scholarly journals ACTH adenomas transforming their clinical expression: report of 5 cases

2015 ◽  
Vol 38 (2) ◽  
pp. E15 ◽  
Author(s):  
Matteo Zoli ◽  
Marco Faustini-Fustini ◽  
Diego Mazzatenta ◽  
Gianluca Marucci ◽  
Eugenio De Carlo ◽  
...  

OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. RESULTS Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18–51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma “shifted” to a functioning adenoma and then regressed back to a silent form with spontaneous resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9% of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5% of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60–177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved. CONCLUSIONS The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.

2019 ◽  
Vol 3 (8) ◽  
pp. 1518-1530 ◽  
Author(s):  
Henrik Falhammar ◽  
Adam Stenman ◽  
Jan Calissendorff ◽  
Carl Christofer Juhlin

Abstract Context Information about adrenal medullary hyperplasia (AMH) is scarce. Objective To study a large cohort of AMHs. Design, Setting, and Participants Nineteen AMH cases were compared with 95 pheochromocytomas (PCCs) without AMH. AMH without (n = 7) and with PCC (n = 12) were analyzed separately. Results Of 936 adrenalectomies, 2.1% had AMH. Mean age was 47.2 ± 15.1 years. Only two (11%) AMHs had no concurrent PCC or adrenocortical adenoma. In AMHs, a genetic syndrome was present in 58% vs 4% in PCCs (P < 0.001). The noradrenaline/metanephrine levels were lower in AMHs, whereas suppression of dexamethasone was less than in PCCs. Cushing syndrome was found in 11% of AMHs. More AMHs were found during screening and less as incidentalomas. PCC symptoms were less prevalent in AMHs. Surgical management was similar; however, fewer of the AMHs were pretreated with alpha-blockers. Adrenalectomy improved blood pressure slightly less in AMHs. The disappearance of glycemic disturbances was similar to the PPCs. During a period of 11.2 ± 9.4 years, a new PCC developed in 32% of patients with AMH, 11% died, but no PCC metastasis occurred (PCCs: 4%, P < 0.001; 14% and 5%). AMHs without PCC had milder symptoms but more often Cushing disease than patients with PCC, whereas AMH with PCC more often displayed a familiar syndrome with more PCC recurrences. Conclusion A total of 2.1% of all adrenalectomies displayed AMH. AMH seemed to be a PCC precursor. The symptoms and signs were milder than PCCs. AMHs were mainly found due to screening. Outcomes seemed favorable, but new PCCs developed in many during follow-up.


Author(s):  
F. A. Zeiler ◽  
M. Bigder ◽  
A. Kaufmann ◽  
P. J. McDonald ◽  
D. Fewer ◽  
...  

Abstract:Introduction:Gamma Knife (GK) radiosurgery for pituitary adenomas can offer a means of tumor and biologic control with acceptable risk and low complication rates.Methods:Retrospective review of all the patients treated at our center with GK for pituitary adenomas from Nov 2003 to June 2011.Results:We treated a total of 86 patients. Ten were lost to follow-up. Mean follow was 32.8 months. There were 21 (24.4%) growth hormone secreting adenomas (GH), 8 (9.3%) prolactinomas (PRL), 8 (9.3%) adrenocorticotropic hormone secreting (ACTH) adenomas, 2 (2.3%) follicle stimulating hormone/luteinizing hormone secreting (FSH/LH) adenomas, and 47 (54.7%) null cell pituitary adenomas that were treated. Average maximum tumor diameter and volume was 2.21cm and 5.41cm3, respectively. The average dose to the 50% isodose line was 14.2 Gy and 23.6 Gy for secreting and non-secreting adenomas respectively. Mean maximal optic nerve dose was 8.87 Gy. Local control rate was 75 of 76 (98.7%), for those with followup. Thirty-three (43.4%) patients experienced arrest of tumor growth, while 42 (55.2%) patients experienced tumor regression. Of the 39 patients with secreting pituitary tumors, 6 were lost to follow-up. Improved endocrine status occurred in 16 (50.0%), while 14 (43.8%) demonstrated stability of hormone status on continued pre-operative medical management. Permanent complications included: panhypopituitarism (4), hypothyroidism (4), hypocortisolemia (1), diabetes insipidus (1), apoplexy (1), visual field defect (2), and diplopia (1).Conclusions:Gamma Knife radiosurgery is a safe and effective means of achieving tumor growth control and endocrine remission/stability in pituitary adenomas.


