Pregnancy following transsphenoidal resection of prolactin-secreting pituitary tumors

This report describes 200 women in the childbearing age group with prolactin-secreting pituitary adenomas treated by transsphenoidal microsurgery. There were 136 patients with microadenomas (10 mm or less in diameter), 30 with macroadenomas, 11 with invasive adenomas, and one with hyperplasia. The overall rate for postoperative normalization of serum prolactin was 57%, and it was 72% for those patients with microadenomas. Pregnancy was desired by 90 women, and 78 (84%) became pregnant, although 10 required postoperative bromocriptine to do so. Serious postoperative complications were rare, and produced no major morbidity. The results of surgery were most favorable in women with microadenomas and preoperative serum prolactin levels of 100 ng/ml or less.     

Hyperprolactinemia in patients with non-functioning adenoma: analysis of 85 patients treated by transsphenoidal operation

Today, many gynecologists consider that the first choice of the treatment of prolactinomas is bromocriptine therapy. Because bromocriptine not only decreases the levels of serum prolactin but also reduces the tumor size. On the other hand, the patients with non-functioning adenoma sometimes show hyperprolactinemia, probably because PIF (prolactin inhibiting factor) cannot reach the normal prolactin-producing cells of the adenohypophysis. Therefore non-functioning adenoma with elevated serum prolactin levels should be distinguished from prolactinoma. Eighty five patients with non-functioning adenoma were treated with transsphenoidal operation at Hiroshima University Hospital, and Kansai Rosai Hospital from May, 1978 to March, 1981 and at Osaka University Hospital, The Center for Adult Diseases, and Kansai Rosai Hospital from April, 1981 to May, 1986. Non-functioning adenomas were diagnosed by clinical feature, endocrinologic examination, and immunohistochemical study. There were 42 male and 43 female patients, whose age ranged from 17 to 76 years (mean: 49). The most frequent chief complaint was visual disturbance (86%). Amenorrhea-galactorrhea was complained by 9 female patients. However, 7 of them had visual disturbance at the same time. Hyperprolactinemia was seen in 21 patients (30%). The highest serum level of prolactin was 163.2 ng/ml. All of the patients had macroadenomas. There were 2 invasive adenomas and 83 expensive adenomas in them. After operation, cure or improvement of the visual disturbance was noted in almost all the patients. The serum levels of prolactin were normalized in 16 of 17 hyperprolactinemic patients. In conclusion, transsphenoidal operation is the best treatment of non-functioning adenomas. However, it is difficult to decide before operation whether the macroadenoma with serum prolactin level between 100 and 200 ng/ml is non-functioning adenoma or prolactinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolactin-secreting adenomas: the preoperative response to bromocriptine treatment and surgical outcome

Controversy exists regarding the effects of bromocriptine on the success of transsphenoidal surgery for patients with prolactinomas. Various studies on this drug have reported adverse effects, improvement, and no effect upon the subsequent surgical outcome. The authors have retrospectively reviewed the case histories of 55 patients with immunocytochemically confirmed prolactin-secreting pituitary adenomas operated on by a transsphenoidal approach between 1981 and 1985. All patients had received bromocriptine in a variety of doses and for variable durations prior to surgery. Thirty-nine patients were women and 16 were men, with an age range of 8 to 72 years. Basal prolactin levels prior to bromocriptine treatment ranged from 38 to 100 ng/ml in 11 patients, from 101 to 200 ng/ml in 12, and greater than 200 ng/ml in 29. The "cure" rates were 54%, 58%, and 38%, respectively. Thirty-one patients had microadenomas, with a postoperative cure rate of 68%; 12 had diffuse expansive adenomas, with a 17% cure rate; and 12 had grossly invasive tumors, with a 17% cure rate. A response to preoperative bromocriptine therapy was defined as a return of the basal prolactin level to normal: 18 patients were responders and 29 were hyporesponders; in eight the data were not available. The postoperative cure rate was 50% for the responders and 31% for the hyporesponders. Taking into account the distribution of tumor type, there was no actual difference in outcome between the responder and the hyporesponder groups. The total bromocriptine dose received preoperatively was nearly identical for all groups. No significant differences in the frequency or extent of fibrosis, calcification, or prolactin immunoreactivity were observed in the 55 patients when compared with 26 control prolactinomas not treated with bromocriptine. It is concluded that short-term bromocriptine treatment does not adversely affect surgical outcome in any of the prolactin-secreting adenoma groups, nor does response or lack of response to bromocriptine predict surgical outcome.     

