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.     

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.     

Bromocriptine for infertile males with mild hyperprolactinemia: hormonal and spermatogenic effects

To clarify the influence of hyperprolactinemia on spermatogenesis and steroidogenesis in infertile male patients, the serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol concentrations were and the effect of bromocriptine treatment on spermatogenesis was examined. A total of 1234 patients were evaluated and 147 men had hyperprolactinemia. Of these, only 30 had PRL concentrations more than twice the upper limit of normal and most of them had a little excess over the upper limit. For 10 of these 30, serum hormone concentrations were measured and semen was analyzed before and after bromocriptine administration. No relationship between the PRL and other hormone concentrations was found. No changes were noted in the LH, FSH, testosterone, or estradiol concentrations, or in the sperm density and motility after treatment. The mean PRL decreased from 26.5 +/- 4.5 to 1.4 +/- 1.8 ng/mL. In infertile men who are mildly hyperprolactinemic, bromocriptine administration does not improve semen analysis, although it does normalize the PRL.     

Effect of tamoxifen on the treatment of pituitary adenomas with bromocriptine

Administration of 2-Br- alpha-ergocryptine (bromocriptine = CB-154) in combination with an estrogen-receptor blocking agent tamoxifen were performed in two patients with prolactinoma and non-functioning adenoma, respectively. Case 1 was a 50-year-old male with hyperprolactinemia, impaired pituitary function and visual disorders, in whom a large invasive sellar mass lesion was disclosed by CT scans, which extended supra- and parasellarly and extracranially into paranasal sinuses and pterygopalatine fossa on the left side. As the effect of bromocriptine therapy was partial in tumor size reduction and decrease of serum PRL level and it could not be gained further improvement except for the well recovered visual acuity, tamoxifen was used together with bromocriptine resulting further reduction of tumor size and normalization of serum PRL level. Unexpectedly the medication was ceased during and after a couple of bypass surgery for angina pectoris, and it was followed by elevation of serum PRL level and regrowth of the sellar tumor as well as impairment of vision. By tamoxifen therapy the visual acuity showed some improvement, but the serum PRL level and the tumor size remained as before. Then the combination therapy with bromocriptine and tamoxifen was started again. Case 2 was a 38-year-old female with three children, who had secondary amenorrhea, galactorrhea, borderline level of serum PRL with impaired pituitary function and visual disorders. Under the diagnosis of a non-functioning pituitary adenoma with supra-sellar extension, a craniotomy was done and intracapsular partial removal of the tumor was made, revealing a chromophobe adenoma in light microscopy and undifferentiated cell adenoma in electron-micrographs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stereotactic Radiotherapy for Cushing's Disease and Prolactinoma

Stereotactic radiotherapy (SRT) for secretory pituitary adenoma offers precise localization of dose with potential sparing of optic and hypothalamic functions. We collated the indications, treatment parameters, and both the clinical and biochemical results of Stereotactic radiotherapy for ACTH- 1 and prolactin-secreting pituitary adenoma. Between May 1990 and February 1996, nine patients (4 males and 5 females) with a mean age of 31.9 years had fractionated SRT for ACTH- or prolactin-secreting pituitary adenomas (Cushing's disease: n = 5; prolactinoma: n = 3; Nelson's syndrome: n = 1). These 9 patients had subtotal transphenoidal resections before SRT. An additional patient with Cushing's disease had aborted transphenoidal surgery and single-fraction Stereotactic radiosurgery (SRS). Prior to SRT, 4 patients received planned conventional fractionated external beam radiotherapy (XRT) (median dose 33.3 Gy). The median SRT dose was 34.5 Gy (range 14.4–50.4 Gy). The median total radiation dose (XRT plus SRT) for patients receiving fractionated treatment was 47.7 Gy. The median follow-up was 62 months (range 22–91 months). One patient with Nelson's syndrome was lost to follow-up. Of the 9 evaluable patients, none required reoperation for growth of pituitary tumor and all had radiographic control as shown by serial MRI scans. In 4 of the 6 patients with Cushing's disease, treatment resulted in normalization of hormone levels and resolution of symptoms. All 4 patients were able to discontinue medications. In 2 patients, normalization occurred within 4 months of treatment. Two patients with Cushing's disease failed, requiring adrenalectomy. For patients with prolactinoma, treatments resulted in a significant decrease of plasma prolactin levels. All patients treated for prolactinoma became asymptomatic; 2 were able to discontinue bromocriptine and 1 patient had a successful pregnancy. After radiation therapy, 1 patient developed new hypopituitarism. None of the patients developed worsened visual acuity, visual fields, or new neurological deficits. SRT with or without XRT may yield meaningful reductions in hormone levels with concomitant clinical improvement in selected patients with prolactinomas or Cushing's disease. In certain situations, combining conventional XRT with SRT is appropriate. Modifications of the Stereotactic radiation delivery may maximally reduce the hypothalamic dose, thereby possibly reducing the risk of clinical hypopituitarism. This treatment is safe and is without visual or other neurological toxicity.     

