Surgical Treatment and Clinical Outcome of GH-Secreting Adenomas in Elderly Patients

Summary. Patients older than 65 years represent 3–5% of all acromegalic patients. The old age of the patients and the higher incidence of cardiovascular and metabolic complications related to acromegaly could increase the intra- and peri-operative risk, so that medical treatment is usually recommended as a therapy of choice. The aim of this retrospective study was to investigate the impact of transsphenoidal surgery in a series of 22 elderly patients with active acromegaly, with special regard to anaesthesiological risk, peri-operative complications, and clinical outcome. Despite an increased anesthesiological risk being present in 16/22 patients, no complication occurred during surgery. Similarly, no post-operative mortality or major complications were observed. Biochemical cure, defined at 6 months by glucose-suppressed plasma GH levels below 1 ng/ml and normal age-corrected IGF-I value levels, was achieved in 68% of patients and no recurrence of disease was observed in the subsequent follow-up (mean 5.2±2.1 years). A significant cardiovascular improvement was observed in cured patients, with a decrease of left ventricular mass index (91.3±20.1 vs 115.9±15.0 g/m²; P<0.005), as measured by echocardiography, as well as a slight but significant decrease of systolic and diastolic blood pressure values (130.0±12.1 mmHg vs 137.6±13.5 mmHg P<0.05; and 84.2±6.4 mmHg vs 88.8±7.5 mmHg P<0.05, respectively). A significant post-operative improvement of glucose tolerance was also observed in this group. We conclude that transsphenoidal surgery, if well planned and carefully performed, is safe and able to induce a significant cardiovascular and metabolic improvement even in elderly acromegalic patients.     

Treatment results of acromegaly as analyzed by different criteria

Summary Results of treatment of acromegaly are often incomparable due to the different criteria which have been used for defining cure or control of disease. At the present time it is widely accepted, that the main criteria of cure must be normalization of IGF-1 and a GH in the OGTT <2 ng/ml. In this retrospective study we investigated the endocrinological results of 56 patients, who were surgically treated because of a GH-producing pituitary adenoma, by different criteria. Twelve of our patients had had additional medical treatment after surgery, two received radiotherapy.At a mean follow-up of 34 months after surgery 66% of patients had a basal GH <5 ng/ml, 64% had a GH in the OGTT <2 ng/ml and 73% had normalization of IGF-1. The combined criteria of OGTT <2 ng/ml and IGF-1 normalization have been fulfilled in 59% of patients. None of these latter patients developed a clinical recurrence during the follow-up period. An optimal result (endocrinological cure, no permanent surgical complications and intact pituitary function) was achieved in 43% of patients. Although surgery was responsible for 19 new pituitary axis deficiencies (7 corticotropic axis, 8 thyrotropic axis and gonadotropic axis), 22 partial deficiencies improved to normalization after surgery (respectively 6, 3, and 13). Pre-operatively 55% of patients had no pituitary deficiency, after surgery this was 61%, leaving a net positive result of 6% less pituitary deficiencies.The authors conclude that normalization of IGF-1 combined with an OGTT <2 ng/ml are adequate criteria for the definition of cure of acromegaly. However, the authors propose to include posttreatment hypopituitarism as an additional criterion by which treatment of acromegaly should be evaluated.     

Does Octreotide Treatment Improve the Surgical Results of Macro-Adenomas in Acromegaly? A Randomized Study