Bromocriptine treatment of invasive giant prolactinomas involving the cavernous sinus: results of a long-term follow up

OBJECT: The aim of this study was to observe long-term clinical outcomes in a group of patients treated with bromocriptine for invasive giant prolactinomas involving the cavernous sinus. METHODS: Data from 20 patients with invasive giant prolactinomas at the authors' institutions between July 1997 and June 2004 were retrospectively reviewed. The criteria to qualify for study participation included: (1) tumor diameter greater than 4 cm, invading the cavernous sinus to an extent corresponding to Grade III or IV in the classification scheme of Knosp and colleagues; (2) serum prolactin (PRL) level greater than 200 ng/ml; and (3) clinical signs of hyperprolactinemia and mass effect. Among the 20 patients who met the criteria, six had undergone unsuccessful transcranial or transsphenoidal microsurgery prior to bromocriptine treatment and 14 patients received bromocriptine as the primary treatment. Eleven of the 20 patients underwent adjuvant radiotherapy. After a mean follow-up period of 37.3 months, the clinical symptoms in all patients improved by different degrees. Tumor volume on magnetic resonance images was decreased by a mean of 93.3%. In 11 patients, the tumor had almost completely disappeared; in the other nine patients, residual tumor invaded the cavernous sinus. Visual symptoms improved in 13 of the patients who had presented with visual loss. Eight patients had normal PRL levels. The postoperative PRL level was more than 200 ng/ml in seven patients. During the course of drug administration, cerebrospinal fluid leakage occurred in one patient, who subsequently underwent transsphenoidal surgery. No case of apoplexy occurred during bromocriptine treatment. CONCLUSIONS: Dopamine agonist medications are effective as a first-line therapy for invasive giant prolactinomas, because they can significantly shrink tumor volume and control the PRL level. Tumor mass vanishes in some patients after bromocriptine treatment; in other patients with localized residual tumor, stereotactic radiosurgery is a viable option so that unnecessary surgery can be avoided. The application of radiotherapy does not reliably shrink tumor volume.     

Transsphenoidal microsurgery for pituitary tumors associated with hyperprolactinemia.

The results of transsphenoidal microsurgery in treating 37 patients (30 women and seven men) with pituitary tumors associated with hyperprolactinemia are presented. Immediate (10-day) postoperative fasting prolactin levels were normal (less than 25 ng/ml) in 19 of 26 patients whose preoperative prolactin level was less than 200 ng/ml, and in only three of 11 patients in whom preoperative prolactin was greater than 200 ng/ml. Twelve of 13 patients with normal preoperative pituitary-target organ function maintained normal axes postoperatively. Thirteen other patients had preoperative deficiencies in one or more pituitary-target organ axes. Postoperatively, in these latter 13 patients, a pituitary-target organ axis that was deficient preoperatively returned to normal in six cases; there was no change in five, and there was impairment in another axis in four instances. Although gross total tumor removal was believed to be complete in 35 of 37 patients, serial postoperative prolactin determinations in four of these 35 patients indicate tumor regrowth. The authors conclude that transsphenoidal microsurgery is currently the operative procedure of choice for the majority of pituitary tumors associated with hyperprolactinemia.     

Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery

OBJECT: Prolactin-secreting pituitary adenomas may be managed by surgery, medication, radiotherapy, or observation. The authors reviewed a consecutive series of patients who were followed for at least 5 years after surgery to assess the prognostic significance of preoperative factors (tumor size and prolactin level) and an immediate postoperative factor (prolactin level obtained the morning after surgery) on long-term hormonal outcome, thereby clarifying the indications for surgical removal of tumor, the definition of successful treatment outcomes, and the nature of "recurrent" tumors. METHODS: Between 1979 and 1991, 241 patients with prolactinomas underwent transsphenoidal resection. Nineteen patients were lost to follow-up review, whereas the remaining 222 patients underwent measurement of their prolactin levels on postoperative Day 1 (POD 1), at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD 1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43 patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (< or = 20 ng/ml) were measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the 43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin were still measured in 130 patients (98%) in Group 1 compared with only five patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml on POD 1 was found to have an elevated hormone level at 5 years. The likelihood of a long-term chemical cure was greater for patients with microadenomas (91% cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels also correlated with hormonal outcome. CONCLUSIONS: Prolactin levels lower than 10 ng/ml on POD 1 predict a long-term chemical cure in patients with microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In contrast, a cure is not likely to be obtained in patients with normal levels ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure rate). A recurrence reported several years after surgery probably represents the presence of persistent tumor that was not originally removed. If the initial operation was performed by an experienced surgeon, however, reoperation is not likely to yield a chemical cure.     

