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C W Burke

Publications and source records attributed to C W Burke.

At least 19 recordsLinked to original sources
PubMed1997

An account of the quality of life of patients after treatment for non-functioning pituitary tumours.

OBJECTIVE: Studies assessing quality of life in GH-deficient adults have shown varying results. This may be due to a number of factors including varying causes of GH deficiency, the use of radiotherapy in treatment and patient selection. We aimed to assess whether anterior pituitary hormone deficiency or external pituitary radiotherapy influenced the quality of life of patients with non-functioning pituitary tumours. PATIENTS: We studied 48 patients treated and under follow-up for non-functioning pituitary tumours on standard hormone replacement therapy excluding GH. There were 21 females and 27 males with a mean age of 59 +/- 12 years. We also studied 42 control patients who had undergone mastoid surgery and were followed at least annually. There were 17 females and 25 males with a mean age of 61 +/- 14 years. DESIGN: All patients attended a research clinic and completed the Short Form 36 (SF36) and General Well Being Schedule (GWBS) to assess quality of life. Thyroid function tests, IGF1 and IGFBP3 were measured on all patients. Gonadotrophin and cortisol measurements were made on the patients with pituitary disease where appropriate. RESULTS: IGF1 and IGFBP3 levels were lower in the pituitary patients compared with controls: 104 +/- 98 vs 143 +/- 37 micrograms.l (P < 0.0001) and 2.9 +/- 0.75 vs 3.3 +/- 0.52 mg/l (P < 0.004). There were no significant differences in the quality of life scores between the pituitary patients and the control subjects. There was also no difference in quality of life between pituitary patients with two or more hormone deficiencies (n = 29) compared with controls. Patients who had received radiotherapy (n = 18), when compared with controls, had a decreased mental health score using the SF36 71 +/- 21 vs 81 +/- 17 (P < 0.05) and decreased total GWBS score 70 +/- 20 vs 82 +/- 17 (P < 0.05). Subscore analysis of GWBS showed this to be due to depression and decreased control of emotions. CONCLUSIONS: We found that the quality of life of patients treated and under follow up for non-functioning pituitary tumours was similar to that of patients treated by mastoid surgery and under similar follow up. The pituitary patients deficient in two hormones and thus most likely to be GH deficient were also similar to the controls. These results suggest that adding GH replacement in this patient group may not be routinely indicated for improvement in quality of life and needs careful assessment. Patients who had received radiotherapy were more depressed and anxious than controls. Further investigation into the psychological and psychomotor effects of radiotherapy in this group of patients is required.

Aged↗
PubMed1995

P53 protein accumulates in Cushings adenomas and invasive non-functional adenomas.

The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state.

Adenoma↗
PubMed1994

An audit of selected patients with non-functioning pituitary adenoma treated by transsphenoidal surgery without irradiation.

OBJECTIVE: To determine whether the rate of tumour regrowth in patients with non-functioning pituitary tumour treated by transsphenoidal surgery and selected for observation without post-operative irradiation is acceptably low, and to identify a group of patients who could appropriately avoid pituitary irradiation. SUBJECTS: One hundred and thirty-two patients treated by transsphenoidal surgery, of whom 98 did not undergo post-operative irradiation. These 98 were selected as having had apparently complete surgical removal, and as lacking features of tumour invasion or rapid growth; 73 of them are being followed by serial pituitary imaging to detect tumour regrowth. RESULTS: Forty-two patients who have been imaged on two or more occasions or more than two years after operation have shown no sign of tumour regrowth; 25 of them have been imaged at 3 or more years after operation, 13 at more than 5 years, and 4 at more than 10 years. Eight patients have shown regrowth as judged by imaging, although only one had pressure symptoms at the time; 5 out of 6 of these recurrences were found within 5 years of operation (two cannot be timed). The unirradiated group of 73 patients showed 90% recurrence-free survival at 5 years (95% confidence limits 80-100%). CONCLUSIONS: Provided that careful surgery and meticulous recall mechanisms for imaging can be ensured, patients so selected may be given the information contained in these results and offered the choice of follow-up by imaging alone, without pre-emptive irradiation. We recommend that they should be imaged 6-8 weeks post-operatively, then at either 6 or 12 months depending on the appearance, and then every 3-5 years for at least 15 years. By this means, many patient-years of good health and relative medical independence can be gained, together with some financial saving.

