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G S Conway

Publications and source records attributed to G S Conway.

At least 19 recordsLinked to original sources
PubMed2006

Fertility outcomes in women with hypopituitarism.

BACKGROUND: Women with hypopituitarism are known to have a poor outcome once pregnancy has been achieved by ovulation induction. There are no data, however, recording the efficacy of ovulation induction and pregnancy rates in this group of subfertile women. METHODS: The outcome of fertility treatments in all 19 women with hypopituitarism attending the fertility clinics of University College London Hospitals over the past 20 years was audited. RESULTS: Ovulation was achieved in almost all women (95%) but occurred in only 60% of treatment cycles. Pregnancy was achieved in 47% of women or 11% of cycles resulting in a live birth rate of 6.7% per cycle. Seven of the 18 pregnancies (39%) miscarried. Only 42% of women treated achieved a live birth. CONCLUSION: Ovulation induction in women with hypopituitarism yields relatively low pregnancy rates in comparison to other causes of anovulation and a high miscarriage rate. Pituitary hormone deficiency beyond gonadotrophins has a major adverse effect on achieving pregnancy.

Adult↗
PubMed2004

Misdiagnosis of seizures: insulinoma presenting as adult-onset seizure disorder.

Once diagnosed with a refractory seizure disorder, patients often receive aggressive and escalating pharmacotherapy. However, a significant proportion of patients referred to neurologists do not have epilepsy. Toxic and metabolic causes of seizures should always be considered as they are potentially curable, and may be fatal if untreated. The following case report highlights the need for careful reassessment of all seizures that are atypical and refractory to medication.

Adult↗
PubMed2003

Spatial abilities following prenatal androgen abnormality: targeting and mental rotations performance in individuals with congenital adrenal hyperplasia.

In most mammals, behaviors that show sex differences are influenced by androgen during early life. In the current study, the hypothesis that androgen influences the development of human spatial abilities was investigated. Participants included 40 females and 29 males with congenital adrenal hyperplasia (CAH), a genetic disorder that causes overproduction of adrenal androgens beginning prenatally, and 29 unaffected female and 30 unaffected male relatives of individuals with CAH. Participants ranged in age from 12-45 years. Measures of spatial abilities included two mental rotations tasks and two targeting tasks, all of which showed large sex differences favoring males in the unaffected relative controls. Females with CAH (exposed to higher than normal levels of androgen prenatally) performed better than unaffected females on the targeting tasks, and resembled unaffected males and males with CAH in this respect. However, females with CAH did not perform better than unaffected females on the measures of mental rotations abilities. Males with CAH showed unaltered performance on the targeting tasks, and impaired performance on the mental rotations tasks. Results are discussed in terms of differences in experiential and hormonal contributions to different spatial abilities, as well as in terms of possible differences in critical periods for hormonal influences on targeting versus mental rotations abilities. Specifically, we speculate that, although androgen may influence targeting abilities prenatally, if hormones influence the development of mental rotations ability, they do so at some other time, perhaps during the first six months of postnatal life.

Adolescent↗
PubMed2002

Turner's syndrome in adulthood.

Turner's syndrome is the most common chromosomal abnormality in females, affecting 1:2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. However, it is becoming increasingly evident that adults with Turner's syndrome are also susceptible to a range of disorders, including osteoporosis, hypothyroidism, and renal and gastrointestinal disease. Women with Turner's syndrome have a reduced life expectancy, and recent evidence suggests that this is due to an increased risk of aortic dissection and ischemic heart disease. Up until recently, women with Turner's syndrome did not have access to focused health care, and thus quality of life was reduced in a significant number of women. All adults with Turner's syndrome should therefore be followed up by a multidisciplinary team to improve life expectancy and reduce morbidity.

Adult↗
PubMed2001

Hypertension is a major risk factor for aortic root dilatation in women with Turner's syndrome.

