Ablative thyroid treatment for thyrotoxicosis due to thyrotropin-producing pituitary tumours.

BACKGROUND: Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) are rare tumours that can be invasive. It has been suggested that thyroid surgery or radioiodine treatment should not be considered in patients with such tumours as these treatments may facilitate rapid and aggressive tumour expansion. AIM: To study the effects of thyroid ablative treatment on tumour size and thyroid status in two patients with TSHomas in whom the size of the adenoma was clearly documented before treatment was started. METHODS: Patients studied were: (1) a female patient with a TSHoma who declined to undergo pituitary surgery and underwent a total thyroidectomy instead and (2) a male patient who opted for radioiodine treatment for his recurrent TSHoma. Changes in tumour size on serial magnetic resonance imaging scans, and restoration of euthyroidism were studied. RESULTS: No marked changes in tumour size or features of aggressiveness occurred in these patients over periods of 8 and 12 years. Euthyroidism was restored and maintained in both patients. CONCLUSIONS: Ablative thyroid treatment can be a safe and successful option to treat TSHomas, but long-term and close follow-up of these patients is mandatory to ensure that the size and behaviour of the tumours do not change markedly.

Cerebral aneurysm associated with an intracranial tumour: staged endovascular and surgical treatment in two cases.

Two cases are reported in which an anterior communicating artery aneurysm was associated with an intracranial tumour. The tumour was a suprasellar meningioma in one case and an optic chiasm/hypothalamic astrocytoma in the other. In both cases, the aneurysm was successfully embolized using Guglielmi detachable coils. Subsequently craniotomy was performed with complete excision of the meningioma and subtotal removal of the astrocytoma. Endovascular techniques can be employed to make the surgical excision of an intracranial tumour co-existing with an incidental aneurysm safer.

New proposals for training in neurosurgery.

The rapidly evolving changes in working patterns, career structure and the regulation of training of doctors have provided an ideal opportunity for proposals to improve the programme for the training of neurosurgeons. The Education and Training Committee of the Society of British Neurological Surgeons (D.G. Hardy, A. J. W. Steers, N. T. Gurusinghe, P. M. Foy, P. van Hille, R. A. Cowie, H. A. Crockard, O. Sparrow and S. Burn) has, in recent months, worked closely with the Specialist Advisory Committee (SAC) in neurosurgery, Department of Health (Modernizing Medical Careers Group, H. A. Crockard, A. Havers, T. Hobbs) and colleagues from the major neuroscience specialties to develop a new programme based on a 'Common Stem' approach. This article describes the principles of the programme. The proposals have received approval by the Council of the SBNS, the Presidents of the four Surgical Royal Colleges and the Senate of Surgery.

Intraspinal oxidised cellulose (Surgicel) causing delayed paraplegia after thoracotomy--a report of three cases.

Oxidised regenerated cellulose (Surgicel) is a commonly used haemostatic agent in neurosurgery, thoracic surgery, and orthopaedics. We present three cases of paraplegia after thoracic surgery during which oxidised cellulose had been used during thoracotomy for haemorrhage control, and was later found to have passed through the intervertebral foramen causing spinal cord compression. In all intraspinal and perispinal procedures, the over-liberal use of Surgicel should be avoided, and attempts made to remove all excess Surgicel once adequate haemostasis is obtained.

CSF rhinorrhoea following treatment with dopamine agonists for massive invasive prolactinomas.

OBJECTIVE: The management of CSF rhinorrhoea following dopamine agonist (DA) treatment for invasive prolactinomas is difficult and there is no clear consensus for its treatment. Our objective was therefore to investigate the different treatments for this condition. DESIGN AND PATIENTS: We examined the case notes of five patients with invasive prolactinomas and CSF rhinorrhoea following DA treatment. The different ways in which this complication had been managed is detailed along with a review of the literature. RESULTS: Five patients aged 24-67 years (3 male) with massive invasive prolactinomas (serum prolactin 95000-500000 mU/l) eroding the skull base were treated with dopamine agonists (3 bromocriptine, 1 cabergoline and 1 both). CSF rhinorrhoea developed in all patients between 1 week and 4 months after commencing dopamine agonist treatment. In two patients (cases 1 and 4), CSF rhinorrhoea ceased within a few days of stopping bromocriptine but restarted when treatment was resumed. One of these (case 4), a 67-year-old woman had no further treatment and CSF leakage stopped completely. She died of unrelated medical problems 3 years later. In one patient staphylococcus aureus meningitis and pneumocephalus developed as a complication of CSF rhinorrhoea. Three patients had endoscopic nasal surgery to repair the fistula using muscle grafts, and to decompress the pituitary tumour, with success in two. One patient had intracranial surgery and dural repair, which was successful in sealing the leak. CONCLUSIONS: We suggest that surgery as soon as is feasible is the treatment of choice for the repair of a CSF leak following dopamine agonist treatment. An additional strategy is the withdrawal of dopamine agonist to allow tumour re-growth to stop the leak.

