Thyroid cancer in patients with hyperthyroidism

OBJECTIVE: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. With the aim of assessing the clinical relevance of this association, we have retrospectively analyzed the incidence of thyroid cancer in 425 hyperthyroid patients seen and treated by surgery in our institutions. METHODS: Among these hyperthyroid patients, we observed 241 (56.7%) cases of multinodular toxic goiter, 120 (28.3%) of uninodular toxic goiter and 64 (15%) cases of Graves' disease. RESULTS: Thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients. Histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in 2 cases. Neoplasia was detected in 4 patients with nodular toxic goiter and in 3 with uninodular toxic goiter. None of the patients with Graves' disease had thyroid cancer. During the follow-up of 74 months (range 4-154), there were no deaths or any recurrences. CONCLUSION: Although the occurrence of thyroid cancer in hyperthyroid patients is a rare event, the presence of a 'cold' nodule in a hyperfunctioning thyroid should be carefully evaluated to exclude the presence of concurrent malignancy.     

Hypothalamic-pituitary-testicular axis in patients with hyperthyroidism

To test whether chronic thyroid hormone excess influences the hypothalamic-pituitary-testicular axis, 8 hyperthyroid men were given two identical intravenous GnRH tests. The first test was performed before any treatment had been instituted, the second 6-13 months later, when medical treatment had made the patients euthyroid. Although basal serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) levels were of similar magnitudes before and after the medical treatment, LH and FSH responsiveness to gonadotropin-releasing hormone (GnRH), as reflected by the hormone incremental areas (U/l X min), were significantly larger in the thyrotoxic state compared with the euthyroid state (LH incremental areas: 3,999 +/- 665 vs. 2,640 +/- 430, p less than 0.02; FSH incremental areas: 825 +/- 193 vs. 542 +/- 98, p less than 0.05). Furthermore, serum T increased significantly in response to GnRH when the patients were hyperthyroid (T incremental area: 162 +/- 51, p less than 0.02), but failed to do so when they were euthyroid (T incremental area: 92 +/- 53, NS). These results imply that chronic thyroid hormone excess makes the pituitary gonadotrophs 'hypersensitive' to exogenous GnRH. This may in turn explain why human Leydig cells respond more powerful to exogenous GnRH in thyrotoxic patients than in euthyroid subjects.     

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.     

Urinary N-acetyl-beta-D-glucosaminidase in the patients with hyperthyroidism

Urinary N-acetyl-beta-D-glucosaminidase (NAG) was measured in patients with hyperthyroidism. The value of urinary NAG in these patients was higher than that in normal subjects and diabetic patients without diabetic nephropathy. This high level of urinary NAG in patients with hyperthyroidism decreased to the level of normal subjects after treatment of hyperthyroidism. Why urinary NAG increases in the patients with hyperthyroidism remains unknown. On the occasion of estimating the significance of the high level of urinary NAG, however, the possibility of the existence of hyperthyroidism has to be considered in addition to renal damage or hyperglycemia which have already been found to increase urinary NAG.     

Increased erythrocyte catalase activity in patients with hyperthyroidism

Levels of human erythrocyte catalase activity were determined in 38 patients with thyroidal dysfunction. In patients with hyperthyroidism, erythrocyte catalase activities were found to be higher than the levels of normal subjects (P less than 0.001). In hypothyroidism, erythrocyte catalase activities were of the same order as those of normal subjects. Significantly high positive correlation was found between erythrocytes catalase activity and the levels of thyroxine (r = 0.5794, n = 36, P less than 0.001), and slight positive correlation was detected between catalase activity and the levels of triiodothyronine (r = 0.3978, n = 33, P less than 0.05). A decreased erythrocyte catalase activity was observed when erythrocytes lysate was incubated with thyroid hormones. It was suggested that erythrocyte catalase activity had close relationship with thyroid state, however, direct effect of thyroid hormones were not observed on erythrocyte catalase assay system in vitro.     

Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism

Thyrotoxicosis is an important but under recognized cause of osteoporosis. Recently, TSH deficiency, rather than thyroid hormone excess, has been suggested as the underlying cause. To investigate the molecular mechanism of osteoporosis in thyroid disease, we characterized the skeleton in mice lacking either thyroid hormone receptor alpha or beta (TRalpha(0/0), TRbeta-/-). Remarkably, in the presence of normal circulating thyroid hormone and TSH concentrations, adult TRalpha(0/0) mice had osteosclerosis accompanied by reduced osteoclastic bone resorption, whereas juveniles had delayed endochondral ossification with reduced bone mineral deposition. By contrast, adult TRbeta-/- mice with elevated TSH and thyroid hormone levels were osteoporotic with evidence of increased bone resorption, whereas juveniles had advanced ossification with increased bone mineral deposition. Analysis of T3 target gene expression revealed skeletal hypothyroidism in TRalpha(0/0) mice, but skeletal thyrotoxicosis in TRbeta-/- mice. These studies demonstrate that bone loss in thyrotoxicosis is independent of circulating TSH levels and mediated predominantly by TRalpha, thus identifying TRalpha as a novel drug target in the prevention and treatment of osteoporosis.     

