NLM CIT. ID: 20114083 TITLE: Indications for surgery in the treatment of hyperprolactinemia. AUTHORS: Zacur HA AUTHOR AFFILIATION: Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. PUBLICATION TYPES: JOURNAL ARTICLE LANGUAGES: Eng REGISTRY NUMBERS: 0 (Dopamine Agonists) ABSTRACT: Indications for pituitary surgery have been described in the medical literature, but they do not necessarily apply to prolactin-secreting (PRL-secreting) pituitary microadenomas or macroadenomas. Reviews of pituitary surgery done for microprolactinomas and macroprolactinomas have not demonstrated any significant beneficial effect on the clinical course of the hyperprolactinemia. At the same time, such surgery has been associated with definite risks, including an overall mortality of 0.9%. There is even the possibility that surgery and radiation for benign pituitary adenomas can facilitate malignant transformation and metastasis. Therefore, medical treatment with a dopamine agonist is the primary choice for all PRL-secreting microadenomas and macroadenomas. Referral for surgical evaluation is reserved for patients in whom neurologic deficits, such as visual field impairment or cranial nerve deficits, do not improve with medical therapy and for certain other, rare situations. NLM PUBMED CIT. ID: 10649823 SOURCE: J Reprod Med 1999 Dec;44(12 Suppl):1127-31 UI - 99452055 AU - Brada M; Burchell L; Ashley S; Traish D TI - The incidence of cerebrovascular accidents in patients with pituitary adenoma. SO - Int J Radiat Oncol Biol Phys 1999 Oct 1;45(3):693-8 AD - Neuro-oncology Unit, The Institute of Cancer Research and the Royal Marsden NHS Trust, Sutton, Surrey, UK. mbrada@icr.ac.uk BACKGROUND AND PURPOSE: Patients with pituitary adenomas are effectively treated with a combination of surgery, radiotherapy, and medical therapy. Nevertheless, long-term studies suggest increased mortality that is independent of tumor control, with cerebrovascular accidents (CVA) as the major contributing cause. The purpose of this study was to define the frequency of CVAs in a cohort of patients with pituitary adenoma and identify potential predisposing factors. PATIENTS AND METHODS: A cohort of 331 United Kingdom (UK) residents with pituitary adenoma treated at the Royal Marsden Hospital (RMH) between 1962 and 1986 was studied. The frequency of CVA was assessed from RMH and referring hospital records and clinicians, by postal questionnaire of referring hospitals and general practitioners, and by examination of all death certificates. The data were analyzed by actuarial methods, and risk factors were assessed by multivariate analysis. The data were compared to the incidence of CVA in the general population using a published UK population cohort. RESULTS: Sixty-four of 331 patients developed CVA after primary treatment of pituitary adenoma. The actuarial incidence of CVA was 4% (95% CI: 2-7%) at 5 years, 11% (95% CI: 8-14%) at 10 years, and 21% (95% CI: 16-28%) at 20 years measured from the date of radiotherapy. The relative risk of CVA compared to the general population in the UK was 4.1. Age was an independent predictive factor for CVA. However, the relative risk in comparison to the general population was independent of age. The relative risk of developing CVA was higher in women compared to men, in patients undergoing debulking surgery compared to less radical procedures, and in patients diagnosed and treated in the 1980s compared to previous decades. The dose of radiotherapy was an additional independent prognostic factor on multivariate analysis. CONCLUSION: Patients with pituitary adenoma treated with surgery and radiotherapy have a significantly increased risk of CVA compared to the general population. The factors which may contribute to the increased risk include the presence of pituitary adenoma and consequent endocrine disturbances and the treatment, particularly the extent of surgery and the dose of radiotherapy. When assessing the value of treatment strategies, it is therefore important to include not only intermediate endpoints of tumor and hormonal control, but also late toxicity, including the incidence of CVA and overall survival as the primary endpoint. The potential predisposing factors for CVA need further elucidation to develop treatment strategies with lower risk and consequently, reduced mortality UI - 99404950 AU - Hensen J; Henig A; Fahlbusch R; Meyer M; Boehnert M; Buchfelder M TI - Prevalence, predictors and patterns of postoperative polyuria and hyponatraemia in the immediate course after transsphenoidal surgery for pituitary adenomas. SO - Clin Endocrinol (Oxf) 1999 Apr;50(4):431-9 AD - Department of Medicine, University of Erlangen-Nuremberg, Germany. johannes.hensen@t-online.de OBJECTIVE: Disturbances of osmoregulation, leading to diabetes insipidus and hyponatraemia are well known complications after surgery in the sella region. This study was performed