[Surgical kyphoplasty for management of axis metastasis: technical note kyphoplastie de C2]. / Traitement par kyphoplastie ouverte d'une métastase de C2 : cas clinique et note technique.

C2 vertebral metastases are seldom encountered. They usually cause disabling pain at the upper cervical level and can also result in life-threatening spinal instability. The technique described herein may provide a valuable minimally invasive option for treating this condition. We report a case of C2 metastasis resulting from gastric adenocarcinoma in a 58-year-old male; since there was no spinal instability, open kyphoplasty was performed at C2, resulting in the healing of the body and the base of the odontoid of the C2 vertebra. The X-ray follow-up more than six months after surgery confirmed the absence of any spinal instability at the craniocervical junction. Open kyphoplasty at C2 provides a means to manage a metastasis located in the body of the C2 vertebra. This method maintains the rotatory function of the upper cervical spine, which seems to be a crucial factor, given the poor prognosis usually associated with this condition.

[Minimally invasive transmuscular approach for the treatment of lumbar far lateral disc herniation]. / Utilisation d'un écarteur musculaire tubulaire dans le traitement chirurgical des hernies discales lombaires extraforaminales.

BACKGROUND: The purpose of this study was to evaluate a minimally invasive surgical technique for the treatment of lumbar far lateral disc herniation. This technique combines the tubular retractor with the operative microscope. OBJECTIVE AND METHODS: This retrospective study analyzed the files of 26 patients: 15 men and 11 women. The average age was 56 years (range, 19-83 years). The most commonly operated level was L3-L4 (46%), then L4-L5 (30.5%) and finally L2-L3 (15.5%). All patients were operated under general anesthesia. The intraoperative radioscopic location was absolutely necessary. A 12-15 mm paramedian incision was made on the side of the herniation (30 mm from the medial line). We then inserted the tubular muscular retraction system followed by the 14 mm diameter working channel. Guided by operating microscope, the articular isthmus was reamed to expose the root and the disc. The disc herniation was then removed after opening and removing the inter-transverse ligament. RESULTS: The average duration of the surgery was 55 min. This operating time decreased as the surgeons gained experience. The radicular pain, estimated using the analogical visual scale, varied from seven before surgery to two during the postoperative period. All the patients were standing up the day after surgery. The average duration of the postoperative stay in the hospital was three days (range, 1-5 days). We noted no complications from the surgical procedure. The average duration of the follow-up was two years (range, 6-36 months). CONCLUSION: This technique combines the advantages of endoscopic surgery (less muscular and osseous damage) and microscope-guided surgery (three-dimensional vision) and provided good functional results in this series.

[Disappearance of retro-odontoid pseudotumor after C1-C2 transarticular fixation screw]. / Disparition d'une pseudotumeur rétro-odontoïdienne sur instabilité C1-C2 par ostéosynthèse transarticulaire C1-C2.

Atlantoaxial degenerative articular cysts are described in various situations like rheumatoid arthritis, dialysis, and fractures... and in the C1-C2 subluxations of degenerative origin. The treatment of these retro-odontoid tumors does not consist in excision of the pseudotumor but in the reduction of instability by cervical fusion. The procedures are varied and comprise neurological and vascular risks. We report a case of C1-C2 subluxation associated with a pseudocyst compressing the cervical spinal cord, which was treated successfully by transarticular screwing without wiring procedure. This technique has never been used previously in this indication. However, the peroperational risks are less important and the results are similar to those of the other procedures.

[Intramedullary spinal tuberculoma: report of one case]. / Tuberculose intramédullaire. A propos d'un cas.

Neurological symptoms of tuberculosis are rare, even if there this pathology has been on the rise for a number of years because of HIV. Intramedullary tuberculoma is an exceptional location. We report the case of a patient with no HIV or immunodepression symptoms with intramedullary tuberculoma, revealed by a clinical presentation of insidious onset of myelopathy. We will discuss the diagnosis, treatment and clinical functional follow-up. The optimal treatment seems to be a combination of microsurgical resection and antibiotic therapy.

[Prognostic implications of biologic markers in intracranial meningiomas: 120 cases]. / Implications pronostiques de différents marqueurs biologiques dans les méningiomes intracrâniens: à propos de 120 cas.

