-
[show abstract]
[hide abstract]
ABSTRACT: In March 2011, the Acromegaly Consensus Group met to revise and update the guidelines on the diagnosis and treatment of acromegaly complications. The meeting was sponsored by the Pituitary Society and the European Neuroendocrinology Association and included experts skilled in the management of acromegaly. Complications considered included cardiovascular, endocrine and metabolic, sleep apnea, bone diseases, and mortality. Outcomes in selected, related clinical conditions were also considered, and included pregnancy, familial acromegaly and invasive macroadenomas. The need for a new disease staging model was considered, and design of such a tool was proposed.
Pituitary 08/2012; · 1.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To clarify the outcome of all cases of Rathke's cleft cysts (RCC) treated surgically and followed up in Oxford during a long-term period.
The records of all patients with RCC seen in the Department of Endocrinology between January 1978 and June 2009 were reviewed.
A total of 33 patients (20 females, median age 43 years) were identified. At presentation, major visual field defects were detected in 58% of patients and gonadotrophin, ACTH and TSH deficiency in 60, 36 and 36% of patients respectively. Desmopressin treatment was required in 18% of patients. Treatment consisted of cyst evacuation combined with or without biopsy/removal of the wall. Post-operatively, visual fields improved in 83% of patients with impairment, whereas there was no reversal of ACTH or TSH deficiency or of diabetes insipidus. All but one subject had imaging follow-up during a mean period of 48 months (range 2-267). Cyst relapse was detected in 22% of patients at a mean interval of 29 months (range 3-48 months); in 57% of them, the recurrence was symptomatic. Relapse-free rates were 88% at 24-months and 52% at 48-months follow-up. At last assessment, at least quadrantanopia was reported in 19% of patients, gonadotrophin, ACTH and TSH deficiency in 50, 42 and 47% of patients respectively. Desmopressin treatment was required in 39% of patients.
In this study of patients with RCC and long-term follow-up, we showed a considerable relapse rate necessitating long-term monitoring. Surgical intervention is of major importance for the restoration of visual field defects, but it does not improve endocrine morbidity, which in the long-term affects a substantial number of patients.
European Journal of Endocrinology 07/2011; 165(1):33-7. · 3.42 Impact Factor
-
Hormone Research in Paediatrics 01/2011; 76 Suppl 1:111-2.
-
[show abstract]
[hide abstract]
ABSTRACT: Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease. In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre. Definitive diagnostic criteria for Nelson's syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800 h plasma level of ACTH (>500 ng/l) in addition to progressive elevations of ACTH (a rise of >30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.
European Journal of Endocrinology 10/2010; 163(4):495-507. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Subjects with non-functioning pituitary adenomas (NFAs) frequently develop GH deficiency due to tumour expansion or as a consequence of tumour therapy. The safety of GH replacement (GHR) in these individuals remains unclear.
To assess the effect of GHR on tumour recurrence in patients with NFAs solely treated by surgical removal.
The study involved all patients with NFA who presented to the Department of Endocrinology in Oxford between January 1989 and July 2005 and were treated solely by surgical removal of the tumour. Patients with follow up < 1 year were excluded. Recurrence was diagnosed on the basis of radiological appearances (detectable tumour after gross total removal or regrowth of pre-existing residue) on regular imaging surveillance.
One hundred and thirty patients were included in the study, and were followed up for a mean period of 6.8 +/- 4.2 years (median 5.7, range 1.2-17.6). Twenty-three patients received GHR [16 male, 7 female, mean age at tumour diagnosis 53.7 +/- 14.6 years (range 20-80)]. The mean duration of GHR was 4.6 +/- 2.5 years (median 5.3, range 0.4-8.7). One hundred and seven subjects did not receive GH therapy [61 male, 46 female, mean age at tumour diagnosis 56.2 +/- 14.0 years (range 20-87)]. Tumour regrowth occurred in 38 non-GH treated subjects (36%) and 8 GHR subjects (35%). Regrowth was detected at a mean of 4.8 +/- 2.8 years (range 1-11 years) in the non-GH treated group, and at 6.5 +/- 2.3 years in the GHR group. In the GHR group, recurrence occurred after a mean of 2.9 +/- 2.2 years (range 0.4-5.9 years) following commencement of GH treatment. The Cox regression analysis showed that after adjusting for sex, age at tumour diagnosis, cavernous sinus invasion at diagnosis and type of tumour removal (partial or complete based on postoperative scan), GH treatment was not a significant independent predictor of recurrence (P = 0.09; hazard ratio = 0.51; 95% CI, 0.24-1.12).
