Biochemical predictors of outcome of pituitary surgery for Cushing's disease.

OBJECTIVE: Transsphenoidal surgery (TS) is the primary therapy for Cushing's disease (CD). The aims of this retrospective study were twofold: (i) investigate early and late results of TS for CD, and (ii) evaluate various postoperative tests in order to predict the outcome of TS. METHODS: We reviewed the long-term outcome in 79 patients with CD who underwent TS (median follow-up 84 months, range 6-197). Within 2 weeks after surgery, morning serum cortisol concentrations were obtained (n = 78) and corticotropin-releasing hormone (CRH) (n = 53) and metyrapone tests (n = 72) were performed. Three groups of outcome were identified: sustained remission, early failure (persistent CD), and late relapse. RESULTS: Immediate postoperative remission was achieved in 51 patients (65%), whereas 28 patients (35%) had persistent CD after TS. Ten patients developed recurrent CD after initial remission (20%). Morning cortisol: all relapses but one recorded serum cortisol >50 nmol/l. A cortisol threshold value of 200 nmol/l has a positive predictive value of 79% for immediate surgical failure (negative predictive failure [NPV] 97%). CRH test: CRH-stimulated peak cortisol > or =600 nmol/l predicted early failure in 78% (NPV 100%). All relapses recorded CRH-stimulated peak cortisol >or =485 nmol/l. Metyrapone test: 11-deoxycortisol >or =345 nmol/l predicted an early failure in 86% of cases (NPV 94%). CONCLUSION: Predictive factors of surgical failure are morning cortisol >or =200 nmol/l, 11-deoxycortisol >or =345 nmol/l after metyrapone and CRH-stimulated cortisol >or =600 nmol/l. CRH and/or metyrapone testing are not superior to morning cortisol concentration in the prediction of outcome of TS. Careful long-term follow-up remains necessary independent of the outcome of biochemical testing.

Bromocriptine increasingly suppresses the in vitro gonadotropin and alpha-subunit release from pituitary adenomas during long term culture.

Prolonged treatment with bromocriptine may lead to a decrease in tumor size in patients with a gonadotroph, alpha-subunit-secreting, or clinically nonfunctioning pituitary adenoma. The effectiveness of the treatment, however, may depend on its duration. We investigated the effects of prolonged incubation with bromocriptine on the release and intracellular hormone and alpha-subunit concentrations in 10 such adenomas in vitro. The release of FSH, LH, alpha-subunit, or a combination of these was demonstrated in 7 tumors. Bromocriptine significantly suppressed this release in 6 tumors. In 5 tumors bromocriptine had an inhibitory effect on gonadotropin and/or alpha-subunit release which increased with duration of culture. Withdrawal of bromocriptine during the culture period led to a recovery of gonadotropin or alpha-subunit release in the 2 tumors in which it was tested. Intracellular hormone and alpha-subunit concentrations in 3 of 4 tumors cultured for 4 or more weeks were significantly lower in bromocriptine-treated than in untreated cells. We conclude that 1) bromocriptine can suppress the in vitro release of gonadotropins and alpha-subunit from the majority of clinically nonfunctioning, gonadotroph, and alpha-subunit-secreting pituitary adenomas; 2) during prolonged incubation of these tumors with bromocriptine, this drug has a time-dependent increasing inhibitory effect on the release and synthesis of gonadotropins and alpha-subunit, which eventually may lead to decreased intracellular concentrations of these glycoproteins.

Intracavitary brachytherapy of cystic craniopharyngiomas.

Visual function, endocrinological status, and radiological outcome are reported in 31 patients harboring a cystic craniopharyngioma, who underwent 35 intracavitary brachytherapy procedures with yttrium-90. In 26 of these patients intracavitary brachytherapy was the primary treatment. The follow-up period ranged from 2 to 80 months (41 +/- 22 months, mean +/- standard deviation). Five patients died from tumor-related causes. Endocrine recovery was modest. Prior to brachytherapy, visual acuity was diminished in 38 eyes and field defects were present in 46. Funduscopy before treatment revealed optic atrophy in 47% of the eyes. Visual acuity improved in 29% of the eyes studied, remained stable in 13%, and deteriorated in 58%. Visual field defects improved in 28% of the eyes studied, remained stable in 20%, and deteriorated in 52%. The possible causes for deterioration in visual function are discussed. Complete resolution of 10 cysts was noted. In 12 patients the size of the cyst decreased; however, in three of these patients new cyst formation took place. The cyst size stabilized in six cases and increased in three. Although there is still a substantial degree of visual function deterioration following intracavitary brachytherapy, morbidity is otherwise low, making this treatment modality a reasonable alternative to craniotomy.

Subdural cysts and diencephalic tumor.

Four children with diencephalic emaciation, three of whom had subdural cysts (effusions), are described. In two of these cases the initial diagnosis was subdural effusion, which delayed the correct diagnosis. Three of the four patients with emaciation of diencephalic origin had large tumors in which the involved part of the diencephalon accounted for only a small part of the total tumor bulk. The fourth patient had a large glioma of the optic chiasm.

[Cushing's disease: successful surgery through improved preoperative tumor localization]. / Ziekte van Cushing: succesvollere chirurgie door verbeterde preoperatieve tumorlokalisatie.