Short-term management of macroprolactinomas with a new injectable form of bromocriptine

Three cases (2 men, 1 woman) of expansive macroprolactinoma treated with a single 50-mg intramuscular dose of a new form of injectable, long-acting bromocriptine are presented. Clinical manifestations included visual disturbances (2 cases), headache (1 case), and hypogonadism (3 cases). Laboratory tests demonstrated high basal serum prolactin (PRL) levels and evidence of involvement of other anterior pituitary hormones in all cases. Treatment was followed by marked improvement of symptoms paralleled by a sharp decrease of serum PRL levels, which normalized in 1 case. Some other anterior pituitary functions also improved. Computed tomography scan revealed shrinkage of the tumor in all cases. There were no local or serious systemic side effects. These initial findings suggest that long-acting injectable bromocriptine has a place in the initial treatment of macroprolactinomas, especially for those with neurological and/or visual manifestations. It can also be used to select patients for surgery, in the cases where clinical and radiological improvement could not be obtained. The effects of long-term use remain to be established by further studies.     

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.     

尿毒症透析患者的卵巢功能

为了解女性尿毒症患者卵巢功能障碍的发病情况,明确发病部位,探索其发病机理。方法 应用酶免疫法(EIA)检测了25例更年期前尿毒症透析患者的泌乳素(PRL)、促卵泡素(FSH)、促黄体素(LH)、雌二醇(E_2)及孕酮(P)的基础水平,并观察了部分患者服用克罗米酚(CC)及溴隐停后以上激素的变化。结果 与近龄健康妇女相比RPL明显升高,FSH、LH亦升高,而孕酮值显著下降。闭经者服用CC后,血LH、FSH和E_2水平上升,谓之CC试验结果阳性。虽PRL广泛升高,用嗅隐停可使之暂时下降,但效果很不稳定,排卵率亦很低。结论 (1)尿毒症女性普遍的月经无周期和缺乏E_2、LH峰,以及孕酮值低下,证实了存在下丘脑-垂体-卵巢轴损害;(2)尿毒症女性CC刺激试验阳性,说明垂体-卵巢轴是正常的,损伤部位在下丘脑;(3)尿毒症女性PRL显著升高,主要是垂体泌乳细胞分泌增加,溴隐停治疗,效果不稳定;(4)尿毒症女性月经紊乱应给对症处理,但无需促排卵治疗,而成功肾移植是最好的治疗方法。     

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。     

Hyperprolactinaemia among infertile patients and its effect on sperm functions

Summary. The effects of hyperprolactinaemia on sperm function were investigated in 264 men with oligozoo-, asthenozoo-, or teratozoospermia and who were attending a male infertility clinic. None of the patients exhibited galactorrhea or complained of impotence. There was no correlation between abnormal values in spermiogram and hyperprolactinaemia. After multiple measurements of serum prolactin concentration, 15 cases (5.7%) were diagnosed as hyperprolactinaemic (≧ 10 ng ml⁻¹). Six of these patients were taking cimetidine and six were taking anti-anxiety drugs. Serum prolactin returned to the normal level after discontinuation of these drugs; thus these 12 cases were considered as drug-induced hyperprolactinaemia. The other three patients were diagnosed as having pituitary microadenomas and received bromocriptine treatment; the serum prolactin levels normalized within 1 month. No changes in sperm concentration, motility or morphology were found after normalization of serum prolactin levels. Sperm fertilizing ability was monitored by the hamster test for 10 months in the three patients with pituitary microadenoma, and no improvement was observed. Results suggest that hyperprolactinaemia, which does not cause symptoms, has little effect on the impairment of sperm functions. Measurement of serum prolactin in infertile men could be justified, however, for early detection of pituitary adenomas.     

