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Papers by Eleni Kousta

Research paper thumbnail of Low birth weight and obesity are associated with increased androgen levels among children with premature adrenarche

Research paper thumbnail of Χορήγηση βιοσυνθετικής αυξητικής ορμόνης σε παιδιά με χρόνια νεφρική ανεπάρκεια τελικού σταδίου που βρίσκονται σε υποκατάσταση

Research paper thumbnail of Premature Adrenarche Leads to Polycystic Ovary Syndrome?: Long-Term Consequences

Annals of the New York Academy of Sciences, 2006

Premature adrenarche is characterized by an early increase in adrenal androgen production that re... more Premature adrenarche is characterized by an early increase in adrenal androgen production that results in the development of pubic hair before the age of 8 years in girls and 9 years in boys, with or without axillary hair, and with no other signs of sexual development. Premature adrenarche has no adverse effects on the onset and progression of gonadarche and final height. However, it can no longer be considered a benign condition as it has been associated with hyperinsulinemia, dyslipidemia, and obesity already in the prepubertal period and polycystic ovary syndrome (PCOS) at adolescence. Furthermore, a possible association between premature adrenarche and metabolic and endocrine abnormalities with low birth weight has been postulated. PCOS, as recently redefined, is the most common endocrine disorder to affect women of reproductive age and has been associated with increased risk for type 2 diabetes and increased prevalence of cardiovascular risk factors at an earlier age than expected. Premature adrenarche and PCOS share similar metabolic disturbances. It may be that metabolic abnormalities start very early in life during the prenatal or prepubertal period and premature adrenarche may be a forerunner of PCOS and the metabolic syndrome in some girls. Large long-term epidemiological studies are needed to allow clear association of the two conditions and assessment of the risk of disease in later life.

Research paper thumbnail of Modern use of clomiphene citrate in induction of ovulation

Human Reproduction Update, 1997

Introduction 359 The use of clomiphene citrate 360 LH hypersecretion, ovarian steroids and pregna... more Introduction 359 The use of clomiphene citrate 360 LH hypersecretion, ovarian steroids and pregnancy outcome 361 Endocrine and non-endocrine factors affecting outcome of induction of ovulation with clomiphene citrate: St. Mary's Hospital series 362 Conclusions 364 References 364 Clomiphene citrate is the treatment of first choice in the management of infertility in normally oestrogenized, anovulatory women (WHO group II). The majority of women with 'pure' anovulatory infertility respond to treatment with clomiphene citrate. The rates of pregnancy and miscarriage are close to those expected in a normal fertile population. Basal hormone concentrations do not predict outcome. An increased body mass index is the only factor which is consistently associated with a decreased response to clomiphene citrate; it follows therefore, that weight reduction should be an important part of therapy in anovulatory women. According to our data, only an increased luteinizing hormone value immediately post clomiphene citrate predicted an adverse pregnancy outcome in women who conceived. Clomiphene citrate, along with other ovulation induction therapies, can cause multiple follicular development, with a risk of ovarian hyperstimulation and multiple pregnancy. Ultrasound monitoring of treatment is important in order to choose the appropriate dose of clomiphene citrate in subsequent cycles and to minimize the risks of hyperstimulation and multiple pregnancy. When couples with other factors contributing to subfertility are excluded, the cumulative conception rate continues to rise after 6 months of treatment with clomiphene citrate, reaches a plateau by treatment cycle 12 and approaches that of the normal population. It has been reported that prolonged use of clomiphene citrate may be associated with an increased risk of a borderline or invasive ovarian tumour. Taking into consideration these observations, we recommend that anovulatory women responsive to clomiphene citrate should be treated for at least 6 cycles before considering more complex or invasive methods of ovulation induction, and that treatment should probably be limited to a maximum of 12 cycles.

Research paper thumbnail of Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility

Research paper thumbnail of Hormones 2005, 4(4):227-231

Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter a... more Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter and brief literature review

Research paper thumbnail of Screening Genes Implicated in Energy Balance for Mutations in Subjects with Diabetes and Prediabetic States

Research paper thumbnail of Long-Term Metabolic Consequences in Patients with a History of Gestational Diabetes

Current Pharmaceutical Design, 2020

Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelin... more Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by ethnicity and its rise is mainly attributed to increasing maternal obesity and age. Gestational diabetes mellitus has important long-term implications, including gestational diabetes recurrence, increased risk for developing type 2 diabetes, metabolic syndrome and cardiovascular disease for the mother. Gestational diabetes mellitus may be viewed as a chronic metabolic disorder that is identified in women during gestation and may provide a unique opportunity for the early identification and primary prevention of type 2 diabetes mellitus and cardiovascular disease in these women. In this mini-review, the evolution of screening tests for gestational diabetes and guidelines a...

Research paper thumbnail of Serum Bisphenol A concentrations in men with idiopathic infertility

Food and Chemical Toxicology, 2019

Background: Bisphenol A (BPA) has been associated with male reproductive dysfunction. However, fe... more Background: Bisphenol A (BPA) has been associated with male reproductive dysfunction. However, few studies have assessed BPA according to the cause of male infertility. Aim: To investigate serum BPA concentrations in infertile men according to infertility cause. Patients and Methods: Men with infertility (n=55) [non-obstructive azoospermia (n=23), cryptorchidism (n=12), varicocele (n=20)] compared with fertile men (n=25). Serum BPA concentrations were measured along with clinical and hormonal assessment. Results: BPA was detected in all men, with no difference between infertile and control groups [median (IQR) 0.19 (0.45) vs. 0.18 (0.28) ng/ml, p=0.689] or among the infertility cause [azoospermia 0.30 (0.69), cryptorchidism 0.12 (0.39), varicocele 0.17 (0.23) ng/ml, p=0.316]. High concentrations of BPA (>3 ng/ml) were observed only in infertile men. Α negative correlation was observed between ΒΡΑ concentrations and AMH (r=-0.320, p<0.01). Conclusions: Although male infertility cannot be attributed to exposure to BPA, high concentrations of BPA could contribute to infertility.

