Pituitary Irradiation Research Articles

Nelson’s syndrome: a giant pituitary

Nelson’s syndrome is a pituitary mass that develops following total bilateral adrenalectomy (TBA) for the treatment of Cushing’s disease. It is one of the most challenging of all endocrine conditions. The frequent aggressiveness of the underlying ACTH-secreting pituitary adenoma (corticotrophinoma) necessitates regular biochemical and radiological screening. Failure to administer prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels during the first year following TBA are the main factors that may predict the occurrence of Nelson’s syndrome. Though, computerized tomography (CT) and magnetic resonance imaging (MRI) have led to the early diagnosis and improvement in management, these tumours are sometimes detected late, through clinical manifestations of invasion and compression of the surrounding structures. With this perspective in mind, we describe a 22-year-old gentleman who presented 10 years after TBA with right sided hemiparesis caused by a corticotroph adenoma.

High-Precision Conformal Fractionated Radiotherapy Is Effective In Achieving Remission In Patients With Acromegaly After Failed Transsphenoidal Surgery

Variable efficacy of pituitary radiotherapy in acromegaly is reported. Here we sought to assess the efficacy of high-precision conformal fractionated radiotherapy (CRT) in patients with acromegaly after failed TSS. A retrospective analysis was conducted a in tertiary care referral center between 1999 to 2013 on 36 acromegaly patients (M: 16, F: 20; median age: 36.0 years) with macroadenoma and mean growth hormone (GH) and insulin-like growth factor-1 (IGF1) upper limits of normal (ULN) of 15.9 ± 14.3 ng/mL and 1.74 ± 0.43, respectively. The cohort was divided into 2 groups: 30 patients (M: 13, F: 17) who were medical treatment naïve, and 6 patients (M: 3, F: 3) who received medical treatment after CRT. Normalization of GH (fasting GH <1 ng/mL), normalization of IGF1 (ULN <1), and remission (normalization of GH and IGF1) were achieved in 20 (55%), 23 (63%) and 20 (55%) patients, respectively. The mean time required to achieve remission was 63 ± 33.4 months. Follow-up duration was the only predictor of achieving remission. GH level declined exponentially by 65% and 89% at 2 and 5 years, respectively. New onset hypopituitarism was noted in 33% of patients. Tumor control was achieved in 100% of patients. In groups 1 and 2, 18 (60%) and 2 (33.3%) achieved remission post-CRT, and the mean times required to achieve remission were 58.6 ± 30.7 months and 102 ± 42.4 months, respectively. High-precision CRT is an effective modality to achieve remission in patients with acromegaly after failed TSS.

Success rate of treating acromegaly at national hospital of Sri Lanka

Introduction: Pituitary surgery, radiotherapy and medical therapy with dopamine agonists (DA), somatostatin analogues (SA) and growth hormone receptor agonists (GHRA) are the main treatment modalities that are recommended for treating acromegaly. Most of these treatment modalities are too expensive or not available in most of the resource settings like ours. The objectives of this study were to describe the demographic factors, presentation and comorbidities in acromegaly patients and to analyze the outcome of the treatment modalities used in our clinical setting, which include remission, recurrence and mortality among patients with acromegaly. Materials and methods: This was a descriptive cross sectional study conducted among 72 acromegaly patients attending endocrinology and pituitary clinics at national hospital of Sri Lanka between January 2012 and June 2013. Pituitary adenomas were classified based on Hardy’s classification. A remission criteria of nadir growth hormone level Results: 54.1% of the patients were females. The mean age of the patients at the time of presentation was 39.52 (SD± 12.8) years and the mean duration of symptoms on presentation was 3.28 years (SD±2.7). The commonest presentations were the changes in facial appearances and the increase in shoes and ring sizes (88%). 81.8% had tumour grade II and above. 14.2% had prolactin co-secretion with GH. 86.1% underwent transsphe noidal surgery (TSS). 37.5% of patients with grade I tumour and 33.3% of patients with grade II tumour achieved remission following TSS. None of the patients with tumour grade III or above achieved remission following (TSS). In our series, overall remission was 22.5%. External beam radiotherapy (EBRT) was effective in 20% in achieving remission. Medical therapy (either cabergoline or bromocriptine) as bridging /primary therapy achieved remission in only 20.8%. Irrespective of the mode of treatment, no recurrence was noted in the patients who achieved remission. The mortality in this case series was 2.7%. Conclusions: Although the grade III and IV tumours has limited success, TSS remains the treatment of choice in acromegaly. EBRT and medical therapy with dopamine agonist have limited efficacy. Most of the other recommended options are very costly or unavailable in Sri Lanka. This study further highlights the importance of establishing specialist pituitary surgery services and introducing modern medical therapy to improve patient outcome.

