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Biomedical subjects

C R Edwards

Publications and source records attributed to C R Edwards.

At least 127 records · Page 7Linked to original sources
PubMed1989

The endocrinopathy of POEMS syndrome.

We describe the clinical features and post mortem findings in a patient with POEMS syndrome (P--polyneuropathy, O--organomegaly, E--endocrinopathy, M--M protein, S--skin changes), with particular emphasis on the evolution of the endocrinopathy over a three year period. In addition to gynaecomastia this case exhibited primary hypothyroidism and primary and secondary adrenal and gonadal failure. The widespread nature of the endocrine changes suggests that a circulating substance interferes with the action of trophic hormones, possibly by inhibiting second messenger production.

Endocrine System Diseases↗
PubMed1989

Licorice inhibits corticosteroid 11 beta-dehydrogenase of rat kidney and liver: in vivo and in vitro studies.

In humans, glycyrrhetinic acid (GE), the active pharmacological ingredient of licorice, produces symptoms resembling those caused by excess mineralocorticoid secretion. We are proposing that 11 beta-dehydrogenase inhibition, and not intrinsic mineralocorticoid activity, is the primary mechanism of licorice induced pseudoaldosteronism. Glycyrrhizic acid (glycyrrhetinic acid glucuronide), when given orally to rats, partially inhibited renal 11 beta-dehydrogenase. In rats treated with dexamethasone before glycyrrhizic acid administration there was similar enzyme inhibition, suggesting that antimineralocorticoid effects of dexamethasone in licorice excess states are not mediated through a direct effect on 11 beta-dehydrogenase activity. Dispersed renal proximal tubular preparations, kidney homogenates, and microsomes readily converted corticosterone to 11-dehydrocorticosterone. GE and its synthetic analog carbenoxolone inhibited the conversion in these systems in a dose-dependent manner. Corticosteroid 11-oxoreductase, which was present in kidney homogenates at a level 10-20% that of 11 beta-dehydrogenase was not inhibited by any of the agents. With homogenate and microsomes, the Ki of GE was about 10(-9)-10(-8) M; with intact tubules, the Ki of GE was about 10(-5)-10(-6) M. It is suggested that a permeability barrier slows the entry of GE into the tubule cells. We conclude that the effects of licorice on corticosteroid metabolism in the kidney are based on its inhibition of 11 beta-dehydrogenase. Our data, supplemented by published evidence, is inconsistent with the conclusion that interaction with mineralocorticoid receptors accounts for the pharmacological effects of GE.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1989

The medical treatment of adrenal disease.

The medical treatment of disorders of the adrenal gland, i.e. Addison's disease, Cushing's syndrome, primary aldosteronism, congenital adrenal hyperplasia and phaeochromocytoma, is described. Although these conditions are rare and may present with subtle symptoms and signs, most are life-threatening hence correct diagnosis and treatment are essential.

Adrenal Gland Diseases↗
PubMed1989

Blood pressure, renin-angiotensin-aldosterone axis and cortisol changes during withdrawal from alcohol.

Nineteen patients who had been drinking on the day of admission had significantly raised levels of renin, aldosterone and cortisol and a non-significant increase in angiotensin II. Five patients were hypertensive (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 95 mmHg) at some point during the study and there was a significant tachycardia. Over the first 4 days of abstinence there were falls in all of the measures reaching significance for renin, cortisol, systolic blood pressure and pulse. There were no correlations between blood pressure and any of the hormones measured although there was a significant association between pulse and both aldosterone and cortisol. It is concluded that the activity in the renin-angiotensin axis and hypothalamic-pituitary-adrenal axis is not responsible for alcohol-related changes in blood pressure.

Adult↗
PubMed1988

131-I radioiodine therapy for hyperthyroidism in patients with Graves' disease, uninodular goitre and multinodular goitre.

