[Results of treatment for male prolactinomas]
[Article in Japanese]
Iwai Y, Yamanaka K, Ishiguro T, Morikawa T, Matsuzaka Y, Komiyama M, Yasui T.
Department of Neurosurgery, Osaka City General Hospital, 2-13-22 Miyakojima-hondori, Miyakojima-ku, Osaka-city, Osaka 534-0021, Japan.
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.
PMID: 12491580 [PubMed - indexed for MEDLINE]
Clinical features and medical treatment of male prolactinomas.
Asano S, Ueki K, Suzuki I, Kirino T.
Department of Neurosurgery, The University of Tokyo Hospital, Japan.
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.
PMID: 11482696 [PubMed - indexed for MEDLINE]
Giant prolactinomas: clinical management and long-term follow up.
Shrivastava RK, Arginteanu MS, King WA, Post KD.
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.
PMID: 12186457 [PubMed - indexed for MEDLINE]
Rapid re-expansion of a macroprolactinoma after early discontinuation of bromocriptine.
Orrego JJ, Chandler WF, Barkan AL.
Pituitary and Neuroendocrine Center, Section of Neurosurgery, Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Prolactin (PRL)-secreting pituitary adenomas are the most common functioning pituitary tumors. Medical treatment with dopamine agonists is the therapy of choice for macroprolactinomas (> or = 10 mm). Withdrawal of bromocriptine after weeks or months of uninterrupted therapy has been associated with rapid tumor re-expansion as evidenced by x-ray and CT scanning of the pituitary region. We report a patient with a giant macroprolactinoma who had a dramatic response to bromocriptine (tumor volume shrinkage of 53% within a month) but rapid re-expansion to its original dimensions one week after discontinuation of bromocriptine. To our knowledge, this is the first time that the rapid shrinkage/re-expansion of a macroprolactinoma has been documented with serial MRI scans.
PMID: 11383485 [PubMed - indexed for MEDLINE]
Results of primary treatment with bromocriptine of prolactinomas with extrasellar extension.
van 't Verlaat JW, Croughs RJ, Hendriks MJ, Bosma NJ.
Department of Neurosurgery, University Hospital Utrecht, The Netherlands.
Nineteen patients, seven women and twelve men, with macroprolactinomas characterized by extrasellar extension and basal prolactin levels above 6 U/l were treated with 10-20 mg bromocriptine daily in four divided doses for a mean period of 3.4 years (range 1.5-5.5 years). Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in sixteen patients. Tumor size was reduced by more than 75% in seventeen patients and by 50-75% in two patients. Tumor reduction was associated with the development of a partial empty sella in fourteen cases. In seventeen cases the pituitary became visible. Diminished visual acuity (six patients), bitemporal hemianopia (nine patients), unilateral and bilateral central scotomas (three patients) and oculomotor palsy (two patients) improved or normalized in all cases. Hypogonadism (all patients), hypothyroidism (nine patients) and hypocorticism (four patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10-20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumor size. The good results in this study may be related to the continued use of a fixed dose regimen of bromocriptine regardless of the plasma prolactin lowering effect.
PMID: 2311021 [PubMed - indexed for MEDLINE]
Extrasellar prolactinomas: successful management of 24 patients using bromocriptine.
Sieck JO, Niles NL, Jinkins JR, Al-Mefty O, el-Akkad S, Woodhouse N.
24 patients with an extrasellar prolactinoma (mean prolactin 4,722 ng/ml), 8 of whom had previously had surgery, received 5-40 mg bromocriptine daily for 13-252 weeks. The mean prolactin level had fallen 89% at 2 days, 95% at 6 weeks, and 15 patients achieved normal values. Tumor shrinkage occurred in all 9 patients rescanned within 2 weeks and later was documented in 23; in 18 the extrasellar tumour disappeared. 12 patients had visual abnormalities; 7, including 2 who had been completely blind, improved within 1 week. 2 patients had normal prolactin levels after withdrawal of bromocriptine, 1 following radiotherapy and the other during two uncomplicated pregnancies. Bromocriptine is safe and effective. We conclude that medical treatment should always precede surgery unless pituitary apoplexy causes sudden deterioration of vision. Most patients will subsequently require radiotherapy or surgery for permanent cure.
PMID: 3949288 [PubMed - indexed for MEDLINE]
· J Clin Endocrinol Metab. 2001 Apr;86(4):1838-9.