UNLABELLED: The recurrence and progression of treated intracranial meningiomas highlights the problem of the type of follow-up that should be used and whether early complementary treatment is indicated. The aim of this study was to evaluate different biochemical markers involved in cell proliferation and transformation to identify new prognostic factors in intracranial meningiomas. Between 1989 and 2003, 120 intracranial meningiomas were studied biochemically. The levels of estrogen receptors (RE), progesterone receptors (RP), cathepsin B (CB), cathepsin L (CL), stefin A (ATA), stefin B (STB), cystatin C (CYSC), urokinase (u-PA), type 1 plasminogen activator inhibitors (PAI-1), cathepsin D (CD) and thymidine kinase activity (TK) were measured in tumor extracts using biochemical assays. RESULTS: Out of 120 meningiomas, 73 were grade I, 39 grade II and eight grade III according to the WHO classification. Of these patients, 17 showed recurrence. The mean follow-up was 47 months. Monofactorial analysis showed that expression of progesterone receptors (RP) had an inverse correlation with recurrence (p=0.0025 %) and that thymidine kinase activity (TK), cathepsin L (CL), the WHO grade and the degree of tumor resection correlated with recurrence (p<0.05). Principal component analysis and linear discriminant analysis confirmed these results. The results of this study confirm the importance of biological parameters (PR, CL, TK) as prognostic factors for the risk of recurrence in intracranial meningiomas.

[Value of relative cerebral blood volume measurement using perfusion MRI in glioma management]. / Intérêt de la mesure du volume sanguin régional cérébral relatif par IRM de perfusion dans la prise en charge des gliomes.

INTRODUCTION: Neoangiogenesis is a critical feature that can differentiate high-grade from low-grade glioma. Conventional MR imaging does not assess this histological feature accurately. The goal of this study was to evaluate the gain in relative cerebral blood volume measurement using perfusion MRI in the management of cerebral gliomas. MATERIALS AND METHODS: Between 1998 and 2001, 32 histologically proven glial tumors were assessed by perfusion MRI using echoplanar imaging (EPI) and gradient-echo techniques. Relative cerebral blood volume (rCBV) was measured in all patients and compared to histological data. RESULTS: rCBV values were significantly correlated to histological grading in all 32 patients (P<0.001). Mean rCBV values were 8.74 (+/-3.79) for glioblastomas, 7.37 (+/-2.83) for anaplastic gliomas and 0.84 (+/-0.61) for low-grade gliomas. Mean rCBV values were significantly different between low- and high-grade gliomas, making it possible to determine a threshold (2.5-3) that can separate these two types of lesion. In determining the histological grading, rCBV was shown to be significantly more accurate than conventional MRI (P<0.005). CONCLUSION: Perfusion MRI using the EPI technique reliably assesses tumoral neoangiogenesis in gliomas preoperatively. The specificity and sensitivity of this technique make this radiological modality a valuable tool in the assessment of cerebral gliomas.

[Percutaneous pedicle screw fixation and kyphoplasty for management of thoracolumbar burst fractures]. / Traitement des fractures de type burst de la charnière thoracolombaire par kyphoplastie et ostéosynthèse percutanée.

OBJECTIVE: To evaluate outcome and potential advantages of a percutaneous posterior approach to burst fractures of the thoraco-lumbar junction without neurological complications by means of a technique combining balloon kyphoplasty and percutaneous pedicule screw fixation. METHODS: In this preliminary study patients who suffered traumatic of the thoraco-lumbar junction presented a Magerl type A3 fracture. The mean age of the patients was 64 years (54-78 years). All had a normal neurological examination. A combined technique using balloon kyphoplasty, that allows restoration of the vertebral height and fixation by means of cement injection with percutaneous osteosynthesis was performed as a minimal invasive alternative treatment. Mean follow-up (plain radiograph and CT scan, pain assessment) was 12 months (range 5-14 months). RESULTS: All patients experienced an early pain relief, successfully mobilized on day 1 after surgery and discharged after a mean stay of 4.5 days. Immediately postoperatively the mean vertebral height restoration was 11.5% and the reduction of the kyphotic angle was 9 degrees. Those results were maintained over the complete follow-up period. Only one patient required analgesic treatment with weak opioids (step II of the WHO pain ladder) 3 months after surgery. CONCLUSIONS: The treatment of burst fractures of the thoraco-lumbar junction with no neurological complication by associating minimally invasive techniques results in good fracture reduction and stabilisation. The main advantage of this approach is to shorten the hospital stay.

