Biomedical subjects

Maria Alevizaki

Publications and source records attributed to Maria Alevizaki.

17 recordsLinked to original sources

PubMed2007

High anticipatory stress plasma cortisol levels and sensitivity to glucocorticoids predict severity of coronary artery disease in subjects undergoing coronary angiography.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and/or increased sensitivity of peripheral tissues to glucocorticoids may be associated with the dysmetabolic syndrome and its cardiovascular sequelae. In this prospective pilot clinical study, we examined possible associations between HPA axis activity and severity of cardiovascular disease. We measured morning serum cortisol and intima media thickness (IMT) of carotid and femoral arteries in 105 subjects before undergoing coronary angiography for suspected coronary artery disease (CAD). In a randomly selected 46 of these subjects, we obtained late afternoon and morning cortisol levels (after ultralow-dose dexamethasone [0.25 mg] treatment) and determined their genotype for the Bcl1 polymorphism of the glucocorticoid receptor gene, which has been associated with increased sensitivity to glucocorticoids. There was significant association between morning preangiography cortisol levels and the number of vessels with severe stenosis in the angiography, independently of age or sex (P = .002), and a trend for a positive correlation between morning cortisol and the IMT of the femoral artery (P = .057). Bcl1 G allele homozygotes had a significantly higher carotid IMT (P = .005) and a nonsignificant tendency for higher waist-hip ratio (P = .059). Hyperactivity of the HPA axis in anticipation of a stressful procedure, such as angiography, may be an index of CAD severity. Chronic HPA axis hyperreactivity combined with tissue hypersensitivity to glucocorticoids may contribute to more severe atherosclerosis and CAD.

Adult↗

PubMed2006

The relative impact of different measures of adiposity on markers of early atherosclerosis.

BACKGROUND: Although there are several methods available to assess adiposity, there is still controversy on the relative clinical utility of each of these methods. This study examines the relative impact of different measures of adiposity on markers of early atherosclerosis. In particular weight changes over time have been poorly assessed in this setting. METHODS: Eighty-six healthy individuals (31 men, age 36.5+/-8.9 years) with a wide range of body-mass index (28.7+/-7.0, 18.9-57.9 kg/m2) without hypertension, diabetes or smoking were examined. In addition to waist circumference and waist-to-hip ratio self-reported weight change since adolescence was also calculated. Ultrasonography was used to measure abdominal fat layers and their ratio. Flow-mediated dilatation of the brachial artery, serum levels of intercellular adhesion molecule (sICAM-1) and mean intima-media thickness of the carotid artery were measured as markers of early atherosclerosis. RESULTS: Stepwise multivariate regression analysis showed waist circumference and waist-to-hip ratio as the only independent predictor of flow-mediated dilatation. Waist circumference and weight change but not current body-mass index were independent predictors of intima-media thickness. These correlations were not influenced by ultrasonographically measured fat layers, C-reactive protein and basal insulin resistance. Body-mass index and weight gain were associated with sICAM-1 but not independently of basal insulin resistance and C-reactive protein. CONCLUSIONS: Waist circumference and weight gain were the strongest predictors of early atherosclerosis in a population of apparently healthy adults. The ultrasonographically measured fat layers did not provide additional information in this population.

Abdominal Fat↗

PubMed2006

Increased prevalence of VNTR III of the insulin gene in women with gestational diabetes mellitus (GDM).

OBJECTIVE: The VNTR polymorphism in the promoter region of the insulin gene (INS-VNTR) affects transcription rate and has been associated with insulin resistance and DM2. Gestational diabetes mellitus (GDM) is a multifactorial disorder, where both impaired insulin secretion and action may be involved. The aim of the study was to examine the distribution of the INS-VNTRs in women with GDM and to investigate possible associations with features of beta cell function and glycaemic control in this population. METHODS: One hundred and sixty-one women with GDM and 111 normal pregnant women (n) were genotyped for INS-VNTR during the 24th-32nd pregnancy week. Glucose and insulin levels were determined during the diagnostic OGTT. The majority of the previous GDM women were also examined at 3-6 months post-partum. RESULTS: VNTR class III/III genotype was significantly more frequent in the GDM group 8.7% versus 2.7%, p=0.02 giving an OR of 3.97 (1.1-14.29). An increased frequency of the VNTR class III allele was found in those GDM women who required insulin for treatment compared to those controlled with diet alone (12.4% versus 4%, p<0.001). Basal insulin levels tended to be lower in GDM women homozygous for the class III allele without reaching statistical significance (p=0.09). CONCLUSIONS: The INS-VNTR class III is more frequent in women who develop GDM, and may be associated with decreased ability of the beta cell to meet the increased insulin requirements as reflected by the need for insulin supplementation for adequate glycaemic control.

