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Pituitary carcinoma is a rare entity comprising 0.1-0.2% of all pituitary tumors and presents significant diagnostic and therapeutic challenges. Intraspinal drop metastasis in these tumors is even rarer. We report a case of a prolactin secreting pituitary carcinoma with intracranial metastasis and multiple intraspinal drop metastasis. This is the first case where 68Gallium labelled [1,4,7,10 - tetraazacyclododecane - 1,4,7,10 - tetraacetic acid] -1- NaI3 - octreotide (68Ga-DOTANOC) whole-body positron emission tomography-computed tomography (PET-CT) has been used in a case of malignant prolactinoma, in an attempt to ascertain the somatostatin receptor (SSTR) expression on tumor cells. Through this paper, we suggest that SSTR targeted radionuclide therapy could have a potential role in aggressive pituitary tumors and pituitary carcinomas similar to the promising role of lutetium-labelled peptides in inoperable or metastasized gastroentero-pancreatic neuroendocrine tumors (GEP-NETs)., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Objective: A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations., Methods: The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing's disease, and prolactinomas were selected and included in the analysis., Results: For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%-98.0%), 44.0% (95% CI 35.0%-53.0%), and 17.0% (95% CI 13.0%-23.0%), respectively. For Cushing's disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%-95.0%), 48.0% (95% CI 35.0%-61.0%), and 21.0% (95% CI 13.0%-31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%-95.0%), 28.0% (95% CI 19.0%-39.0%), and 12.0% (95% CI 6.0%-24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes., Conclusions: SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.

BACKGROUND The aim of this study was to review outcomes of gamma knife radiosurgery (GKRS) for prolactinoma and report our experience with it. MATERIAL AND METHODS We reviewed the patient database in our center and identified 24 patients with prolactinoma who underwent GKRS from 1993 to 2016.  Complete endocrine, clinical, and radiological data were available on these individuals before and after GKRS. RESULTS Data from 5 males and 19 females with a median age of 30.5 years (range, 18.1 to 51.1) were reviewed. The median follow-up was 109.3 months (range, 23.2-269.3). The median margin dose of GKRS was 15 Gy (range, 10.5 to 23.6). In total, prolactin (PRL) normalization after GKRS was achieved in 66.7% of patients. Endocrine remission (normal PRL levels after discontinuation of dopamine agonists) was achieved in 10 patients (41.7%), and endocrine control (normal PRL levels while taking dopamine agonists) was achieved in 6 patients (25.0%). All of the patients showed tumor control. New-onset hypopituitarism post-GKRS occurred in 4 patients (16.7%). No new visual dysfunction or cranial nerve dysfunction were observed after GKRS. CONCLUSIONS For treatment of prolactinomas, GKRS may provide relatively high rates of endocrine remission and tumor control, as well as a low rate of new-onset hypopituitarism. GKRS may be an effective and safe treatment for prolactinomas.

Purpose: Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of dopamine agonist (DA)-resistant prolactinomas. In our study, we report on our experience in treating prolactinoma patients by GKRS., Methods: Twenty-eight patients were followed-up after GKRS for 26-195 months (median 140 months). Prior to GKRS, patients were treated with DAs and 9 of them (32.1%) underwent previous neurosurgery. Cavernous sinus invasion was present in 16 (57.1%) patients. Indications for GKRS were (i) resistance to DA treatment (17 patients), (ii) drug intolerance (5 patients), or (iii) attempts to reduce the dosage and/or shorten the length of DA treatment (6 patients)., Results: After GKRS, normoprolactinaemia was achieved in 82.1% of patients, out of which hormonal remission (normoprolactinaemia after discontinuation of DAs) was achieved in 13 (46.4%), and hormonal control (normoprolactinaemia while taking DAs) in 10 (35.7%) patients. GKRS arrested adenoma growth or decreased adenoma size in all cases. Two patients (8.3%) developed hypopituitarism after GKRS. Prolactinoma cystic transformation with expansive behaviour, manifested by bilateral hemianopsia, was observed in one patient., Conclusions: GKRS represents an effective treatment option, particularly for DA-resistant prolactinomas. Normoprolactinaemia was achieved in the majority of patients, either after discontinuation of, or while continuing to take, DAs. Tumour growth was arrested in all cases. The risk of the development of hypopituitarism can be limited if the safe dose to the pituitary and infundibulum is maintained.

The aim of the study was to evaluate the clinical features and long-term therapeutic outcome of giant prolactinoma (gPRLoma) in men and to compare them with those of a group of male patients with non-gPRL macroprolactinomas (non-gPRLomas). A retrospective and multicenter study of gPRLomas in men diagnosed in a 20-year period was performed. Clinical data and treatment outcome were registered. The diagnosis of gPRLoma was established when the maximal tumor diameter was ≥40 mm or the tumor had ≥20 mm of suprasellar extension associated to hyperprolactinemia (PRL>1000 ng/ml). Non-gPRLoma was considered when tumor diameter was  ≥ 10 mm and<40 mm associated to hyperprolactinemia (PRL≥200 ng/ml). Twenty-three patients with gPRLoma (age 38.3±13.5 years) followed for at least 3 months (follow-up 87.1±60.5 months, range 3-211 months) were evaluated. A group of 42 patients with non-gPRLoma (age 42±16.6 years; NS; follow-up 89±65.9 months, range 3-222 months; NS) served as a control group. More than half (56.5%) of the gPRLoma patients were younger than 40 years at diagnosis. Visual disturbances were significantly more common in gPRLoma than in non-gPRLoma patients (65.2 vs. 25.6%; p=0.004). Prevalence of hypopituitarism was similar in both groups of patients (73.9% vs. 80.9%; gPRLoma vs non-gPRLoma; NS). Serum PRL concentrations were significantly higher in gPRLoma than in non-gPRLoma patients [median (IR), 3978 ng/ml (1179-9012) vs. 907 ng/ml (428-3119); p<0.001]. Maximum tumor diameter in gPRLomas was 4.8±0.8 cm and 2.4±0.7 cm in non-gPRLoma (p<0.001). All patients were treated with dopamine agonists (DA). Twelve (52.2%) gPRLoma patients and 32 (73.8%) non-gPRLoma patients were treated with DA as monotherapy (p=0.045). Surgery was used in 12 (52.2%) gPRLoma patients and in 12 (28.6%) non-gPRLoma patients (p=0.054). Lastly, radiotherapy was used in 5 (21.7%) gPRLoma patients and in 6 (14.2%) non-gPRLoma patients (NS). At last visit, PRL was similar in both groups of patients [16 ng/ml (4-30) vs. 11 ng/ml (4-25); gPRLomas vs. non-gPRLomas; ns] and tumor size decreased significantly (p<0.001) in both groups of patients. Clinical cure (maintained normoprolactinemia without therapy for>1 year and no radiological evidence of pituitary tumor) was achieved in 2 (8.7%) gPRLoma patients and in 2 (4.8%) non-gPRLoma patients (NS). gPRLomas in men are usually diagnosed at a mean age of 40 years, an age similar to that of non-gPRLomas. The only clinical difference with non-gPRLomas is their greater prevalence of visual disturbances. The therapeutic approaches and tumor outcomes were similar to those obtained in patients with non-gPRLomas. Complete cure in gPRLoma is rare, but similar to that achieved in non-gPRLomas, reached in less than 10% of patients., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival., Design: Multicenter retrospective study by members of the French Society of Endocrinology., Methods: Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph ( n  = 23) or lactotroph ( n  = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment., Results: The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders ( P  = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success., Discussion: Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols., (© 2017 European Society of Endocrinology.)

