Intraventricular versus intravenous colistin for the treatment of extensively drug resistant Acinetobacter baumannii meningitis.

BACKGROUND AND PURPOSE: Reports on the safety and efficacy of intraventricularly administered (IVT) colistin for the treatment of Acinetobacter baumannii ventriculomeningitis in adults are limited and no comparative studies of IVT colistin versus intravenous (IV) therapy alone have been published. This study compared outcomes of patients with postneurosurgical ventriculomeningitis caused by extensively drug-resistant A. baumannii treated with IV colistin or IV plus IVT colistin. METHODS: In an 11-year period, information on 18 consecutive patients with extensively drug-resistant A. baumannii ventriculomeningitis was collected. Infection was defined on the basis of (i) isolation of A. baumannii from the cerebrospinal fluid (CSF); (ii) laboratory evidence of CSF infection; (iii) signs/symptoms of central nervous system (CNS) infection. Patients were divided into group 1 (nine patients, IV colistin alone) and group 2 (nine patients, IV plus IVT colistin). RESULTS: Cerebrospinal fluid sterilization was documented for 12 of 18 patients (66.6%). The CSF sterilization rate was 33.3% in group 1 and 100% in group 2 (P = 0.009). The mean time to CSF sterilization was 21 days (range 8-48). Five patients died due to A. baumannii CNS infection (all in group 1), and five deaths were unrelated to A. baumannii ventriculomeningitis. Intensive care unit mean length of stay was shorter in group 2 (20.7 vs. 41.6 days, P = 0.046). Crude relative risk ratio of cumulative incidence of persistent CNS infection in group 1 versus group 2 was 13. No cases of chemical meningitis due to intrathecal colistin administration were encountered. CONCLUSIONS: Intraventricular colistin administration is much more effective than IV therapy alone and does not seem to add further toxicity.

Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma: final report of a pilot study.

BACKGROUND: Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM). PATIENTS AND METHODS: Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥ 70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m(2) on days 1, 8, 15), fotemustine (FTM; 40 mg/m(2) on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m(2) on days 1-5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity. RESULTS: A total of 32 patients were enrolled. Hematologic toxicity G1-2 was observed in 18.7 % of patients and G3-4 in 9.4 %. One patient (3.1 %) had complete response, 3 (9.4 %) had partial response, 8 (25 %) had stable disease for at least 8 weeks, while 20 patients (62.5 %) experienced progressive disease. The clinical benefit was 37.5 %. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8 %. CONCLUSION: LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted.

Concurrent and adjuvant temozolomide-based chemoradiotherapy schedules for glioblastoma. Hypotheses based on two prospective phase II trials.

AIM: To investigate the impact of nonstandard concomitant temozolomide (TMZ) administration in two prospective phase II studies for glioblastoma (GBM). PATIENTS AND METHODS: From October 2000 to June 2008, 104 patients were enrolled in two studies: 25 in RT-TMZ-10.00 and 79 in RT-TMZ-01.04. Adjuvant radiotherapy (RT) was used with a total dose of 59.4 Gy (1.8 Gy/day). Patients received concomitant TMZ (75 mg/m(2)/day) from Monday to Friday during the first and last weeks of RT in the RT-TMZ-10.00 study and from Monday to Friday during all weeks of RT in the RT-TMZ-01.04 trial. Adjuvant TMZ (200 mg/m(2)) was administered for 5 days every 28 days. RESULTS: Median progression-free (PFS) and overall survival (OS) were 9 and 16 months, respectively, with no significant difference between the two groups (p = 0.5 and 0.14, respectively). The 2- and 5-year OS rates were 32 and 3 %, respectively, and similar to those observed with standard treatment regimens. CONCLUSION: Our data support the hypothesis that adjuvant TMZ is more important than concomitant chemotherapy (CH) and that RT is the more important element of the concomitant treatment schedule.

The role of radiotherapy in adult medulloblastoma: long-term single-institution experience and a review of the literature.