Prolactin reduction after combined therapy for prolactin macroadenomas

The ability of surgery or bromocriptine to produce endocrine control of a prolactin macroadenoma decreases as the prolactin level increases. Guidelines for the use of multimodality therapy have not been developed for tumors associated with markedly elevated prolactin levels. We reviewed the records of 21 patients with prolactin levels greater than 200 ng/ml treated by transsphenoidal surgery and postoperative radiotherapy with or without a dopamine agonist. Values before and after treatment were available for 19 patients (13 men and 6 women). The mean basal prolactin level before treatment for the entire group was 2410 ng/ml. Surgery and radiotherapy resulted in a 90% reduction and serum prolactin levels within normal limits in 0 of 7 patients, versus the combination of surgery, radiotherapy, and dopamine agonist, which resulted in a 99.5% reduction and values within the normal range in 12 of 12 patients. Spontaneous physiological improvement was not often observed. One woman and two men were able subsequently to have children. A plan for these patients is discussed.     

Results of treatment for male prolactinomas

We evaluated the results of medical treatment for male prolactinomas. We encountered eight patients with male prolactinomas. The age was 25 to 54 years old (mean 43 years) and the chief clinical symptoms were visual acuity/field defect in three patients, pituitary apoplexy in one patient, disturbance of ejection in one patient, generalized convulsion in one patient, headache in one patient and general fatigue in one patient. The serum prolactin level was 279 to 7,360 ng/ml (mean 2,832 ng/ml). The tumors in all patients were large with a mean diameter of 34.9 mm (range, 21 to 43 mm). In only one patient, the operation was performed due to pituitary apoplexy. All the patients were treated by medication, with bromocriptine being used in seven patients and terguride in one. The follow-up period was 0.8 to 13 years (mean 5.9 years) and, in all patients, the medical treatment was continued. The tumor decreased in size in all patients and the serum prolactin level at the last follow-up observation was 0.5 to 70.5 ng/ml (mean 26.9 ng/ml). All the neurological symptoms disappeared in the early stage of treatment. As for the complications of medical treatment; in one patient, orthostatic hypotension occurred during the initial administration of bromocriptine and one patient suffered CSF leakage two months after the administration of bromocriptine, so the repair of the sella floor by transsphenoidal surgery was necessary. The medical treatment for male prolactinomas is effective for a long term and should be the primary treatment for the male prolactinomas. In conclusion, patients can maintain a good quality of life for a long time by using dopamine agonists.     

Long-term effects of radiotherapy and bromocriptine treatment in patients with previous surgery for macroprolactinomas

The long-term effect of radiotherapy and bromocriptine treatment was retrospectively evaluated in 25 patients who had previously undergone transsphenoidal surgery for treatment of macroprolactinomas. Surgery had reduced the median serum prolactin (PRL) value from 613 micrograms/l, a reduction of 53%. Postoperative bromocriptine was administered to 21 of the 25 patients. In 14 of these patients, serum PRL values became normal or almost normal with medication. There were no radiological or ophthalmological signs of progressive tumor growth during bromocriptine treatment. Fourteen patients received postoperative radiotherapy. After withdrawal of bromocriptine in 13 of these patients an average of 7 years after radiotherapy, the median serum PRL value had further decreased by 95%. The PRL reduction was similar for all doses applied, 38 to 52 Gy. After withdrawal of bromocriptine in 8 patients not receiving radiotherapy an average of 7 years after operation, the median serum PRL level had further decreased by 75%. At follow-up, 18 additional instances of pituitary insufficiency had developed in the group receiving radiotherapy, compared with 8 cases of insufficiency in the group not receiving radiotherapy. Thus, because bromocriptine has a long-standing effect on prolactin secretion, and radiotherapy is associated with a notably high incidence of pituitary insufficiency, we propose that photon irradiation should be considered mainly for patients who are not candidates for surgical or medical treatment.     