Objectives: To determine the influence of secretory status on long-term outcome after fractionated radiotherapy (RT) for gross residual pituitary adenoma., Materials and Methods: This is a retrospective study of 116 consecutively treated patients who met the following inclusion criteria: tissue diagnosis of pituitary adenoma, visible tumor at the time of RT, treatment with fractionated RT, and imaging follow-up of ≥2 years. Hypersecretion of growth hormone, adrenocorticotrophic hormone, prolactin, or thyroid-stimulating hormone was documented in 30 patients (26%). The RT dose in most (78%) patients was 45 Gy at 1.8 Gy per fraction. The major outcome endpoint is clinical and biochemical control, meaning no growth on follow-up scans and normalization of hypersecretion, if present before RT., Results: Long-term tumor control was outstanding for nonsecretory tumors: 96% at 10 years. There was a major drop in the control rate of secretory tumors: 10-year clinical and biochemical control was 62% (P<0.0001 vs. 96%). Multivariate analysis confirmed secretory status as the only independent prognostic factor (variables analyzed were sex, age, tumor size, RT dose, and secretory status)., Conclusions: Secretory pituitary adenomas have a worse prognosis than nonsecretory tumors after 45 to 50 Gy of conventionally fractionated RT. As a result of this finding, our plan is to increase the intensity of RT in secretory tumors, but our data did not evaluate this approach. The treatment guidelines that we currently use in pituitary adenoma are as follows. Radiosurgery (20 to 30 Gy) is our first-choice treatment of a secretory tumor that cannot be completely resected. When treating gross residual pituitary adenoma with fractionated RT, we use the following dose schedules: Nonsecretory: 45 Gy at 1.8 Gy/fraction, once-daily fractionation. Secretory: 54 Gy at 1.8 Gy/fraction once daily or 55.2 Gy at 1.2 Gy/fraction with twice-daily treatment.

Purpose: There are limited treatment options for progressive atypical pituitary adenomas and carcinomas. Peptide receptor radionuclide therapy that targets somatostatin receptors has recently been proposed as a potential treatment option. The theoretical rationale for efficacy is elegant but evaluation of outcomes in the first patients treated for this indication is required to assess whether further study is warranted., Methods: We performed a case review of the three pituitary patients we have treated with (177)Lutetium DOTATATE in our institution (two atypical adenomas, one carcinoma) and dosimetric analysis of the radiation uptake in one patient., Results: Treatment was well tolerated. One patient with slowly progressive pituitary carcinoma has stable disease 40 months after completing the planned 4 cycles of treatment. Two patients with rapidly progressive atypical adenomas terminated treatment early due to continued disease progression. Dosimetric evaluation revealed inhomogenous uptake across the tumour (1.3-11.9 Gy with one cycle)., Conclusion: We have found mixed results in our first 3 patients with stable disease achieved only in the patient with the more slowly progressive tumour. As only a limited number of centres offer Peptide receptor radionuclide therapy, a formal study with prospective data collection may be feasible and if carried out should include dosimetric evaluation of absorbed dose.

We report a case of sarcomatous transformation of a prolactin (PRL)-producing pituitary adenoma in a 27-year-old man. He originally presented with bitemporal visual disturbance, headache, and hyperprolactinemia 8 years earlier. Tumor shrinkage was confirmed by magnetic resonance imaging (MRI) during treatment with dopamine-receptor agonist. However, 3 years later transsphenoidal surgery had to be performed because of tumor re-growth. Histopathological examination revealed a PRL-producing adenoma with fibrotic changes. One year later, he presented with right-sided visual disturbance, and tumor re-growth was confirmed using MRI. He underwent transcranial surgery, followed by radiation therapy (50 Gy in 25 fractions). The histological and immunostaining features were similar in both specimens obtained from the two operations. Four years later, he presented with left-sided visual disturbance, and tumor re-growth was confirmed using MRI. The mass lesion dramatically increased in size within 2 months, and partial removal of the tumor by craniotomy was performed. The specimen was histologically diagnosed as malignant fibrous histiocytoma (MFH). Regardless of aggressive chemotherapy, his clinical symptoms and imaging findings worsened rapidly. He died 7 months after the diagnosis of MFH. Because patients with pituitary tumor undergoing radiotherapy face the possibility of developing such neoplasm, long-term follow-up is required.

We evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm3 (range 0.3–11.6). The marginal tumor dose (median= 15 Gy, range 12–25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12–185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined asa decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six(27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging-defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy.

