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Biomedical subjects

C W Burke

Publications and source records attributed to C W Burke.

At least 19 recordsLinked to original sources
PubMed1992

Dopamine agonists and pituitary tumor shrinkage.

The primary aim of this review has been to clarify the tumor shrinking effects of dopamine agonists on pituitary macroadenomas of different cell types. Shrinkage is most dramatic for macroprolactinomas and is due to cell size reduction. Seventy-nine percent of 271 definite macroprolactinomas were reduced in size by at least 25%, and 89% shrank to some degree. Most shrinkage occurs during the first 3 months of treatment, although in a minority shrinkage is delayed. Dopamine agonist resistance during long-term therapy is exceptional. Drug withdrawal nearly always leads to a return of hyperprolactinemia, even after several years treatment, although early tumor reexpansion is unusual. About 10% of true macroprolactinomas do not shrink with dopamine agonists; the molecular mechanisms of such resistance have yet to be determined. Alternative formulations of BC and new dopamine agonists (CV 205-502 and cabergoline) are useful for the minority of patients unable to tolerate oral BC, but do not seem to further improve overall shrinkage rates. The risks of pregnancy have probably been overstated, and BC is suitable primary treatment for women with prolactinomas of all sizes; the drug can be used safely during pregnancy in the event of clinically relevant tumor expansion. The interpretation of different degrees of hyperprolactinemia is discussed and management strategies suggested. Most patients with macroprolactinomas now avoid surgery, but drug-induced, time-dependent tumor fibrosis should be remembered if surgery is contemplated. Nonfunctioning pituitary tumors are mostly of gonadotroph cell origin and may be associated with significant disconnection hyperprolactinaemia. Seventy-six of 84 well-characterized tumors showed no tumor shrinkage during dopamine agonist therapy. Possible explanations include abnormalities of dopamine receptor number and function. Preliminary evidence suggests that dopamine agonists may restrain the growth of some functionless tumors; most of these tumors, however, can be satisfactorily debulked using transsphenoidal surgery. In contrast to macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH-secreting) rarely shrink during dopamine agonist therapy, although the number of tumors studied is small.

Adenoma↗
PubMed1990

Vasopressin antagonist in early postoperative diabetes insipidus.

23 patients without diabetes insipidus before transfrontal (hypothalamic) or trans-sphenoidal (pituitary) surgery were studied prospectively to investigate the pathogenesis of early postoperative diabetes insipidus. 12 patients who underwent trans-sphenoidal surgery and who did not develop diabetes insipidus were used as controls. All received prophylactic corticosteroid replacement. Blood samples were obtained immediately after operation, at the onset of diabetes insipidus, and 24 h later. Immediately after trans-sphenoidal pituitary surgery, plasma vasopressin (AVP) was raised but had fallen to subnormal concentrations by the onset of diabetes insipidus. After transfrontal hypothalamic surgery diabetes insipidus occurred sooner and was associated with high plasma AVP immunoreactivity--but the plasma showed no antidiuretic bioactivity and greatly attenuated the antidiuretic response to standard AVP. Early diabetes insipidus after hypothalamic surgery is associated with release of a substance, presumably an analogue, from the damaged hypothalamo-neurohypophyseal system, which acts as an antagonist to normal AVP activity; after trans-sphenoidal operations diabetes insipidus seems to be caused by failure of AVP release.

Adolescent↗
PubMed1990

Transsphenoidal surgery for Cushing's disease: does what is removed determine the endocrine outcome?

