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Biomedical subjects

G H Beastall

Publications and source records attributed to G H Beastall.

At least 55 records · Page 3Linked to original sources

Hilus cell pathology and hirsutism.

Hilus cell abnormalities are uncommon causes of hirsutism with virilization. Although hilus cell tumours have been well described, hilus cell hyperplasia is rare and is poorly defined clinically. We describe three cases of hilus cell hyperplasia and compare them with a case of hilus cell tumour. Both pathologies were associated with increased testosterone and oestradiol secretion. Suppression of testosterone to the 'normal range' in response to exogenous oestrogen was seen only in the cases with hyperplasia; only partial responsiveness was seen in the case with hilus cell tumour. Bilateral oophorectomy offers the potential for cure for both hilus cell hyperplasia and tumour.

Aged↗

The loss of circadian rhythm for intact parathyroid hormone and nephrogenous cyclic AMP in patients with primary hyperparathyroidism.

The measurement of serum intact parathyroid hormone (PTH) (1-84) over a 24-h period has shown the existence of a circadian rhythm in normal males which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate (N-cAMP) in normals which are also absent in primary hyperparathyroidism. Serum calcium, adjusted for variations in albumin concentrations, showed a transient fall in normal subjects prior to the nocturnal rise in PTH (1-84). A similar transient fall in serum adjusted calcium was observed in the hyperparathyroid patients. Serum phosphate showed a circadian rhythm in normal subjects, and an attenuated rhythm persisted in primary hyperparathyroidism. These data suggest that both ionic factors and higher centres play important roles in the fine control of PTH (1-84) secretion.

Adult↗

The circadian rhythm of intact parathyroid hormone-(1-84): temporal correlation with prolactin secretion in normal men.

Serum PTH-(1-84), PRL, and adjusted calcium concentrations were determined at 30-min intervals for a 24-h period in six normal adult men. PTH-(1-84) and PRL both exhibited two peaks of increased secretion [1600-1900 and 0200-0600 h for PTH-(1-84); 2000-2200 and 0400-0800 h for PRL]. For each subject there was a striking similarity in the magnitude of secretion of the two hormones and a consistent temporal relationship. Thus, the maximum correlation coefficients of 0.62-0.83 were obtained for the six subjects when the PRL surge lagged that of PTH-(1-84) by 0.5-3.5 h. In contrast, the correlation between PTH-(1-84) and adjusted calcium was weaker (r = -0.36 to -0.66) and showed no consistent temporal relationship (0.0-10.5 h). These data support the concept of higher center control of PTH-(1-84) secretion with the possible involvement of factors common to the control of PRL secretion.

Adult↗

Measuring free thyroxin by using magnetic antibody-containing microcapsules.

We describe a novel magnetic-separation microencapsulated antibody displacement assay for free thyroxin. The method is rapid (results available in just over an hour), with a detection limit of 3 pmol/L, and an interassay precision of less than 10% over the range 8-75 pmol/L. Results are not influenced by changes in the concentration of thyroxin-binding globulin or albumin, nor by the presence of circulating anti-thyroxin antibodies or physiological concentrations of nonesterified (free) fatty acids. A reference interval of 8.4-18.4 pmol/L was established for a large euthyroid adult population. Patients with various nonthyroidal illnesses exhibited a similar reference interval (6.2-17.4 pmol/L). Results from pregnant women, at all stages of gestation, were within the nonpregnant euthyroid reference interval. Complete discrimination was obtained between the euthyroid reference interval and values from patients with untreated thyrotoxicosis (24-75 pmol/L). Excellent, though incomplete, discrimination was obtained for patients with untreated hypothyroidism (less than 3.0-9.0 pmol/L). Results for a group of patients defined as having compensated euthyroidism (5.0-15 pmol/L) showed considerable overlap with the euthyroid reference interval. Patients taking thyroxin, who were clinically euthyroid and whose serum concentration of thyrotropin was within its euthyroid reference interval, had free thyroxin concentrations in the range 13.4-24.2 pmol/L. We discuss the validity of this assay in clinical practice.

Analysis of Variance↗

Thyroid hormone concentrations in epileptic patients.

