[Chordoma]. / Les chordomes.

PURPOSES: To review in the literature, all the epidemiological, clinical, radiological, histological and therapeutic data regarding chordomas as well as various notochordal entities: ecchordosis physaliphora, intradural and intraparenchymatous chordomas, benign notochordal cell tumors, parachordomas and extra-axial chordomas. To identify different types of chordomas, including familial forms, associations with tuberous sclerosis, Ollier's disease and Maffucci's syndrome, forms with metastasis and seeding. To assess the recent data regarding molecular biology and progress in targeted therapy. To compare the different types of radiotherapy, especially protontherapy and their therapeutic effects. To review the largest series of chordomas in their different localizations (skull base, sacrum and mobile spine) from the literature. MATERIALS: The series of 136 chordomas treated and followed up over 20 years (1972-2012) in the department of neurosurgery at Lariboisière hospital is reviewed. It includes: 58 chordomas of the skull base, 47 of the craniocervical junction, 23 of the cervical spine and 8 from the lombosacral region. Similarly, 31 chordomas in children (less than 18 years of age), observed in the departments of neurosurgery of les Enfants-Malades and Lariboisière hospitals, are presented. They were observed between 1976 and 2010 and were located intracranially (n=22 including 13 with cervical extension), 4 at the craniocervical junction level and 5 in the cervical spine. METHODS: In the entire Lariboisière series and in the different groups of localization, different parameters were analyzed: the delay of diagnosis, of follow-up, of occurrence of metastasis, recurrence and death, the number of primary patients and patients referred to us after progression or recurrence and the number of deaths, recurrences and metastases. The influence of the quality of resection (total, subtotal and partial) on the prognosis is also presented. Kaplan-Meier actuarial curves of overall survival and disease free survival were performed in the entire series, including the different groups of localization based on the following 4 parameters: age, primary and secondary patients, quality of resection and protontherapy. In the pediatric series, a similar analysis was carried-out but was limited by the small number of patients in the subgroups. RESULTS: In the Lariboisière series, the mean delay of diagnosis is 10 months and the mean follow-up is 80 months in each group. The delay before recurrence, metastasis and death is always better for the skull base chordomas and worse for those of the craniocervical junction, which have similar results to those of the cervical spine. Similar figures were observed as regards the number of deaths, metastases and recurrences. Quality of resection is the major factor of prognosis with 20.5 % of deaths and 28 % of recurrences after total resection as compared to 52.5 % and 47.5 % after subtotal resection. This is still more obvious in the group of skull base chordomas. Adding protontherapy to a total resection can still improve the results but there is no change after subtotal resection. The actuarial curve of overall survival shows a clear cut in the slope with some chordomas having a fast evolution towards recurrence and death in less than 4 years and others having a long survival of sometimes more than 20 years. Also, age has no influence on the prognosis. In primary patients, disease free survival is better than in secondary patients but not in overall survival. Protontherapy only improves the overall survival in the entire series and in the skull base group. Total resection improves both the overall and disease free survival in each group. Finally, the adjunct of protontherapy after total resection is clearly demonstrated. In the pediatric series, the median follow-up is 5.7 years. Overall survival and disease free survival are respectively 63 % and 54.3 %. Factors of prognosis are the histological type (atypical forms), localization (worse for the cervical spine and better for the clivus) and again it will depend on the quality of resection. CONCLUSIONS: Many different pathologies derived from the notochord can be observed: some are remnants, some may be precursors of chordomas and some have similar features but are probably not genuine chordomas. To-day, immuno-histological studies should permit to differentiate them from real chordomas. Improving knowledge of molecular biology raises hopes for complementary treatments but to date the quality of surgical resection is still the main factor of prognosis. Complementary protontherapy seems useful, especially in skull base chordomas, which have better overall results than those of the craniocervical junction and of the cervical spine. However, we are still lacking an intrinsic marker of evolution to differentiate the slow growing chordomas with an indolent evolution from aggressive types leading rapidly to recurrence and death on which more aggressive treatments should be applied.

Malignant head/neck paragangliomas. Comparative study.