OBJECTIVE: To study the effect of improved preoperative tumour localisation on the outcome of transsphenoidal surgery for Cushing's disease. DESIGN: Retrospective. SETTING: University Hospital Rotterdam, the Netherlands. METHODS: The case records were studied of 61 patients, operated on for Cushing's disease due to a corticotrophin-secreting microadenoma (diameter < 10 mm), in the period January 1985-September 1995. From 1985, preoperative tumour localisation was performed with computed tomography (CT), from 1989 with Magnetic Resonance Imaging (MRI) and Bilateral Simultaneous Inferior Petrosal Sinus Sampling (BSIPSS). The definition of a successful operation was: morning serum cortisol < 500 nmol/l, and of cure: morning serum cortisol < 140 nmol/l or 24-hr cortisoluria < 250 nmol. RESULTS: In 1985-1988, a microadenoma was localised preoperatively in 8/22 patients (36%), the operation was successful in 12 (55%), of which 4 (18%) were cured. In 1989-1991, a microadenoma was localised in 12/15 patients (80%), the operation was successful in 11 (73%), of which 4 (27%) were cured. In 1992-1995 a microadenoma was localised preoperatively in 23/24 patients (96%), the operation was successful in 19 (79%), of which 17 (71%) were cured. In the cured group, there was a low incidence (< 10%) of postoperative hypopituitarism in all three periods. There were 1, 0 and 1 recurrences of Cushing's disease respectively after initial cure. CONCLUSION: In our institution, improved preoperative localisation of corticotrophin-secreting hypophyseal microadenomas was associated with an important increase of success and cure rate of transsphenoidal surgery, while there was no increase in postoperative hypopituitarism or recurrences of Cushing's disease.

Interobserver agreement in assessment of vestibulo-ocular responses.

In 30 comatose head injured patients vestibulo-ocular responses were elicited by caloric stimulation. Inter- and intra-observer agreement of these responses was studied. The responses were shown in the form of a film to ten doctors who classified them into four categories: no reaction, tonic reaction, paradoxical nystagmus and nystagmus. The level of the coefficient Kappa (a chance-corrected measure of interobserver agreement) was 0.50; this is within the range of levels for most components of clinical examination reported in the literature.

Interobserver agreement in assessment of ocular signs in coma.

There is interobserver agreement in the assessment of various ocular signs found in coma patients. As measure for observer agreement the parameter kappa (K) was determined for (in-)equality of pupils, reaction of pupils, spontaneous eye movements, and oculocephalic responses. The agreement in the assessment of the pupils to light and in the assessment of (in-)equality of pupils appeared to be satisfactory, but more disagreement occurred in assessing spontaneous eye movements and oculocephalic responses.

Pyruvate kinase inhibition in the diagnosis of gliomas with an intermediate degree of malignancy.

The aim of the investigation was to see if the histological diagnosis of brain tumors showing an intermediate degree of malignancy can be improved by the measurement of L-alpha-alanine inhibition of pyruvate kinase isoenzymes. The inhibition of pyruvate kinase activity was measured in 51 gliomas with different grades of malignancy. It was confirmed that benign tumors have a low level of inhibition (less than 50%) and that the more malignant the tumor, the higher the level of inhibition became, reaching more than 75%. However, when grade II and III astrocytomas and grade II and III oligodendrogliomas were analyzed, their level of inhibition was found to be variable. Grade II showed low and moderate levels of inhibition and grade III moderate and high levels. In turn, inhibition levels ranging from 50 to 75% were not only found in brain tumors with an intermediate grade of malignancy, but also in a number of benign and malignant tumors. When the survival times of patients with brain tumors were compared with both the histological diagnosis and pyruvate kinase inhibition, the prediction of the survival time on the basis of low and high levels of inhibition correlated well with the histological diagnosis. In contrast, when moderate levels of inhibition were measured, the prediction of the patients' survival remained uncertain and no improvement was found in the prediction for tumors showing an intermediate degree of malignancy on the basis of histology.

Risk factors for meningitis after transsphenoidal surgery.

To evaluate possible risk factors for meningitis, we retrospectively reviewed 228 transsphenoidal operations (in which a standard regimen of amoxicillin prophylaxis was used) for sellar pathology. The incidence of meningitis was 3.1% (seven of 228 cases). Cultures of preoperative specimens from the anterior nasal vestibule in three of seven patients yielded Staphylococcus aureus, but none of these patients developed S. aureus meningitis. Two of three patients with significant preoperative paranasal sinus abnormalities developed meningitis compared with only five of 225 patients without significant paranasal sinus abnormalities (P < .005). Three of 22 patients with intraoperative cerebrospinal fluid (CSF) leakage developed meningitis compared with four of 206 patients without intraoperative CSF leakage (P < .05). Six of seven patients with postoperative CSF rhinorrhea and only one of 221 patients without postoperative CSF rhinorrhea developed meningitis (P < .00001). In conclusion, postoperative CSF leakage is an important risk factor for meningitis after transsphenoidal surgery. Cultures of preoperative specimens from the anterior nasal vestibule did not have any predictive value in our study.