Although the majority of ACTH-producing adenomas recur, surgery is always the first therapeutic option. The available medications (ketoconazole, somatostatin analogues) are aimed at decreasing the effects of excess cortisol or decreasing ACTH release, but they are not curative.

What is the treatment of choice for a 38-year-old man diagnosed with Cushing's disease in relation to a pituitary macroadenoma of 22 mm in diameter?

Initially try medical treatment and, if not effective, resort to surgery.

Selective surgical resection of the adenoma.

Radiotherapy to try to reduce tumor size.

[Cushing's disease. A challenge of size].

Cushing's syndrome constitutes a real challenge for the clinician who has to elucidate its etiology. ACTH determinations should allow to classify the etiology as belonging to either the ACTH-dependent or the ACTH-independent group, but variable biological characteristics of pituitary or ectopic ACTH secreting tumors may complicate the investigation. For small pituitary adenomas, magnetic resonance imaging (MRI) has increased the sensitivity of detection over CT scans; however, the small average size of 4-5 mm of corticotroph adenomas, including a significant proportion of tumors of less than 3 mm, limits MRI to a sensitivity which varies between 42-80%. In situations where a pituitary tumor is small (< 6 mm or not detectable by MRI), it is recommended to perform bilateral petrosal sinus sampling including a stimulation of ACTH secretion by CRH administration, to confirm the pituitary source of ACTH prior to undertaking pituitary exploration. Transsphenoidal selective removal of the pituitary corticotroph adenoma is the treatment of choice; immediate surgical success rate is high (75-90%) when the tumor is a microadenoma visible at MRI. However success rate decreases (50-60%) when surgical exploration is performed without radiological detection. The other end of the spectrum of size of the corticotroph adenomas includes either tumors larger than 10 mm (macroadenomas) or tumors invading the cavernous sinus; in either case, immediate success rate of surgical removal is only 50-70%. Radiotherapy coupled to medical (ketoconazole, op "DDD) or surgical (bilateral laparoscopic adrenalectomy) control of hypercorticism may be necessary. Longer follow-up series indicate a relapse rate of up to 25% after 10 years, suggesting frequent incomplete resection. It is hoped that further progress in our understanding of the molecular basis of the pathophysiology of this disease will allow the development of new therapeutic strategies which will circumvent the current limitations resulting in part, from the size of these tumors.

[The treatment of Cushing's disease].

The differential diagnosis of Cushing's disease remains difficult to establish. The selective transsphenoidal adenomectomy is the initial treatment of choice. In a group of 65 patients, 50 (77%) initially responded to surgery with correction of their hypercortisolism. Forty-three out of 51 (84%) patients with small pituitary tumors responded favourably to surgery, but recurrency occurred in 10% of the cases. Medical treatment with steroids inhibitors or antagonists is only an adjuvant treatment. In case of surgery failure or recurrency, bilateral adrenalectomy is usually performed. Conventional radiotherapy may be used after surgery in presence of macroadenomas or invasive adenomas. Correction of the hypercortisolism, after a second surgery, was achieved in 50% of the cases and was always associated with a panhypopituitarism.

Cushing's disease

Treatment The first-line treatment of Cushing's disease is surgical resection of ACTH-secreting pituitary adenoma; this surgery involves removal of the tumor via transsphenoidal surgery (TSS). There are two possible options for access to the sphenoidal sinus, including of endonasal approach (through the nostril) or sublabial approach (through an incision under the upper lip); many factors such as the size of nostril, the size of the lesion, and the preferences of the surgeon cause the selection of one access route over the other.

Radiation therapy in the multimodal treatment approach of pituitary adenoma.

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. 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. 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. 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.

[Treatment of pituitary adenoma].

RECOMMENDED TREATMENTS: The different therapeutic strategies proposed for pituitary adenomas are relatively well-known thanks to numerous studies evaluating their effect on outcome. Unfortunately, large comparative clinical trials are difficult to construct due to the small number of cases of this rare condition. Therapeutic recommendations are thus generally based on the opinion of recognized experts. MICROADENOMA: Small (< 10 mm) prolactin-secreting adenomas should be treated surgically, generally by transsphenoidal adenomectomy, or medically by dopaminergic agonists: bromocriptin, quinagolide or cabergolin (the two latter drugs are more effective and better tolerated than their parent compound bromocriptin). MACROADENOMA: The expected success rate for surgical treatment of macroadenomas is low and dopaminergic agonists is generally recommended (including cases with visual impairment since the effect can be very rapid). Prolactin levels can be lowered and tumor volume reduced (in > 70% of cases). ACROMEGALY: Surgery is the firs intention treatment for acromegaly. In case of unsuccessful surgery (the criteria for "cure" are much more strict in 1998 than previously), somatostatin analog and/or hypothalamo-hypophyseal radiotherapy are recommended. Slow release formulations of somatostatin analogs can now be given by monthly (octreotide LP) or biweekly (lanreotide LP) injections. CUSHING'S DISEASE: Cure can be achieved in > 80% of cases with surgery, the first intention treatment of choice. If surgery is unsuccessful, radiotherapy can be proposed associated with anticortisol drugs (mitotane), if needed, while waiting for the late effect of radiotherapy. CLINICALLY SILENT ADENOMAS: Non-functional adenomas should be operated. Some propose adjuvant radiotherapy in all cases and others only if residual tissue persists post-operatively.