Summary  It is not clear whether the pre-operative treatment of GH-secreting pituitary adenomas with Octreotide improves the surgical remission rates of acromegaly. In a prospective controlled study the results of transsphenoidal surgery in newly diagnosed GH-secreting macro-adenomas were compared in patients with (n=11, group A) and without (n=13, group B) preoperative Octreotide treatment. During the treatment with a daily dosage of 470±160 μg Octreotide for 16, 5±10 weeks, the GH- and IGF-1-values of group A dropped significantly from 38, 9±34, 1 to 6, 8±4, 9 μg/l and from 2, 7±1 to 1, 7±0, 7 arbitrary units respectively. The adenoma-shrinkage from 5, 9±5, 8 to 4, 7±4, 9 cm³ missed statistical significance by little. There was no statistically significant difference between the postoperative acromegaly remission rates of 55% in group A and 69% in group B. Of the adenomas that postoperatively were not in remission, 80% in group A and 75% in group B disclosed an infiltrative growth pattern not influenced by the Octreotide pretreatment. All other patients not cured presented with initial GH-values of >50μ{\rm g/l}. There was no statistically significant difference between the postoperative anterior pituitary function in the two patient groups. In this study Octreotide was not beneficial in improving the results of GH-secreting pituitary macro-adenoma surgery. However, larger prospective controlled studies are needed to address this issue.     

Endocrinological Outcome Following First Time Transsphenoidal Surgery for GH-, ACTH-, and PRL-Secreting Pituitary Adenomas

Summary. Summary.   Background: To study remission rates and pituitary functions following transsphenoidal surgery of newly diagnosed GH-, ACTH-, and PRL-secreting pituitary adenomas.   Methods: Out of a series of 329 newly diagnosed pituitary adenomas, 131 (39.8%) were hormone (67 GH-, 27 ACTH-, 37 PRL-) secreting. PRL-secreting adenomas were subjected to surgery because they failed to respond to previous medical treatment therapy. The data on secreting adenomas, regarding the results of standardised endocrinological testing, MRI findings and water metabolism disturbances, were extracted retrospectively from the pituitary data-base of the hospital. The mean follow-up was 3.7 years.   Results: The overall remission rate for PRL-secreting adenomas (27%) was significantly lower than for GH- (71.6%) and ACTH-secreting (81.5%) ones. Remission rates correlated negatively with the magnitude of preoperative hormone excess (not in Cushing's disease), tumour size (not in prolactinoma) and invasiveness. Generally, the improvement of the adenopituitary functions was statistically significant during the first three postoperative months, and thereafter remained unchanged. Diabetes insipidus persisting for more than three months occurred with similar frequency in the three patient groups (in 9.4% of GH-, in 6.7% of ACTH-, and in 10% of PRL-secreting adenomas). Tumour regrowths occurred more often in PRL-(20%) than in ACTH- (9.1%) and GH- (0%) secreting tumours.   Conclusions: In GH- and ACTH-secreting pituitary adenomas, remission rates were significantly higher and recurrence rates lower than in PRL-secreting adenomas, which had failed to respond to previous medical therapy. The overall postoperative adenopituitary function was improved in all patient groups. Diabetes insipidus occurred with similar frequency in all patient groups. When reporting on results of surgery for secreting pituitary adenomas, not only remission and recurrence rates, but also the results of the pituitary function should be included. Published online June 20, 2002     

The choice of treatment after incomplete adenomectomy in acromegaly: Proton- versus highvoltage radiation

Summary The authors report the results of a study designed to compare the effectiveness of two different types of radiation in patients with acromegaly where surgical therapy had failed to normalize growth hormone (GH). Longterm follow-up after conventional high voltage radiation in 17 patients and proton therapy in 13 patients confirmed a similar reduction of GH levels in both groups. After 4.5 years a decrease of about 80% was achieved. After conventional radiation GH was normal in 8 (47%) and near normal in 6 (35%) while proton therapy resulted in normalization in 5 and improvement in 5 (38%).The slightly better results of conventional radiation must be attributed to lower pretreatment levels of GH. Side effects as additional pituitary deficits and oculomotor palsies were more often seen after proton treatment. Since the results of both radiation methods are similar and proton therapy has a tendency to more serious side effects we recommend conventional radiation as secondary treatment of acromegaly.This work represents part of a doctoral thesis by Barbara Lutz, M.D.     