GH replacement in patients with NFA treated by surgery alone is not associated with an increased risk of tumour recurrence.
Clinical Endocrinology 04/2009; 70(3):435-8. · 3.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The nadir GH value following an oral glucose tolerance test (OGTT) and the mean GH levels obtained from a GH day curve (GHDC) are among the tools currently used for assessing therapeutic end-points in surgically treated acromegaly. The latter test, however, is cumbersome and costly.
To evaluate, by using a modern, two-site chemiluminescent immunometric GH assay, the degree of discordance between the nadir GH following an OGTT and the mean GH obtained from a GHDC after surgical treatment of acromegaly and to check whether the OGTT can replace reliably the GHDC for the assessment of the disease status postoperatively.
Forty-nine patients [25 males/24 females, median age 52 years (range 18-70)] with a GH-secreting pituitary adenoma who had been surgically treated previously underwent hormonal evaluation of their disease status. The GHDC comprised of 9 x 30-min samples for GH collected in the morning after an overnight fast and rest.
Seven per cent of patients with mean GH <1.7 mug/l (5 mU/l) in the GHDC had nadir GH >0.7 mug/l (2 mU/l) in the OGTT, and 10% of those with mean GH >1.7 mug/l had nadir GH <0.7 mug/l in the OGTT (all cases with discrepancies had normal IGF-I). GH value at time 0 min <0.6 mug/l in the OGTT had positive predictive value 100% and negative predictive value 75% in predicting nadir GH <0.3 mug/l (1 mU/l) in the OGTT. Nadir GH <0.8 mug/l in the OGTT had positive predictive value 97% and negative predictive value 95% in predicting mean GH <1.7 mug/l in the GHDC. Mean GH in the OGTT <1.4 mug/l had a positive predictive value 90% and negative predictive value 95% in predicting mean GH <1.7 mug/l in the GHDC. Mean GH in the OGTT <2.5 mug/l had positive predictive value 100% and negative predictive value 81% in predicting normal IGF-I. GH at time 0 min in the GHDC <2.1 mug/l had positive predictive value 90% and negative predictive value 90% in predicting mean GH <1.7 mug/l in the GHDC.
The hormonal data obtained from an OGTT (mean and nadir GH) can provide comprehensive information on the status of acromegaly following surgery and can replace the GHDC cost-effectively. Furthermore, a morning fasting GH sample has an excellent positive predictive value in predicting biochemical cure and an optimal prognostic profile in predicting "safe" mean GH levels.
Clinical Endocrinology 04/2009; 71(6):840-5. · 3.17 Impact Factor
-
B M K Biller,
A B Grossman,
P M Stewart,
S Melmed,
X Bertagna,
J Bertherat,
M Buchfelder,
A Colao,
A R Hermus,
L J Hofland, [......],
J R Lindsay,
J Newell-Price,
L K Nieman,
S Petersenn,
N Sonino,
G K Stalla,
B Swearingen,
M L Vance, J A H Wass,
M Boscaro
[show abstract]
[hide abstract]
ABSTRACT: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder.
Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing's syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing's disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing's disease, and 5) management of ectopic ACTH syndrome, Nelson's syndrome, and special patient populations.
Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking.
Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority.
ACTH-dependent Cushing's syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing's syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing's disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing's syndrome, early diagnosis and prompt therapy are warranted.
Journal of Clinical Endocrinology & Metabolism 08/2008; 93(7):2454-62. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Macroadenomas causing acromegaly are cured surgically in only around 50% of patients. Primary medical treatment with somatostatin analogues has been suggested to be a means of treating patients with a potentially poor surgical outcome. Previous retrospective studies have also suggested that surgical debulking of pituitary tumours causing acromegaly improves control by somatostatin analogues. No prospective study using lanreotide has been carried out thus far to assess whether this is the case.
We carried out a prospective study to assess whether surgical debulking of pituitary macroadenomas causing acromegaly improved the subsequent control of acromegaly by the somatostatin analogue lanreotide.