Anticonvulsants are associated with decreased serum thyroid hormone concentrations. We have studied thyroid function in 54 epileptic patients on a variety of drugs (19 on carbamazepine, 13 on phenytoin, 10 on sodium valproate, 12 on polypharmacy). For comparison, 14 untreated epileptics and 11 healthy unmedicated volunteers were included as controls. Total thyroxine (T4) concentrations were reduced in patients taking enzyme-inducing drugs (carbamazepine and/or phenytoin) compared with both controls and patients taking sodium valproate. Similar differences were shown with each individual drug. All nine patients whose circulating T4 was below the lower limit of the reference range were taking enzyme inducers. Free thyroxine concentrations were also reduced in individuals treated with carbamazepine and phenytoin with five values falling beneath the reference range. Tri-iodothyronine and thyrotropin appeared unaffected by anticonvulsant administration. Thyrotropin releasing hormone stimulation revealed no true hypothyroidism. The lowering effect of anticonvulsant drugs on circulating total and free T4 was not exhibited by the non-inducing sodium valproate. These data support the influence of enzyme induction as a likely mechanism for reduced thyroxine concentrations in treated epileptic patients.

Anticonvulsants↗

Hyperinsulinism associated with primary renal cell carcinoma.

A case is reported of a patient with symptomatic hyperinsulinism associated initially with a renal cell carcinoma and then later, with secondary deposits from the same tumor. Evidence points to a strong possibility of renal tumor involvement in the production of insulin hypersecretion.

Carcinoma, Renal Cell↗

The effect of testosterone replacement on plasma lipids and apolipoproteins.

Ten men with Klinefelter's syndrome were studied to assess the effect of testosterone replacement on plasma lipids and apolipoproteins. Measurements taken before the insertion of a testosterone ester implant were compared with those obtained 1 week and 4 weeks later. Mean plasma testosterone, androstenedione, total cholesterol and calculated LDL-cholesterol increased significantly after 1 and 4 weeks. No significant changes were seen in total plasma concentrations of HDL-cholesterol, HDL-cholesterol subfractions 2 and 3 or in apoplipoproteins A-I, A-II or B. A significant correlation was seen between total cholesterol and plasma oestradiol concentrations (Rs = 0.61; P less than 0.001). A significant negative correlation was seen between the concentrations of total testosterone and total triglyceride (Rs = -0.56; P less than 0.005) but not with the other lipid parameters. Testosterone replacement is associated with slight but potentially adverse changes in plasma cholesterol levels.

Adult↗

Prolactin response to TRH is unaltered by pulsatile infusion of LHRH.

Eleven boys with constitutional delay of puberty and 7 patients with hypogonadotrophic hypogonadism underwent standard thyrotrophin-releasing hormone (TRH) tests prior to and following 6 days' pulsatile infusion of luteinizing hormone-releasing hormone (240 ng/kg/pulse). There were no significant differences in basal, peak or incremental prolactin responses to TRH between the 2 groups of patients and there were no differences in the magnitude of prolactin response to TRH in either group of patients during pulsatile therapy when compared with preinfusion responses.

Adolescent↗

Serum thyroglobulin--its measurement and clinical use.

Radioimmunoassays (RIA) have been shown to be unreliable in measuring serum thyroglobulin levels in patients with antithyroglobulin antibodies. The aim of this study was twofold. Firstly to compare the abilities of two immunoradiometric assays (IRMA), one commercially available, the other an 'in house' assay, with a conventional RIA. In addition the prognostic value of serum thyroglobulin levels in patients likely to relapse following a course of antithyroid drugs for Graves' disease was examined. The results obtained showed both of the IRMA methods to be unaffected by the presence of antithyroglobulin antibodies. Serum thyroglobulin levels were found to be poor predictors of relapse or remission following a 12 month course of antithyroid drugs.

Animals↗

The effects of pulsatile GnRH infusion upon the diurnal variations in serum LH and testosterone in pre-pubertal and pubertal boys.