BACKGROUND: The objective of this study was to report 11 cases of malignant head and neck paraganglioma and to compare their epidemiological, clinical, and genetic characteristics, their natural history and their treatment with those of a series of 131 benign paragangliomas. PATIENTS AND METHODS: Retrospective analysis of 142 patients with head and neck paraganglioma managed between 2001 and 2008. Age at the time of diagnosis, gender, primary tumour site, presence of other non-head/neck paragangliomas and/or metastases diagnosed by imaging (CT, MRI, Octreoscan or (18)F-FDG PET), histology, urinary catecholamine and metanephrine levels, family history, and genetic test results were recorded. RESULTS: This series comprised 131 benign head and neck paragangliomas, mostly observed in women with a mean age at diagnosis of 45 years and a predominance of tympanojugular sites (followed by carotid and vagal sites) with 5% of secreting tumours and 20% of multifocal tumours. Eleven patients (7.7%) with a 1:1 sex ratio presented criteria of malignancy. These patients, with a lower mean age (38 years), predominantly presented carotid lesions with a higher rate of secreting and multifocal tumours, 27% and 46% respectively. The main sites of metastases were bone and lymph nodes. No tympanic paragangliomas were observed. CONCLUSIONS: Malignant paragangliomas are mainly observed in young patients with multifocal tumours, particularly carotid tumours, and are predominantly related to subunit SDH-B mutation. The work-up in these high-risk patients must include whole body scintigraphy and spine MRI. Malignancy is not necessarily associated with a poor short-term prognosis due to the slow course of the disease.

First Bite Syndrome: a little known complication of upper cervical surgery.

INTRODUCTION: First Bite Syndrome (FBS) is a rare pain syndrome sometimes occurring after surgery of the upper cervical region. It presents as excruciating pain, triggered at the beginning of a meal by chewing, swallowing or even simple contact with generally acidic food, waning on subsequent bites and recurring with identical features after pausing for several minutes or at the next meal. OBJECTIVES: Retrospective review of 17 patients who developed FBS after upper cervical surgery. RESULTS: Seventeen patients developed FBS between 1999 and 2010 following surgery for paraganglioma in eight cases, vagal or sympathetic schwannoma in five cases (including one malignant tumour), pleiomorphic adenoma in three cases and Warthin's tumour of the deep lobe of the parotid in one case. The cervical sympathetic trunk was sacrificed in 10 cases and the external carotid artery was ligated in six cases. Horner's sign was observed postoperatively in 12 patients. The characteristic pain of FBS was triggered by chewing or simple contact with essentially acidic food. CONCLUSION: FBS must be identified by the head and neck surgeon and distinguished from the usual postoperative pain. The generally accepted hypothesis is that of sympathetic denervation with parasympathetic secretory hyperactivity, but Horner's sign was present in only 12 of the 17 patients of our series, suggesting that other pathogenic mechanisms may be involved. FBS is difficult to treat, but the pain gradually becomes less severe. The patient must be informed about this rare complication that can impact on postoperative quality of life.

Role of positron emission tomography (PET) in head and neck cancer.

F-18 fluorodeoxyglucose positron emission tomography is now part of the initial stage III and IV cancer work-up and each time that metastasis or the presence of a second cancer is suspected that may contraindicate major surgery. Similarly, this exam should be undertaken when the conventional work-up is negative but there is isolated metastatic adenopathy. In therapeutic follow-up, a 3- or 4-month delay must be respected to prevent false-positive exams caused by inflammation. Although FDG-PET seems very promising in determining target volumes in radiotherapy, its implementation raises a number of problems that can only be resolved through the collaboration of all of the different specialists.

[Scintigraphy by l'Octreoscan in the management of head and neck paragangliomas]. / La scintigraphie à l'Octréoscan dans la prise en charge des paragangliomes de la tête et du cou.

OBJECTIVE: To assess the usefulness of somatostatin receptor scintigraphy [Octreoscan] in a series of 18 patients referred for a suspicion of paraganglioma of the head and neck between July 2001 and February 2002. PATIENTS AND METHODS: Sixteen patients had one or several paragangliomas of the head and neck diagnosed on conclusive conventional imaging including CT and MR scan. In two patients, radiological data were not conclusive. Planar images were obtained 4 and 24 hr after the iv injection of 148-185 MBq [Octreoscan]. RESULTS: Twenty-two hot spot lesions were detected. Twenty of these lesions corresponded to the twenty known paragangliomas. The volume of the smallest tumor was 0.2 cm(3). In one patient, intense thyroid nodule uptake led to the surgical diagnosis of oncocytoma. In two lesions, where conventional imaging was not conclusive, arteriography showed a typical aspect of meningioma; one patient was operated on and histology confirmed this diagnosis. No evidence of abnormal uptake was seen in site previously operated on (3 patients). CONCLUSION: Octreotide scintigraphy is a very sensitive method for detection of paraganglioma of head and neck. It provides information on potential tumor sites in the whole body after one single injection. It could be used as a screening test in patients at risk (familial or known paraganglioma) in order to detect paraganglioma at an early stage and, thus to reduce the surgical morbidity, as well as in the follow-up after surgery to detect recurrences.