2011 ◽  
Vol 114 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Gabriel Zada ◽  
Whitney W. Woodmansee ◽  
Shakti Ramkissoon ◽  
Jordan Amadio ◽  
Vania Nose ◽  
...  

Object The 2004 WHO classification of pituitary adenomas now includes an “atypical” variant, defined as follows: MIB-1 proliferative index greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity. The authors review the incidence of this atypical histopathological subtype and its correlation with tumor subtype, invasion, and surgical features. Methods The records of 121 consecutive patients who underwent transsphenoidal surgery for pituitary adenomas during an 18-month period were retrospectively reviewed for evidence of atypical adenomas. Results Eighteen adenomas (15%) met the criteria for atypical lesions; 17 (94%) of the 18 were macroadenomas. On imaging, 15 (83%) demonstrated imaging evidence of surrounding invasion, compared with 45% of typical adenomas (p = 0.004). Atypical tumors occurred in 12 female (67%) and 6 male (33%) patients. Patient age ranged from 16 to 70 years (mean 48 years). Nine patients (50%) had hormonally active tumors, and 9 had nonfunctional lesions. Four (22%) of the 18 patients presented to us with recurrent tumors. Immunohistochemical analysis demonstrated the following tumor subtypes: GH-secreting adenoma with plurihormonal staining (5 patients [28%]); null-cell adenoma (5 patients [28%]); silent ACTH tumor (3 patients [17%]), ACTH-staining tumor with Cushing's disease (2 patients [11%]), prolactinoma (2 patients [11%]), and silent FSH-staining tumor (1 patient [6%]). The MIB-1 labeling index ranged from 3% to 20% (mean 7%). Conclusions Atypical tumors were identified in 15% of resected pituitary adenomas, and they tended to be aggressive, invasive macroadenomas. More longitudinal follow-up is required to determine whether surgical outcomes, potential for recurrence, or metastasis of atypical adenomas vary significantly from their typical counterparts.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yanli Li ◽  
Lisha Wu ◽  
Tingting Quan ◽  
Junyi Fu ◽  
Linhui Cao ◽  
...  

ObjectiveThis study aimed to report the characteristic of tumor regrowth after gamma knife radiosurgery (GKRS) and outcomes of repeat GKRS in nonfunctioning pituitary adenomas (NFPAs).Design and MethodsThis retrospective study consisted of 369 NFPA patients treated with GKRS. The median age was 45.2 (range, 7.2–84.0) years. The median tumor volume was 3.5 (range, 0.1–44.3) cm3.ResultsTwenty-four patients (6.5%) were confirmed as regrowth after GKRS. The regrowth-free survivals were 100%, 98%, 97%, 86% and 77% at 1, 3, 5, 10 and 15 year, respectively. In multivariate analysis, parasellar invasion and margin dose (&lt;12 Gy) were associated with tumor regrowth (hazard ratio [HR] = 3.125, 95% confidence interval [CI] = 1.318–7.410, p = 0.010 and HR = 3.359, 95% CI = 1.347–8.379, p = 0.009, respectively). The median time of regrowth was 86.1 (range, 23.2–236.0) months. Previous surgery was associated with tumor regrowth out of field (p = 0.033). Twelve patients underwent repeat GKRS, including regrowth in (n = 8) and out of field (n = 4). Tumor shrunk in seven patients (58.3%), remained stable in one (8.3%) and regrowth in four (33.3%) with a median repeat GKRS margin dose of 12 (range, 10.0–14.0) Gy. The actuarial tumor control rates were 100%, 90%, 90%, 68%, and 68% at 1, 3, 5, 10, and 15 years after repeat GKRS, respectively.ConclusionsParasellar invasion and tumor margin dose (&lt;12 Gy) were independent risk factors for tumor regrowth after GKRS. Repeat GKRS might be effective on tumor control for selected patients. For regrowth in field due to relatively insufficient radiation dose, repeat GKRS might offer satisfactory tumor control. For regrowth out of field, preventing regrowth out of field was the key management. Sufficient target coverage and close follow-up might be helpful.