Pituitary adenomas are generally considered benign tumors; however, a subset of these tumors displays aggressive behavior and are not easily cured. The protocol for nonsurgical treatment of aggressive pituitary lesions is less standardized than that of other central nervous system tumors. Aggressive surgical treatment, radiation, dopamine agonists, antiangiogenic drugs, and other chemotherapeutics all have roles in the treatment of aggressive pituitary tumors. More studies are needed to improve outcomes for patients with aggressive pituitary tumors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Review the medical and surgical management of patients with prolactinomas and provide an in-depth appraisal of the role of radiotherapy in the treatment of prolactinomas. A thorough review of the pertinent literature was carried out and relevant topics were identified. Topics covered in this comprehensive review include: indications for the use of radiotherapy, choice between conventional radiotherapy and stereotactic radiosurgery, as well as the benefits and potential complications associated with each modality. Due to the excellent response rates with medical management, and rapid symptom relief afforded by resection or debulking surgery in patients who do not respond or tolerate medical therapy, radiotherapy is reserved for patients who do not respond to dopamine agonists and surgery. Both external beam radiotherapy and stereotactic radiosurgery retain important roles in the treatment of refractory or recurrent prolactinomas. Choosing the optimal approach is crucial in maximizing tumor control outcomes and minimizing the risks associated with treatment. The primary determinants of optimal radiation approach are proximity of the tumor to the optic apparatus and tumor size, with radiosurgery being our recommended treatment of choice unless the tumor is larger than 3-4 cm or within 3 mm of the optic nerves, chiasm or tracts. Optimal multidisciplinary management requires the identification of appropriate candidates for radiotherapy in order to take full advantage of treatment options available for each patient.

Background: Radiation therapy is often used in the treatment of pituitary tumor. Diplopia due to radiation damage to the ocular motor cranial nerves has been infrequently reported as a complication in this clinical setting., Methods: Retrospective case series of 6 patients (3 men and 3 women) with pituitary adenoma, all of whom developed diplopia following transsphenoidal resection of pituitary adenoma with subsequent radiation therapy. None had evidence of tumor involvement of the cavernous sinus., Results: Five patients developed sixth nerve palsies, 3 unilateral and 2 bilateral, and in 1 patient, a sixth nerve palsy was preceded by a fourth cranial nerve palsy. One patient developed third nerve palsy. Five of the 6 patients had a growth hormone-secreting pituitary tumor with acromegaly. Following transsphenoidal surgery in all 6 patients (2 had 2 surgeries), 4 had 2 radiation treatments consisting of either radiosurgery (2 patients) or external beam radiation followed by radiosurgery (2 patients)., Conclusions: Patients with pituitary tumors treated multiple times with various forms of radiation therapy are at risk to sustain ocular motor cranial nerve injury. The prevalence of acromegalic patients in this study reflects an aggressive attempt to salvage patients with recalcitrant growth hormone elevation and may place the patient at a greater risk for ocular motor cranial nerve damage.

Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. The most important clinical problems associated with prolactinomas are hypogonadism, infertility and hyposexuality. In patients with macroprolactinomas, mass effects, including visual field defects, headaches and neurological disturbances, can also occur. The objectives of therapy are normalization of prolactin levels, to restore eugonadism, and reduction of tumor mass, both of which can be achieved in the majority of patients by treatment with dopamine agonists. Given their association with minimal morbidity, these drugs currently represent the mainstay of treatment for prolactinomas. Novel data indicate that these agents can be successfully withdrawn in a subset of patients after normalization of prolactin levels and tumor disappearance, which suggests the possibility that medical therapy may not be required throughout life. Nevertheless, multimodal therapy that involves surgery, radiotherapy or both may be necessary in some cases, such as patients who are resistant to the effects of dopamine agonists or for those with atypical prolactinomas. This Review reports on efficacy and safety of pharmacotherapy in patients with prolactinomas.

A 62-year-old woman presented with simultaneous subarachnoid hemorrhage (SAH) and massive epistaxis. The patient had been treated for pituitary prolactinoma by two transsphenoidal surgeries, gamma knife radiosurgery, and conventional radiation therapy since age 43 years. Cerebral angiography showed left petrous internal carotid artery (ICA) aneurysm with slight stenosis on the adjacent left petrous ICA. She underwent superficial temporal artery-middle cerebral artery (STA-MCA) double anastomosis with endovascular internal trapping without complication the day after onset. Postoperative course was uneventful; the patient did not develop symptomatic vasospasm, recurrent epistaxis, or cerebrospinal fluid rhinorrhea. Postoperative angiography demonstrated complete disappearance of the aneurysm with patent STA-MCA anastomosis. The patient was discharged 2 months after surgery without neurological deficit. The present case is extremely rare with simultaneous onset of SAH and epistaxis caused by ruptured petrous ICA aneurysm. The transsphenoidal surgeries and radiation therapies might have been critical in the formation of the petrous ICA aneurysm.

Objective: To investigate the long-term outcome of fractionated stereotactic radiotherapy (FSRT) [45 Gy (range 45-54) in 25 fractions] in patients with pituitary adenomas characterized by tumour progression or hormonally active disease despite surgery and/or medical therapy., Design: This was an observational follow-up study of 5.25 years (median; range 1.7-10.4)., Patients and Measurements: Pituitary tumour volume, visual acuity/fields, hypersecretion, hypopituitarism, cerebrovascular disease, second brain tumours and mortality were examined at regular intervals after FSRT in 30 patients with pituitary adenomas (20 nonfunctioning macroadenomas, 10 functioning). Prior to FSRT, 83% had been operated 1-3 times, 47% had visual field deficits/impaired vision and 50% pituitary dysfunction. Progressive disease, stable disease, partial and complete tumour response were defined by MRI., Results: Tumour growth control was 100%. At the end of follow-up, 30% had stable disease, 60% partial and 10% complete tumour response. Visual function was preserved and 36% of patients with prior field deficits improved. GH decreased from 4.2 (range, 2.3-6.5) to 1.1 (range, 0.5-1.5) microg/l (P < 0.001) in patients with acromegaly, and medical therapy could be reduced. In large prolactinomas, partial response or complete tumour response was achieved. FSRT was well tolerated. Pituitary function remained normal in 27%, 33% of patients had stable dysfunction, 17% deteriorated further and 23% developed new dysfunction. There were no cerebrovascular events, second brain tumours or FSRT-related deaths., Conclusion: According to this long-term follow-up study, FSRT is an efficient and safe adjuvant therapy for pituitary adenomas refractory to conventional treatments.

Objective: The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator., Materials and Methods: Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1-18 months, with a median follow-up of 6 months., Results: Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3-18 months) with no in-field failures and were able to obtain encouraging toxicity profiles., Conclusion: Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity.