Primary medical therapy of micro- and macroprolactinomas in men.
Pinzone JJ, Katznelson L, Danila DC, Pauler DK, Miller CS, Klibanski A.
Neuroendocrine Unit and the General Clinical Research Center, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
The presentation and long-term therapeutic responses of PRL-secreting pituitary tumors in men have been only partially studied. Gender-specific differences in tumor size at clinical presentation and possible differences in tumor biology in men compared to women make it important to determine treatment outcomes of male patients with prolactinomas. We performed a retrospective review of men with prolactinomas medically managed at Massachusetts General Hospital between 1980 and 1997. We identified 46 male patients with prolactinomas managed with medical therapy alone. Twelve patients had microadenomas, defined as a serum PRL level greater than 15 ng/mL and a normal pituitary scan or a tumor smaller than 1 cm. Thirty-four patients had macroprolactinomas, defined by a serum PRL greater than 200 ng/mL and pituitary adenoma larger than 1 cm. Bromocriptine, quinagolide, and/or cabergoline were administered as medical therapy. All patients had at least one follow-up visit, and the most recent serum PRL measurement after initiating dopamine agonist therapy was reported. Baseline clinical characteristics for patients with macroprolactinomas and microprolactinomas showed a larger proportion of patients with macroprolactinomas reporting a history of headache (74% vs. 0%), whereas the prevalence of sexual dysfunction and testosterone deficiency was similar between the two groups. Median serum PRL at presentation was 99 ng/mL (range, 16-385 ng/mL) vs. 1,415 ng/mL (range, 387-67,900 ng/mL), in the microprolactinoma and macroprolactinoma groups, respectively. A normal PRL level was achieved in a similar percentage of men with microprolactinomas vs. macroprolactinomas (83% vs. 79%, respectively). Although the majority of patients in both groups were treated with bromocriptine, a comparable number of patients with microprolactinomas vs. macroprolactinomas achieved a normal PRL level with cabergoline therapy. The response rates for bromocriptine and cabergoline were similar in both groups. No patient with a microprolactinoma required hormone replacement therapy, in contrast to patients with macroprolactinomas, who required thyroid, testosterone, and/or glucocorticoid replacement therapy. No patient had evidence of an increase in tumor size during therapy. In summary, we investigated the clinical presentation and treatment outcome in men with prolactinomas. We found that normalization of serum PRL levels occurs in approximately 80% of men with prolactinomas. Of importance, dopamine agonist administration yielded similar biochemical remission rates in men with microprolactinomas and macroprolactinomas.
· Clinical Trial
PMID: 10999785 [PubMed - indexed for MEDLINE]
Prolactinoma in 53 men: clinical characteristics and modes of treatment (male prolactinoma).
Berezin M, Shimon I, Hadani M.
Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel.
The data of 53 men treated for hyperprolactinemia were reviewed retrospectively to determine the efficacy of the medical and surgical treatment. The clinical assessment, radiological and neuro-ophthalmological investigations and hormonal measurements were performed before treatment as well as during the follow-up period. Imaging evaluation included computed tomography and/or nuclear magnetic resonance of the pituitary. The hormonal profile examined was PRL, FSH, LH and testosterone, as well as TSH, T4, T3 and cortisol. Thirty patients were treated solely by dopamine agonists (DA), twenty-two men had pituitary surgery in addition to DA treatment, and one patient was operated with no need for medical treatment. Decreased sexual function was the most frequent presenting symptom (85% of the men). Most of the patients had large invasive macroadenomas, with suprasellar extension. More than 40% had visual field defects. Baseline PRL (mean +/- SE) was 51,842 +/- 9,292 mU/L and decreased to a level below 575 mU/L in 70% of the patients after DA therapy. Mean testosterone, FSH, and LH levels increased slightly but significantly from the low baseline values. Complete clinical response to DA was achieved in 49% of the men
and the tumor mass disappeared entirely in 21%, and incompletely in 42%. The surgical success rate (transsphenoidal or trans-cranial operation) was low--only one of the 23 patients operated recovered completely, and most of the patients were left with hormonal deficits and hyperprolactinemia. These findings indicate that continuous medical treatment with DA should be the preferred mode of treatment for male prolactinomas. Removal of these large tumors is recommended only when the tumors are life-threatening or if drug resistance or severe adverse reactions to DA develop.