The aim of the present study was to determine the effects of exogenous GnRH pulsatile infusions on the diurnal variations of LH and testosterone secretion which occur in late pre-puberty and early puberty. GnRH infusions were administered to 12 short stature males in pre-puberty or early puberty, over 6-day periods. In 6 patients, GnRH doses of 2.5, 7.5 and 15 micrograms/pulse were used and 24-h profiles of serum LH and testosterone were measured before and at the end of the infusions. In the remaining 6 patients GnRH was administered at a dose of 7.5 micrograms/pulse and profiles between 21.00 and 06.00 h the following day were determined. Pre-infusion profiles demonstrated nocturnal LH and testosterone rises in all patients. Median pre-infusion serum LH prior to midnight was 2.2 U/l (range 1.0-5.4) rising to 3.7 U/l (range 1.9-10.7) during GnRH administration (p less than 0.005). After midnight, median pre-treatment serum LH concentration was 4.3 U/l (range 2.7-7.5) which remained unaltered by GnRH administration (median 4.8 U/l, range 2.9-7.9, p greater than 0.05). Median pre-therapy serum testosterone before midnight was 0.8 nmol/l (range 0.1-7.1) rising significantly (p less than 0.05) to 4.1 nmol/l (range 0.2-8.0). Following therapy, post-midnight median serum testosterone rose from 4.8 (range 0.4-9.4) to 7.0 nmol/l (range 0.5-13.9, p greater than 0.05). Diurnal variation in LH and testosterone secretion, therefore, is maintained during exogenous GnRH administration to pre-pubertal and pubertal boys. Response to exogenous GnRH pulses may be significantly influenced by endogenous GnRH.

Adolescent↗

The circadian rhythm of intact parathyroid hormone (1-84) and nephrogenous cyclic adenosine monophosphate in normal men.

A pronounced circadian rhythm has been demonstrated for intact parathyroid hormone (1-84) in the serum of normal male adults. The broad nocturnal rise of parathyroid hormone (1-84) secretion appears to be of physiological significance, for it is accompanied by a significant rise in nephrogenous cyclic adenosine monophosphate. The rate of return of parathyroid hormone (1-84) to baseline concentrations varies between individuals, an observation which has implications for the optimal time of sampling for the investigation of possible mild hyperparathyroidism.

Adult↗

Adrenal androgens in insulin-dependent diabetes mellitus.

The adrenal androgens dehydroepiandrosterone sulphate (DHAS) and androstenedione (A2) are major secretory products of the adrenal gland, although their precise function is unclear. There is limited evidence to suggest adrenal androgen levels may be altered in diabetes, and that insulin secretion may influence these hormones. Therefore we have measured fasting levels of serum DHAS, A2, testosterone, oestradiol (in males only), sex hormone binding globulin (SHBG), HbA1 and C-peptide (basal and glucose stimulated), in 17 post-pubertal, uncomplicated patients with insulin-dependent diabetes mellitus (IDDM), and made comparisons to 17 of their sex and age-matched (to within 5 yr) non-diabetic siblings. Concentrations of the adrenal androgens were within the laboratory normal range in all the subjects and no differences were noted between the diabetics and their siblings or between males and females. No correlations were noted between the hormones and either HbA1 or C-peptide. In contrast to previous reports we have found that C-peptide status does not influence adrenal androgen levels, and that normal concentrations of these androgens are found in non-ketotic patients with IDDM.

Adrenal Cortex Hormones↗

How sensitive are immunometric assays for thyrotropin?

The usual method for calculation of the "sensitivity" of thyrotropin immunometric assays is multireplicate analysis of the zero analyte standard. Although this is a statistically valid estimate of the scatter likely to be found in the response variable, it is unrelated to normal analytical practice (usually analysis in duplicate) and estimates intra-assay errors only. This study was designed to assess the analytical performance of 10 immunometric assays used routinely for measurement of thyrotropin in human serum. Response data from each assay were accumulated to provide (a) an estimate of "sensitivity" from multireplicate analysis and (b) an estimate of "minimum detection limit," relating directly to errors associated with routine performance and derived from a minimum of 500 duplicate analyses. We conclude that the "minimum detection limit" should be promoted as a more meaningful measure of assay performance at low analyte concentrations than the "sensitivity" derived from multireplicate analysis of the zero-analyte standard.

Evaluation Studies as Topic↗

Counterregulatory hormonal responses to hypoglycaemia in type 1 (insulin-dependent) diabetes: evidence for diminished hypothalamic-pituitary hormonal secretion.

