Long-Term Follow-up of Patients with Pituitary Macroadenomas after Postoperative Radiation Therapy

Langsenlehner, Tanja; Stiegler, Claudia; Quehenberger, Franz; Feigl, Guenther C.; Jakse, G; Mokry, Michael; Langsenlehner, Uwe; Kapp, Karin S.; Mayer, Ramona

doi:10.1007/s00066-007-1706-1

Cited by 38 publications

(22 citation statements)

References 41 publications

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“…However, very high rates of new hypopituitarism (77%) are reported (Minniti et al 2005a). With long (more than 10 years) follow-up, in some series almost all patients developed hypopituitarism (Littley et al 1989, Langsenlehner et al 2007. Newer stereotactic techniques (single-dose stereotactic radiosurgery (SRS) fractionated stereotactic RT) have improved efficacy and reduced the frequency of side effects due to the more localized delivery of radiation (Minniti et al 2012).…”

Section: Medical Treatmentmentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Căpățînă¹,

Wass²

2015

Journal of Endocrinology

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Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three-quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population.

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Section: Medical Treatmentmentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Căpățînă¹,

Wass²

2015

Journal of Endocrinology

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“…4,[23][24][25][26]28,33,35,37,45,[47][48][49][51][52][53]61,65 Stereotactic radiosurgery helps reduce some of the risks of conventional radiotherapy, including hypopituitarism, radiation-induced tumors, carotid stenosis, and stroke, as well as neurocognitive side effects. 1,30,38,39,56 Gamma Knife radiosurgery (GKRS) is highly effective at preventing radiographic progression of residual and recurrent adenomas. Most large radiosurgical series demonstrate a tumor control rate approaching 90%.…”

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confidence: 99%

Early versus late Gamma Knife radiosurgery following transsphenoidal resection for nonfunctioning pituitary macroadenomas: a matched cohort study

Pomeraniec¹,

Dallapiazza²,

Xu³

et al. 2016

JNS

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N oNfuNctioNiNg pituitary adenomas constitute approximately 15% to 30% of pituitary tumors 10,16 and typically present with symptoms of mass effect, including vision loss, headaches, and hypopituitarism from compression of the normal pituitary gland. Selective adenomectomy via a transsphenoidal approach remains the primary treatment modality by providing decompression and the prospect for cure. Complete resection rates vary significantly and can be limited due to tumor size and propensity for microscopic invasion of the surrounding structures. 2,5,31,32,43,56 Previously reported long-term outcomes following transsphenoidal surgery for nonfunctioning macroadenomas suggest that even gross-total resection carries a 10% to 20% rate of tumor recurrence at distant follow-up. 6,8,9,13,19,21,34,43,46,58,64,66 Subtotal resection without adjuvant treatment reportedly results in the progression of adenoma growth in 50% to 60% of patients within 10 years of surgery. 9,22,34,43,46,48 For these reasons, patients with nonfunctioning tumors may undergo secondary operations and/ or adjuvant radiotherapy for the treatment of residual or progressive disease. obJective Gamma Knife radiosurgery (GKRS) is frequently employed to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of radiographic progression of tumor. methods This is a retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS between 1996 and 2013 at the University of Virginia Health System. Patients were stratified based on the interval between resection and radiosurgery. Operative results and imaging and clinical outcomes were compared across groups following early (≤ 6 months) or late (> 6 months) radiosurgery. results Sixty-four patients met the study criteria and were grouped based on early (n = 32) or late (n = 32) GKRS following transsphenoidal resection. There was a greater risk of tumor progression after GKRS in the late radiosurgical group (p = 0.027) over a median radiographic follow-up period of 68.5 months. Furthermore, there was a significantly higher occurrence of post-GKRS endocrinopathy in the late radiosurgical cohort (p = 0.041). Seventeen percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 64% in the late cohort (p = 0.036). This difference was primarily due to a significantly higher rate of tumor growth during the observation period of the late treatment cohort (p = 0.014). Of these patients with completely new endocrinopathies, radiation-associated pituitary insufficiency developed in 1 of 2 patients in the early group and in 3 of 7 (42.9%) patients in the late group. coNclusioNs Early treatment with GKRS appears to decrease the rate of radiographic and symptomatic progression of subtotally resected nonfunctioning pituitary macroadenomas compared w...