Women with Turner's syndrome (TS) have a threefold increase in mortality, primarily as a result of their cardiovascular complications. Recently, the risk of fatal aortic dissection has come to light as a major cause of mortality in women with TS. The aim of this study was to assess the prevalence of aortic root dilatation in a group of women with TS and to investigate the factors contributing to its development. Thirty-eight women with TS attending a dedicated adult Turner clinic were examined clinically and by M-mode and two-dimensional echocardiography on at least one occasion. Aortic root dilatation was defined as an aortic root diameter greater than the 95th centile for body surface area. Fasting serum lipid concentrations were measured in all women. Additionally, 18 subjects underwent noninvasive assessment of central arterial stiffness using applanation tonometry. Fifty percent of subjects were hypertensive and a similar number had an abnormal echocardiogram. A bicuspid aortic valve was present in 33% of subjects, 16 women (42%) had ascending aortic root dilatation. This was associated with a bicuspid aortic valve in four women and hypertension in 11. Two women had isolated aortic root dilatation. Aortic root diameter was significantly associated with systolic blood pressure (r = 0.5, P = 0.003) and left ventricular thickness (r = 0.5, P = 0.02). There was no association with serum lipids or arterial compliance. Structural cardiac abnormalities are present in up to 50% of women with Turner's syndrome. Aortic root dilatation is a significant risk in women with Turner's syndrome and is closely dependent on blood pressure. Aortic root dilatation does not appear to be related to atherosclerosis and is more likely to be due to a mesenchymal defect. Regular surveillance of the aortic root diameter is essential in all women with Turner's syndrome and hypertension should be treated aggressively when present in order to minimize the risk of potentially fatal aortic dissection.

Adolescent↗
PubMed2001

Idiopathic gonadotrophin deficiency: genetic questions addressed through phenotypic characterization.

OBJECTIVE: The association of idiopathic hypogonadotrophic hypogonadism (IHH) with congenital olfactory deficit defines Kallmann's syndrome (KS). Although a small proportion of IHH patients have been found to harbour defined genetic lesions, the genetic basis of most IHH cases remains to be elucidated. Genes currently recognized to be involved comprise KAL (associated with X-linked-KS), the GnRH receptor (associated with resistance to GnRH therapy), DAX 1 (associated with adrenohypoplasia congenita) and three loci also associated with obesity, leptin (OB), leptin receptor (DB) and prohormone convertase (PC1). Because of the rarity of the condition and the observation that patients are almost universally infertile without assistance, familial transmission of IHH is encountered infrequently and pedigrees tend to be small. This has constrained the ability of conventional linkage studies to identify other candidate loci for genetic IHH. We hypothesized that a systematic clinical evaluation of a large patient sample might provide new insights into the genetics of this rare disorder. Specifically, we wished to examine the following propositions. First, whether normosmic (nIHH) and anosmic (KS) forms of IHH were likely to be genetically discrete entities, on the basis of quantitative olfactory testing, analysis of autosomal pedigrees and the prevalence of developmental defects such as cryptorchidism and cleft palate. Second, whether mirror movements and/or unilateral renal agenesis were specific phenotypic markers for X-linked-KS. DESIGN AND PATIENTS: We conducted a clinical study of 170 male and 45 female IHH patients attending the endocrinology departments of three London University teaching hospitals. Approximately 80% of data were obtained from case records and 20% collected prospectively. Parameters assessed included olfaction, testicular volume, family history of hypogonadism, anosmia or pubertal delay, and history or presence of testicular maldescent, neurological, renal or craniofacial anomalies. Where possible, the clinical information was correlated with published data on genetic analysis of the KAL locus. RESULTS: Olfactory acuity was bimodally distributed with no evidence for a spectrum of olfactory deficit. Testicular volume, a marker of integrated gonadotrophin secretion, did not differ significantly between anosmic and normosmic patients, at 2.0 ml and 2.2 ml, respectively. Nevertheless, the prevalence of cryptorchidism was nearly three times greater in anosmic (70.3%, of which 75.0% bilateral) than in normosmic (23.2%, of which 43.8% bilateral) patients. Individuals with nIHH, eugonadal isolated anosmia and/or KS were observed to coexist within 6/13 autosomal IHH pedigrees. On three occasions, fertility treatment given to an IHH patient had resulted in the condition being transmitted to the resulting offspring. Mirror movements and unilateral renal agenesis were observed in 24/98 and 9/87 IHH patients, respectively, all of whom were identifiable as X-KS males on the basis of pedigree analysis and/or defective KAL coding sequence. Abnormalities of eye movement and unilateral sensorineural deafness were observed in 10/21 and 6/111 KS patients, respectively, but not in nIHH patients. DISCUSSION: Patients with IHH are almost invariably either anosmic (KS) or normosmic (nIHH), rather than exhibiting intermediate degrees of olfactory deficit. Moreover, the prevalence of cryptorchidism is nearly three times greater in KS than in nIHH despite comparable testicular volumes, suggesting a primary defect of testicular descent in KS independent of gonadotrophin deficiency. Disorders of eye movement and hearing appear only to occur in association with KS. Taken together, these findings indicate a clear phenotypic separation between KS and nIHH. However, pedigree studies suggest that autosomal KS is an heterogeneous condition, with incomplete phenotypic penetrance within pedigrees, and that some cases of autosomal KS, nIHH and even isolated anosmia are likely to have a common genetic basis. The prevalences of anosmia, mirror movements and unilateral renal agenesis among X-KS men are estimated to be 100, 85 and 31%, respectively. In sporadic IHH, mirror movements and unilateral renal agenesis are 100% specific phenotypic markers of de novo X-KS. By comparison, only 7/10 X-KS families harboured KAL coding defects. Clinical ascertainment, using mirror movements, renal agenesis and ichthyosis as X-KS-specific phenotypic markers, suggested that de novo X-KS was unlikely to comprise more than 11% of sporadic cases. The majority of sporadic KS cases are therefore presumed to have an autosomal basis and, hence, the preponderance of affected KS males over females remains unexplained, though reduced penetrance in women would be a possibility.