Research paper thumbnail of Growth hormone deficiency in a patient with autoimmune polyendocrinopathy type 2

Hormones (Athens, Greece)

Autoimmune polyglandular syndrome (APs) type 2 is characterized by the presence of Addison's ... more Autoimmune polyglandular syndrome (APs) type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus and is rare in children. A 12.5 yr old prepubertal boy presented with symptoms related to Addison's disease and a large goiter. He was euthyroid with positive thyroid antibodies, low cortisol, aldosterone and very high adrenocorticotropin (ActH) and renin levels. Growth hormone (GH) secretion and an MrI scan of the pituitary were normal. He was started on hydrocortisone, fludrocortisone and subsequently on L thyroxine. Eighteen months later, decreased growth rate was noted and GH deficiency was detected, apparently secondary to autoimmune hypophysitis. Interestingly, he did not develop any other pituitary hormone deficiencies. He was started on GH therapy and had a good treatment response in the next 3 years. the combination of adrenal and thyroid insufficiencies with autoimmune hypophysitis is a ...

Research paper thumbnail of Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter. Brief literature review

HORMONES, 2005

Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter i... more Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter is a rare entity. We present a 27-year old asymptomatic woman with a recent history of a painless mass in the left side of her lower neck. Thyroid function tests were normal. An ultrasound of her neck showed a multinodular goiter and a 3.4 cm solid mass in the left lower cervical area. These findings were confirmed by an MRI scan of her neck. The Tc99m Pertechnetate scan showed the presence of a functioning area under the left lobe of the thyroid gland. The patient underwent surgery. The cervical mass was identified as a structure separate from the left lobe of the thyroid, without any attachments to the body of the gland and was uniformly resected. A subtotal thyroidectomy was also performed. The histology revealed that the separate structure represented ectopic thyroid tissue. The patient had an uneventful postoperative recovery, subsequent to which she was euthyroid and had normal calcium levels.

Research paper thumbnail of Early metabolic defects following gestational diabetes in three ethnic groups of anti-GAD antibodies negative women with normal fasting glucose

HORMONES, 2007

ObJEctIVE: to characterise early metabolic abnormalities and the impact of ethnicity following ge... more ObJEctIVE: to characterise early metabolic abnormalities and the impact of ethnicity following gestational diabetes mellitus (GDM). DEsIGN: Women with a history of GDM belonging to three different ethnic groups were evaluated. Using the insulin-modified, frequently-sampled intravenous glucose tolerance test (FsIVGtt) and HOMA we studied 34 European, 16 south Asian and 10 Afro-caribbean women with normal fasting glucose following GDM and 44 European, 16 south Asian and 19 Afro-caribbean controls to assess insulin action and secretion. rEsULts: European post-GDM women had lower insulin sensitivity by FsIVGtt [0.6 (0.1-5.1) vs 1.5 (0.8-2.8) x10-4 •min-1 •pmol-1 •l-1 , p=0.010, adjusted for bMI p=0.054] and by HOMA [72(22-235) vs 153(55-421)%, p=0.004, adjusted for BMI p=0.006], and reduced β-cell function [lower disposition index 0.05(0.01-0.40) vs 0.11(0.05-0.25)min-1 , p=0.017] compared with controls. South Asian post-GDM women had decreased β-cell function [lower HOMA (%B) (73 (37-147) vs 124 (59-262) %, p=0.048 and acute insulin response to glucose (463 (131-1639) vs 1039 (393-2748) pmol/l h, p=0.052] than controls. Afro-caribbean post-GDM women had lower glucose disappearance rate [1.3(0.6-2.8) vs 2.6 (1.8-3.8) 10-2 /min, p=0.003] than controls, suggesting subtle glucose intolerance. cONcLUsIONs: Women with a history of GDM of three different ethnic groups, even in the presence of normal fasting glucose, display a range of metabolic abnormalities, including β-cell dysfunction with variable insulin resistance. These derangements may be influenced by ethnicity.

Research paper thumbnail of Polycystic ovary syndrome. Revised diagnostic criteria and long-term health consequences

HORMONES, 2005

The diagnostic criteria for polycystic ovary syndrome (PCOS) have recently been revised. The poly... more The diagnostic criteria for polycystic ovary syndrome (PCOS) have recently been revised. The polycystic ovarian morphology has been introduced as part of the criteria and an international consensus has been achieved providing the basis for future research and collaboration. It is now accepted that polycystic ovary syndrome has important long-term health implications, including metabolic disorders and increased risk factors for cardiovascular disease. The overall risk of developing type 2 diabetes among women with PCOS was found to be increased 3-7 times. Women with PCOS have increased levels of cardiovascular risk factors: insulin resistance, obesity, dyslipidaemia, hypertension and markers of abnormal vascular function. However, the level of risk for cardiovascular disease remains uncertain. The limited epidemiological data available to date have shown no increase in cardiovascular events although the incidence of cerebrovascular events was increased. The evidence for an increased risk for endometrial carcinoma among women with PCOS is limited. Long-term epidemiological studies of women with well defined PCOS are needed in order to assess the risk of long-term health consequences, to identify the subgroups among PCOS women who need to be targeted and to determine the timing and nature of measures for intervention and prevention.

