Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour?

OBJECTIVE: To assess the incidence of second brain tumours in patients operated and irradiated for pituitary tumours. DESIGN AND PATIENTS: The study base consisted of a consecutive series of 325 patients operated and irradiated for pituitary tumours, excluding patients with acromegaly and Cushing's disease. Comparison was made with the general population from the same catchment area as the patients. The follow-up period started in 1958 and on an individual basis patients were followed from the onset of postoperative irradiation until December 1995, or until date of death, emigration or a second brain tumour diagnosis, whichever occurred first. RESULTS: Three brain tumours (two astrocytomas and one meningioma) were observed, compared with 1-13 expected (standardized incidence ratios (SIR) 2.7; 95% confidence interval (CI) 0.6-7.8). CONCLUSION: The present study gives no firm support for an increased incidence of a second brain tumour in patients operated and irradiated for pituitary tumours. A crude meta-analysis of the present and previously published cohort studies of patients with irradiated pituitary tumours gives an SIR of 6.1 (95% CI 3.16-10.69). Thus, the results of the meta-analysis are in favour of an increased risk for second brain tumours. A genetic trait that predisposes to both pituitary tumours and brain tumours is an alternative causal factor. There is no definite proof that cranial irradiation per se is the causal factor. This question cannot be fully answered until sufficient cohort studies of nonirradiated pituitary tumour patients have been carried out.     

Cerebrovascular disease in patients with pituitary tumors.

Several studies have shown that patients with acromegaly have increased mortality rates for cardiovascular disease and cerebrovascular disease (CVD). Similar associations have also been seen for patients with hypopituitarism or with non-functional pituitary adenomas. This review summarizes these data and discusses the relative importance of different risk factors for cardiovascular, especially CVD, mortality among patients with acromegaly or non-functional pituitary adenomas, and for those with hypopituitarism as a result of other causes.     

Outcome from surgical management of secretory pituitary adenomas in Christchurch,New Zealand

Abstract
Background:  Recent evidence has highlighted the importance of the neurosurgeon in the management of secretory pituitary tumours, but most reports are from major centres.
Aims:  To audit the surgical outcome of patients with acromegaly and Cushing's disease treated in a small centre (Christchurch, New Zealand) by a dedicated neurosurgeon with an interest in pituitary disease, and follow-up through an outpatient Department of Endocrinology.
Methods: All cases of acromegaly and Cushing's disease admitted for surgery in Christchurch Hospital between 1984 and 2000 were audited. Data concerning preoperative findings, surgical remission rate, complications and follow-up were obtained from 44 patients (28 acromegaly, 16 Cushing's disease).
Results: Of the 28 acromegalic patients, 14 patients (50%) had a mean growth hormone level <2.5 µg/L within the first postoperative week. Of the 15 Cushing's disease patients in whom the pituitary fossa was explored, 13 patients (87%) entered a postoperative remission, defined as an 08.00 h cortisol <200 nmol/L (normal range 250−800 nmol/L). No perioperative deaths occurred. Two of the 43 patients (4.7%) developed permanent diabetes insipidus, while eight of the 28 patients who were operated on for acromegaly (29%) eventually required some replacement treatment for hypopituitarism during follow-up (one presented with apoplexy and seven were treated with postoperative radiotherapy).
Conclusion: In a small centre with a dedicated pituitary surgeon, operative remission rates approach those obtained in larger, more specialized centres. However, given New Zealand's small, but geographically spread population, consideration should be given to establishing one or two units for the surgical management of secretory pituitary adenomas. (Intern Med J 2003; 33: 168−173)     

Outcome of fractionated stereotactic radiotherapy in patients with pituitary adenomas resistant to conventional treatments: a 5·25‐year follow‐up study

