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.     

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.     

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.     

首选溴隐亭治疗侵袭性巨大泌乳素腺瘤的综合治疗

目的观察首选溴隐亭治疗侵袭性巨大泌乳素腺瘤（IGPs）综合治疗的远期疗效。方法符合IGPs诊断标准的患者34例,均首选溴隐亭进行治疗,其中11例同时配合放疗。服药期间根据肿瘤缩小后的残留部位、有无继续显著缩小、有无耐药等情况决定是否手术或立体定向放射外科治疗或二者联合应用。术后继续以小剂量溴隐亭维持治疗。结果平均随访33．6个月,33例患者症状显著改善,1例放疗后视力改善不明显。肿瘤体积平均缩小91．4％,泌乳素平均下降约97．1％,睾酮下降、皮质醇功能低下分别由治疗前的17例、10例降至6例、6例。溴隐亭治疗期间出现脑脊液鼻漏2例,1例自行缓解,1例行经蝶、开颅联合入路切除肿瘤、修补瘘口;4例出现不同程度的耐药现象。结论IGPs应首选药物治疗,部分患者仅通过药物治疗即可达到影像学上肿瘤消失的目的,大部分患者需辅助经蝶手术、立体定向放射外科治疗,可以明显缩短治疗时间、减少药物的用量甚至停药,但要慎行放疗。     

Treatment of prolactinoma based on the results of transsphenoidal operations

Ninety-eight patients (16 male, 82 female) with prolactinomas were treated by transsphenoidal operation. The postoperative course was closely related to the tumor size and the preoperative levels of serum prolactin. In 37 (74%) of 50 patients with microadenomas, the levels of serum prolactin returned to normal postoperatively. There were 48 patients with macroadenomas; 27 of these were expansive and 21 were invasive. In 9 (33%) of the 27 patients with expansive macroadenomas, the postoperative levels of prolactin returned to normal; this was not the case in any of the 21 patients with invasive macroadenomas. Of 81 premenopausal women, 35 (43%) resumed normal menstruation postoperatively. All patients with preoperative deficits in the visual field experienced postoperative improvement. There were no postoperative deaths or serious complications in this series. Our data indicate that microprolactinomas are highly curable by transsphenoidal operation alone. In women who plan to have children, prolactinomas should be removed immediately. On the other hand, in patients with macroprolactinomas who manifest high levels of serum prolactin, initial treatment with bromocriptine should be considered because there is little hope for surgical cure and postoperative bromocriptine treatment might be necessary.     

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.     

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.     

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.     

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).     

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.     

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)     

侵袭性垂体泌乳素腺瘤的治疗策略

目的 探讨侵袭性垂体泌乳素腺瘤的治疗策略.方法 纳入侵袭性垂体泌乳素腺瘤的标准是:(1)Knosp分级Ⅲ或Ⅳ级,即肿瘤侵袭海绵窦;(2)血浆泌乳素(PRL)9.1 nmol/L;(3)高PRL分泌症状或占位效应.符合上述标准者80例,其中单纯药物(溴隐亭)治疗21例,首选药物治疗结合手术和(或)放疗组21例,首选手术治疗结合药物和(或)放疗组(首选手术治疗组)38例.残留海绵窦肿瘤行伽玛刀治疗11例.结果 平均随访62个月,MRI检查肿瘤消失57例(71%),其中单纯药物治疗组12例,首选药物治疗结合手术和放疗组16例,首选手术治疗组29例.其余23例残留肿瘤均在鞍旁海绵窦内.PRL水平正常者52例(65%),其中首选手术治疗组31例,单纯药物治疗组10例.PRL9.1 nmol/L者7例.视力改善者33例,与治疗前一致者40例,恶化7例.垂体功能低下者9例.结论 对侵袭性泌乳素腺瘤,提倡以多巴胺受体激动剂为首选治疗的个体化治疗方案.手术后仍要服用溴隐亭并进行密切随访观察.海绵窦残留肿瘤可以行伽玛刀治疗.     