We report clinical presentation, response to medical treatment, and long-term follow-up of 39 children and adolescents with prolactinoma (F:M; 30:9) (30 macro and 9 microadenoma) diagnosed at the age of 9-20 years. Mean duration of follow up was 56 months. All patients were treated with bromocriptine (BC) at doses ranging from 2.5 to 20 mg/day or by cabergoline at doses ranging from 0.5 to 2 mg/week orally. Two patients received external conventional radiotherapy after surgery. In patients with macroprolactinoma (F:M; 21:9), headache and/or visual defects were the first symptoms. All females had primary or secondary amenorrhea. Growth arrest was not observed in any patient and pubertal development was appropriate for their age. Spontaneous or provocative galactorrhea was observed in 23 patients (all females) and none of male patient had gynecomastia. Mean serum prolactin (PRL) concentration at the time of diagnosis was 322.50 ng/ml in patients with microadenoma, 522.38 ng/ml in patients with macroadenoma and 2,294.86 ng/ml in patients with macroadenoma with suprasellar extension. In 25 patients, BC normalized PRL levels and caused variable, but significant, tumor shrinkage. Cabergoline normalized PRL concentrations in 14 patients. Pregnancy occurred in 6 patients while on treatment. Pregnancies were uncomplicated, and the patients delivered normal newborns at term. Impairment of other pituitary hormone secretion was documented at the time of diagnosis in only one patient. Postoperatively six patients had other pituitary hormone deficiencies. In conclusion, the medical treatment with dopaminergic compounds is effective and safe in patients with prolactinoma with onset in childhood, allowing preservation of the anterior pituitary function.

There are two principal types of treatment for pituitary adenomas: fractionated conventional radiation therapy, based on biological selectivity, and radiosurgery, which is delivered in a single dose, based on anatomic selectivity and indicated preferentially for small tumors sufficiently distant from the optic chiasm. Conventional radiation therapy is effective against secretion in 60-80% of cases and radiosurgery in 40-50%, depending on the type of secretion. Maximum antisecretory efficacy is not reached immediately: this delay is longer for conventional radiation therapy (5-10 years) than for radiosurgery (2-3 years). In both cases, antisecretory treatment must be started, while awaiting remission. Radiation therapy and radiosurgery make it possible to stabilize or diminish tumor volume in 70-100% of cases. This is especially useful in the case of an active residue after surgery for non-secreting adenoma, but the long-term side effects of radiation must be borne in mind. The principal side effect is the onset of a pituitary deficiency (in more than 50% of cases after radiation therapy, 20% after radiosurgery). The risk increases with time since treatment. Other very long-term side effects have been described with radiation therapy: radiation-induced tumors, cerebral necrosis, strokes, etc. The role of radiosurgery and radiation therapy is growing ever more limited, because of the increasing efficacy of drug treatments and the excellent surgical results of experienced teams.

Context: Cabergoline fails to normalize hyperprolactinemia in a considerable proportion of prolactinomas, especially macroadenomas., Objective: We examined the effect of individualized high-dose cabergoline treatment on hyperprolactinemia in prolactinomas., Patients: The study included 122 women and 28 men (93 microadenomas and 57 macroadenomas). Forty-seven had undergone transsphenoidal surgery. According to the preceding medical treatment, the participants were separated into untreated (group U; n = 60), intolerant (group I; n = 64), and resistant (group R; n = 26) groups., Interventions: We promptly increased cabergoline dose on the basis of individual prolactin levels. Length of treatment was 1 yr., Results: Cabergoline normalized hyperprolactinemia in all patients except one. The proportion of prolactin normalization in both groups U and I was 83% at 3 months and 95% at 6 months. By contrast, that in group R was 35% at 3 months and 58% at 6 months. Mean cabergoline dose in milligrams per week at the time of prolactin normalization was 2.0 +/- 0.3 in group U, 0.9 +/- 0.1 in group I, and 5.2 +/- 0.6 in group R. Prolactin normalization rate at the 3 mg/wk dose was 84% overall but only 35% in group R. Serum progesterone or testosterone levels, diminished in 122 women or 16 men, respectively, were recovered in all except one resistant and four postmenopausal or panhypopituitary patients., Conclusion: Individualized high-dose cabergoline treatment can normalize hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of tumor size or preceding treatments. Hyperprolactinemia could be controlled in poor responders within 1 yr with doses higher than 3 mg/wk.

Pituitary carcinomas are very rare tumors, nearly always presenting as widely invasive masses, although the hallmark of these lesions is the finding of distant metastases. One third of reported cases are prolactin (PRL)-secreting tumors. We report the case of a fatal pituitary carcinoma evolving within 4 years from a PRL-secreting microadenoma. A 22-year-old woman presented because of galactorrhea. Evaluation of the patient disclosed slight hyperprolactinemia and magnetic resonance imaging (MRI) showed a 7-mm intrapituitary lesion, which responded to treatment with cabergoline. About 4 years after the first evaluation she developed sudden headache, ptosis, and diplopia in the right eye. MRI disclosed the growth of a large pituitary mass, invading the right cavernous sinus. Despite two trans-sphenoidal surgical procedures followed by gamma-knife radiosurgery, the patient showed rapid local progression of the tumor and the occurrence of new lung lesions, probably of metastatic nature. The patient died 7 months after the development of her first neurological symptoms because of tumor apoplexy and subsequent subarachnoid hemorrhage. This case represents the first documented rapid evolution from a microprolactinoma initially responding to dopamine agonists to a fatal pituitary carcinoma.

Resistance to dopamine agonists occurs in a subset of patients with prolactin-secreting pituitary tumors. The resistance is mediated by loss of pituitary D2 receptors and occurs in both microadenomas and macroadenomas. Cabergoline is the most effective dopamine agonist and tumors that do not respond to bromocriptine or quinagolide frequently respond to cabergoline. Treatment options include maximizing the dose of the dopamine agonist, changing agonists, trans-sphenoidal surgery and radiation therapy. The goal of therapy is to restore and maintain gonadal and neurologic function, and this might occur in the absence of a normal prolactin level or a significant change in tumor size. Trans-sphenoidal pituitary surgery should be reserved for patients who are intolerant of medical therapy, or in whom this has failed. Radiation therapy has a limited role in treatment of resistant prolactinomas and should be reserved for patients in whom medical and surgical therapy has failed.

Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma. One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone-secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy. Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.

In this article, the role of conventional radiotherapy and radiosurgery in the management of pituitary tumors is discussed. After a brief review about the mechanism of action and different techniques of irradiation therapy, the therapeutic effectiveness and side effects are analysed in the various types of pituitary tumors. Conventional fractionated radiotherapy has long been used to control growth and/or hormonal secretion of residual or recurrent pituitary tumors. Nevertheless, there is still a controversy concerning patient selection for radiotherapy, because several potentially significant side effects including hypopituitarism may develop. Stereotactic radiosurgical methods may have several advantages over conventional radiotherapy; they can be applied, for example, in patients with residual or recurrent pituitary tumors who had previously received conventional radiotherapy. However, long-term follow-up data with these relatively new techniques are still limited.

Objective: To assess the medium-term outcome in a cohort of patients with residual or recurrent pituitary adenoma treated with fractionated stereotactic conformal radiotherapy (SCRT)., Patients and Methods: Ninety-two patients (median age 50 years) with a residual or recurrent nonfunctioning (67) or a secreting (25) pituitary adenoma were treated between 1995 and 2003. Eighteen patients had a GH-secreting, five PRL-secreting and two an ACTH-secreting pituitary adenoma. Vision was impaired in 39 patients, with visual field deficit (35) and/or reduced visual acuity (25). Sixty-four patients had partial or complete hypopituitarism before SCRT. The treatment was delivered stereotactically by four noncoplanar conformal fixed fields using a 6-MV linear accelerator to a dose of 45 Gy in 25 fractions., Results: At a median follow-up of 32 months (range 4-108) the 1, 3 and 5 years actuarial progression-free survival is 99%, 98% and 98%, and overall survival is 98%. Three patients recurred 5 months, 1 year and 9 years after SCRT requiring surgery. In secreting adenomas, hormone levels declined progressively, becoming normal in more than a third of patients with GH-secreting and PRL-secreting pituitary tumours. 50% of baseline GH level was achieved in just under 2 years. The treatment was well tolerated with minimal acute toxicity. Hypopituitarism was the most common long-term effect; 22% of patients had worsening of pituitary function. One patient developed unilateral quadrantopia without tumour progression., Conclusion: SCRT as a high-precision technique of localized irradiation achieves tumour and hormone control of pituitary adenomas comparable with previously published data on the efficacy of conventional radiotherapy. Despite the potential advantage of reducing the volume of normal brain irradiated, the theoretical benefit over conventional radiotherapy in terms of the reduction in long-term morbidity has not yet been demonstrated and requires longer follow-up. Potential effect on long-term cognitive function has not been tested.

The management of invasive giant prolactinomas (IGP) has been an area of some controversy. The relative roles of transsphenoidal surgery, craniotomy, radiation therapy and dopamine agonist based medical therapy are gradually becoming clarified. We report the results of management of 30 patients with IGP. Surgery was the initial therapy in 18 patients and was nearly always followed by adjunctive treatment with radiotherapy and/or bromocriptine. A second group of 12 patients had initial therapy with bromocriptine; 6 had subsequent radiotherapy and only 1 had transsphenoidal surgery. Outcomes with regard to relief of mass effect, visual improvement, pituitary function and complications of therapy were superior in the bromocriptine treated patients.

Modulation of tumour oxygenation may be used to increase or decrease tumour hypoxia in order to improve the effect of radiotherapy or bioreductive drugs, respectively. Magnetic resonance imaging (MRI) and near infrared spectroscopy (NIRS) are techniques sensitive to blood deoxyhemoglobin concentration (Hb) that can be used to investigate tumour hypoxia indirectly via blood oxygenation levels. In this study we have used NIRS to determine absolute Hb and changes in deoxyhemoglobin and oxyhemoglobin (HbO) in subcutaneous rodent tumours for challenges that alter blood flow and oxygenation, with the aim to better interpret our MRI data. Both carbogen [95% O2 + 5% CO2] and 100% O2 breathing produced a similar and significant reduction in Hb and increase in HbO, but a negligible change in HbT (= Hb + HbO). In contrast, N2 breathing to terminal anoxia and intravenous hydralazine produced a negligible increase in Hb, but large reductions in HbO and HbT. HbT is proportional to blood volume, so our data suggests large blood volume decreases occur with challenges likely to cause reduced arterial blood pressure. Hence MRI techniques that measure the R2* relaxation rate, which varies linearly with total Hb, will underestimate the effects of hypotensive agents at increasing tumour hypoxia.

Malignant prolactinomas, as with other pituitary carcinomas, are rare tumors. The authors describe a 14-year-old boy who presented with visual loss caused by a pituitary prolactinoma. He underwent transsphenoidal surgery, radiotherapy, and dopamine agonist therapy, but 6 years after the initial diagnosis his pituitary tumor regrew and bone and pulmonary metastases developed. The authors review the literature and discuss the clinical presentation of malignant prolactinomas, their rarity, histological characteristics, distribution of the metastases, different treatment approaches, and their poor prognosis.

Purpose: To test the prognostic potential of tumor R2* with respect to radiotherapeutic outcome. Blood oxygenation level dependent (BOLD) MRI images are sensitive to changes in deoxyhemoglobin concentration through the transverse MRI relaxation rate R2* of tissue water, hence the quantitative measurement of tumor R2* may be related to tissue oxygenation., Methods and Materials: Tumor growth inhibition in response to radiation was established for both GH3 prolactinomas and RIF-1 fibrosarcomas with animals breathing either air or carbogen during radiation. In a separate cohort, the baseline R2* and carbogen (95% O2, 5% CO2)-induced DeltaR2* of rat GH3 prolactinomas and murine RIF-1 fibrosarcomas were quantified using multigradient echo (MGRE) MRI prior to radiotherapy, and correlated with subsequent tumor growth inhibition in response to ionizing radiation, while the animals breathed air., Results: A radiation dose of 15 Gy caused pronounced growth delay in both tumor models and transient regression of the GH3 prolactinomas. When the animals breathed carbogen during radiation, the growth delay/regression was enhanced only in the GH3 prolactinomas. The GH3 prolactinomas, which exhibit a relatively fast baseline R2* and large DeltaR2* in response to carbogen breathing prior to radiotherapy, showed a substantial reduction in normalized tumor volume to 66 +/- 3% with air breathing and 36 +/- 5% with carbogen seven days after 15 Gy irradiation. In contrast, the effect of 15 Gy on the RIF-1 fibrosarcomas, which give a relatively slow baseline R2* and negligible DeltaR2* response to carbogen prior to treatment, showed a much smaller growth inhibition (143 +/- 3% with air, 133 +/- 12% with carbogen)., Conclusion: Quantitation of tumor R2* and carbogen-induced DeltaR2* by MGRE MRI provides completely noninvasive prognostic indicators of a potential acute radiotherapeutic response., (Copyright 2004 Wiley-Liss, Inc.)