Prolactin Secreting Pituitary Adenomas: Analysis of 429 Surgically Treated Patients, Effect of Adjuvant Treatment Modalities and Review of the Literature

Summary ? Objective. We performed this retrospective analysis to determine the efficacy of surgery and radiotherapy over hormonal and volumetric control of prolactinomas, many of which had failed during dopa-agonist therapy. In the same analysis, the efficiency of topical bromocriptine application as a preliminary study was compared with standard treatment modalities.  Materials and Methods. Between 1982–1997, 429 prolactinoma patients who underwent surgery at Hacettepe University Neurosurgery Department and at Bayındır Medical Center were included in this study. All patients were classified according to Hardy's classification scheme and were further divided into `invasive' and `non-invasive' groups based on this radiological classification system. The mean follow-up time was 38.4 months. One hundred and thirty five patients had peroperative bromocriptine application into the sellar cavity¹ and these, either receiving radiotherapy (RT) or not, were analysed separately from the other 294 patients. In the early postoperative period, 104 of these patients were given conventional radiotherapy with median dose of 4500 cGy. We focused on the effects of surgery and radiotherapy over volumetric and hormonal tumour control on the basis of invasion characteristics and the early results of topical bromocriptine application in macroprolactinoma patients; and compared our results with the literature.  Results. Statistical analysis revealed that radiotherapy was not effective over hormonal and volumetric tumour control for prolactinomas. We did not observe any correlation to dural invasion of the sellar floor, recurrence, and the disease-free survival time. Topical bromocriptine application seemed to improve the volumetric control in 135 selected macroprolactinoma patients but not hormonal response compared with the standard treatment modalities.  Conclusion. Conventional radiotherapy is not as effective as expected for prolactinomas and should not be preferred considering its adverse effects. Tumoural infiltration of the sellar dura mater is not a prognostic criterion for recurrence expectation and, therefore, should not be a criterion for radiotherapy after surgery. After subtotal removal, postoperative dopa-agonist therapy should be considered even if the patient was intolerant or resistant to previous treatment since surgery seems to improve patients' drug tolerance and cooperation due probably to the lower dose requirement. The early results of topical bromocriptine application seem to improve volumetric tumour control but this should not be accepted as a judgement since we need to wait for later results and to expand the sample size for more reliable interpretation.     

Presurgical octreotide treatment in acromegaly: no improvement of final growth hormone (GH) concentration and pituitary function. A long-term case-control study

Summary Background. The effect of presurgical long-acting somatostatin analogue (SSA) treatment on operative outcome in acromegaly is as yet uncertain and long-term observations are lacking. We evaluated in an acromegaly case-control study the effect of octreotide pre-treatment on short- and long-term postoperative GH concentrations, pituitary function and glucose tolerance.Methods. 48 patients with a pituitary macro-adenoma – micro- and giant adenomas excluded – were evaluated. 24 patients received presurgical octreotide treatment (secondary surgery, prospectively studied). Another 24 thoroughly matched patients had been operated on without prior octreotide therapy (primary surgery, retrospective evaluation). No patient had received any other treatment prior to operation/octreotide. Standardized testing was performed at diagnosis, following octreotide treatment, after surgery and then yearly for 10.3±0.9yrs (mean±SE, primary surgery) and 4.1±0.6yrs (secondary surgery). Immediate and 4-year postoperative results were compared. All work-up was strictly identical in both groups, except for imaging techniques. Partial remission was defined as mean GH profile (6-h/7-point) concentration <2.5µg/L, and complete remission as GH nadir <1µg/L during OGTT plus normal IGF-I concentration (when available).Findings. The median profile GH (µg/L) values and the OGTT GH nadir values post-surgery (2.4/1.0 vs 1.8/0.7, primary and secondary surgery, resp.) as well as 4yrs later (2.1/1.15 vs 2.3/0.8) were not significantly different between the groups. The 10-year results of the primary surgery group were not significantly different from its 4-year results. Subgroup analysis of pre-treated patients revealed no significant difference between those with and without tumour shrinkage, or between those with and without parasellar tumour extension. Postoperatively pituitary function was not significantly different between the groups. After 4-years the pituitary-adrenal axis was slightly more impaired in the secondary surgery group rather than following primary surgery, while the pituitary-gonadal axis was not different.Conclusion. Presurgical octreotide treatment has no significant short- or long-term beneficial effect on GH concentration or pituitary function.     