[Cranial vault chondroma: a case report and literature review]. / Chondrome de la convexité: revue de la littérature à propos d'un cas.

Intracranial chondromas are unusual tumors, which most commonly arise from cartilage rets in the synchondrosis at the base of the skull. They are most likely found in the sellar and parasellar regions, usually located extradurally. In rare instances, these tumors originate from the dura mater of the convexity. In these cases their neuroradiological features may mimic other intracranial tumors. We present the case of a 50-year-old male presenting a large parasagittal tumor originating in the frontal convexity. MRI-scans revealed a cavitated tumor strongly enhanced after gadolinium infusion mimicking a parasagittal meningioma. There was no obstruction of the superior sagittal sinus as shown by cerebral angiogram. Total excision was achieved and the postoperative course was uneventful. No complementary treatment was therefore considered. The histological examination diagnosis was chondroma. Radiological workup performed at four years follow-up did not reveal any recurrence of the lesion. Pathogenic, clinico-radiological and therapeutic issues are discussed and the literature reviewed.

[Open kyphoplasty for management of metastatic spine fracture]. / Traitement par kyphoplastie à foyer ouvert des métastases rachidiennes.

INTRODUCTION: Metastatic spine fractures are very frequent, often occurring in patients with severe medical conditions. Open kyphoplasty and vertebroplasty are part of the classic management of this of fracture. In certain conditions such as spinal cord compression caused by epidural metastatic cancer or collapse of the vertebral body implying a local kyphosis, surgery should allow decompression of the spinal cord and stabilisation of the spine in a simple act. The purpose of this study is to assess a surgical technique combining surgical decompression by laminectomy frequently associated with posterior transpedicular instrumentation and at the same time, an open kyphoplasty to stabilize the anterior part of the spine. MATERIAL AND METHODS: The same procedure was performed in 14 patients during an 18-month period. The average age of the patients was 54 years. All patients suffered severe pain before the surgical procedure (VSA mean: 7). Neurological deficiency was noted in 10 of the 14 patients with this spinal cord compression. Nineteen vertebrae were treated; a short posterior instrumentation was necessary in 11 patients. The average operative time was 90 minutes. Of the patients with neurological deficiency, the clinical status improved after surgery in all. The average VSA of this series 3 days after surgery was 2. The mean quantity of PMMA injected was 7 cc. Two PMMA leaks, one in the intervertebral disc and one forward, were identified on the postoperative CT scan. The average hospital stay was 7 days. CONCLUSION: This procedure enables surgical decompression, vertebral body consolidation and consequently spinal stabilization of the spine. We did not have any complications related to this procedure which, particularly for the elderly population, is an attractive alternative to major surgery such as vertebrectomy.

[Endovascular treatment of idiopathic intracranial hypertension. Analysis of eight consecutive patients]. / Traitement endovasculaire de l'hypertension intracrânienne bénigne étiquetée "idiopathique". Analyse de huit cas consécutifs.

INTRODUCTION: Optic nerve sheath fenestration or ventricular shunting are classically proposed after failure of medical treatment. Idiopathic intracranial hypertension is caused by venous sinus obstruction in an unknown percentage of cases. Recently, endoluminal venous sinus stenting was proposed as an alternative treatment. PATIENTS AND METHOD: Between September 2003 and December 2004, eight consecutive patients with a diagnosis of idiopathic intracranial hypertension underwent MRI venography and direct retrograde cerebral angiography. RESULTS: There were five females and three males aged 22 to 55 years. All patients had vision disorders. The cerebrospinal fluid pressure ranged from 27 to 45 mmHg with normal composition. All patients presented at least one sinus stenosis. Endovascular stenting of the stenotic venous sinus was performed under intravenous heparin administration. Anti-platelet therapy was administered for 3 months post treatment. Intra-sinus pressures were invariably reduced by stenting. Mean follow-up was 18 months. All patients improved clinically. The cerebrospinal fluid pressure had normalized at 3-month follow-up in all patients. In all patients, multidetector row CT-angiography or MRI venography was performed at 3-, 6- and 12-month follow-up and demonstrated the patency of the stent. DISCUSSION: The importance of venous sinus disease as a cause of idiopathic intracranial hypertension is probably underestimated. Patients with idiopathic intracranial hypertension should be evaluated with direct retrograde cerebral venography and manometry. In patients with venous sinus lesions, treatment by an endoluminal venous sinus stent is a safe and effective alternative for amenable lesions.