Cushing's disease

Some tumors do not contain a discrete border between the tumor and pituitary gland; therefore, careful sectioning through the pituitary gland may be required to identify the location of the tumor. The probability of successful resection is higher in patients where the tumor was identified at initial surgery in comparison to patients where no tumor was found initially; the overall remission rates in patients with microadenomas undergoing TSS are in range of 65%–90%, and the remission rate in patients with macroadenomas are lower than 65%. Patients with persistent disease after initial surgery are treated with repeated pituitary surgery as soon as the active persistent disease is evident; however, reoperation has a lower success rate and increases the risk of pituitary insufficiency.

Diagnosis and treatment of pituitary adenomas.

Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is performed for partially resected tumors or when GH levels remain elevated (eventually after a trial of somatostatin analog). Somatostatin analogs, now available in slow release form, are proposed when surgery is contra-indicated, or has failed to normalize GH levels, or in waiting for the delayed effects of radiation therapy. If the probability of surgical cure is low (e.g. in patients with very large and/or invasive tumors), then somatostatin analogs may be reasonable primary therapeutic modality provided that the tumor does not threaten vision or neurological function. Pegvisomant, the new GH-receptor antagonist, is indicated in case of resistance to somatostatin analogs. Patients with PRL-secreting microadenomas may be treated either with trans-sphenoidal surgery or medically with DA agonists. In patients with macroadenomas, even in the presence of chiasmatic syndrome, DA agonists are now proposed as primary treatment. Indeed, effects on visual disturbances are often very rapid (within a few hours or days) and tumoral shrinkage is usually very significant. For patients with ACTH-secreting adenomas, primary therapy is generally trans-sphenoidal surgery by a skilled surgeon, whether or not a microadenoma is visible on MRI. Radiotherapy is reserved for patients who are subtotally resected or remain hyper-secretory after surgery. In waiting for the effects of radiotherapy, adrenal steroidogenesis inhibitors (mitotane, ketoconazole) may be indicated. If drugs are not available or not tolerated, bilateral adrenalectomy may be proposed. For patients with clinically non functioning adenomas (generally gonadotropin-secreting adenomas on immunocytochemistry), trans-sphenoidal surgery with or without postoperative radiation therapy is performed for almost all patients whether or not they have visual consequences of their tumor. Selected patients with small, incidentally discovered microadenomas may be carefully followed without immediate therapy.

Transsphenoidal surgery in Cushing disease: 10 years of experience in 34 consecutive cases.

Cushing disease is a rare disorder. Because of their small size the adrenocorticotropic hormone (ACTH)-producing tumors are often not detectable on neuroimaging studies. To obtain a cure with transsphenoidal surgery (TSS) may therefore be difficult. In this report the authors present 10 years of experience in the treatment of patients with Cushing disease who were followed up with the same protocol and treated by the same surgeon. Thirty-four patients, 26 of them female and eight of them male (mean age 40 years, range 13-74 years) were studied. All had obvious clinical signs and symptoms of Cushing syndrome. Magnetic resonance (MR) imaging was performed in all patients, and inferior petrosal sinus (IPS) sampling was done in 14. In 12 patients MR imaging indicated a pituitary tumor; 10 were microadenomas and two were macroadenomas. In six patients with no visible tumor, the results of IPS sampling supported the diagnosis. All patients underwent TSS; the mean follow-up duration was 6 +/- 0.5 years. Selective adenomectomy was performed in 32 and hemihypophysectomy in the other two patients. A cure was obtained in 31 patients (91%) after one TSS and in two more patients after further TSS; one patient was not cured despite two TSSs and one underwent bilateral adrenalectomy. Disease recurrence was seen in two patients after 3 years, and they were successfully treated with stereotactic gamma knife surgery. Half of the patients had an ACTH deficiency postoperatively, whereas one third had other pituitary hormone insufficiencies. There were no serious complications attributable to the surgical intervention. Transsphenoidal surgery with selective adenomectomy is an effective and safe treatment for Cushing disease. In the patients presented in this study, the surgical outcome seemed to depend on careful preoperative evaluation and the surgeon's experience. For optimal results in this rare disease the authors therefore suggest that the endocrinological, radiological, and surgical procedures be coordinated in a specialized center.

Outcomes of therapy for Cushing's disease due to adrenocorticotropin-secreting pituitary macroadenomas.