Acute insulin-induced hypoglycaemia in humans provokes autonomic neural activation and counterregulatory hormonal secretion mediated in part via hypothalamic stimulation. Many patients with Type 1 (insulin-dependent) diabetes have acquired deficiencies of counterregulatory hormonal release following hypoglycaemia. To study the integrity of the hypothalamic-pituitary and the sympatho-adrenal systems, the responses of pituitary hormones, beta-endorphin, glucagon and adrenaline to acute insulin-induced hypoglycaemia (0.2 units/kg) were examined in 16 patients with Type 1 diabetes who did not have autonomic neuropathy. To examine the effect of duration of diabetes these patients were subdivided into two groups (Group 1: 8 patients less than 5 years duration; Group 2: 8 patients greater than 15 years duration) and were compared with 8 normal volunteers (Group 3). The severity and time of onset of hypoglycaemia were similar in all 3 groups, but mean blood glucose recovery was slower in the diabetic groups (p less than 0.01). The mean responses of glucagon, adrenaline, adrenocorticotrophic hormone, prolactin and beta-endorphin were similar in all 3 groups, but the mean responses of growth hormone were lower in both diabetic groups than in the normal group (p less than 0.05). The mean increments of glucagon and adrenaline in the diabetic groups were lower than the normal group, but these differences did not achieve significance; glucagon secretion was preserved in several diabetic patients irrespective of duration of disease. Various hormonal responses to hypoglycaemia were absent or diminished in individual diabetic patients, and multiple hormonal deficiencies could be implicated in delaying blood glucose recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Hormonal responses in pubertal males to pulsatile gonadotropin releasing hormone (GnRH) administration.

Twenty-two boys (9 with delayed puberty and 13 with short stature) ages 12.3 - 17.8 yr, and 10 adult males with idiopathic hypogonadotropic hypogonadism (ages 17.3 - 41.1 yr) have been studied following pulsatile, sc GnRH therapy (240 ng/kg/pulse) over 6 days. Mean pre- and post-therapy LH and FSH concentrations were estimated by 15 min blood sampling over 3-h periods immediately before and at the end of the treatment period. There were significant correlations between the mean pre- and posttreatment LH and FSH concentrations (r = 0.82, p less than 0.001 and r = 0.51, p less than 0.02, respectively) for the 2 groups of peripubertal boys when assessed together. Nine of the 10 adults with hypogonadism showed proportionately greater gonadotropin increments following pulsatile therapy when compared with the peripubertal boys. Standard bolus GnRH tests (100 micrograms iv) did not differentiate between the three groups of patients before pulsatile GnRH therapy. Bolus GnRH tests could predict the subsequent response to pulsatile therapy in the peripubertal boys only. There was no significant change in LH increments following the GnRH bolus tests in either group, after pulsatile GnRH administration (p greater than 0.1). Early response to pulsatile GnRH administration is dependent upon the maturity of the hypothalamic-pituitary-testicular axis in males with delayed puberty or short stature. Patients with hypogonadotropic hypogonadism do not show this relationship.

Adolescent↗

Endocrine effects of examination stress.

1. We have studied endocrine function in nine healthy young men 16 weeks before and immediately after Final degree examinations. Factors other than psychological stress which might have affected hormone levels were excluded. 2. The presence of psychological stress at the time of examinations was confirmed by finding increased values for two self-rating anxiety scales. 3. Urine metadrenaline excretion was increased in all subjects at the time of examination. Serum and early morning urine cortisol as well as pituitary-testicular and pituitary-thyroid function and prolactin levels were unaffected by examination stress. 4. This study questions the popular belief that psychological stress stimulates prolactin secretion and suppresses pituitary-testicular function.

Adult↗

Prolonged hypogonadism in male patients with rheumatoid arthritis during flares in disease activity.

The pituitary-gonadal axis was assessed in 10 male patients during hospital admissions lasting 3-6 weeks (median 3 weeks) for flares for rheumatoid arthritis. Despite significant improvements in the Ritchie indices from median 16 (range 9-23) to 8.5 (range 5-20) (p less than 0.01) and ESR from median 67 mm/h (range 46-115 mm/h) to 58 mm/h (range 15-116 mm/h) (p less than 0.05) there were no significant changes in serum testosterone, LH, FSH, prolactin (PRL), cortisol or androstenedione during the admission periods. At follow-up (median 14 months, range 5-18 months after admission) there were further improvements in articular indices (median 7, range 3-13; p = NS) and ESR (median 20 mm/h, range 4-62 mm/h; p less than 0.05) and rheumatoid factor titres had fallen from median 1/1025 (range 1/126 to 1/1024) to median 1/512 (range 1/64 - 1/512). One patient showed biochemical features of progressive testicular failure. In the remaining patients, serum and derived free testosterone levels were significantly increased (p less than 0.01 respectively) and serum LH reduced (p less than 0.01). There were no changes, at this time, in prolactin, cortisol or androstenedione. Rheumatoid flares appear to be associated with prolonged suppression of testicular function.

Adult↗