· Clinical Trial
PMID: 7594238 [PubMed - indexed for MEDLINE]
Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal.
Passos VQ, Souza JJ, Musolino NR, Bronstein MD.
Neuroendocrine Unit, Hospital das Clinicas, University of Sao Paulo Medical School, 05403-000, Sao Paulo, Brazil.
Bromocriptine (BRC) and other dopamine agonist drugs are the first-choice treatment for prolactinomas. However, the major disadvantage is the need for prolonged therapy. We retrospectively studied 131 patients [62 microprolactinoma (MIC), 69 macroprolactinoma (MAC)], who achieved serum prolactin (PRL) normalization during BRC use. Twenty-seven percent of them (31% MIC and 69% MAC) underwent previous surgery. Twenty-seven patients (20.6%: 25.8% MIC and 15.9% MAC) persisted with normoprolactinemia after a median time of 44 months of BRC withdrawal. The median time of BRC use was 47 months. There were no statistically significant differences regarding age, gender, BRC initial dose, length of BRC use, tumor size, pregnancy during treatment, previous surgery, or radiotherapy among patients who persisted with normoprolactinemia and those who did not, using both univariate and multivariate analysis. BRC-induced prolactinoma cell alterations are highly controversial; and so, whether the mechanism of PRL normalization after BRC withdrawal is related to BRC use or whether it is attributable to natural history is a matter for debate. A periodic assessment of PRL levels during BRC (and other dopamine-agonist drugs) withdrawal is recommended to avoid the unnecessary maintenance of therapy in a subset of patients with prolactinomas.
PMID: 12161478 [PubMed - indexed for MEDLINE]
· Clin Endocrinol (Oxf). 1991 Mar;34(3):173-4.
Withdrawal of bromocriptine after long-term therapy for macroprolactinomas; effect on plasma prolactin and tumour size.
van 't Verlaat JW, Croughs RJ.
Department of Neurosurgery, Rudolf Magnus Institute, Academic Hospital, Medical Faculty, Utrecht, The Netherlands.
The present study describes the effect on plasma prolactin values and tumour size of bromocriptine withdrawal in 12 patients who had been treated for macroprolactinomas for a period of 3.5-7 (mean 4.9) years. Pretreatment plasma prolactin values ranged from 12,000 to 210,000 (mean: 66,000) mU/l. Immediately before bromocriptine withdrawal plasma prolactin values were in the normal range (less than 350 mU/l for men; less than 450 mU/l for women). Bromocriptine treatment was associated with tumour reduction in all cases. The following observations were made upon withdrawal of bromocriptine: (1) In 11 patients hyperprolactinaemia redeveloped although plasma prolactin levels remained below 600 mU/l in two of these patients during a follow-up period of 1 year. In the other nine patients bromocriptine treatment was reinstituted after 4-12 weeks. (2) Hyperprolactinaemia was associated with tumour reexpansion in one case and increased density of the tumour in two cases. (3) In one patient plasma prolactin remained undetectable during a follow-up period of 1 year and no tumour re-expansion was found. It is concluded that tumour regrowth is uncommon and of small extent after cessation of long-term bromocriptine treatment for macroprolactinomas.
PMID: 2036725 [PubMed - indexed for MEDLINE]
Mucocele-like formation leading to neurological symptoms in prolactin-secreting pituitary adenomas under dopamine agonist therapy.
Abe T, Ludecke DK.
Department of Neurosurgery, Showa University School of Medicine, Tokyo, Japan.
BACKGROUND: Mucocele-like formation associated with pituitary adenomas, to the best of our knowledge, has been paid little attention. We report three adult male patients with a mucocele-like formation that developed behind the tumor and led to neurological symptoms in prolactin-secreting pituitary adenomas (prolactinomas) under dopamine agonist therapy. CLINICAL PRESENTATION: Three adult male patients with prolactinomas developed hyperprolactinemia and new neurological symptoms during dopamine agonist treatment. In each case, the pathogenesis of these symptoms was due in part to a mass enlargement with development of a mucocele-like formation behind a prolactinoma. In our patients, a prolactinoma with a suprasellar extension originally filled the sphenoid sinus. When dopamine agonist therapy became ineffective, new symptoms, such as progressive visual impairment other than typical hemianopsia or headache, developed and mass enlargement was found on MRI. MRI demonstrated two different components: an enhancing prolactinoma and a nonenhancing mucocele-like formation behind the tumor. Two patients had compression of the optic nerves by a mass. Transnasal removal of mucoceles and adenomas led to resolution of the neurological symptoms. CONCLUSION: Early suspicion of a mucocele-like formation under dopamine agonist therapy for prolactinomas is important in order to avoid a delay in surgery, because a change in medical treatment will be ineffective.