Research paper thumbnail of Effects of growth hormone treatment on very-low-density lipoprotein apolipoprotein B100 turnover in adult hypopituitarism

Metabolism, 2000

Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-de... more Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels. Recent studies have shown that such patients exhibit increased hepatic secretion of VLDL apolipoprotein B100 (VLDL apo B100). To examine the effects of growth hormone (GH) replacement on VLDL apo B100 turnover, 13 GH-deficient hypopituitary patients (8 women and 5 men; aged 47 _+ 3 years, mean-+ SEM; body mass index [BMI], 30-+ 2 kg/m z) entered a double-blind placebo-controlled study for 6 months (GH 0.125 IU/kg/wk for 4 weeks, and then 0.25 IU/kg/wk). GH was subsequently used in all patients for a further 6 months. A 5-hour [1-13C] leucine infusion was administered at baseline and at 6 months. The secretion rate of VLDL apo B100 was derived by kinetic analysis following quantitation of isotopic enrichment by gas chromatography/mass spectrometry. The GH-treated group (6 patients) demonstrated a similar fractional secretion rate (FSR) for VLDL apo B100 at 0 and 6 months. The pool size and absolute secretion rate (ASR) also were unaffected significantly by GH therapy. No significant changes were observed in the placebo group (7 patients). Treatment with GH for 6 months caused an increase in the high-density lipoprotein (HDL) cholesterol concentration (13 patients, 1.27-+ 0.13 v 1.16 _+ 0.10 mmol/L, respectively, P = .05), whereas total cholesterol and triglyceride concentrations did not change. Nonesterified fatty acids (NEFAs) increased during GH therapy (471 _ 43 i~mol/L at 6 months v 349-49 i~mol/L at baseline, P < .0005). The data suggest that GH does not affect VLDL apo B100 turnover in a significant way.

Research paper thumbnail of Pleiotropic Genetic Syndromes with Developmental Abnormalities Associated with Obesity

Journal of Pediatric Endocrinology and Metabolism, 2009

Childhood obesity is a common and complex problem that may persist in adulthood. It may present a... more Childhood obesity is a common and complex problem that may persist in adulthood. It may present as a component of genetic syndromes associated with dysmorphic features, developmental abnormalities, mental retardation and/or learning disabilities and often neuroendocrine dysfunction. Although the chromosomal abnormalities of these rare syndromes are already known, the specific genetic and pathophysiological mechanisms leading to the distinct phenotypes and obesity still remain unclarified. New exciting genetic pathways contributing to syndrome phenotype and leading to obesity have recently been identified. Prader-Willi syndrome is caused by loss of expression of the C/D box HBII-84 cluster of snoRNAs. Dysfunction of the primary cilium, thought to have important signalling functions, may contribute to disease phenotype and obesity in Bardet-Biedl, Alstrom and Carpenter syndromes. In this mini-review current knowledge of clinical and genetic characteristics is summarized as well as the pathogenesis of these syndromes with special emphasis on the pathogenesis of obesity.

Research paper thumbnail of Results of thyroxine therapy on thyroid nodules size in children with Hashimoto's thyroiditis

Endocrine …, 2008

... Elvira Posaghidou, Eleni Kousta, Petros Papachilleos, Aphroditi Kitsopoulou, Marina Vakaki, A... more ... Elvira Posaghidou, Eleni Kousta, Petros Papachilleos, Aphroditi Kitsopoulou, Marina Vakaki, Aspasia Fotinou, Dimitris Ioanidis, Asteroula Papathanasiou &amp; Charalambos Hadjiathanasiou. Department of Endocrinology, Children&#x27;s Hospital &#x27;P.and A. Kyriakou&#x27;, Athens, Greece. ...

Research paper thumbnail of Elevation of soluble E-selectin levels following gestational diabetes is restricted to women with persistent abnormalities of glucose regulation

Clinical Endocrinology, 2002

Increased levels of the soluble adhesion molecule sE-selectin have been reported in normoglycaemi... more Increased levels of the soluble adhesion molecule sE-selectin have been reported in normoglycaemic women with previous gestational diabetes but not in other groups at increased risk of future type 2 diabetes. To explore the basis for these discrepant findings, we studied the relationship between sE-selectin and glucose regulation in a large group of women with previous gestational diabetes. Comparison of sE-selectin levels between a study cohort ascertained on the basis of recent gestational diabetes and suitable control subjects. One hundred and forty women with recent gestational diabetes (104 European, 20 South Asian and 16 Afro-Caribbean) and 125 normoglycaemic control women (90 European, 19 South Asian and 16 Afro-Caribbean). sE-selectin, fasting lipids, insulin and current glucose regulation status. There was no overall difference in sE-selectin levels between women with a history of gestational diabetes and control women among the 3 ethnic groups. European post-GDM women with abnormal glucose regulation postpartum (n = 30) had higher sE-selectin than control women (67 (54-91) ng/ml vs. 57 (43-75) ng/ml, P = 0.049). There was no difference in sE-selectin between normoglycaemic European women with a history of gestational diabetes (n = 74) and control women, even though the former displayed metabolic abnormalities predictive of diabetes. In those European post-GDM women with normal glucose regulation postpartum, sE-selectin levels were negatively correlated with time since delivery (r = -0.25, P = 0.04), suggesting that the previously described elevation of sE-selectin following GDM pregnancies slowly resolves postpartum. There was no correlation between sE-selectin levels and features of insulin resistance. In contrast to previous findings, this larger study does not support a role for sE-selectin as a marker, independent of prevailing glucose levels, of early metabolic abnormalities or future diabetes risk in women with previous gestational diabetes.