Adenoma↗
PubMed1994

Quinagolide efficacy and tolerability in hyperprolactinaemic patients who are resistant to or intolerant of bromocriptine.

OBJECTIVE: To audit the efficacy of quinagolide (CV205-502, Norprolac, Sandoz) in lowering prolactin, and its tolerability, in patients with bromocriptine resistance (BCR) or bromocriptine intolerance (BCI), in view of the paucity of results published in patients specifically with BCR or BCI, by collating results in our own patients with the reports in the literature. DESIGN: Open prospective, uncontrolled administration of quinagolide in patients with BCR (defined for this report as failure to attain normal prolactin levels after 4 months of bromocriptine at maximum tolerated doses), or BCI (defined as a patient request to cease bromocriptine treatment because of side-effects at doses that were required, or failed, to normalize PRL levels). MEASUREMENTS: Prolactin levels, menses or pregnancy, and side-effects. PATIENTS: Six with BCR, and six with BCI (microprolactinoma in 7, macroprolactinoma in 5), treated with quinagolide 75 micrograms nightly increasing incrementally to a maximum of 450 micrograms. One patient who had taken part in a multicentre study of quinagolide in macroprolactinomas had BCI, and 11 further patients in the endocrine clinic who had BCR or BCI were offered quinagolide therapy under named-patient compassionate arrangements. RESULTS: Normal prolactin in 4/5 with BCR (3/6 with side-effects, none of them quinagolide intolerant), and normal prolactin in 2/6 with BCI (4/6 with side-effects, two of them quinagolide intolerant). CONCLUSIONS: Results in our 12 patients are broadly in line with those in 51 patients with bromocriptine resistance and 39 with bromocriptine intolerance extracted from various published reports, which together suggest that prolactin can be normalized in 16% of patients with bromocriptine resistance by quinagolide in doses of 225 micrograms or less, and in a further 20% by higher doses up to 600 micrograms. In bromocriptine intolerance, prolactin was normalized by quinagolide in doses of 225 micrograms or less in 58% of published cases and in 3 more patients by higher doses up to 1050 micrograms. About half the patients with bromocriptine resistance or bromocriptine intolerance who are treated with quinagolide experience side-effects, and around 7% are quinagolide intolerant. Doses need not exceed 225 micrograms, until failure to respond at this dose level is demonstrated.

Adult↗
PubMed1994

p53 Protein accumulates in Cushings adenomas and invasive non-functional adenomas.

The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state.

Adenoma↗
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↗
PubMed1989

Perifusion studies of bromocriptine-treated and untreated macroprolactinomas: effects of dopamine, bromocriptine and TRH.

There have been no detailed in-vitro studies of PRL secretion by human macroprolactinoma cells exposed to bromocriptine (BC) to within a few days of surgical removal. We have studied cells from four such tumours (serum PRL 7.05-247 U/l) and six untreated tumours (serum PRL 4-80.35 U/l) using a perifusion technique. The BC-treated tumours had shown tumour shrinkage and were treated until 40-96 h before surgery, but in one patient serum PRL had not suppressed below 15 U/l despite chronic treatment. Pretreatment serum PRL responses to TRH were blunted in all 10 patients. During perifusion with dopamine (DA, 5 mumol/l) untreated prolactinomas had a higher PRL secretion rate (19.3 +/- 2.7 microU/mg tissue/min, mean +/- SEM) than BC-treated (3.9 +/- 0.7, P = 0.005). When DA was removed, PRL secretion from untreated tumours increased to 129.7 +/- 18.7 microU/mg/min, but in three of the BC-treated, little increase occurred. In the fourth (from the patient whose serum PRL had not fully suppressed) PRL secretion increased from 4.4 to 25.6 microU/mg/min after DA withdrawal, and DA and BC dose-related inhibition of PRL was similar to that observed in untreated tumours. TRH (10 ng/ml), without DA, provoked increased PRL release from both untreated (266% basal secretion, n = 3) and BC-treated (298%, n = 3) tumours; this effect was completely inhibited by DA (5 mumol/l). The absence of hormones other than PRL following potassium (55 mmol/l) excluded contaminating normal pituitary. We conclude: (1) The effects of BC on prolactinoma PRL secretion may persist for at least 4 days; (2) partial in-vivo BC resistance can be due to factors other than DA receptor malfunction; (3) the apparent discrepancy between in-vivo and in-vitro TRH responses was consistent with the presence of increased hypothalamic DA tone in vivo; and (4) BC may have differential effects on TRH and DA-controlled PRL pools in the tumourous lactotroph.