PMID: 10511086 [PubMed - indexed for MEDLINE]
Diagnosis and drug therapy of prolactinoma.
Ciccarelli E, Camanni F.
Division of Endocrinology, University of Turin, Italy.
A prolactin-secreting pituitary tumour is the most frequent cause of hyperprolactinaemia that commonly occurs in clinical practice. Prolactinomas occur more frequently in women than in men and may differ in size, invasive growth and secretory activity. At presentation, macroadenomas are more frequently diagnosed in men. Specific immunohistochemical stains are necessary to prove the presence of prolactin in the tumour cells. The main investigations in the diagnosis of a prolactin-secreting adenoma are hormonal and radiological. As prolactin is a pulsatile hormone, it is a general rule to obtain several blood samples by taking a single sample on 3 separate days or 3 sequential samples (every 30 minutes) in restful conditions. Prolactin levels of 100 to 200 micrograms/L are commonly considered diagnostic for the presence of a prolactinoma; however, prolactinoma cannot be excluded in the presence of lower levels, and prolactin levels > 100 micrograms/L are present in some patients with idiopathic hyperprolactinaemia. Several dynamic function tests have been proposed to differentiate idiopathic from tumorous hyperprolactinaemia. Although they could be used for group discrimination, these tests cannot be used for individual patients. To differentiate between a prolactinoma and a pseudoprolactinoma, thyrotrophin response to a dopamine receptor antagonist may be used, as only prolactinomas may have an increased response. A short course of dopaminergic drugs may also be of some help, as in macroprolactinomas only a shrinkage may be observed. After hyperprolactinaemia is confirmed, imaging with computerised tomography (CT) and magnetic resonance imaging (MRI) are necessary to define the presence of a lesion compatible with a pituitary tumour. There is now a general agreement that medical therapy is of first choice in patients with prolactinomas. Bromocriptine, the most common drug used in this condition, is a semisynthetic ergot alkaloid that directly stimulates specific pituitary cell membrane dopamine D2 receptors and inhibits prolactin synthesis and secretion. In most patients, a reduction or normalisation of prolactin levels is usually observed, together with the disappearance or improvement of clinical symptoms. The sensitivity to bromocriptine is variable and patients may need different dose of the drug. Bromocriptine is also able to shrink the tumour in most patients; however, a few reports of disease progression during therapy have been described. The need for close follow-up, including prolactin levels and CT or MRI studies, is therefore emphasised. Bromocriptine is conventionally given in 2 or 3 daily doses; however, a single evening dose has been shown to be equally effective. Bromocriptine is usually well tolerated by the majority of patients; some adverse effects (nausea, vomiting, postural hypotension) may be initially present, but they usually wear off in time. To prevent such adverse effects it is advisable to start treatment with a low dose during the evening meal and gradually increase the dose over days or weeks. A few patients are unable to tolerate oral bromocriptine, so different formulations of bromocriptine or alternative dopamine agonist drugs (lisuride, terguride, metergoline, dihydroergocryptine, quinagolide, cabergoline, pergolide) have been proposed. Of particular clinical relevance because of their good tolerability and sustained activity are cabergoline and quinagolide. Particular attention should be paid to pregnancy in prolactinoma patients, as tumour enlargement has been reported. As the risk for this occurrence is low in patients with microprolactinoma, there is a general agreement that the drug can be stopped once pregnancy is diagnosed. In patients with macroprolactinoma the risk of tumour enlargement is higher. Therefore, primary therapy with bromocriptine until the tumour has shrank is suggested before pregnancy is attempted. Bromocriptine should be stopped as soon as pregnancy is confirmed, but re
· Review, Tutorial
PMID: 8736617 [PubMed - indexed for MEDLINE]
The effect of dopamine agonist therapy on large functionless pituitary tumours.
Grossman A, Ross R, Charlesworth M, Adams CB, Wass JA, Doniach I, Besser GM.