Whole-body (201)Tl scintigraphy can detect exercise lower limb perfusion abnormalities in asymptomatic diabetic patients with normal Doppler pressure indices.

Significant lower limb arterial obstruction is usually detected by Doppler ankle-brachial pressure index (ABPI) measurement. However, ABPI is non-contributory in cases of diabetic medial sclerosis or calcifications and is unsuitable for the detection of small vessel involvement. Thallium-201, a perfusion agent, is frequently used for the investigation of coronary artery disease, and whole-body (201)Tl scintigraphy (WBS) has also been reported to be useful in the assessment of peripheral artery disease (PAD). Thus, we evaluated the clinical feasibility of simultaneous myocardial and lower limb perfusion assessment. WBS was performed after treadmill exercise and myocardial scintigraphy, and again 4 h later. Calf (201)Tl fractional activities (percentage of whole-body (201)Tl uptake) were calculated. We determined a threshold value of normal post-exercise calf (201)Tl uptake (mean of the (201)Tl fractional uptakes minus 2 SD) in a control group of nine healthy volunteers. We checked its accuracy in a pilot group of 25 diabetic patients with proven PAD. This method permitted the detection of lower limb perfusion abnormalities in 38% of 47 asymptomatic diabetic patients with no evidence of PAD. In conclusion, for asymptomatic diabetic patients, whole-body (201)Tl scintigraphy after a treadmill test seems an efficient method of showing lower limb perfusion abnormalities not detected by ABPI measurement. It allows the evaluation of vascular status with no additional inconvenience for patients when performed after myocardial scintigraphy.

A comparison of radiopharmaceutical agents used for the diagnosis of pulmonary embolism.

Radioactive gas or technetium-99m aerosols are used to perform pulmonary ventilation scintigraphy. The aim of this study was to compare three radiopharmaceuticals, Kryptoscan, Technegas and Venticis II, in terms of their costs and user preferences rather than on the basis of diagnostic efficacy. For each radiopharmaceutical agent, an analysis questionnaire was sent to nuclear medicine departments setting out the criteria (and subcriteria) to be assessed: diagnosis quality: imaging quality, distribution homogeneity, examination procedures and capacity to examine particular patients (e.g. smokers); safety: for patient, paramedical and medical staff and the environment; use: availability in cases of emergency, ergonomics of the apparatus, simplicity and time of preparation. A score, ranging from 0 to 5, and a weighting (importance of one criterion with regard to the others) were assigned to each criterion. The direct cost of a ventilation (drugs, generator systems, disposable materials) was calculated for each radiopharmaceutical agent according to the number of patients examined per day (1-6) and the number of examination days per week (2-5). Fourteen questionnaires concerning at least two of the products were returned out of the 30 mailed. A 'preference score' was calculated using Pharma Decision software. The mean score of Kryptoscan was significantly higher than that of Venticis II (444 vs. 286, P < 0.001) and higher than the mean score of Technegas (444 vs. 344, P < 0.01). For Venticis II and Technegas, the changes in patient direct costs were minor and depended on the number of patients per day and the number of examination days per week. Respectively, they were: $US 117.66 (5 patients.day-1; 5 days.week-1) to $US 147.74 (2 patients.day-1; 2 days.week-1) and $US 56.60 (6 patients.day-1; 5 days.week-1) to $US 132.08 (2 patients.day-1; 2 days.week-1). The direct cost of ventilation using Kryptoscan varied only according to the number of patients examined per day: $US 104.66 (6 patients.day-1) to $US 266.47 (2 patients.day-1). This study shows that Kryptoscan appears to be preferable for ventilation scintigraphy whenever at least four patients are examined daily.

Somatostatin receptor scintigraphy in pituitary adenomas: a somatostatin receptor density index can predict hormonal and tumoral efficacy of octreotide in vivo.