Medulloblastoma (MB) occurs infrequently in adult patients and standard treatment is still controversial. We report our long-term, single-institution experience of adult MB and a review of the literature. We analysed adult patients with histologically proved MB treated by postoperative radiotherapy. Primary endpoints were local control (LC), disease-free survival (DFS), and overall survival (OS). Acute toxicity was reported according to CTC-NCI score vers. 3.0 and specific neuropsychological assessment analysis was performed to define late brain toxicity. From 1990-2008, 13 patients were treated by craniospinal (CSI, 12/13) or cranial irradiation (1/13, because of bad clinical conditions). Median follow up was 101 months (64-218). Complete radiological response was observed in 12/13 patients and a partial response in 1/13. Ten-year LC, OS, and DFS were 91, 76, and 84%, respectively. Two patients died because of local and spinal progression after 13 and 62 months. Acute G3 haematological toxicity (RTOG score) was observed for one patient only. The neuropsychological analysis did not reveal late toxicity related to brain radiotherapy. This experience confirms the efficacy and safety of radiotherapy in adult MB patients, resulting in very interesting 10-year LC and OS.

Cerebral blood flow autoregulation during intracranial hypertension: a simple, purely hydraulic mechanism?

OBJECTIVE: In this paper, we re-propose the role of a hydraulic mechanism, acting where the bridging veins enter the dural sinuses in cerebral blood flow (CBF) autoregulation. MATERIALS AND METHODS: We carried out an intraventricular infusion in ten albino rabbits and increased intracranial pressure (ICP) up to arterial blood pressure (ABP) levels. We measured CBF velocity by an ultrasound probe applied to a by-pass inserted in a carotid artery and recorded ICP by an intraventricular needle. Diastolic and pulsatile ICP and ABP values were analyzed from basal conditions up to brain tamponade and vice versa. CONCLUSIONS: A biphasic pattern of pulsatile intracranial pressure (pICP) was observed in all trials. Initially, until the CBF velocity remained constant, pICP increased (from 1.2 to 5.4 mmHg) following a rise in diastolic intracranial pressure (dICP); thereafter, in spite of a further rise in dICP, pICP decreased (2.87 mmHg) following CBF velocity reduction until intracranial circulation arrest (pICP=1.2 mmHg). A specular pattern was observed when the intraventricular infusion was stopped and CBF velocity returned to basal levels. These findings can be interpreted as indicating a hydraulic mechanism. Initially, when CBF is still constant, pICP rise is due to an increase in venous outflow resistance; subsequently, when CBF decreases following a further increase in venous outflow resistance, the vascular engorgement produces an arteriolar vasodilation. This vasodilation determines an increase in vascular wall stiffness, thus reducing pulse transmission to surrounding subarachnoid spaces.

Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes.

INTRODUCTION: Hypercortisolism requires a prompt therapeutic management to reduce the risk of development of a potential fatal emergency. A synchronous bilateral adrenalectomy (SBA) is effective in recovering hypercortisolism. However, specific indications for an SBA are not available. We aimed to evaluate the outcome of patients who underwent an SBA and to identify biomarkers able to predict the requirements of an SBA. PATIENTS AND METHODS: A mono-centric and longitudinal study was conducted on 19 consecutive patients who underwent SBA for ACTH-dependent hypercortisolism between December 2003 and December 2017. This study population was compared to two control groups composed of patients cured after the resection of the ACTH secreting pituitary adenoma (Group A: 44 patients) and of the ACTH-secreting neuroendocrine tumours (Group B: 8 patients). RESULTS: Short- or long-term SBA complications or the recurrence of hypercortisolism did not occur. A single patient experienced Nelson syndrome. Clinical features after SBA showed improvement in the glico-metabolic assessment, hypertension, bone metabolism and the occurrence of hypokalaemia and infections. The younger the age at the time of Cushing's disease diagnosis, the longer the duration of active hypercortisolism, higher values of plasmatic ACTH and Cortisol (1 month after pituitary neurosurgery) and higher values of Ki67 in pituitary adenomas were detected in this study population as compared to Group A. CONCLUSIONS: SBA is an effective and safe treatment for patients with unmanageable ACTH-dependent hypercortisolism. A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing.