Fifteen patients (12 male) with large pituitary tumours and serum prolactin levels below 1000 mU/l were given dopamine agonist therapy (bromocriptine, mesulergine or pergolide) for a mean of 9 months (range 3-36 months). Serum prolactin became undetectable in all. Despite this, significant suprasellar extensions and any associated neurological defect remained in 14 patients, who therefore were referred for surgery. In one patient there was evidence of spontaneous pituitary infarction unrelated to dopamine agonist therapy. At operation 12 patients had apparently functionless pituitary adenomas which failed to immunostain for prolactin, one had an epidermoid cyst and one a Rathke's pouch cyst. We conclude that patients with large pituitary tumours and only a mildly elevated serum prolactin are unlikely to have prolactinomas, and that such tumours are not likely to show significant tumour shrinkage with medical treatment with dopamine agonists.
PMID: 4028461 [PubMed - indexed for MEDLINE]
Necrotic changes in prolactinomas after long term administration of bromocriptine.
Gen M, Uozumi T, Ohta M, Ito A, Kajiwara H, Mori S.
Six prolactinoma patients were studied endocrinologically and their tumors were examined histologically after long term bromocriptine therapy. In patient 1 with a large prolactinoma, a marked reduction in size and a remarkable decrease in elevated serum PRL levels occurred after bromocriptine treatment for 8 months. The histological findings consisted of two components, i.e. shrunken island-like cell nests and acellular spaces. Some degenerative and necrotic tumor cells, hyaline substance, and fibrosis were observed with light and electron microscopy in these acellular spaces. Island-like cell nests consisted of atrophic cells having disproportionally scanty cytoplasm. The same histological findings were observed in four other patients. However, in another patient whose tumor decreased in size only slightly during bromocriptine therapy, the specimen had few acellular spaces. Thus, long term bromocriptine treatment of patients with prolactinomas may result in necrosis of some adenoma cells in some patients.
PMID: 6746860 [PubMed - indexed for MEDLINE]
Treatment of macroprolactinomas at Auckland Hospital 1975-91.
Wallace EA, Holdaway IM.
Department of Endocrinology, Auckland Hospital.
AIM. A retrospective review of management of patients with macroprolactinomas at Auckland Hospital 1974-93 to determine the efficacy of treatment. METHODS. Patients were identified from departmental patient disease index records and treatment outcome assessed. RESULTS. Thirty four patients (24 male, 10 female) were identified. The mean serum prolactin was 89,700mIU/L. Visual field defects were present in 20 and 24 were hypogonadal at presentation. Initial treatment was with bromocriptine (n = 24) or surgery (n = 7). Twelve medically treated patients were subsequently treated surgically (3 because of pituitary haemorrhage or infarction, nine because of slow or absent response to medication). Visual field improvement was similar in the medical and surgical groups and major treatment complications occurred in 3 of the medical and 3 of the surgical patients. Radiotherapy was given to 25 patients. Overall treatment responses over a mean follow up of 4 years were similar in surgically and medically treated patients. Overall only a third of patients had a normal serum prolactin at last follow up, pregnancy had occurred in 20% of potentially fertile patients and 35% were hypopituitary. CONCLUSIONS. Bromocriptine is a satisfactory first line treatment for macroprolactinomas, but although treatment reduces tumour size and reverses field defects in 75% of cases only one third of patients achieve a normal prolactin over medium term follow up.
PMID: 7885646 [PubMed - indexed for MEDLINE]
[Prolactinoma in man: clinical and histological characteristics]
[Article in French]
Trouillas J, Delgrange E, Jouanneau E, Maiter D, Guigard MP, Donckier J, Perrin G, Jan M, Tourniaire J.
Laboratoire d'Histologie et Embryologie moleculaires, unite INSERM U433, Faculte de medecine Lyon-RTH Laennec, 69372 Lyon cedex 08, France.
Prolactinoma usually occurs a small intrasellar tumor in women or as a large tumor in men. To determine whether the predominance of macroprolactinomas in men is due to a delay in diagnosis as has been suggested, or whether there is a sex-related difference in growth rate we conducted a retrospective study in 45 men and 51 women with prolactinomas. Preoperative prolactin level (PRL) was 2,789 573 ng/ml and mean tumor size was 26 2 mm. Prolactin levels and tumor size were significantly higher in women (292 74 ng/ml and 10 1 mm; p<0.01). There was no correlation with age at diagnosis or duration of symptoms. Giant tumors were only observed in men (n=8). Frequency of resistance to bromocriptine (30% vs 5%, p<0.01) and invasive tumors (52% vs 27%, p<0.001) were significantly higher in men than in women. Likewise, proliferation rate was higher for the prolactinomas in men (Ki-67: 2.6 1.1% positive nuclei vs 0.4 0.2%; p=0.08; PCNA: 5.0 2.3% vs 3.7 1.1%). In conclusion, prolactinomas in men are more aggressive than in women. They grow rapidly, often invade the cavernous sinus and are resistant to bromocriptine; proliferation rates can be increased.