Objective To investigate the long‐term outcome of fractionated stereotactic radiotherapy (FSRT) [45 Gy (range 45–54) in 25 fractions] in patients with pituitary adenomas characterized by tumour progression or hormonally active disease despite surgery and/or medical therapy. Design This was an observational follow‐up study of 5·25 years (median; range 1·7–10·4). Patients and measurements Pituitary tumour volume, visual acuity/fields, hypersecretion, hypopituitarism, cerebrovascular disease, second brain tumours and mortality were examined at regular intervals after FSRT in 30 patients with pituitary adenomas (20 nonfunctioning macroadenomas, 10 functioning). Prior to FSRT, 83% had been operated 1–3 times, 47% had visual field deficits/impaired vision and 50% pituitary dysfunction. Progressive disease, stable disease, partial and complete tumour response were defined by MRI. Results Tumour growth control was 100%. At the end of follow‐up, 30% had stable disease, 60% partial and 10% complete tumour response. Visual function was preserved and 36% of patients with prior field deficits improved. GH decreased from 4·2 (range, 2·3–6·5) to 1·1 (range, 0·5–1·5) μg/l (P < 0·001) in patients with acromegaly, and medical therapy could be reduced. In large prolactinomas, partial response or complete tumour response was achieved. FSRT was well tolerated. Pituitary function remained normal in 27%, 33% of patients had stable dysfunction, 17% deteriorated further and 23% developed new dysfunction. There were no cerebrovascular events, second brain tumours or FSRT‐related deaths. Conclusion According to this long‐term follow‐up study, FSRT is an efficient and safe adjuvant therapy for pituitary adenomas refractory to conventional treatments.     

Mortality in patients treated for Cushing's disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma

CONTEXT: Increased mortality in patients with pituitary tumors after surgical treatment has been reported. However, it is unknown to what extent excess mortality is caused by pituitary tumors and their treatment in general and to what extent by previous exposure to hormonal overproduction. OBJECTIVE: The aim of the study was to compare mortality between patients treated for Cushing's disease and nonfunctioning pituitary macroadenomas (NFMAs). DESIGN: This was a follow-up study. PATIENTS: We included 248 consecutive patients with pituitary adenomas treated by transsphenoidal surgery in our hospital for NFMAs (n = 174) and ACTH-producing adenomas (n = 74). The mean duration of follow-up after surgery was 10.1 +/- 7.2 yr for the whole cohort. OUTCOME MEASURES: The standardized mortality ratio (SMR) was calculated for the whole cohort and also for the two diseases separately. Cox regression analysis was used to compare mortality in patients with Cushing's disease with NFMA patients. RESULTS: Patients with Cushing's disease (39.1 +/- 16.1 yr) were significantly younger at time of operation than NFMA patients (55.3 +/- 13.4 yr). The SMR for the whole cohort was 1.41 [95% confidence interval (CI), 1.05-1.86]. The SMR in NFMA patients was 1.24 (95% CI, 0.85-1.74) vs. 2.39 (95% CI, 1.22-3.9) in patients with Cushing's disease. In patients with Cushing's disease, compared with NFMAs, the age-adjusted mortality was significantly increased: hazard ratio 2.35 (95% CI, 1.13-4.09, P = 0.008). CONCLUSIONS: Mortality in patients previously treated for Cushing's disease is increased, compared with patients treated for NFMAs. This implies that previous, transient overexposure to cortisol is associated with increased mortality.     

Gamma knife radiosurgery for acromegaly--long-term experience

OBJECTIVE: The Leksell gamma knife (LGK) is one of the treatment options for pituitary adenomas. We report on our long-term experience treating acromegaly using LGK. DESIGN: Since 1993 we have followed 96 acromegaly patients through periods of from 12 to 120 months. The mean follow-up period was 53.7 +/- 26.8 months. Seventy-two patients were treated with neurosurgery prior to LGK; for 24 LGK was the primary treatment. Thirteen patients were irradiated twice, due to persistent activity of the adenoma or its residue. Pituitary functions were tested at 6-month intervals, post-irradiation. The target tumour volume for radiosurgery was between 93.3 and 12 700 mm3 (median 1350 mm3). RESULTS: Fifty per cent of the patients achieved mean GH < 2.5 microg/l within 42 months, normalized their IGF-I within 54 months, and achieved GH suppression in the oral glucose tolerance test (oGTT) < 1 microg/l with normal IGF-I within 66 months. LGK effectiveness was dependent on initial adenoma hormonal activity (GH and IGF-I serum levels), not on the size of the adenoma. Patients with primary neurosurgery followed by LGK irradiation had better outcomes than those with LGK alone. Irradiation arrested all adenoma growth, causing tumour shrinkage in 62.3% of patients. Twenty-six developed hypopituitarism when irradiated by 15 Gy (or more) on functional peritumoral pituitary tissue. No hypopituitarism appeared using lower doses. CONCLUSIONS: In acromegaly, LGK is a useful adjunct to primary neurosurgery when treating post-surgical residues because it can limit the duration of medical therapy. It can be used as a primary therapy when neurosurgery is not possible.     