The aim of the study was to determine current U.K. neuro-oncology practice. A questionnaire was sent to all U.K. clinical oncologists who treat primary brain tumours. Results were distributed to these doctors with an invitation to attend a workshop in September 2000 to debate areas of differing practice and to review the existing related evidence. A further workshop was held in May 2002. The questionnaire responses and discussion of controversial areas, including the management of high-grade gliomas, low-grade gliomas, meningiomas, pituitary adenomas and multiple-brain metastases are included in this paper.

Background: Pituitary adenomas without clinically active hypersecretion are summarized under the term non-functioning pituitary adenomas (NFPA). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. Therefore, an expert group of the German Society of Endocrinology met in February 2002 and worked out concise practical management solutions., Diagnosis: The diagnosis is initiated by magnetic resonance imaging (MRI) as in pituitary incidentalomas, or by mass effects with loss of pituitary function, mild hyperprolactinemia, or by neurologic and/or ophthalmologic symptoms. Except for null-cell adenomas and oncocytomas, different hormones, mainly gonadotropins, are found by immunohistology., Treatment: No reliable medical tumor therapy of NFPA could be established. Small tumors need yearly follow-up by MRI, endocrine, and ophthalmologic assessment. The effectiveness of transnasal selective microsurgery in > 90% has been proven. With improvements of surgical facilities like better visualization, transcranial surgeries are rarely necessary. Surgery and endocrine management have to be under control of experienced specialists, and will be described in detail within the direct perioperative period and the necessary long-term followup. Large immediate or later mostly slowly regrowing tumor rests may be treated again by surgery or special radiotherapy.

The aim of this study is to evaluate the use of conventional external radiotherapy in patients with pituitary adenomas. Between October 1970 and May 1998, 27 patients with pituitary adenoma were followed at the Department of Endocrinology and Diabetes of the Hospitais da Universidade de Coimbra. They received radiation therapy at Instituto Português de Oncologia. Seven of those tumors were classified as nonfunctioning adenomas, 17 as growth-hormone-secreting adenomas, 2 as prolactinomas and 1 as adrenocorticotropic adenoma. Twenty-six patients received radiation as adjuvant therapy after incomplete resection and one patient as primary treatment. The majority of these cases were treated using the parallel opposed-field technique with a total dose between 45 and 52 Gy. The patients were submitted, before and after radiotherapy, to a protocol in order to assess the efficacy of this treatment. Some of the results were analyzed. Reduction of tumor mass was achieved in 66.6% of nonfunctioning tumors and in 25% of the secreting ones. Reduction or stabilization of hormonal levels was achieved in 55% of the cases and normalization in 30%. The average duration of follow-up was 126.3 months. Complications observed: hypopituitarism, stroke (3 patients), cerebral edema (1 patient), memory loss (2 patients) and hearing loss (2 patients). None of the patients developed brain tumors.

Background: Pituitary tumors are relatively uncommon, comprising 10-12% of all intracranial tumors. The treatment consisting of surgery, radiotherapy and drug therapy or a combination of these modalities is aimed at the control of tumor cell proliferation and--in endocrine active tumors--the reduction of hormone secretion. However, the slow proliferation characteristics of pituitary tumors necessitate long-term studies for the evaluation of the treatment results. In the last decade there has been continuous improvement in surgical procedures, radiotherapy techniques and drug generation. In this paper, literature will be reviewed to assess the role of modern radiotherapy and radiosurgery in the management of pituitary adenomas., Material and Methods: Nowadays, magnetic resonance imaging for the definition of the target volume and a real three-dimensional (3-D) treatment planning with field conformation and the possibility for non-coplanar irradiation has to be recommended. Most groups irradiate these benign tumors with single doses of 1.8-2.0 Gy up to a total dose of 45 Gy or 50.4 Gy in extensive parasellar adenomas. Adenomas are mostly small, well circumscribed lesions, and have, therefore, attracted the use of stereotactically guided high-precision irradiation techniques which allow extreme focussing and provide steep dose gradients with selective treatment of the target and optimal protection of the surrounding brain tissue., Results: Radiation therapy controls tumor growth in 80-98% of patients with non-secreting adenomas and 67-89% for endocrine active tumors. Reviewing the recent literature including endocrine active and non-secreting adenomas, irradiated postoperatively or in case of recurrence the 5-, 10- and 15-year local control rates amount 92%, 89% and 79%. In cases of microprolactinoma primary therapy consists of dopamine agonists. Irradiation should be preferred in patients with macroprolactinomas, when drug therapy and/or surgery failed or for patients medically unsuitable for surgery. Reduction and control of prolactin secretion can be achieved in 44-70% of patients. After radiotherapy in acromegaly patients somatomedin-C and growth hormone concentrations decrease to normal levels in 70-90%, with a decrease rate of 10-30% per year. Hypercortisolism is controlled in 50-83% of adults and 80% of children with Cushing's disease, generally in less than 9 months. Hypopituitarism is the most common side effect of pituitary irradiation with an incidence of 13-56%. Long-term overall risk for brain necrosis in a total of 1,388 analyzed patients was estimated to be 0.2%. Other side effects are rare too, and do also depend on the damage produced by tumor itself or preceding surgery. They include deterioration of vision in 1.7% of all cases, vascular changes in 6.3%, neuropsychological disorders such as dementia in 0.7% and secondary malignancies in 0.8%, if single doses of 2.0 Gy and total doses of 50 Gy are not exceeded., Conclusion: Conventional radiation therapy of pituitary adenoma is highly effective. It is recommended after subtotal resection of primary tumors such as macroadenomas, after gross total resection from endocrine active adenomas with postsurgical hormone secretion and for recurrent tumors. Radiosurgery seems to be a possible treatment alternative in experienced centers, and only in patients with adenomas smaller than 25-30 mm with a minimum distance of 2-3 mm to the chiasm.

