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H E Turner

Publications and source records attributed to H E Turner.

30 records · Page 2Linked to original sources

Are markers of proliferation valuable in the histological assessment of pituitary tumours?

The prediction of tumour behaviour and response to treatment has led to interest in the assessment of the proliferative potential of tumours. Pituitary tumours are usually histologically benign but are capable of aggressive growth and local invasion, although distant metastasis is limited to the very rare pituitary carcinoma. These differences in tumour behaviour may determine both the prognosis and also the effectiveness of treatment whether it be surgery, drugs or radiotherapy. Immunohistochemistry using antibodies to Ki-67 and proliferating cell nuclear antigen (PCNA) which are expressed in cells that have entered the cell cycle, can be used to assess the proportion of the cells from a tumour that are proliferating. The percentage of positively stained nuclei (labelling index (LI)) may be helpful in predicting appropriate management, as there is a relationship in many tumours between labelling index, invasiveness and tumour recurrence. This has been shown to be true for pituitary tumours, although there may be significant overlap such that low LI may be seen in the rare, aggressive, metastatic pituitary carcinomas, and high LI in indolent tumours. Thus although assessment of proliferation may be helpful in arousing suspicion as to subsequent tumour recurrence or invasiveness, this technique also demonstrates that there are other important and as yet unidentified processes that determine pituitary tumour behaviour.

Bromodeoxyuridine↗

A comparison of lanreotide and octreotide LAR for treatment of acromegaly.

BACKGROUND AND OBJECTIVE: Two long-acting depot somatostatin analogues have recently been licensed for the treatment of acromegaly. We wished to assess the effectiveness of both these drugs in suppressing mean GH to a target of < 5 mU/l in patients with acromegaly unselected for responsiveness to octreotide, and also to compare the effects of both drugs METHODS: We prospectively studied 10 unselected patients with acromegaly who were treated first with lanreotide (LAN) and then octreotide LAR (LAR) following a washout period. The target for therapy was to achieve mean GH less than 5 mU/l. RESULTS: Five (50%) patients achieved mean GH < 5 mU/l on lanreotide 30 mg every 10 days, and 7 out of 9 (77.8%) achieved this level when the dose frequency was increased to every 7 days. On 20 mg octreotide LAR, 6 (60%) patients achieved the target mean GH and a further 2 (80%) when the dose was increased to 30 mg. Normalization of IGF-1 occurred in 5/9 (55.6%) patients who received lanreotide and 7/10 (70%) of those who received octreotide LAR. There was a significant difference in mean GH attained on the 2 drugs. The patients' mean GH was significantly lower when treated with octreotide LAR 20 mg every 4 weeks compared with lanreotide 30 mg every 10 days (P = 0.037). Maximal suppression of mean GH with 30 mg octreotide LAR or 7 day dosing of lanreotide was significantly greater on octreotide LAR (P < 0.02). CONCLUSIONS: At current dose recommendations, lanreotide and octreotide LAR are both effective in lowering mean GH to 'safe' (< 5 mU/l) levels in 80% patients but octreotide LAR treatment leads to significantly lower mean GH.

Acromegaly↗

Audit of selected patients with nonfunctioning pituitary adenomas treated without irradiation - a follow-up study.