Radiotherapy of pituitary tumors

The treatment of pituitary adenomas with conventional radiotherapy is safe and effective. Radiation controls the mass effects of large tumors in 80 to 90 per cent of patients and is especially valuable in preventing recurrence after partial resection. In acromegaly, about 80 per cent of patients are controlled; with Cushing's disease, the ultimate cure rate is from 50 to 80 per cent; the control rate for prolactin-secreting adenomas is not yet established. With appropriate radiation technique, including proper dose and daily fraction size, clinically significant complications other than hypopituitarism are rare.     

Expression of the transferrin receptor in human anterior pituitary adenomas is confined to gonadotrophinomas

OBJECTIVE  The human pituitary gland is affected selectively by conditions associated with iron deposition, but the mechanisms for this are unknown. In this study we have determined whether the transferrin receptor, which mediates iron uptake by cells, could be detected immunocytochemically in human pituitary adenomas in vitro .
PATIENTS  Data were derived from 35 patients undergoing transsphenoidal surgery and included 13 with clinically non-functioning adenomas, 15 with acromegaly, 4 prolactinomas, 2 patients with Cushing's disease and one patient with Nelson's syndrome.
MEASUREMENTS  Transferrin receptor immunopositivity was determined for each adenoma in dispersed cell culture using a specific monoclonal antibody.
RESULTS  Eight of 13 clinically functionless adenomas showed immunopositive transferrin receptor expression, whilst adenomas from 15 patients with acromegaly, 4 prolactinomas, 2 Cushing's syndrome and one patient with Nelson's syndrome were negative. The eight transferrin receptor positive tumours were gonadotrophinomas and accounted for eight of the nine tumours which secreted and immunostained for FSH; all eight also secreted and immunostained for LH.
CONCLUSIONS  These findings may reflect a special requirement for iron by gonadotrophin secreting cells in comparison to other pituitary cell types and this could underlie the reasons why in the normal pituitary these cells are especially susceptible to malfunction in iron overload syndromes such as genetic haemochromatosis and β-thalassaemia.     

Mortality and pituitary disease

Outcome data from large series confirm increased mortality of patients with pituitary tumours, predominantly due to vascular disease. Control of cortisol secretion and growth hormone (GH) hypersecretion (together with cardiovascular risk factor reduction) is key in the normalisation of mortality rates in patients with Cushing's disease and acromegaly, respectively, though some excess mortality may persist even in "cured" patients.     

Medical therapy for clinically non-functioning pituitary adenomas

Surgery is the first-line treatment of patients with clinically non-functioning pituitary adenomas (NFAs). Because of lack of clinical syndrome these tumours are diagnosed with a variable delay, when patients suffer from compression symptoms (hypopituitarism, headache and visual field defects) due to the extension of the tumour outside the pituitary fossa. Surgery is followed by residual tumour tissue in most patients. In these cases, radiotherapy is generally used to prevent tumour regrowth. However, NFA cell membranes, in analogy with GH- and PRL-secreting adenomas, express somatostatin and dopamine receptors. Treatment with somatostatin analogues (SSA) and dopamine agonists (DA) induced some beneficial effects on visual field defects and was also followed by tumour shrinkage in a minority of cases. DA seem to be more effective on tumour shrinkage than SSA. More recently, a combination treatment with both SSA and DA have been tested in a few patients with interesting results. Lack of randomized, placebo-controlled trials prevents any conclusion on the efficacy of these drugs. By contrast, use of gonatotrophin-releasing hormone analogues has been abandoned.     

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.     