Reduced serum acylated ghrelin levels in patients with hyperthyroidism

BACKGROUND AND OBJECTIVE: Recent studies have revealed that circulating ghrelin levels seem to play a role in energy homeostasis. The effect of hyperthyroidism on ghrelin levels is not fully known. METHODS: Serum levels of ghrelin and its relationship with insulin resistance were evaluated in 48 patients with hyperthyroidism and 43 euthyroid healthy controls. Thyroid hormones, insulin, glucose, ghrelin levels and lipid parameters were measured in all subjects. Insulin sensitivity was determined using the homeostasis model assessment. RESULTS: Serum ghrelin levels were significantly decreased in hyperthyroid patients than in controls (32.5 +/- 23.3 vs. 54.1 +/- 35.5 pg/ml, p < 0.001). Circulating ghrelin levels significantly correlated with age (r = -0.26, p = 0.01), fasting glucose (r = -0.21, p = 0.01), free triiodothyronine (r = -0.18, p = 0.04), free thyroxine (r = -0.23, p = 0.02) and thyroid stimulating hormone (r = 0.21, p = 0.04), but not with blood pressure, body mass index, lipid parameters, insulin and homeostasis model assessment (p > 0.05). Multiple regression analysis revealed glucose level to be the most important predictor of circulating ghrelin level. CONCLUSION: These results indicate that hyperthyroidism has effect on serum ghrelin levels. Further studies are needed for the exact mechanism.     

Thyroid cancer in youth

Study was made of 11 patients under 20 years of age with thyroid cancer. Nine were girls and two boys. Eight of the patients had first sought medical advice because of cervical adenopathy. Nine of the patients had had x-ray therapy to the head and neck previous to the diagnosis of the thyroid cancer.     

Thyroid activity in patients with major depression

Hypothalamus-pituitary-thyroid (HPT) axis dysfunction has been associated with pathophysiology of major depression. The aim of the study was to determine serum levels of total 3,5,3'-triiodothyronine (T3), total thyroxine (T4) and thyroid-stimulating-hormone (TSH) in patients with major depression and healthy controls. The study included 53 medication-free patients with depression and 49 healthy controls. Exclusion criteria for patients was: other axis-I and axis-II diagnoses, intensive psychotherapy or electroconvulsive therapy, prior clinical and/or laboratory evidence of hypo- or hyperthyroidism, alcohol or nicotine dependence, pregnancy, hormone supplement therapy, somatic illnesses (diabetes, renal or hepatic disorders), infections or autoimmune diseases, recent surgical treatment or significantly changed body weight. For controls: the presence of psychiatric disorders and/or thyroid dysfunctions. The diagnosis of major depression was made using structured clinical interview based on DSM-IV criteria. The results showed significantly lower T3 and TSH levels in patients compared to controls. There was no significant difference in T4 values between patients with depression and control subjects. The results showing altered levels of thyroid hormones in depression indicate that further research on thyroid hormone activity can contribute to the better understanding of the biological basis of depression. Based on the high frequency of the subtle neuroendocrine disorders coexisting with depression, the association of thyroid abnormalities and depression should not be underestimated. Future research should identify different behavioral endophenotypes characteristic for depression, which would greatly facilitate delineating the biological phenomena associated with this psychiatric illness.     

Markers of endothelial dysfunction in patients with iodine induced hyperthyroidism

INTRODUCTION: It has been reported that hyperthyroidism is associated with an altered endothelial function and increased risk of arterial thromboembolism. The aim of our study was to estimate chosen markers of endothelial dysfunction in iodine-induced thyrotoxicosis (IIT). MATERIALS AND METHODS: The groups studied consisted of 41 hyperthyroid subjects, who had been treated with amiodarone (n = 6) or vitamin preparations supplemented with iodine (n = 35) and 40 persons with normal thyroid function. The following parameters were measured: thyroglobulin antibodies (TG Ab), thyroid peroxidase antibodies (TPO Ab), THS receptor antibodies (TR Ab), soluble adhesion molecules: sVCAM-1 and sICAM-1, von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), fibrinogen and urine iodine concentration. RESULTS: Patients with IIT had significantly higher levels of sVCAM-1 (p < 0.01), IL-6 (p < 0.005), fibrinogen (p < 0.005) and CRP (p < 0.05) in comparison to healthy subjects, whereas sICAM-1, PAI-1 and vWF concentrations did not differ between the groups studied. The highest sVCAM-1 levels were observed in patients with amiodarone induced thyrotoxicosis, and fibrinogen and CRP--in subjects receiving vitamin preparations. There were significant correlations between sVCAM-1 concentration and the levels of sICAM-1 (r = 0.341; p = 0.029) and PAI-1 (r = 0.347; p = 0.026), as well as with urine iodine concentration (r = 0.448; p = 0.004). IL-6 concentration correlated with vWF (r = 0.456; p = 0.003), TPO Ab (r = 0.328; p = 0.036) and PAI-1 level (r = 0.319; p = 0.042). CONCLUSION: Iodine induced thyrotoxicosis is associated with an increase of sVCAM-1 and IL-6 levels, possibly reflecting inflammatory and destructive processes in the thyroid gland. However, increased procoagulant activity was not found in patients with IIT.     

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.