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Biomedical subjects

W M Hague

Publications and source records attributed to W M Hague.

36 records · Page 2Linked to original sources
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↗
PubMed1984

Renal morphological changes in idiopathic acute fatty liver of pregnancy.

Renal morphological changes are described in four cases of idiopathic acute fatty liver of pregnancy. Light microscopy showed mild glomerular hypercellularity together with thickening and narrowing of capillary loops. In two cases the tubules showed lipid accumulation which included free fatty acids. Electron microscopy showed mesangial cell interposition between the basal lamina and endothelial cells. Glomeruli contained electron dense material in a subendothelial location. Immunoperoxidase stains showed diffuse segmental deposits of fibrin/fibrinogen and IgM in relation to glomerular capillary loops. IgG and C3 were found in three and two cases respectively. Pathogenetic mechanisms including disseminated intravascular coagulation, immune complex deposition and alterations in lipid metabolism are discussed. Coexistent preeclampsia is considered to be an unlikely explanation for the changes. There is a possibility that these renal changes comprise an early feature of idiopathic acute fatty liver of pregnancy.

Acute Disease↗
PubMed1983

Malignant hypertension in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

Two brothers, aged 20 and 12, with the 11 beta-hydroxylase deficient form of congenital adrenal hyperplasia, are presented. They had refused treatment for the previous four years until the younger was admitted with malignant hypertension, partial blindness and evidence of myocardial damage. The elder was therefore admitted for assessment and found to have less severe hypertension. Gas liquid chromatographic analysis of the steroids in urine from each revealed a possible difference in the enzyme defect between the two brothers--the younger having a complete, while the elder had only a partial block. Family studies have confirmed no association with the HLA locus.

Adrenal Hyperplasia, Congenital↗
PubMed1983

Acute fatty liver of pregnancy.

Six further cases of acute fatty liver of pregnancy are presented and discussed in relation to the world literature on this rare disease of pregnancy, the aetiology of which is still unknown. The importance of vomiting in late pregnancy is emphasized. A common feature seems to be a metabolic stress, possibly related to infection, which tips a susceptible liver into metabolic failure.

Acute Disease↗
PubMed1982

Long-term effects of cyproterone acetate on the pituitary adrenal axis in adult women.

Function of the pituitary-adrenal axis was assessed in 16 adult female patients who had been taking cyproterone acetate for greater than 1 year. Some evidence of reduced basal cortisol output was seen in 25% of the patients, but plasma cortisol levels could be stimulated both by hypoglycaemia and by direct corticotrophin (ACTH) stimulation. The latter effect was confirmed by analysis of steroid excretion in urine although basal excreation rates indicated extensive adrenal suppression. These results suggest that cyproterone acetate does have some glucocorticoid activity which is able partially to suppress the pituitary--adrenal axis, but leaves it still responsive to stress.

Adult↗