非侵袭型垂体泌乳素腺瘤经蝶显微手术疗效分析

目的 分析非侵袭型垂体泌乳素腺瘤经蝶手术疗效,为临床治疗的选择提供参考.方法 回顾性分析我科近10年来经蝶手术治疗的234例患者手术疗效,并分析影响手术疗效的因素.结果 术后出现一过性水、电解质紊乱者127例(54.3%).治愈188例(80.3%),缓解12例(5.1%),进步20例(8.5%),无效14例(6.0%).无手术死亡.患者性别、肿瘤大小和术前泌乳素水平对经蝶术后疗效有极显著影响,而术前病程、术前服用溴隐停与否、肿瘤质地、肿瘤是否卒中、术中鞍膈下降程度等对经蝶手术疗效没有明显影响.经蝶手术的总费用为(12 912.0±2361.2)元.结论 经蝶显微手术治疗可以作为非侵袭型垂体泌乳素腺瘤尤其是微腺瘤和大腺瘤的一级治疗方法.     

Giant prolactinomas: clinical management and long-term follow up

OBJECT: Giant prolactinomas are rare tumors whose treatment and outcome has only been addressed in isolated case reports. The authors document the long-term follow-up findings and clinical outcome in a group of patients with giant prolactinomas. METHODS: This study is a retrospective chart and clinical review of more than 2000 cases of pituitary tumors treated at the authors' institution, of which 10 met the criteria for inclusion (prolactin level > 1000 ng/ml, diameter > 4 cm on neuroimaging studies, and clinical signs of hyperprolactinemia/mass effect). The average follow-up duration was 6.7 years after initial treatment with either bromocriptine or transsphenoidal resection. In more than 90% of the patients in this series the disease was controlled by medical treatment with bromocriptine alone; the other 10% required early surgery via transsphenoidal resection. All patients had improvement in visual symptoms. All tumors had extrasellar components, five of which exhibited frank invasion of the cavernous sinus. Tumor volume on magnetic resonance imaging was decreased on average by 69%; this occurred at a faster rate and in larger amounts when treated with bromocriptine than has been reported in the literature for macroprolactinomas. CONCLUSIONS: According to long-term follow-up findings, giant prolactinomas are exquisitely responsive to dopamine agonist therapy. In giant prolactinomas the prolactin level does not correlate with size. The main indication for early surgery is intratumoral hematoma, whereas our main indications for late surgery are cerebrospinal fluid leakage caused by medical treatment, or an increasing prolactin level despite medical therapy. Checking prolactin levels in suspicious sellar and/or suprasellar lesions may be diagnostic and prevent unnecessary surgery.     

Clinical and histological correlations in prolactinomas,with special reference to bromocriptine resistance

Summary Background. Prolactinomas usually exhibit a benign course and can be safely and effectively managed by dopamine agonists (DA). However, some are locally invasive and may show resistance to DA therapy, and the management of such cases remains controversial. The aim of the present study was to determine whether histological features and markers of cell proliferation correlated to the clinical behaviour of prolactinomas and with DA resistance.Method. This retrospective study included 74 cases (36 men and 38 women) who had monohormonal prolactinomas removed by transsphenoidal surgery. The prolactinomas were categorized on the basis of tumour size (48 macroadenomas), invasion of the cavernous sinus (n = 31), and resistance to bromocriptine (BRC) therapy (n = 14). Group 1 consisted of non-invasive microprolactinomas (n = 24), group 2 of non-invasive macroprolactinomas (n = 19), group 3 of invasive non-BRC-resistant tumours (n = 19), and group 4 of invasive BRC-resistant tumours (n = 12). The later group included one case of carcinoma with bone and lung metastases. Seven additional parameters were studied, these being age, sex, basal prolactin (PRL) levels, the Ki-67 and PCNA labelling indices (LI), mitotic count, and cellular atypia.Findings. Age and preoperative PRL levels did not correlate to the histological parameters studied. Tumour size and invasion were related to cellular atypia and the Ki-67 LI. BRC-resistant tumours were more frequently invasive (12/14) than BRC-responsive tumours (11/30; p = 0.002) and were more frequent in men than in women (33 versus 5%; p = 0.003). BRC-resistant tumours had a higher Ki-67 LI and mitotic count (4.2±2.0% and 4±1, respectively) than other tumours (0.7±0.2% and 1±0, respectively; p<0.05). The strongest correlations with tumoural staging were seen with male sex and high mitotic activity. Six out of the 12 invasive BRC-resistant macroprolactinomas, including the PRL secreting carcinoma, exhibited histological features of aggressiveness (a mitotic count ≥3 [i.e. in the fourth quartile] and/or a high Ki-67 LI and cellular atypia).Conclusions. In this surgical retrospective series, histological signs of aggressiveness are present in 50% of invasive and BRC-resistant prolactinomas, which are more frequent in men than in women. This fits with the behaviour of BRC-resistant prolactinomas, which can continue to grow despite DA treatment. These findings justify the long-term follow up of these tumours, and the use of surgery and/or radiotherapy if there is concern about the control of tumour growth.     

