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Biomedical subjects

Leonidas H Duntas

Publications and source records attributed to Leonidas H Duntas.

15 recordsLinked to original sources
PubMed2007

Short-term hypothyroidism after Levothyroxine-withdrawal in patients with differentiated thyroid cancer: clinical and quality of life consequences.

Acute hypothyroidism induced by thyroid hormone withdrawal in patients with differentiated thyroid cancer during monitoring for remnant or metastatic disease, seriously affects multiple organs and systems, and especially in severe cases can impair quality of life. Indeed, it may induce untoward cardiovascular effects and can be hazardous in patients with underlying cardiovascular disease, particularly in the elderly. Moreover, acute hypothyroidism deranges the lipid profile and exacerbates neuropsychiatric illness. The introduction of recombinant human TSH (rhTSH) as a diagnostic and therapeutic tool in the care of patients with thyroid cancer has widened the scope of disease management. The use of rhTSH prevents derangement of various systems at approximately equivalent societal costs to that of withdrawal and promotes compliance while preserving the patient's normal daily functioning and productivity. Its reliability allied with its safety render this compound a valid alternative in the monitoring of patients with differentiated thyroid carcinoma as well as providing an alternative therapeutic procedure whenever LT4-withdrawal may be hazardous or in cases of patient non-compliance.

Blood Pressure↗
PubMed2006

The role of selenium in thyroid autoimmunity and cancer.

The essential micronutrient selenium (Se) occurs in the form of the amino acid selenocysteine in selenoproteins which exert various effects, while maintaining the cell reduction-oxidation balance. The discovery that all three deiodinases that convert thyroxine (T4) into triiodothyronine (T3) contain selenocysteine illustrates how the production of the active thyroid hormone is dependent on Se status. The selenoenzyme families of glutathione peroxidases (GPx) and thioredoxin reductases (TRx) possess powerful antioxidant properties and form a complex defense system that protects thyrocytes from oxidative damage. Se supplementation in patients with autoimmune thyroiditis seems to modify the immune response, probably by enhancing plasma GPx activity and decreasing excess levels of hydrogen peroxide. However, the enhancement of immunocompetence may also be the result of the synergistic action of various selenoproteins and not exclusively of GPx. There is evidence supporting considerable oxidative stress in Graves' disease where Se supplementation, because of its free radical scavenging properties, may increase the enzymatic antioxidant activity. TRx has been found significantly elevated in GD revealing its involvement in the pathogenesis of this condition and representing a potential future target for therapeutical intervention. Low Se serum levels have also been associated with increased risk of thyroid cancer and may play a role in carcinogenesis. It is noteworthy, that the Food and Drug Administration has recently determined that there is sufficient evidence to warrant a qualified health claim for Se and cancer. Furthermore, the recent discovery that defects in the SECIS-binding protein 2 (SBP2), which is an indispensable protein for the incorporation of Se into the selenoproteins, result in thyroid dysfunction, together with the recognition of the many roles of selenoprotein P in Se distribution and storage in the human body, reveal not only the indispensability of Se and the selenoproteins as essential factors in thyroid metabolism and pathogenesis, but open up new prospects for enhanced treatment.

Animals↗
PubMed2005

Brain somatic cross-talk: ghrelin, leptin and ultimate challengers of obesity.