to examine the prevalence and predictors of polyuria and hyponatraemia after a complete and selective removal of pituitary adenomas was attempted via the transnasal-transsphenoidal approach. DESIGN: 1571 patients with pituitary adenomas (238 Cushing's disease, 405 acromegaly, 534 hormonally inactive adenomas, 358 prolactinoma, 23 Nelson's syndrome, and 13 thyrotropinoma) were daily examined within a 10-day postoperative inpatient observation period. Prevalence of patterns of polyuria (> 2500 ml) and oliguria/hyponatraemia (< 132 mmol/l) were surveyed as well as predictors of postoperative morbidity. RESULTS: 487 patients (31%) developed immediate postoperative hypotonic polyuria, 161 patients (10%) showed prolonged polyuria and 37 patients (2.4%) delayed hyponatraemia. A biphasic (polyuria- hyponatraemia) and triphasic (polyuria-hyponatraemia-polyuria) pattern was seen in 53 (3.4%) and 18 (1.1%) patients, respectively. Forty-one patients (2.6%) displayed immediate postoperative (day 1) hyponatraemia. Altogether, 8.4% of patients developed hyponatraemia at some time up to the 10th day postoperative, with symptomatic hyponatraemia in 32 patients (2.1%). Risk analysis showed that patients with Cushing's disease had a fourfold higher risk of polyuria than patients with acromegaly and a 2.8- fold higher risk for postoperative hyponatraemia. Younger age, male sex, and intrasellar expansion were associated with a higher risk of hypotonic polyuria, but this was not considered clinically relevant. CONCLUSIONS: The analysis illustrates that disturbances in osmoregulation resulting in polyuria and pertubations of serum sodium concentration are of very high prevalence and need observation even after selective transsphenoidal surgery for pituitary adenomas, especially in patients with Cushing's disease. NLM CIT. ID: 99154854 TITLE: Trans-sphenoidal surgery for microprolactinoma: an acceptable alternative to dopamine agonists? AUTHORS: Turner HE; Adams CB; Wass JA AUTHOR AFFILIATION: Department of Endocrinology, Radcliffe Infirmary, Oxford, UK. PUBLICATION TYPES: JOURNAL ARTICLE LANGUAGES: Eng REGISTRY NUMBERS: 0 (Dopamine Agonists) 9002-62-4 (Prolactin) ABSTRACT: AIMS: Reported cure rates following trans-sphenoidal surgery for microprolactinoma are variable and recurrence rates in some series are high. We wished to examine the cure rate of trans-sphenoidal surgery for microprolactinoma, and to assess the long-term complications and recurrence rate. DESIGN: A retrospective review of the outcome of trans-sphenoidal surgery for microprolactinoma, performed by a single neurosurgeon at a tertiary referral centre between 1976 and 1997. PATIENTS: All thirty-two patients operated on for microprolactinoma were female, with a mean age of 31 years (range 16-49). Indications for surgery were intolerance of dopamine agonists in ten (31%), resistance in six (19%) and resistance and intolerance in four (12.5%). Two patients were from countries where dopamine agonists were unavailable. RESULTS: The mean pre-operative prolactin level was 2933 mU/l (range 1125-6000). All but 1 had amenorrhoea or oligomenorrhoea, with galactorrhoea in 15 (46.9%). Twenty-five (78%) were cured by trans-sphenoidal surgery, as judged by a post-operative serum prolactin in the normal range. During a mean follow-up of 70 months (range 2 months to 16 years) there was one recurrence at 12 years. Post-operatively, one patient became LH deficient, two patients became cortisol deficient and two became TSH deficient. Out of 21 patients tested for post-operative growth hormone deficiency, 6 (28.6%) were deficient. Five patients developed post-operative diabetes insipidus which persisted for greater than 6 months. There were no other complications of surgery. The estimated cost of uncomplicated trans-sphenoidal surgery, and follow-up over 10 years, was similar to that of dopamine agonist therapy. CONCLUSION: In patients with hyperprolactinaemia due to a pituitary microprolactinoma, transsphenoidal surgery by an experienced pituitary surgeon should be considered as a potentially curative procedure. The cost of treatment over a 10 year period is similar in uncomplicated cases to long-term dopamine agonist therapy. NLM PUBMED CIT. ID: 10037250 SOURCE: Eur J Endocrinol 1999 Jan;140(1):43-7 NLM CIT. ID: 99129658 TITLE: Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long-term results. AUTHORS: Tyrrell JB; Lamborn KR; Hannegan LT; Applebury CB Wilson CB AUTHOR AFFILIATION: Department of Medicine, University of California, San Francisco 94143-0350, USA. PUBLICATION TYPES: JOURNAL ARTICLE LANGUAGES: Eng ABSTRACT: OBJECTIVE: Prolactinomas are frequently treated primarily with dopamine agonists; however, these agents have disadvantages and require life-long therapy. We therefore reassessed transsphenoidal microsurgery as an alternative therapy. METHODS: We reviewed the data for 121 female patients