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Biomedical subjects

W M Hague

Publications and source records attributed to W M Hague.

At least 19 recordsLinked to original sources
PubMed1995

Subjects with polycystic ovaries without hyperandrogenaemia exhibit similar disturbances in insulin and lipid profiles as those with polycystic ovary syndrome.

Polycystic ovaries (PCO) are detected using ultrasonography in a proportion of women who do not have clinical symptoms of the polycystic ovary syndrome (PCOS). The aim of this study was to compare the metabolic and endocrine differences between women with such ultrasound-detected PCO and women with PCOS, and to relate these changes to clinical presentation with particular reference to cycle irregularity. A group of 118 women showing PCO on vaginal ultrasound scan was divided into those who had no hyperandrogenaemia (n = 21) and those who had increased androgens and a clinical presentation normally associated with PCOS (n = 97). These were compared with a reference group of 26 normal subjects. Glucose tolerance, lipid concentrations and endocrine profiles were compared between groups. Apart from higher concentrations of androgens in the PCOS group, there were no significant differences between the PCO and PCOS groups in either fasting and stimulated insulin and glucose or in concentrations of sex hormone-binding globulin, gonadotrophins and blood lipids or in ovarian volume. Both PCO and PCOS subjects with cycle irregularity had significantly higher concentrations of serum fasting and stimulated insulin independent of androgens and body mass index than those with normal cycles. It was concluded that: (i) PCO and PCOS patients have equivalent disturbances in relation to insulin and glucose metabolism as well as lipid and lipoprotein disturbances compared to reference subjects; (ii) higher serum insulin values are associated with menstrual irregularity in both groups; (iii) ultrasound evidence for PCO predicts similar metabolic sequelae to PCOS and can therefore be used for studies of the genetics and long term risks for this condition.

Androgens↗
PubMed1995

Aspirin and prevention of preeclampsia. Position statement of the use of low-dose aspirin in pregnancy by the Australasian Society for the Study of Hypertension in Pregnancy.

1. A heterogeneous group of randomized trials have been conducted using low-dose aspirin to prevent preeclampsia. The results do not support widespread use of low-dose aspirin to prevent preeclampsia. 2. On the basis of existing literature, it is reasonable to use prophylactic low-dose aspirin from early pregnancy in the following groups: (i) Women with prior fetal loss after the first trimester, with placental insufficiency (ii) Women with severe fetal growth retardation in a preceding pregnancy either due to preeclampsia or unexplained (iii) Women with severe early-onset preeclampsia in a previous pregnancy necessitating delivery at or before 32 weeks' gestation. 3. On the basis of existing literature, it is recommended that aspirin not be used in the following groups: (i) Healthy nulliparous women (ii) Women with mild chronic hypertension (iii) Women with established preeclampsia. 4. The data are sufficient to support further trials in more homogeneous select subgroups of women considered at risk of developing preeclampsia.

Aspirin↗
PubMed1994

Transient diabetes insipidus and acute fatty liver of pregnancy.

OBJECTIVE: To review the association of transient diabetes insipidus and acute fatty liver of pregnancy. DESIGN: A retrospective study. SETTING: Six women presenting with polyuria and polydipsia in the third trimester or in the immediate postpartum period, referred over a two and a half year period; five out of six were primigravida. All had raised liver transaminases and biopsy-proven acute fatty liver of pregnancy. Four out of six also had pre-eclampsia. SUBJECTS: Tertiary referral centre. MAIN OUTCOME MEASURES: There were no maternal deaths and only one fetal death. Desamino-cys-1-D-arg-8-vasopressin administration produced a reduction in urine output in all five women to whom it was administered. In all cases symptoms had resolved by the end of the fourth postpartum week. Three of the women have had subsequent pregnancies uncomplicated by either transient diabetes insipidus or acute fatty liver of pregnancy. CONCLUSIONS: The association of transient diabetes insipidus and acute fatty liver of pregnancy appears more common than previously recognised. Both may be part of the spectrum of pre-eclampsia.

Acute Disease↗
PubMed1992

Premature menopause management.