Research paper thumbnail of The effects of growth hormone replacement therapy on overnight metabolic fuels in hypopituitary patients

Clinical Endocrinology, 2000

ABSTRACT Hypopituitary adults on conventional replacement have low concentrations of metabolic fu... more ABSTRACT Hypopituitary adults on conventional replacement have low concentrations of metabolic fuels throughout the night, possibly related to GH deficiency or to decreased cortisol levels overnight. We investigated whether GH replacement corrects the overnight fuel deficiency. We measured circulating levels of metabolic fuels: glucose, non-esterified fatty acids (NEFA), glycerol and 3-hydroxybutyrate (3-OHB) and insulin concentrations over 24 h (from 0730 h to 0700 h) in hypopituitary adults before and after GH treatment in a randomized double-blind placebo-controlled trial of 3 months&#39; duration. Thirteen hypopituitary patients, 8 women and 5 men, were studied. Six patients (4 women and 2 men) received GH and 7 patients (4 women and 3 men) were allocated to receive placebo. There was no difference in fasting (0730 h), area under the curve (AUC) between 2400 h and 0700 h (overnight) and AUC over 24 h for plasma glucose, 3-OHB, glycerol and insulin concentrations as a result of GH treatment. Fasting and overnight AUC for NEFA were significantly higher on GH treatment ((mean +/- SEM) 243 +/- 29 vs. 446 +/- 90 micromol/l, P = 0.03, 1522 +/- 208 vs. 2167 +/- 123 micromol/l H, P = 0.046, respectively), but AUC over 24 h was not affected significantly. No significant changes in any fuel were seen in the placebo group. The changes in fasting, overnight and 24 h AUC for glucose, 3-OHB, glycerol and insulin levels with GH and with placebo for 3 months were similar. The changes in fasting and overnight AUC for NEFA before and after 3 months were significantly different in the group treated with GH vs. the group treated with placebo (median (lower-upper quartile) 104 (90-276) vs. -89 (-98 to 26) micromol/l, P = 0.002; 633 (263-967) vs. -895 (-1379 to -494) micromol/l h, P = 0.002, respectively), but the changes in 24-h AUC for NEFA were not significant between the two groups. GH replacement in hypopituitary adults increases fasting and overnight (between 2400 h and 0700 h) non-esterified fatty acid concentrations, consistent with the known lipolytic effect of GH. GH did not influence the concentrations of other metabolic fuels or insulin.

Research paper thumbnail of Prevalence and features of pancreatic islet cell autoimmunity in women with gestational diabetes from different ethnic groups

BJOG: An International Journal of Obstetrics and Gynaecology, 2001

Objective To assess the prevalence and characteristics of islet cell autoimmunity amongst women w... more Objective To assess the prevalence and characteristics of islet cell autoimmunity amongst women with gestational diabetes selected from South Asian and Afro-Caribbean as well as European populations. Design Cross-sectional retrospective survey of subject cohort. Population Three hundred and twenty-one women with a recent history of gestational diabetes (173 European, 86 South Asian and 62 Afro-Caribbean), a median (range) of 22 (1-150) months postpartum. Results Antibodies to Glutamic acid decarboxylase were found in 13 (4%) of these women. There was no difference in the prevalence of anti-glutamic acid decarboxylase positivity between the three ethnic groups (European 4.6%, South Asian 3.5%, Afro-Caribbean 3.2%). Anti-glutamic acid decarboxylase positive women were leaner than anti-glutamic acid decarboxylase negative women (body mass index, median (upper-lower quartile) 23.9 (22.5±26.7) vs 26.6 (23.4-30.5)kg/m 2 , P 0.03, P 0.049 allowing for ethnicity). There was no difference between glutamic acid decarboxylase-positive and glutamic acid decarboxylase-negative women for age, family history of diabetes, waist/hip ratio, prevalence of insulin treatment during pregnancy, postpartum glucose status, lipid pro®le and indices of insulin action and beta-cell function. Conclusions Markers of islet cell autoimmunity are found as frequently in gestational diabetes women of South Asian and Afro-Caribbean origin, as they are in European subjects. Identi®cation of future risk of type 1 diabetes is relevant to the planning of clinical management and intervention strategies in women with gestational diabetes of all major ethnic groups.

Research paper thumbnail of Endocrine Indices of PCOS in Women with Polycystic Ovaries but without Diagnostic Features of PCOS: A Study of an Infertility Clinic Population

Open Journal of Obstetrics and Gynecology, 2020

Background: The presence of polycystic ovarian morphology (PCO) without the other characteristics... more Background: The presence of polycystic ovarian morphology (PCO) without the other characteristics of the polycystic ovarian syndrome (PCOS) is insufficient for the diagnosis of PCOS and there is little justification for follow up in endocrine clinics for women with PCO morphology alone.