Intrasellar germinoma treated with low-dose radiation

Summary A radiation dose lower than what had previously been recommended was given to a case of intrasellar germinoma in a 17-year-old patient who suffered from migraine-like headache for 2 years, amenorrhoea for 3 months and a body-weight loss of 10 kg over 4 months. Baseline assessment of pituitary hormone reserve was within the lower limits of the normal range, except for an elevated serum prolactin level (PRL). Magnetic resonance imaging (MRI) showed an abnormal, slightly enhanced mass in the pituitary fossa, extending along the pituitary stalk and to the hypothalamus. Transsphenoidal removal of the intrasellar part of the tumour was performed and microscopic sections of the surgical specimens revealed a pure germinoma. Adjunctive radiation therapy (RT) was given 3 weeks after surgery. A total dose of only 27 Gy was delivered to this patient. The patient’s menstrual cycles resumed in 4 months. Repeated MRI follow-up showed no recurrence of the tumour.     

Management of pituitary apoplexy: clinical experience with 40 patients

Summary Background. Pituitary apoplexy is a rare major clinical event with neurological, neuro-ophthalmological, cardiovascular and hormonal consequences, resulting from an acute infarction of pituitary adenoma. We report our experience with a series of 40 patients presenting with pituitary apoplexy.Patients. Forty patients (27 males, 13 females; mean age, 51.2yr) were admitted to our medical center between years 1985–2002 with acute presentation of pituitary apoplexy. Visual field defects occurred in 61% and ocular paresis in 40% of subjects. Sixty-three percent of adenomas were nonfunctional, and prolactinomas comprised 31%.Results. Thirty-four patients underwent transsphenoidal pituitary decompression. Visual fields and ophthalmoplegia improved in 81% and 71%, respectively. During follow-up (4.5±5.4yr), 79% of patients developed hypogonadotrophic hypogonadism, central hypothyroidism appeared in 54% and hypocortisolism – in 40% of patients. Permanent diabetes insipidus was diagnosed in 8%. Serial sellar MRI showed disappearance of pituitary tumor in 63% of operated subjects. Six patients (3 with PRL-secreting and 3 nonfunctional adenomas) were treated medically (corticosteroids, dopamine agonists), two patients (out of three) with visual deficits improved, and tumor shrinkage was noted in four.Conclusions. We present a large series of patients with pituitary apoplexy. Most subjects were operated, but six were treated conservatively. Almost all patients improved clinically, including those who were not operated, but hormonal deficiencies are very common.     

Complications of transsphenoidal surgery in patients with pituitary adenoma: experience at a single centre

Summary Objective. This paper reports the complications of transsphenoidal surgery for pituitary adenomas in a series of 1240 consecutive patients operated at our Institute between 1990 and 2004 (first operations) and indicate the clinical characteristics of patients which affected surgical morbidity and mortality. Methods. According to tumour type, there were 420 (33.9%) non-functioning pituitary adenomas (NFPA), 349 (28.1%) GH-secreting, 288 (23.2%) ACTH-secreting, 155 (12.5%) prolactin (PRL)-secreting, and 28 (2.3%) TSH-secreting adenomas. The mean age of patients was 43.7 ± 0.4 yr and 122 patients (9.9%) were 65 yr or older; the female/male ratio was 1.5/1. There were 370 (29.8%) microadenomas and 870 (70.2%) macroadenomas of which 54 (4.4%) were giant adenomas. Results. The series mortality was 0.2%, the medical morbidity 1.9%, and the surgical morbidity 3.5%. Medical complications were significantly more frequent in patients older than 65 yr (4.9 vs. 1.4%; p = 0.009) and in patients with giant adenomas (5.6 vs. 1.6%; p = 0.03). Multivariate analysis showed that both variables were independently associated with a higher morbidity rate. The surgical morbidity was increased in giant adenomas (15 vs. 3%; p = 0.0001), in NFPA (6.2 vs. 2.1% in secreting adenomas; p = 0.0002) and in patients older than 65 yr (6.6 vs. 3.1%; p = 0.05). Multivariate analysis showed that only giant size was independently associated with an increased surgical morbidity rate. Conclusions. In our experience, the size of the adenoma was a risk factor for medical and surgery related complications and age over 65 yr for medical complications alone.     

