Bilateral spontaneous pneumothoraces complicating AIDS-related Pneumocystis carinii pneumonia.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J S Bevan
Publications and source records attributed to J S Bevan.
The presentation and management of pituitary tumours in the elderly.
Twenty-two patients presenting with pituitary tumours (16 non-functioning) after the age of 70 years were identified in a review of all patients assessed in Oxford hospitals between 1982 and 1986. They were matched with younger patients, to compare modes of presentation and treatment outcome. Younger patients presented more commonly than elderly with symptoms of deficiency of adrenocorticotrophic hormone, thyroid-stimulating hormone or gonadotrophin, although the prevalence of biochemical deficiency was similar in the two groups. Trans-sphenoidal adenomectomy was performed on 12 elderly patients with visual impairment. Of those with field loss, seven improved, one was unchanged and two deteriorated after surgery, though one of the last was improved by haematoma evacuation, and two cranial nerve palsies resolved. There were no other peri-operative complications in the elderly. Transsphenoidal surgery is the treatment of choice for non-functioning tumours causing visual failure; it decompresses the adenoma with minimal morbidity and endocrine impairment, and is well tolerated by elderly patients.
Adenoma↗
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↗
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↗
Cholinergic blockade with pirenzepine improves carbohydrate tolerance and abolishes the GH response to meals in normal subjects.
Pretreatment of normal male volunteers with the cholinergic muscarinic receptor-blocking drug pirenzepine (200 mg p.o.) abolishes the delayed GH response to a meal stimulus. In addition, the glycaemic and insulin responses to meals are significantly reduced following this dose of pirenzepine. The data suggest that the effect of pirenzepine on the glucose response to meals is at least partly independent of the inhibition of GH release. Our findings are of relevance to the further investigation of cholinergic muscarinic antagonist in diabetes mellitus.
Adult↗
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↗
Bilateral renal cortical abscesses in a young woman with type 1 diabetes.
Serious complications of urinary tract infection, such as papillary necrosis or perinephric abscess, occur more frequently in diabetic patients. However, severe bilateral renal parenchymal infection with multiple intrarenal abscesses is not well recognized. We described an 18-year-old insulin-dependent diabetic woman with such infection, in whom renal imaging showed progression to a major perinephric abscess, but only after 5 weeks of intensive antibiotic therapy. Complete recovery followed surgical drainage and no renal cortical scarring was present on computerized tomographic scan 18 months later.
Abscess↗
Development of an invasive macroprolactinoma: a possible consequence of prolonged oestrogen replacement. Case report.
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Adult↗
Pituitary metastasis from malignant bronchial carcinoid.
Metastases from a carcinoid tumor to the pituitary gland have, to our knowledge, not been described. We present a 49-year-old woman diagnosed as having a primary carcinoid tumor arising in the submucosa of a large bronchus who 8 years later presented with multiple metastases including one to the pituitary gland, which was in partial failure of pituitary function. This case illustrates than when confronted with a pituitary tumor resembling an adenoma but negative for pituitary hormones, the possibility of a metastasis from a carcinoid tumor should be considered.
Adenoma↗
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↗
Factors in the outcome of transsphenoidal surgery for prolactinoma and non-functioning pituitary tumour, including pre-operative bromocriptine therapy.
Radical transsphenoidal surgery in 58 patients with large non-functioning pituitary tumours relieved pressure symptoms and disconnection hyperprolactinaemia without loss of pituitary function, and verified the diagnosis. Pre-operative bromocriptine did not cause any shrinkage of non-functioning tumours (n = 8), even up to 48 weeks. Thirty-two patients not given postoperative radiotherapy are being followed-up, and although two show minor CT scan evidence of tumour regrowth, for the others the delay in radiotherapy is enabling reproduction where required. In 20 patients with non-invasive macroprolactinomas radical surgery caused no loss of pituitary function but cured eight, of whom one has relapsed; none of eight invasive prolactinomas was cured by surgery. Pre-operative bromocriptine caused marked size reduction in seven of seven macroprolactinomas, but if continued beyond 6 weeks induced tumour fibrosis and uneven shrinkage which made surgery dangerous and unproductive. Selective transsphenoidal surgery relieved hyperprolactinaemia in 70% of patients with meso- (n = 15) or microprolactinoma (n = 24) usually without loss of pituitary function: the relapse rate was 1 per 88 patient years of follow-up. Invasive prolactinomas, and macroprolactinomas showing uneven shrinkage with a short (up to 4 weeks) course of bromocriptine should have radiotherapy rather than surgery, while the patients most suited to surgery are those with mesoprolactinomas, or some macroprolactinomas with compact intrasellar shrinkage after short-term bromocriptine. Microprolactinomas generally did not benefit from surgery as compared to conservative therapy. In none of the tumour groups were the surgical findings an accurate predictor of postoperative pituitary function.