We studied 201 consecutive patients who received a relatively fixed dose of radioiodine for the treatment of hyperthyroidism between the years 1981-6. Patients with Graves' disease (170) were initially treated with a mean (SE) dose of 369 (10) MBq 131-I with a remission rate of 94% at 6 months and a cumulative relapse rate of 12% at one year and 21% at 5 years. The cumulative incidence of hypothyroidism was 26% at 3 months, 55% at 6 months, 61% at 1 year and 66% at 5 years. Patients with a uninodular goitre (10) were initially treated with a mean (SE) dose of 438 (85) MBq 131-I with a remission rate of 100% at 6 months, without relapse at 1 year but relapsing in 17% at 5 years. The cumulative incidence of hypothyroidism was 26% at 3 months, 30% at 6 months, 40% at 1 year and 40% at 5 years. Patients with a multinodular goitre (21) were initially treated with a mean (SE) dose of 613 (77) MBq 131-I with a remission rate of 79% at 6 months and a cumulative relapse rate of 26% at 1 year and 39% at 5 years. The cumulative incidence of hypothyroidism was 5% at 3 months, 14% at 6 months, 24% at 1 year and 24% at 5 years.

Aged↗
PubMed1988

Localisation of 11 beta-hydroxysteroid dehydrogenase--tissue specific protector of the mineralocorticoid receptor.

In vitro the mineralocorticoid receptor is non-specific and does not distinguish between aldosterone and cortisol. In vivo certain tissues with this receptor are aldosterone selective (eg, kidney and parotid) whereas others with the same receptor are not (eg, hippocampus and heart). Experiments in rats showed that 11 beta-hydroxysteroid dehydrogenase (which converts cortisol to cortisone in man and corticosterone to 11-dehydrocorticosterone in the rat) was much more highly concentrated in aldosterone-selective tissues than in non-selective tissues. The localisation in the selective tissues was such that the enzyme could act as a paracrine or possibly an autocrine mechanism protecting the receptor from exposure to corticosterone. Autoradiographic studies showed that protection is lost when the enzyme is inhibited; 3H-corticosterone and 3H-aldosterone were bound to similar sites. These findings seem to explain why sodium retention, hypokalaemia, and hypertension develop in subjects with congenital deficiency of 11 beta-OHSD and those in whom the enzyme has been inhibited by liquorice.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1988

A rational approach for assessing the hypothalamo-pituitary-adrenal axis.

In 70 paired insulin tolerance tests (ITTs) and short 'Synacthen' tests (SSTs), both of which have been advocated for assessment of the hypothalamo-pituitary-adrenal (HPA) axis, there were 51 passes on both tests, 9 failures on both, and 10 discrepant results (9 failures on the SST, 1 failure on the ITT). There was a close correlation between the maximum cortisol value achieved in the two tests. A survey of British endocrinologists showed that only 24% used the SST to assess the HPA axis. It is suggested that the SST should be used for the initial assessment of the HPA axis and the ITT reserved for patients who fail the SST, those on corticosteroid therapy, and those who have had an acute pituitary insult within 14 days.

Acute Disease↗
PubMed1988

Use of an enzyme linked immunosorbent assay (ELISA) for quantification of proteins on the surface of materials.

This study demonstrates the usefulness of an enzyme linked immunosorbent assay (ELISA) for detection and quantification of protein on the surface of materials. Bovine serum albumin (BSA) and bovine gamma globulin (BGG) were the proteins used. Titanium and stainless steel were the materials tested. The proteins were detected with the use of rabbit antiserum specific for BSA and for BGG. This reaction was quantitated by the use of horseradish peroxidase conjugated goat anti-rabbit gamma globulin. The technique is described in detail. The technique was demonstrated to be suitable for quantitation of protein from 0.01 mg/mL to 0.1 mg/mL on the surface of 3 mm X 10 mm materials. The technique was also demonstrated to be suitable for determining the surface area of solid materials. It is a simple technique and suitable for most biomaterials laboratories.

Adsorption↗
PubMed1988

Dexamethasone-suppressible hyperaldosteronism: studies on overproduction of 18-hydroxycortisol in three affected family members.