Vancomycin versus cefazolin prophylaxis for cerebrospinal shunt placement in a hospital with a high prevalence of meticillin-resistant Staphylococcus aureus.

International guidelines suggest that a high prevalence of meticillin-resistant Staphylococcus aureus (MRSA) infections should influence the use of vancomycin for surgical prophylaxis. In order to compare the efficacy and adverse effects of vancomycin versus cefazolin as antimicrobial prophylaxis for insertion of cerebrospinal fluid (CSF) shunts, a randomised prospective clinical trial was performed. Over a 16-month period, all consecutive adult patients who underwent CSF shunt insertion at a university hospital with a high prevalence of MRSA infections were included. Patients were randomly allocated to receive either vancomycin or cefazolin before surgery and followed-up for four weeks for the development of infections. Of the 176 patients included in the study, 88 received vancomycin and 88 cefazolin. Shunt infections were significantly less likely to be observed in patients who were on vancomycin prophylaxis (4% vs 14%; P=0.03). All isolated staphylococci were resistant to meticillin. Mortality of patients with post-surgical infections was higher in the cefazolin group (P=0.02). Our data suggest that use of vancomycin as prophylactic agent for cerebrospinal shunt placement reduces the rate of shunt infections in the context of high prevalence of MRSA.

Intratumoral vs systemic administration of meta-tetrahydroxyphenylchlorin for photodynamic therapy of malignant gliomas: assessment of uptake and spatial distribution in C6 rat glioma model.

Malignant gliomas, with an incidence of 5 cases per 100,000 population per year, represent the most common primary brain tumour. They have an overall survival length of less than 2 years. Many different adjuvant therapies have been developed. Among them, Photodynamic Therapy (PDT), that is based on photochemical reactions between light and tumoral tissue selectively labelled with exogenous photosensitizing agents. Among photosensitizers, m-THPC (Temoporfin), seems to be the most promising one for the treatment of brain tumors, but, unfortunately, it causes problems of high skin photosensitivity. To by-pass this problem, we devised an intratumoral route of administration of this photosensitizer. The aim of this study is to investigate and compare the uptake of m-THPC in brain tumor and normal tissue after systemic and intratumoral administration of the drug. 30 female Wistar rats received m-THPC 12 days after C6 tumor implantation. Temoporfin was administered intratumorally in 24 rats at two different concentrations. 6 rats constituted the control group and received m-THPC by means of an intraperitoneal injection. The brains were extracted at 4 h, 24 h and 96 h after Temoporfin injection. The samples were examined with a confocal laser scanning microscope. All samples showed high fluorescence emission exclusively in the tumour area, without appreciable differences between the samples taken at the different times of sacrifice and the two routes of administration. No fluorescence whatsoever was detected among normal brain tissue surrounding the tumour. The intratumoral route appears to give comparable results to the systemic one, regarding intracellular uptake efficiency and tumour--normal tissue ratio, with the advantage of a much shorter time needed to reach optimal intratumoural concentration--that is just four hours from m-THPC injection.

DIAGNOSIS OF ENDOCRINE DISEASE: Primary empty sella: a comprehensive review.