Gastrin in pituitary tumours

Twelve of 87 pituitary adenomas from patients with acromegaly, Cushing's syndrome. Nelson's syndrome, hyperprolactinaemia and without symptoms of hormone hypersecretion contained gastrin in concentrations from 0.5 to 166 pmol/g. Only ACTH-producing tumours contained gastrin, which occurred in forms smaller than those present in the normal adenohypophysis. The results indicate that corticotropic tumours may synthesize gastrin in moderate amounts.     

Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas

CONTEXT: Although the majority of pituitary macroadenomas are clinically nonfunctioning, treatments as well as follow-up strategy for this condition lack evidence from randomized studies. Evidence Acquisition: We evaluated the evidence of treatment and follow-up strategies for clinically nonfunctioning adenomas. PubMed was searched for articles on nonfunctioning adenomas in November 2007, and references of selected articles were assessed for potentially relevant articles. Evidence Synthesis: All evidence for treatment and follow-up for nonfunctioning adenomas is based on observational studies. The most effective treatment is transsphenoidal surgery, indicated in patients with visual field defects. A wait-and-see approach may be considered in nonfunctioning macroadenomas not reaching to the optic chiasm. Some of these tumors ( approximately 10%) will show spontaneous regression, whereas in approximately 50% there will be progression within 5 yr observation. Postoperative radiotherapy should not be applied to all patients after surgery but can be considered in patients with large postoperative remnants of the tumor. During follow-up careful assessment and replacement of pituitary insufficiencies should be performed. Magnetic resonance imaging is advised with intervals of 1-3 yr and evaluation of visual fields when appropriate. Recurrence rates are reported to be 6-46% after transsphenoidal surgery, whereas after postoperative radiotherapy, recurrence rates of 0-36% are reported. Long-term sequelae of nonfunctioning macroadenomas are hypopituitarism, persistent visual field defects, and decreased quality of life. Whether nonfunctioning macroadenomas are associated with an increased mortality is still a matter of debate. CONCLUSION: Clinically nonfunctioning pituitary macroadenomas, although benign in nature, need individualized treatment and lifelong radiological and endocrinological follow-up.     

Diagnosis and management of pituitary tumours in the elderly: a review based on personal experience and evidence of literature

An increasing proportion of pituitary adenomas are recognized in the elderly, raising the question of their optimal diagnosis and management. Age-related endocrine changes and associated diseases may significantly modify the clinical presentation and hormonal evaluation of these patients. About 80% of pituitary adenomas in this age group are non-secreting, requiring careful differential diagnosis with non-adenomatous sellar lesions. In this group, visual deterioration and hypopituitarism remain the leading symptoms. Recognized secreting tumours are mainly GH-secreting, most of them intrasellar, followed by prolactinomas, which present as clinically non-secreting and are usually invasive. Cushing's disease appears as a very rare eventuality in the elderly. Optimal therapeutic management should aim to control the disease while preserving or improving patient's quality of life. Transsphenoidal surgery has proved to be an efficient and well-tolerated option for non-secreting adenomas with visual defects and intrasellar GH-secreting adenomas, being able to improve metabolic and cardiovascular complications of acromegaly even in this age group. In contrast, dopamine-agonist drugs can be proposed as a primary therapy for prolactinomas even in the presence of severe neurological complications. Because the use of radiotherapy is hampered by its delay of action and potential neurological side effects, its indications should be better defined in this age group. The clinical importance of hypopituitarism should not be underestimated, and thyroid- and adrenal-replacement therapy are mandatory in the presence of documented hormone deficiency, carefully avoiding overtreatment in order to limit possible side effects on the cardiovascular system and bone mineralization. Indications for GH- and sex steroid-replacement therapy still await age-specific guidelines.     