We reviewed our experience with 21 patients who had Cushing's disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. All patients had typical clinical and biochemical features of ACTH-dependent hypercortisolism. Their mean maximal tumor diameter was 1.6 +/- 0.1 cm, and the range was 1.0-2.7 cm. Six patients had cavernous sinus invasion, three had invasion of the floor of their sella, and nine had suprasellar extension. The observed remission rate was significantly lower in macroadenoma patients than in microadenoma patients (67% vs. 91%; chi 2 = 5.7; P < 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6-475; P < 0.008) and presence of a maximum tumor diameter 2.0 cm or more (odds ratio, 12.9; 95% confidence interval, 1.4-124; P < 0.02) emerged as the only predictors of residual disease after surgery. The observed recurrence rate was significantly higher in macroadenoma patients than in microadenoma patients (36% vs. 12%; chi 2 = 4.2; P < 0.05). Macroadenoma patients tended to suffer from recurrences earlier than did microadenoma patients (16 vs. 49 months). Stepwise multiple logistic regression did not identify any predictors of disease recurrence in macroadenoma patients. Eight macroadenoma patients underwent a total of nine repeat surgical procedures, but none of these resulted in clinical remissions. Only four of seven (57%) patients followed for a sufficient period of time achieved normal urinary free cortisol levels after conventional radiotherapy. Three (75%) of these four patients had re-recurrent hypercortisolism after brief periods of eucortisolism. Pharmacological agents and adrenalectomy were effective in the management of hypercortisolism in patients with residual and recurrent disease. Our results indicate that ACTH-secreting macroadenomas are more refractory to conventional treatments than are ACTH-secreting microadenomas.

Long-term results after microsurgery for Cushing disease: experience with 426 primary operations over 35 years.

The aim of this paper was to demonstrate the long-term results following microsurgery in a single surgeon's continuous series of patients with Cushing disease (CD), to assess the influence of changes in surgical procedures, and to compare the results with those of other treatment modalities. In particular, preoperative diagnosis, tumor size, results of histological examination, and complications were considered. Between 1971 and 2004, 426 patients suffering from newly diagnosed CD underwent primary surgery. Pre-operative measures included clinical examination, endocrinological workup (testing of the hypothalamic-pituitary-adrenal axis, and 2- and 8-mg dexamethasone overnight suppression tests), sellar imaging (polytomography, computed tomography, and magnetic resonance [MR] imaging), and in patients with negative results on imaging studies, inferior petrosal sinus sampling. Follow-up examinations consisting of endocrinological workup, and imaging took place 1 week and 3 months after surgery and then at yearly intervals. During microsurgery as first treatment, the adenoma finding rate was 86.6%. After selective adenomectomy, the remission rate was 75.9%, and this rate showed no improvement over the years. The best results were achieved in microadenomas confirmed on MR imaging or histopathological investigation. The recurrence rate (15%) and the complication rate (5.9%) declined over the years. If no adenoma was found, exploration of the sella turcica was performed in 45.6%, hypophysectomy in 3.5%, and hemihypophysectomy in 50.9% of these patients, leading to an early remission in 37.9%. In case of persistence or recurrence, further treatment (repeated operation, adrenalectomy, radio-therapy, or medical treatment) was used to control the disease. Microsurgery remains the treatment of first choice in CD, even though no improvement in remission rates was observed over the years, because complication or remission rates for other treatment options are comparable or worse.

Pituitary radiotherapy for Cushing's disease.

The treatment of choice for Cushing's disease is pituitary surgery. Second-line treatments include repeat pituitary surgery, radiation therapy, medical therapy, and bilateral adrenalectomy. The most used modalities to irradiate patients with Cushing's disease include fractionated radiotherapy and single-dose Gamma Knife. We aim to review the efficacy and safety of radiotherapy in patients with persistent or recurring Cushing's disease. Remission of Cushing's disease after radiotherapy ranges from 42 to 83%. There seems to be no clear difference according to the technique of radiation used. Most patients experience remission of disease within 3 years from treatment, with only few cases reaching normal cortisol secretion after a longer follow-up. Control of tumor growth varies from 93 to 100%. Severe side effects of radiotherapy, such as optic neuropathy and radionecrosis, are uncommon. New-onset hypopituitarism is the most frequent side effect of radiation, occurring in 30-50% of patients treated by fractionated radiotherapy while it has been reported in 11-22% of patients after Gamma Knife. Radiotherapy is an effective second-line treatment in patients with Cushing's disease not cured by surgery. Consideration of the advantages and disadvantages of radiotherapy in comparison with other therapeutic options should always be carried out in the single patient before deciding the second-line therapeutic strategy for persisting or recurring Cushing's disease.

Cushing's disease

Pituitary radiation therapy is another option for treatment of postoperative persisting hypercortisolemia following unsuccessful transsphenoidal surgery. External-beam pituitary RT is more effective treatment for pediatric CD in children with cure rates of 80–88%. Hypopituitarism specifically growth hormone deficiency has been reported as the only most common late morbidity of this treatment; GHD has been reported in 36% and 68% of the patients undergoing post-pituitary RT for Cushing's disease. Bilateral adrenalectomy is another treatment that provides immediate reduction of cortisol level and control of hypercortisolism. However, it requires education of patients, because lifelong glucocorticoid and mineralocorticoid replacement therapy is needed for these patients. One of the major complications of this treatment is progression of Nelson's syndrome which is caused by enhance level of tumor growth and ACTH secretion post adrenalectomy in 8–29% of patients with CD.