Fifty-seven patients with pituitary-dependent Cushing's syndrome and eight with Nelson's syndrome underwent transsphenoidal pituitary exploration, with removal of macroscopically abnormal tissue in 64 patients and detailed histology of this in 63. The cure rate by stringent criteria 1 month later was 48 (83%) of the 58 with assessable data, who were followed for 225 patient-years. Two patients relapsed later, a rate of one per 112 patient-years of follow-up. In 27% of patients, the macroscopically abnormal tissue removed was histologically indistinguishable from normal pituitary gland but the cure rate was 82%, and a quarter of the patients in this group assessable for recovery of normal ACTH function gained it. Another 53% of biopsies showed corticotroph adenomas, and the cure rate in these was 89% though rather more (69%) recovered normal ACTH function. The remaining 20% of biopsies were consistent with corticotroph hyperplasia. The cure rate varied little whether the lesion was diffuse or localized, whether or not it was in the invasion zone/interlobar cleft, whether or not there was pituitary enlargement, or whether the surgery was radical or selective. Six patients, of whom three are cured, showed surgical or radiological evidence of invasion outside the pituitary fossa. The data are consistent with the idea that pituitary adenoma is merely the end stage of some other process in the corticotrophs, and cure often follows removal of a lesion other than adenoma. Of patients who were permanently cured, 47% regained normal ACTH function within 3 years of operation (none later), 53% remaining ACTH-deficient at 3 years or more. Of all patients 48% acquired gonadotrophin deficiency, 28% have TSH deficiency and 25% permanent diabetes insipidus. All these pituitary function deficits were more common after radical surgery and in patients with normal histology, The literature contains so little objective data on these functions that we cannot say whether the endocrine damage in our patients is exceptional or not.

Adenoma↗
PubMed1979

Marriage matters.

Explore the source record for details and available documents.

Counseling↗
PubMed1978

An immunological method for the purification of radiolabelled thyroxine.

A method for the removal of iodothyronine and iodide impurities from radiolabelled thyroxine is described. The principle of the method is to bind iodothyronine contaminants to specific antisera, and then to separate the antiserum-bound contaminants and iodide from the thyroxine by column chromatography. As reported here, the method is optimised for the removal of more than 98% of contaminating 3,5,3'-triiodothyronine and 99.8% of contaminating iodide from between 10 ng and 100 ng of thyroxine, where the molar ratio of thyroxine: 3,5,3'-triiodothyronine before purification is greater than or equal to 10:1. Recovery of purified thyroxine is more than 80%. The performance of the method is superior to that of preparative dialysis.

Animals↗
PubMed1977

Thyroid hormone kinetics: improved method for quantitative separation and measurement of the various radioiodothyronine injection.

An accurate and reproducible method for measurement of radioactive species in blood after in vivo injection of labelled iodothyronines is described. By extraction with high-affinity antisera, radioactive reverse T3 and T3 are separated from serum quantitatively. Radioiodide is quantitatively separated from radio-thyronine species and serum proteins by Sephadex G50 filtration. The residual mixture of radio-T4 and iodoprotein is quantitatively resolved by ion-exchange adsorption. Minimal misclassification of radiospecies occurs, and can be corrected for. Mean recoveries of various radiospecies added to serum were: radioiodide 98.9%, radio-rT3 87.6%, radio-L-T3 94.5%, radio-T4 98.0% and radioiodoprotein 94.5%. The performance of the method is superior to that of chemical methods such as trichloracetic acid precipitation, ion-exchange or alkaline Sephadex extraction, and chromatographic separation.

Chromatography, Gel↗
PubMed1976

Triiodothyronine and thyroxine in urine. I. Measurement and application.