OBJECTIVE: Non-functioning pituitary adenomas (NFA) are the commonest type of pituitary macroadenoma. Although the initial definitive management of these tumours is almost always trans-sphenoidal surgery, the use of postoperative radiotherapy remains controversial. Radiotherapy has been shown to significantly reduce the risk of tumour regrowth. An audit of patients with NFAs treated with trans-sphenoidal surgery without irradiation was performed at our centre five years ago, and suggested that careful selection and follow-up could avoid the need for adjuvant radiotherapy. We have repeated this audit to assess the longer term effects of this management strategy. METHODS AND PATIENTS: The case notes and imaging of the original cohort of 65 of 73 patients (50 males, mean age 52) who had undergone trans-sphenoidal surgery (TSA) for NFA between July 1979 and 1992, had not received irradiation and were followed up by imaging were reviewed. Tumour regrowth was defined as enlargement of the pituitary tumour. Mean follow-up was 76 months (range 12-173). RESULTS: Pituitary tumour regrowth has occurred in 21 of the 65 patients (32%) during a mean follow-up of 76 months compared with 8/73 (11%) in 1994 (P = 0.002). The tumour regrowth was detected at a mean of 5.4 years (range 2-14 years). Lifetable analysis of the whole unirradiated group showed 82% recurrence free survival at 5 years (95% confidence limits 72-92%), and 56% at 10 years (95% confidence limits 38-74%). Eight (12%) patients required a second surgical procedure (6 TSA and 2 craniotomies). There was no relationship between recurrence and whether a total surgical removal was thought to have been performed. CONCLUSION: Despite careful selection of patients with non-functioning pituitary adenomas, tumour regrowth occurs in a significant proportion. These results show that continued follow-up in these patients is essential as significantly more patients showed evidence of tumour regrowth at this second assessment compared with the 1994 data. Until we are able to predict which tumours are likely to regrow postoperatively, radiotherapy should be considered for all patients with non-functioning pituitary adenomas as even in carefully selected cases, the regrowth rate is approaching 50% at 10 years.

Adenoma↗

The enhanced peroxidase one step method increases sensitivity for detection of Ki-67 in pituitary tumours.

AIM: To compare the Ki-67 labelling index determined using the enhanced peroxidase one step (EPOS) method with that using the standard ABC technique in pituitary tumours. METHODS: Adjacent sections were immunostained using the EPOS and ABC techniques with the same Ki-67 antibody and same antigen retrieval method. RESULTS: The labelling index measurements with the EPOS Ki-67 antibody were significantly higher than when using the traditional ABC method, and there was a positive correlation between the two techniques when performed on the same cases. This suggests that a higher proportion of cells are within the cell cycle than previously thought, although it gives no direct information on the rate of proliferation of the tumour. CONCLUSIONS: It appears that the EPOS system is not only more convenient but may be more sensitive than traditional techniques for detecting Ki-67 in the nuclei of cells, thus demonstrating more accurately which cells have entered the cell cycle.

Cell Division↗

Trans-sphenoidal surgery for microprolactinoma: an acceptable alternative to dopamine agonists?

AIMS: Reported cure rates following trans-sphenoidal surgery for microprolactinoma are variable and recurrence rates in some series are high. We wished to examine the cure rate of trans-sphenoidal surgery for microprolactinoma, and to assess the long-term complications and recurrence rate. DESIGN: A retrospective review of the outcome of trans-sphenoidal surgery for microprolactinoma, performed by a single neurosurgeon at a tertiary referral centre between 1976 and 1997. PATIENTS: All thirty-two patients operated on for microprolactinoma were female, with a mean age of 31 years (range 16-49). Indications for surgery were intolerance of dopamine agonists in ten (31%), resistance in six (19%) and resistance and intolerance in four (12.5%). Two patients were from countries where dopamine agonists were unavailable. RESULTS: The mean pre-operative prolactin level was 2933 mU/l (range 1125-6000). All but 1 had amenorrhoea or oligomenorrhoea, with galactorrhoea in 15 (46.9%). Twenty-five (78%) were cured by trans-sphenoidal surgery, as judged by a post-operative serum prolactin in the normal range. During a mean follow-up of 70 months (range 2 months to 16 years) there was one recurrence at 12 years. Post-operatively, one patient became LH deficient, two patients became cortisol deficient and two became TSH deficient. Out of 21 patients tested for post-operative growth hormone deficiency, 6 (28.6%) were deficient. Five patients developed post-operative diabetes insipidus which persisted for greater than 6 months. There were no other complications of surgery. The estimated cost of uncomplicated trans-sphenoidal surgery, and follow-up over 10 years, was similar to that of dopamine agonist therapy. CONCLUSION: In patients with hyperprolactinaemia due to a pituitary microprolactinoma, transsphenoidal surgery by an experienced pituitary surgeon should be considered as a potentially curative procedure. The cost of treatment over a 10 year period is similar in uncomplicated cases to long-term dopamine agonist therapy.

Adolescent↗

Pituitary tumours in the elderly: a 20 year experience.