We treated 26 consecutive patients [10 males and 16 females--median age 53.5 years (range 22-70)] with macroadenoma causing acromegaly unselected for somatostatin response for 16 weeks with lanreotide, maximizing GH and IGF-I suppression, if necessary, by incremental dosing. Surgical resection was carried out and the patients were re-assessed off medical treatment at 16 weeks following surgery. Those with nadir GH > 2 mU/l in the oral glucose tolerance test (OGTT) and a mean GH in the GH day curve (GHDC) > 5 mU/l were subsequently restarted on lanreotide and the responses were assessed at the same time points as during the preoperative lanreotide treatment.
GH values fell on lanreotide treatment and prior to surgery they were considered 'safe' (mean GH in GHDC < 5 mU/l) in eight patients (30.7%). After surgery, they were 'safe' in 18 patients (69.2%). The figures for normal IGF-I were 11 (42.3%) before surgery and 23 (88.5%) after surgery. After surgery, six patients had nadir GH > 2 mU/l in the OGTT and 'unsafe' GH levels (mean GH in GHDC > 5 mU/l); on re-exposure to lanreotide, GH levels fell in all patients and at the end of 16 weeks postsurgery, they were 'safe' in three of them (50%) (P < 0.05). Pituitary tumour volume was also assessed prospectively, preoperatively on lanreotide and showed a mean fall of 33.1%. Eighty-three percent of patients had > 20% shrinkage.
In this first prospective study using lanreotide, surgical debulking of pituitary tumours causing acromegaly improved subsequent postoperative control by the somatostatin analogue lanreotide. Surgery should, therefore, be considered in patients with macroadenoma causing acromegaly, even if there is little prospect of surgical cure. Lanreotide causes significant pituitary tumour shrinkage in the majority of patients.
Clinical Endocrinology 06/2008; 68(6):970-5. · 3.17 Impact Factor
-
J S Bevan,
J Newell-Price, J A H Wass,
S L Atkin,
P M Bouloux,
J Chapman,
J R E Davis,
T A Howlett,
H S Randeva,
P M Stewart,
A Viswanath
[show abstract]
[hide abstract]
ABSTRACT: The introduction of ready-to-use lanreotide Autogel has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety.
Multicentre (10 UK regional endocrine centres), open-label, nonrandomised, controlled study. Patients elected either to receive/administer unsupervised home injections after injection technique training (Test group) or continued to receive injections from a healthcare professional (Control group). Patients received monthly injections of lanreotide Autogel at their established dose. Effects were monitored for up to 40 weeks.
Thirty patients (15 per treatment group) with acromegaly treated with a stable dose of lanreotide Autogel (60, 90 or 120 mg) for > or = 4 months before screening. Measurements The main outcome measure was the proportion of patients/partners who successfully administered injections throughout the study.
All Test group patients/partners qualified to administer injections. Fourteen of 15 patients fulfilled all criteria for successful administration of unsupervised injections (95% confidence interval, 70%-99%). Fourteen of 15 Test and 14/15 Control patients maintained growth hormone and IGF-1 control. Local injection tolerability was good for both treatment groups, and safety profiles were similar. All Test group patients continued with unsupervised injections after the study.
Patients with acromegaly or their partners were able to administer lanreotide Autogel injections with no detrimental effect on efficacy and safety; therefore, unsupervised home injections are a viable alternative to healthcare professional injections for suitably motivated patients.
Clinical Endocrinology 03/2008; 68(3):343-9. · 3.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Collision lesions of the sellar region are relatively uncommon. Most contributions include a pituitary adenoma or a cyst/cystic tumor, particularly a Rathke cleft cyst. The association of craniopharyngioma with an adenoma is particularly rare. Among reported cases, some have included secondary prolactin cell hyperplasia due to pituitary stalk section effect. Herein, we report two collision lesions, including a gonadotroph adenoma with adamantinomatous craniopharyngioma and a corticotroph adenoma with Rathke's cleft cyst. Clinicopathologic correlation and a review of the literature are undertaken.
Pituitary 02/2008; 11(3):317-23. · 1.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Unsuccessful surgery for acromegaly has major consequences for the patient as well as financial consequences for the National Health Service (NHS). Surgical expertise affects the outcome. We have used the UK National Acromegaly Register to assess surgical outcomes in different centres to investigate whether these match the previously published case series.