Management of prolactinomas associated with very high serum prolactin levels

The authors have reviewed the results of transsphenoidal microsurgical management in 69 patients with prolactin-secreting pituitary adenomas who had preoperative serum prolactin levels over 200 ng/ml. The patients were divided into three groups based on their preoperative serum prolactin levels: over 200 to 500 ng/ml (Group A); over 500 to 1000 ng/ml (Group B); and over 1000 ng/ml (Group C). The percentage of successful treatment ("control rate") was 68%, 30%, and 14%, respectively, in these three groups of patients. Based on these results, the authors offer guidelines for the management of patients with prolactin-secreting pituitary adenomas associated with exceptionally high serum prolactin levels. The surgical control rate of 68% in Group A seems to justify surgery for these patients, while primary medical care with bromocriptine is recommended for most patients with serum prolactin levels over 500 ng/ml.     

A case of prolactinoma with galactorrhea in man

A 28-year-old man was admitted to the Kyushu University Hospital with an episode of severe headache. When driving a car, he suddenly developed severe headache and this was followed by nausea and vomiting. he had been quite well except for slightly decreased libido before this episode. On admission, he showed galactorrhea. The pubic and axillary hairs appeared normal and the development of the external genital organs seemed normal. However, the movement of the sperma was decreased. Ophthalmologic examination was negative. Endocrinological studies revealed hyperprolactinemia of 697 ng/ml, and the serum prolactin level was suppressed by bromocriptine and L-DOPA loading test. The serum testosterone level was 282 ng/dl. Growth hormone and gonadotropin levels were normal. Plain films of the skull and tomograms of the sella showed double floor and slight ballooning. CT scan showed an isodensity mass in and above the sella, and this mass was slightly enhanced with contrast media. The suprasellar extension was better demonstrated by metrizamide cisternography and CT. The diagnosis of prolactinoma was made, and a radical removal of the tumor was done through the transsphenoidal route. During surgery, dark reddish fluid was aspirated in an amount of 1.8 ml. Histologically the tumor was chromophobe adenoma, and immunohistochemical stain revealed prolactin granules in the majority of the tumor cells. Postoperative serum prolactin level decreased to 150 ng/ml and finally returned to normal by administration of 2.5 mg of bromocriptine. The serum testosterone level was slightly elevated. The movement of the sperma showed no improvement. There were no postoperative complications such as hypopituitarism and CSF rhinorrhea. The usefulness of combination therapy of operation and medication with bromocriptine was suggested.     

The neurosurgical management of prolactinomas

BACKGROUND: The objective was to discuss the neurosurgical management of the prolactinomas. METHODS: Five-hundred-fifty patients suffering from prolactinoma were treated with trans-sphenoidal and transcranial approach. The diagnosis of prolactinoma was based on various degree of high level prolactinemia, galactorrhea, gonodal disturbance, neurological examination and radiological findings. In all cases the adenoma was histologically verified. The patients were investigated according to the anatomo-radiological classification of Hardy and Vesina, and the range of preoperative PRL basal levels. RESULTS: Follow-up was ascertained in 81% of patients who were followed for a mean of 7.2 year (1-10 year). While the total removal percentage was 98% in the group with microprolactinoma, this ratio dropped to 63.9% for macroadenomas and 23.5% for giant adenomas. Early improvement of prolactin level ratio was 81.6% in microprolactinomas, 28.3 in macroadenomas and 11.7% in giant adenomas. Hormonal cure was 64.3% in microadenomas, 6.7% in macroadenomas and 0% in giant adenomas. The ratio of hormonal cure was decreasing in patients with high prolactin levels. In the follow-up recurrence of prolactinomas occurred in 39% of the patients. CONCLUSIONS: Medical treatment is the first step in prolactin secreting adenomas. Trans-sphenoidal microsurgery became popular in treatment of prolactinomas because of low operative morbidity and mortality. Patients with recurrence should be evaluated for second step treatment (surgery, bromocriptine, or radiotherapy).     