A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.

We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. (11)C-methionine PET-CT can aid the detection of ACTH-secreting tumours in Cushing's syndrome and facilitate targeted therapy.

The Treatment of Cushing's Disease.

Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 78% and relapse in around 13% of patients during the 10-year period after surgery, so that nearly one third of patients experience in the long-term a failure of surgery and require an additional second-line treatment. Patients with persistent or recurrent CD require additional treatments, including pituitary radiotherapy, adrenal surgery, and/or medical therapy. Pituitary radiotherapy is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hypopituitarism. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy has recently acquired a more important role compared to the past, due to the recent employment of novel compounds able to control cortisol secretion or action. Currently, medical therapy is used as a presurgical treatment, particularly for severe disease; or as postsurgical treatment, in cases of failure or incomplete surgical tumor resection; or as bridging therapy before, during, and after radiotherapy while waiting for disease control; or, in selected cases, as primary therapy, mainly when surgery is not an option. The adrenal-directed drug ketoconazole is the most commonly used drug, mainly because of its rapid action, whereas the glucocorticoid receptor antagonist, mifepristone, is highly effective in controlling clinical comorbidities, mainly glucose intolerance, thus being a useful treatment for CD when it is associated with diabetes mellitus. Pituitary-directed drugs have the advantage of acting at the site responsible for CD, the pituitary tumor. Among this group of drugs, the dopamine agonist cabergoline and the somatostatin analog pasireotide result in disease remission in a consistent subgroup of patients with CD. Recently, pasireotide has been approved for the treatment of CD when surgery has failed or when surgery is not an option, and mifepristone has been approved for the treatment of Cushing's syndrome when associated with impairment of glucose metabolism in case of the lack of a surgical indication. Recent experience suggests that the combination of different drugs may be able to control cortisol excess in a great majority of patients with CD.

TU‐CD‐304‐02: Planning and Delivery of Fully Dynamic Trajectory Modulated Arc Therapy On Pituitary Adenoma: Dosimetric Advantages Over Conventional Volumetric Modulated Arc Therapy

Purpose:To assess the potential benefit of trajectory modulated arc therapy (TMAT) for treatments of small benign intracranial tumor, pituitary adenoma.Methods:A TMAT planning platform that incorporates complex source motion trajectory involving synchronized gantry rotation with translational and rotational couch movement was used for the study. The platform couples an interactive trajectory generation tool with a VMAT algorithm that performs multi‐resolution, progressive sampling MLC optimization on a user‐designed trajectory. A continuous couch rotation of 160° angular span with ±20° mini gantry arcs was used to emulate a non‐coplanar horizontal arc‐like trajectory. Compared to conventional non‐coplanar gantry arcs (60°‐100° gantry rotation with couch kicks), TMAT limited the unnecessary low to medium dose spread in the anterior and posterior directions, where primary OARs (e.g., brainstem, optic chiasm, optic nerves, and lens) are in close proximity to the targeted pituitary tumor volume. For 5 standard fractionation pituitary adenoma cases (50.4Gy/28fractions), TMAT and non‐coplanar VMAT plans were generated and compared under equivalent objectives/constraints. TMAT delivery was implemented and demonstrated on Varian TrueBeam via XML scripts.Results:Both techniques showed good target coverage while OARs were able to meet the constraints on QUANTEC guidelines. Notably, TMAT decreased the dose deposition in the anterior‐to‐posterior direction surrounding PTV. TMAT significantly reduced the mean doses on brainstem, optic nerves, eyes and lens by 47.29%±13.17%, 28.51%±8.68%, 80.82%±8.71% and 65.38%±19.99% compared with VMAT, all p≤0.01. Percentage reductions of maximum point dose in eyes and lens were 75.68%±10.30% and 70.72%±18.62% respectively for TMAT versus VMAT, all p≤0.01. A representative isocentric TMAT pituitary plan was delivered via an XML script with 200 control points and 282 MUs.Conclusion:Deliverable TMAT plans were achieved in developer mode in TrueBeam. TMAT was shown to be superior for pituitary adenoma irradiation in terms of OARs sparing.

Radio-induced meningioma: a long-term consequence of pituitary radiotherapy

Radio-induced meningioma: a long-term consequence of pituitary radiotherapy

Cushing's syndrome: epidemiology and developments in disease management.