Adult↗

PubMed2006

Abnormal endothelial function in female patients with hypothyroidism and borderline thyroid function.

BACKGROUND: It has been suggested that hypothyroidism is associated with an increased risk for cardiovascular disease. The aim of this study was to assess non-invasively NO-dependent endothelial function of resistance arteries in subjects with hypothyroidism of varying severity. METHODS: Ninety-six female subjects (aged: 42+/-13 years) comprised the study population. Subjects were divided into five groups based on TSH levels at presentation: Group 0 (n=23) with TSH: 0.3-2.0 microU/ml, Group 1 (n=22) with TSH: 2.1-4.0 microU/ml (upper normal), Group 2 (n=18) with TSH: 4.1-10 microU/ml (subclinical hypothyroidism), Group 3 (n=22) with TSH >10 microU/ml (overt hypothyroidism). One additional group with well-controlled hypothyroidism on L-thyroxine therapy (Group 4, n=11, TSH: 0.3-2.0 microU/ml) was also studied. Endothelial function of resistance arteries was assessed by measuring forearm blood flow response during reactive hyperemia utilizing venous occlusion strain-gauge plethysmography. RESULTS: Duration of reactive hyperemia was significantly different among groups of subjects with varying hypothyroidism (83.7+/-58.3 s, 53.2+/-35.7 s, 52.8+/-47.5 s, 12.9+/-13.3 s and 69.5+/-26.2 s in Groups 0, 1, 2, 3 and 4, respectively, p<0.001, ANOVA). Duration of reactive hyperemia was significantly shorter in subjects with upper normal TSH values (Group 1) compared to controls (53.2+/-35.7 s vs. 83.7+/-58.3 s, p=0.013), while it was comparable to that of subjects with subclinical hypothyroidism (Group 2) (52.8+/-47.5 s). However, duration of reactive hyperemia in Group 1 was significantly longer compared to Group 3 (overt hypothyroidism) (53.2+/-35.7 s vs. 12.9+/-13.3 s, p=0.002). Similarly, duration of reactive hyperemia in subjects with subclinical hypothyroidism was significantly longer compared to subjects with overt hypothyroidism (52.8+/-47.5 s vs. 12.9+/-13.3 s, p=0.003). Duration of reactive hyperemia in Group 4 (well-controlled hypothyroidism on L-thyroxine therapy) did not differ significantly compared to controls. There was a highly significant linear correlation between duration of reactive hyperemia and TSH (r=-0.383, p<0.001). CONCLUSION: Endothelial dysfunction was detected in the microvasculature of patients with hypothyroidism. Duration of reactive hyperemia decreased with increasing TSH levels. Since endothelial dysfunction is a factor leading to atherosclerosis, this abnormality may partly explain predisposition of patients with thyroid failure to cardiovascular disease.

Adult↗

PubMed2006

Severity of cardiovascular disease in women: relation with exposure to endogenous estrogen.

OBJECTIVES: Coronary artery disease (CAD) is more common in men than in women. Endogenous sex steroids may be the main factor responsible, as long-term estrogen action appears to be protective. The aim of the study was to investigate the predisposing factors responsible for the severity of CAD in women. METHODS: One hundred and eight women (100 menopausal) undergoing coronary angiography were studied. Reproductive function was recorded. The severity of CAD was assessed by the number of arteries with severe stenosis, the presence of angina and myocardial infarctions (MI). RESULTS: The time since menopause (TSM) was significantly longer in women with angina and with MIs compared to those without (20.3+/-8.7 years versus 15.8+/-8.7 years and 22.6+/-8.6 years versus 18.1+/-8.9 years, p<0.05), independently of chronological age. The age at menopause was significantly younger in women who had 2 MIs compared to those with 1 or 0 MI (41.5+/-3.5, 47.5+/-5.3 and 48.4+/-5.4 years, respectively; p=0.04); the total duration of menstrual cyclicity was inversely related to the number of MIs (35.6+/-5.8, 34.2+/-5.3 and 28.3+/-3.3 years, 0, 1 and 2 MIs, respectively; p=0.03). CONCLUSIONS: The severity of CAD in women referred for coronary angiography is correlated with measures of exposure to endogenous estrogen. Both the TSM and the age at menopause are aggravating factors for MI, independently of age. There is an independent protective effect of the duration of estrogen exposure on the number of MIs; this has not been reported before and supports the protective role of the length of exposure to endogenous estrogen, especially for the occurrence of MI in this selected group of women.