Prevalence, predictors and patterns of postoperative polyuria and hyponatraemia in the immediate course after transsphenoidal surgery for pituitary adenomas

OBJECTIVE: Disturbances of osmoregulation, leading to diabetes insipidus and hyponatraemia are well known complications after surgery in the sella region. This study was performed to examine the prevalence and predictors of polyuria and hyponatraemia after a complete and selective removal of pituitary adenomas was attempted via the transnasal-transsphenoidal approach. DESIGN: 1571 patients with pituitary adenomas (238 Cushing's disease, 405 acromegaly, 534 hormonally inactive adenomas, 358 prolactinoma, 23 Nelson's syndrome, and 13 thyrotropinoma) were daily examined within a 10-day postoperative inpatient observation period. Prevalence of patterns of polyuria (> 2500 ml) and oliguria/hyponatraemia (< 132 mmol/l) were surveyed as well as predictors of postoperative morbidity. RESULTS: 487 patients (31%) developed immediate postoperative hypotonic polyuria, 161 patients (10%) showed prolonged polyuria and 37 patients (2.4%) delayed hyponatraemia. A biphasic (polyuria-hyponatraemia) and triphasic (polyuria-hyponatraemia-polyuria) pattern was seen in 53 (3.4%) and 18 (1.1%) patients, respectively. Forty-one patients (2.6%) displayed immediate postoperative (day 1) hyponatraemia. Altogether, 8.4% of patients developed hyponatraemia at some time up to the 10th day postoperative, with symptomatic hyponatraemia in 32 patients (2.1%). Risk analysis showed that patients with Cushing's disease had a fourfold higher risk of polyuria than patients with acromegaly and a 2.8-fold higher risk for postoperative hyponatraemia. Younger age, male sex, and intrasellar expansion were associated with a higher risk of hypotonic polyuria, but this was not considered clinically relevant. CONCLUSIONS: The analysis illustrates that disturbances in osmoregulation resulting in polyuria and pertubations of serum sodium concentration are of very high prevalence and need observation even after selective transsphenoidal surgery for pituitary adenomas, especially in patients with Cushing's disease.     

Cyclin D and cyclin E expression in normal and adenomatous pituitary

OBJECTIVES: Cyclins play an important role in the regulation of cell progression through the cell cycle. Over-expression of the cyclins has been shown in many different tumour types. Pituitary adenomas are a common form of endocrine neoplasia in the human, but have been little studied in terms of the expression of the principal cyclins regulating checkpoint exit, cyclin D1 and cyclin E. METHODS: We therefore investigated the expression of cyclin D1 and cyclin E in a range of benign and metastatic pituitary tumours. We studied a total of 95 pituitaries, including normal pituitary (n=20), Cushing's disease (n=19), somatotroph tumours (n=19), non-functioning adenomas (n=18), prolactinomas (n=7), aggressive tumours (n=9) and pituitary carcinoma (n=3). All tumours and normal tissue were immunostained for cyclin D1 and cyclin E using a standard technique, and were then subjected to blinded analysis by a single observer and the extent of staining quantified on the basis of 500 cell counts per tissue. The distribution of positive staining between different tissues was analysed by non-parametric test procedures. RESULTS: There was no cytoplasmic staining for cyclin D1 in any tissue. Nuclear staining was generally sparse, but was statistically more frequent in non-functioning and aggressive tumours compared with other tumour types or normal pituitary. Cyclin E was also sparsely expressed, but was specifically increased in corticotroph tumours from patients with Cushing's disease. CONCLUSIONS: We report cyclin D1 over-expression in aggressive and non-functioning pituitary tumours, and that cyclin E expression is more frequently seen in Cushing's disease. The high level of cyclin E expression in Cushing's disease may relate to the low level of p27 protein expression previously reported in corticotroph tumours.     