17Beta-hydroxysteroid dehydrogenase type 1, 2, 3, and 4 expression and enzyme activity in human anterior pituitary adenomas.

17Beta-hydroxysteroid dehydrogenase (17betaHSD) isoforms reversibly catalyze the final step in the formation of estradiol (E2) from estrone (E1) and the formation of testosterone from androstenedione. We have investigated 17betaHSD type 1, 2, 3, and 4 gene expression and 17betaHSD estrogenic activity in human anterior pituitary adenomas. 17BetaHSD messenger ribonucleic acid (mRNA) expression was studied by RT-PCR in 42 pituitary tumors and 3 normal pituitaries, 17betaHSD activity was studied in 11 tumors and 17betaHSD type 1 was immunolocalized in vitro in 6 tumors. 17BetaHSD type 1 gene expression was detected in 34 of 42 adenomas in all tumor subtypes; 17betaHSD type 2 mRNA was detected in 18 of 42 adenomas, but not in prolactinomas; 17betaHSD type 3 mRNA was detected in 12 of 42 adenomas, but not in corticotropinomas; 17betaHSD type 4 was expressed in 20 of 42 adenomas by all adenoma subtypes. Reversible 17betaHSD activity was found in 9 of 11 adenomas, and 17betaHSD type 1 immunopositivity was cytoplasmically distributed in all 6 adenomas in vitro. All 4 17betaHSD isoforms are variably expressed in human anterior pituitary adenomas, which also show 17betaHSD enzyme activity, suggesting that 17betaHSD may play an important role in regulating the local cellular levels of estradiol.

Cystic lymphocytic hypophysitis, visual field defects and hypopituitarism.

A 45-year-old man presented with anterior pituitary failure, requiring thyroxine, hydrocortisone and androgen replacement. An MRI scan revealed a large cystic pituitary mass and thickening of the pituitary stalk. Over three years, diabetes insipidus and bitemporal hemianopia developed and the cystic mass had enlarged on MR scanning. Transphenoidal resection was performed with normalisation of the visual fields. Histology revealed lymphocytic hypophysitis, which is rare in men. The presentation with cystic enlargement is unique.

Effect of cell density on hormonal secretion from human pituitary adenomas in vitro.

UNLABELLED: Cell density effects were investigated on tumorous hormonal secretion from 10 pituitary adenomas: 3 somatotrophinomas secreting GH and PRL; 7 gonadotrophinomas, 3 co-secreted both FSH and LH, all 7 secreted LH. Enzymatically dispersed tissue was plated out in 24-well plates at 5 x 10(5), 10(5), 5 x 10(4) and 10(4) cells/well in serum-free media. Media were collected weekly for 2 weeks. RESULTS: In 3 of 3 somatotrophinomas, GH and PRL secretion was higher (p < 0.05) at both week 1 and 2 from 10(4) cells/well, but similar at other cell densities. In all 3 gonadotrophinomas, the FSH secretory rate was highest at 5 x 10(5) cells/well which fell as cell density decreased. Conversely, in 7 of 7 gonadotrophinomas the LH secretory rate was highest at 10(4) cells/well (p < 0.01) which fell as cell density increased. CONCLUSION: These data suggest that paracrine factors may modulate tumorous GH, PRL, FSH and LH secretion, and show that FSH and LH secretion vary inversely as cell density increases.

A comparison of proliferation indices in human anterior pituitary adenomas using formalin-fixed tissue and in vitro cell culture.