Surgical treatment of clinically nonsecreting pituitary adenomas in elderly patients

OBJECTIVE: The goal of this study was to evaluate the efficacy and safety of transsphenoidal pituitary surgery for elderly patients, using improved techniques of the past decade. METHODS: We retrospectively analyzed 32 surgically treated cases of clinically nonsecreting pituitary adenomas in patients more than 70 years of age (mean, 73.9+/-3.4 yr). These patients were identified in a review of 982 patients with pituitary adenomas who were treated at University Hospital Eppendorf, Hamburg, between January 1991 and November 1999. RESULTS: The mean preoperative duration of symptoms was 1.9 years (2 wk to 11 yr). The chiasmatic syndrome was present for 27 patients (84.4%). All patients underwent transsphenoidal surgery. Seven patients underwent reoperations. Preoperative assessments of anterior pituitary function revealed growth hormone deficiencies for 21 of 27 patients (77.8%), thyroid insufficiencies for 10 of 30 patients (33.3%), and adrenal insufficiencies for 13 of 29 patients (44.8%). Hypogonadism and hyperprolactinemia were observed for 76.7% and 46.9% of the patients, respectively. All tumors were macroadenomas, ranging from 18 to 50 mm (average, 33.6 mm) in size, including 7 enclosed and 25 invasive adenomas. Complete microscopic tumor resection was achieved in 24 cases, and subtotal removal was performed in 8 cases. There were no severe perioperative complications. In the cases involving hyperprolactinemia, serum prolactin levels were normalized for 8 of 11 patients (72.7%). Normal thyroid function was recovered for 1 of 10 patients (10.0%) with preoperative hypothyroidism. However, growth hormone or adrenal insufficiencies persisted for all patients with preoperative insufficiencies. Visual disturbances were improved for 19 of 23 patients (82.6%). All patients recovered well after surgery, with an average hospital stay of 16.3 days. Histological and immunohistochemical studies demonstrated gonadotroph adenomas in 56.7% of cases, null-cell adenomas in 26.7%, and oncocytomas in 13.3%. CONCLUSION: Surgical treatment of nonsecreting pituitary adenomas causing visual disturbances is standard, even for elderly patients. In this series, transsphenoidal surgery was a safe procedure, with minimal morbidity and excellent tolerance. Age alone is not a contraindication for active treatment, particularly with transsphenoidal surgery.     

Preoperative short-term administration of octreotide for facilitating transsphenoidal removal of invasive growth hormone-secreting macroadenomas

The somatostatin analog octreotide was administered prior to transsphenoidal surgery in three patients with tumors that extended to the suprasellar space and one side of the cavernous sinus. Octreotide, 100 micrograms twice a day, was subcutaneously injected for 2 weeks. Octreotide administration reduced the serum growth hormone (GH) levels in these patients from 82 to 22 ng/ml, from 148 to 12 ng/ml, and from 129 to 9 ng/ml. The tumor size shrank by about 50%, and the suprasellar extension disappeared in two patients. The main tumor was sharply dissected from the normal pituitary gland at surgery. Intracavernous portions were removed using a curette. Postoperatively, GH levels were less than 5 ng/ml in two patients, and 8.5 ng/ml in one patient. Follow-up magnetic resonance imaging revealed a small residual tumor in one side of the cavernous sinus in all patients. Follow-up GH levels were less than 5 ng/ml in one patient, and less than 2 ng/ml in two patients treated with bromocriptine. Preoperative administration of octreotide for 2 weeks reduced tumor volume and allowed near-total surgical resection of invasive macroadenomas without compromising the treatment course. Residual tumor due to intracavernous extension can be managed with bromocriptine or gamma knife radiosurgery.     