Factors predicting pituitary adenoma invasiveness in acromegalic patients

Forty-four adult acromegalic patients carrying growth hormone-producing pituitary macroadenomas were investigated with neuroradiological and endocrinological techniques. Plasma growth hormone and somatomedin-C levels were repeatedly measured before surgical removal of tumors and during the follow-up period. Twenty-five patients presented preoperatively with an invasive adenoma that involved the cavernous sinus (CS). Diagnosis of tumor invasivity was made according to distinct neuroradiological criteria and was confirmed or rejected during surgery. Significantly higher basal growth hormone levels were found in patients with CS invasion than in cases without tumor growth in the CS. Evidence is presented that plasma growth hormone level in acromegalics is a more sensitive indicator for predicting tumor invasiveness than somatomedin-C. Growth hormone basal values before surgery and the extent of their decrease after removal of tumor correlate with adenoma growth in the parasellar compartments and should be used as a prognostic factor to aid in planing adjuvant tumor treatment.     

In- and out-hospital mortality rate in surgical patients

Background: Death rates after surgery are increasingly analysed for clinical audit and quality assessment. Many studies commonly provide information only on deaths that occur during hospital stay, known as in-hospital death rates. By using hospital data set linked to death certificate registry, we recorded in- and out-hospital deaths within 30 and 60 post-operative days.

Methods: The study included all consecutive surgical procedures (denominator) under general or locoregional anaesthesia in adult patients admitted for elective or non-elective inpatient surgery. Patients undergoing planned day-case surgery or obstetrical procedures were excluded. The primary outcome was 30- and 60-day post-operative mortality rate (numerator) whether before or after discharge.

Results: The study material consisted of a sample of 36,494 surgical procedures corresponding to 28,202 patients. At 30-day, 384 (crude mortality rate of 1.1%) patients died, 314 (82%) during their hospitalisation and 70 (18%) after discharge. Factors that were associated with in-hospital mortality are ASA scores, emergency, duration of surgery and rate of admission to critical care unit. Within the 30–60 days interval, we recorded 231 supplemental deaths, 103 (45%) after discharge.

Conclusion: In-hospital mortality alone is an incomplete measure of mortality even within 30 days of care. To identify the missing deaths, hospital records need to be linked to data from death certificate. This connection with the national death registry will allow obtaining the rate of in-hospital and out-hospital death.     