The proportion of the elderly in the population is increasing, and the appreciation and management of medical problems in this age group will therefore become more important. We therefore decided to determine the clinical features and types of pituitary tumour presenting in the elderly, and to examine the treatment and outcome in this group. We conducted a retrospective case-note review from a specialist endocrine and neurosurgical unit in a tertiary referral centre. Eighty-four patients aged 65 years and over on diagnosis of a pituitary tumour were referred to the unit between 1975 and 1996. There were 45 males and 39 females, and the mean age was 72.4 years (range 65-86). Over half of the pituitary lesions were non-functioning adenomas (NFAs) (60.7%). GH-secreting tumours were present in 11 (13.1%) and macroprolactinomas in 7 (8.1%). Four patients had microadenomas and 17 had miscellaneous pituitary-related lesions. Visual deterioration was the commonest mode of presentation in 33 (39.3%), but 54 (64.3%) had evidence of visual impairment on detailed examination. Despite the majority of patients (80.8%) having coexisting medical conditions, trans-sphenoidal surgery was performed in 60 (71.4%) and was well tolerated with a zero peri- and post-operative mortality rate, and post-operative complications in 11 (13.1%). Pituitary tumours in the elderly are most frequently NFAs that present with visual deterioration and hypopituitarism. The fact that 46.5% were pan-hypopituitary on diagnosis and that 64.3% of patients had visual impairment suggests a delay in diagnosis in this age group. Despite significant coexisting medical pathology in this large series of patients, surgery was safe and successful in the majority.

Acromegaly↗

Differing effects on gall-bladder motility of lanreotide SR and octreotide LAR for treatment of acromegaly.

BACKGROUND: Octreotide treatment may be associated with gall stone development in up to 50% of patients with acromegaly. Two new sustained-release formulations of somatostatin analogue have been recently developed: lanreotide SR (Somatuline) and octreotide LAR (Sandostatin LAR). The incidence of gall-stone development in patients receiving these drugs has been shown to be less than 20%, but the duration of follow-up has been limited. OBJECTIVE: Prospectively to assess and compare the effects of the two new long-acting somatostatin agonists on gall bladder motility in patients with acromegaly. METHOD AND PATIENTS: Eleven patients with active acromegaly were studied. Three patients had asymptomatic gall stones at the start of the study. Ultrasound scans were performed before commencement of the treatment, and repeated during treatment with lanreotide SR and octreotide LAR. The presence of gall stones, fasting gall bladder volume (FV), residual volume (RV) and maximal percentage gall bladder emptying were measured. RESULTS: One patient developed asymptomatic small gall stones after treatment with octreotide LAR for 4 months. FV and RV were both significantly larger when patients received treatment with lanreotide SR or octreotide LAR compared with pretreatment values (P<0.05 for both). Maximal percentage gall bladder emptying was significantly reduced in patients receiving lanreotide SR or octreotide LAR compared with pretreatment (P<0.01), but was less impaired in patients receiving lanreotide SR than in those receiving octreotide LAR (P<0.01). CONCLUSIONS: Gall bladder motility is impaired in patients receiving either of these new long-acting preparations, and long-term follow-up will be needed to establish the true incidence of gall stones.

Acromegaly↗

Pituitary tumours in the elderly.

Pituitary tumours in the elderly are a neglected topic in the literature of endocrinology and gerontology. Data from autopsy studies in the elderly show that the commonest tumours are microadenomas, which are either immunocytochemically negative or stain for prolactin. Prolactin-secreting pituitary tumours, however, appear rarely in clinical series of patients in this age group and non-functioning adenomas are the commonest tumour seen, although pituitary metastasis and craniopharyngiomas also occur. Diagnosis can be difficult, but the commonest presentation is visual field loss. Hypopituitarism may be diagnosed late and incidental radiological diagnosis is not uncommon. There are few data which specifically answer the question, but there is a suggestion that the syndromes associated with hormonal hypersecretion may be milder in this age group. Conventional treatment with drugs, surgery and radiotherapy should be decided on an individual basis as these therapies appear to be well tolerated and beneficial in selected patients.

Adenoma↗

Lupus or lupoid hepatitis with mesenteric vasculitis.

A 15-yr-old girl with lupus presented with hepatitis and later a mesenteric vasculitis requiring bowel resection. The gastroenterological manifestations of lupus are reviewed with particular reference to hepatic involvement.

Adolescent↗