UNLABELLED: Previous studies have failed to predict somatostatin analog response with somatostatin receptor scintigraphy in pituitary adenomas. In vitro studies have shown that the density of somatostatin receptors in pituitary tumors might be critical for octreotide response. METHODS: The density of somatostatin receptors was calculated in vivo combining the uptake index obtained from somatostatin receptor scintigraphy and the tumor volume obtained by MRI. The ratio of these two values, called density index (DI), was established in 32 of 37 consecutive patients with pituitary adenomas (11 had growth hormone-secreting adenomas, 4 thyroid-stimulating hormone-secreting and 17 nonfunctioning). It was compared with hormonal response, assessed in 15 secreting adenomas on growth hormone or thyroid stimulating hormone suppression (which was considered significant when it reached at least 50% of basal level), and with tumor shrinkage (which was considered significant when > or =20% of pretherapeutic value) in 12 secreting and 14 nonfunctioning adenomas. RESULTS: In agreement with previous reports, uptake index is not predictive of octreotide response. In contrast, DI predicts both hormonal suppression and tumor shrinkage (P = 0.009 and P = 0.0002, respectively) obtained with octreotide therapy. DI sensitivity, specificity and accuracy were 92% each, and a positive correlation was found between DI and the percentage of tumor shrinkage (r = 0.54, P = 0.004). CONCLUSION: The combination of scintigraphic and MRI data allows the computation of a DI for somatostatin receptors that points out patients who can profit from somatostatin analog treatment.

A new quantitative D-dimer assay appropriate in emergency: reliability of the assay for pulmonary embolism exclusion diagnosis.

Plasma D-dimers, degradation products of cross-linked fibrin, are elevated in several thrombotic diseases. In the last decade, their measurement has been performed with specific monoclonal antibody based ELISA assay, with a high negative predictive value of such pathologies. However these methods have a low clinical impact since they cannot be used in emergency because they are time consuming and require series. Recently, rapid tests have been proposed with similar accuracy and are feasible for use in emergency conditions. The aim of our study was to evaluate the potential value of a new quantitative rapid assay, based on agglutination of latex microparticles coated with two monoclonal antibodies specific for D-dimers (Liatest D-Di, Diagnostica Stago), in the exclusion diagnosis of pulmonary embolism (PE). Eighty-five consecutive suspected PE patients were included in the study. D-dimer determination was performed with both standard ELISA and Liatest D-Di just before pulmonary scintigraphy. Sixty-nine patients were free of PE and 16 had PE. Our results confirm the excellent sensitivity and negative predictive values of the conventional D-dimer ELISA. Using a cut-off value of 500 ng/ml, the sensitivity and the negative predictive values of Liatest D-Di were 94% and 96%, respectively. Only one case of PE had a D-dimer value at 480 ng/ml, close to the cut-off value. This study demonstrates that the Liatest D-Di assay is sensitive enough to be used as the first step in the assessment of PE. However, the best cut-off value has to be determined to get an exclusion diagnosis with certainty.

Somatostatin receptor imaging in somatotroph and non-functioning pituitary adenomas: correlation with hormonal and visual responses to octreotide.

OBJECTIVE: A multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH-secreting and non-functioning pituitary adenomas. SUBJECTS AND METHODS: Somatostatin receptor scintigraphy was performed in 48 patients (19 acromegaly, 29 non-functioning pituitary adenomas with ophthalmological defects). Results were expressed as an uptake index of the pituitary area. A threshold for positivity was determined in 23 subjects considered as controls. Thirty-five patients were treated for 1 month with octreotide (300 micrograms daily). The therapeutic response was assessed on GH and IGF-I suppression or evolution of the ophthalmological defects. The relationships between the somatostatin receptor scintigraphy result, the therapeutic effect of octreotide and in vitro studies performed in 12 tumours were studied. RESULTS: From the results of control subjects the uptake index threshold for positivity was 2. In patients, somatostatin receptor scintigraphy was positive in 64% and there was no relationship between uptake index and tumour size. In GH tumours, somatostatin receptor scintigraphy was positive in 68%; uptake index was related to octreotide-induced GH and IGF I suppression. The positive predictive value was 100% and the negative predictive value was 50%. In vitro studies showed detectable binding sites for somatostatin with sst2 and sst5 expression in the 4 GH tumours studied although somatostatin receptor scintigraphy was negative in 2 cases. In non-functioning pituitary adenomas somatostatin receptor scintigraphy was positive in 62%. Based on visual effects, the positive predictive value was 61% and the negative predictive value was 100%. A wide distribution of somatostatin binding sites was found in 8 non-functioning pituitary adenomas with expression of sst2 only. CONCLUSION: In the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non-functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.