Energy balance is largely regulated by the central nervous system (CNS), which senses metabolic status from a wide range of humoral and neural signals, and controls energy intake. Accumulating evidence supports the model that stimulation of leptin- and ghrelin-responsive pathways, including the central melanocortin system, in the hypothalamus, contributes to the maintenance of body weight. Ghrelin is the brain-gut peptide with growth hormone-releasing and appetite-inducing activities. It is mainly secreted from the stomach and acts as an afferent signal to the hypothalamus and hindbrain. Leptin, the adipocyte hormone, is believed to tonically act as an afferent signal from adipose tissue to the brain, in particular hypothalamus, as a part of negative feedback loop regulating the size of energy stores and energy balance. Dysregulation of these pathways is a marker of changes in energy balance. Ghrelin is negatively correlated with weight and obese subjects have lower ghrelin levels than lean subjects, consistent with a compensatory rather than causal role for ghrelin in obesity. On the contrary, circulating leptin levels correlate in proportion to adiposity being high in obesity suggesting that human obesity is associated with insensitivity to leptin. The leptin resistance in diet-induced obesity emphasizes that environmental factors can modulate leptin sensitivity. It is speculated that through hypothalamic/pituitary axis ghrelin and leptin operate as a metabolic switch. Ghrelin actually transfers information from the stomach to the hypothalamus in cooperation with leptin and provides calories that growth hormone (GH) needs for growth and repair. Pharmacological manipulations of circulating hormone levels may work well in "cheating" the brain regarding information from the periphery. It might also be necessary to combine two or three agents to fight obesity. A combination of drugs that decrease preprandial appetite (ghrelin antagonist) and increase post-prandial satiety (gut hormone fragment peptide YY 3-36) might have a chance of achieving sustained weight loss. The administration of exogenous satiety hormone peptide YY 3-36 (PYY) may prevent the action of appetite-stimulating hypothalamic circuits on the anorexigenic melanocortin pathways.

Adipose Tissue↗
PubMed2004

Adiponectin: novelties in metabolism and hormonal regulation.

Adiponectin is a protein secreted exclusively by white adipose tissues and is abundantly present in human plasma. Adiponectin was found decreased in obese and diabetes mellitus type 2 patients and increased with weight reduction. A negative correlation between circulating adiponectin levels and body mass index and insulin resistance has been demonstrated. Plasma adiponectin concentrations were found lower in diabetes mellitus type 2 patients with coronary artery disease. Moreover, studies in aortic endothelial cells revealed that the protein exerts a dose-dependent decrease of the surface expression of vascular adhesion molecules and cytokine production from macrophages, suggesting the implication of adiponectin in atherosclerosis and inflammation. Weight loss and treatment with thiazolidinediones stimulate endogenous adiponectin production. Peripheral administration of adiponectin leads to reduction of visceral adiposity and increase of free fatty acid oxidation and insulin resistance. Furthermore, it enhances the expression of uncoupling proteins and sympathetic nerve activity in adipose tissues. Experimental studies in mice have shown that intraperitoneal administration of adiponectin lowers plasma glucose. These data show adiponectin to be an important factor in the issue of obesity and its associated disorders, and indicate a potential future utilization of adiponectin as a drug in the treatment of metabolic syndrome.

Adiponectin↗
PubMed2003

Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis.

OBJECTIVE: Selenium (Se) in the form of selenocysteine is an essential component of the family of the detoxifying enzymes glutathione peroxidase (Gpx) and of the iodothyronine selenodeiodinases that catalyse the extrathyroidal production of tri-iodothyronine (T(3)). Thus, Se deficiency may seriously influence the generation of free radicals, the conversion of thyroxine (T(4)) to T(3) and the autoimmune process. Therefore, we performed a randomised, placebo-controlled prospective study to investigate the effects of Se treatment on patients with autoimmune thyroiditis (AIT). DESIGN AND METHODS: Sixty five patients aged 22-61 years (median age 48 years) with AIT were recruited into two groups. Group I (Gr I) (n=34) was treated with selenomethionine (Seme) 200 microg, plus L-thyroxine (LT(4)) to maintain TSH levels between 0.3-2.0 mU/l, whereas group II (Gr II) (n=31) received LT(4) plus placebo over a period of 6 months. Moreover, the pharmacokinetics of Seme were studied in 10 patients and eight volunteers at baseline and 2 h, 4 h, 6 h and 24 h after oral administration of a 200 microg tablet of Seme. Finally, Se levels were measured at the end of the study in some patients of both groups and their results were correlated with thyroid hormone levels. RESULTS: In the pharmacokinetics study, basal serum concentration of Se (75+/-6 microg/l) was within the reference range (70-125 microg/l), it promptly increased at 2 h, peaked at 4 h (147+/-17 microg/l; P<0.0001) and it was abundant in serum at 24 h. In Gr I, antibodies against thyroid peroxidase (anti-TPO) levels showed an overall decrease of 46% at 3 months (from 1875+/-1039 U/l to 1013+/-382 U/l; P<0.0001) and of 55.5% at 6 months. In Gr II the overall decrease of anti-TPO amounted to 21% at 3 months and to 27% at 6 months (from 1758+/-917 U/l to 1284+/-410 U/l; P<0.005). There were no significant changes of antibodies against thyroglobulin levels between the groups. At the end of this study Se levels were found to be statistically significantly increased in Gr I (n = 9/34) compared with Gr II (n=11/31) (97+/-8.4 vs 79+/-8; P<0.01) but no correlation with thyroid hormone was found. CONCLUSIONS: Seme is proven to be rapidly absorbed by the gastrointestinal tract. It appears to be useful as adjunctive therapy with LT(4) in the treatment of AIT. The exact mechanism(s) is not very well determined, it might enhance the activity of detoxifying enzymes and enforce the defense against oxidative stress.

