic nodule-like regions. Repeat ultrasonography after intervals of 9-18 months showed enlargement of large hypoechoic regions in 2 patients. In the patients with abnormal ultrasound findings, serum TSH was uniformly low or suppressed both at baseline and after administration of 7 micrograms/kg TRH. The mean serum T3 level in this group was significantly higher than that in controls (2.9 +/- 0.2 vs. 2.3 +/- 0.1 nmol/L; P less than 0.05), whereas mean serum T4, free T4, and T4-binding globulin levels did not differ from those of controls. In the remaining 11 patients, thyroid ultrasonography was normal, and the serum levels of T3, T4, free T4, and TSH were normal. Bioassay showed no detectable thyroid-stimulating activity in the plasma of the MAS patients with suppressed TSH levels. None of the patients became overtly thyrotoxic over 3-6 yr of observation, and their serum iodothyronine levels remained stable. We conclude that thyroid dysfunction is common in girls with MAS, but that it may be clinically occult and not rapidly progressive. The thyroid dysfunction, like that of the ovaries, is associated with structural abnormalities in the gland itself, together with suppressed levels of the respective stimulating hormones.

The Occurrence of Thyrotropin Binding-Inhibiting Immunoglobulins and Thyroid-Stimulating Antibodies in Patients with Silent Thyroiditis

Silent (painless) thyroiditis has been recognized as a clinical entity for over a decade and is characterized by spontaneously resolving thyrotoxicosis. Its etiology is uncertain; however, a few reports have indicated the occurrence of TSH binding-inhibiting immunoglobulins (TBII) and thyroid-stimulating antibodies (TSAb) in some of the patients. The present study was undertaken to evaluate thyroid function and the occurrence of TBII and TSAb and thyroid autoantibodies (antithyroglobulin and antimicrosomal) in 53 patients with silent thyroiditis during the course of their disease. The patients were divided into 2 major groups: I) those who developed transient hypothyroidism and II) those who did not. All patients initially had significantly increased concentrations of serum T4, free T4, and free T3, suppressed TSH levels, and decreased thyroid radioiodine uptake. TBII and TSAb were initially positive in 8 (15.1%) and 10 patients (18.9%), respectively. Forty patients were available for follow-up. TBII was positive in 6 of 24 (25.0%), and TSAb was positive in 8 of 24 (33.3%) of the patients who developed transient hypothyroidism during the course of their disease. Among the patients who did not become hypothyroid at any time, TBII was positive in only 2 of 16 (12.5%), and none of the patients became TSAb positive. The findings indicate that increased TSAb and TBII activity may be detected in patients with silent thyroiditis and, when present, are associated with transient hypothyroidism during the course of the disease.

Molecular biology of thyrotropin.

Introduction THE pituitary glycoprotein hormone TSH is synthesized and secreted by the thyrotropes in the anterior pituitary. TSH acts on the thyroid gland to increase the production of the thyroid hormones T3 and T4, which then act on organs throughout the body to modulate growth and various metabolic processes. High levels of the thyroid hormones in turn feed back at the level of the pituitary to suppress synthesis and secretion of TSH, and the thyroid hormone concentration is the most important physiological regulator of TSH levels (1–5). Additional regulation can occur via hypothalamic hormones such as TRH and dopamine, which stimulate and suppress TSH levels, respectively (1, 2) (Fig. 1). Thyroid and hypothalamic hormones interact to modulate both circulating levels of TSH and the transcription of the genes encoding the hormone. TSH is one of three pituitary glycoprotein hormones that consists of two dissimilar noncovalent subunits, α and β. The α-subunit is common to all three, including TSH and the...

Relative ontogeny of opioid and catecholaminergic regulation of thyrotropin secretion in the rat.

In order to study the ontogeny of TSH regulation in the rat, we have compared TSH secretion in neonatal and adult rats after treatment with morphine, TRH and apomorphine, clonidine, and exposure to cold. Apomorphine attenuated exogenous TRH-induced TSH release in both neonatal and adult rats. Morphine suppressed TSH levels at every age tested. Although clonidine and cold exposure elicited TSH secretion in adults, neonatal rats did not respond to either treatment. These findings suggest that opioid and dopaminergic controls of TSH release mature before central noradrenergic regulation in developing rats. This lack of noradrenergic control may account for the absence of the response to cold exposure in the neonate.

Hyperthyroidism due to non-tumoural inappropriate TSH secretion

Inappropriate hypersecretion of TSH was investigated in a 25 year old man whose hyperthyroidism had relapsed 4 years after subtotal thyroidectomy. Serum TSH levels were further increased by both TRH and metoclopramide and were partially suppressed by triiodothyronine (120 micrograms/day). The serum alpha-subunit: TSH molar ratio was less than 1.0, and computerised axial tomography showed no evidence of a pituitary tumour. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. A long-acting somatostatin analogue (SMS 201-995), 50 micrograms injected sc twice-daily for three days, suppressed TSH levels and nearly normalised thyroid hormone levels. Somatostatin analogues may be therapeutically useful in thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion.

The effects of dopaminergic blockade on serum TSH and prolactin levels in thyrotoxicosis.

In the first part of this study, we have demonstrated that, in 7 patients with untreated thyrotoxicosis, a 7 day regime of the long acting dopamine antagonist metoclopramide (10 mg orally 8 hourly) produces more adequate dopaminergic blockade at pituitary level than a single oral 10 mg dose of the compound as assessed by serum prolactin responses. Subsequently, we have employed this protracted oral metoclopramide regime to evaluate the contribution of dopaminergic tone to the abnormal TSH and prolactin responsiveness of thyrotoxicosis. Serum TSH and prolactin responses to iv TRH (200 micrograms) were measured in 10 untreated thyrotoxic patients before and after a 7 day period of metoclopramide 10 mg orally 8 hourly. Ten euthyroid individuals were studied in similar fashion, their serum samples being analysed for prolactin levels alone, thus providing a control group for prolactin responsiveness to TRH, before and after metoclopramide. In the thyrotoxic patients basal TSH levels did not change as a consequence of metoclopramide therapy and the TSH response to TRH remained flat. Basal prolactin levels were similar in thyrotoxic and euthyroid individuals and the increase in prolactin, seen in both groups after metoclopramide, was smaller in the thyrotoxic group than in the euthyroid group. Prolactin responsiveness to TRH was significantly impaired in the thyrotoxic subjects as compared to euthyroid subjects. After metoclopramide there was a significant decline in prolactin responsiveness in the euthyroid group, and a similar, though insignificant, trend in the thyrotoxic patients. We conclude that in thyrotoxicosis dopaminergic tone plays no major part in the suppression of TSH levels, nor in the impaired prolactin responsiveness to TRH.

The effect of somatostatin on TSH levels in patients with primary hypothyroidism.

Somatostatin, a growth hormone inhibiting factor (GHIF), was infused into 8 patients with primary hypothyroidism at a dosage of 1000 mug for 105 min. GHIF caused a suppression of TSH levels from 42.6 to 76.9% of preinfusion levels with a mean nadir of 65.0 +/- 4.0%;(mean +/- SEM).