Advantages of SPECT in technetium-99m-sestamibi parathyroid scintigraphy.

UNLABELLED: We demonstrate several advantages of SPECT in parathyroid scintigraphy. METHODS: Forty-four parathyroid 99mTc-MIBI scintigrams were obtained before surgery in 43 patients suffering from hyperparathyroidism. For each patient, we obtained dynamic views and planar and SPECT images of the neck and thorax. For 15 patients, we also acquired a delayed static view of the neck 2 hr after tracer injection. Abnormal thyroid-area glands were detected with factor analysis of dynamic structure (FADS) of the initial dynamic acquisition. In the 15 patients with delayed views of the neck, we compared FADS and the double-phase study results to detect glands in the thyroid uptake area. Glands outside the thyroid area were demonstrated on planar views. The location of enlarged glands was more precisely defined on the tomographic slices. The anatomic and histologic findings and the evolution of hypercalcemia after surgery were taken as reference. RESULTS: Sixty-four abnormal glands were found during surgery, including 39 observed in patients who underwent reoperation for persistent or recurrent hyperparathyroidism. Twenty-two of these glands were in an abnormal location, including 10 in the mediastinum. SPECT allowed the detection of three glands not demonstrated on planar views or FADS. Fifty-eight glands were correctly localized scintigraphically, including 34 in patients who underwent reoperation. Therefore, SPECT raised the sensitivity from 86% to 90.5% and from 79.5% to 87% in the reoperated patients. Tracer uptake in the low mediastinal area was better analyzed on tomographic slices than on planar views. Only seven false-positive results were depicted by planar views or FADS; none were depicted on SPECT. CONCLUSION: A combination of FADS and SPECT permits detection of small glands, even in a posterior location, inside or outside the thyroid area. This scintigraphic method enables the surgeon to define more precisely details about the location of the enlarged gland and contributes to improved parathyroid surgery.

Radioisotope bone scanning in chronic osseous sarcoidosis.

Sarcoidosis is rarely recognized as an osseous manifestations alone. Patients with osseous involvement usually have a chronic multivisceral form of the disease. The authors report a case of osseous sarcoidosis without other visceral involvement. A bone scan was requested to evaluate the extent of the bone involvement and explore buttocks pain.

[Hypophyseal adenomas: functional and tumor evaluation and therapeutic approaches]. / Adénomes hypophysaires: bilan tumoral et fonctionnel et abords thérapeutiques. therapeutic approaches]

Patients with pituitary adenomas present with hypersecretion syndrome(s), and/or pituitary failure(s), and/or signs of mass effect, or incidentally. Pituitary function evaluation, visual acuity and field check-up, and MRI or at least CAT are compulsory for diagnosis, and for therapeutic approach; surgery for Cushing's disease, dopamine agonists for prolactinomas, somatostatin analogs or surgery for thyrotroph adenomas, surgery and/or somatostatin analogs and/or radiotherapy in acromegaly, surgery with additional irradiation in most adenomas of other types, or even expectation in some instances.

Indium-111 pentetreotide scintigraphy in malignant lymphomas.

Somatostatin receptor imaging (SRI) was carried out as part of the initial staging of 26 patients with histologically proven Hodgkin's (3) and non-Hodgkin's (23) lymphoma, and in the assessment of the first treatment's efficacy in seven of these patients. Static acquisitions over the whole body were performed 4 and 24 h after intravenous administration of 150 MBq of indium-111 pentetreotide. SRI data were compared with the results of conventional methods (clinical data, abdominal and thoracic computed tomography, bone marrow biopsy). Only 50 of the 86 (58%) confirmed extra-medullary tumour sites were detected by SRI. Twelve previously unknown localizations were visualized in seven patients. The Ann Arbor clinical stage was modified in only one of them. When tumoral tracer uptake was present, a tumour uptake index (TUI) was calculated using two regions of interest (one over the tumoral hot spot and one over the shoulder) on 24-h planar images. The patients were classified into three groups: high tumour uptake (TUI > 2.5 in all tumour sites, group A, six patients), low tumour uptake (1.5 < TUI < 2.5 in all tumour sites, group B, 18 patients), and no tumour uptake (group C, two patients). The sensitivity of SRI detection was higher in group A (90%) than in group B (52%) (P < 0.001). Six weeks after the fourth chemotherapy cycle, conventional methods and SRI were concordant in five of seven investigated cases (four complete remissions and one residual active thoracic mass showing tracer uptake), and discordant in two. SRI demonstrated residual tumoral tracer uptake in these two patients, who had previously been considered to be in complete remission. In conclusion, SRI does not seem to be reliable for the initial staging of lymphomas because of the highly variable and usually low tumoral tracer uptake. It may be more useful in the diagnosis of residual masses after treatment. However, further studies are needed to assess its specificity.