Adult↗
PubMed2002

Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism.

The increased low-density lipoprotein cholesterol (LDL-C) levels in hypothyroidism may enhance the formation of oxidized LDL (oxi-LDL) that may consequently generate foam cells by their uptake by the macrophages. The goal of this study was to investigate whether plasma circulating oxi-LDL levels are elevated in mild and in overt hypothyroidism, if the concentration of oxi-LDL is influenced in a short-term treatment period by thyroid hormone, and whether correlations exist between serum concentration of thyrotropin (TSH), thyroid hormone, and cholesterol. Thirty-nine patients with overt hypothyroidism (OH), 41 patients with mild thyroid failure (MTF), and 57 controls (CNTR) were investigated. Serum TSH concentrations were increased in OH (18 +/- 6 mU/L) and in MTF (6 +/- 2 mU/L), whereas in CNTR the levels were 1.6 +/- 0.3 mU/L. Plasma circulating levels of oxi-LDL were measured by a new enzyme-linked immunosorbent assay (ELISA) kit (normal range, 40-75 mU/L) and they were found statistically significantly increased in OH compared to MTF (86 +/- 16 mU/L vs. 73 +/- 13 mU/L; p < 0.01) and to CNTR (62 +/- 11 mU/L; p < 0.001). Smokers in all groups exhibited statistically significant higher plasma oxi-LDL levels compared to nonsmokers. The percentage of increase amounted to 17.7% in OH, to 9.8% in MTF, and to 8% in CNTR. Replacement treatment with levothyroxine over a period of 3 months in 12 of 39 patients with OH and in 14 of 41 patients with MTF resulted in a statistically significant decrease of oxi-LDL only in the OH group. Thus, plasma oxi-LDL decreased in OH from 82 +/- 12 mU/L to 73 +/- 10 mU/L (p < 0.05), to the upper normal level, and in MTF from 68 +/- 5 mU/L to 64 +/- 5 mU/L, respectively. In conclusion, we can state that circulating oxi-LDL levels are elevated in untreated overt hypothyroidism, they tend to be higher in mild thyroid failure, they are severely affected by smoking, however, they need a longer time course to decrease via thyroxine treatment.

Adult↗
PubMed2002

Thyroid disease and lipids.

