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Biomedical subjects

G H Beastall

Publications and source records attributed to G H Beastall.

At least 73 records · Page 4Linked to original sources

Androgen levels in men with diabetes mellitus.

Patients in varying degrees of diabetic ketoacidosis had low serum testosterone levels which rose following recovery (5.4 +/- 1.3----13.7 +/- 1.7 nmol/l, p less than 0.02, mean +/- SE). Blood glucose control of 30 non-ketotic diabetic men (15 insulin-dependent and 15 non-insulin-dependent) did not correlate significantly with serum testosterone concentrations. Although previous authors had suggested that the adrenal androgen status of diabetic patients might be abnormal, adrenal androgens androstenedione and dehydroepiandrosterone sulphate (DHEAS) were similar in our 30 men to age-matched healthy men.

Androgens↗

Responses to acute insulin-induced hypoglycaemia in diabetic patients: a comparison of short-acting human and porcine insulins.

A comparison was made of the metabolic, hormonal, haemodynamic and symptomatic responses to acute hypoglycaemia induced by short-acting porcine and human insulins in 16 fasting, insulin-dependent diabetic patients, 8 of whom had diabetes for less than 5 years (Group A) and 8 of whom had diabetes for greater than 15 years (Group B). Each patient received an intravenous injection of 0.2 units/kg of insulin on two separate occasions. No differences were found between the groups in the rate of fall of blood glucose or the blood glucose nadir with either insulin, but in Group B, glucose recovery was more rapid after human insulin (p less than 0.01). No differences in the responses of blood lactate, plasma free fatty acids, glucagon or prolactin were observed between the groups. In Group B the rises of growth hormone and cortisol occurred more rapidly following human insulin (p less than 0.01), while the rise in adrenaline was greater following porcine insulin. Haemodynamic changes were identical following each species of insulin in both diabetic groups. A questionnaire was used to score 18 symptoms of hypoglycaemia on a 7 point scale. No significant differences were found in the mean scores of each symptom of hypoglycaemia or in the total symptom score. Thus recovery of blood glucose from hypoglycaemia was slightly more rapid after administration of human insulin to diabetic patients of long duration, but it is unlikely that these marginal differences would confer any clinical advantage in this subgroup.

Adolescent↗

Growth hormone, body composition and somatomedin C after treatment of acromegaly.

Acromegaly is associated with abnormal indices of body composition (as determined by exchangeable sodium, exchangeable potassium and total body water estimations) which may be corrected by treatment. We related these indices of body composition to the attained growth hormone levels (mean of five daytime values) in 42 treated acromegalics. Somatomedin C was measured in 30 subjects. The mean duration of treatment was 7.7 years (range 1-26). Exchangeable sodium, potassium and total body water were significantly lowered by treatment. After treatment of acromegaly subjects whose growth hormone level was below 5 mU/l achieved normal body composition more often than those with higher levels. Growth hormone concentration of below 5 mU/l after treatment should be regarded as more appropriate index of control of acromegaly than the higher levels previously recommended.

Acromegaly↗

Mechanisms leading to hypogonadism in men with burns injuries.

A profound and persistent depression of serum testosterone concentrations was found in 19 men with burns injuries. This could not be explained by changes in sex hormone binding globulin capacity, hyperprolactinaemia, classical primary testicular failure, or a hypogonadotrophic state. Pulsatile release of luteinising hormone was found in control subjects but was absent or diminished in burnt patients with low serum testosterone concentrations. In addition, these patients showed reduced biological activity of luteinising hormone as measured by bioassay even though normal concentrations of luteinising hormone were detected by radioimmunoassay. The temporary hypogonadism after burns injury and possibly in other clinical states may be related to hypothalamic dysfunction, which leads to abnormal generation of luteinising hormone releasing hormone and non-pulsatile secretion of luteinising hormone of reduced biological activity.

Adult↗

The effects of omeprazole on endocrine function in man.