Effects of induced hypoprolactinemia on testicular function during gonadal maturation in the rat

We have evaluated the effects of hypoprolactinemia during gonadal maturation in the male rat. Intact 30-day-old rats were injected daily for 10 days with three different doses of bromocriptine (0.75, 1.5 or 3.0 mg/kg of body weight/day). At the end of the treatment period, the animals were sacrificed, serum was collected for prolactin (PRL), LH, and androgen measurements. Intratesticular testosterone and 5 alpha-androstanediol (androstanediol) were measured following celite column chromatography and a specific radioimmunoassay. In addition, the production of androgens by decapsulated testes and dispersed Leydig cells was also studied in vitro. Serum levels of PRL (9.4 +/- 1.9 ng/ml) were suppressed to undetectable levels in the three bromocriptine-treated groups, whereas LH levels were not altered. All three doses of bromocriptine markedly depressed serum testosterone (plus DHT) and androstanediol. Intra-testicular testosterone and androstanediol were diminished (25% and 35%, respectively, P less than 0.05) during hypoprolactinemia. Decapsulated testes and dispersed Leydig cells from bromocriptine-treated animals showed a significant reduction in the basal secretion of testosterone (plus DHT) and androstanediol, and in androgen responses to submaximal hCG stimulation. Maximal steroidogenic responses from bromocriptine-treated rats were similar to controls. The present findings show that, during puberty, bromocriptine influences testicular steroidogenesis, and these effects may be partly due to changes in PRL levels. A direct effect of this dopaminergic agonist on the male gonad cannot be completely ruled out.     

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.     

Growth of prolactinoma despite lowering of serum prolactin by bromocriptine

Four patients with macroprolactinomas treated with bromocriptine had tumor growth and visual loss despite marked reduction in their serum prolactin levels. Explanations for this dissociation of tumor growth and prolactin measurement might include noncompliance. Patients treated with bromocriptine require periodic examination by computed tomographic scan or magnetic resonance imaging and neuro-ophthalmological evaluation in addition to monitoring of serum prolactin.     

Therapeutic efficacy of a somatostatin analogue (SMS 201-995) in active acromegaly

Twelve patients with active acromegaly, six of whom had not responded to previous combined surgery, radiotherapy, and bromocriptine administration, were treated with an octapeptide long-acting somatostatin analogue, SMS 201-995, given subcutaneously for up to 1 year. Growth hormone (GH) levels decreased by 50% to 90% after a single 25-micrograms SMS 201-995 injection in all patients, including two who were resistant to bromocriptine therapy. After GH values reached a nadir, they returned to preinjection values over a 12-hour period and no rebound was seen. Assessment of the GH-lowering effect of the drug at weekly intervals for the first 6 weeks and monthly thereafter disclosed no tachyphylaxis. Gradual increase of the dose from 50 to 150 micrograms daily led to a significant increase in clinical improvement. Shrinkage of the size of the pituitary tumor was documented in three of nine evaluated cases. Abdominal cramps of a transient nature not associated with diarrhea were noted in two patients but there were no other side effects. Hematological and biochemical blood and urine tests, including serum thyroxine and cortisol levels, did not reveal any abnormality during chronic treatment. This study demonstrates the safety and efficacy of SMS 201-995 in the short-term treatment of acromegaly.     

Gangliocytoma masquerading as a prolactinoma. Case report.

The authors describe the case of a 36-year-old man who presented with bitemporal hemianopsia and a serum prolactin concentration of 1440 ng/ml. Magnetic resonance imaging of the pituitary revealed a presumed macroadenoma with suprasellar and temporal lobe extension. Although the patient's prolactin level was lowered to 55 ng/ml by bromocriptine therapy, no tumor shrinkage occurred. Fourteen months later, progression of visual field defects necessitated transsphenoidal resection, which was incomplete. Immunocytochemical analysis of the biopsy tissue was positive for prolactin and, in view of the clinical picture, more detailed analysis was not performed. External-beam radiotherapy was given 2 years later because of enlargement of residual tumor. Subsequently, despite a fall in the serum prolactin concentration to less than 20 ng/ml in response to the course of bromocriptine, the mass displayed further extension into the temporal lobe. Nine years after the patient's initial presentation, he underwent transfrontal craniotomy for sudden deterioration in visual acuity caused by hemorrhage into the mass. No adenohypophyseal tissue was identified in the resected tissue. The mass was composed of dysplastic neurons that were strongly immunoreactive for synaptophysin and neurofilament (indicating neural differentiation) and prolactin. Review of the original biopsy specimen indicated that the prolactin-positive cells had striking neuronal morphological characteristics. The final diagnosis in this case is prolactin-secreting gangliocytoma. Although exceedingly rare, this disease must be added to the differential diagnosis in cases of "prolactinoma" when bromocriptine therapy is followed by a marked decline in serum prolactin that is not accompanied by significant tumor shrinkage. Furthermore, in such instances, consideration should be given to "obtaining a biopsy sample prior to electing for radiotherapy.     