Research paper thumbnail of Low birth weight and obesity are associated with increased androgen levels among children with premature adrenarche

Research paper thumbnail of Χορήγηση βιοσυνθετικής αυξητικής ορμόνης σε παιδιά με χρόνια νεφρική ανεπάρκεια τελικού σταδίου που βρίσκονται σε υποκατάσταση

Research paper thumbnail of Premature Adrenarche Leads to Polycystic Ovary Syndrome?: Long-Term Consequences

Annals of the New York Academy of Sciences, 2006

Premature adrenarche is characterized by an early increase in adrenal androgen production that re... more Premature adrenarche is characterized by an early increase in adrenal androgen production that results in the development of pubic hair before the age of 8 years in girls and 9 years in boys, with or without axillary hair, and with no other signs of sexual development. Premature adrenarche has no adverse effects on the onset and progression of gonadarche and final height. However, it can no longer be considered a benign condition as it has been associated with hyperinsulinemia, dyslipidemia, and obesity already in the prepubertal period and polycystic ovary syndrome (PCOS) at adolescence. Furthermore, a possible association between premature adrenarche and metabolic and endocrine abnormalities with low birth weight has been postulated. PCOS, as recently redefined, is the most common endocrine disorder to affect women of reproductive age and has been associated with increased risk for type 2 diabetes and increased prevalence of cardiovascular risk factors at an earlier age than expected. Premature adrenarche and PCOS share similar metabolic disturbances. It may be that metabolic abnormalities start very early in life during the prenatal or prepubertal period and premature adrenarche may be a forerunner of PCOS and the metabolic syndrome in some girls. Large long-term epidemiological studies are needed to allow clear association of the two conditions and assessment of the risk of disease in later life.

Research paper thumbnail of Modern use of clomiphene citrate in induction of ovulation

Human Reproduction Update, 1997

Introduction 359 The use of clomiphene citrate 360 LH hypersecretion, ovarian steroids and pregna... more Introduction 359 The use of clomiphene citrate 360 LH hypersecretion, ovarian steroids and pregnancy outcome 361 Endocrine and non-endocrine factors affecting outcome of induction of ovulation with clomiphene citrate: St. Mary's Hospital series 362 Conclusions 364 References 364 Clomiphene citrate is the treatment of first choice in the management of infertility in normally oestrogenized, anovulatory women (WHO group II). The majority of women with 'pure' anovulatory infertility respond to treatment with clomiphene citrate. The rates of pregnancy and miscarriage are close to those expected in a normal fertile population. Basal hormone concentrations do not predict outcome. An increased body mass index is the only factor which is consistently associated with a decreased response to clomiphene citrate; it follows therefore, that weight reduction should be an important part of therapy in anovulatory women. According to our data, only an increased luteinizing hormone value immediately post clomiphene citrate predicted an adverse pregnancy outcome in women who conceived. Clomiphene citrate, along with other ovulation induction therapies, can cause multiple follicular development, with a risk of ovarian hyperstimulation and multiple pregnancy. Ultrasound monitoring of treatment is important in order to choose the appropriate dose of clomiphene citrate in subsequent cycles and to minimize the risks of hyperstimulation and multiple pregnancy. When couples with other factors contributing to subfertility are excluded, the cumulative conception rate continues to rise after 6 months of treatment with clomiphene citrate, reaches a plateau by treatment cycle 12 and approaches that of the normal population. It has been reported that prolonged use of clomiphene citrate may be associated with an increased risk of a borderline or invasive ovarian tumour. Taking into consideration these observations, we recommend that anovulatory women responsive to clomiphene citrate should be treated for at least 6 cycles before considering more complex or invasive methods of ovulation induction, and that treatment should probably be limited to a maximum of 12 cycles.

Research paper thumbnail of Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility

Research paper thumbnail of Hormones 2005, 4(4):227-231

Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter a... more Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter and brief literature review

Research paper thumbnail of Screening Genes Implicated in Energy Balance for Mutations in Subjects with Diabetes and Prediabetic States

Research paper thumbnail of Long-Term Metabolic Consequences in Patients with a History of Gestational Diabetes

Current Pharmaceutical Design, 2020

Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelin... more Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by ethnicity and its rise is mainly attributed to increasing maternal obesity and age. Gestational diabetes mellitus has important long-term implications, including gestational diabetes recurrence, increased risk for developing type 2 diabetes, metabolic syndrome and cardiovascular disease for the mother. Gestational diabetes mellitus may be viewed as a chronic metabolic disorder that is identified in women during gestation and may provide a unique opportunity for the early identification and primary prevention of type 2 diabetes mellitus and cardiovascular disease in these women. In this mini-review, the evolution of screening tests for gestational diabetes and guidelines a...

Research paper thumbnail of Serum Bisphenol A concentrations in men with idiopathic infertility

Food and Chemical Toxicology, 2019

Background: Bisphenol A (BPA) has been associated with male reproductive dysfunction. However, fe... more Background: Bisphenol A (BPA) has been associated with male reproductive dysfunction. However, few studies have assessed BPA according to the cause of male infertility. Aim: To investigate serum BPA concentrations in infertile men according to infertility cause. Patients and Methods: Men with infertility (n=55) [non-obstructive azoospermia (n=23), cryptorchidism (n=12), varicocele (n=20)] compared with fertile men (n=25). Serum BPA concentrations were measured along with clinical and hormonal assessment. Results: BPA was detected in all men, with no difference between infertile and control groups [median (IQR) 0.19 (0.45) vs. 0.18 (0.28) ng/ml, p=0.689] or among the infertility cause [azoospermia 0.30 (0.69), cryptorchidism 0.12 (0.39), varicocele 0.17 (0.23) ng/ml, p=0.316]. High concentrations of BPA (>3 ng/ml) were observed only in infertile men. Α negative correlation was observed between ΒΡΑ concentrations and AMH (r=-0.320, p<0.01). Conclusions: Although male infertility cannot be attributed to exposure to BPA, high concentrations of BPA could contribute to infertility.