Primary empty sella (PES) is characterized by the herniation of the subarachnoid space within the sella, which is often associated with variable degrees of flattening of the pituitary gland in patients without previous pituitary pathologies. PES pathogenetic mechanisms are not well known but seem to be due to a sellar diaphragm incompetence, associated to the occurrence of upper sellar or pituitary factors, as intracranial hypertension and change of pituitary volume. As PES represents in a majority of cases, a neuroradiological findings without any clinical implication, the occurrence of endocrine, neurological and opthalmological symptoms, due to the above describes anatomical alteration, which delineates from the so called PES syndrome. Headache, irregular menses, overweight/obesity and visual disturbances compose the typical picture of PES syndrome and can be the manifestation of an intracranial hypertension, often associated with PES. Although hyperprolactinemia and growth hormone deficit represent the most common endocrine abnormalities, PES syndrome is characterized by heterogeneity both in clinical manifestation and hormonal alterations and can sometime reach severe extremes, as occurrence of papilledema, cerebrospinal fluid rhinorrhea and worsening of visual acuity. Consequently, a multidisciplinary approach, with the integration of endocrine, neurologic and ophthalmologic expertise, is strongly advocated and recommended for a properly diagnosis, management, treatment and follow-up of PES syndrome and all of the related abnormalities.

Preoperative embolization of meningiomas with polyvinyl alcohol particles: The benefits are not outweighed by risks.

PURPOSE: The purpose of this study was to define the feasibility, the efficacy and the safety of preoperative embolization (POE) of meningiomas using polyvinyl alcohol (PVA) particles. MATERIALS AND METHODS: Between January 2006 and June 2014, 191 consecutive patients were referred to our institution for the treatment of meningiomas; of these 57 patients were excluded from the study. A total of 64 patients (22 men and 42 women) with a mean age of 58.4±10.8 [SD] years (range: 14-82years) who underwent POE with PVA particles, achieving extensive (>90%) devascularization were ultimately included and compared to 70 patients who had surgery without POE. Surgical time and intraoperative blood loss were compared between the two groups. The duration of procedures and complications related to POE were analyzed. RESULTS: No differences were found between the two groups with respect to intraoperative blood loss. A significant reduction in surgical time was observed for the group who had POE (207.4±79.5 [SD] min vs. 226.9±117.6 [SD] min; P=0.028). In a subgroup analysis, the size and location of meningiomas did not influence these results. The duration of procedures was 41.4±10.5 [SD] min. Minor complications related to POE occurred in 3 out of 64 patients (4.7%). CONCLUSION: POE of meningiomas using PVA particles is effective in reducing surgical time, when extensive tumor devascularization is achieved. However, radiation exposure, the duration of procedures and complications related to POE with PVA particles do not justify this technique in most patients.

Expression of iNOS, CD163 and ARG-1 taken as M1 and M2 markers of microglial polarization in human glioblastoma and the surrounding normal parenchyma.

Microglia and macrophages appear to be the most common cells in the GBM microenvironment. In the present study we investigated the status of macrophages/microglia activation in surgical specimens from 41 patients diagnosed with grade IV GBM. For each patient we analyzed both the center of tumor and the parenchyma surrounding the tumor. The specimens were stained for: i) IBA1, a 17-kDa EF hand protein specifically expressed in microglia/macrophages ii) CD163, a cell surface antigen associated with M2 phenotype; iii) iNOS, taken as a functional marker of M1 phenotype, and iv) ARG-I, taken as a functional marker of M2 phenotype. Staining was scored in a double-blinded score on a scale from 0 to 5. Our results suggest that CD163 expression is higher within the tumor than in surrounding periphery in both male and female patients; while iNOS is higher within the tumor in males, no significant difference was found for ARG-1. In addition, analyzing the data in TGCA database, we found that CD163 expression was significantly and inversely correlated with mean survival times, with average survival times ranging from 448days in patients having low expression, to 319 in mid, and 353 in patients with high CD163 expressing tumors. In contrast, no significant association was found between survival time and ARG-1 or iNOS expression.

Preliminary experience with 4K ultra-high definition endoscope: analysis of pros and cons in skull base surgery.