Prolactinomas are a common cause of reproductive/sexual dysfunction. Once other causes of hyperprolactinemia have been excluded with a careful history and physical examination, routine chemistries, a pregnancy test and a TSH, imaging with MRI or CT will delineate the size and extent of the tumor. Medical therapy is the initial treatment of choice. When infertility is the primary indication for treatment, bromocriptine use has an extensive safety experience and is preferred. However, for other indications, cabergoline appears to be more efficacious and better tolerated. Transsphenoidal surgery remains an option, especially for patients with microadenomas, when medical therapy is ineffective.

Background: Recent data has raised skepticism regarding the long-term effectiveness of radiotherapy (RxT) in acromegaly and its role as an ancillary tool to neurosurgery (Tx)., Patients: We evaluated 72 acromegalic patients previously submitted to RxT. Data were discarded in 23 patients, who were lost to follow-up, operated on after RxT or irradiated with techniques different from external conventional fractionated RxT. Among the remaining 49 (five with mixed GH-prolactin adenoma), 34 were irradiated after surgical failure and 15 as primary treatment. A second cycle of RxT was administered in two., Results: (i) GH/IGF-I. After a median follow-up of 14 years (range 3-41), normal age-matched IGF-I levels were reached in eight patients (16%) after 10 years, and GH levels <2.5 microg/l in six (12%) after 9 years. The rate of persistently pathological hormonal levels was still 90% at 25 years. All patients with GH/IGF-I normalization had undergone irradiation without any antisecretory drug. Neither basal GH nor tumor size affected the outcome of RxT. In three patients (6%) a relapse/worsening occurred. (ii) Tumor size. Tumor shrank after 8.5 years in 24 patients (49%), in nine of whom during GH-suppressive treatment. Tumor shrinkage was not predictive of hormonal normalization. (iii) Side-effects. Hypopituitarism was diagnosed in four patients (selective in three and global in one) and GH deficiency in one. Three patients had neurological side-effects and meningioma was shown in two patients., Conclusion: RxT is unable to cure acromegaly, because it seldom achieves hormonal normalization even after a very prolonged follow-up. Concomitant antisecretory treatment seems to counteract its effects. RxT can still play a role in those patients with large tumor remnants, because of its capacity to shrink tumor size.

Today, pituitary adenomas are readily amenable to surgical treatment, and complication rates are low. With the exception of prolactin-producing adenomas, transsphenoidal or transcranial surgery is usually the treatment of choice. Indications for surgery are considered to be visual field deficits, functional disorders of the optomotor cranial nerves, or hypo-/hyperfunction of the pituitary. If treatment leads to normalization of the secretory dynamics, the long-term prognosis is favorable. If residual tumor or persistent overproduction of pituitary hormones is detected postoperatively, radiotherapy is applied. Endoscopic surgical procedures, intra-operative imaging and peri-operative determination of hormone levels enable the radicality of tumor removal to be further increased.

Prolactinomas constitute the largest group of pituitary adenomas in autopsy series. However, their relative incidence in recent surgical series is much less impressive since medical treatment with dopamine agonists is routinely employed, which in many cases leads to tumor shrinkage and normalization of prolactin levels. The clinical symptoms of hyperprolactinemia are menstrual dysfunction and galactorrhea in women and loss of libido and potency in men. Prolactinomas may present also as space occupying sellar mass lesions impinging on the adjacent structures like the pituitary gland, cavernous sinus and optic nerves. The standard primary treatment is medical by dopamine agonists. Prolactinomas are the prototype of tumors, the growth of which can be reliably and safely inhibited by specific drugs other than cytostatic chemotherapy. These unfortunately have side effects, like orthostatic hypotension, nausea and vomiting. The effects induced by dopamine agonists are suppressive but not tumoricidal. Thus, the therapeutic effect is only maintained as long as the drug is administered. Consequently. in most cases, treatment has to be continued life-long with a few exceptions, in whom normoprolactinemia persists even after discontinuation of dopamine agonists. Main indications of surgery in prolactinomas are intolerance of the medication, and tumors not responding to dopamine agonists. Occasionally, these may ultimately require radiation therapy. Remission rates in large series of surgically treated prolactinomas vary between 54% and 86%. In our consecutive series of 540 surgically treated prolactinomas, the normalization rate after transsphenoidal surgery basically depended on the preoperative prolactin levels, tumor size and extension. The remission rate of 82% in microprolactinomas with initial prolactin levels <200 ng/ml would even in small adenomas make one consider surgical treatment as an interesting alternative to long-term medical treatment.

We herein describe a 40-year-old woman with hyperprolactinemia, an empty sella and two extrasellar intracranial recurrent tumors which were revealed 23 years after the first transfrontal craniotomy and 18 years after the second transfrontal surgery and irradiation to a provable prolactin-producing pituitary macroadenoma. One recurrent tumor was in the right orbital apex causing right oculomotor nerve palsy, and the other tumor was in the right apex partispetrosae and foramen jugulare. Although her serum prolactin level decreased after the administration of bromocriptine mesilate, and the size of the two tumors remained unchanged, a malignant fibrous histiocytoma, which might have been induced by the irradiation 18 years before, grew rapidly in the right suprasellar-prepontine cistern to the right pedunculus cerebralis, leading to a poor prognosis. This case confirmed the importance of the life-lasting follow-up of pituitary adenomas treated with surgery and/or irradiation therapy. Not only ectopic recurrence of the primary tumor but also post-irradiation tumors may become apparent long after the removal of the primary tumor.