Pituitary Surgery

Surgery, more specifically transsphenoidal approach, remains the primary treatment chosen for the majority of pituitary tumors (except for prolactinomas where medical treatment is indicated) allowing for pathologic analysis and complete or partial tumor removal. Transcranial approaches, employing craniotomies, are still needed in some patients with giant pituitary adenomas and in many of those harboring craniopharyngiomas. However, the surgical treatment of pituitary tumors is challenging because of their complex anatomical location and their heterogenous histology. Due to the proximity of critical structures, a successful surgical procedure may often not be achievable due to the high risks related to the procedure itself. Therefore, the treatment of pituitary tumors in 2020 commonly requires a multimodal approach, including surgery, radiosurgery, radiation therapy, and medical therapy. Recently, efforts have been made to develop intraoperative imaging, by increasing the diffusion of radiosurgery. Furthermore, the development of Pituitary Tumor Centers of Excellence (PTCOE) is becoming crucial to provide the optimal treatment for a single patient. There is in fact sufficient evidence that the best and optimal outcome in terms of tumor resection and correction of hormonal over secretion as well as the lowest rate of complications are obtained in centers of excellence with sufficiently experienced, specialized surgeons and a high patient load. Technological developments will probably even gain increasing importance in the future.     

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.     

Dopamine agonist-resistant prolactinomas

The authors' object in this paper was to review the definition, epidemiology, biology, resistance mechanisms, and treatment options for dopamine agonist-resistant prolactinomas (DARPs). Prolactinomas are relatively unique among primary brain tumors in that medical treatment alone using dopamine agonists carries a high probability of disease control or even radiographic and endocrine remission, and thus has replaced surgery as the first line of therapy. Unfortunately, slightly less than 10% of patients with prolactinomas do not experience normalization of their prolactin levels in response to dopamine agonists, and harbor tumors that are resistant to dopamine agonist therapy. A literature review underscores that in male patients these DARPs are more likely to be invasive macroadenomas than dopamine agonist-responsive prolactinomas and that they are also more angiogenic, more proliferative, and more likely to exhibit cellular atypia. Estrogen receptor antagonists and temozolomide are the most commonly applied medical therapies in cases in which resection and radiosurgery have not induced remission of the hyperprolactinemia. Dopamine agonist-resistant prolactinomas exhibit aggressive behavior and tend to be large, invasive, hyperangiogenic tumors with high mitotic indices, which makes their management via surgery, radiosurgery, or alternative medical therapies challenging, thus underscoring the need for novel medical therapies or treatment regimens that target these lesions.     

Pituitary Adenomas

Opinion statement Treatment of pituitary adenomas can be pharmacologic or surgical. First-line treatment of prolactinomas is usually medical, using either bromocriptine or cabergoline. Other symptomatic pituitary adenomas typically should be treated with transsphenoidal surgery. Radiation therapy can be adjunctive for residual or recurrent tumor. The prognosis for endocrinologic and visual improvement is usually good.     

A case of male cystic pituitary adenoma with hyperprolactinemia--clinical study of 6 cases of male prolactinoma

A case of male cystic prolactinoma is reported. And six cases of male prolactinoma including the present case were experienced in our department, and they were studied clinically. A 40-year-old male was admitted to our hospital with complaints of decreased libido and bitemporal visual depression. Physical examination revealed neither gynecomastia nor galactorrhea. Decreased visual acuity, bitemporal hemianopia, and pale optic disc were disclosed. On endocrinological study, high serum level of prolactin and hyposecretion of the other pituitary hormones were shown. Plain skull x-ray films showed ballooning of the sella turcica. CT scan revealed a low density area in the pituitary fossa extending to the suprasellar region. This was visualized as a homogeneous high signal intensity in the T1 weighted magnetic resonance imaging. Surgical treatment was made by transsphenoidal approach. A considerable amount of dark reddish fluid was suctioned through an incision of the thinned dura mater. Postoperative course was uneventful, and the bitemporal hemianopia was much improved. The serum level of prolactin was normalized after administration of bromocriptine. Male prolactinomas were thought to constitute 20% of all prolactinomas and male cystic prolactinoma was a rare clinical entity. Since the serum level of prolactin became to be measured routinely, six male prolactinomas have been experienced in our department. Their clinical feature were summarized as follows; Mean age of the patients was 33.2 +/- 9.8 years. Marked suprasellar extension and associated visual disturbance were common. All lesions except in the present case were solid tumor. Mean serum level of prolactin was 3398.3 +/- 2758.4 ng/ml. Pituitary apoplexy during the test of insulin, TRH and LH-RH simultaneous loading was noted in two cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short-term preoperative treatment of macroprolactinomas by dopamine agonists