Multiple endocrine neoplasia type 1

Treatment The treatment of choice of parathyroid tumors is open bilateral exploration with subtotal (3/4) or total parathyroidectomy. Autoimplantation may be considered in case of a total parathyroidectomy. Optimal timing for this operation has not yet been established but it should be performed by an experienced endocrine surgeon. Endocrine pancreatic tumor are treated with surgery and cytotoxic drugs in case of malignant disease. Pituitary tumors are treated with surgery (acromegaly and Mb. Cushing) or medicins (prolactinomas). Culture and society In the video game Trauma Team, Gabriel Cunningham's son, Joshua Cunningham, is diagnosed with Wermer's syndrome. It is also mentioned in the South Korean drama "Medical Top Team", as Dr. Choi Ah Jin (Oh Yeon-seo) is diagnosed with MEN-1. See also Acromegaly Multiple endocrine neoplasia Multiple endocrine neoplasia type 2a Multiple endocrine neoplasia type 2b Prolactinoma References

Anovulation

Treatment for hyperprolactinemia: For anovulatory women with hyperprolactinemia without symptoms, they can forgo treatment and continue with close follow up and medical observation. If symptoms of hyperprolactinemia are present, dopamine agonists, such as bromocriptine, are first line treatment which act by inhibiting production of prolactin by the pituitary and can shrink a prolactin-secretin lesion (i.e. prolactinoma) if present. In rare cases, endoscopic transnasal transsphenoidal surgery and radiotherapy, may be required to resect and shrink a prolactinoma if greater than 10 mm in size. Importantly, individuals should be able to conceive following normalization of serum prolactin levels and shrinking or removal of the tumor.

Nelson's syndrome

Cause Common causes include bilateral adrenalectomy for the treatment of Cushing's disease, and hypopituitarism. The onset of the disease can occur up to 24 years after a bilateral adrenalectomy has been performed, with an average of up to 15 years after. A preventative measure that can be utilized is prophylactic radiotherapy when a bilateral adrenalectomy is being performed in order to prevent Nelson's syndrome from manifesting. Screening can also be done with the help of an MRI in order to visualize the pituitary for tumors. If tumors are not present then an MRI should be performed at intervals. Hyper-pigmentation and fasting ACTH levels within plasma above 154 pmol/l are predictive of Nelson's syndrome after an adrenalectomy. Risk factors include being younger in age and pregnancy.

Stereotactic radiosurgery for pituitary adenomas: imaging, visual and endocrine results.

To determine the endocrine, ophthalmologic, and tumor growth control responses after stereotactic radiosurgery using the gamma unit, we reviewed our experience in 35 patients with pituitary adenomas. Twenty-four females and 11 males (mean age 47 years, range 9-81 years) had radiosurgery with average follow-up of 26 months (range 6-60 months). Most patients were refractory to surgical removal. Fifteen patients had Cushing's disease. Prior transsphenoidal resection was performed in 14 patients (6 had two prior operations), fractionated radiotherapy in 3, and adrenalectomy in 2. In 11 evaluable patients, the hormone response was normalized in 8, decreased in 2 and increased in 1. Five patients remained on cortisol suppression. Of 12 patients with imaging follow-up, 4 had decreased tumor size, 6 had no change, and 2 had an increase; these 2 patients underwent subsequent surgery. Ten patients had acromegaly, and 6 had undergone prior surgery. Of 8 evaluable patients, growth hormone secretion has normalized in 3, decreased in 3, and increased in 2. Six tumors decreased in size, and 2 were unchanged. One patient had repeat resection 21 months after radiosurgery and one patient underwent repeat radiosurgery. Ten patients had non-secreting adenomas; all 10 had prior operations (1-4 operations, 6 underwent frontal craniotomy) and 5 had undergone fractionated radiotherapy. Eight patients had panhypopituitarism prior to radiosurgery. Four tumors decreased in size and 6 were without change.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary disorders. Drug treatment options.

Pituitary diseases are relatively common entities in the general population. They include pituitary adenomas and hypopituitarism. Pituitary tumours can cause symptoms of mass effect and hormonal hypersecretion that can be reversed with surgical resection or debulking of the adenoma, radiotherapy, or medical treatment. Transsphenoidal adenomectomy is the treatment of choice for acromegaly, Cushing's disease, gonadotropin-secreting tumours; and thyrotropin (TSH)-secreting adenomas. Pituitary irradiation and medical therapy are secondary options. Conversely, medical treatment is the primary choice for prolactinomas. Dopamine agonists are very effective in the treatment of prolactin (PRL)-secreting tumours, with rates of control as high as 80 to 90% for microprolactinomas (< 10 mm) and 60 to 75% for macroprolactinomas (> or = 10 mm). Somatostatin analogues have also shown efficacy in patients with acromegaly who have not responded to surgery or in patients with TSH-secreting adenomas who have not improved with surgery and radiotherapy. In patients with Cushing's disease, who are not cured surgically or who relapse after pituitary adenomectomy and irradiation, steroidogenic inhibitors can be an efficient method of controlling the hypercortisolism. Pituitary insufficiency is the partial or complete loss of the anterior hypophyseal function, which is due to hypothalamic or pituitary disease. Although the classic sequence of loss of pituitary secretion is growth hormone (GH), gonadotropins, TSH, and corticotropin (ACTH), the order to begin the replacement therapy of the deficient hormone(s) is cortisol, thyroxine, androgens/estrogens and, if necessary, GH. There are multiple preparations that can be used to achieve clinical and biochemical improvement. In general, the hormone replacement therapy is lifelong.