Transsphenoidal treatment of non-neoplastic intrasellar cysts. A report of 38 cases

Thirty-eight patients underwent transsphenoidal microsurgical treatment of non-neoplastic intrasellar cysts: 36 had cyst drainage and biopsy of the cyst wall, and in two the cyst was totally removed. Surgical morbidity was 8%. The mean follow-up time was 46.3 months; 100% patient follow-up evaluation was achieved. Sixteen female patients (mean age 24.6 years) had pars intermedia cysts: 88% had menstrual irregularities, 63% had galactorrhea, 31% had headache, and 56% had hyperprolactinemia. Within these groups, menstrual cycles returned in 86%, galactorrhea ceased in 90%, headaches resolved in 80%, and serum prolactin levels were restored to normal in 66%. Eight females and three males had Rathke's cleft cysts (mean age 34.0 years): of these 11 patients, 91% had headaches and 18% had hyperprolactinemia; of the eight females, 63% had amenorrhea and 63% had galactorrhea. Within these groups, serum prolactin levels normalized in 50%, and 80% noted reduced headache. Of the females, 80% had return of menses and 50% noted cessation of galactorrhea. Six males and two females had arachnoid cysts (mean age 42.2 years): 50% had headaches; 50% were asymptomatic. Preoperatively, 50% of these patients had hypothyroidism and 25% had adrenal hypofunction. Postoperatively, 75% of patients with headache noted improvement, and 33% of patients with abnormal thyroid function had normal function. Adrenal function did not improve. Three patients had an intrasellar cysticercosis cyst, epidermoid cyst, and postoperative cyst, respectively. All had evidence of partial hypopituitarism; none improved postoperatively. The results indicate that different types of pituitary cysts produce different clinical syndromes, and suggest that simple transsphenoidal drainage and partial removal of the cyst wall can provide safe and effective therapy.     

Transsphenoidal surgery for acromegaly: endocrinological follow-up of 98 patients

OBJECTIVE: Transsphenoidal surgery is the preferred treatment modality for growth hormone (GH)-secreting pituitary adenomas. In many series, the reported postoperative remission is based mainly on achievement of GH levels less than 2 ng/ml. Strict criteria for insulin-like growth factor I normalization and even lower GH levels (<1 ng/ml) are now suggested to define cure of acromegaly, but the evidence does not yet support such low GH levels in epidemiological follow-up. We analyzed our postoperative results in a large cohort of patients with acromegaly. METHODS: Ninety-eight patients harboring GH-secreting adenomas (46 microadenomas and 52 macroadenomas) underwent transsphenoidal surgery between 1990 and 1999. Ninety-one patients were operated for the first time, and 12 patients underwent reoperations because of previous surgical failure (7 had undergone surgery elsewhere previously). Biochemical remission was defined as a repeated fasting or glucose-suppressed GH level of 2 ng/ml or less, and a normal insulin-like growth factor I level. RESULTS: Remission was achieved in 74% of all patients after one operation, including 84% of patients with microadenomas and 64% of patients with macroadenomas. Seventy-three percent of patients with macroadenomas 11 to 20 mm in size achieved remission, as compared with a 20% remission rate for patients with adenomas larger than 20 mm. Patients with preoperative random GH levels lower than 50 ng/ml had a better outcome (85% remission), whereas GH greater than 50 ng/ml was associated with remission in 30% of the patients. Only one of the patients (8%) with postoperative active disease who underwent a second operation achieved remission. Recurrence was rare (one patient), and all failed surgical attempts could be detected during the immediate postoperative evaluation. CONCLUSION: On the basis of strict postoperative GH and insulin-like growth factor I criteria to define remission, our series demonstrates the efficacy of transsphenoidal surgery for acromegalic patients with microadenomas and noninvasive macroadenomas. However, patients with large adenomas (>20 mm) and preoperative GH greater than 50 ng/ml have a poor prognosis and require adjunctive medical or radiation therapy to control GH hypersecretion.     

Treatment and long-term follow-up results of prolactin secreting pituitary adenomas

The authors have reported data on a retrospective study, carried out in order to evaluate the short- and the long-term follow-up results of transsphenoidal microsurgery for prolactin-secreting pituitary adenomas; and to point out the indications for an eventual additional bromocriptine treatment. Prior to surgery, the patients were tested according to the study protocol. Patients were grouped differently according to their adenoma size. We found a good correlation between adenoma size and hormonal values. The surgical treatment led to an immediate endocrine cure in 47 patients (48.9%), with the majority occurring in microprolactinomas. Post-operatively, the cure rate was maintained in 45 patients. The Authors deem the transphenoidal microsurgery the therapy of first choice for microadenoma and mesoadenoma treatment, especially whenever there is bromocriptine intolerance. On the contrary, in invasive macroadenomas, bromocriptine is a necessary additional therapy both to shrink large tumors sufficiently for subsequent transsphenoidal approach and in incompletely removed tumors or persistent hyperprolactinemia.