Androgen status in women with late onset or persistent acne vulgaris.
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Acne Vulgaris↗
Biomedical subjects
C R Edwards
Publications and source records attributed to C R Edwards.
Factors in the control of plasma renin activity and concentration in Type 1 (insulin-dependent) diabetes.
Possible factors involved in the control of plasma renin activity (PRA) and concentration (PRC) have been analysed in 49 patients with long-standing Type 1 diabetes and in 40 healthy controls matched for age and sex. Eighteen of the diabetic subjects were clinically free of all microvascular and macrovascular complications of their disease (Group A); 31 had proliferative retinopathy (Group B). Both lying and standing PRA and PRC were similar in Group A and healthy controls. Mean PRA was 50-115% higher in Group B diabetics than in controls (P less than 0.001 supine and erect) and 50-70% higher than in Group A diabetics (P less than 0.05 supine and erect); PRC also was 60% higher in Group B than in Group A (P less than 0.05 supine and erect). Control subjects showed significant falls in both PRA and PRC with increasing age, while Groups A and B showed significant falls in PRA or PRC with age. Group A showed a significant inverse correlation between systolic blood pressure and supine PRC (r = -0.57), but this was not significant in the controls and was completely absent in Group B. With correction for the effect of age there were significant relationships of PRA and PRC with sodium excretion in the controls and in Group A, but not in Group B. PRA and PRC are thus normal in uncomplicated long-standing Type 1 diabetes, but regulation of renin secretion appears to be impaired in patients with microvascular disease. Renin secretion inappropriate to their blood pressure and sodium status may contribute to maintenance of their relative hypertension.
Adult↗
How effective is external pituitary irradiation for growth hormone-secreting pituitary tumors?
Forty-six patients with GH-secreting pituitary tumours were treated with conventional external pituitary irradiation through two opposed fields to a total dose of 3750 cGy over 15 fractions. Thirty-patients received external radiotherapy as primary treatment and 16 received radiotherapy combined with pituitary surgery. The mean (+/- SD) serum GH in the former group was 74.3 +/- 74.8 mU/l before treatment, falling by 28% per year over 0-5 years and by 16% per year over 0-20 years. The mean (+/- SD) serum GH in the latter group was 265.4 +/- 209.3 mU/l before treatment, falling by 76% in the first year--a direct result of surgical removal of tumour--then by 30% per year over 1-5 years and 16% per year over 1-20 years. Progressive failure of normal anterior pituitary function developed by 10 years, with variable loss of gonadotrophin, corticotrophin and thyrotrophin function. The respective figures for patients treated with radiotherapy alone were 47.4, 29.6 and 16.0% and for the combined group were 70.2, 53.9 and 38.1%. Whilst external pituitary irradiation appears to reduce serum GH concentrations in patients with GH-secreting pituitary tumours the major disadvantages of this form of treatment are the time taken to achieve a cure and the high incidence of hypopituitarism. Nevertheless there did not appear to be any other serious side effects.
Acromegaly↗
Traditional methods of follow-up for thyroid disease--in descent?
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Costs and Cost Analysis↗
The specificity of ketanserin in the inhibition of serotonin-induced steroidogenesis in the rat adrenal zona glomerulosa.
Although the biological effects of ketanserin were originally attributed to its specific interaction with serotonin type 2 (5HT2) receptors, at high doses (greater than 10(-8)M) it also appears to act as an alpha 1-antagonist in some tissues. This in vitro study examines the possibility that Ketanserin may inhibit serotonin-induced steroidogenesis by blockade of alpha 1-receptors. Rat zona glomerulosa cells prepared by collagenase digestion of adrenal capsular tissue were incubated at 37 degrees C in Krebs-Ringer bicarbonate buffer (0.2% glucose, 0.2% bovine serum albumin) for 30 min with increasing doses of serotonin (10(-9)-10(-6)M) alone or in the presence of ketanserin (10(-6)M), methysergide (a 5HT-receptor antagonist) 10(-6)M) or prazosin (an alpha 1-antagonist)(10(-6)M). Cyclic AMP, Corticosterone and aldosterone outputs were measured by radioimmunoassay. Serotonin produced correlative sigmoidal dose responses for cyclic AMP, corticosterone and aldosterone which were inhibited by ketanserin and methysergide but not by prazosin. These results suggest that ketanserin does not act by alpha 1-blockade in the adrenal zona glomerulosa but rather as a specific 5HT-receptor antagonist.