Transsphenoidal surgery for pituitary adenoma in elderly patients

Summary   Background. As the population continues to age, the number of elderly patients with symptomatic pituitary tumours will continue to increase. Little information exists as to the safety of pituitary surgery in this patient population. The current study was undertaken to evaluate the presentation and perioperative risk associated with transsphenoidal surgery in patients over the age of 70. Methods. A retrospective chart review was undertaken for patients over the age of 70 undergoing transsphenoidal surgery at the Penn State Hershey Medical Center between 1995 and 2005. Findings. Sixty-four patients over the age of 70 were identified with an average age of 73.4 years (range 70–84). The average follow-up period was 44 months (range 14–104). Symptoms of mass effect were the presenting complaint in 72% of patients while 9% had documentation of growth on imaging studies. Twelve percent presented with a history consistent with apoplexy. Three patients (5%) presented with acromegaly. Post-operative hospital stay averaged 2.6 days (range 2–7). Eight patients had new hormonal deficits post-operatively (1 ACTH, 3 TSH, 2 ACTH/TSH, 2 vasopressin). There were no cardiopulmonary complications and no deaths within 90 days of surgery. Conclusions. Transsphenoidal surgery can be performed in patients over the age of 70 without undo significant risks. Surgical removal of pituitary adenomas should be considered the mainstay of treatment in elderly patients in whom treatment is necessary. Patients who are medically suitable candidates should be offered surgical resection as would their younger counterparts. Correspondence: Jonas M. Sheehan, M.D., Hershey Medical Center, Department of Neurosurgery, Penn State College of Medicine, 500 University Drive, Hershey, 17033 Pennsylvania, USA.     

DDAVP use in patients undergoing transsphenoidal surgery for pituitary adenomas

Summary Background. Disorders of fluid and sodium regulation, often termed “diabetes insipidus,” are a frequent occurrence following surgery for pituitary adenomas. The present study was undertaken to identify the incidence of diabetes insipidus after pituitary surgery and its associated factors. Methods. A retrospective review of the medical records 300 patients who underwent transsphenoidal surgery for pituitary adenoma was undertaken. Information regarding patient gender, perioperative serum sodium levels and urinary output volumes, tumor size, previous pituitary surgery, tumor subtype, and the use of DDAVP was gathered. A multivariate statistical analysis was performed. Findings. Follow-up data were available on 288 patients. During the inpatient postoperative hospital stay, DDAVP was administered to 19% of all patients and 16% of patients not taking DDAVP preoperatively. Of patients with normal fluid/sodium regulation preoperatively, DDAVP was prescribed for 9% at discharge and 4% at 6 weeks postoperatively. Only 1.4% of patients were taking vasopressing replacement at the time of last follow-up. Significant correlations were found between gender, previous surgery, serum sodium levels, and urine volumes at various time points. Immunohistochemical type of tumor and tumor size were not related to DDAVP requirement. Conclusions. Transient hypotonic polyuria is frequently encountered after pituitary surgery. However, only a small number of patients will develop a long-term requiring for ongoing medical treatment. Previous surgery, female gender, and elevated serum sodium and urine volumes in perioperative period were associated with DDAVP requirement.     

Osteopenia occurs in a minority of patients with acromegaly and is predominant in the spine

Acromegaly may induce abnormalities in bone metabolism; however, there are limited data related to bone mineral density (BMD) in this condition. To evaluate the effects of an excess of growth hormone/ insulin-like growth fractor I (GH/IGF-I) in the skeleton, we measured the BMD in spine and femoral region, total body calcium and body composition in 45 patients (24 females and 21 males) aged 21–77 years (median 43 years) with acromegaly for 11.4+7.5 years (range 0.5–26 years) using a dual-energy X-ray absorptiometer (Lunar DPX). Thirty-four patients had had hypogonad-ism for 8.6+6.5 years (1–24 years). Mean serum GH and IGF-I levels were respectively 159±183 µg/1 and 843±497 jig/1. Total body calcium was increased in the acromegalics (males: 1272±217 g, range 916–1816 g; females: 1041±223 g, range 739–1609 g) when compared with normal individuals (males: 1115±144 g, range 856–1398 g; females: 909±144 g, range 511–1311 g;p=0.01). The lean body mass was significantly higher in acromegalic patients(p<0.001) compared with normal individuals. There was a tendency for a lower fat percentage in the acromegalics; however, this difference was not significant. Osteopenia (1Z-score below the mean) was found in the spine in 20% (n=9) of the patients, while BMD was decreased in the femoral region in only 8.8% (n=4). The group with osteopenia had a greater duration of hypogonadism than the normal BMD group (14±11 years vs 4.4±4.0 years;p=0.01). A negative correlation was also found between the duration of hypogonadism and BMD in spine (r=–0.4;p=0.003) and femoral region (r=–0.37;p=0.013). The hypogonadal patients had a lower BMD in spine (p<0.005), but not in other regions analyzed. No correlation was found between duration of hypersomato-tropism, GH/IGF-I levels and BMD. We conclude that the majority of patients with acromegaly have preserved BMD despite the presence of hypogonadism.     