During the last two decades endoscopic skull base surgery observed a continuous technical and technological development 3D endoscopy and ultra High Definition (HD) endoscopy have provided great advances in terms of visualisation and spatial resolution. Ultra-high definition (UHD) 4K systems, recently introduced in the clinical practice, will shape next steps forward especially in skull base surgery field. Patients were operated on through transnasal transsphenoidal endoscopic approaches performed using Olympus NBI 4K UHD endoscope with a 4 mm 0° Ultra Telescope, 300 W xenon lamp (CLV-S400) predisposed for narrow band imaging (NBI) technology connected through a camera head to a high-quality control unit (OTV-S400 - VISERA 4K UHD) (Olympus Corporation, Tokyo, Japan). Two screens are used, one 31" Monitor - (LMD-X310S) and one main ultra-HD 55" screen optimised for UHD image reproduction (LMD-X550S). In selected cases, we used a navigation system (Stealthstation S7, Medtronic, Minneapolis, MN, US). We evaluated 22 pituitary adenomas (86.3% macroadenomas; 13.7% microadenomas). 50% were not functional (NF), 22.8% GH, 18.2% ACTH, 9% PRL-secreting. Three of 22 were recurrences. In 91% of cases we achieved total removal, while in 9% near total resection. A mean follow-up of 187 days and average length of hospitalisation was 3.09 ± 0.61 days. Surgical duration was 128.18± 30.74 minutes. We experienced only 1 case of intraoperative low flow fistula with no further complications. None of the cases required any post- or intraoperative blood transfusion. The visualisation and high resolution of the operative field provided a very detailed view of all anatomical structures and pathologies allowing an improvement in safety and efficacy of the surgical procedure. The operative time was similar to the standard 2D HD and 3D procedures and the physical strain was also comparable to others in terms of ergonomics and weight.

Spontaneous haematoma of ligamentum flavum. Case report and literature review.

Spontaneous infarction of the ligamentum flavum is a very rare cause of mielo-radicular compression. In the literature only four cases are reported, all characterized by a clinical history of slowly progressive mielo-radiculopathy and good outcome after surgical treatment. A 70 year-old female patient presented with a four months clinical history of spontaneous, sub-continuous, progressive lumbar pain with bilateral irradiation to the L4-L5 dermatomers, right leg monoparesis and hypoaesthesia affecting tactile, thermal and pain sensivity, urinary incontinence and constipation. CT scan and MRI evidenced an extradural ovalar lesion in correspondence of the L1-L2 levels, that exerted compression over the dural sac, dislocating it anteriorly. The patient underwent a L1-L2 laminectomy and the lesion was totally resected. Rapid improvement of the patient's symptomatology has been noticed in the postoperative period, with complete recovery during the following month. Histologic examinations demonstrated that the mass was a haematoma of the ligamentum flavum. It's our opinion, that a picture of ligamentum flavum haematoma should be taken into account in differential diagnosis of posterior mielo-radicular compression. The progressive growth of the haematoma may explain the long clinical history of these patients and surgical treatment, even if delayed, permits an excel-lent clinical outcome.

Pure surgical treatment of 109 aneurysms.

AIM: Target of this study was to investigate outcomes after pure surgical treatment of intracranial aneurysms. METHODS: Patients with intracranial supratentorial circle aneurysms were retrospectively reviewed between July 1994 and October 1998. Studied cases were admitted at the Department of Neurosurgery of S. Maria-Hospital, Terni, a Government supported General Hospital. One hundred and nine Hunt and Hess Grade 0 to III patients with supratentorial circle aneurysms was studied in order to determine whether advances in the surgical management of intracranial aneurysms have improved surgical outcomes and which factors may predict outcome. All patients were managed only with standard neurosurgical aneurysms clipping procedures. Outcomes evaluation was made at patients' discharge and classified on the base of the Glasgow Outcome Scale (GOS). Surgical timing, SAH grading, pre and post surgical symptomatic vasospasm, temporary clipping, and intraoperative aneurysm rupture were correlated with outcomes. RESULTS: Surgical results showed a 75% excellent outcome. Mortality rate was 3%. Hunt and Hess grade 0 highly influenced outcome. Differences in outcomes among grades I to III were not significant. No differences in outcomes related to temporary clipping were noted. A low rate of intraoperative aneurysm rupture is reported: 5 out of 109 cases. In all these cases outcome was good, with neither mortality or morbidity. CONCLUSIONS: Results indicate a progressive improvement in surgical outcomes, suggesting that there still exist margins for improvements in pure surgical management of intracranial aneurysms.