Adrenal Cortex↗
Development and optimisation of a radioimmunoassay for plasma captopril.
A specific and sensitive radioimmunoassay has been developed to monitor plasma levels of captopril, the first orally active angiotensin-converting enzyme inhibitor. Because of the reactive nature of the captopril thiol group, captopril was measured as the captopril-N-ethylmaleimide complex (captopril-NEM). Accuracy studies, using samples with known added concentrations of captopril, were satisfactory (r = 0.95, p less than 0.001, y = 0.97x - 2.02), and the radioimmunoassay results compared well with those determined by a gas chromatography/mass spectrometric method (r = 0.98, p less than 0.0005, y = 1.2x - 19). The minimum detection limit of the assay was 2 micrograms captopril/litre plasma.
Antibody Specificity↗
The hypothalamic-pituitary-adrenal axis.
Anterior pituitary corticotrophin cells secrete ACTH as part of a larger precursor molecule, pro-opiomelanocortin. Post-translational cleavage of this precursor yields three major peptides: ACTH, beta-LPH and N-POMC. Experiments both in vivo and in vitro suggest that N-POMC may act as a prohormone amplifier for ACTH-induced adrenal steroidogenesis and as regulator of adrenocortical cell growth. The secretion of POMC is under the control of CRF. These findings are discussed in relation to the pathophysiology of corticotrophinoma. The primary defect in this condition appears to reside at the level of the anterior pituitary cell and is readily amenable to treatment by trans-sphenoidal microsurgery. The estimation of plasma ACTH concentrations is proving useful in the monitoring of various clinical conditions including Addison's disease and congenital adrenal hyperplasia.
Adrenal Cortex↗
The endocrine and metabolic effects of cimetidine.
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Administration, Oral↗
Pro-opiocortin related peptides in human pituitary and ectopic ACTH secreting tumours.
Basal and stimulated secretion of N-terminal pro-opiocortin (Pro-gamma-MSH), ACTH and LPH from seven pituitary and three ectopic ACTH secreting tumours have been studied in vitro using a perfused isolated cell system. The peptides were shown to be released concomitantly and in equimolar amounts. The pituitary tumours responded to stimulation with rat stalk median eminence extracts (SME) and synthetic AVP. However, peptide release from the ectopic tumours, although pulsatile, remained autonomous. Prior to surgery, gel-chromatographic profiles of plasma immunoreactive ACTH showed only one peak, which eluted in the position of 1-39 ACTH, in patients with the pituitary tumours, but there was a second peak of large molecular weight ACTH present in the plasma from those with the ectopic ACTH syndrome. This second form of ACTH could not be detected in any of the tumour cell column effluents. An eighth pituitary tumour was atypical, in its unusually large size, clinically aggressive nature and spectrum of peptide release. Although peptide release in response to stimulation with SME was similar to that observed with the other pituitary tumours, the chromatography of the plasma ACTH resembled the ectopic plasma pattern, showing two peaks of immunoreactivity.
ACTH Syndrome, Ectopic↗
Male gonadal function in coeliac disease: 2. Sex hormones.
Hypogonadism, infertility, and sexual dysfunction occur in some men with coeliac disease. We have measured plasma testosterone, dihydrotestosterone, sex-hormone binding globulin, oestradiol, and serum luteinising hormone in 41 men with coeliac disease and have related these findings to jejunal morphology, fertility, semen quality, and sexual function. To determine the specificity of these observations in coeliacs we also studied 19 nutritionally-matched men with Crohn's disease, and men with chronic ill-health due to rheumatoid arthritis and Hodgkin's disease. The most striking endocrine findings in untreated coeliacs were increased plasma testosterone and free testosterone index, reduced dihydrotestosterone (testosterone's potent peripheral metabolite), and raised serum luteinising hormone, a pattern of abnormalities indicative of androgen resistance. As jejunal morphology improved hormone levels appeared to return to normal. This specific combination of abnormalities was not present in any of the disease control groups and, to our knowledge, androgen resistance has not been described previously in any other non-endocrine disorder. Plasma oestradiol concentration was modestly raised in 10% of coeliacs and 11% of patients with Crohn's disease. Unlike plasma androgens and serum luteinising hormone in coeliacs, plasma oestradiol was not clearly related to jejunal morphology. Androgen resistance and associated hypothalamic-pituitary dysfunction appear to be relatively specific to coeliac disease and cannot be explained merely in terms of malnutrition or chronic ill-health. In addition, our findings suggest that this endocrine disturbance may be related to sexual dysfunction in coeliac disease but its relationship to disordered spermatogenesis in this condition has not been clearly established.