Retrospective and prospective observational study by analysis of anonymized national computer register records derived from individual clinical case records from 22 UK endocrine units and their associated pituitary surgical services.
Cases of acromegaly, presenting in 1970-2004, with levels of GH or IGF-1 (785 and 430 cases, respectively) recorded prior to transsphenoidal adenomectomy and in the 12 months postsurgery, before any subsequent pituitary surgery or radiotherapy. GH-lowering pharmacological therapy was permitted only if suspended for biochemical testing.
Percentage of cases with 'safe' mean postoperative GH levels (< 5 mU/l) and/or IGF-1 in the age- and sex-adjusted normal range.
'Safe' GH, normal IGF-1, or both was achieved for 26%, 29% and 20% of extrasellar macroadenomas (> 1 cm), respectively, 39%, 39% and 29% of intrasellar macroadenomas, 56%, 51% and 37% of microadenomas (< 1 cm) and 39%, 39% and 28% of cases overall. In centres contributing more than 10 patients' data, rates of safe GH levels ranged from 20% to 68% and IGF-1 from 19% to 55%. Success rates in attaining safe postsurgical levels of GH improved only slightly in the UK between 1974 and 1999 but markedly thereafter.
Surgical outcomes for acromegaly in UK centres vary widely and historically have not, except in a few centres, matched those of large published series, which mostly have a success rate around 60%. Results have, however, improved substantially since 2000 and in the most successful units match those of the best published series. Experience is an important determinant of surgical success in acromegaly and the very recent improvement in surgical results in the UK coincides with a trend to concentrate pituitary surgery in the hands of a smaller number of specialists. Therefore, patients should be offered surgery by a dedicated pituitary surgeon with a caseload sufficient to offer the prospect of safe postsurgical GH and IGF-1 levels for the majority of cases.
Clinical Endocrinology 01/2008; 68(1):136-42. · 3.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Series of patients systematically investigating the outcome of clinically nonfunctioning pituitary adenomas (NFAs) not treated by surgery or radiotherapy during long follow-up periods are limited. Most reports involve the follow-up of selected cases of incidentally found lesions, rendering their results unreliable on the assessment of the pros and cons of a 'watch and wait' policy.
To investigate the outcome of a series of consecutive patients with presumed NFA (microadenoma or macroadenoma), who were not offered treatment at presentation (for a number of reasons) and were regularly followed up, and to identify possible factors predicting subsequent increase in tumour size.
All patients presenting to the Department of Endocrinology in Oxford between 1989 and 2005 with presumed NFA were studied retrospectively. Inclusion criteria were: (i) imaging features suggestive of a pituitary adenoma, (ii) no clinical and/or biochemical evidence of hormonal hypersecretion by the tumour, (iii) monitoring being the initial choice of management, and (iv) at least one repeat scan during the follow-up period. Subjects presenting with acute apoplexy were excluded. Follow-up management included clinical evaluation, assessment of the visual acuity and fields and imaging at regular intervals. The duration of observation was estimated from the dates of first and last scan.
Forty subjects were included in the study [18 males/22 females, median age 52 years (range 18-89), 16 with microadenoma/24 with macroadenoma]. The mean follow-up period was 42 months (range 8-128). During the observation interval, 12.5% of the microadenomas and 50% of the macroadenomas increased in size. The 48-month probability for enlargement was 19% for the microadenomas and 44% for the macroadenomas. Among the subjects with tumour enlargement, 57% showed new or worse visual field defects (all had macroadenomas) and 21% showed chiasmatic involvement on imaging without visual deterioration (all had macroadenomas). New or worse visual field defects were found in 67% of the macroadenomas showing increase in size. No microadenoma enlarged to cause visual deterioration. In microadenomas, sex and age at presentation were not predictors of enlargement. In macroadenomas, sex, age, visual field defects or cavernous sinus invasion at presentation were not predictors of enlargement.
The 'watch and wait' policy seems reasonable for microadenomas but is probably not a safe approach for macroadenomas, which appear to have a significant growth potential; in these cases, given the lack of established medical treatment, the decision for surgical intervention should balance the presence of significant comorbidities and the anaesthetic/peri-operative risks at presentation against the probability of tumour enlargement and its consequences, as well as the possible loss of advantages associated with early operation.