Characteristics and consequences of duodenogastric reflux in children on total parenteral nutrition (TPN) for severe gastrointestinal disorders.

This study was carried out to determine the frequency and composition (biliary and/or pancreactic) of duodenogastric reflux (DGR) in children with severe gastro-intestinal disorders on total parenteral nutrition (TPN), and to assess its consequences in terms of gastric histology (gastric per endoscopic biopsies) and secretion (acid, pepsin and sialic acid output). Sixteen children (mean age: 20 months) with severe gastro-intestinal disorders requiring TPN (mean duration: 9.5 months) were studied. DGR was demonstrated by measuring gastric choline and trypsin outputs. Serum gastrin levels were measured in all patients. Seven children (44%) had a DGR, with a significant increase in choline output (p < 0.02). Trypsin output was elevated in one patient only. Exudative gastritis and increased sialic acid output occurred in the presence and in the absence of DGR. DGR did not alter the basal acid and pepsin secretions. The serum gastrin levels were normal except in one case. These results show that DGR occurs frequently in children suffering from severe gastro-intestinal disorders on TPN, that it is mainly of biliary origin and that exudative gastritis is very frequent but not correlated with DGR. It suggests that DGR causes little injury in children on TPN, perhaps because of their decreased pancreatic secretion.

Somatostatin receptor imaging in non-functioning pituitary adenomas: value of an uptake index.

Somatostatin receptor imaging (SRI) was performed in five patients with known non-functioning pituitary adenomas. To determine whether the pituitary uptake correlates with response to octreotide therapy, an uptake index (UI) was calculated. Pituitary adenomas were detected in all five patients. The UI was, respectively, 15.1, 3.7, 2.2, 2.2 and 2.2 (the UI calculated in 12 normal subjects was between 1 and 1.9). Only the patient with the highest UI (15.1) had a dramatic improvement in tumour volume and visual function in response to octreotide therapy. The UI might be a good predictive parameter of octreotide therapy efficacy in non-functioning adenomas.

[Bone metastases in epidural invasion of gastrinoma]. / Métastases osseuses avec extension épidurale d'un gastrinome.

Malignant gastrinoma is a nonbeta islet cell tumor which rarely disseminates to the bone. However, in the case reported herein, diffuse metastatic bone disease with symptomatic epidural spread developed. Somatostatin and 99mTc-HDP bone scans demonstrated hot spots in the same sites, establishing that the bone lesions contained somatostatin receptor. Irradiation was effective in relieving pain.

Shrinkage of a primary thyrotropin-secreting pituitary adenoma treated with the long-acting somatostatin analogue octreotide (SMS 201-995).

The long-acting somatostatin agonist octreotide can control TSH hypersecretion from most thyrotropic adenomas. Octreotide therapy has even been shown to improve chiasmal dysfunction. We report another patient in whom octreotide therapy was associated with gradual suppression of TSH hypersecretion, which escaped partially, dramatic and very rapid and sustained improvement of chiasm compression, and dramatic and sustained shrinkage of an unresectable TSH-secreting pituitary tumour. Unusual and prolonged gastrointestinal adverse reactions eventually disappeared except for steatorrhea. In conclusion, octreotide may be considered as first line treatment in patients with unresectable thyrotropic adenomas.

[Long-term treatment of Cushing's disease using ketoconazole. Possibility of therapeutic escape]. / Traitement prolongé de la maladie de Cushing par le kétoconazole. Possibilité d'un échappement thérapeutique.

Five women suffering from Cushing's disease were treated with ketoconazole 800 mg per day for 2 to 28 months (mean 12.4 months). Four of them had full clinical and biochemical regression. However, after 8 months of therapy the disease failed to respond in three of these four women. Increasing the ketoconazole dosage up to 1,200 mg per day was ineffective in two patients. Such an escape phenomenon, not described until now, will restrict the use of ketoconazole in the treatment of Cushing's disease, although the drug is easy to administer and well tolerated globally and by the liver in most cases.