The authors compared detection methods for cell proliferation in human anterior pituitary adenomas using histological sections and dispersed cell culture. After tumor cells had been grown for 4 days in dispersed culture, bromodeoxyuridine (BUdR), proliferating cell nuclear antigen (PCNA), and Ki-67 were compared by double immunostaining and contrasted with single staining of PCNA and Ki-67 indices in the corresponding histological sections from 12 human pituitary adenomas. In vitro, the BUdR labeling index was positive in six of 12 tumors (range < 0.1-5.1%), 10 of 12 tumors were PCNA-positive (range < 0.1-100%), and Ki-67 was positive in 10 of 12 adenomas (range < 0.1-8%). In vitro, BUdR and Ki-67 gave similar proliferative indices for 10 of 12 adenomas. In vivo, the PCNA labeling index was positive in 12 of 12 adenomas (range 0.9-95%) and Ki-67 was positive in 11 of 12 adenomas (range < 0.1-2%). Tumors with a labeling index less than 0.1% were considered to be negative for proliferation. High PCNA values were found in vitro and in vivo, whereas Ki-67 labeling indices were similar in vitro and in vivo for nine of 12 adenomas. It is concluded that Ki-67 proliferative indices in vivo reflect those found in vitro, at least after 4 days in dispersed culture, but that PCNA overestimates pituitary adenoma proliferation in histological sections as well as in dispersed culture.

Apoptosis and p53 suppressor gene protein expression in human anterior pituitary adenomas.

Human anterior pituitary adenomas proliferate and express the p53 tumour suppressor gene protein, but it is not known if apoptosis (programmed cell death) occurs. Therefore, the detection of apoptosis was undertaken in tumorous human anterior pituitary tissue and compared with p53 protein expression, tumour type and tumour size. Apoptosis (detected by the in situ end labelling technique) and p53 suppressor gene protein (detected by DO.1-antibody immunocytochemistry) were determined in formalin-fixed and paraffin-embedded tissue from 37 human pituitary adenomas (2 macroprolactinomas, 9 somatotrophinomas and 26 non-functioning adenomas). Two normal anterior pituitaries were also included in this study. Pre-operative tumour size was scored 1 to 4 from magnetic resonance imaging radiology. Apoptosis was found in 7 of 29 tumours (24%), 11% of somatotrophinomas and 33% of non-functioning adenomas, although this difference was not significant. The p53 tumour suppressor protein was found in 7 of 31 tumours (23%), 33% of somatotrophinomas and 19% of non-functioning adenomas. Apoptosis and p53 protein expression were not found in normal anterior pituitary. In conclusion, apoptosis occurs in human anterior pituitary adenomas, but no significant association was found between apoptosis and p53 protein expression, tumour type or tumour size.

Subtotal petrosectomy in the treatment of cerebrospinal fluid fistulae of the lateral skull base.

Cerebrospinal fluid (CSF) fistulae almost invariably lead to meningitis, even in the absence of other clinically obvious sequelae of the fistula such as a CSF fluid leak. The only effective means of reducing the risk of meningitis is surgical closure of the fistula. If surgery is to be recommended to patients with CSF fistulae even if they are currently asymptomatic, the morbidity of the procedure must be a principal determinant of the chosen technique. Recovery after the extracranial approach to a CSF fistula is much more rapid than after an intracranial procedure. The extracranial route is also free of the long-term risk of epilepsy which accompanies a craniotomy. The principal disadvantage of the lateral extracranial approach, failure of treatment, has been largely eliminated following studies into the obliteration of simple bony cavities using free adipose grafts. This paper describes our use of the extracranial approach to closure of CSF fistulae of the lateral skull base.

Idiopathic spontaneous cerebrospinal fluid rhinorrhoea and pneumocephalus: case report and literature review.

We report a case of idiopathic spontaneous cerebrospinal fluid rhinorrhoea associated with marked intraventricular pneumocephalus. The patient, a 60-year-old male, presented with confusion and urinary incontinence. CT cisternography failed to provide preoperative localization of the site of leakage.

Ease and accuracy of evaluation of fetal hands during obstetrical ultrasonography: a prospective study.

Hand malformations characterize many congenital syndromes, including mendelian disorders, skeletal dysplasias, and karyotype abnormalities. Although identification of a hand anomaly alters obstetrical management, evaluation of the fetal hands is not included in current ultrasonographic guidelines. We prospectively studied the utility of allotting up to 5 min to examine fetal hands during obstetrical ultrasonography. Both hands were visualized in 87% of patients (188 of 215). Eight hand abnormalities were present at delivery. Six had been identified antenatally, four during the study with ultrasonography. There were no false positives. Four fetuses with hand malformations were aneuploid. Fetal hands should be examined during a comprehensive obstetrical sonographic evaluation, especially when risk factors for aneuploidy are present.