[Operative treatment of complex lombosacral fracture dislocation: L5 chance fracture with trans S1-S2 dislocation]. / Traitement chirurgical d'une fracture complexe de la charnière lombo-sacrée: luxation S1-S2 et fracture de type chance de L5.

Sacral fractures are uncommon injuries that are often diagnosed late, the transverse fracture dislocation of the sacrum at the S1-S2 level associated with a L5 Chance fracture has never been reported. The purpose of this report is to describe operative treatment of transverse fracture dislocation of the sacrum at the S1-S2 level associated with a L5 Chance fracture. A 17-year-old woman sustained multiple injuries in a road accident and presented with hypovolumic shock. Radiological assessment demonstrated transverse fracture dislocation of the sacrum at the S1-S2 level associated with a L5 Chance-fracture. Neurologic examination demonstrated L5 root deficit and perineal hypoesthesia. Operative treatment was undertaken. The procedure consisted of laminectomy of L5, S1, and S2 and osteosynthesis of L3-L4 - S3-S4 (in sacral alae). Attempts to reduce dislocation failed. Postoperative recovery was uneventful. One year after operative treatment the patient presented no neurologic deficit and had resumed normal activity. Follow-up radiological imaging demonstrated consolidation of fracture zones. Management for uncommon lumbrosacral junction injuries must take into account various parameters including hemodynamic condition, neurologic status, and stability of the spinal lesions. Decompression of neural impingement and stabilization of fractures by osteosynthesis appear to be a useful alternative that allows patients to stand again and begin rehabilitation quickly.

[The value of dynamic cervical MRI in management of selected patients presenting traumatic cervical cord injury]. / Intérêt de l'IRM cervicale dynamique dans la prise en charge de certains patients victimes de traumatismes vertébraux médullaires.

OBJECTIVE: The purpose of this report is to describe our experience with dynamic cervical MRI for detection of cervical spinal cord instability in patients presenting spinal cord trauma without fracture or dislocation of the spinal column. MATERIAL AND METHODS: Since January 2000 a total of 95 patients presenting spinal cord trauma have been treated in our department. All patients underwent MRI for diagnostic work-up. Dynamic MRI was performed if spinal cord instability was suspected. Whenever possible, high-quality plain radiography dynamic views were obtained (coma, severe deficit, study of the cervicothoracic junction). RESULTS: Dynamic MRI allowed diagnosis of spinal cord instability in 6 patients with a mean age of 65 years (range, 45 to 75). Instability occurred during extension in 4 patients and during flexion and extension in one case. In the remaining case instability was associated with herniation of a cervical disc due to a severe cervical sprain. All 6 patients underwent early surgical stabilization that allowed improvement in-hospital patient care and quick transfer to rehabilitation centers. CONCLUSION: Dynamic MRI can be a useful tool to detect unstable spinal cord instability in some patients presenting noncompressive spinal cord injuries.

[Idiopathic acute obstructive hydrocephalus. Case report]. / Hydrocephalie aigue obstructive idiopathique. à propos d'un cas.