Research paper thumbnail of Growth hormone deficiency in a patient with autoimmune polyendocrinopathy type 2

Hormones (Athens, Greece)

Autoimmune polyglandular syndrome (APs) type 2 is characterized by the presence of Addison's ... more Autoimmune polyglandular syndrome (APs) type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus and is rare in children. A 12.5 yr old prepubertal boy presented with symptoms related to Addison's disease and a large goiter. He was euthyroid with positive thyroid antibodies, low cortisol, aldosterone and very high adrenocorticotropin (ActH) and renin levels. Growth hormone (GH) secretion and an MrI scan of the pituitary were normal. He was started on hydrocortisone, fludrocortisone and subsequently on L thyroxine. Eighteen months later, decreased growth rate was noted and GH deficiency was detected, apparently secondary to autoimmune hypophysitis. Interestingly, he did not develop any other pituitary hormone deficiencies. He was started on GH therapy and had a good treatment response in the next 3 years. the combination of adrenal and thyroid insufficiencies with autoimmune hypophysitis is a ...

Research paper thumbnail of Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter. Brief literature review

HORMONES, 2005

Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter i... more Ectopic thyroid tissue in the lower neck with a coexisting normally located multinodular goiter is a rare entity. We present a 27-year old asymptomatic woman with a recent history of a painless mass in the left side of her lower neck. Thyroid function tests were normal. An ultrasound of her neck showed a multinodular goiter and a 3.4 cm solid mass in the left lower cervical area. These findings were confirmed by an MRI scan of her neck. The Tc99m Pertechnetate scan showed the presence of a functioning area under the left lobe of the thyroid gland. The patient underwent surgery. The cervical mass was identified as a structure separate from the left lobe of the thyroid, without any attachments to the body of the gland and was uniformly resected. A subtotal thyroidectomy was also performed. The histology revealed that the separate structure represented ectopic thyroid tissue. The patient had an uneventful postoperative recovery, subsequent to which she was euthyroid and had normal calcium levels.

Research paper thumbnail of Early metabolic defects following gestational diabetes in three ethnic groups of anti-GAD antibodies negative women with normal fasting glucose

HORMONES, 2007

ObJEctIVE: to characterise early metabolic abnormalities and the impact of ethnicity following ge... more ObJEctIVE: to characterise early metabolic abnormalities and the impact of ethnicity following gestational diabetes mellitus (GDM). DEsIGN: Women with a history of GDM belonging to three different ethnic groups were evaluated. Using the insulin-modified, frequently-sampled intravenous glucose tolerance test (FsIVGtt) and HOMA we studied 34 European, 16 south Asian and 10 Afro-caribbean women with normal fasting glucose following GDM and 44 European, 16 south Asian and 19 Afro-caribbean controls to assess insulin action and secretion. rEsULts: European post-GDM women had lower insulin sensitivity by FsIVGtt [0.6 (0.1-5.1) vs 1.5 (0.8-2.8) x10-4 •min-1 •pmol-1 •l-1 , p=0.010, adjusted for bMI p=0.054] and by HOMA [72(22-235) vs 153(55-421)%, p=0.004, adjusted for BMI p=0.006], and reduced β-cell function [lower disposition index 0.05(0.01-0.40) vs 0.11(0.05-0.25)min-1 , p=0.017] compared with controls. South Asian post-GDM women had decreased β-cell function [lower HOMA (%B) (73 (37-147) vs 124 (59-262) %, p=0.048 and acute insulin response to glucose (463 (131-1639) vs 1039 (393-2748) pmol/l h, p=0.052] than controls. Afro-caribbean post-GDM women had lower glucose disappearance rate [1.3(0.6-2.8) vs 2.6 (1.8-3.8) 10-2 /min, p=0.003] than controls, suggesting subtle glucose intolerance. cONcLUsIONs: Women with a history of GDM of three different ethnic groups, even in the presence of normal fasting glucose, display a range of metabolic abnormalities, including β-cell dysfunction with variable insulin resistance. These derangements may be influenced by ethnicity.

Research paper thumbnail of Polycystic ovary syndrome. Revised diagnostic criteria and long-term health consequences

HORMONES, 2005

The diagnostic criteria for polycystic ovary syndrome (PCOS) have recently been revised. The poly... more The diagnostic criteria for polycystic ovary syndrome (PCOS) have recently been revised. The polycystic ovarian morphology has been introduced as part of the criteria and an international consensus has been achieved providing the basis for future research and collaboration. It is now accepted that polycystic ovary syndrome has important long-term health implications, including metabolic disorders and increased risk factors for cardiovascular disease. The overall risk of developing type 2 diabetes among women with PCOS was found to be increased 3-7 times. Women with PCOS have increased levels of cardiovascular risk factors: insulin resistance, obesity, dyslipidaemia, hypertension and markers of abnormal vascular function. However, the level of risk for cardiovascular disease remains uncertain. The limited epidemiological data available to date have shown no increase in cardiovascular events although the incidence of cerebrovascular events was increased. The evidence for an increased risk for endometrial carcinoma among women with PCOS is limited. Long-term epidemiological studies of women with well defined PCOS are needed in order to assess the risk of long-term health consequences, to identify the subgroups among PCOS women who need to be targeted and to determine the timing and nature of measures for intervention and prevention.