Adolescent↗
PubMed2001

Autoimmune thyroid syndrome in women with Turner's syndrome--the association with karyotype.

OBJECTIVE: Females with Turner's syndrome (TS) are at an increased risk of developing autoimmune thyroid disease. Studies assessing the influence of karyotype on thyroid autoimmunity in adults with TS have yielded conflicting results but have been limited by small numbers. The aim of this study was to determine the frequency of thyroid autoimmunity in a large cohort of women with TS and to assess the influence of karyotype on the development of thyroid disease. DESIGN, PATIENTS AND MEASUREMENTS: Data were available for 145 women with TS attending a dedicated adult Turner clinic. The mean age was 26 years (range 16-52 years). Information regarding the presence of thyroid disease, karyotype, thyroid autoantibodies and thyroid function was recorded in all. The chi-squared test with Yates' correction was used to assess the association between karyotype and thyroid autoimmunity. RESULTS: Forty-one per cent of women with TS had positive thyroid autoantibodies and 16% of women were hypothyroid on replacement therapy with thyroxine. However, 83% of women with an X-isochromosome had positive thyroid autoantibodies compared with 33% of women with other karyotypes (P < 0.0001). Women with an isochromosome-X karyotype were also significantly more likely to become frankly hypothyroid and require thyroxine compared with other karyotypes (37.5% isochromosome-X vs. 14% 45, X vs. 6% other karyotypes P = 0.0034). CONCLUSIONS: In this large cohort of women with TS we have shown that the risk of developing autoimmune thyroid disease is particularly high in women with an X-isochromosome, suggesting that a gene on the long arm of the X chromosome (Xq) may play an important pathogenetic role in the development of autoimmune thyroid disease.

Adolescent↗
PubMed2001

Hormone replacement therapy may improve hepatic function in women with Turner's syndrome.