2002 ◽  
Vol 97 ◽  
pp. 525-528 ◽  
Author(s):  
Shinji Matsuda ◽  
Toru Serizawa ◽  
Makato Sato ◽  
Junichi Ono

Object. The purpose of this paper is to report a unique complication of gamma knife radiosurgery (GKS) for trigeminal neuralgia (TN). The nature of this complication and its related factors are discussed. Methods. Forty-one medically refractory patients with TN were treated with GKS. All patients received 80 Gy to the proximal trigeminal nerve root, using a 4-mm collimator and a single isocenter. Follow up consisted of three monthly outpatient sessions after GKS. Improvement, recurrence, complications, and changes in magnetic resonance imaging were recorded. To evaluate the factors behind the complications, a subgroup of 33 patients was assessed in whom the follow-up duration was more than 9 months. The follow-up duration was 3 to 36 months (mean 13 months). The results were excellent in 20 patients, good in 11, and fair in seven. No patient had a poor result. Three patients suffered recurrences. Seven patients suffered complications 9 to 24 months after GKS. All seven patients complained of facial numbness and hypesthesia was recorded. Three of them also complained of “dry eye” with diminution or absence of corneal reflex but no other abnormalities of the cornea and conjunctiva were found on ophthalmological examination. In these three patients, hypesthesia of the first division of the trigeminal nerve area had been found before their “dry eye” symptoms appeared. The irradiated volume on the brainstem was significantly related to this complication. Conclusions. The dry eye symptom seems to be a special form of sensory disturbance. An overdose of radiation to the brainstem may play an important role in the manifestation of this complication.


2005 ◽  
Vol 102 ◽  
pp. 71-74 ◽  
Author(s):  
Piero Picozzi ◽  
Marco Losa ◽  
Pietro Mortini ◽  
Micol Angela Valle ◽  
Alberto Franzin ◽  
...  

Object. The authors studied the efficacy of gamma knife radiosurgery (GKS) in the prevention of regrowth of nonfunctioning pituitary adenomas (NPA). Methods. One hundred nineteen patients were included in this study and were divided into two groups. All patients had undergone surgery in our department and recurrent or residual adenoma was demonstrated on postoperative MR imaging. Group A consisted of 68 patients who were followed without additional treatment. Group B was composed of 51 patients who received GKS within 1 year after microsurgery. There was no significant demographic difference between the two groups. In Group B the mean margin dose was 16.5 ± 0.3 Gy (range 13–21 Gy). Fifty one and one tenth percent of patients in Group A were recurrence free at 5 years and 89.8% in Group B (p < 0.001). In Group B patients, tumor volume decreased from a baseline value of 2.4 ± 0.2 cm3 to 1.6 ± 0.2 cm3 at last follow up (p < 0.001). Conclusions. The results of this study suggest that GKS is effective in controlling growth of residual NPA for at least 5 years following initial maximal surgical debulking compared with no radiation therapy. Thus, GKS is recommended after microsurgery when visible tumor can be detected on imaging studies.