PMID: 10970951 [PubMed - indexed for MEDLINE]
The neurosurgical management of prolactinomas.
Gokalp HZ, Deda H, Attar A, Ugur HC, Arasil E, Egemen N.
Department of Neurosurgery, Faculty of Medicine, University of Ankara, Turkey.
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).
PMID: 11126446 [PubMed - indexed for MEDLINE]
The use of surgery for the treatment of prolactinomas.
van't Verlaat JW.
Department of Neurosurgery, University Hospital, Utrecht, The Netherlands.
Success with trans-sphenoidal surgery for microprolactinomas is good (57 to 93% cure rate) but tumours can recur. Conversely, the results of surgery for macroprolactinomas are not so good (14 to 39% cure rate) and cure is rarely effected when plasma prolactin levels are > 10 U/l. Surgical therapy for prolactinoma should be reserved for patients with dopaminergic resistance or intolerance and complications (e.g. haemorrhage and rhinorrhoea) to dopamine agonist therapy. Trans-sphenoidal surgery was used to treat 11 microprolactinoma patients who had compliance problems to dopaminergic therapy. Postoperative plasma prolactin levels were normal in all patients. During follow-up (range 0.5 to 8 years, mean 3.9 years) six patients remained normoprolactinaemic, four patients developed slightly elevated plasma prolactin levels ( < 0.7 U/l), and one patient developed a macroadenoma resistant to bromocriptine and CV 205-502. He underwent a second operation, followed by radiotherapy and bromocriptine. His plasma prolactin was reduced to 3.3 U/l. One patient with a prolactinoma extending into the left cavernous sinus had a tumour cyst in the left temporal lobe. During treatment with CV 205-502 he developed a haemorrhage in the tumour cyst necessitating craniotomy.
· Review, Tutorial
PMID: 8103958 [PubMed - indexed for MEDLINE]
Comparison of endonasal endoscopic surgery and sublabial microsurgery for prolactinomas.
Cho DY, Liau WR.
Department of Neurosurgery, China Medical College Hospital, Taichung, Taiwan, Republic of China.
BACKGROUND: Endonasal endoscopy is a promising minimally invasive surgery for the treatment of pituitary adenomas; it is also a good alternative to traditional sublabial microsurgery. In this study, we compared endoscopic surgery with microsurgery and evaluated both for their safety and effectiveness. We chose prolactinomas for study because their hormone and symptomatic changes facilitated the comparison. METHODS: During the past five years, 44 randomized prolactinoma patients underwent pituitary adenomectomy. Group A (22 patients) underwent endonasal endoscopic surgery for prolactinomas. Group B (22 patients) underwent sublabial transsphenoidal microsurgery for prolactinomas. RESULTS: In groups A and B, patients with prolactinoma exhibited significantly reduced postoperative prolactin levels, return of menstrual cycle, and relief of galactorrhea, (Wilcoxon signed rank test) (p < 0.001). But there were no statistically significant differences in the effectiveness of the procedures used in group A and group B. Visual improvement in cases of macroadenoma was satisfactory in both groups. Hospital stay in group A ranged from 2-5 days, with a mean of 3.2 days. Hospital stay in group B ranged from 4-8 days with a mean of 5.3 days. The hospital stay for group A patients was shorter (2.1 days) than for group B (Student t test, p < 0.05). The operative time was shorter by 1 hour in Group A (mean: 1.7 hours vs. mean: 2.7 hours, p < 0.05). There were fewer complications in group A (4.5%) than in group B (27%), p < 0.05. CONCLUSIONS: The endoscopic era of pituitary surgery may be coming. Endonasal endoscopic surgery may have the same effectiveness as traditional microsurgery. However, endoscopic surgery may shorten hospital stay and operative time, and lead to fewer complications. It seems to be a good minimally invasive surgical technique for prolactinomas.