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.     

Malignant prolactinoma with multiple intracranial metastases studied with positron emission tomography

A rare case of a patient with multiple intracranial metastases from a prolactin-secreting pituitary neoplasm is described. At the age of 14 years, the patient had been operated on for a sellar tumor; he presented 12 years later with severe headache, at which time computed tomographic and magnetic resonance imaging scans revealed multiple intracranial metastases. Histopathology examination showed pituitary neoplastic cells with positive immunostaining for prolactin. The patient was investigated with positron emission tomography (PET) and dopamine D2-receptor binding, and the amino acid metabolism of the tumor was characterized in vivo. High dopamine D2-receptor binding and high amino acid metabolism were found in the tumor. The patient was subsequently treated with bromocriptine injections that resulted in a decrease in serum prolactin levels, decreased dopamine D2-receptor binding, reduced amino acid metabolism, and a reduction in tumor volume. This case demonstrates a beneficial effect of bromocriptine treatment in a patient with prolactinoma with multiple intracranial metastases. It also illustrates the great potential of PET in the in vivo characterization of the D2-binding and the high sensitivity of 11C-labeled L-methionine in the follow-up of treatment in patients with pituitary adenomas.     

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 apoplexy. Clinical course, endocrine evaluations and treatment analysis.

BACKGROUND: The purpose was to analyze clinical manifestations, hormonal changes, diagnosis difficulties and treatment of pituitary apoplexy (PA). EXPERIMENTAL DESIGN: A retrospective study of clinical records from patients with pituitary adenomas admitted from January 1980 to June 1996; the purpose was to identify the patients with clinical evidence compatible with PA. Setting: Neurosurgery unit of an institutional hospital. Patients: Sixteen (12.8%) of 125 patients with pituitary adenomas were analyzed because they had pituitary apoplexy. Interventions: Surgical treatment by the trans-sphenoidal or transcranial route or both routes; dexamethasone (DXM) treatment with 16 mg/day i.v. Measures: Hormone assays were performed either by radioimmunoassay or by chemical luminescence. RESULTS: Tumors were nonfunctioning in nine patients and functioning in seven. TSH and prolactin basal serum levels were impaired in 55.5% and 10%, respectively; after exogenous TRH 80% of the patients did not show stimulation of TSH and prolactin secretions. LH and FSH levels were low in 63.6% and 54.6% of the patients, respectively; gonadotrophin-releasing hormone (GnRH) testing was abnormal in 75% of the patients evaluated. Cortisol levels were low in 50% of the patients. After insulin-induced hypoglycemia, cortisol and GH failed to rise in 25% and 40% of cases, respectively. Ten patients were submitted to surgical treatment, but none during PA. The average time from the onset of apoplectic symptoms and surgery was 70+/-50 days. Only one patient died two months after surgery. Five patients were treated with dexamethasone (DXM) during the apoplectic symptoms: three patients died; one patient had good quality of life; the other patient was treated initially with DXM with improvement of vision, but after surgery he developed panhypopituirarism. Two other patients did not receive specific treatment for PA. CONCLUSIONS: PA is not a rare pituitary adenoma complication and its prognosis may be poor; baseline hormone levels showed a wide range of abnormalities of pituitary function; surgical treatment was required in the majority of patients and the prognosis was relatively good; on the contrary, the treatment with DXM only had high levels of mortality.     

Elevated serum prolactin level in the Zollinger-Ellison syndrome

To estimate the prevalence of prolactinoma in the Zollinger-Ellison syndrome (ZES), serum prolactin (PRL) levels were measured by radioimmunoassay in 36 patients with ZES. Eight patients had elevated PRL levels; however, in one patient the finding was attributed to primary hypothyroidism rather than a prolactinoma. The seven other patients were believed to have previously undiagnosed prolactinomas on the basis of elevated serum PRL levels; the presence of pituitary tumors were confirmed in four by demonstration of sella turcica erosions or enlargement. Serial determinations over three to six years showed a tendency for serum PRL levels to increase modestly in four of six patients. Thus far, two patients have undergone transsphenoidal tumor resections with good results. This study suggests that the prevalence of prolactinoma in patients with ZES is substantial (10% for those with isolated ZES and 54% for those with ZES with multiple endocrine neoplasia, type 1, syndrome), and that early diagnosis is possible with measurement of serum PRL levels. Since levels of PRL tend to increase and clinically significant pituitary tumors can develop, determinations of serial serum PRL levels are recommended for all patients with ZES.