We report a newly diagnosed family in which a father and his two sons were found to be hypertensive and to have the rare familial condition dexamethasone-suppressible hyperaldosteronism (DSH). All three patients became normotensive on dexamethasone treatment alone and have been successfully maintained on low doses of the drug for 6 months since diagnosis. Each of the patients had extremely high plasma and urinary concentrations of the recently discovered steroid 18-hydroxycortisol, which were more than ten times higher than the upper normal limit. Plasma levels were readily suppressed by dexamethasone treatment. The hypothesis that 18-hydroxycortisol might derive from 18-hydroxylation of recirculating cortisol was tested by measuring plasma 18-hydroxycortisol levels during low-dose and high-dose hydrocortisone infusions, in a normal subject and in one of the patients with DSH. During the high-dose infusions (with plasma cortisol levels of 3000-5000 nmol/l) there was net production of 18-hydroxycortisol within 8 h, but this was not observed during the low-dose infusions (plasma cortisol levels 300-400 nmol/l). The origin of 18-hydroxycortisol remains uncertain: these findings do not support the recirculation theory, but lend weight to the alternative hypothesis that 18-hydroxycortisol is produced in transitional adrenocortical tissue. This steroid is of considerable value in the differential diagnosis of primary hyperaldosteronism and may also be important as a marker of transitional adrenal cell function.

Adrenal Cortex↗
PubMed1988

Syndrome of apparent mineralocorticoid excess. A defect in the cortisol-cortisone shuttle.

The first adult case of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) deficiency is described. The impaired conversion of cortisol to cortisone (indicated by urinary cortisol and cortisone metabolites and failure to metabolize 11 alpha-[3H]cortisol to [3H]H2O), was associated with hypertension, hypokalemia, and suppression of the renin-angiotensin-aldosterone system. When established on a fixed Na+/K+ intake, dexamethasone, given orally, produced a natriuresis and potassium retention. Plasma renin activity became detectable. When hydrocortisone (10 mg daily s.c. for 4 d) was added, there was marked Na+ retention, a kaliuresis (urinary Na+/K+ falling from 1.2 to 0.15), with suppression of plasma renin activity and an increase in blood pressure. These changes were also seen with the subject on no treatment. Conversion of cortisone to cortisol was not affected. These results suggest that cortisol acts as a potent mineralocorticoid in 11 beta-OHSD deficiency. The major site for the oxidation of cortisol to cortisone is the kidney. In this patient congenital deficiency of 11 beta-OHSD results in high intrarenal cortisol levels which then act on renal type I mineralocorticoid receptors. This condition can be treated with dexamethasone, which suppresses cortisol secretion and binds to the type II glucocorticoid receptor. We suggest that 11 beta-OHSD exerts a critical paracrine role in determining the specificity of the type I receptor. In the normal state cortisol is converted by 11 beta-OHSD to cortisone which thus allows aldosterone to bind preferentially to the type I receptors in the kidney and gut. In this patient deficiency of 11 beta-OHSD results in high intrarenal cortisol concentrations that then bind to the type I receptor.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1988

Lithium carbonate--a competitive aldosterone antagonist?

Plasma renin activity (PRA), aldosterone (aldo) levels, electrolyte levels, and blood pressures were measured in 16 patients with affective disorders taking lithium prophylactically, and in 16 age and sex-matched control subjects. PRA and aldo levels were significantly elevated in the lithium-treated group. There was no difference between the groups in plasma electrolytes or erect and supine blood pressures, arguing against secondary aldosteronism. In the lithium-treated group, there was a significant positive correlation between both PRA and plasma aldo vs serum lithium. We postulate that lithium inhibits the action of aldosterone on the distal tubule in the kidney. Activation of the renin angiotensin system maintains normal blood pressure and plasma electrolytes.

Adult↗
PubMed1988

Dual effect of etomidate on mineralocorticoid biosynthesis.

The effects of the intravenous anesthetic agent etomidate on adrenal steroidogenesis were studied in 14 pre-menopausal women undergoing abdominal hysterectomy. Anesthesia was induced with either thiopentone (group A) or etomidate (groups B and C) and maintained with nitrous oxide-oxygen 0.5% halothane (groups A and B) or an infusion of etomidate to supplement nitrous oxide-oxygen (group C). Serum concentrations of cortisol, aldosterone and 11-deoxycorticosterone (DOC) were measured pre-induction, at the end of surgery, and at 4, 10 and 24 hours after induction. In group A, concentrations of all three hormones were significantly elevated in response to surgery. In group B, the increases in cortisol and aldosterone were obtunded, but there was a greater increase in DOC at 4 hours after induction. In group C, there were no increases in cortisol or aldosterone up to 4 hours after induction, and the increase in DOC was significantly lower than in group B. These results suggest that etomidate inhibits adrenal steroidogenesis at two separate sites. With low doses of the drug, as used for induction, 11 beta-hydroxylase is inhibited lowering both cortisol and aldosterone secretion. The reduction in aldosterone is, however, offset by a rise in DOC. With higher doses, there is an additional early pathway effect so that the compensatory rise in DOC is reduced.