We have assessed the effect of omeprazole on various endocrine functions in man. Eight healthy subjects took 60 mg omeprazole or placebo daily for 1 week in a double-blind, randomized, cross-over study. On Day 7 basal concentrations of follicle-stimulating hormone (FSH), luteinising hormone (LH), prolactin, testosterone, thyroid-stimulating hormone (TSH), and serum thyroxine (T4) and tri-iodothyronine (T3) were measured, followed by the gonadotrophin response to luteinising hormone releasing hormone (LHRH) and the prolactin and TSH responses to thyrotrophin releasing hormone (TRH). There were no differences in basal or stimulated values between omeprazole and placebo. In a second study, a further 8 subjects were similarly treated, and on Day 7 serial measurements of cortisol and 11-deoxycortisol were made before and for 2.5 h after intravenous adrenocorticotrophin (ACTH). There were no differences in basal values or pattern of response to ACTH for either hormone. Omeprazole in clinical practice is unlikely to cause any significant interference in endocrine function.

Adult↗

Circadian variation of thyrotrophin, determined by ultrasensitive immunoradiometric assay, and the effect of low dose nocturnal dopamine infusion.

The effect of low dose dopamine infusion on the circadian rhythm of thyrotrophin (TSH), prolactin and cortisol in a group of six healthy male volunteers is reported. Subjects were infused in random order with either saline (154 mmol/l NaCl solution; control) or dopamine (0.1 and 1 microgram min-1 kg-1) between 21.00 and 01.00 hours, in random order. The serum TSH profile was characterized by a maximal peak occurring at 23.00 hours and higher nocturnal than diurnal values. Superimposed on this are short term oscillations in serum TSH levels, typical of an ultradian rhythm. The maximal peak in TSH, occurring at 23.00 hours, was abolished by dopamine infused at a rate of 1 microgram min-1 kg-1, and was unaffected by the lower rate of dopamine infusion (0.1 microgram min-1 kg-1). The serum prolactin profile was characterized by a peak occurring soon after the onset of sleep (23.30-00.30 hours), which fell during the morning, and began to rise in late evening. Low dose dopamine (0.1 microgram min-1 kg-1) had a slight but insignificant effect with decreased prolactin levels at the end of the infusion whereas the higher dopamine dose was associated with significantly lower prolactin levels during and throughout the infusion. There was a rebound to levels significantly higher than control on cessation of the infusion. Cortisol levels were unaffected by dopamine.

Adult↗

Assays for follicle stimulating hormone and luteinising hormone: guidelines for the provision of a clinical biochemistry service.

The measurement of serum follicle stimulating hormone (FSH) and luteinising hormone (LH), together with the appropriate sex steroid, is of great value in the investigation of delayed and precocious puberty, hypogonadism, subfertility, polycystic ovarian disease and hypothalamic-pituitary disorders. Dynamic function testing of the hypothalamic-pituitary-gonadal axis should be restricted to a few defined situations. Sequential LH measurements, either in serum or in urine, may be used to time ovulation during artificial insemination or in vitro fertilisation programmes. No special precautions are necessary when sampling for FSH and LH measurement; serum is preferred to plasma and should be stored frozen before assay. Aliquots of timed urine specimens of known volume should be stored frozen without preservative. Gonadotrophin results should be available within 2-3 weeks; laboratories unable to meet this schedule are advised to send their samples to a Regional Centre for assay. Reagents for the radioimmunoassay of FSH and LH are readily available, and standard techniques have been developed for their use. Laboratories using 'in-house' methods should pay particular attention to the matrix used for preparing standard solutions, the purification of radioligands and the optimisation of the separation system. Low cost matched reagents of proven performance are available in kit form from the Chelsea Hospital for Women; several commercial kits are also available, although few are widely used in the UK. The overall performance of laboratories in the UK External Quality Assessment Scheme (EQAS) for FSH and LH has remained steady for several years. Of the 130 participants, only about 15% in each scheme have 'good' performance (cumulative bias less than 10%, plus cumulative variability of bias less than 10%), whilst a similar proportion have 'unacceptable' performance (cumulative bias greater than 20% and/or cumulative variability of bias greater than 25%). The remaining 70% of laboratories have 'adequate' performance but are at risk of producing results that are clinically misleading. Within any one method group, the performance of FSH and LH assays are closely related. Optimal assay performance depends upon sensible laboratory management to ensure skilled operators, a regular programme of reagent/kit renewal, comprehensive internal and external quality assessment, and attention to detail in all aspects of gonadotrophin assay. The working range of each individual assay should be defined and no absolute result reported from outside this range.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

ACTH deficiency: hypothalamic or pituitary in origin?