A prospective study of mortality associated with anaesthesia and surgery: risk indicators of mortality in hospital

The aims of this study were to: 1) determine the incidences and causes of mortality associated with anaesthesia and surgery, 2) identify important factors associated with mortality in hospital, and 3) estimate the mortality risk associated with anaesthesia and surgery when a combination of risk factors are present. A total of 7306 anaesthetized patients undergoing abdominal, urological, gynaecological, or orthopaedic surgery were included in the study. Of these, 0.05% (1:1800) died during anaesthesia, 0.1% (1:730) during the recovery period, and the overall mortality rate in hospital was 1.2% (1:81). Most deaths occurred in the elderly (greater than or equal to 70 years of age) and were unavoidable due to progression of the presenting condition, such as advanced cancer, or co-existing diseases such as cardiopulmonary or renal failure. Of the patients who developed myocardial infarction (MI) following anaesthesia, 67% (8/12) died in the postoperative period. Half of the MI patients who died received regional anaesthesia, and in addition suffered from periods of cardiovascular dysfunction intraoperatively. By utilizing logistic regression analysis, a model for prediction of mortality risk was developed. The model included five significant preoperative predictive variables: age; patients with history of chronic heart disease, and renal disease; emergency surgery; and the type of operation. With this model it is possible to distinguish between patients with very different mortality risks.     

Microprolactinomas in males treated by transsphenoidal surgery

Summary ¶Objective. To support the opinion that transsphenoidal surgery can be an effective alternative to medical treatment for microprolactinomas in men. Design. Clinical study with retrospective data analysis. Patients and methods. Of 46 men who were operated on for prolactinoma in the Department of Neurosurgery of the University of Vienna General Hospital between 1985 and 2000 a microadenoma was detected 11 times (24%). Results. Median patient age was 41 years (range 32 to 54 years). Symptoms were of endocrine nature in all patients with erectile dysfunction, infertility and gynaecomastia being the initial complaints and having lasted for a median of 13 months (range 7–68 months). Preoperative median serum prolactin (PRL) was elevated to 120ng/ml (range 41–1000ng/ml). Radiography by MRI revealed microadenomas with a median diameter of 8mm (range 4–10mm). All patients were operated on via the transsphenoidal approach. Endocrine cure as defined by a serum PRL <25ng/ml was achieved in 8 of 11 patients (73%) after a median follow-up of 7 years (range 2–13 years). In none of the 3 patients with preoperative serum PRL levels >150ng/ml was a normoprolactinaemia obtained after surgery: 2 require further dopamine-agonist therapy after surgery, 1 after late follow-up.Surgery and medical treatment could restore potency and libido in all but 1 patient, 2 of 3 patients remain infertile. Conclusion. Prolactinomas in males are potentially curable by surgery if detected at an early stage. They most commonly present with insidious signs and symptoms of endocrine disturbances such as loss of libido, impotence and sterility. We stress the importance of early determination of serum prolactin and high resolution magnetic resonance tomography of the sella in male patients with hyperprolactinaemia as this may prevent the possible progression to larger tumours which are rarely curable by surgery and necessitate life-long medical therapy.Published online October 13, 2003     

Intra- and postoperative plasma ACTH concentrations in patients with Cushing's disease cured by transsphenoidal pituitary surgery