Acute hydrocephalus is rarely encountered in adults without venticuloperitoneal or venticuloatrial shunts. The purpose of this report is to describe a case of acute hydrocephalus due to no identifiable cause. A 40-year-old man developed a typical clinical picture of intracranial hypertension within a 24-hours period. On the morning of hospitalization, the patient consulted his physician for severe headache followed quickly by nausea and vomiting. After cerebral CT-scan, the patient was referred to our department. His condition rapidly worsened, with confusion, then drowsiness. Magnetic resonance imaging (MRI) demonstrated quadri-ventricular hydrocephalus with a Chiari I malformation. In view of his rapidly deteriorating clinical condition, emergency endoscopic third ventriculostormy was performed. The patient recovered rapidly and was discharged 8 days after the procedure. Diagnostic work-up included lumbar puncture showing normal cerebrospinal fluid (thereby eliminating multiple sclerosis, low-grade intracranial hemorrhage, and meningitis (bacterial, viral, fungal)), spinal MRI depicting no medullary lesions, and brain angiography revealing no vascular abnormalities. Follow-up brain MRI carried out at six months after hospitalization demonstrated normal ventricles and complete disappearance of the Chiari I malformation. No conclusion can be drawn as to whether the Chiari I malformation was the consequence or cause of hydrocephalus. The explanation of this acute hydrocephalus is the acute decompensation without identifiable cause of idiopathic stenosis of the foramen of Magendie and Luschka. Treatment with endoscopic third ventriculostomy is effective.

Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy.

PURPOSE: Most primary oligodendrogliomas and mixed gliomas (oligoastrocytoma) respond to treatment with procarbazine, lomustine, and vincristine (PCV), with response rates of approximately 80%. However, limited data on second-line treatments are available in patients with recurrent tumors. A novel second-generation alkylating agent, temozolomide, has recently demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme and anaplastic astrocytoma. This study describes the effects of temozolomide in patients with recurrent anaplastic oligodendroglioma (AO) and anaplastic mixed oligoastrocytoma (AOA). PATIENTS AND METHODS: Forty-eight patients with histologically confirmed AO or AOA who had received previous PCV chemotherapy were treated with temozolomide (150 to 200 mg/m2/d for 5 days per 28-day cycle). The primary end point was objective response. Secondary end points included progression-free survival (PFS), time to progression, overall survival (OS), safety, and tolerability. RESULTS: Eight patients (16.7%) experienced a complete response, 13 patients (27.1%) experienced a partial response (objective response rate, 43.8%), and 19 patients (39.6%) experienced stable disease. For the entire treatment group, median PFS was 6.7 months and median OS was 10 months. For objective responders, median PFS was 13.1 months and median OS was 16 months. For complete responders, PFS was more than 11. 8 months and OS was more than 26 months. Response correlated with improved survival. Temozolomide was safe and well tolerated. Twelve patients developed grade 1/2 thrombocytopenia and three patients developed grade 3/4 thrombocytopenia. CONCLUSION: Temozolomide is safe and effective in the treatment of recurrent AO and AOA.

[Transsacral approach to lumbosacral extraforaminal disc herniations]. / Traitement chirurgical des hernies discales extraforaminales L5/S1 par voie trans-sacrée.

INTRODUCTION: The lateral approach is classically used for surgical treatment of extraforminal disc herniations (EDH). However, its use at the level of the L5-S1 space can require more or less extensive resection of the facet joint. This study reports our experience in the treatment of L5-S1 EDH using the transsacral approach described by Muller and Reulen in 1998. MATERIAL AND METHODS: From February 2002 to October 2004, 12 patients presenting EDH at the L5-S1 level underwent treatment using the transsacral approach. There were 8 men and 4 women. Mean age was 55 years (range: 36 to 75 years). All patients presented lumbalgia and L5radiculalgia. Only one patient had dysesthesia. Five patients presented motor deficits and 3 presented sensory deficits. Surgical treatment was proposed after failure of medical treatment and two L5 corticoids infiltrations. RESULTS: All patients were re-examined two months after the procedure. Mean follow-up was 15 months. Complete resolution of radiculalgia with no paresthesia was achieved in all patients. Patients presenting preoperative motor deficit recovered fully after treatment. All patients resumed normal activity. CONCLUSION: The transsacral approach is a valid alternative to the lateral approach for treatment of L5-S1 EDH. The amount of operative exposure achieved using this technique is sufficient to avoid joint injury that can result in chronic postoperative lumbalgia. Another advantage is that excision of the protruding disc fragment can be achieved without mobilization of the nerve root or dorsal root ganglion, thus avoiding postoperative dysesthesia.

[Endoscopic treatment of a voluminous benign symptomatic cyst of the pineal region responsible for an obstructive hydrocephalus]. / Traitement endoscopique d'un volumineux kyste bénin symptomatique de la région pinéale responsable d'une hydrocéphalie obstructive.