Clinical Endocrinology 01/2008; 67(6):938-43. · 3.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Macroprolactinomas (MPRLs) may result in nonsurgical (spontaneous or dopamine agonist induced) cerebrospinal fluid (CSF) rhinorrhea; however, the incidence of and mechanisms underlying this phenomenon are poorly understood.
The objective of the study was to determine the incidence of nonsurgical rhinorrhea and identify biochemical, radiological, and histopathological factors associated with leakage.
A retrospective review of MPRL patients (n = 114) was compared with patients with nonfunctioning pituitary adenoma (NFA) (n = 181) seen over a 19-yr period (1985-2004).
Incidence of CSF rhinorrhea, factors predictive of leakage, and differential expression of candidate markers of invasiveness were measured.
Nonsurgical CSF rhinorrhea occurred in 8.7% of MPRLs (10 of 114) [2.6% spontaneous (three of 114), 6.1% dopamine agonist induced (seven of 114)], whereas no NFAs developed nonsurgical rhinorrhea. There was a clear male preponderance in MPRLs with nonsurgical rhinorrhea (males to females, 9:1, P = 0.008). Dopamine agonist resistance was more frequent in MPRLs with rhinorrhea than with MPRLs without rhinorrhea [30% (n = 10) vs. 5% (n = 104) P = 0.003]. Baseline prolactin levels, rate of prolactin decline in response to dopamine agonists, and tumor volume at diagnosis did not predict CSF leakage. Candidate markers of invasiveness, specifically the protease-activated receptor 1 and e-cadherin expression scores and tumor macrophage density, were not significantly different between groups; MPRL+CSF rhinorrhea (n = 6), MPRL without CSF rhinorrhea (n = 9), and NFAs (n = 9).
The incidence of nonsurgical CSF rhinorrhea in MPRL patients (8.7%) is higher than expected. Dopamine agonist resistance is more common in MPRLs with CSF rhinorrhea; however, whether this is a mechanistic relationship requires further study. Protease-activated receptor 1 expression, e-cadherin expression, and macrophage infiltration rates do not distinguish tumors with from those without CSF rhinorrhea.
Journal of Clinical Endocrinology & Metabolism 11/2007; 92(10):3829-35. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The role of angiogenesis and lymphangiogenesis in thyroid cancer pathogenesis has not been elucidated. Patterns for tumour behaviour and metastasic spread vary according to tumour type and whether differences in the angiogenic or lymphangiogenic phenotype influence the route for tumour metastases or determine a more aggressive behaviour has not been fully explored. The angiogenic and lymphangiogenic phenotypes of a large cohort of thyroid proliferative lesions (n=191) were studied. Using immunohistochemistry for CD34, lymphatic vessel endothelial receptor-1 (LYVE-1) (specific markers for vascular and lymphatic endothelium respectively), vascular endothelial growth factor (VEGF-A), VEGF-C and fibroblast growth factor-2 (FGF-2), this study analyses microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic factors in normal thyroid (NT; n=19), multinodular goitre (n=25), toxic multinodular goitre (n=8), Graves' hyperplasia (n=22), follicular adenoma (n=54), papillary carcinoma (PC; n=27), incidental papillary microcarcinoma (PMC; n=8), follicular carcinoma (FC; n=20) and medullary carcinoma (MC; n=8). MVD was decreased in proliferative lesions, benign and malignant, compared with NT (P<0.0001). In contrast, VEGF-A expression was increased in thyroid carcinomas (PC, FC and MC) when compared with PMC, benign lesions and NT (P<0.0001). LVD was higher in PC and PMC (P=0.001), and VEGF-C expression was increased in PC (P<0.0001). Despite higher LVD and increased expression of VEGF-A and VEGF-C in thyroid cancers, these markers were not related to poor prognosis in terms of tumour size, multifocality and/or presence of lymphatic or distant metastases. In conclusion, angiogenesis is reduced in thyroid proliferative lesions compared with NT tissue. However, VEGF-A expression is upregulated in thyroid cancers. Lymphangiogenesis and VEGF-C expression are increased in thyroid tumours prone to lymphatic metastases. This may be an important mechanism underlying the differences in metastatic behaviour between papillary and follicular thyroid cancer.
Endocrine Related Cancer 09/2006; 13(3):931-44. · 4.36 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There has been recent controversy as to the effectiveness of conventional pituitary irradiation in reducing circulating GH levels to less than 2.5 ng/ml and/or normalization of serum IGF-I.