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“…Clomiphene failure to restore gonadal function in most patients with treated NFPA is likely to reflect a much lower functional reserve of gonadotrophic cells and/or GnRH neurons in these patients, as compared with prolactinoma patients (20). In fact, because of the poor efficacy of currently available medical treatment for NFPA, as opposed to the high efficacy of dopamine agonists in prolactinomas, NFPA patients are frequen- tly submitted to multiple surgeries and radiotherapy (1)(2)(3)(4)(5), increasing the risk of irreversible pituitary damage. In unresponsive patients, clomiphene not only failed to increase, but also significantly decreased testosterone levels.…”

Section: Discussionmentioning

confidence: 99%

“…Hypogonadotropic hypogonadism in patients with NFPA is highly prevalent both at diagnosis and after conventional treatment with pituitary surgery and/or radiotherapy (1)(2)(3)(4)(5). Untreated hypogonadism decreases patient quality of life and fertility and increases cardiovascular risk (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas

Ribeiro

Abucham

2011

Arq Bras Endocrinol Metab

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INTRODUCTIONC linically nonfunctioning pituitary adenomas (NFPA) are usually diagnosed due to compressive symptoms, most typically visual field abnormalities, headache and hypopituitarism. Hypogonadotropic hypogonadism in patients with NFPA is highly prevalent both at diagnosis and after conventional treatment with pituitary surgery and/or radiotherapy (1-5). Untreated hypogonadism decreases patient quality of life and fertility and increases cardiovascular risk (6-8).Male hypogonadal patients are usually treated with testosterone replacement, most often with intramusCopyright © ABE&M todos os direitos reservados. 267Arq Bras Endocrinol Metab. 2011;55/4 cular injections that require frequent applications and induce large fluctuations in serum testosterone levels, with corresponding fluctuations in patient energy, libido, sexual performance and mood. In addition, testosterone replacement has an inhibitory effect on spermatogenesis and fertility, which is undesirable in patients who want to have children (7,8).Clomiphene is a well-known selective estrogen receptor modulator that increases gonadotropin secretion via hypothalamic-pituitary action (9). Clomiphene has been extensively used in the evaluation of the gonadotropic axis and in the induction of ovulation. Clomiphene has also been shown to revert hypogonadotropic hypogonadism in several conditions, such as falciform anemia, uremia, alcohol and steroid abuse, and in the stimulation of gonadotropin secretion in patients with sulpiride-induced hyperprolactinemia and gonadotropin suppression (10-14). More recently, we have shown that clomiphene led to the recovery of gonadal function in most male patients with prolactinomas and persistent hypogonadism under dopamine agonist treatment, irrespective of prolactin levels (15). In this study, we evaluated the therapeutic potential of clomiphene in reverting hypogonadism in patients with conventionally treated NFPA. PATIENTS AND METHODS PatientsTwelve consecutive adult male patients with NFPA, previously treated with surgery with or without radiotherapy, seen during one year at the Neuroendocrine Unit of the Endocrinology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, presented hypogonadotropic hypogonadism and were considered to be included the protocol. Hypogonadotropic hypogonadism was defined by total testosterone levels below 300 ng/dL (10.5 nmol/L), and normal/low LH levels after at least two months of surgery. Testosterone replacement was discontinued for at least two months before evaluation. Three patients were excluded from the study due to prostate disease, limitations in schedule, or cognitive deficit. Nine patients completed the study. Study designThis study was an interventional, open label, uncontrolled, single-arm, prospective trial with oral clomiphene citrate (Clomid ® , Medley, kindly provided by Dr. Enrico Repetto), 50 mg/day for 12 weeks, designed to assess the effects of the drug on serum testosterone levels of male patients with NFPA previously treated with surgery. Th...

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Long-Term Follow-up of Patients with Pituitary Macroadenomas after Postoperative Radiation Therapy

Cited by 38 publications

References 41 publications

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Early versus late Gamma Knife radiosurgery following transsphenoidal resection for nonfunctioning pituitary macroadenomas: a matched cohort study

Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas

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