Asymptomatic non neoplastic cysts of the pineal region are common incidental findings in adults. On the contrary, voluminous and symptomatic cysts of the pineal region are rare and their management are not well defined. We present the case of a 32-year-old woman suffering who suffered from mild intracranial hypertension, gait disturbance and vertigo for one year. The neuroradiological workup showed a voluminous cyst of the pineal region responsible for an obstructive hydrocephalus. An endoscopic etiological treatment was decided. The operation consisted in a marsupialization of the cyst in the third ventricle with a stereotactic guidance system. A frozen section of the cyst wall failed to show tumoral cells. Immediate postoperative course was uneventful. Intracranial hypertension symptoms resolved in 24 hours. Clinical examination and neuropsychological testing were normal at two years postoperatively. The two years follow-up cerebral MRI demonstrated a remnant cystic cavity without mass effect and the patency of the aqueduct of Sylvius. Endoscopic treatment of symptomatic pineal cysts constitutes an interesting therapeutic alternative in the management of this pathology.

[Endovascular treatment of benign intracranial hypertension by stent placement in the transverse sinus. Therapeutic and pathophysiological considerations illustrated by a case report]. / Traitement endovasculaire d'un syndrome d'hypertension intracrânienne bénigne par mise en place d'un stent dans le sinus lateral. Considerations thérapeutiques et physiopathologiques à propos d'un cas.

We report a case of benign intracranial hypertension in a 31-year-old man treated by endovascular stent placement in the right transverse sinus. The patient presented with a typical benign intracranial hypertension syndrome. Ophthalmologic findings showed bilateral papilledema with a 7/10 loss visual acuity loss in the right eye and 2/10 in the left eye. At lumbar puncture, cerebrospinal fluid (CSF) pressure was 40 mmHg. Magnetic resonance imaging (MRI) showed slit ventricles and dilatation of optic nerve sheaths. optiques. After failure of medical treatment, the patient was referred to our neurosurgical department for therapeutic decision. Direct retrograde cerebral venography showed predominant cerebral venous drainage via the right transverse sinus which exhibited stenosis in its proximal third. Mamometry revealed a 25 mmHg pressure gradient across the point of stenosis. Due to possible venogenic benign intracranial hypertension, endovascular stent placement was proposed and accepted by the patient. At 3 months follow-up, the patient was symptoms free, papilledema had disappeared and visual acuity was 10/10 on both eyes. CSF pressure on lumbar puncture was 11 mmHg. The pathophysiological aspects and therapeutic management of this pathology illustrated by this are discussed along with a careful and exhaustive review of the literature.

Different pathways of secretion for glycosylated and nonglycosylated human prolactin.

Human prolactinoma cells in culture secrete the monomeric nonglycosylated form of human PRL (NG-hPRL) and its glycosylated variant (G-hPRL). We have performed pulse-chase experiments to investigate the individual patterns of release of these two molecular variants. The cells were pulse labeled for 10 min with [35S]methionine and then chased for increasing periods of time up to 24 h. The secretion of newly synthesized G- and NG-hPRL was followed by immunoprecipitation of the chase medium and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Both forms were rapidly released (10 min of chase), but presented with different rates of secretion. Half-maximal release of G-hPRL occurred with 60-min chase, while 110 min were necessary for NG-hPRL. More than 50% of initially labeled G-hPRL was released in the medium vs. only 20% for NG-hPRL. Incubation of the cells with 8-chloroadénosine-cAMP during a 2-h chase period resulted in a 3.6-fold increase in the release of newly synthesized NG-hPRL and had only a slight effect on newly synthesized G-hPRL release (1.7-fold increase). The intracellular transit of labeled G- and NG-hPRL was investigated in cells treated by the ionophore monensin. The secretions of both newly synthesized forms were inhibited to the same extent, probably via an arrest of the transit at the level of the median Golgi, as judged by the delay of acquisition to endoglycosidase-H resistance for G-hPRL in monensin-treated cells. In contrast, Western blot analysis of the same medium-showed that monensin abolished the secretion of G-hPRL and had little effect on NG-hPRL. Our results on the different rates of secretion of G- and NG-hPRL indicate a sorting of the two forms into different compartments in the secretory pathway, with G-hPRL being secreted at a higher rate than NG-hPRL, possibly via a different intracellular route. The differential effects of 8Cl-cAMP and monensin further suggest that G-hPRL may be constitutively secreted after synthesis, while NG-hPRL secretion may involve a storage step.