Research paper thumbnail of Effects of growth hormone treatment on very-low-density lipoprotein apolipoprotein B100 turnover in adult hypopituitarism

Metabolism, 2000

Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-de... more Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels. Recent studies have shown that such patients exhibit increased hepatic secretion of VLDL apolipoprotein B100 (VLDL apo B100). To examine the effects of growth hormone (GH) replacement on VLDL apo B100 turnover, 13 GH-deficient hypopituitary patients (8 women and 5 men; aged 47 _+ 3 years, mean-+ SEM; body mass index [BMI], 30-+ 2 kg/m z) entered a double-blind placebo-controlled study for 6 months (GH 0.125 IU/kg/wk for 4 weeks, and then 0.25 IU/kg/wk). GH was subsequently used in all patients for a further 6 months. A 5-hour [1-13C] leucine infusion was administered at baseline and at 6 months. The secretion rate of VLDL apo B100 was derived by kinetic analysis following quantitation of isotopic enrichment by gas chromatography/mass spectrometry. The GH-treated group (6 patients) demonstrated a similar fractional secretion rate (FSR) for VLDL apo B100 at 0 and 6 months. The pool size and absolute secretion rate (ASR) also were unaffected significantly by GH therapy. No significant changes were observed in the placebo group (7 patients). Treatment with GH for 6 months caused an increase in the high-density lipoprotein (HDL) cholesterol concentration (13 patients, 1.27-+ 0.13 v 1.16 _+ 0.10 mmol/L, respectively, P = .05), whereas total cholesterol and triglyceride concentrations did not change. Nonesterified fatty acids (NEFAs) increased during GH therapy (471 _ 43 i~mol/L at 6 months v 349-49 i~mol/L at baseline, P < .0005). The data suggest that GH does not affect VLDL apo B100 turnover in a significant way.

Research paper thumbnail of Pleiotropic Genetic Syndromes with Developmental Abnormalities Associated with Obesity

Journal of Pediatric Endocrinology and Metabolism, 2009

Childhood obesity is a common and complex problem that may persist in adulthood. It may present a... more Childhood obesity is a common and complex problem that may persist in adulthood. It may present as a component of genetic syndromes associated with dysmorphic features, developmental abnormalities, mental retardation and/or learning disabilities and often neuroendocrine dysfunction. Although the chromosomal abnormalities of these rare syndromes are already known, the specific genetic and pathophysiological mechanisms leading to the distinct phenotypes and obesity still remain unclarified. New exciting genetic pathways contributing to syndrome phenotype and leading to obesity have recently been identified. Prader-Willi syndrome is caused by loss of expression of the C/D box HBII-84 cluster of snoRNAs. Dysfunction of the primary cilium, thought to have important signalling functions, may contribute to disease phenotype and obesity in Bardet-Biedl, Alstrom and Carpenter syndromes. In this mini-review current knowledge of clinical and genetic characteristics is summarized as well as the pathogenesis of these syndromes with special emphasis on the pathogenesis of obesity.

Research paper thumbnail of Results of thyroxine therapy on thyroid nodules size in children with Hashimoto's thyroiditis

Endocrine …, 2008

... Elvira Posaghidou, Eleni Kousta, Petros Papachilleos, Aphroditi Kitsopoulou, Marina Vakaki, A... more ... Elvira Posaghidou, Eleni Kousta, Petros Papachilleos, Aphroditi Kitsopoulou, Marina Vakaki, Aspasia Fotinou, Dimitris Ioanidis, Asteroula Papathanasiou &amp; Charalambos Hadjiathanasiou. Department of Endocrinology, Children&#x27;s Hospital &#x27;P.and A. Kyriakou&#x27;, Athens, Greece. ...

Research paper thumbnail of Elevation of soluble E-selectin levels following gestational diabetes is restricted to women with persistent abnormalities of glucose regulation

Clinical Endocrinology, 2002

Increased levels of the soluble adhesion molecule sE-selectin have been reported in normoglycaemi... more Increased levels of the soluble adhesion molecule sE-selectin have been reported in normoglycaemic women with previous gestational diabetes but not in other groups at increased risk of future type 2 diabetes. To explore the basis for these discrepant findings, we studied the relationship between sE-selectin and glucose regulation in a large group of women with previous gestational diabetes. Comparison of sE-selectin levels between a study cohort ascertained on the basis of recent gestational diabetes and suitable control subjects. One hundred and forty women with recent gestational diabetes (104 European, 20 South Asian and 16 Afro-Caribbean) and 125 normoglycaemic control women (90 European, 19 South Asian and 16 Afro-Caribbean). sE-selectin, fasting lipids, insulin and current glucose regulation status. There was no overall difference in sE-selectin levels between women with a history of gestational diabetes and control women among the 3 ethnic groups. European post-GDM women with abnormal glucose regulation postpartum (n = 30) had higher sE-selectin than control women (67 (54-91) ng/ml vs. 57 (43-75) ng/ml, P = 0.049). There was no difference in sE-selectin between normoglycaemic European women with a history of gestational diabetes (n = 74) and control women, even though the former displayed metabolic abnormalities predictive of diabetes. In those European post-GDM women with normal glucose regulation postpartum, sE-selectin levels were negatively correlated with time since delivery (r = -0.25, P = 0.04), suggesting that the previously described elevation of sE-selectin following GDM pregnancies slowly resolves postpartum. There was no correlation between sE-selectin levels and features of insulin resistance. In contrast to previous findings, this larger study does not support a role for sE-selectin as a marker, independent of prevailing glucose levels, of early metabolic abnormalities or future diabetes risk in women with previous gestational diabetes.

