Clinical features and medical treatment of male prolactinomas

Summary  Background. Prolactinomas found in male patients show distinct clinical features compared to those in female patients, which may warrant a different treatment strategy.  Method. To clarify their clinical features and to evaluate the treatment results, specifically the results of surgical treatment and non-surgical treatment solely with oral bromocriptine, we retrospectively reviewed our experience in male prolactinoma cases.  Findings. From 1988 to 1998, we had 184 pituitary adenoma patients, and thirteen of those were male patients with a pure prolactinoma. Of the thirteen patients, eight underwent transsphenoidal surgery followed by oral bromocriptine (surgical group), and five were treated solely with bromocriptine or terguride (non-surgical group). In both groups, the visual symptoms and signs resolved after the treatment, and the serum prolactin levels were normalised with minimal maintenance dose of bromocriptine. Notably, improvement of the visual symptom in the three non-surgically treated patients was observed within a week following the bromocriptine administration.  Interpretation. Although surgery would continue to play an important part of treatment in some cases with a large tumour, our experience suggests that drug treatment without surgery can be a safe and effective option in the management of male prolactinoma patients.     

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)     

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.     

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.     

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.     

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)     

The surgical treatment of non-functioning pituitary adenomas in the ninth decade

There are no reports of surgical treatment for non-functioning pituitary adenomas in the 9th decade of life, and it is thought that these patients often select conservative treatment and observation, because of their worry about deterioration of their general condition due to invasive surgery and because hypopituitarism and other medical problems are often present. However, it is also true that there is necessity for considering surgical treatment for the pituitary adenomas even in the 9th decade when there is a complaint of visual disturbance. We carried out the palliative surgical removal of three non-functioning pituitary adenomas with visual disturbance in the 9th decade and report these surgical treatments and outcomes. The improvement of visual disturbance was obtained in all three cases. The only perioperative complication was pneumothorax caused by barotrauma. The palliative transsphenoidal surgical removal of non-functioning pituitary adenomas for the purpose of improvement of visual disturbance is a safe procedure in the 9th decade of life.     

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.     

Results of surgical management of 319 pituitary adenomas

Summary Of the 510 patients with pituitary adenoma treated surgically at our hospital in the period 1956–1984 319 were treated by the microsurgical technique, in the period 1973–1984, 235 by transsphenoidal approach and 84 by subfrontal-pterional approach. The transsphenoidal route was used almost exclusively in microadenomas, in intrasellar adenomas, in suprasellar adenomas with midline development, in adenomas invading the sphenoidal sinus and in haemorrhagic adenomas with considerable suprasellar development. In some giant adenomas the transsphenoidal route was used in a first stage operation for debulking the tumour, later removed by transcranial route. The latter route was preferred in large adenomas and especially in adenomas with laterosellar development. In some patients with PRL secreting adenomas post-operative treatment with bromocriptine proved useful when the hormone levels failed to noramlize. Post-operative radiotherapy was of value in invasive adenomas and in cases in which tumour removal was not radical.     

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.     

Coexisting corticotroph and lactotroph adenomas: case report with reference to the relationship of corticotropin and prolactin excess.

A 57-year-old obese woman with hypertension, diabetes mellitus, osteoporosis, and a 40-year history of secondary amenorrhea was diagnosed with corticotropin-dependent Cushing's syndrome. Dynamic endocrine testing and radiological evaluation did not reveal definitively the source of the excess corticotropin. Bilateral adrenalectomy was performed with resolution of the signs and symptoms of hypercortisolism. Four years later, the patient was noted to have rising serum corticotropin levels and an enlarging pituitary mass; hyperprolactinemia also was documented. A diagnosis of Nelson-Salassa syndrome was made, and she underwent a transsphenoidal adenomectomy. A histological examination of the specimen revealed two distinct, albeit contiguous, adenomas: a corticotroph adenoma and a lactotroph adenoma. Postoperatively, the serum prolactin and corticotropin levels decreased significantly. Although the stalk section effect resulting from compression by a pituitary adenoma can raise serum prolactin levels, a concurrent lactotroph adenoma should be considered in patients with nonfunctional or functional pituitary adenomas of other types associated with significantly elevated prolactin levels. The mechanisms underlying simultaneous adrenocorticotropic hormone and prolactin excess are discussed.     

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).     

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.     

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.     

Sarcomatous transformation of a prolactinoma associated with development of a fatal internal carotid artery pseudoaneurysm--case report

A 21-year-old female with a 5-year history of prolactinoma was referred to our hospital because of cerebrospinal fluid leakage and meningitis immediately following a third transsphenoidal operation for a rapidly growing tumor. Histological examination of the tumor removed at the second transsphenoidal operation found atypical epithelial and sarcomatous components. Administration of bromocriptine, radiotherapy, and chemotherapy were initiated. Emergent craniotomy was required for rapid regrowth of the tumor. Histological examination found predominant sarcomatous components. Tumor growth was difficult to control. The patient died of subarachnoid hemorrhage due to rupture of a pseudoaneurysm involving the C1 portion of the right internal carotid artery. Pituitary adenoma rarely shows malignant transformation. In this case, prolactinoma underwent malignant change to sarcoma. Development of the pseudoaneurysm may have resulted from surgical manipulation, radiotherapy, or tumor invasion.     

Endonasal endoscopic transsphenoidal chiasmapexy with silicone plates for empty sella syndrome: technical note

Silicone plates sutured together to form blocks were used for extradural elevation of the sella floor in two patients who underwent chiasmapexy for visual disturbance associated with empty sella syndrome. A 36-year-old woman had been treated for prolactinoma for about 19 years with bromocriptine and then presented with left visual disturbance. A 79-year-old man presented with right blurred vision of unknown cause other than empty sella. The sella turcica was accessed via the endonasal transsphenoidal approach under endoscopic guidance. The bony sellar floor was opened with a drill. Two or three pieces of 1-mm-thick silicone plate were sutured to make a block. Two or three blocks were inserted into the epidural space to elevate the sellar contents. Visual symptoms improved in both patients. Silicone is biocompatible and not absorbable. Silicone plates are elastic and easy to handle during insertion, but firm enough to support the sella. The elevation can be adjusted by changing the number of plates in the block. The endonasal endoscopic approach is minimally invasive and particularly suitable for transsphenoidal extradural chiasmapexy for empty sella syndrome.     

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.     

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.     

Triple Pituitary Adenoma in Cushing's Disease: Case Report

Summary A case of a triple pituitary adenoma identified in a surgically removed pituitary gland from a 52-year-old woman operated on for Cushing's disease is presented. The histology revealed 3 distinctly separate microadenomas, 1 corticotroph and 2 immunoreactive for prolactin (PRL). The latter were apparently silent, since the serum PRL levels were within normal range. The problems associated with the inability to identify multiple adenomas pre-operatively and the possible failure of selective transsphenoidal adenomectomy in case of multiple adenomas are emphasised.