Treatment of secretory pituitary adenoma with radiation therapy.

A retrospective review of 44 patients with secretory pituitary adenoma treated with radiation therapy (median total dose of 4,500 cGy with a median fraction size of 225 cGy) was performed to analyze response rates and possible variables associated with failure to respond and with complications. The treatment technique used for 75% of the patients was a combination field; an opposed-lateral fields technique was used for the remainder. Median follow-up was 78.5 months, with 59% followed up for more than 60 months and 34% for more than 120 months. Overall survival was 90%, and disease-free survival was 62%. Response rates were 86% for the group with prolactinoma, 67% for the group with acromegaly, and 50% for the group with Cushing disease; the overall response rate was 71%. Findings of suprasellar extension and those from treatment with opposed-lateral fields correlated significantly with failure to respond. A higher percentage of patients with invasive macroadenomas also failed to respond. More complications were found in patients treated with opposed-lateral fields, but the numbers were too small to reach significance. Radiation therapy remains an important adjunct for the treatment of many patients with secretory pituitary adenoma.

Low-grade myofibroblastic sarcoma

Treatment and prognosis Past treatments for LGMS, including surgery, radiotherapy, and chemotherapy, have not been systematically investigated nor validated. Currently, the primary and most common treatment for non-metastatic LGMS is surgical resection with, where possible, removal of all tumor cells in order to reduce this tumor's recurrence rate (e.g. ~27% and ~38% in two different studies). Following this surgery, individuals should undergo long-term observation to check for post-surgical recurrences and the uncommon instances of metastases. One study suggested that tumor cells with high rates of proliferation, tumors containing areas of necrosis, tumor sizes >10 cm in largest diameters, and deep-seated tumors are at higher risks for metastasizing.

[Radiosurgical treatment of hypophyseal adenomas with the gamma knife: results in a group of 163 patients during a 5-year period].

Gamma knife radiosurgery of pituitary adenomas is considered to be very perspective. It can be a very useful complement of traditional microsurgery, pharmacotherapy or fractionated radiotherapy which are seldom a sufficient treatment on their own. The modern radiosurgery does not offer the experience representative enough in this indication. We can offer results of medium long follow-up for tumor growth and hormonal hypersecretion of pituitary adenomas in a relatively large series of patients. We have analyzed a group of 163 patients with pituitary adenoma treated with gamma knife during 5 years and followed 12-60 months, median 24 months after irradiation. An antiproliferative effect has been achieved in 1-2 years using the minimal dose to the margin 16-35 Gy, median 20 Gy in all our patients who were controlled by MRI (n = 126 patients). One half of these adenomas evidently decreased their size. Our effective antiproliferative dose was safe for the surrounding structures. The hormonal normalization has been achieved at 50.4% from 133 hypersecreting adenomas (39/91 = 43% of acromegalics, 11/13 = 85% of patients with Cushing's disease, 2/9 = 22% of patients with Nelson's syndrome, 11/18 = 61% of prolactinomas). The median latency was 12 months. The minimal dose to the margin was 10-45 Gy, median 35 Gy. Rare side effects were provoked only by increasing the dose to influence the hypersecretion-the development of partial hypopituitarism in 3.1% of patients, the panhypopituitarism in 0.6% of patient and there was 1 hemianopic visual field defect (0.6%). Radiosurgery by gamma knife has a similar value for pituitary adenomas as microsurgery has with different distribution of advantages and drawbacks. This makes it suitable for the combined treatment where pharmacotherapy has its place under special conditions. Fractionated radiotherapy has now a marginal importance.

Nelson's syndrome

Research Through multiple advancements within the medical field, caregivers have been able to stray away from utilizing bilateral adrenalectomy as the treatment for Cushing's disease. This has decreased the risk of patients presenting with Nelson's syndrome. Alternative treatments for Nelson's syndrome have been discovered. The most utilized technique for Nelson's syndrome has been transsphenoidal surgery. In addition, pharmacotherapy, radiotherapy, and radiosurgery have been utilized accompanying a surgical procedure. Pharmacological drugs can also be given accompanying a transsphenoidal surgery including the following: pasireotide, temozolomide and octreotide. Within rats/mice, rosiglitazone has been an effective measure, however this has not been discovered in humans yet. References External links Pituitary disorders Syndromes Rare diseases

Radiotherapy in the management of giant pituitary adenomas.