A human pituitary adenoma secreting thyrotropin and prolactin: immunohistochemical, biochemical, and cell culture studies.

A 43-yr-old woman, who had previously had a subtotal thyroidectomy, presented with hyperthyroidism and amenorrhea-galactorrhea due to a pituitary adenoma secreting TSH, TSH-alpha, and PRL. Her serum T4 concentration was 14 micrograms/dl; T3, 5.7 ng/ml, and TSH, 19-33 microU/ml. Serum TSH was not altered by TRH stimulation or T3 suppression. Basal plasma PRL levels were 19-27 ng/ml and plasma PRL doubled after TRH stimulation. A 900-mg pituitary tumor, removed by transphenoidal surgery, was studied in cell culture. After dispersion, tumor cells were maintained on an extracellular matrix produced by bovine corneal endothelial cells in a defined serum-free medium. The hormones released in the culture medium were analyzed by high pressure gel chromatography. Three fractions of tumor TSH were found, with respective apparent mol wts of 45,000 (11%), 28,000 (70%), and 20,000 (19%). Tumoral PRL eluted as a single peak of apparent mol wt of 24,000. Pharmacological studies of TSH, TSH-alpha, and PRL release using thyroid hormones (T3), dopamine agonist (bromocriptine), TRH, and cholera toxin yielded the following results: 1) T3 after 3 days of incubation produced a dose-dependent inhibition of TSH, TSH-alpha, and PRL release. Maximal inhibition (81%) was obtained at 10(-9) M and half-maximal inhibition at 4-6 X 10(-11) M. 2) Bromocriptine produced rapid and partial inhibition of hormone release. Maximal inhibition (51%) was obtained at 10(-8) M and half-maximal inhibition at 5 X 10(-10) M. 3) TRH at 10(-8) M concentration significantly stimulated PRL release but it had no effect on TSH release. 4) Adenylate cyclase activation by 10(-11) M cholera toxin increased TSH (152%), TSH-alpha (150%), and PRL (220%). Immunohistochemical analysis of serial 2 micron sections of the tumor showed that: 1) TSH-alpha immunoreactive cells were the most numerous, 2) TSH-beta positive cells were always positive for TSH-alpha, 3) PRL immunoreactivity was found either uniquely in some cells and colocalized with TSH-alpha immunoreactivity in other cells. However, by electron microscopy, the tumor cells were thyrotrophs. These data indicate that in this patient's tumor: 1) cells secreting TSH were responsive in vitro to near physiological concentrations of thyroid hormones. 2) The colocalization of PRL and TSH-alpha immunoreactivities in some cells raises the possibility either of fusion of differentiated pituitary cells synthesizing distinct hormones or of transformation of less differentiated multipotential pituitary cells.

Bromocriptine effects on cultured human prolactin-producing pituitary adenomas: in vitro ultrastructural, morphometric, and immunoelectron microscopic studies.

In an effort to better characterize the ultrastructural, morphometric, and immunocytochemical changes induced by 10(-8) M bromocriptine (BR), tumor cells from three surgically removed PRL-producing pituitary adenomas were cultured on an extracellular matrix in serum-free medium. In each instance, the treated cultures were compared to control cells at the end of 24 h and 16 days. PRL RIAs were performed on culture medium. A decrease in cell and nucleus surface area was found on day 16 in two cultures. This supports the well known shrinkage of BR-treated PRL-producing adenomas. BR induced no change in these parameters in the tumor from a third patient who was partly resistant to the drug. Changes in the secretory process were discernible as of day 1 in all three tumors, with a dramatic reduction of exocytosis and intracellular accumulation of PRL-immunoreactive granules. This induced delayed inhibition of protein synthesis, demonstrated by preembedding immunocytochemistry on day 16. These results, obtained for the first time in human PRL-producing adenomas, are informative as to the subcellular events subsequent to short term BR treatment and illustrate that secretory inhibition and tumor shrinkage are not necessarily linked.