Adolescent↗
Water and electrolyte balance in subjects with a permanent ileostomy.
Water and electrolyte balance has been studied in 39 patients with a permanent ileostomy, who had had a proctocolectomy for ulcerative colitis. The findings have been compared with those in 39 healthy subjects who were matched for age and sex. The ileostomists were found to lose excessive quantities of water and sodium in the ileostomy effluent compared with the corresponding losses in normal faeces. The mean plasma total protein and albumin concentrations were increased in the ileostomists suggesting a state of chronic dehydration. The daily urinary output of sodium was low and the output of potassium was high. The urinary pH was low. The ileostomists had raised mean concentration of aldosterone in the plasma (p less than 0.001) and it is suggested that this is responsible for the body's partial compensation for the depletion of sodium and water, including the so-called ileostomy adaptation.
Albumins↗
Bromocriptine improves reduced libido and potency in men receiving maintenance hemodialysis.
Twenty-five men on maintenance hemodialysis commenced a placebo-controlled, double-blind, crossover trial of bromocriptine for erectile impotence. Eight patients on bromocriptine and one on placebo failed to complete the trial due to side-effects and 2 were withdrawn following renal transplantation. Libido or the frequency and/or quality of erections or both improved in 11 of the remaining 14 patients during bromocriptine treatment. A significant (P less than 0.01) improvement in patients' perception of sexual performance occurred on bromocriptine compared with placebo. The 3 patients in whom potency failed to improve had the lowest serum testosterone concentrations. Bromocriptine is usually effective in the management of impotence in males receiving maintenance hemodialysis provided pretreatment serum testosterone is above the lower end of the normal range, but side-effects are relatively common.
Adult↗
Human gamma-melanotropin precursor potentiates corticotropin-induced adrenal steroidogenesis by stimulating mRNA synthesis.
Circulating human gamma-melanotropin precursor (76 amino acids) [N-POC(1-76) enhances the corticosterone and aldosterone response to corticotropin by isolated perfused rat adrenal cells [Al-Dujaili, Hope, Estivariz, Lowry & Edwards (1981) Nature (London) 291, 156-159]. Actinomycin D (4 x 10(-6) mol/litre) did not significantly affect corticotropin-induced corticosterone or aldosterone outputs, but completely inhibited the potentiating action of gamma-melanotropin precursor on rat adrenal cells. This suggests that the precursor enhances corticotropin-induced steroidogenesis via an increase in available mRNA produced from DNA transcription.
Adrenal Glands↗
An in vitro stimulatory effect of indoleamines on aldosterone biosynthesis in the rat.
The effect of the indoleamines, serotonin, 5-methoxy-tryptamine, 5-methoxytryptophol and melatonin on aldosterone biosynthesis by rat adrenals in vitro has been studied. In all experiments incremental doses of each of the indoleamines tested produced a progressive increase in aldosterone secretion. Serotonin (10(-6) mol/l) produced a 5-fold increase in aldosterone secretion by isolated perfused rat zona glomerulosa cells obtained from animals on a normal sodium diet compared to the basal levels. Higher (9-fold) responses were elicited when the cells were from sodium deficient rats and lower (3-fold) when the rats were sodium loaded. 5-methoxytryptamine (10(-6) mol/l) was a more potent aldosterone agonist (8-fold increase) and the aldosterone response was similarly affected by change in sodium intake. Smaller responses were found when cells were stimulated by 5-methoxytryptophol (10(-4) mol/l, 3.5-fold) or melatonin (10(-4) mol/l, 3-fold). The dopamine agonist serotonin antagonist Lisuride completely inhibited the aldosterone response to 5-methoxytryptamine (10(-8) mol/l) and serotonin (10(-7) mol/l). These results suggest that pineal indoles could play a role in aldosterone biosynthesis and indicate that changes in sodium balance affect the aldosterone response to indoles in the same way as has been described for other aldosterone secretagogues.