Serum prolactin response to thyrotropin-releasing hormone and metoclopramide in patients with prolactin-secreting tumors before and after transsphenoidal surgery.

Seven female patients with amenorrhea, galactorrhea, and hyperprolactinemia were examined before and after selective transsphenoidal removal of a PRL-secreting microadenoma. Before adenomectomy, metoclopramide (MCP; 10 mg orally) and TRH (200 micrograms iv) did not increase PRL blood levels in any of the seven patients. On the contrary, after oral administration of 10 mg MCP, a positive response was noted in a group of eight lactating women 3 days postpartum. After surgery, serum PRL level returned to normal in all patients. A positive PRL response to MCP and TRH was found in six of the seven patients 1 month after surgery. One patient, who had the lowest PRL level, failed to show a PRL increase after both stimuli. These findings indicate that hypothalamic pituitary function can be restored to normal after transsphenoidal removal of PRL-secreting pituitary tumors.

Postoperative evaluation of dopaminergic tone in prolactinoma patients. II. Plasma thyrotropin response to metoclopramide.

In 24 patients who had a PRL-secreting pituitary adenoma, diagnosed by pituitary dynamic function tests and CT scan, and confirmed at surgery, the TSH response to a dopamine (DA)-antagonist drug, metoclopramide (MCP), was studied pre- and postoperatively to elucidate whether altered DA tone was present and related to hyperprolactinemia. Preoperatively, a TSH response to MCP occurred in 18 patients. Plasma TSH levels did not increase after MCP in 5 patients who had a macroprolactinoma and in 1 patient with a microprolactinoma located just beneath the diaphragm of the sella turcica. Postoperatively, in all patients who had a prolonged clinical remission and normalization of PRL dynamic tests TSH did not respond to MCP (9 of 24 patients). In 4 patients who had normal or borderline PRL levels in the immediate postoperative period, the TSH response to MCP disappeared, but became evident later together with progressive elevation of PRL levels. TSH increases after MCP occurred in all patients who had abnormal PRL levels after surgery, except in 2 patients with a macroprolactinoma infiltrating the neighboring structures. In conclusion, these results confirm the existence of increased DA tone in patients with a prolactinoma. However, the presence of an increased TSH response to DA antagonist drugs could be masked in patients who had large tumors or tumors located just beneath the sellar diaphragm. The TSH test after MCP administration can readily detect increased DA tone in the postoperative period even when PRL levels remain slightly elevated or borderline.

Dopaminergic mechanisms regulating prolactin secretion in patients with prolactin-secreting pituitary adenoma. Long-term studies after selective transsphenoidal surgery.

Twenty-seven female patients with prolactin-secreting pituitary microadenoma, were studied at different intervals following selective transsphenoidal removal of the tumor. Postoperatively, all patients had normal prolactin (PRL) levels and regular menstrual cycles were restored. Sixteen of 27 patients showed positive responses to TRH and metoclopramide (MCP) within 1 mo after surgery. On the contrary, 9 patients showed evaluation of these patients demonstrated that normal neuroendocrine relationships were restored after several months since positive PRL responses to TRH and MCP could be elicited in such patients. The remaining 2 patients who showed basal PRL levels in the upper range of normal, exhibited negative responses to TRH and MCP. These patients had progressively to TRH and MCP exhibited 10-20 mo after surgery a normal decrease in PRL levels following administration of carbidopa plus L-Dopa. Negative responses to carbidopa plus L-Dopa were instead obtained in 6 postoperative patients with elevated PRL levels and negative responses to TRH and MCP. These results suggest that: 1) Hyperprolactinemia induced by "autonomous" pituitary adenomas increases hypothaLamic dopamine (DA) secretion, which in turn inhibits PRL secretion by nonadenomatous lactotropes. 2) Total selective removal of the microadenoma acutely decreases PRL concentration, but a functional inhibition of the normal lactotrope can persist for a period of few months following surgery in a certain number of patients. 3) Prolonged reduction of PRL concentration is accompanied to a normal DA tone with reestablishment of normal neuroendocrine relationships.