· Clinical Trial
· Randomized Controlled Trial
PMID: 12517610 [PubMed - indexed for MEDLINE ACROMEGALY
The role of growth hormone in the regulation of protein metabolism with particular reference to conditions of fasting.
Moller N, Norrelund H.
Medical Department M (Endocrinology and Diabetes), Arhus Kommunehospital, Arhus, Denmark.
Growth hormone (GH) has potent protein anabolic actions, as evidenced by a significant decrease in lean body mass and muscle mass in chronic GH deficiency, and vice versa in patients with acromegaly. Depending on the prevailing physiological conditions and on which tissues and which proteins are under examination, the mechanisms involved include both stimulation of protein synthesis and restriction of protein breakdown. Apart from the possible direct effects of GH on protein dynamics, a number of additional anabolic agents, such as insulin, insulin-like growth factor-I and free fatty acids (FFA), are activated. Some of the most recent studies in the field have demonstrated a decisive role of stimulation of lipolysis and high circulating levels of FFA in orchestrating the maintenance of the protein pool of the body. Copyright 2003 S. Karger AG, Basel
PMID: 12566723 [PubMed - in process]
[Effect of lanreotide on prolactin level in patients with pituitary mixed tumors]
[Article in French]
Wasko R, Sawicka J, Stachowiak C, Kozak W, Junik R, Sowinski J.
Clinique d'Endocrinologie, Academie de Medecine de l'Universite de Karol Marcinkowski de Poznan 60-355. Przybyszewskiego 49, Pologne.
Acromegaly is a disease caused by a pituitary tumor (somatotropinoma) or by ectopic secretion of GH or IGF-1. About 15% of tumors secrete not only GH but PRL as well. Last time a lanreotide and an octreotide (the somatostatine analogues) are useful in the therapy of acromegaly. We observed the influence of the lanreotide on GH and prolactin. We noticed that the lanreotide caused not only serum level reduction of a growth hormone but also prolactine in patients with mixed pituitary tumors.
PMID: 12527855 [PubMed - as supplied by publisher]
Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly.
Beauregard C, Truong U, Hardy J, Serri O.
OBJECTIVE: Acromegaly has long been associated with increased mortality but few long-term follow-up data are available in patients treated for this disease. We therefore studied a group of 103 patients who underwent transsphenoidal adenomectomy for acromegaly between 1970 and 1999 and were followed for one to 30 years. DESIGN AND PATIENTS: A retrospective chart review was performed on 103 patients living in the province of Quebec, Canada. Mortality data were obtained by hospital charts, contact with the patient's family or death certificates. Stringent biochemical criteria were used to define remission (random GH < 2.5 micro g/l, or GH nadir after an oral glucose load is < 1 micro g/l and IGF-I within the normal range) and patient survival in the group in remission and the group with persistent disease were compared to survival of the population of Quebec, Canada, using the probabilities of the Poisson distribution. RESULTS: There were four deaths in the perioperative period, one of which was directly related to surgery. Initial remission was obtained in 82% of microadenomas, 60% of macroadenomas and 24% of invasive adenomas. The long-term (>/= 10 years) remission rate for surgery alone was 52%. A second transsphenoidal surgery, radiation therapy and/or octreotide were used in a subset of patients with persistent disease. Long-term remission was obtained in 63% of patients. Five (mean age, 64 years) of the 57 patients in remission died; this rate did not differ significantly from the mortality rate expected in the general population (P = 0.18). Thirteen (mean age, 59.8 years) of the 34 patients with persistent disease died; this rate was significantly higher than that expected in the general population (P = 0.008). CONCLUSIONS: Our observations confirm that uncontrolled acromegaly increases mortality compared to the general population and that mortality rates similar to the general population are restored once remission is induced.
PMID: 12519417 [PubMed - in process]
From the Clinical Research Centers
Primary Medical Therapy of Micro- and Macroprolactinomas in Men1
Joseph J. Pinzone, Laurence Katznelson, Daniel C. Danila, Donna K. Pauler, Caleb S. Miller and Anne Klibanski
Neuroendocrine Unit and the General Clinical Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
The presentation and long-term therapeutic responses of PRL-secreting pituitary tumors in men have been only partially studied. Gender-specific differences in tumor size at clinical presentation and possible differences in tumor biology in men compared to women make it important to determine treatment outcomes of male patients with prolactinomas.