Cushing’s syndrome is a rare disorder resulting from prolonged exposure to excess glucocorticoids. Early diagnosis and treatment of Cushing’s syndrome is associated with a decrease in morbidity and mortality. Clinical presentation can be highly variable, and establishing the diagnosis can often be difficult. Surgery (resection of the pituitary or ectopic source of adrenocorticotropic hormone, or unilateral or bilateral adrenalectomy) remains the optimal treatment in all forms of Cushing’s syndrome, but may not always lead to remission. Medical therapy (steroidogenesis inhibitors, agents that decrease adrenocorticotropic hormone levels or glucocorticoid receptor antagonists) and pituitary radiotherapy may be needed as an adjunct. A multidisciplinary approach, long-term follow-up, and treatment modalities customized to each individual are essential for optimal control of hypercortisolemia and management of comorbidities.

Second Attempt of Cabergoline Withdrawal in Patients with Prolactinomas after a Failed First Attempt: Is it Worthwhile?

Successful discontinuation of cabergoline (CAB) treatment has been reported in 31–75% of prolactinomas patients treated for at least 2 years. In contrast, it is not well established whether CAB therapy can be successfully withdrawn after a failed first attempt. This prospective open trial was designed to address this topic and to try to identify possible predictor factors. Among 180 patients with prolactinomas on CAB therapy, the authors selected those who fulfilled very strict criteria, particularly additional CAB therapy for at least 2 years, normalization of serum prolactin (PRL) levels following CAB restart, no tumor remnant >10 mm, no previous pituitary radiotherapy or surgery; and current CAB dose ≤1.0 mg/week. Recurrence was defined as an increase of PRL levels above the upper limit of normal. A total of 34 patients (70.6% female) treated with CAB for 24–30 months were recruited. Ten patients (29.4%) remained without evidence of recurrence after 24–26 months of follow-up. Twenty-four patients (70.6%) recurred within 15 months (75% within 12 months) after drug withdrawal and ~80% were restarted CAB. Median time to recurrence was 10.5 months (range, 3–15). Despite overlapping values, non-recurring patients had significantly lower mean PRL levels before withdrawal. Moreover, the recurrence rate was lower in subjects without visible tumor on pituitary magnetic resonance imaging (MRI) than in those with small remnant tumor (60 vs. 79%), though the difference was not statistically significant (P = 0.20). No other characteristic could be identified as a predictor of successful CAB discontinuation. In conclusion, a second attempt of CAB withdrawal after two additional years of therapy may be successful, particularly in patients with lower PRL levels and no visible tumor on pituitary MRI. Close monitoring of PRL level is mandatory, especially within the first year after withdrawal, where most recurrences are detected.

An observational study on adrenal insufficiency in a French tertiary centre: Real life versus theory

BackgroundPatients suffering from adrenal insufficiency, whether primary (PAI) or secondary (SAI) have an increased mortality risk and increased morbidity. There are no guidelines on hydrocortisone replacement therapy and little is known on patients’ management in current practice. We described patients’ profiles and treatment in a tertiary referral centre. MethodsData were collected retrospectively from medical charts. PAI and SAI patients were described and compared. ResultsTwo hundred and one patients (79 PAI+122 SAI) were included. They had a mean duration of disease of 11.2years. Main causes of PAI were autoimmune diseases (31%) and adrenalectomy (26%). SAI was caused primarily by pituitary tumors (61%) and irradiation (20%). Mean dose of daily hydrocortisone (HC) was 27.5 and 19.9mg/day in PAI and SAI patients respectively, with a majority of patients dividing the dose into 2 intakes (46.8 and 72.2% in PAI and SAI groups, respectively). SAI patients exhibited more cardiovascular risk factors than PAI patients. The HC daily dose was slightly higher in patients with dyslipidemia (in both PAI and SAI groups) and in those with high blood pressure (in the SAI group only). One third of patients were out of work, due to unemployment, sick leaves, or disability. ConclusionsThe management of AI is far from standardized, and individual tailorization is difficult with currently available means of treatment. Under- and overdose of hydrocortisone likely leads to complications, and altered quality of life reflected by a high rate of “out of work” patients.