Summary.  Background: The optimal treatment of choice for ACTH-producing pituitary adenomas is their complete removal by the transsphenoidal surgical approach. ACTH-producing pituitary adrenomas are, however, often small in size not detectable with neuro-imaging techniques, which may result in difficulties during their surgical removal. With the advent of rapid methods for plasma ACTH measurement, a few neurosurgical centers introduced intra-operative plasma ACTH determinations in peripheral and central blood samples to help improve the outcome of pituitary surgery in patients with Cushing's disease.  Method: To evaluate the usefulness of this new method, we performed, under standardized conditions, intra-operative plasma ACTH measurements with a rapid immunochemiluminometric method at different stages of transsphenoidal pituitary surgery in 7 patients with Cushing's disease.  Findings: We found that from the beginning of anesthesia until the end of operation, ACTH concentrations in venous plasma were highly variable by both the rapid and the standard methods. In most cases the changes in venous plasma ACTH concentrations that occurred until the end of surgery failed to indicate the removal of the ACTH-producing pituitary adenoma. However, a more than 50% decrease of venous plasma ACTH concentrations by the rapid assay was observed 2 h after completion of the operation in all but one of the patients. As evidenced by a long-term hormonal and clinical remission, these changes in plasma ACTH levels in all patients were accompanied by a complete removal of the ACTH-producing pituitary adenoma.  Interpretation: These findings indicate a slow disappearance of ACTH from the circulation after a successful pituitary surgery in patients with Cushing's disease. Published online October 10, 2002 Correspondence: Dr. K. Rácz, 2nd Department of Medicine, Semmelweis University Medical School, 1088 Budapest, Hungary     

Current Treatment Strategies and Factors influencing Outcome in Patients with Bacterial Brain Abscess

Summary  We clearly determined the key to managing patients with brain abscess by retrospectively evaluating the factors affecting poor outcome in these patients. This study included 113 patients with brain abscess diagnosed in the CT era. Basic characteristics and therapeutic parameters were estimated as independent predictors of poor outcome by using univariate and multivariate logistic regression analysis. Patients with poor outcomes more frequently had deeply-located abscesses (p<0.02), IVROBA (intraventricular rupture of brain abscess) (p<0.001) and were in a severely deteriorated neurological state (p<0.001) than those with good outcomes. Multiple logistic regression analysis predicted that IVROBA (ORs, 24.5; 95% CI, 3.04 to 197.9) and severely deteriorated cases (ORs, 13.7; 95% CI, 2.34 to 80.8) resulting from IVROBA increased the relative risk of poor outcome. Patients with IVROBA more frequently had also deeply-located abscesses (p<0.005), positively immunocompromised states (p<0.05) an (p<0.003) than those without IVROBA. Patients with metastatic abscess had also IVROBA (p<0.006). Multiple logistic regression analysis anticipated that deeply-located abscess (ORs, 3.90; 95% CI, 1.38 to 11.04), and metastatic abscess (ORs, 12.26; 95% CI, 1.35 to 111.2) increased the relative risk of IVROBA. Patients in an obtunded state and with marked neurological deficit had IVROBA more often than patients in an alert state and/or mild neurological deficit (ORs, 3.23; 95% CI, 1.17 to 8.86, (p<0.03) before treatment. Our findings suggest that IVROBA strongly influences poor outcome in patients with brain abscess. The key to decreasing poor outcomes may be the prevention and management of IVROBA, by evaluating intracranial pressure pathophysiology. IVROBA should be aggressively treated by aspiration methods for the abscess coupled with appropriate intravenous and intrathecial administration of antibiotics.     

Clival pituitary adenoma with acromegaly: case report and review of literature.

The pituitary develops as a result of complex, intricate, and precise neuro-embryological events in the sixth to eighth weeks of gestation. Some ectopic cell rests can become adenomatous. Rarely, these cell rests in the clivus can be the site of formation of adenoma. Our patient, a 35-year-old parous woman, was being treated for acromegaly, and imaging studies revealed a clival mass lesion. Trans-sphenoidal excision was done and immunohistochemistry revealed the tumor to be a growth hormone-secreting tumor.