treated surgically for prolactinomas between 1976 and 1979 (Group 1) and 98 patients treated between 1988 and 1992 (Group 2). RESULTS: Of 219 women, 92% with preoperative prolactin (PRL) values of < or = 100 ng/ml and 91% with intrasellar microadenomas experienced initial remission; 80 to 88% of patients with intrasellar macroadenomas or macroadenomas showing moderate suprasellar extension or focal sphenoid sinus invasion experienced remission. Women with PRL values of > 200 ng/ml and those with larger and more invasive adenomas experienced poorer outcomes (37-41% remission). Lower preoperative PRL values and adenoma stage were the best predictors of initial surgical outcomes. At the most recent evaluations, 89% of women who experienced initial remission continued to experience clinical remission; 85% exhibited normal PRL values, and 5% demonstrated mild, asymptomatic, recurrent hyperprolactinemia (PRL values of < 34 ng/ml). In Group 1, 84% of patients continued to experience remission (82% with normal PRL values) after a median follow-up period of 15.6 years. In Group 2, 97% of patients continued to experience remission (88% with normal PRL values) after a median follow-up period of 3.2 years. Lower postoperative PRL values were the best predictors of long-term remission. CONCLUSION: Transsphenoidal microsurgery is an effective alternative to long-term medical therapy for selected patients with prolactinomas. Successful outcomes and long-term remission were achieved in patients with microadenomas and noninvasive macroadenomas. NLM PUBMED CIT. ID: 9932878 SOURCE: Neurosurgery 1999 Feb;44(2):254-61; discussion 261-3 UI - 98374136 AU - Hofle G ; Gasser R ; Mohsenipour I ; Finkenstedt G TI - Surgery combined with dopamine agonists versus dopamine agonists alone in long-term treatment of macroprolactinoma: a retrospective study. SO - Exp Clin Endocrinol Diabetes 1998;106(3):211-6 AD - Department of Internal Medicine, University of Innsbruck, Austria. Guenter.Hoefle@uibk.ac.at We retrospectively analysed the long-term treatment results (median 8 years) of 31 patients with macroprolactinoma. 17 patients were treated by pituitary surgery (group 1) followed by long-term dopamine agonist therapy whereas 14 patients received long-term dopamine agonist therapy alone (group 2). 2 patients of group 1 and 1 patient of group 2 had external pituitary irradiation because of progressive disease. The two groups were comparable with respect to age, gender and initial prolactin (PRL) levels. At the end of the observation period dopamine agonist dosage could be reduced by 50% in group 1 and by 39.3% in group 2. Pituitary function did not change substantially during therapy. Complete remissions (no visible tumour in CT or MRI, normal PRL levels under current dopamine agonist medication) were achieved in 23.5% of group 1 vs. 21.4% of group 2, partial remissions (reduction of PRL and tumour size) in 35.3% vs. 64.3%, stable disease in 23.5% vs. 7.1% and progressive disease in 17.7% vs. 7.1% (differences not significant). Visual field defects showed 28.4% remissions (complete and partial) in group 1 versus 50% in group 2. Dopamine agonist therapy could be stopped definitively in only 1 patient of group 2 with an invasive macroprolactinoma. Initial surgical reduction of tumour load followed by medical therapy does not seem to guarantee a better long-term outcome than dopamine agonist therapy alone if the patient responds to and tolerates dopamine agonist therapy. Surgery should be reserved for non- responders, drug-intolerant or non-compliant patients, and for those with acute severe neurological compromise. UI - 97160354 AU - Ciric I; Ragin A; Baumgartner C; Pierce D TI - Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. SO - Neurosurgery 1997;40(2):225-36; discussion 236-7 AD - Division of Neurosurgery, Evanston Hospital, Northwestern University Medical School, Illinois, USA. AB - OBJECTIVE: The primary objectives of this report were, first, to determine the number and incidence of complications of transsphenoid- al surgery performed by a cross-section of neurosurgeons in the United States and, second, to ascertain the influence of the surgeon's experience with the procedure on the occurrence of these complications. The secondary objective was to review complications of transsphenoidal surgery from the standpoint of their causation, treatment, and prevention. METHODS: Questionnaires regarding 14 specific complications of transsphenoidal surgery were mailed to 3172 neurosurgeons. The data reported were analyzed from the 958 respondents (82%) who reported performing the operation. The neurosurgeons surveyed were asked to estimate the number of transsphenoidal operations performed, to identify any complications observed, and to estimate the percentage of operations that had resulted in any of the 14 specific complications. The 958 respondents were placed into