OBJECTIVE: Women with Turner's syndrome (TS) have recently been shown to be at an increased risk of developing chronic liver disease. There has been some concern that oestrogen replacement therapy may exacerbate hepatic dysfunction. The aim of this study was to assess hepatic function in women with TS and to determine the effect of oral oestradiol valerate on liver enzymes. DESIGN AND PATIENTS: A retrospective review of liver enzymes of 80 women with TS, followed by a prospective study looking at serum liver enzyme concentrations in 20 women with TS following 3 months on and off hormone replacement therapy (HRT) (oestradiol valerate, 2 mg/levonorgestril 75 microg). MEASUREMENTS: Liver enzymes (gamma glutamyl transferase, aspartate transaminase and alkaline phosphatase), albumin and bilirubin were measured on and off HRT. Viral hepatitis serology and liver autoantibodies were tested in patients with abnormal liver function. RESULTS: Thirty-five out of 80 women (44%) had elevated serum liver enzyme concentrations. Two women (2.5%) had a mildly raised serum bilirubin, but protein synthesis was normal in all subjects. HRT resulted in a significant fall in all liver enzymes (P < 0.05) but did not affect serum protein concentrations CONCLUSIONS: Women with Turner's syndrome often have elevated liver enzymes. Oestrogen/progestagen therapy using oestradiol valerate improves liver function in this group of patients. The mechanisms behind this are unclear.

Adolescent↗
PubMed2001

3 beta hydroxysteroid dehydrogenase autoantibodies in patients with idiopathic premature ovarian failure target N- and C-terminal epitopes.

The steroid cell enzyme 3 beta hydroxysteroid dehydrogenase (3 beta HSD) has been identified as a target of steroid cell autoantibodies, and autoantibodies to this enzyme are present in patients with premature ovarian failure and patients with autoimmune polyendocrine syndrome 1. The aim of the present study was to develop a radioligand binding assay for 3 beta HSD autoantibodies and to exploit this to examine regions of the molecule targeted by autoantibodies. We generated a construct of 3 beta HSD coupled to a luciferase fusion partner in order to maximize the yield of (35)S-radiolabeled protein. Labeled 3 beta HSD was then immunoprecipitated and the autoantibodies quantified by phosphoimaging. Autoantibodies to 3 beta HSD were detected in 12 of 100 (12%) idiopathic premature ovarian failure patients and 0 of 103 (0%) healthy age-matched controls (P < 0.0001). Three overlapping fragments of 3 beta HSD cDNA were cloned downstream of luciferase to examine autoantibody binding sites. Two of nine sera with 3 beta HSD autoantibodies (22%) displayed reactivity to the N terminus of 3 beta HSD, and seven (77%) showed reactivity to the C terminal; no sera reacted with the middle region. Our study demonstrates a markedly enhanced disease specificity of autoantibodies to 3 beta HSD detected using this novel assay and shows that distinct regions of the molecule are targeted.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

Recommendations for the diagnosis and management of Turner syndrome.

Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the care of affected individuals were published in 1994. In the light of recent advances in diagnosis and treatment of TS, an international multidisciplinary workshop was convened in March 2000, in Naples, Italy, in conjunction with the Fifth International Symposium on Turner Syndrome to update these recommendations. The present paper details the outcome from this workshop. The genetics and diagnosis of the syndrome are described, and practical treatment guidelines are presented.

Adolescent↗
PubMed2000

Serum vascular endothelial growth factor concentrations in postmenopausal women: the effect of hormone replacement therapy.

OBJECTIVE: To assess serum vascular endothelial growth factor (VEGF) concentrations in healthy postmenopausal women in relation to hormone replacement therapy (HRT) and the presence or absence of a uterus. DESIGN: Cross-sectional study. SETTING: The Middlesex Hospital. PATIENT(S): A total of 199 postmenopausal women were enrolled: 132 had uterus in situ and 67 had had hysterectomies. Of the 67 women who had had hysterectomies, 6 received no HRT, 20 received tibolone, 25 received transdermal E2, and 16 received conjugated equine estrogens. Of the 132 women with uteri in situ, 34 received no HRT, 56 received tibolone, 24 received transdermal E2 with sequential norethisterone acetate, and 18 received conjugated equine estrogens with sequential levonorgestrel. INTERVENTION(S): Serum VEGF level measurement. MAIN OUTCOME MEASURE(S): Serum VEGF concentrations. RESULT(S): Women who received HRT had higher VEGF concentrations than those not receiving HRT. Among women who received no HRT, those with uterus in situ had higher VEGF levels than did those who had had hysterectomies. Among women who had had hysterectomies, VEGF concentrations were higher in those who received conjugated equine estrogens than in those who did not receive HRT and those who received tibolone or transdermal E2. Among women with uterus in situ, no difference was found between subgroups. CONCLUSION(S): Postmenopausal women with uterus in situ and those who received HRT had higher VEGF concentrations than did those who had had hysterectomies and who did not receive HRT. Among women receiving HRT, those who received conjugated equine estrogens alone had higher VEGF concentrations. This estrogen-mediated increase in serum VEGF concentrations may be a mechanism by which HRT benefits the cardiovascular system.