Neurosurgery ◽  
2007 ◽  
Vol 61 (2) ◽  
pp. 270-280 ◽  
Author(s):  
M. Necmettin Pamir ◽  
Türker Kiliç ◽  
Muhittin Belirgen ◽  
Ufuk Abacioğlu ◽  
Nural Karabekiroğlu

Abstract OBJECTIVE To analyze pituitary adenoma volume changes after gamma knife radiosurgery (GKRS) in patients with 3 years of follow-up and to investigate factors that might affect these changes. METHODS Between January 1997 and March 2004, a total of 1930 patients were treated in the Gamma Knife Unit of the Marmara University Department of Neurosurgery in Istanbul, Turkey. Three hundred sixty of these patients had pituitary adenomas (PAs). This prospectively designed clinical study documents the radiological-volumetric analysis for the first 100 of these patients with PAs who had a minimum of 3 years of follow-up and met the study requirements. Each tumor was assessed with serial magnetic resonance imaging scans after radiosurgery; at each time point, adenoma volume was expressed as a percentage of the tumor's initial volume. Volume changes were investigated relative to margin dose, the cavernous sinus infiltration, and endocrinological type of adenoma. RESULTS At the end of the first year after GKRS, the PA volumes had decreased to approximately 90% of the initial volume on average. The corresponding approximate averages for the ends of Years 2 and 3 were 80 and 70% of the initial volume, respectively. At 3 years after GKRS, the PAs in the group with a peripheral dose of less than 17 Gy were reduced to approximately 80% of the initial volume on average. In contrast, the tumors in the patients with marginal doses of 21 to 23 Gy were reduced to approximately 60% of the initial volume at this stage. The adenomas treated with the highest marginal doses (&gt;27 Gy) showed the earliest volume decreases after GKRS (6–9 mo after the procedure). Cavernous sinus noninfiltrating adenomas showed greater volume decreases after GKRS; on average, these masses were reduced to approximately 50% of their initial volume at 3 years. In contrast, the PAs that had infiltrated the cavernous sinus had only dropped to approximately 80% of their initial volume at this stage. The growth hormone-secreting PAs showed the maximum volume decrease with GKRS. On average, these lesions were approximately 60% of their initial volume at the 3-year stage. The nonfunctioning tumors and the prolactin-secreting adenomas showed similar volume changes over time. On average, these tumors had dropped to approximately 75 and 70% of the initial volume, respectively, by 3 years after GKRS. CONCLUSION Gamma knife radiosurgery halts the growth of pituitary adenomas. Cavernous sinus extension and margin dose are the most important determinants of adenoma volume after this type of therapy.


Neurosurgery ◽  
2014 ◽  
Vol 75 (3) ◽  
pp. 227-237 ◽  
Author(s):  
Cheng-Chia Lee ◽  
Ching-Jen Chen ◽  
Chun-Po Yen ◽  
Zhiyuan Xu ◽  
David Schlesinger ◽  
...  

Abstract BACKGROUND: Functioning pituitary adenomas (FPAs) can be difficult to delineate on postoperative magnetic resonance imaging, making them difficult targets for stereotactic radiosurgery (SRS). In such cases, radiation delivery to the entire sella has been utilized as a radiosurgical equivalent of a total hypophysectomy. OBJECTIVE: To evaluate the outcomes of a cohort of patients with FPA who underwent SRS to the whole-sellar region. METHODS: This is a retrospective review of patients who underwent whole-sellar SRS for FPA between 1989 and 2012. Sixty-four patients met the inclusion criteria: they were treated with whole-sellar SRS following surgical resection for persistently elevated hormone levels, and (1) no visible lesions on imaging studies and/or (2) tumor infiltration of dura or adjacent venous sinuses observed at the time of a prior resection. The median radiosurgical volume covering sellar structures was 3.2 mL, with a median margin dose of 25 Gy. RESULTS: The median endocrine follow-up was 41 months; 22 (68.8%) patients with acromegaly, 20 (71.4%) patients with Cushing disease, and 2 (50.0%) patients with prolactinoma achieved endocrine remission. The 2-, 4-, and 6-year actuarial remission rates were 54%, 78%, and 87%, respectively. New-onset neurological deficit was found in 4 (6.3%) patients following treatment. New-onset hypopituitarism was observed in 27 (43.5%) patients, with panhypopituitarism in 2 (3.2%). Higher margin/maximum dose were significantly associated with a higher remission rate and development of post-SRS hypopituitarism. CONCLUSION: Whole-sellar SRS for invasive or imaging-negative FPA following failed resection can offer reasonable rates of endocrine remission. Hypopituitarism following whole-sellar SRS is the most common complication.