Research paper thumbnail of The effects of growth hormone replacement therapy on overnight metabolic fuels in hypopituitary patients

Clinical Endocrinology, 2000

ABSTRACT Hypopituitary adults on conventional replacement have low concentrations of metabolic fu... more ABSTRACT Hypopituitary adults on conventional replacement have low concentrations of metabolic fuels throughout the night, possibly related to GH deficiency or to decreased cortisol levels overnight. We investigated whether GH replacement corrects the overnight fuel deficiency. We measured circulating levels of metabolic fuels: glucose, non-esterified fatty acids (NEFA), glycerol and 3-hydroxybutyrate (3-OHB) and insulin concentrations over 24 h (from 0730 h to 0700 h) in hypopituitary adults before and after GH treatment in a randomized double-blind placebo-controlled trial of 3 months&#39; duration. Thirteen hypopituitary patients, 8 women and 5 men, were studied. Six patients (4 women and 2 men) received GH and 7 patients (4 women and 3 men) were allocated to receive placebo. There was no difference in fasting (0730 h), area under the curve (AUC) between 2400 h and 0700 h (overnight) and AUC over 24 h for plasma glucose, 3-OHB, glycerol and insulin concentrations as a result of GH treatment. Fasting and overnight AUC for NEFA were significantly higher on GH treatment ((mean +/- SEM) 243 +/- 29 vs. 446 +/- 90 micromol/l, P = 0.03, 1522 +/- 208 vs. 2167 +/- 123 micromol/l H, P = 0.046, respectively), but AUC over 24 h was not affected significantly. No significant changes in any fuel were seen in the placebo group. The changes in fasting, overnight and 24 h AUC for glucose, 3-OHB, glycerol and insulin levels with GH and with placebo for 3 months were similar. The changes in fasting and overnight AUC for NEFA before and after 3 months were significantly different in the group treated with GH vs. the group treated with placebo (median (lower-upper quartile) 104 (90-276) vs. -89 (-98 to 26) micromol/l, P = 0.002; 633 (263-967) vs. -895 (-1379 to -494) micromol/l h, P = 0.002, respectively), but the changes in 24-h AUC for NEFA were not significant between the two groups. GH replacement in hypopituitary adults increases fasting and overnight (between 2400 h and 0700 h) non-esterified fatty acid concentrations, consistent with the known lipolytic effect of GH. GH did not influence the concentrations of other metabolic fuels or insulin.

Research paper thumbnail of Prevalence and features of pancreatic islet cell autoimmunity in women with gestational diabetes from different ethnic groups

BJOG: An International Journal of Obstetrics and Gynaecology, 2001

Objective To assess the prevalence and characteristics of islet cell autoimmunity amongst women w... more Objective To assess the prevalence and characteristics of islet cell autoimmunity amongst women with gestational diabetes selected from South Asian and Afro-Caribbean as well as European populations. Design Cross-sectional retrospective survey of subject cohort. Population Three hundred and twenty-one women with a recent history of gestational diabetes (173 European, 86 South Asian and 62 Afro-Caribbean), a median (range) of 22 (1-150) months postpartum. Results Antibodies to Glutamic acid decarboxylase were found in 13 (4%) of these women. There was no difference in the prevalence of anti-glutamic acid decarboxylase positivity between the three ethnic groups (European 4.6%, South Asian 3.5%, Afro-Caribbean 3.2%). Anti-glutamic acid decarboxylase positive women were leaner than anti-glutamic acid decarboxylase negative women (body mass index, median (upper-lower quartile) 23.9 (22.5±26.7) vs 26.6 (23.4-30.5)kg/m 2 , P 0.03, P 0.049 allowing for ethnicity). There was no difference between glutamic acid decarboxylase-positive and glutamic acid decarboxylase-negative women for age, family history of diabetes, waist/hip ratio, prevalence of insulin treatment during pregnancy, postpartum glucose status, lipid pro®le and indices of insulin action and beta-cell function. Conclusions Markers of islet cell autoimmunity are found as frequently in gestational diabetes women of South Asian and Afro-Caribbean origin, as they are in European subjects. Identi®cation of future risk of type 1 diabetes is relevant to the planning of clinical management and intervention strategies in women with gestational diabetes of all major ethnic groups.

Research paper thumbnail of Endocrine Indices of PCOS in Women with Polycystic Ovaries but without Diagnostic Features of PCOS: A Study of an Infertility Clinic Population

Open Journal of Obstetrics and Gynecology, 2020

Background: The presence of polycystic ovarian morphology (PCO) without the other characteristics... more Background: The presence of polycystic ovarian morphology (PCO) without the other characteristics of the polycystic ovarian syndrome (PCOS) is insufficient for the diagnosis of PCOS and there is little justification for follow up in endocrine clinics for women with PCO morphology alone.