Urinary triiodothyronine (T3) and thyroxine (T4) were measured by RIA, and T4 was also measured by competitive protein binding (CPB). pH 1-hydrolysable conjugates were 48% of total urinary T3, and enzyme- or pH 1-hydrolysable conjugates were 55% and 61% of total urinary T4. The mean unconjugated T3 excretion was 34.3 ng/h (0.99 mug T3/g creatinine) in normal subjects (no day-night rhythm found), 1.56 mug/g in late pregnancy, 0.82 mug/g in neonates (1-12 days), and was also unchanged in persons with high or low thyroxine-binding globulin (TBG). In thyrotoxicosis, mean T3 excretion was 281 ng/h, no values being in the normal range. In primary hypothyroidism it was 18.3 ng/h, but over half the values were in the normal range. The mean urinary unconjugated T4 was 82.2 ng/h (1.37 mug T4/g creatinine) in normal subjects, 1.6 mug/g in neonates, and unchanged in persons with high or low TBG, except that in pregnancy high values were compatible with increases protein excretion. Apparently increased day-time T4 excretion compared with night-time excretion may also be due to changes in protein excretion rate. The mean T4 in thyrotoxicosis was 337 ng/h (12% of values in the normal range) and 32.8 ng/h in primary hypothyroidism (over half the normal range). All the assays, especially that of T4 by CPB gave readings which were incorrect with protein concentrations above 100 mg/l. Urinary T3 and T4 assays for clinical purposes have few practical advantages over serum assays, despite the relationship of urine T3 and T4 to serum unbound levels.

Adolescent↗
PubMed1976

Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein.

Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4.

Chromatography, Gel↗
PubMed1976

Free cortisol in obesity; effect of fasting.

Plasma and urinary corticosteroids were measured in 13 obese subjects before and after high and low protein diets, and after fasting. During isocaloric high and low protein diets, urinary 17-oxogenic steroids and to a lesser extent urinary free cortisol excretion rose and fell in parallel with protein intake. Plasma unbound cortisol levels were not much changed by high or low protein intake. However, during 7 to 11 days total fasting, there was a highly significant rise in plasma unbound cortisol at 24.00. A smaller rise occurred at 09.00. The overall effect was a considerable diminution of the day-night variation of plasma unbound coritsol levels during fasting, and a rise in prevailing unbound cortisol levels and urinary free cortisol excretion. In 3 subjects tested these changes were reversed immediately by glucose re-feeding.

17-Ketosteroids↗
PubMed1976

Drug controlled of Cushing's syndrome. Combined aminoglutethimide and metyrapone therapy.

Eighteen patients with Cushing's syndrome (16 pituitary-dependent Cushing's disease, 1 ectopic ACTH syndrome, 1 primary adrenal adenoma) were given a combination of aminoglutethimide and metyrapone, with the object of controlling cortisol overproduction using less toxic doses than would be required with each drug alone. A preliminary trial of this combination using doses of aminoglutethimide of 1 g or more a day was assessed over 2 weeks. Control of cortisol overproduction and clinical improvement was achieved but side effects led to withdrawal of the drugs in 6 out of the 12 patients. A lower dose trial of this combination over 2 weeks, using 750 mg/day of aminoglutethimide also controlled cortisol overproduction and side effects led to drug withdrawal in only 2 out of 6 patients. Four of these patients were successfully controlled with even lower doses (500-750 mg/day of aminoglutethimide) for longer periods (26 days-1 year). This low regimen which consists of aminoglutethimide 500-750 mg daily, metyrapone 2 g daily, dexamethasone 0.5 mg b.d. and fludrocortisone 0.1 mg daily, is useful for preparing patients for operative treatments and may be used as a long-term treatment of milder cases.

Adrenocorticotropic Hormone↗
PubMed1975

Thyroid hormones in the elderly sick: "T4 euthyroidism".

Thyroid function and serum levels of triiodothyronine (T3) and thyroxine (T4) were investigated in 79 euthyroid geriatric patients. Of the 59 inpatients and 20 outpatients 35 (59%) and 2, respectively, had low T3 levels. In contrast, 7 (12%) and 6 (30%), respectively, had raised T4 levels. Two further patients were excluded from the study because of raised levels of thyroid-stimulating hormone. Thyroxine-binding globulin was greatly increased in both groups of patients, but low serum albumin levels were present in 31 (39%). Despite these changes free T3 and T4 indices closely followed total T3 and T4 levels. The difference between the two groups of patients did not correlate with body weight, diagnostic categories, age, drug treatment, or duration of stay in hospital.

Aged↗