three experience groups, based on the number of transsphenoidal operations performed. The data were analyzed by using chi 2 tests and Spearman correlation coefficients. The secondary objectives were met through a detailed review of the literature, in light of our experience. RESULTS: Of the respondents, 87.3% reported having performed < 200 operations and 9.7% reported 200 to 500 previous operations. The remaining 3% reported more than 500 previous operations. More extensive previous experience with transsphenoidal surgery was associated with a greater likelihood of having witnessed each specific complication. The mean operative mortality rate for all three groups was 0.9%. Anterior pituitary insufficiency (19.4%) and diabetes insipidus (17.8%) were complications with the highest incidence of occurrence. The overall incidence of cerebrospinal fluid fistulas was 3.9%. Other significant complications, such as carotid artery injuries, hypothalamic injuries, loss of vision, and meningitis, occurred with incidence rates between 1 and 2%. An inverse relationship was found between the experience group and the likelihood of complications, as indicated by significant negative Spearman correlation coefficients for all but 2 of the 14 complicati- ons listed in the survey (P < 0.05). Thus, increased experience with transsphenoidal surgery seems to be associated with a decreased percentage of operations resulting in complications. Some caution should be exercised in interpreting these data, because they are based on the respondents' estimates. CONCLUSION: Transsphenoidal surgery seems to be a reasonably safe procedure, with a mortality rate of less than 1%. However, a significant number of complications do occur. The incidence of these complications seems to be higher, with statistical significance, in the hands of less experienced surgeons. The learning curve seems to be relatively shallow, because a statistically significantly decreased incidence of morbidity and death could be documented after 200 and even 500 transsphenoidal operations. Better understanding of the indications for transsphenoi- dal surgery and improved familiarity with the regional anatomy should further lower the incidence of death and morbidity resulting from this procedure in the hands of all neurosurgeons. (101 Refs) UI - 96306025 AU - Otten P; Rilliet B; Reverdin A; Demierre B; Berney J TI - [Pituitary adenoma secreting prolactin. Results of their surgical treatment] SO - Neurochirurgie 1996;42(1):44-53 AD - Clinique de Neurochirurgie, Hopital Cantonal Universitaire de Geneve, Suisse. AB - A retrospective study of 75 patients operated for pituitary prolactin-secreting adenomas between 1972 and 1992 is presented. 57 were women, 18 males. The major symptom was amenorrhea for women and impotence for men. Prolactinemia is correlated to the size of adenoma and thus permits a prediction of surgical results. Most of the patients with a prolactinemia under 300 ng/ml were cured by surgery alone. Surgical treatment alone at the-term follow-up cure 87% of the micro-adenomas, 17% of the enclosed adenomas, and none of the invasive adenomas. In this study there is only 7% of true recurrence. According to the high cure rate and low frequency recurrence after transphenoidal surgery for micro-adenomas we suggest this approach as the first choice treatment. On the other hand the best treatment for macro-prolactinomas is medicamentous. UI - 96336113 AU - Soule SG; Farhi J; Conway GS; Jacobs HS; Powell M TI - The outcome of hypophysectomy for prolactinomas in the era of dopamine agonist therapy. SO - Clin Endocrinol (Oxf) 1996;44(6):711-6 AD - Department of Medicine, UCL Medical School, Middlesex Hospital, London, UK. AB - OBJECTIVE: Dopamine agonists are the primary therapeutic modality for the majority of patients with prolactinomas, with pituitary surgery reserved for those patients intolerant of or resistant to these agents. Most published surgical series, however, contain patients treated by surgery as the primary therapeutic modality. Previous exposure to dopamine agonists or the selection of patients with prolactinomas resistant to conventional therapy may potentially compromise the surgical success rate. The purpose of this study was to evaluate the efficacy and safety of pituitary surgery for prolactinomas in a tertiary referral centre where the majority of patients were operated on after treatment with dopamine agonists. DESIGN: A retrospective review of the outcome of pituitary surgery for prolactinomas performed at a tertiary neurosurgical centre by a single neurosurgeon. PATIENTS: Twenty-three patients underwent excision of a macro and 11 excision of a micro-prolactinoma. MEASUREMENTS: Pituitary tumour diameter was determined by CT or MRI imaging. Pre and post-operative measurements were made of serum PRL concentration (off dopamine agonist therapy), free T4, free T3, LH and