Bromocriptine↗
PubMed1989

Studies of two thyrotrophin-secreting pituitary adenomas: evidence for dopamine receptor deficiency.

Of 22 previously reported patients with TSH-secreting pituitary adenomas challenged with dopamine agonists, 18 showed no decrease in serum TSH. There have been few in-vitro studies of these rare tumours so the mechanism of the dopaminergic resistance has remained obscure. We describe two further patients with thyrotrophinomas; the first was thyrotoxic (T3 6.1 nmol/l, TSH 7 mU/l) and the second was diagnosed after radioiodine for presumed Graves' disease. The second patient had an alpha-subunit: TSH molar ratio less than unity (0.27). In-vivo TSH responses to TRH, bromocriptine and domperidone were compared with those of the resected tumour cells in vitro, the latter studied using a continuous perifusion system. Dopamine receptors were sought in membranes from each tumour using a radioreceptor assay employing 3H-spiperone. Patient 1 showed significant increases in serum TSH (7 to 13 mU/l) and alpha-subunit (18.7 to 385 ng/ml) after 200 micrograms TRH (i.v.) but patient 2 showed no such increases (TSH: 69 to 72 mU/l, alpha-subunit: 4.9 to 5.2 ng/ml). Neither patient showed a change in serum TSH following bromocriptine 2.5 mg (orally) or domperidone 10 mg (i.v.), though serum PRL responded normally. Serum TSH from patient 1 was of apparently normal molecular size but increased bioactivity (B/I ratio 3.8) and that from patient 2 was of increased molecular size but reduced bioactivity (B/I ratio 0.1). Tumour cells from each patient immunostained for TSH beta and alpha-subunit, and secreted TSH in vitro. The first showed dose-dependent TSH release after TRH (1-100 ng/ml) which could not be inhibited by dopamine (5 mumol/l) but the second was unresponsive to TRH in vitro. Neither tumour showed inhibition of TSH release by dopamine (5 mumol/l) or bromocriptine (0.01-10 nmol/l) and neither contained membrane-bound dopamine receptors. The results suggest that the dopaminergic resistance typical of most TSH-secreting pituitary adenomas may be due to altered or absent membrane-bound dopamine receptors.

Adenoma↗
PubMed1989

Intrasellar gangliocytoma containing gastrin and growth hormone-releasing hormone associated with a growth hormone-secreting pituitary adenoma.

A 74-year-old acromegalic found to have an intrasellar gangliocytocytoma and GH-secreting pituitary adenoma is described. The gangliocytoma contained immunoreactive gastrin and, to a lesser extent, GHRH, and the adenoma immunostained for GH. Gastrin has not been previously reported in hypothalamic gangliocytomas. Since this peptide has been demonstrated in normal hypothalamus and pituitary, and provokes GH release when administered intraventricularly, it may have caused GHRH release from the gangliocytoma by a local paracrine action and led to adenoma formation and acromegaly.

Adenoma↗
PubMed1988

The human leucocyte sodium pump in Cushing's syndrome.