We performed a retrospective review of men with prolactinomas medically managed at Massachusetts General Hospital between 1980 and 1997. We identified 46 male patients with prolactinomas managed with medical therapy alone. Twelve patients had microadenomas, defined as a serum PRL level greater than 15 ng/mL and a normal pituitary scan or a tumor smaller than 1 cm. Thirty-four patients had macroprolactinomas, defined by a serum PRL greater than 200 ng/mL and pituitary adenoma larger than 1 cm. Bromocriptine, quinagolide, and/or cabergoline were administered as medical therapy. All patients had at least one follow-up visit, and the most recent serum PRL measurement after initiating dopamine agonist therapy was reported.
Baseline clinical characteristics for patients with macroprolactinomas and microprolactinomas showed a larger proportion of patients with macroprolactinomas reporting a history of headache (74% vs. 0%), whereas the prevalence of sexual dysfunction and testosterone deficiency was similar between the two groups. Median serum PRL at presentation was 99 ng/mL (range, 16–385 ng/mL) vs. 1415 ng/mL (range, 387–67,900 ng/mL), in the microprolactinoma and macroprolactinoma groups, respectively.
A normal PRL level was achieved in a similar percentage of men with microprolactinomas vs. macroprolactinomas (83% vs. 79%, respectively). Although the majority of patients in both groups were treated with bromocriptine, a comparable number of patients with microprolactinomas vs. macroprolactinomas achieved a normal PRL level with cabergoline therapy. The response rates for bromocriptine and cabergoline were similar in both groups. No patient with a microprolactinoma required hormone replacement therapy, in contrast to patients with macroprolactinomas, who required thyroid, testosterone, and/or glucocorticoid replacement therapy. No patient had evidence of an increase in tumor size during therapy.
In summary, we investigated the clinical presentation and treatment outcome in men with prolactinomas. We found that normalization of serum PRL levels occurs in approximately 80% of men with prolactinomas. Of importance, dopamine agonist administration yielded similar biochemical remission rates in men with microprolactinomas and macroprolactinomas.
VERKLARENDE WOORDENLIJST Acromegalie
Een ziekte die ontstaat als een hypofysegezwel veel groeihormoon produceert. Bijnieren
Kliertjes vlak boven de nieren gelegen die diverse hormonen produceren waaronder cortisol en adrenaline. Bromocriptine (merknaam: Parlodel)
Middel ter verlaging van het peil van het groeihormoon. Carpaal tunnelsyndroom
Tinteling en soms zwakte van de handen door samendrukking van de zenuw in de pols. Dit is ‘s nachts vaak erger. De symptomen verdwijnen als het peil van uw groeihormoon door behandeling daalt. Endocrien systeem
Het systeem van hormoon-vormende klieren overal in het lichaam, en de daardoor aangemaakte hormonen, die veel aspecten van het leven zoals groei en voortplanting reguleren. Endocrinoloog
Een internist die gespecialiseerd is in de behandeling van ziekten van het endocrien systeem. Gonaden
De geslachtsklieren - de eierstokken (ovaria) bij de vrouw, de zaadballen (testikels) bij de man. Groeihormoon
Een door de hypofyse aangemaakt hormoon dat de groeisnelheid reguleert. Het wordt voor namelijk tijdens de slaap aangemaakt. Hypofyse
Klier ter grootte van een erwt, gelegen in de schedelbasis. Deze klier reguleert de productie van hormonen door talrijke andere klieren in het lichaam. Hypopituitarisme
Te zwakke werking van de hypofyse waardoor aanmaak van de hypofyse-hormonen afneemt. Octreotide (merknaam: Sandostatine)
Een middel ter verlaging van het groeihormoon-peil. Parlodel
Merknaam van bromocriptine. Radiotherapie
Aandoening veroorzaakt door productie van teveel groeihormoon in de kindertijd, voor de groei is afgerond. Hierdoor worden mensen veel langer dan anders het geval zou zijn geweest. Sandostatine
Merknaam van octreotide. Schildklier
Een klier gelegen voor en opzij van de luchtpijp iets onder het strottenhoofd. Deze klier produceert hormonen die voor veel lichamelijke processen onmisbaar zijn. Transsfenoidale operatie
Een hypofyse-operatie waarbij een insnijding wordt gemaakt voor de boventanden en achter de bovenlip, of soms ook in de neus. Met dank aan Novartis Pharma BV, Arnhem