Premature menopause is most commonly iatrogenic, but may be due to an autoimmune or other ovarian disorder, or it may be idiopathic. The diagnosis is established by a raised serum FSH. Fertility can only be reliably achieved using donor oocytes; otherwise oestrogen replacement therapy should be offered.

Female↗
PubMed1990

HLA associations in patients with polycystic ovaries and in patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency.

Ninety-nine Caucasian patients with ultrasonically detected polycystic ovaries (PCO) were typed for human leucocyte (HLA) antigens. Fifty patients with congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency were similarly typed. Among the patients with PCO, there was a significant increase in the frequency of HLA DRW6 (P = 0.0027) compared with that found in a control population, which remained significant (P = 0.027) when corrected for the number of antigens tested. This difference was reduced, but remained significant (P = 0.006), when the patients with CAH and PCO were added. There was also a significant decrease in the frequency of HLA DR7 (P = 0.017) among the patients with PCO compared with a control population, but there was no distortion of the frequencies of HLA A, B or Cw antigens. Among the patients with CAH, previously well documented associations of HLA B14 and DR1 with non-classical disease were confirmed. The frequency of HLA Bw47 was increased among the whole group of CAH patients (P = 0.05) but was not increased among those with classical salt-wasting (SW) or simple virilizing (SV) disease. Family studies were performed in close female relatives of 16 of the PCO patients and 21 of the CAH patients but no evidence for genetic linkage between HLA and PCO status could be found. These data suggest that there is no significant component of disturbed adrenal steroid 21-hydroxylase activity to account for the PCO morphology, although there may be some other genetic factor, more proximal to the centromere on chromosome 6, affecting the development of polycystic ovaries.

Adrenal Hyperplasia, Congenital↗
PubMed1990

The prevalence of polycystic ovaries in patients with congenital adrenal hyperplasia and their close relatives.

Seventy-seven female patients (36 adults and 41 children aged under 16 years) with congenital adrenal hyperplasia (CAH) were assessed using pelvic ultrasound, as well as with standard endocrine tests and HLA typing. Forty-six close female relatives were also tested for ovarian morphology using ultrasound after assessment of their heterozygous state using HLA typing. The association of CAH with ultrasonically detected polycystic ovaries (PCO) was confirmed in 30/36 (83%) adult patients, 4/10 (40%) postpubertal girls and 1/31 (3%) pre and peripubertal girls: in all, 35/46 (76%) postmenarcheal patients. Six out of nine (67%) pre-menopausal mothers of patients with PCO, and 8/10 (80%) sisters of patients with PCO also had PCO. The proportions of both CAH patients and heterozygote subjects with PCO were significantly greater than that found in a normal population (P less than 0.0001). The finding, however, of two homozygous non-CAH-affected adult sisters with PCO and, conversely, of 10 heterozygous adult relatives and of 12 postmenarcheal CAH patients with normal ovaries, indicates that the ovarian morphological change may be independent of the adrenal lesion.

Adolescent↗
PubMed1989

Steroid responses to ACTH in women with polycystic ovaries.

Sixty-three women with ultrasonically detected polycystic ovaries (PCO) were investigated for a disorder of adrenal steroid biosynthesis. Serum was obtained before, and at 30 and 60 min after, the administration of 250 micrograms tetracosactrin, and assayed for 17 alpha-OH-progesterone, 21-deoxycortisol, 17 alpha-OH-pregnenolone and dehydroepiandrosterone by radioimmunoassay following paper chromatography. Results were compared with those in 11 women with normal ovaries, seven adult females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), and 15 women heterozygous for this defect. Although the basal-peak steroid concentration differences were significantly greater when ACTH tests were conducted between 1400 and 1700 h than between 0900 and 1000 h, absolute peak steroid concentrations were not different at either time of day. Four of 63 (6.4%) women with PCO had responses to ACTH characteristic of non-classical (late onset) 21OHD CAH, and about half the remainder had responses characteristic of 21OHD heterozygotes. There was no clear cut evidence for a deficiency in 3 beta-hydroxysteroid dehydrogenase activity in women with PCO.