Because corticosteroids have important effects on sodium homeostasis, we studied leucocyte 22Na efflux in patients with Cushing's syndrome. The ouabain-sensitive 22Na+ efflux rate constant was raised in Cushing's syndrome (mean +/- SD 2.84 +/- 0.32 vs 2.35 +/- 0.53/h, P less than 0.001, n = 15). This efflux rate constant correlated with the urinary free cortisol (rs = 0.61, P less than 0.02), but less significantly with the 0900 h plasma cortisol (rs = 0.46, P less than 0.08). There was no correlation with the supine plasma aldosterone. Intracellular sodium content was significantly lower in Cushing's syndrome (21.1 +/- 4.6 vs 27.8 +/- 9.5 mmol/kg dry weight, P less than 0.01), with a raised intracellular potassium to sodium content ratio (16.1 +/- 3.3 vs 12.9 +/- 3.6, P less than 0.01). After treatment of the Cushing's syndrome by trans-sphenoidal adenomectomy or adrenalectomy, these defects in cellular sodium balance were corrected. Thus, the distribution of sodium between intra- and extracellular fluid may be affected by adrenal corticosteroids via an action on the sodium pump.

Adult↗
PubMed1988

Body fat topography in women with androgen excess.

The relationship between body fat distribution and androgen excess was determined in 168 premenopausal women of varying degrees of androgen excess. In 84 women with the polycystic ovary syndrome or idiopathic hirsutism, the waist:hips girth ratio (WHR) was 0.81 +/- 0.01 (mean +/- s.e.m.) and was significantly greater (P less than 0.001) than in an age- and weight-matched group of 84 non-hirsute women (0.77 +/- 0.01), indicating upper body fat predominance in the hirsute subjects. Plasma testosterone was directly correlated with the WHR (r = 0.55, P less than 0.001) and this relationship was independent of obesity level, supporting the hypothesis that plasma androgens are an important determinant of body fat topography in premenopausal women.

Adipose Tissue↗
PubMed1987

Acute and chronic pituitary failure resembling Sheehan's syndrome following bites by Russell's viper in Burma.

Pituitary function was investigated in 9 patients in shock after Russell's viper bites and in 24 individuals who had been severely envenomed 2 weeks to 24 years previously. 3 out of 9 patients had hypoglycaemia and inappropriately low serum cortisol, plasma growth hormone, and plasma prolactin concentrations. 4 who died had pituitary haemorrhage and 1 had adrenal haemorrhage as well. Of the 24 who had apparently recovered from bites, 7 had clinical features of hypopituitarism and no response in plasma growth hormone or prolactin concentrations to symptom-producing insulin-induced hypoglycaemia. 4 of these 7 had a sluggish serum cortisol response to 'Synacthen Depot' and 5 had an abnormal cortisol response to hypoglycaemia. 4 men with symptoms who were tested had low serum testosterone concentrations; serum thyroxine was also low in these men but not in 2 women with menstrual disturbances and impaired insulin responses. Of the 17 individuals without clinical evidence of endocrine disease, 4 had pituitary hormonal abnormalities. Russell's viper envenoming may thus produce a disorder resembling Sheehan's syndrome.

Acute Disease↗
PubMed1987

Misinterpretation of prolactin levels leading to management errors in patients with sellar enlargement.

Serum prolactin concentrations and clinical features were correlated with the histopathologic diagnosis in 128 patients, without acromegaly or Cushing's syndrome, referred for surgical treatment of a presumed pituitary adenoma. A serum prolactin concentration of more than 8,000 mU/liter was always due to a prolactin-secreting adenoma. Prolactin levels of less than 8,000 mU/liter occurred with a variety of pathologic diagnoses. Fifteen patients had lesions other than pituitary adenomas, most commonly intrasellar craniopharyngioma; 10 of these had modest hyperprolactinaemia (maximum, 5,260 mU/liter) and four had received inappropriate bromocriptine therapy. Adenomas that were not prolactinomas frequently caused mild hyperprolactinaemia, although this was usually less than 3,000 mU/liter; three of these patients, however, had serum prolactin concentrations greater than this (maximum, 8,000 mU/liter). If the serum prolactin concentration is less than 3,000 mU/liter in the presence of significant pituitary enlargement, surgical removal is essential for both diagnosis and treatment since only prolactin-secreting adenomas are likely to shrink with dopamine agonist therapy. A serum prolactin concentration between 3,000 and 8,000 mU/liter is consistent with any diagnosis, whether the fossa is greatly enlarged or not, and great care must be taken with dopamine agonist therapy in such patients.

Adenoma↗