Adult↗

PubMed2006

Gonadotrophin resistance.

Gonadotrophin resistance is caused by inactivating mutations in receptors (Rs) of the two gonadotrophins, i.e. luteinizing hormone (LH) and follicle-stimulating hormone (FSH), presenting as hypergonadotrophic hypogonadism and infertility/subfertility in both sexes. These conditions are extremely rare, but must be kept in mind upon differential diagnosis of disorders of sexual maturation, hypogonadism and infertility. In 46,XY individuals inactivation of LHR causes a disturbance in male-type sexual differentiation that ranges from male pseudohermaphroditism (complete lack of genital masculinization) to mild conditions such as cryptorchidism and hypospadias, depending on completeness of the receptor inactivation. In women, the phenotype is milder, presenting mainly as anovulatory amenorrhoea and hypo-oestrogenization. Inactivation of FSHR causes in otherwise normally masculinized men small testis size and variably reduced spermatogenesis, but not azoospermia or absolute infertility. In women the phenotype is more severe, with primary or early secondary amenorrhoea, arrested follicular maturation and anovulatory infertility. Incomplete forms with milder phenotype and partial responsiveness to FSH have also been described. Although gonadotrophin resistance is a very rare condition, its correct diagnosis is important for the selection of adequate treatment.

Amino Acid Sequence↗

PubMed2006

Hypothyroidism as a protective factor in acute stroke patients.

OBJECTIVE: It has been reported that hypothyroidism is associated with better survival in elderly persons. We investigated possible associations of thyroid status with clinical outcome in patients with acute stroke. DESIGN: Retrospective analysis. PATIENTS: Consecutive patients (median age 70 years) admitted for acute stroke. MEASUREMENTS: Total T3, T4 and TSH levels. Stroke severity evaluation using the Scandinavian Stroke Scale (SSS) and the Glasgow Coma Score (GCS). Handicap and survival assessment over 12 months. RESULTS: Of 744 patients where thyroid function tests were available within the first 24 h of stroke, 13 had elevated TSH (>or= 10 microU/ml; range 10-42 microU/ml) (hypo-group), 51 had mildly elevated TSH (3.3-9.9 microU/ml) and 680 had nonelevated TSH < 3.3 microU/ml. In the hypo-group transient ischaemic attacks (TIA's) were more prevalent (46.2%) compared to the groups of mildly elevated TSH (11.8%) and nonelevated TSH (12.4%, P < 0.002). Hypo-group had more frequently an adequate level of consciousness (GCS 14-15 = fully alert): 92.3%vs 74.5% and 63.7% (P = 0.033), a milder neurological deficit (SSS score 45-58) 76.9%vs 39.2% and 38.7% (P = 0.02) compared to the other two groups, respectively, and a tendency for lower glucose levels on admission. One year outcome tended to be better with respect to survival and handicap. CONCLUSIONS: Acute stroke patients with laboratory findings compatible with pre-existing hypothyroidism on admission, appear to have better clinical presentation and outcome; we speculate that a reduced response to stress and previous TIA's, possibly related to endogenous 'preconditioning', may contribute to this phenomenon.

Acute Disease↗

PubMed2006

The adrenal gland may be a target of LH action in postmenopausal women.