Introduction: The aim of this study was to investigate the hormone production in pituitary gland tumors following fractionated external irradiation in rats., Materials and Methods: Sixty female Wistar rats 3 to 4 month of age at the beginning of the experiments, were subjected to fractionated roentgen-rays exposure, 2 Grays (Gy) daily, either up to 20, 40 or 60 Gy. The animals were sacrificed either 6 month or 1 year after completion of the randomly assigned irradiation protocol., Results: We found 9 pituitary tumors in 60 irradiated rats (15%). All tumors proved to be adenomas. Immunohistochemical analysis of hormone production in remnants of the normal adenohypophysis revealed immunoreactivity for growth hormone (GH), adrenocorticotropic hormone (ACTH), prolactin (PRL), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). In adenomas, 4 cases were immunoreactive for TSH, 4 for GH, 2 for PRL, and 2 for FSH. The tumors were not reactive with anti-ACTH and anti-LH (luteinizing hormone)., Discussion: We concluded that irradiation accelerates the development of pituitary gland adenomas. In our series these tumors were predominantly incidental findings at necropsies after pre-termed follow-up, with a variety of hormone producing tumor cells. However, 4 of 9 tumors in our study were not producing hormones.

Objective: Stereotactic conformal radiotherapy (SCRT) is a high precision technique of fractionated radiotherapy which ensures accurate delivery of radiation with reduction in the volume of normal tissue irradiated as compared to conventional external beam radiotherapy. We describe the technique and preliminary experience of SCRT in patients with residual and recurrent pituitary adenomas., Patients and Methods: Between February 1995 and March 1999, 22 patients (mean age: 45.3, range: 20-67 years) with residual or recurrent pituitary adenomas (13 nonfunctioning, nine secretory) were treated with SCRT. All were immobilized in a relocatable Gill-Thomas-Cosman (GTC) frame and tumour was localized on a postcontrast planning computerized tomography (CT) and MRI scan. The gross tumour volume (GTV) and the critical structures were outlined on contiguous 2-3 mm separated slices. A margin of 5 mm (12 patients) to 10 mm (10 patients) was grown around GTV in three-dimensions (3-D) to generate the planning target volume (PTV). The treatment was delivered by three (five patients) and four (17 patients) maximally separated conformal fixed fields with each field conformed to the shape of the tumour using customized lead alloy blocks (19 patients) or multileaf collimator (three patients). The patients were treated on a 6-MV linear accelerator to a dose of 45 Gy in 25 fractions (18 patients) and 50 Gy in 30 fractions (four patients)., Results: The technique of SCRT has become a part of the routine work of the radiotherapy department. The treatment was well tolerated with minimal acute toxicity. One patient developed transient quadrantanopia 2 weeks after treatment with full recovery after a short course of corticosteroids. One patient had a transient visual deterioration 7 months after treatment due to cystic degeneration of the tumour which fully recovered following surgical decompression. Nine of the 15 patients presenting with visual impairment had improvement after treatment and the visual status remained stable in all others. One patient with acromegaly and one with a prolactinoma achieved normalization of elevated hormonal abnormality four and 10 months after SCRT, respectively. The remaining seven patients with a secretory adenoma had declining hormone levels at last follow-up. Newly initiated hormone replacement therapy was required in five patients. At a median follow-up of 9 months (range 1-44 months), the 1 and 2 year actuarial progression free and overall survival were 100%., Conclusion: Stereotactic conformal radiotherapy is a high precision technique suitable for the treatment of pituitary adenomas requiring radiotherapy. Preliminary results suggest effective tumour control and low toxicity within the range expected for conventional external beam radiotherapy. While the technique is of potential benefit in reducing the volume of normal brain irradiated, the advantages in terms of sustained tumour control and reduced toxicity over conventional radiotherapy need to be demonstrated in long-term prospective studies.

Background: We evaluated the efficacy of postoperative radiation therapy (RT), prognostic factors for local control probability, dose response relationship and treatment sequelae in 75 patients with pituitary adenoma., Materials and Methods: A total dose of 48-60 Gy (median: 50 Gy) was delivered with a conventional fractionation schedule after surgery. Of 75 patients, 55 (73%) were followed for more than 5 years and 27 (36%) were followed for more than 10 years with a median of 95 months., Results: Five- and 10-year local control probabilities were 87.1% and 85.0%, respectively. Univariate analysis revealed that age (p = 0.007), tumor volume smaller than 30 cm3 (p = 0.018) and the absence of prolactin secretion (p = 0.003) were significantly favorable prognostic factors for local control probability. After multivariate analysis combining these 3 factors, tumor volume smaller than 30 cm3 (p = 0.017) and age (p = 0.039) were statistically significant. Patients with prolactinoma greater than 30 cm3 showed particularly poor local control rates. No significant improvement of the local control rate was detected with increasing total irradiation doses between 48 and 60 Gy (p = 0.29). The most common side effect was hypopituitarism, and there were no severe sequelae such as optic neuropathy or brain necrosis., Conclusion: Except with prolactinoma, the dose of postoperative RT for pituitary adenoma should not exceed 50 Gy. Large prolactinoma, however, was very difficult to control with the irradiation doses between 50 and 60 Gy, and would be good candidates for stereotactic radiosurgery or stereotactic radiation therapy.

Purpose: Local control for pituitary adenomas treated with external beam radiation therapy was retrospectively analyzed to evaluate the efficacy of radiation., Materials and Methods: Thirty-eight patients treated with radiation therapy between 1979 and 1994 were analyzed. The median age was 46. Nineteen newly diagnosed tumors were treated with surgery and radiation therapy, while the others were recurrent cases. Twenty-two tumors were non-functioning, while 10 produced growth hormone (GH) and three each were prolactin-, and adrenocorticotropic hormone (ACTH)-producing tumors. The median-radiation dose was 50 Gy in 25 fractions., Results: Non-functioning adenomas and prolactin-producing adenomas were completely controlled, judging from the absence of tumor progression on neuroimaging studies and clinical symptoms, and normalization of the serum prolactin level (< 25 ng/ml). On the other hand, local control was obtained in only one of the 3 patients with ACTH-producing adenomas, and the control rate at 10 years was only 46% for GH-producing adenomas. Panhypopituitarism developed in 35% of the patients after radiation therapy. No other serious complications were noted., Conclusion: Non-functioning pituitary adenomas and prolactin-producing adenomas were well controlled with external radiation therapy combined with surgery. However, dose escalation might be necessary to control GH-or ACTH-producing tumors. It is important to replace corticosteroid hormone and thyroid hormone in many patients.