Aged↗
PubMed2000

The prevalence of polycystic ovaries in women with type 2 diabetes mellitus.

OBJECTIVE: Polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus are both common conditions associated with insulin resistance and compensatory hyperinsulinaemia. Previous reports have noted that impaired glucose tolerance and diabetes are common in women with PCOS. In this report we present the results of the converse study: the prevalence of polycystic ovaries in premenopausal women presenting with type 2 diabetes mellitus. SUBJECTS: Subjects were recruited from a hospital Diabetes Clinic. A search of computerized records identified 49 premenopausal women with type 2 diabetes mellitus being treated with diet alone or oral hypoglycaemic agents of whom 38 (76%) patients agreed to be studied. DESIGN: A cross-sectional study recording clinical, demographic and anthropometric data. Measurements of fasting metabolic parameters, reproductive endocrine profiles and ovarian dimensions were taken. RESULTS: Eighty-two percent of women with type 2 diabetes mellitus had polycystic ovaries on ultrasound. Of these women, 52% had clinical evidence of cutaneous hyperandrogenism and/or menstrual disturbance. Correlations between metabolic and reproductive parameters were consistent with a stimulatory action of insulin on the ovary. There was no significant difference between the PCO and non-PCO groups with respect to metabolic profiles. CONCLUSIONS: Women with type 2 diabetes mellitus have a higher prevalence of polycystic ovaries than that reported in the general population. Not all women with hyperinsulinaemia due to type 2 diabetes mellitus, however, develop PCO suggesting that hyperinsulinaemia alone is not sufficient for the expression of this ovarian morphology.

Adult↗
PubMed2000

Clinical presentation of PCOS following development of an insulinoma: case report.

A 24 year old woman presented with a prolonged clinical history of fasting and exertional hypoglycaemia, and was subsequently diagnosed with an insulinoma. Concurrent symptoms of oligomenorrhoea and hyperandrogenism of similar duration were noted. Biochemically, hyperinsulinaemia was observed in association with a raised serum luteinizing hormone (LH), raised testosterone and androstendione concentrations. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS) but minimal change was observed in the ovarian ultrasound appearances. This case demonstrates the role of insulin in mediating the hypersecretion of both LH and androgens in women with polycystic ovaries. We suggest that hyperinsulinaemia converted occult 'polycystic ovaries' to become clinically manifest as 'polycystic ovary syndrome'. This paradigm has clear implications for women with insulin dependent diabetes mellitus who presumably have systemic hyperinsulinaemia.

Adult↗
PubMed2000

Female sex preponderance for idiopathic familial premature ovarian failure suggests an X chromosome defect: opinion.

Premature ovarian failure (POF) is defined as ovarian failure occurring before the age of 40 years. A genetic aetiology is suggested by the occurrence of families with two or more affected females. We have characterised the pattern of inheritance of 41 cases of familial POF and compared them to published pedigrees. In eleven families a clear genetic association of POF could be identified. In the remaining 30 families the mechanism of inheritance was obscure. We found a female sex preponderance in the siblings of 30 families with idiopathic POF and in previously published series of idiopathic familial POF. In contrast, other known causes of POF, such as blepharophimosis ptosis epicanthus and inversus and autosomal recessive gonadal dysgenesis, had no altered sex ratio. One of our series of 30 pedigrees demonstrated transmission of POF susceptibility through fathers, which we believe is the first to be described in the literature. We present a group of five consanguineous families where we assume the mode of inheritance is autosomal recessive and where there was no female sex preponderance. Female sex preponderance for idiopathic familial POF suggests an X chromosome defect is inherited as a major cause of ovarian failure.

Chromosome Aberrations↗