OBJECTIVE: LH receptor expression and function have been demonstrated in the human adrenal cortex, but their involvement in normal adrenal function remains elusive. Because cortisol levels have been reported to be higher in postmenopausal women than in age-matched men, the aim of the present study was to investigate a possible association of adrenal function with the elevated LH levels in postmenopausal women. DESIGN AND METHODS: A group of 112 endocrinologically normal postmenopausal women (mean age 67.6, range 50-88 years) was evaluated. A basal fasting morning sample of peripheral blood was taken for the determination of LH, cortisol, dehydroepiandrosterone-sulphate (DHEA-S), oestradiol (E2), testosterone, sex hormone-binding globulin (SHBG), insulin and glucose. Information about reproductive function, anthropometric parameters and arterial blood pressure was recorded. RESULTS: The correlation of LH and cortisol was bimodally distributed, with a significant linear correlation up to the LH level of 41 U/l (n = 78, P<0.01), after which the increase of cortisol levelled off. Significant associations were also found between serum DHEA-S and LH levels (P<0.05), as well as between cortisol and testosterone (P<0.0001), but not between E2 and LH. Multivariate analysis showed that the association of cortisol with LH was independent of age and testosterone; the association of DHEA-S with LH was independent of E2, cortisol and age. Significant associations were also found between E2, testosterone and DHEA-S levels (P<0.001). CONCLUSIONS: These results indicate that adrenal cortisol and DHEA-S production may be stimulated by the highly elevated postmenopausal levels of LH; the physiological significance of this association and plausible contribution to the metabolic syndrome observed after the menopause remain to be evaluated.

Adrenal Cortex↗

PubMed2005

Arterial stiffness is increased in subjects with hypothyroidism.

BACKGROUND: The association between hypothyroidism and increased vascular resistance, arterial wall thickening and endothelial dysfunction is well recognized. The aim of the present study was to examine if hypothyroid subjects have increased arterial stiffness, a risk factor for cardiovascular morbidity and mortality. METHODS: Sixty-five subjects (59 females and 6 males) with normal thyroid function or hypothyroidism of varying degree were investigated by radial artery applanation tonometry and pulse wave analysis, for evaluation of arterial stiffness. RESULTS: Serum TSH values were positively correlated with central systolic blood pressure (r=0.258, p=0.037), central pulse pressure (r=0.316, p=0.010), augmentation pressure (r=0.299, p=0.015) and negatively with reflection time index (RTI), which indicates the pressure wave velocity (r=-0.311, p=0.012). Hypothyroid patients presented higher central systolic pressure and pulse pressure, higher augmentation pressure and lower RTI, indicating increased arterial stiffness in these subjects. RTI was independently related to age, central systolic pressure and TSH. Mild changes of arterial stiffness were observed even in subjects with TSH range 2.01-4.0 muU/ml suggesting that this group may have an early stage of mild thyroid failure. CONCLUSIONS: Hypothyroidism, even in the subclinical stage, is associated with changes in arterial stiffness. The observed abnormalities in arterial stiffness may have detrimental effects on left ventricular function and coronary perfusion in hypothyroid subjects.

Adult↗

PubMed2005

TSH may not be a good marker for adequate thyroid hormone replacement therapy.

The objective of this study was to evaluate parameters of thyroid function and indices of peripheral thyroid hormone action (such as SHBG) in patients whose hypothyroidism was considered well controlled under current criteria. Eighty-five patients with T4-treated hypothyroidism, 28 of whom had athyria, were compared with 114 normal individuals with the same TSH levels. T3 levels were significantly lower in hypothyroidism although mean T4 and fT4 levels were significantly higher. Furthermore, mean SHBG levels were significantly lower in hypothyroidism independently of age. The difference remained when stricter criteria for adequate treatment were applied (TSH < 2.5 microgU/ml). Significant negative correlations were found between logTSH and T3. The slopes of the regression lines of T3 to TSH were significantly different in the control group and the hypothyroid group: thus, for the same TSH levels, T3 levels were lower in the hypothyroid group. We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect, provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels.

Biomarkers↗

PubMed2004

Absence of the genetic variant Val79Met in human chorionic gonadotropin-beta gene 5 in five European populations.

Chorionic gonadotropin (CG) is an essential signal in establishment and maintenance of pregnancy in humans and higher primates. A G-to-A transition in exon 3 of human CGbeta gene 5, changing the naturally occurring valine residue to methionine in codon 79 (Val(79)Met) has been reported at carrier frequency 4.2% in a random population from the Midwest of the United States. The biological activity of the variant hCG was similar to that of wild-type (WT) hCG. However, the Val(79)Met beta-subunit displayed impaired ability to assemble with alpha-subunit, and the amount of hCG alpha/beta heterodimers formed and secreted by transfected cells was seriously impaired in the previous study. Because of these functional implications we found it important to study the occurrence of the Val(79)Met hCGbeta variant in other populations. By using a PCR-RFLP method, a search for the Val(79)Met hCGbeta variant was carried out on a total of 580 DNA samples from five European populations (Finland, Denmark, Greece, Germany and the UK). The results demonstrated an absence of the polymorphism in these populations. Hence, the naturally occurring variant (Val(79)Met) of the hCGbeta gene 5, found previously at high frequency in the US, is clearly less common, or absent, in the European populations studied.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMed2003

Molecular analysis of the estrogen receptor alpha gene in men with coronary artery disease: association with disease status.