During a period of 3 years, 25 patients with intra- and extrasellar macroprolactinomas were pretreated with dopamine agonists for a period of 2 to 6 1/2 weeks prior to transsphenoidal microsurgical tumor resection. Dopamine agonists were administered orally to 17 patients, intramuscularly to three patients, and both orally and intramuscularly to five patients. Repeated computerized tomography (CT) examinations revealed that all neoplasms except one cystic tumor were reduced in size during the course of dopamine-agonist administration. No complications attributable to medical pretreatment were observed. Tumor shrinkage increased the efficacy of surgery, especially in cases with considerable extrasellar extension of the adenomas. Within 3 months following adenomectomy, prolactin levels were adjusted to normal levels in 19 patients by additional low-dose treatment with dopamine agonists. Thin-collimation CT assessments performed at least 3 months after surgery showed no evidence of residual tumor tissue in 23 patients. It is concluded that administration of dopamine agonists for some weeks prior to surgery is a useful adjunct to transsphenoidal microsurgery for macroprolactinomas. The new injectable form of bromocriptine is particularly valuable for this purpose.     

Prolactinoma in a child showing high MIB-1 labeling index: a case report

We report a very rare case of a prolactin secreting pituitary tumor (prolactinoma) which occurred in a 12-year-old boy. The tumor showed an extremely high MIB-1 index. The clinical implication in the postoperative management of childhood prolactinoma is discussed. The patient showed right third nerve palsy, and MRI revealed a pituitary tumor invading the right cavernous sinus. Preoperative hormonal evaluation showed a very high prolactin level (2800 ng/ml). The patient underwent transsphenoidal surgery, and the third nerve palsy disappeared just after the procedure. MIB-1 index obtained by using immunostaining was 18.9%. Postoperative prolactin level remained high (2200 ng/ml), and the patient was treated with 10 mg/day of bromocriptine. Prolactinomas in children with high MIB-1 index show resistance to treatment with bromocriptine. In the postoperative management of a childhood prolactinoma, it should be considered how to control sufficiently high serum prolactin level to expect sexual development while preserving other normal residual pituitary functions. If control with bromocriptine, fails radiation treatment should be adopted with careful observation of the increase in height and the progress of sexual development of the patient.     

Pediatric pituitary tumors

This retrospective review of pediatric patients with pituitary tumors causing onset of symptoms by 17 years of age was done to define their pathological distribution, clinical presentation, treatment, and prognosis. Eighteen patients were evaluated and treated from 1979 to 1989. Five had Cushing's disease and 13 had prolactin-secreting tumors. The mean age at the onset of symptoms was 14.7 years, with a range of 7 to 17 years. The mean follow-up period was 4.6 years, and the series consisted of 15 girls and 3 boys. Four of the 5 patients with tumors secreting adrenocorticotropic hormone were girls. The five patients exhibited obesity, hypertension, and growth retardation. The mean age of this group of patients at diagnosis was 12.2 years, and all had intrasellar lesions removed by the transsphenoidal approach. Adenoma was documented in 4 cases by histopathology. There was complete resolution of the endocrinological and clinical abnormalities in each case. The group of patients with prolactinomas comprised 11 girls and 2 boys, and their mean age at diagnosis was 15.7 years. The girls exhibited either primary or secondary amenorrhea. Seven had macroadenomas and 4 had microadenomas. Nine of the 11 girls underwent transsphenoidal resection, and surgery failed in 6, based on hormonal or radiological data. The two boys had suprasellar tumor extension and required multiple surgical procedures plus radiation therapy for control of the tumor mass.