17-alpha-Hydroxypregnenolone↗
PubMed1988

Inappropriate ACTH concentrations in two patients with functioning adrenocortical carcinoma.

Two female patients with functioning adrenocortical carcinomas had plasma ACTH detectable by RIA at presentation. In both patients there was evidence for biological activity of ACTH. There was no evidence for an ectopic source of ACTH, nor for a pituitary tumour. Urinary steroid analysis showed patterns of multiple hormone secretion characteristic of adrenocortical carcinomas. The finding of detectable ACTH concentrations in a patient with Cushing's syndrome does not exclude the presence of an adrenocortical tumour.

Adrenal Gland Neoplasms↗
PubMed1988

Familial polycystic ovaries: a genetic disease?

High resolution ultrasonography was used to establish the presence of polycystic ovaries (PCO) in 50 women with symptoms of polycystic ovary syndrome and in 17 women with congenital adrenal hyperplasia. One hundred and thirty-seven post-menarcheal, premenopausal female members of the families of these patients were scanned to assess the heredity of the condition. Familial PCO was found in 56 of the 61 pedigrees (92%) in which sufficient members were available for study. The frequency of PCO in the relatives of the patients with congenital adrenal hyperplasia was no different from that found in the main group. Twenty-four out of thirty-six (67%) mothers of probands and 45 out of 52 (87%) sisters of probands were affected. The segregation ratio (fraction of females affected) for all sibships was 107 out of 133 (80.5%). The volumes of the polycystic ovaries (mean 9.97 ml, 95% confidence limits (CL) +/- 0.75) were significantly different from those of the normal ovaries (mean 5.38 ml, 95% CL +/- 0.26) (P less than 0.0001), although there was no significant difference between the volumes of the ovaries of the probands and those of their affected relatives. Even after allowing for a high frequency of PCO in the general population (22%), the observed segregation ratios were significantly different from those predicted for autosomal dominant (P less than 10(-4)) and X-linked dominant (P = 0.0002) modes of inheritance. A number of mechanisms which might account for the observed segregation ratio are considered. These include meiotic drive due to a genetic segregation distorted, vertical transmission of an infective agent, and environmental factors, such as the effect of maternal androgen on gonadal development.

Female↗
PubMed1988

Heterogeneity in the gene locus for steroid 21-hydroxylase deficiency.

DNA was analysed from 33 patients with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. In each case Southern blots were prepared from a number of restriction enzyme digests and hybridised with probes for both the 21-hydroxylase and the adjacent fourth component of complement (C4). Evidence for deletion of the active 21-hydroxylase gene (CYP21B) was found in 13 cases and in 10 of these the deletion included the adjacent C4B gene, leading to a hybrid CYP21A/CYP21B gene. Deletion of CYP21B alone was found in one patient, the remaining two cases appearing to have the active gene replaced by the inactive pseudogene. Duplications of the CYP21A-C4B region and deletion of the pseudogene are also described. In a further 12 cases no gross abnormality could be found.

Adrenal Hyperplasia, Congenital↗
PubMed1987

Hypergonadotropic amenorrhea--etiology and outcome in 93 young women.

Ninety-three cases of amenorrheic women aged 40 years or less in whom serum FSH concentrations were found to be greater than 20 units/l have been reviewed. The etiology and diagnosis of this uncommon but serious condition and the potential for spontaneous recovery of ovarian follicular activity (17.1%) are discussed. Management is reviewed in the light of ultrasonic, karyotypic and immunological findings.

Adult↗
PubMed1986

Autoimmune premature ovarian failure with polyendocrinopathy and spontaneous recovery of ovarian follicular activity.

Premature ovarian failure accounts for 10% of cases of secondary amenorrhea, and in most cases its cause remains unknown. One mechanism by which it occurs is autoimmune destruction. A 21-year-old patient is described in whom autoimmune ovarian failure occurred in association with Addison's disease and primary hypothyroidism. Although premature ovarian failure is generally considered irreversible, the patient subsequently resumed spontaneous ovarian follicular activity.

Addison Disease↗