BACKGROUND: The vasoprotective effects of estrogens are known to be mediated by their respective estrogen receptors (ER) alpha (ERalpha) and beta (ERbeta), which are present on the vascular wall. The amino-terminal part of the ERalpha appears to be important; genetic alterations in this region have been associated with arterial hypertension. This region has not been studied in atherosclerotic disease. In the present study, we examined the association between coronary artery disease (CAD) and alterations of the NH(2)-terminal part of ERalpha coding region. METHODS: Genomic DNA was isolated from 50 healthy men and 40 men with CAD confirmed by coronary angiography. The coding sequences of exons 1 and 2 were amplified by polymerase chain reaction (PCR) and analyzed by either denaturing gradient gel electrophoresis (DGGE) or single stranded conformational polymorphism (SSCP), or both, sequencing and restriction fragment length polymorphism (RFLP), as appropriate. In the same subjects, biochemical and vascular parameters were also determined by using the appropriate methodology. RESULTS: In exon 1, the codon 10 polymorphism was detected in both patients and healthy men either in heterozygous or homozygous form. The codon 87 polymorphism was detected mainly in homozygous form and only five individuals were heterozygotes. No mutations were found in exon 2. Statistical analysis of the allele distribution for either codon 10 or 87 between patients and healthy men showed no significant difference. In patients, the biochemical parameters were not statistically significantly different between ERalpha codon 10 genotypes or alleles. However, there was a clear effect of the TCT/TCT genotype and TCT allele on the vascular parameters whereas the right internal carotid artery (RICA) intima-media thickness was significantly associated with TCT/TCT genotype and TCT allele. CONCLUSIONS: We conclude that ERalpha genotypes play no role in the incidence of CAD disease, however, ERalpha codon 10 may be a genetic factor controlling some vessels' angiographic complications.

Adult↗

PubMedDate not supplied

Thyroid function in patients with Alzheimer disease: implications on response to anticholinesterase treatment.

Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in Alzheimer disease (AD). The aim of the present study was to explore thyroid function in patients with AD before and after acetylcholinesterase inhibition treatment to possibly identify variances in response. Thyroid function tests were evaluated in 28 AD patients and 24 age and sex-matched controls. Nineteen of the patients were reevaluated after (4 mo) treatment with donepezil. Serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), the free fractions (fT3, fT4) and thyroid autoantibodies were determined using standard methods. All subjects were clinically euthyroid. Patients presented with higher fT4 and anti-thyroperoxidase levels, as compared with the controls. Significant reduction in T4, fT3, fT4, and anti-thyroperoxidase levels were observed 4 months after treatment. Responders had higher T4 and fT4, than nonresponders, followed by significant reductions after treatment. The above, within the normal range alterations, may represent a direct effect on hormone release from the thyroid gland and/or increased conversion of T4 to T3 within the brain. Higher T4 and fT4 levels before treatment might predict a favorable response to donepezil treatment.

Aged↗

PubMedDate not supplied

Iodine 131 treatment for differentiated thyroid carcinoma in patients with end stage renal failure: dosimetric, radiation safety, and practical considerations.

BACKGROUND: Iodine 131 ablation following total thyroidectomy is considered an indispensable element of successful treatment of differentiated thyroid carcinoma (Dtc). because of the essential role of the kidneys in iodine clearance, (131)I therapy of Dtc in patients with end stage renal disease, particularly those maintained on haemodialysis, present a number of special features: the (131)I activity needs to be modified, the haemodialysis sessions need to be adjusted at the time of (131)I therapy, and there are radiation safety considerations during dialysis. there is considerable controversy over these crucial questions in the reports published so far in the literature, which concern a total of fourteen patients. OBJECTIVE: the aim of our study was to present our experience on (131)I treatment of 5 Dtc patients with end stage renal disease. DESIGN: the data of 5 Dtc patients with end stage renal disease, treated with (131)I, were retrospectively analysed; four cases were treated for remnant ablation and one for locoregional progression. In order to allow for prolonged plasma clearance of (131)I, we used a lower activity of radioiodine, reduced to roughly 40-50% of the empirically calculated activity used for normal individuals; dialysis sessions were performed immediately before and at 48 hours after (131)I administration. All patients had (131)I retention measurements performed post dialysis; in two of them some additional measurements such as iodine clearances were also performed. RESULTS: None of the patients experienced any short-term side effects, while they all had undetectable thyroglobulin levels on the first post therapy evaluation off thyroxine. (131)I elimination in the first haemodialysis was about 60%. staff incidental exposure and (131)I contamination were insignificant. CONCLUSIONS: On the basis of our experience, an empiric activity of 40-50% of that used for normal individuals appears to be effective as well as safe. these encouraging findings are discussed in relation with other reports in the literature.