Neurosurgery ◽  
2005 ◽  
Vol 56 (4) ◽  
pp. 699-705 ◽  
Author(s):  
Yoshiyasu Iwai ◽  
Kazuhiro Yamanaka ◽  
Katsunobu Yoshioka

Abstract OBJECTIVE: We evaluated the effectiveness of gamma knife radiosurgery in the treatment of nonfunctioning pituitary adenomas. METHODS: Between January 1994 and December 1999, we treated 34 patients with nonfunctioning pituitary adenomas. Thirty-one of these patients were followed for more than 30 months. Their mean age was 52.9 years. All patients underwent resection before radiosurgery. In four patients, treatment was performed with staged radiosurgery. The treatment volume was 0.7 to 36.2 cm3 (median, 2.5 cm3). The treatment dose ranged from 8 to 20 Gy (median, 14.0 Gy) to the tumor margin. In 15 patients (48.4%), the tumor either compressed or was attached to the optic apparatus. The maximum dose to the optic apparatus was from 2 to 11 Gy (median, 8 Gy). RESULTS: Patients were followed for 30 to 108 months (median, 59.8 mo). The tumor size decreased in 18 patients (58.1%), remained unchanged in 9 patients (29.0%), and increased in four patients (12.9%). The 5-year actual tumor growth control rate was 93%. Among patients with tumor growth, two cases were secondary to cyst formation. Two patients (6.5%) required adrenal and thyroid hormonal replacement during the follow-up period after radiosurgery because of radiation-induced endocrinopathy. None of the patients sustained new cranial nerve deficits, which included optic neuropathy. CONCLUSION: In this series, radiosurgery had a high tumor growth control rate during the long-term follow-up period. Furthermore, we observed a low morbidity rate, with endocrinopathies and optic neuropathies. This low rate included even patients in whom the tumor compressed or was attached to the optic apparatus. We emphasize the necessity of long-term follow-up to evaluate late complications.


2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 71-74 ◽  
Author(s):  
Piero Picozzi ◽  
Marco Losa ◽  
Pietro Mortini ◽  
Micol Angela Valle ◽  
Alberto Franzin ◽  
...  

Object. The authors studied the efficacy of gamma knife radiosurgery (GKS) in the prevention of regrowth of nonfunctioning pituitary adenomas (NPA). Methods. One hundred nineteen patients were included in this study and were divided into two groups. All patients had undergone surgery in our department and recurrent or residual adenoma was demonstrated on postoperative MR imaging. Group A consisted of 68 patients who were followed without additional treatment. Group B was composed of 51 patients who received GKS within 1 year after microsurgery. There was no significant demographic difference between the two groups. In Group B the mean margin dose was 16.5 ± 0.3 Gy (range 13–21 Gy). Fifty one and one tenth percent of patients in Group A were recurrence free at 5 years and 89.8% in Group B (p < 0.001). In Group B patients, tumor volume decreased from a baseline value of 2.4 ± 0.2 cm3 to 1.6 ± 0.2 cm3 at last follow up (p < 0.001). Conclusions. The results of this study suggest that GKS is effective in controlling growth of residual NPA for at least 5 years following initial maximal surgical debulking compared with no radiation therapy. Thus, GKS is recommended after microsurgery when visible tumor can be detected on imaging studies.


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