The level within the hypothalamic-pituitary axis at which isolated ACTH deficiency occurs, can be more clearly identified by assessing this axis with corticotrophin-releasing factor (CRF) and insulin induced hypoglycaemia. We report a case where lack of response to both tests, suggests a pituitary origin for this rare endocrine deficiency.

Adrenal Cortex Function Tests↗

The parallel effects of a very low molecular weight heparin (CY222) on anti Xa activity and thyroid hormone levels in blood.

A very low molecular weight heparin fragment (CY222) was administered by subcutaneous injection to a group of normal volunteers. This drug caused increased anti Xa activity with peak levels being observed two hours after injection. This coincided with changes in thyroid hormone levels especially with a fall in red cell thyroxine levels. Larger doses of CY222 caused a fall in serum total thyroxine and triiodothyronine, a rise in free thyroxine and a fall in TSH levels. It was thought that these findings may be due to the production of a circulating inhibitor of cellular uptake of thyroxine and that this might be related to the elevated levels of serum free fatty acids produced by the heparin.

Factor X↗

A study of hypothalamic-pituitary-adrenal suppression following curative surgery for Cushing's syndrome due to adrenal adenoma.

The hypothalamic-pituitary-adrenal axis was investigated in all six patients requiring glucocorticoid replacement 2.5-11 years after unilateral adrenalectomy for adrenal adenomas causing Cushing's syndrome. The hypothalamic-pituitary-adrenal axis was assessed by insulin induced hypoglycaemia and CRF testing in each patient. Two patients showed normal cortisol and ACTH responses to hypoglycaemia. Two patients showed subnormal cortisol responses to hypoglycaemia in the presence of high or normal basal ACTH concentrations. ACTH concentrations increased with both hypoglycaemia and CRF. Two patients showed subnormal cortisol responses to hypoglycaemia and CRF. One of these patients showed an ACTH rise following hypoglycaemia but not CRF. Defects at either hypothalamic-pituitary or adrenal levels were demonstrated and recovery of the axis appears to commence at the hypothalamic-pituitary level.

Adenoma↗

Adrenal androgens and illness.

We have studied the adrenal androgen status of medically ill patients, patients before and after cholecystectomy and during recovery from burns injury. In patients ill for less than 2 weeks, serum androstenedione concentrations (mean +/- SEM) were raised (7.94 +/- 0.98 nmol/l) as compared with a control group (4.83 +/- 0.38 nmol/l, P less than 0.005) or with patients ill for more than 2 weeks (5.21 +/- 0.46 nmol/l, P less than 0.02); serum dehydroepiandrosterone sulphate (DHAS) levels were lower in patients ill for more than 2 weeks (1.21 +/- 0.42 mumol/l) than in either the acutely ill group (5.98 +/- 1.06 mumol/l, P less than 0.001) or the control ill group (5.56 +/- 0.59 mumol/l, P less than 0.001). In post-operative patients serum DHAS levels fell to below pre-operative levels reaching a nadir at day 8 (0.54 +/- 0.19 vs 1.66 +/- 0.56 mumol/l, P less than 0.02). In burned patients serum cortisol levels were increased on admission (661 +/- 91 vs 359 +/- 30 nmol/l, P less than 0.005) and remained high over the study period. Serum androstenedione concentrations were also high on admission (7.5 +/- 1.0 vs 3.9 +/- 0.3 nmol/l, P less than 0.02). Serum DHAS concentrations were similar to control values on admission (6.8 +/- 1.2 vs 5.2 +/- 0.7 mumol/l), fell to low levels thereafter reaching a nadir during week 3 (1.6 +/- 0.6 mumol/l, P less than 0.001). Steroid synthesis in times of chronic illness may be diverted from adrenal androgen to corticosteroid pathways ensuring maintained secretion of cortisol, which is essential to the health of ill patients.

Adrenal Cortex↗

Male hypogonadism--a non-specific consequence of illness.

