Surgical debulking of pituitary macroadenomas causing acromegaly improves control by lanreotide.

BACKGROUND: 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. OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up.

BACKGROUND: 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. AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease: a single centre audit.

OBJECTIVE: An undetectable postoperative serum cortisol has been regarded as a definition of cure in Cushing's disease. However, we noted disease recurrence amongst patients with Cushing's disease despite undetectable postoperative cortisol levels, and this led us to audit our data. We have also previously assessed surgical outcome for acromegaly and microprolactinoma for a single surgeon. The aims of this study were two-fold: (i) to investigate the treatment and surgical outcome of patients with Cushing's disease. In particular, we wished to compare the data with outcome for other pituitary tumours in our centre; and (ii) to determine whether undetectable cortisol following surgery is predictive of long-term cure for Cushing's disease. PATIENTS AND METHODS: We performed a retrospective audit of 97 patients; mean age 39.1 (range: 14-82) years, 78/97 (80.4%) female, mean follow-up 92 months (range: 6 months to 29 years), with Cushing's disease seen in our unit between 1969 and 1998. We documented diagnostic investigation, immediate surgical outcome and disease recurrence in these patients. RESULTS: All patients had elevated urinary free cortisol (mean 1270.6 nmol/l, range: 327-3245 nmol/l). In total, 95.5% of patients did not suppress with low-dose dexamethasone suppression testing. Hypokalaemia (K < 3.2 mmol/l) was present in 15.6% of patients; 17.5% of patients did not show cortisol suppression with high-dose dexamethasone and 15.8% of patients did not show an ACTH rise of > 50% following corticotrophic releasing hormone (CRH) administration. There was no significant (> 3) gradient in ACTH or cortisol following CRH during inferior petrosal sinus sampling in 27.3% of patients who had the test. A pituitary tumour was demonstrated on imaging in 55.8% of patients; 10.3% were macroadenomas. Mortality rate following trans-sphenoidal surgery was 1%. Following surgery, the immediate postoperative remission rate (undetectable postoperative cortisol) was 68.5%. However, 11.5% of these patients developed disease recurrence during a mean follow-up period of 36.3 months. Considering microadenomas, Cushing's disease patients had an immediate postoperative remission rate of 63.2% which is significantly lower (P < 0.05) compared to a remission rate of 91.1% in acromegaly. Additionally, new postoperative gonadotrophin deficiency (13.9%) and TSH deficiency (25.8%) was higher in patients with Cushing's disease compared to patients with acromegaly or microprolactinoma. Immediate postoperative remission rates improved from 50% in the first decade of a surgeon's career to consistently above 60% in the second and third decades, demonstrating a trend which may be attributed to surgical experience. CONCLUSIONS: (i) Despite strict criteria for immediate postoperative remission and recurrence, undetectable postoperative cortisol is not always predictive of long-term remission. (ii) Despite an aggressive surgical approach, immediate postoperative remission rates for Cushing's disease are lower compared to other microadenomas. The development of new pituitary hormonal deficiency following surgery is also commoner than that seen amongst other microadenomas. These data have important implications for the follow-up of patients with Cushing's disease.

Cryohypophysectomy for bone pain of metastatic breast cancer.

In a series of 22 patients, cryohypophysectomy gave relief of bone pain from metastatic breast cancer for 3 months in 55% of patients and for 6 months in 32% of patients. On average they were pain free for 55% of their remaining life. Advantages of this technique are the avoidance of a major operation, the mild disturbance to the patient, a short hospital stay and the paucity of significant complications apart from a need for hormone replacement.