Evaluation of dopaminergic tone in hyperprolactinemia. III. Thyroid-stimulating hormone response to metoclopramide in differential diagnosis and postoperative follow-up of prolactinoma patients.

Recently, it has been shown that patients with a PRL-secreting pituitary adenoma have a greater thyroid stimulating hormone (TSH) release after dopamine (DA)-receptor blockade than normal subjects. We have compared the TSH and PRL responses to metoclopramide (MCP) in normal and postpartum lactating women with those in 28 patients with hyperprolactinemia of different origin. Patients with a PRL-secreting pituitary adenoma were also tested after transsphenoidal removal of the tumor in order to establish the prognostic value of this test in such patients. Following MCP administration, percent increases in plasma PRL levels were greater in normal female subjects than postpartum lactating women. Plasma TSH levels did not increase in postpartum women and had a modest increment in normal subjects. In patients with hypothalamic tumors and empty sella syndrome plasma PRL and TSH levels showed modest or no increases after MCP administration. In ten patients harboring a microprolactinoma, plasma TSH levels showed an exaggerated increment after DA-receptor blockade. Postoperatively, despite normal or borderline PRL levels in the immediate postoperative period, a TSH response to MCP was present (in five patients one to two weeks after the operation, and in five patients one to three years after the operation), suggesting an increased DA activity even in the absence of hyperprolactinemia. In conclusion, the TSH test can easily detect increased DA-activity in patients with a microprolactinoma both preoperatively and postoperatively. It is possible that some patients with increased DA-activity in presence of normal PRL levels and normal PRL responsiveness to stimulation will experience a recurrence of hyperprolactinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative growth hormone response to thyrotropin-releasing hormone and oral glucose tolerance test in acromegaly: a retrospective evaluation of 50 patients.

The objective of this study was to investigate the relationship between growth hormone (GH) dynamic tests (thyrotropin-releasing hormone [TRH] test and oral glucose tolerance test [OGTT]), insulin-like growth factor-I (IGF-I) plasma values, tumor size, and clinical outcome in patients with GH-secreting pituitary adenomas. Furthermore, we investigated the potential prognostic utility of the above biochemical parameters in the follow-up of patients with acromegaly. We studied 50 acromegalic patients (18 males and 32 females; mean age, 40 years; range, 16 to 69) who underwent trans-sphenoidal removal of a GH-secreting pituitary adenoma from 1990 to 1994. Preoperatively, we evaluated (1) GH plasmatic levels after an oral glucose load (OGTT) (blood samples were drawn at -15, 0, 30, 60, 90, 120, 150, and 180 minutes after oral administration of 0.75 g/kg body weight [BW] of glucose), (2) GH plasma levels after a TRH test (200 microg as an intravenous [IV] bolus), and (3) basal IGF-I plasma levels after an overnight fast. From 3 to 12 months after surgery we evaluated (1) GH plasma values after an OGTT, and (2) basal plasma IGF-I, free triiodothyronine (FT(3)), free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and urinary free cortisol. The same tests were performed every year for 5 years. All of the patients were classified into 4 subgroups according to the system of Hardy and Vezina. Preoperatively, "controlled" patients (n = 29) had a GH paradoxical response to TRH (n = 28) and an unresponsiveness to OGTT (n = 29); 23 of them belonged to the I and II classes. Only 5 poorly controlled patients (n = 21) showed a preoperative paradoxical response to TRH and 9 had a preoperative GH partial inhibition after OGTT; 19 of them belonged to the III and IV classes. Our data suggest that in the preoperative period in acromegalic patients the simultaneous presence of a GH paradoxical response to TRH and lack of GH inhibition after OGTT is inversely related to the tumor size and therefore more likely to be restored to normal by surgical treatment.