Adenoma↗
Cushing's syndrome in pregnancy: the timing of definitive treatment.
Cushing's syndrome in pregnancy is rare but associated with a high fetal loss rate, premature labour and excessive maternal morbidity. There has been controversy regarding the safety and efficacy of surgical treatment during pregnancy. We describe two further cases, both due to adrenal adenomas, in whom the diagnosis was made at 28 and 31 weeks gestation. Both cases suffered from severe myopathy. The first case was not treated during pregnancy and developed wound and urinary infections after caesarean section and subsequent adrenalectomy. An incisional hernia in the caesarean section scar has been repaired twice. The second had an adrenalectomy when 29 weeks pregnant with rapid resolution of the features of Cushing's syndrome, particularly the myopathy, and had an uneventful vaginal delivery. The second case, and a review of those previously described, indicates that surgical treatment during pregnancy is safe and significantly reduces fetal losses, premature labour and maternal morbidity.
Adenoma↗
Pituitary apoplexy following isosorbide administration.
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Humans↗
Pituicytoma (pilocytic astrocytoma). Case report.
Tumors of the posterior pituitary are rare and the previous nomenclature has been confusing. A 40-year-old man presented with visual failure and disconnection hyperprolactinemia (830 mU/liter) due to a large invasive pituitary tumor shown to be a pituicytoma (pilocytic astrocytoma). Its astrocytic nature was confirmed by positive immunostaining for glial fibrillary acidic protein and the finding of cytoplasmic filaments on electron microscopy. This case report contains the pathological description of a pituicytoma and illustrates that a non-adenomatous pituitary lesion may masquerade as a pituitary adenoma. Large pituitary lesions associated with serum prolactin concentrations of less than 3000 mU/liter require early surgical biopsy.
Adult↗
Non-functioning pituitary adenomas do not regress during bromocriptine therapy but possess membrane-bound dopamine receptors which bind bromocriptine.
Dopaminergic binding to membranes from 20 well-characterized non-functioning pituitary tumours was investigated using the radioligand [3H]spiperone; nine had failed to regress during pre-operative bromocriptine therapy. Five macroprolactinomas and six normal pituitaries were similarly investigated. High affinity dopaminergic binding sites were defined in all tissues studied. Mean dissociation constants were similar for the three groups (0.92, 0.55 and 0.51 nmol/l, respectively) but mean site numbers were greater in the prolactinomas (698) than in non-functioning tumours (131) or normal pituitaries (136 fmol/mg protein). In a pool of non-functioning tumour membranes ligand competition experiments confirmed that binding was dopaminergic. Stereospecificity was demonstrated using the (+) and (-)isomers of butaclamol. Bromocriptine was present in three non-functioning tumours that had been exposed to the drug within 24 h of surgery and it largely prevented [3H]spiperone binding; membrane washing restored [3H]spiperone binding to control values. We conclude that non-functioning tumours possess high affinity membrane-bound dopaminergic binding sites similar to those in normal pituitary and macroprolactinomas, but apparently fewer in number than in the latter. Though bromocriptine binds to dopamine receptors on non-functioning tumours in vivo, this does not result in tumour regression.
Adenoma↗
Sensitive and specific bromocriptine radioimmunoassay with iodine label: measurement of bromocriptine in human plasma.
Plasma bromocriptine assays must have high sensitivity because plasma concentrations are low, and high specificity because bromocriptine is extensively metabolised. This paper describes the simple preparation of a radioiodine-labelled derivative of dihydroergocriptine and its use in a radioimmunoassay employing an antiserum directed against the intact bromocriptine molecule. The method could measure plasma bromocriptine at concentrations of 0.05 nmol/L, had between-assay coefficients of variation of less than 10% and was more convenient than previous assays using tritium radiolabels.
Adenoma↗
Effect of bromocriptine treatment on the fibrous tissue content of prolactin-secreting and nonfunctioning macroadenomas of the pituitary gland.
We performed a quantitative study using a point-counting technique at the light microscope level of the fibrous tissue content of PRL-secreting and nonfunctioning pituitary macroadenomas from patients treated or untreated with bromocriptine (BC) before surgery. There was a significant increase in the fibrous tissue content of PRL-secreting, but not nonfunctioning, tumors after BC treatment. The extent of the increase in fibrous tissue in prolactinomas correlated with the duration of treatment with BO.
Adenoma↗
Thyroxine malabsorption following intestinal bypass surgery.
Jejuno-ileal bypass surgery for morbid obesity results in small bowel malabsorption. This may produce various nutritional or mineral deficiencies. A patient who became hypothyroid following bypass surgery required a larger than normal dose of thyroxine, presumably because of impaired absorption. In such patients it is particularly important to measure serum thyrotrophin concentrations in assessing the replacement dose of thyroxine.
Dose-Response Relationship, Drug↗