The description of giant pituitary adenoma is not clear yet. In this study we tried to identify which adenomas can be defined as giant pituitary adenomas when tumor control and progression free survival (PFS) are taken as end points and we also tried to evaluate prognostic factors other than tumor size. Between January 1981 and December 1997, 74 patients with pituitary macroadenomas more than 2 cm in size were treated. Of these 30 had tumors of more than 4 cm, while 44 patients were with tumors of 2-4 cm. Two patients received primary radiotherapy, while 72 were treated postoperatively. In the postoperative group, 52 patients underwent immediate radiotherapy after surgery and 20 were treated with irradiation after regrowth or progression of the tumor after initial surgery. The mean and median tumor doses were 5518 and 5425 cGy, respectively. Overall primary tumor control rate was 84%. The local control rates among patients with tumors more than 4 cm and among patients with tumors 2-4 cm after radiotherapy were 73 and 91%, respectively. PFS was 65% for patients who had a tumor size of more than 4 cm and 87% for the patients with tumor size of 2-4 cm (P = 0.09). Young age (<20) and tumors of unclassified histology were the bad prognostic factors. Six months after radiotherapy normalisation or improvement in hormonal hypersecretion and visual field and acuity deficits were 82 and 63%, respectively. Tumors more than 4 cm in size may be more convenient for the definition of 'giant pituitary adenoma' when tumor control and PFS are taken as the end points.

Pleomorphic xanthoastrocytoma

Treatment Surgery is often the treatment of choice. Total resection (removal of the tumor) is often possible. However, the best choice of treatment will depend on many individual factors, including: The patient's medical history and overall health condition The type, location, and size of the tumor The patient's age How well the patient tolerates specific medications, procedures, or therapy How slowly or quickly the tumor is expected to progress If surgery is performed and the tumor is completely resected, further treatment may not be required. The patient will, however, need repeated MRIs to monitor for tumor re-growth. For tumors that recur, another surgical resection might be attempted. For tumors that could not be completely removed, radiation therapy may also be recommended. Also called radiotherapy, this treatment uses high-energy radiation to damage or kill cancer cells and shrink tumors.

The efficacy of conventional radiation therapy in the management of pituitary adenoma.

To evaluate the efficacy of conventional radiotherapy for reducing tumor size and endocrine hypersecretion of pituitary adenomas. We reviewed the records of 91 patients with pituitary adenoma, who were first treated between 1969 and 1994 and had been followed for more than 2 years (median, 8.2 years.) Of these patients, 86 had received postoperative radiotherapy, and 5 had received radiotherapy alone. The median total dose was 51 Gy. Clinical symptoms related to mass effects or endocrine hypersecretion were assessed. The efficacy of radiotherapy was evaluated before treatment and during the follow-up period (1-14 years; median, 3 years) by estimating tumor size on computed tomography or magnetic resonance imaging in 56 patients, as well as by endocrine testing in the 22 patients who had secreting adenomas. Local control rate, prognostic factors, and side effects were analyzed. Mass-effect symptoms improved in 72% and 79% of patients who had such symptoms due to nonsecreting adenomas and secreting adenomas, respectively. Symptoms of endocrine hypersecretion abated in 67% of patients who had such symptoms. Excessive hormone levels normalized in 74% of patients who showed endocrine hypersecretions. The greatest size reduction was seen 3 years after the completion of radiotherapy (24% CR, 62% PR, 12% NC, and 3% PD in nonsecreting adenomas, and 32% CR, 36% PR, 27% NC, and 5% PD in secreting adenomas). Three patients with secreting adenomas (2 with prolactinoma and 1 with Cushing's disease) showed a mismatch between reduction in tumor size and normalization of endocrine hypersecretion. The 10-year local control rates were 98%, 85%, 83%, and 67% for nonsecreting adenoma, growth-hormone-secreting adenoma, prolactinoma, and Cushing's disease, respectively. Univariate analyses showed that disease type and radiation field size were significant prognostic factors. Brain necrosis occurred in 1 patient who received a 60-Gy dose of irradiation. We conclude that conventional external radiotherapy with 50 Gy is safe and sufficient to control pituitary adenoma. Careful observation is required in the management of secreting adenomas because the effects on tumor size and endocrine hypersecretion may be mismatched in some secreting adenomas.

Surgery_Schwartz

production, CT or MRI scans of the chest and anterior mediastinum are performed first, followed by imaging of the neck, abdomen, and pelvis if the initial studies are negative.Treatment Laparoscopic adrenalectomy is the treatment of choice for patients with adrenal adenomas. Open adrenalectomy is reserved for large tumors (≥6 cm) or those suspected to be adrenocortical cancers. Bilateral adrenalectomy is curative for primary adrenal hyperplasia.The treatment of choice in Cushing’s disease is transsphe-noidal excision of the pituitary adenoma, which is successful in 80% of patients. Pituitary irradiation has been used for patients with persistent or recurrent disease after surgery. However, it is associated with a high rate of panhypopituitarism, and some patients develop visual deficits. This has led to increased use of stereotactic radiosurgery, which uses CT guidance to deliver high doses of radiotherapy to the tumor (photon or gamma knife) and also bilateral laparoscopic

Outcomes of Patients with Nelson's Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers.

Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era. To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS. Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis. Management of Cushing's disease (CD) prior to NS diagnosis included surgery+adrenalectomy (n = 30; eight patients had 2 and one had 3 pituitary operations), surgery+radiotherapy+adrenalectomy (n = 17; two received >1 courses of irradiation, two had ≥2 pituitary surgeries), radiotherapy+adrenalectomy (n = 2), and adrenalectomy (n = 19). Primary management of NS mainly included surgery, radiotherapy, surgery+radiotherapy, and observation; 10-year tumor progression-free survival was 62% (surgery 80%, radiotherapy 52%, surgery+radiotherapy 81%, observation 51%). Sex, age at CD or NS diagnosis, size of adenoma (micro-/macroadenoma) at CD diagnosis, presence of pituitary tumor on imaging prior adrenalectomy, and mode of NS primary management were not predictors of tumor progression. Mode of management of CD before NS diagnosis was a significant factor predicting progression, with the group treated by surgery+radiotherapy+adrenalectomy for their CD showing the highest risk (hazard ratio 4.6; 95% confidence interval, 1.6-13.5). During follow-up, 3% of patients had malignant transformation with spinal metastases and 4% died of aggressively enlarging tumor. At 10 years follow-up, 38% of the patients diagnosed with NS showed progression of their corticotroph tumor. Complexity of treatments for the CD prior to NS diagnosis, possibly reflecting corticotroph adenoma aggressiveness, predicts long-term tumor prognosis.

Long-term results of stereotactic gamma knife radiosurgery for pituitary adenomas. Specific strategies for different types of adenoma.

Long-term results of gamma knife radiosurgery for pituitary adenomas are presented and treatment strategies for different adenoma types are discussed. Two hundred and sixty-seven patients with pituitary adenoma have been treated by gamma knife radiosurgery during the past 12 years. There were 131 cases of nonfunctioning and 136 cases of functioning adenomas, in which 71 GH-producing, 33 PRL-producing and 32 ACTH-producing adenomas were included. Retreatment with the gamma knife was done in 8 cases because of large tumors or uncontrolled hormones. Micro- and small adenomas could be cured by gamma knife radiosurgery alone. Surgical or chemical debulking was necessary before radiosurgery for a large tumor with extrasellar extension. Retreatment was effective and safe in some cases. Nonfunctioning adenomas showed higher control rates than functioning adenomas even with lower dose treatment. Cushing disease showed the best response because of the smallest tumor size with the highest dose treatment. Acromegaly and prolactinoma were difficult to control because of larger tumors with lower dose treatment. The rate of hormone normalization was also high in Cushing disease but lower in prolactinoma and lowest in acromegaly. High-dose treatment was necessary for functioning adenomas to control tumor growth and oversecretion of hormones. In conclusion, gamma knife radiosurgery was effective and safe for the treatment of pituitary adenomas. However, the treatment strategies should be specific to each adenoma type according to the radiosensitivity, chemosensitivity and biological nature of the tumor.

Diagnostic problems and operative treatment of pituitary microadenomas.

Over an average observation period of 53 months 26 patients with endocrinological active microadenoma of the hypophysis (12 M. Cushing, 14 acromegaly) were retrospectively examined. Only in 11 cases did the CT-examination demonstrate intrasellar tumour expansion. Both the problems of and the criteria for CT-diagnosis of microadenoma were demonstrated. In 22 cases (84%) the microsurgical transsphenoidal exstirpation of the adenoma led to an adequate reduction in both ACTH and HGH. No postoperative deterioration of the other hypophysial functions was seen. It could be further demonstrated that where the surgical therapy failed local radiation therapy with high voltage radiation of the hypophysis region led to a reduction of the abnormal hormone secretion. The comparism of our results with those reported in the literature led us to suggest a combined therapy concept in which the indication for operative, conservative and radiation therapy is delineated.

[Use of the radiosurgery knife in the treatment of hypophyseal adenomas].