Galanin in human pituitary adenomas: frequency and clinical significance

OBJECTIVES: Galanin (GAL) is a neuropeptide widely expressed in the central and peripheral nervous system and in neuroendocrine tissue, including the adenohypophysis where, in humans, it is expressed in corticotrophs and in ACTH-producing adenomas. Previous analyses of human tissue have used antiserum against porcine GAL for detection of GAL immunoreactivity (GAL-IR) and no pathophysiological correlates have been reported. Given significant differences between the sequence of porcine and human GAL peptides, the aim of this study was to use antiserum raised against synthetic human GAL to investigate GAL-IR in non tumorous pituitaries and in pituitary adenomas, and to correlate GAL-IR with the clinical and hormonal characteristics of patients with Cushing's disease. PATIENTS: Six nontumorous pituitaries were obtained from autopsy and 151 pituitary adenomas, comprising 62 functioning (16 corticotroph, 26 somatotroph, 19 lactotroph and one thyrotroph) and 89 nonfunctioning adenomas, were obtained by surgery. RESULTS: All non tumorous pituitary glands showed GAL-IR in corticotrophs, in basophil cells within the neurohypophysis and in nerve fibres of the neurohypophysis. GAL-IR was found in a subset (10 of 16) of patients with ACTH-secreting tumours causing Cushing's syndrome. GAL-IR was rarely expressed in somatotroph adenomas and prolactinomas, but was expressed in approximately one-third of nonfunctioning tumours. GAL-IR was found in almost 90% of nonfunctioning tumours that were positive for ACTH. There were no significant differences in sex ratio, age at presentation or 24-h urinary free cortisol secretion in the subset of patients with Cushing's disease positive (n = 10) or negative (n = 6) for GAL-IR. However, Cushing's patients positive for GAL-IR tended to have smaller tumours and achieved a higher cure rate than those without (100 vs. 50%, P = 0.017). CONCLUSIONS: Galanin is present in normal and tumorous human pituitaries. In addition, GAL colocalizes exclusively in corticotrophs of normal pituitaries and is coexpressed almost exclusively in corticotrophs from functioning and nonfunctioning tumours. The finding that corticotroph adenomas can function irrespective of the presence of GAL suggests that GAL may not play a pathophysiological role in Cushing's disease. However, the better surgical outcome observed in patients with Cushing's disease who had tumours positive for GAL-IR suggests that the expression of GAL confers a less aggressive tumour phenotype.     

THE SIGNIFICANCE OF ELEVATED LEVELS OF GASTRIN IN PATIENTS WITH PITUITARY ADENOMA

Six patients were studied with pituitary adenomas and elevated concentrations of gastrin similar to those found in cases of benign antral gastrinoma syndrome. Chromatography of the serum using Sephadex-G50 revealed different molecular forms of gastrin according to the type of adenomas. In those cases of acromegaly and gonadotrophinoma, gastrin-34 and unsulphated gastrins constitute the predominant forms. In contrast, in cases of Cushing's disease, gastrin-17, sulphated as well as non-sulphated were the predominant types; the chromatographic pattern was similar to that observed in two patients with antral gastrinoma syndrome who acted as controls. These findings demonstrate that pituitary adenomas might secrete gastrin. Taking into account that gastrin-34 and unsulphated gastrins were the predominant forms in cases of acromegaly, gonadotrophinoma and non-functioning adenoma, it is assumed that those molecular forms are mainly produced in the anterior lobe of the hypophysis. Conversely, gastrin-17 was the principal molecular form in cases of Cushing's disease confirming the close relationship of the synthesis of gastrin and corticotrophin peptides. The cases with Cushing's disease exhibited a serum gastrin pattern similar to that observed in the two cases with antral syndrome in which the predominant immunoreactive form of gastrin in gastrin-17 exhibiting a degree of sulphation corresponding to that of antral gastrin. It is concluded that the circulating excess of gastrin originated in the pituitary tumour tissue and the molecular form varied with the type of pituitary adenoma.     

Mortality following pituitary radiotherapy

External beam radiotherapy has been used in the management of pituitary adenomas for nearly a century, preventing tumor regrowth following surgery for non-functioning pituitary adenomas and suppressing functional hypersecretion in those which are hormonally active. However, it has been linked with a number of potentially significant complications including formation of secondary intracranial tumors, cognitive impairment, hypopituitarism and cerebrovascular disease, as well as increased mortality. Radiation may cause a variety of vascular injuries and hemodynamic changes to the cerebral vasculature, and several authors have reported cerebrovascular complications and an increase in cerebrovascular mortality in patients receiving radiotherapy for pituitary and other central nervous system tumors. Ten years following pituitary radiotherapy, over 50% of patients develop deficiencies in one or more anterior pituitary hormones. A number of studies have demonstrated increased mortality in patients with hypopituitarism, predominantly due to cerebrovascular and cardiovascular disease. However, no clear answer has emerged with regards to causation, and pituitary radiotherapy has only been linked directly to mortality in one of these studies. Questions remain unanswered, and the use of conventional external beam radiotherapy in the management of pituitary disease must involve a critical risk-benefit analysis in each case.