Adult↗
PubMed1987

Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age.

The sodium retention associated with liquorice ingestion has been thought to be due to a direct mineralocorticoid effect, despite the fact that it does not seem to occur in patients or animals with severe adrenal insufficiency. This study in seven normal subjects given liquorice showed that sodium retention is associated with a significant change in cortisol metabolism indicating inhibition of 11-beta-hydroxysteroid dehydrogenase (11 beta-OHSD). Congenital deficiency of this enzyme produces a syndrome of apparent mineralocorticoid excess. It is suggested that in both conditions there is a defect in the renal conversion of cortisol to cortisone by 11 beta-OHSD which results in high intrarenal cortisol levels, acting on type 1 mineralocorticoid receptors to cause sodium retention.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1987

Development and validation of an improved radioimmunoassay for serotonin in platelet-rich plasma.

A radioimmunoassay (RIA) using a 125I-tracer is described for measurement of serotonin (5-hydroxytryptamine, 5-HT) in human platelet-rich plasma (PRP). Antisera were raised against 5-HT-succinamate conjugated to bovine albumin and, to improve assay sensitivity, the analyte was made chemically similar to the immunogen by conversion to N-acetylserotonin prior to assay, using the specific amino reagent N-acetoxysuccinimide. The assay shows good correlation with a high-pressure liquid chromatography (HPLC) reference method (5-HT RIA = 1.007 X 5-HT HPLC + 29.3, r = 0.936, p less than 0.001, n = 40), indicating that no significant cross-reactions were detected. Samples of PRP are diluted 1/20 to fall within the working range (80-15% B/B0) of the assay, which is 4.75-325 nmol/l, (0.95-65.0 pmol/tube), corresponding to 95-6500 nmol/l in PRP. Intra- and interassay coefficients of variation were 5.0-10.5% and 12.0-21.2% respectively for serotonin concentrations of 250-2,500 nmol/l added to platelet-poor plasma. With this improved assay, it is possible to analyse up to 100 samples/day, compared with 10-20 samples/day by HPLC.

Acetylation↗
PubMed1987

Lithium inhibits the action of fludrocortisone on the kidney.

A patient with autoimmune Addison's disease treated with hydrocortisone and fludrocortisone became mineralocorticoid-deficient whilst taking lithium carbonate for a bipolar illness. During an in-patient metabolic balance study she required 1.0 mg fludrocortisone daily and dietary sodium supplementation to make plasma renin activity and serum potassium normal, and to abolish postural hypotension. We present data to suggest that lithium carbonate inhibits the action of fludrocortisone on the distal renal tubule.

Addison Disease↗
PubMed1987

Hair growth and androgen responses in hirsute women treated with continuous cyproterone acetate and cyclical ethinyl oestradiol.

Eighteen hirsute women (8 with polycystic ovarian syndrome, 10 with idiopathic hirsutism) were treated for up to 12 months with cyproterone acetate, 150 mg daily, and ethinyl oestradiol, 50 micrograms on days 5-25 of the menstrual cycle. Hair growth rate and density were measured from standardized serial photographs of a shaved skin area. A significant reduction was seen in mean hair growth rate, total plasma testosterone, free testosterone index, plasma dehydroepiandrosterone, and plasma androstenedione. LH and FSH also fell and sex hormone binding globulin level increased. No significant changes occurred in hair density or in serum PRL levels. A significant correlation was observed between hair growth rate and total plasma testosterone for the pooled results (r = 0.35, P less than 0.005). No significant correlations were seen between hair density and the endocrine parameters studied.

Adult↗