Our objectives were to determine the effects of conventional pituitary irradiation on 1) lowering of serum GH and IGF-I levels, 2) the proportion of patients who achieve a GH level less than 2.5 ng/ml and a normal age-corrected IGF-I and the time taken to achieve this, and 3) the incidence of hypopituitarism and other adverse effects.
We conducted retrospective data collection from 14 centers throughout the United Kingdom.
We studied 1840 patients with acromegaly, of whom 884 had received conventional pituitary irradiation.
We assessed circulating GH and IGF-I levels and pituitary function at intervals after irradiation.
Mean GH levels declined from 13.5 to 5.3 ng/ml at 2 yr after irradiation, to 2.0 ng/ml by 10 yr, and to 1.1 ng/ml at 20 yr. Twenty-two percent of patients achieved a level less than 2.5 ng/ml by 2 yr, 60% by 10 yr, and 77% by 20 yr. The interval to achieve this depended on the preirradiation GH level. IGF-I levels fell in parallel to those of GH with 63% of patients having a normal level by 10 yr. The proportions of patients with new pituitary hormone deficiencies 10 yr after irradiation were 18% for LH/FSH, 15% for ACTH, and 27% for TSH. No other side effects were noted.
In this, the largest series reported, conventional pituitary irradiation is shown to be an effective and safe means of reducing both serum GH and IGF-I concentrations in patients with acromegaly.
Journal of Clinical Endocrinology & Metabolism 05/2006; 91(4):1239-45. · 6.50 Impact Factor
-
S Melmed,
F Casanueva,
F Cavagnini,
P Chanson,
L A Frohman,
R Gaillard,
E Ghigo,
K Ho,
P Jaquet,
D Kleinberg,
S Lamberts,
E Laws,
G Lombardi,
M C Sheppard,
M Thorner,
M L Vance, J A H Wass,
A Giustina
[show abstract]
[hide abstract]
ABSTRACT: In November 2003, the Pituitary Society and the European Neuroendocrine Association sponsored a consensus workshop in Seville to address challenging issues in the medical management of acromegaly. Participants comprised 70 endocrinologists and neurosurgeons with international expertise in managing patients with acromegaly. All participants participated in the workshop proceedings, and the final document written by the scientific committee reflects the consensus opinion of the interactive deliberations. The meeting was supported by an unrestricted educational grant from Ipsen. No pharmaceutical representatives participated in the program planning or in the scientific deliberations.
European Journal of Endocrinology 01/2006; 153(6):737-40. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Craniopharyngiomas account for 2-5% of all primary intracranial tumours. Despite their benign histological appearance, they are often associated with an unfavourable prognosis and their optimal treatment remains controversial.
To analyse the natural history and treatment outcome of children and adults presenting to the Departments of Paediatrics and Endocrinology with craniopharyngioma between 1964 and 2003.
The records of 121 patients (age range 2.5-83 years, 42 aged < 16 and 79 aged > or = 16) were identified. The mean follow-up period since presentation was 103 months (8.6 years) (range 0.3-468 months). Sixteen patients underwent gross total removal (A), 3 gross total removal + radiotherapy (B), 51 partial removal (C), 33 partial removal + radiotherapy (D), 6 cyst evacuation alone (E) and 3 cyst evacuation + radiotherapy (F). The clinical, imaging and endocrinological data at presentation and during follow-up were analysed.
Headache and visual field defects were the most common presenting clinical features (64% and 55%, respectively). Ninety-four per cent of the tumours had an extrasellar component and 23% of them were associated with hydrocephalus. There was a significant difference in the recurrence-free survival rates between groups A-D [at 10 years: 100% (A), 100% (B), 38% (C) and 77% (D), P < 0.01], which persisted even when analysing patients operated after 1980. The median time of first recurrence was 2.5 years (range 0.5-36). The peri-operative mortality of the patients who had any type of neurosurgical intervention due to recurrence was higher than that observed after primary surgery (24%vs. 1.8%) (P < 0.01). The rate of re-accumulation of the cyst fluid was 58% during the first year in patients of group E, whereas none of the subjects of group F experienced such an event during their follow-up period. There was no reversal of pre-existing pituitary hormone deficits after any surgical intervention. The probabilities of GH, FSH/LH, ACTH, TSH deficiency and diabetes insipidus at the 10-year follow-up were 88%, 90%, 86%, 80% and 65%, respectively. After excluding the non-tumour-related deaths, the 10-year survival rate following presentation was 90%. Patients with recurrence had a significantly lower probability for survival compared with those without it (at 10 years: 70%vs. 99%, P < 0.01). At the 10-year follow-up the probability of the presence of major visual field defects was 48%, hyperphagia/obesity 39%, epilepsy 12% and hemi-/monoparesis 11%. In this large series no substantial differences in the outcome of tumours diagnosed during childhood or adult life were found.