testosterone (males). Post-operative restoration of a menstrual cycle was taken to indicate resolution of hypogonadism in female patients. RESULTS: The majority (73.9%) of the patients with macro and all with micro-prolactinomas had received dopamine agonists preoperatively. Of the 23 patients with macroprolactinomas, in whom the median preoperative PRL concentration was 13255 mU/l, 17 (73.9%) had radiological evidence of suprasellar extension and 5 (21.7%) cavernous sinus invasion. Only 4 (17.4%) of the patients with macroprolactinomas had a normal serum PRL post-operatively, although there was an improvement in visual fields in 66% of those with preoperative defects. The median preoperative PRL concentration was 4309 mU/l in the patients with microprolactinomas, significantly lower than in the macroprolactinoma group (P = 0.02). Despite a significant fall in serum PRL postoperatively (median PRL 860 mU/l, P = 0.0001), only 45.5% of patients had a normal serum PRL concentrati- on after surgery. CONCLUSIONS: The cure rate following pituitary surgery for prolactinomas in a tertiary referral centre was low when compared with previous series in which surgery was used as the primary therapeutic modality. We suggest this may result both from dopamine agonist pretreatment and the referral of prolactinomas resistant to conventional therapy. The outcome is probably a more realistic reflection of the results of pituitary surgery for prolactinomas as currently practised in the majority of neuroendocri- ne centres. UI - 96336296 AU - Giovanelli M; Losa M; Mortini P; Acerno S; Giugni E TI - Surgical results in microadenomas. SO - Acta Neurochir Suppl (Wien) 1996;65:11-2 AD - Department of Neurosurgery, San Raffaele IRCCS, University of Milano, Italy. AB - Pituitary microadenomas are small tumors whose maximal diameter is less than 1 cm. The aim of surgical removal of microadenomas should be not only the reversal of hormone hypersecretion but also the preservation of normal anterior pituitary function. Our series includes 230 patients with a microadenoma who had their first operation in our department: 45 were GH-secreting, 92 were PRL- secreting, 90 were ACTH-secreting, and 3 were TSH-secreting. Remission of disease was achieved in 81%, 77%, 91%, and 100% of GH-, PRL-, ACTH-, and TSH-secreting adenomas, respectively. There was no perioperative mortality and only 5 patients experienced a major complication. A total of 7 patients had diabetes insipidus for at least 6 months after operation. Hypopituitarism, not present in any patients before operation, developed in 3.5% of the cases. Our experience confirms that patients with microadenomas have the best chances of a successful operation. Since tumor size should gradually increase with time, we underscore the need of early diagnosis and treatment in patients with pituitary adenomas. UI - 96358472 AU - Giovanelli M; Losa M; Mortini P TI - Surgical therapy of pituitary adenomas. SO - Metabolism 1996;45(8 Suppl 1):115-6 AD - IRCCS San Raffaele, University of Milano, Italy. AB - In a series of approximately 1,000 patients with pituitary adenoma who were operated on at our institution from 1970 to 1994, 932 were operated on for the first time. Most microadenomas were corticotropin (ACTH)-secreting, whereas all nonfunctioning adenomas were macroaden- omas, reflecting internal surgical policy. Only 48 of 932 patients (5.1%) had transcranial surgery. Using stringent criteria for the definition of a cure, we obtained remission of disease in 54.9%, 87.3%, 66.7%, and 46.2% of all patients with growth hormone (GH)-, ACTH-, thyrotropin (TSH)-, and prolactin (PRL)-secreting adenomas, respectively. The good result in patients with Cushing's disease is related to the higher percentage of microadenomas (approximately equal to 80%) in this group. Unfavorable prognostic characteristics for all adenomas are increasing tumor size, invasiveness, infiltrati- on, and high serum levels of the hypersecreted hormone. The absence of a reliable tumor marker makes it difficult to assess the results of surgery in patients with nonfunctioning pituitary adenoma, but normalization or improvement of visual defects occurred in 72.4% of patients. Permanent worsening of vision was detected in 2.2%, mostly operated on through the transcranial approach, but they had large tumors and so were at greater risk. Accordingly, there was a higher death rate in patients who received the transcranial operation (two of 48; 4.2%) than in patients operated on through the trans- sphenoidal route (seven of 884; 0.8%). However, between 1970 and 1980, the mortality rate was 1.6% (six of 367 patients), while between 1981 and 1994, it was 0.5% (three of 565 patients), stressing the importance of surgical experience and perioperative medical management in improving the safety of pituitary surgery. (7 Refs)
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