The composition and the transport of lipoproteins are seriously disturbed in thyroid diseases. Overt hypothyroidism is characterized by hypercholesterolaemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B (apo A) because of a decreased fractional clearance of LDL by a reduced number of LDL receptors in the liver. The high-density lipoprotein (HDL) levels are normal or even elevated in severe hypothyroidism because of decreased activity of cholesteryl-ester transfer protein (CETP) and hepatic lipase (HL), which are enzymes regulated by thyroid hormones. The low activity of CETP, and more specifically of HL, results in reduced transport of cholesteryl esters from HDL(2) to very low-density lipoproteins (VLDL) and intermediate low-density lipoprotein (IDL), and reduced transport of HDL(2) to HDL(3). Moreover, hypothyroidism increases the oxidation of plasma cholesterol mainly because of an altered pattern of binding and to the increased levels of cholesterol, which presents a substrate for the oxidative stress. Cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Hypothyroidism is often accompanied by diastolic hypertension that, in conjunction with the dyslipidemia, may promote atherosclerosis. However, thyroxine therapy, in a thyrotropin (TSH)-suppressive dose, usually leads to a considerable improvement of the lipid profile. The changes in lipoproteins are correlated with changes in free thyroxine (FT(4)) levels. Hyperthyroidism exhibits an enhanced excretion of cholesterol and an increased turnover of LDL resulting in a decrease of total and LDL cholesterol, whereas HDL are decreased or not affected. The action of thyroid hormone on Lp(a) lipoprotein is still debated, because both decrease or no changes have been reported. The discrepancies are mostly because of genetic polymorphism of apo(a) and to the differences between the various study groups. Subclinical hypothyroidism (SH) is associated with lipid disorders that are characterized by normal or slightly elevated total cholesterol levels, increased LDL, and lower HDL. Moreover, SH has been associated with endothelium dysfunction, aortic atherosclerosis, and myocardial infarction. Lipid disorders exhibit great individual variability. Nevertheless, they might be a link, although it has not been proved, between SH and atherosclerosis.

Humans↗
PubMedDate not supplied

Doping: a challenge to the endocrinologist. A reappraisal in view of the Olympic Games of 2004.

The aim of this review is to provide an update on drug abuse by athletes, their mode of action and the technical difficulties of detection. The most common doping agents are the anabolic steroids (AS), testosterone derivatives modified to take advantage of the anabolic rather than the androgenic properties of the hormone. However, there are numerous side-effects that discourage their use. Several other substances and hormones, GH and rhEPO are currently used alone or combined to enhance performance. The diversity in nature of the substances used requires a constant alertness of physicians to detect drug abuse in sports. Doping is not limited to the professional athletes. It seems to be a generalized phenomenon that reflects modern society's concept of success. Therefore, the campaign to eradicate doping must also focus on individual responsibility. Since modern-day doping is strongly related to hormonal preparations, endocrinologists may play a pivotal role in providing information, protecting athletes' health and, moreover, retaining the ethical value of sport.

Journal Article↗
PubMedDate not supplied

The use of recombinant human thyrotropin (Thyrogen) in the diagnosis and treatment of thyroid cancer.

The introduction of human recombinant thyrotropin (rhTSH/Thyrogen) into the diagnosis of thyroid cancer has substantially ameliorated the patient's quality of life through the avoidance of debilitating hypothyroidism. With the aim of updating the use of Thyrogen, we report 7 cases which were treated with Thyrogen for diagnostic or therapeutic purposes. All 7 patients were thyroidectomised and radioiodine ablated and all had detectable [> 1 ng/ml] basal serum thyroglobulin (b-Tg) levels. Thyrogen stimulation resulted in a rise of Tg (s-Tg) in all patients. Five patients had negative whole body scanning (WBS) and no clinical or radiological signs of disease. Two patients with a b-Tg value of 5 ng/ml and 11 ng/ml, respectively showed a s-Tg of 17 ng/ml and 84 ng/ml, respectively, whereas WBS was negative. Both of these patients received 100 mCi (3700 MBq) 131I. Owo patients had a positive Tg and positive WBS with skull, lung and hepatic metastases and received 150 131I after preparation with Thyrogen. Six months later one of these patients was free of disease and the other will be evaluated during the coming months. In conclusion, Thyrogen emerges as a reliable and safe agent for the diagnosis of thyroid cancer. Furthermore, it appears that Thyrogen could be used in the treatment of metastases as an alternative to thyroid hormone withdrawal.

Journal Article↗