BACKGROUND. Surgery of pituitary adenomas did not produce quite satisfactory results. Therefore radiosurgery using Leksell's gamma knife has become the most widely used method which-with the contribution of MRI-meets the most important demands of aimed irradiation: a sufficiently high dose of radiation of the tumour and minimal radiation load of functionally important surrounding structures. The objective of the investigation was to assemble experience with this therapeutic method. METHODS AND RESULTS. During the period between October 1992 and September 1994 a total of 41 patients were treated: 16 men, 12-66 years old, mean age 40.8 years; 25 women age 16-76 years, mean age 50.2 years. Female:male ratio 1.5 : 1. In 30 patients (73.2%) a microsurgical operation had preceded, in 5 (12.2%) conventional fractionated radiotherapy and in 11 patients (26.9%) primary radiosurgery. As far as the type of pituitary adenoma is concerned, it conditioned acromegaly in 30, Cushing's syndrome in 3 or Nelson's syndrome in 1, or a prolactinoma was involved (in 2 patients). In five instances the adenoma was hormonally inactive. Its localization was most frequently intrasellar (36), less frequently parasellar (5). The range of administered doses varied as regards the maximum between 12.5 and 80 Gy, the average being 46.8 Gy, to the periphery of the adenoma a dose of 10-49 Gy was administered, on average 24.7 Gy using a 50-80% isodose. The time interval after treatment is relatively short for detailed analysis or evaluation. During current evaluation the authors did not observe in any of the patients progression of the disease, and in several patients diminution of the tumour was found. Karnofski's score seemed to improve. CONCLUSIONS. Radiosurgery, using Leksell's gamma knife, is after failure of conservative and microsurgical therapeutic possibilities suitable further treatment of pituitary adenoma. In indicated cases it may be the first choice. Postirradiation follow up indicates promising effects, for more detailed evaluation a several years' interval is necessary.

Treatment of pituitary-dependent Cushing's syndrome: long-term results of unilateral adrenalectomy followed by external pituitary irradiation compared to transsphenoidal pituitary surgery.

The preferred treatment of Cushing's disease (CD) nowadays is transsphenoidal pituitary surgery (TPS). Prior to TPS, patients at the Leiden University Medical Centre were treated by unilateral adrenalectomy followed by external pituitary irradiation (UAPI). We report on long-term results of both UAPI and TPS and compare remission, relapse rates, and complications. A retrospective study was carried out on 130 patients with CD. Patients with pituitary macroadenoma were excluded. Eighty-six and 44 patients underwent UAPI and TPS, respectively. Of these patients, 85 and 41 were evaluable for long-term results. Remission following UAPI and TPS was identical at 64% (54/85 and 27/41). Cumulative relapse was also comparable - 17% (9/54) and 22% (6/27), respectively, - for UAPI and TPS, although the mean follow-up periods were different - 21.4 years and 8.5 years, respectively. Cumulative disease-free survival curves after UAPI and TPS are identical until 5 years of follow-up, but diverge thereafter indicating more sustained remissions following UAPI (P = 0.17, Wilcoxon statistic). Pituitary dysfunction following UAPI (36%) and pituitary surgery (55%) likewise did not differ significantly. However, pituitary dysfunction was an immediate event after TPS, whereas it developed after a mean interval of 17.8 years following UAPI.Low-dose dexamethasone testing during follow-up had no value in predicting therapeutic outcome. The results of unilateral adrenalectomy followed by external pituitary irradiation do not justify that this therapy is totally abandoned in favour of transsphenoidal pituitary surgery. Unilateral adrenalectomy followed by external pituitary irradiation is a valid therapeutic modality for the treatment of Cushing's disease, and could be considered as alternative to bilateral adrenalectomy and under some circumstances to transsphenoidal pituitary surgery.

Myxofibrosarcoma

The recommended treatment for individuals presenting with localized MFS tumors is radical surgical resection. The resection should include a 2 cm margin of soft tissue surrounding the tumor, with planned resection of the entire area as defined by MRI-detected increased signals on T2-weighted images. This is done to ensure that all tumor tissue is removed in order to avoid the high risks of local recurrences and worsening prognoses. Historically, about 10% of patients treated with radical surgery developed recurrences at the surgical site and a significant number of these patients developed metastatic disease. Consequently, adjuvant radiotherapy has been used to help reduce these recurrences and metastatic transformations. For patients with a limb tumor that cannot be resected (less than 5% of all cases)), limb amputation is the treatment of choice. Recurrent and metastatic MFS first-line treatment has employed two chemotherapy drugs, anthracycline and Ifosfamide, while second-line

[The place of radiosurgery in the treatment of hypophyseal adenoma].

Since 1984, the neurosurgical team of Sainte-Anne Hospital in Paris has taken in charge almost 750 patients for linear accelerator radiosurgery. But only a small percentage of them were harbouring a pituitary tumor. That is why the present paper is based mostly on literature data. Pituitary adenoma radiosurgery (RS) is a second intention therapeutic method. It should be recommended only after failure of medical and/or surgical treatment. Two main methods can be used: linear accelerator-radiosurgery and Cobalt-60 gamma unit. Both procedures provide equivalent results in terms of dosimetry, accuracy and clinical data. Results of various series presented in recent and updated literature have been studied and analysed. They show and confirm the efficiency of radiosurgery on tumor and hormone secretion controls, with few cases of pituitary insufficiency. However, results were disappointing concerning visual disorders, particularly if visual dysfunction and impairment existed before radiosurgery. All authors agree nowadays on different points: a) indications: invasive adenomas, with an incomplete resection, or adenomatous recurrences, b) contraindications: tumoral size > 20 mm, distance to visual pathways < 5 mm, c) imperative precautionary measures: less than 8 Gray must be delivered on visual pathways, less than 40 Gray on oculomotor nerves. In some cases, stereotactic fractioned radiotherapy may be an alternative treatment for large tumors close to visual pathways.