5-Methoxytryptamine↗
A direct radioimmunoassay for 11-deoxycortisol.
A rapid, sensitive and highly specific radioimmunoassay (RIA) for 11-deoxycortisol has been developed and used for the measurement of serum concentrations. Antisera were raised using 11-deoxycortisol -3-carboxymethyloxime-bovine serum albumin as immunogen and showed minimal cross reaction with related steroids. 11-Deoxycortisol-3-carboxymethyloxime was coupled to 125 I-iodohistamine to produce a labelled antigen of high specific activity (s.a. 680 Ci/mmol). The assay was performed for 1h at room temperature and pH 4. Results were correlated with those after extraction, high pressure liquid chromatography and RIA of serum samples (y= 0.78x + 36.9; r = 0.97, p less than 0.001). The accuracy of the method was satisfactory (y = 1.00x - 0.61; r= 0.95; p less than 0.001). Assay sensitivity was 0.3 nmol/l. 11-Deoxycortisol concentrations in normal subjects at 09.OOh were 26-46 nmol/l (37.2 +/- 5.7; x- +/- 1 S.D.). The assay should facilitate the investigation of patients with possible abnormalities of adrenocortical function.
17-Hydroxycorticosteroids↗
Relationship between plasma testosterone and dihydrotestosterone concentrations and male facial hair growth.
Linear facial hair growth and the density of facial hair were measured by a photographic method and their relationship to plasma testosterone (T) and dihydrotestosterone (DHT) concentrations was examined in twelve healthy men. In addition, we investigated eight men with coeliac disease in whom we have previously demonstrated reversible androgen resistance. The divergence of plasma T (increased) and DHT (decreased) concentrations in this condition enabled examination of possible independent actions of these androgens on facial hair growth. Linear facial hair growth was significantly reduced in coeliac patients compared with controls and correlated with plasma DHT but not with plasma T concentration. Conversely, hair density was significantly greater in coeliacs than controls and correlated only with plasma T concentration. These abnormalities of facial hair growth and hair density appeared more marked in treated patients receiving a gluten-free diet. These findings suggest that T and DHT may have independent roles in the control of male facial hair growth, i.e. T for hair follicle priming and DHT for promotion of linear growth. The relationship between hair growth abnormalities in coeliac disease and withdrawal of dietary gluten requires further investigation.
Adult↗
Circulating testosterone, sex hormone binding globulin and prolactin in women with late onset or persistent acne vulgaris.
Serum testosterone, sex hormone binding globulin (SHBG) and prolactin were measured in thirty-eight women with acne which persisted or started after the age of 18 years. One or more of these levels were abnormal in 76% of patients. Increased testosterone or low SHBG were present alone or in combination in 60% of patients. This group was presumed to have a raised level of non-protein bound, metabolically-available testosterone. Hyperprolactinaemia, which was present in 45% of patients, may be important in view of the reported association with increased adrenal androgens. The hormonal abnormalities may be causally related to the acne and a greater understanding of them may lead to better treatment.
Acne Vulgaris↗
Increased plasma renin activity in type 1 diabetes with microvascular disease.
Plasma renin activity was measured in thirty-one subjects with Type 1 diabetes and proliferative retinopathy, and in seventeen matched diabetic subjects without evidence of any complications of their disease. The two groups were comparable for age, sex, smoking habits and duration of diabetes. Systolic and diastolic blood pressures were significantly higher in the patients with retinopathy (P less than 0.025 and P-0.05 respectively) and HbA1 was greater (P less tha 0.005) than in the patients without complications. Plasma renin activity, both lying and standing, was higher in the patients with retinopathy than in the uncomplicated group (P less than 0.05 for each). There were no correlations between plasma renin activity and mean blood pressure, HbA1 or fasting blood glucose. These findings raise the possibility that the renin-angiotensin system might be implicated in the pathogenesis of diabetic microvascular.
Adult↗