Report of a controlled clinical trial comparing automated percutaneous lumbar discectomy and microdiscectomy in the treatment of contained lumbar disc herniation.

STUDY DESIGN: The results of a randomized controlled trial comparing automated percutaneous lumbar discectomy (APLD) with lumbar microdiscectomy for the treatment of small contained lumbar discal herniations are reported. All patients gave full informed consent and were assessed by an independent observer. Seventy-one patients with radiologically confirmed small contained lumbar disc herniations were randomly assigned to undergo either APLD or lumbar microdiscectomy. All patients were formally assessed by the independent assessor using the Macnab outcome classification at 3 weeks, 2 months, and 6 months after the procedure with follow-up being continued for the duration of the study. OBJECTIVE: The objective was to complete the first randomized and blinded study with sufficient numbers to provide a valid statistical evaluation of these procedures. SUMMARY OF BACKGROUND DATA: No previous randomized controlled study comparing these methods has been previously reported. METHODS: Each procedure was performed by the same surgeon using standard techniques. Statistical analysis was by the chi-square method. RESULTS: In the APLD group only 9 of 31 (29%) had satisfactory outcomes as compared to 32 of 40 (80%) for the microdiscectomy group. Of those patients in the APLD group who had an unsatisfactory outcome and who then opted to undergo surgery (20 of 22 patients), the final success rate was only 65%. Thus, the cumulative success rate of the group initially randomized to APLD including those undergoing either APLD alone or APLD and microdiscectomy after unsuccessful APLD was 22 of 31 (71%). CONCLUSION: In this group of patients, APLD is seen to be ineffective in the treatment of contained lumbar disc herniation.

Effects of basic fibroblastic growth factor on the function and proliferation of human clinically non-functional pituitary adenomas which secreted glycoprotein hormones in vitro.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion, viability, proliferation, attachment and morphology of ten dispersed human clinically non-functional (NF) adenomas were examined in vitro. Four clinically NF adenomas secreting FSH and/or LH in vitro were unaffected by 10 nM bFGF over a 4-h period. Over 4 days 10 nM bFGF stimulated LH secretion (66% and 72%, P < 0.01) from two out of seven clinically NF adenomas secreting LH, whilst FSH (three tumours) and alpha-subunit secretion (three tumours) were unaffected. One adenoma co-secreting LH and alpha-subunit and one secreting LH alone were studied over 21 days; LH secretion fell progressively, but the decline was significantly less (P < 0.05) with bFGF (10 nM) treatment after 14 and 21 days in both adenomas, whilst the fall in alpha-subunit secretion was unaffected by bFGF treatment. A 24-h GnRH test performed at the start and end of the 21-day period in one of these tumours showed an increase in both basal and stimulated LH secretion in the bFGF-treated group over control (124%, P < 0.001). There was no effect of bFGF (10 nM) on viability, S-phase proliferation, attachment or morphology of adenoma cells over a 4-day period. These results suggest that bFGF has a role in tumorous LH secretion from these adenomas, but is not mitogenic (at least over 4 days) and is without effect on other parameters of in vitro differentiated function.

Anticonvulsant and antibiotic prophylaxis in head injury.

The evidence for and against the prophylactic use of anticonvulsants and antibiotics in head injury is reviewed. There is a lack of blinded placebo-controlled trials in this area. On balance there is no compelling evidence to support the use of either anticonvulsant or antibiotic prophylaxis in head injury, with the possible exception of antibiotic prophylaxis in compound depressed skull fractures and penetrating brain injuries.

Hyperthyroidism secondary to a pituitary adenoma secreting TSH, FSH, alpha-subunit and GH.

A 51-year-old man had been treated for hyperthyroidism with antithyroid drugs for 8 years. He was then found to have a large pituitary adenoma with biochemical evidence of overproduction of TSH, FSH and alpha-subunit. Subsequent immunocytochemical and tissue culture studies confirmed secretion of these hormones. In addition, the tumour stained for GH and was capable of GH production in vitro. This combination of hormones produced by a pituitary adenoma has not been previously reported.