Craniopharyngiomas remain tumours associated with significant morbidity. Gross total removal provides favourable results in terms of recurrences. If this cannot be achieved safely, adjuvant radiotherapy is beneficial in preventing tumour re-growth. Childhood- and adult-onset lesions generally behave similarly.
Clinical Endocrinology 04/2005; 62(4):397-409. · 3.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tumours are dependent on angiogenesis for growth and inhibition of angiogenesis has become a target for antineoplastic therapy. In the pituitary, unlike other tissues, vascularization is lower in adenomas compared to the normal gland. Despite this finding, a relationship between increased vascularity and several aspects of prolactinoma behaviour such as size, invasiveness, surgical outcome and malignancy, has been demonstrated. The process of angiogenesis is the result of a balance of stimulating and inhibiting factors. It is likely that an interaction between gene expression (such as pituitary tumour transforming gene (PTTG) and a novel gene located within the Edpm5 quantitative trait locus), hormonal stimuli including oestrogens, dopamine, 16 kDa fragments of prolactin and proangiogenic and antiangiogenic growth factors (for example, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2), determine the final angiogenic phenotype of prolactinomas, and thus subsequent tumour behaviour. The elucidation of all the factors involved in the regulation of angiogenesis and their interactions might open new possibilities in the treatment of prolactinomas, especially in those cases with resistance or intolerance to dopamine agonists.
Pituitary 02/2005; 8(1):17-23. · 1.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angiogenesis and lymphangiogenesis are involved in tumoral growth and metastatic spread. There is little information on angiogenesis and no available data on lymphangiogenesis in parathyroid glands (PTG). Using immunohistochemistry for CD34, LYVE-1 (specific markers for vascular and lymphatic endothelium, respectively), vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, this study analyzes microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic growth factors in 13 normal PTG, 77 parathyroid adenomas (PTA), and 17 primary parathyroid hyperplasia (PPH). MVD was higher in PPH and PTA, compared with PTG (P < 0.001). There was no difference in VEGF-A expression among groups. In contrast, FGF-2 expression was higher in PPH, compared with PTA and PTG (P < 0.0001). FGF-2 scores and MVD were significantly correlated (r = 0.43). LVD did not differ among groups, and VEGF-C expression was unrelated to LVD. There was no relationship between MVD and tumor behavior (adenoma size, PTH, or calcium). In conclusion, this study shows increased angiogenesis in parathyroid proliferative lesions compared with normal glands and suggests that FGF-2 is proangiogenic in parathyroid tissue. In PTA, tumor behavior is not related to angiogenic phenotype. This is the first demonstration of lymphatic vessels in PTG, but the lack of correlation with VEGF-C expression suggests that VEGF-C is not the primary lymphangiogenic factor.
Journal of Clinical Endocrinology & Metabolism 06/2004; 89(6):2890-6. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angiogenesis, the process of development of a new vasculature, plays a crucial role in tumour growth. In the pituitary, unlike other tissues, vascularization is lower in adenomas compared to the normal gland. Despite this finding, a relationship between increased vascularity and some aspects of tumour behaviour such as size, invasiveness, surgical outcome and malignancy, has been demonstrated. The process of angiogenesis is the result of a balance of stimulating and inhibiting factors. It is likely that an interaction between gene expression (such as pituitary tumour transforming gene), hormonal stimuli including oestrogens, corticosteroids, dopamine, 16-kDa fragments of prolactin and growth hormone, somatostatin analogues, and pro- and anti-angiogenic growth factors (e.g. vascular endothelial growth factor and fibroblast growth factor), determine the final angiogenic phenotype of pituitary tumours, and thus subsequent tumour behaviour.
Frontiers of hormone research 02/2004; 32:133-45. · 1.71 Impact Factor