Adult↗

PubMedDate not supplied

Pitutaty insufficiency. Diagnosis masked by a toxic thyroid adenoma.

A patient with undiagnosed pituitary insufficiency who also had a toxic thyroid adenoma is presented. The T3 secreted by the adenoma apparently corrected the secondary thyroid failure, but also aggravated the secondary adrenal failure and almost precipitated adrenal crisis. The diagnostic work-up in such an unusual co-existence is discussed, in particular since the clinical diagnosis of pituitary insufficiency in the elderly is not easily established.

Journal Article↗

PubMedDate not supplied

Differentiated thyroid cancer in Greece: 1963-2000. Relation to demographic and environmental factors.

Thyroid cancer (TC) is a relatively rare neoplasia, accounting for 0.35%-0.38% of total deaths due to cancer in Greece. Environmental/nutritional factors are considered to play a role in its pathogenesis. The aim of this retrospective review of patients' histories from three of the largest specialized centers in southern Greece, from 1963 to 2000, was to assess associations of differentiated TC (DTC) with demographic and environmental factors. The total number of DTC cases was 610 (119 men or 19.5%, and 491 women or 80.5%), of which 442 cases (72%) were papillary DTCs (pure papillary type: 54.5% and mixed papillary-follicular type: 45.5%), 90 cases (15%) were of the pure follicular type, while 78 cases (13%) were classified as suspicious lesions, requiring follow-up, but not definitively carcinomas. The mean age (+/-SD) at diagnosis for all groups was 42.3+/-1.3 years. Fifty percent of the patients were living in Athens at the time of diagnosis. The diagnosis was delayed in patients living in villages compared to those living in cities (mean age +/-SD): 43.7+/-14.1 years and 40.9+/-13.8 years, respectively; p<0.05, t-test). Patients who were born in iodine-sufficient areas (n=162/193, 84%; X(2)=5.09, P=0.02) had papillary carcinoma more frequently compared to patients who were born in previously iodine-deficient areas (n=159/214, 74%). During the observation period (1963-2000) there appeared to be three different trends in the incidence of newly diagnosed cases: a random variation during the first nine years and a steady increase during the second two decades (starting before the Chernobyl nuclear accident) followed by a significant decline during the last few years. We suggest that the observed variations in the incidence of DTC could be related to the availability of diagnostic tools as well as to increased awareness.

Journal Article↗

PubMedDate not supplied

Structure-function relationships of glycoprotein hormones; lessons from mutations and polymorphisms of the thyrotrophin and gonadotrophin subunit genes.

The pituitary glycoprotein hormones thyrotrophin (thyroid-stimulating hormone, TSH), lutrophin (luteinising hormone, LH) and follitrophin (follicle-stimulating hormone, FSH), as well as the placental choriongonadotrophin (human chorionic gonadotrophin, hCG) are composed of a common alpha-subunit and a specific beta-subunit, coupled by noncovalent interactions. Formation of alpha/beta dimers is necessary for their biological function. Mutations and polymorphisms in the genes encoding these hormones are relatively rare, apparently because of their vital role in the regulation of reproductive and metabolic functions. However, a few genetic alterations in these genes have been identified and offer valuable, novel information about the structure-function relationships of the glycoprotein hormones. The purpose of this review is to present the known mutations and polymorphisms of the TSH, LH and FSH subunit genes and describe their functional consequences as causative factors of hypothyroidism and hypogonadism. Because genuinely inactivating TSH and gonadotrophin mutations are extremely rare, they are unlikely to be encountered in clinical practice. However, some of the polymorphisms are relatively common and because they may change the immunoreactivity of the hormone, they may result in aberrant laboratory findings.

Journal Article↗