Depressed thyroid hormone levels are commonly found in sick patients. Low serum testosterone concentrations have also been described in men suffering from a number of illnesses. To investigate whether this might be a non-specific marker of illness, various endocrine parameters were measured in 30 male patients in a general medical ward. Patients were suffering from a wide spectrum of medical disorders and were not receiving drugs known to affect endocrine function. Results were compared with a healthy age-matched control group. Serum testosterone concentrations (mean +/- SE) were low in the patient group (8.9 +/- 1.1 vs. 18.2 +/- 1.4 nmol/l, p less than 0.001), correlated significantly with serum T3 levels but were not related to prognosis. Half the patients had testosterone levels below the normal control range. Changes in testosterone concentrations could not be explained on the basis of binding protein changes, hyperprolactinaemia or depressed pituitary secretion of gonadotrophins. Depression of serum testosterone concentrations is a non-specific marker of illness.

Adolescent↗

Oestradiol levels in diabetic men with and without a previous myocardial infarction.

Elevated oestradiol levels have been found in men with a previous myocardial infarction and it has been suggested that hyperoestrogenaemia may explain partly the increased risk of coronary heart disease in diabetes mellitus. Therefore we have measured concentrations of oestradiol and testosterone (the main substrate for oestradiol) in a group of diabetic men with a previous myocardial infarction (n = 15), a matched group of diabetic men without overt cardiovascular disease (n = 13) and a group of healthy, non-diabetic men (n = 15). The diabetics had elevated oestradiol levels (p less than 0.03) despite lower testosterone levels (p less than 0.02) compared with control subjects. In the diabetic patients, a correlation between oestradiol and testosterone was found (r = 0.55, p less than 0.02) which suggested that the elevated oestradiol levels were only partly derived from the aromatization of testosterone. There were no differences in oestradiol or testosterone levels between the two diabetic groups. This study has shown that endogenous hyperoestrogenaemia is a consistent finding in diabetic men, irrespective of whether they have or have not sustained a previous myocardial infarction. The source of the raised oestradiol levels is uncertain. It is unclear whether hyperoestrogenaemia can be regarded as a risk for myocardial infarction in diabetic men.

Diabetes Complications↗

The effect of tamoxifen therapy on thyroid function tests.

Serum tri-iodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations were measured in 50 postmenopausal patients with breast cancer receiving tamoxifen therapy. Ten patients (20%) showed an elevation of serum total T4 concentrations and two of these patients showed additional elevation of serum total T3 levels. One patient had a persistently raised free T4 concentration and was considered to be thyrotoxic. Serum thyroxine-binding globulin (TBG) was estimated in six patients with elevated total T4 concentrations and was found to be raised in each case. Total serum T4 concentrations rose in seven of ten additional patients after starting tamoxifen therapy. However this change did not reach statistical significance. This trend in serum T4 concentrations was not shown in ten normal volunteers taking tamoxifen for 1 week.

Breast Neoplasms↗

The effect of 5-fluorouracil on rat adrenal function.

This study was undertaken to determine the effects of 5-fluorouracil on corticosteroidogenesis and adrenal size in the rat. The rats were injected intraperitoneally with 5-FU (12.5 mg kg-1 or 25 mg kg-1), normal saline or actinomycin D (0.02 mg kg-1), daily for 10 days. High-dose 5-FU induces adrenal hyperplasia, in association with mild impairment of corticosteroidogenesis (manifest by lower corticosterone and higher ACTH levels). The response to low-dose 5-FU and actinomycin D is of lesser adrenal hyperplasia, relative to high-dose 5-FU (P less than 0.05) and elevated corticosterone levels. There may be a dose-related effect on the suppression of corticosteroidogenesis in the rat by 5-FU.

Adrenal Cortex↗

Organon OD 14 (tibolone) and menopausal dynamic hormone profiles.

Hormonal profiles were studied in 15 post-menopausal women, 7 of whom had been treated with Organon OD 14 (Tibolone) and 8 with placebo tablets for 3 yr. In the Tibolone-treated group, the sex hormone binding globulin (SHBG) levels were significantly lower, while the estimated free testosterone levels, the testosterone/SHBG ratio and the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) were significantly higher than in the placebo group. Prolactin and triiodothyronine (T3) concentrations were lower in the actively treated group, although the differences were not statistically significant. No significant differences were observed with respect to thyroxine (T4), TSH, basal cortisol or cortisol response to synacthen.

Anabolic Agents↗