Empty Sella Syndrome: A Case Report and Literature Review

An empty sella occurs due to herniation of the arachnoid through an incompetent diaphragma sellae. Over time, cerebrospinal fluid (CSF) pulsations may enlarge the sella and compress the gland against the floor of the sella. Empty sella syndrome is considered as a less common entity and is usually asymptomatic and an incidental finding. However, it can be a manifestation of increased intracranial pressure and can be occasionally severe. Compression of the pituitary gland may affect function, or traction on the optic chiasm and nerves may cause visual symptoms. An empty sella may be classified as primary when this occurs in persons who have not received pituitary radiation or pituitary surgery, while an empty sella discovered following such procedures is classified as secondary empty sella. In this report, we presented a 41-year-old multiparous patient who presented to us with symptoms of headache and left sided hemi-sensory disturbance. Examination was unrevealing except for the fact that she was obese. On evaluation, she was detected to have impaired blood sugars, dyslipidemia and vitamin insufficiency. MRI brain revealed presence of Empty Sella. Further hormonal analysis was normal. She was treated conservatively and regular follow-up was advised.

Time to recovery of adrenal function after curative surgery for Cushing's syndrome depends on etiology.

Successful tumor resection in endogenous Cushing's syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy. The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing's disease (CD), adrenal CS, and ectopic CS. We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983-2014. The mean follow-up time was 8 years. We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease. The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03-1.1 y) in ectopic CS, 1.4 years (IQR, 0.9-3.4 y) in CD, and 2.5 years (IQR, 1.6-5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822-0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses. Time to recovery of adrenal function is dependent on the underlying etiology of CS.

Detection of recurrent Cushing's disease: proposal for standardized patient monitoring following transsphenoidal surgery.

Transsphenoidal surgery (TSS) is first-line treatment for Cushing’s disease (CD), a devastating disorder of hypercortisolism resulting from overproduction of adrenocorticotropic hormone by a pituitary adenoma. Surgical success rates vary widely and disease may recur years after remission is achieved. Recognizing CD recurrence can be challenging; although there is general acceptance among endocrinologists that patients need lifelong follow-up, there are currently no standardized monitoring guidelines. To begin addressing this need we created a novel, systematic algorithm by integrating information from literature on relapse rates in surgically-treated CD patients and our own clinical experiences. Reported recurrence rates range from 3 to 47 % (mean time to recurrence 16–49 months), emphasizing the need for careful post-surgical patient monitoring. We recommend that patients with post-operative serum cortisol <2 µg/dL (measured 2–3 days post-surgery) be monitored semiannually for 3 years and annually thereafter. Patients with post-operative cortisol between 2 and 5 µg/dL may experience persistent or subclinical CD and should be evaluated every 2–3 months until biochemical control is achieved or additional treatment is initiated. Post-operative cortisol >5 µg/dL often signifies persistent disease and second-line treatment (e.g., immediate repeat pituitary surgery, radiotherapy, and/or medical therapy) may be considered. This follow-up algorithm aims to (a) enable early diagnosis and treatment of recurrent CD, thereby minimizing the detrimental effects of hypercortisolism, and (b) begin addressing the need for standardized guidelines for vigilant monitoring of CD patients treated by TSS, as demonstrated by the reported rates of recurrence.

Comparison of CCC and ETAR dose calculation algorithms in pituitary adenoma radiation treatment planning; Monte Carlo evaluation

AbstractAimsTo verify the accuracy of two common absorbed dose calculation algorithms in comparison to Monte Carlo (MC) simulation for the planning of the pituitary adenoma radiation treatment.Materials and methodsAfter validation of Linac's head modelling by MC in water phantom, it was verified in Rando phantom as a heterogeneous medium for pituitary gland irradiation. Then, equivalent tissue-air ratio (ETAR) and collapsed cone convolution (CCC) algorithms were compared for a conventional three small non-coplanar field technique. This technique uses 30 degree physical wedge and 18 MV photon beams.ResultsDose distribution findings showed significant difference between ETAR and CCC of delivered dose in pituitary irradiation. The differences between MC and dose calculation algorithms were 6.40 ± 3.44% for CCC and 10.36 ± 4.37% for ETAR. None of the algorithms could predict actual dose in air cavity areas in comparison to the MC method.ConclusionsDifference between calculation and true dose value affects radiation treatment outcome and normal tissue complication probability. It is of prime concern to select appropriate treatment planning system according to our clinical situation. It is further emphasised that MC can be the method of choice for clinical dose calculation algorithms verification.

Infection of a Rathke Cleft Cyst: A Rare Cause of Pituitary Abscess

Only 20 cases of abscess formation within a Rathke cleft cyst have been reported. Case report and review of the English-language literature. A 64-year-old female was admitted with a 12-mo history of headache and decreased visual acuity and had bilateral papilledema and bitemporal hemianopsia with impairment of visual acuity. Magnetic resonance imaging demonstrated a sellar and suprasellar mass measuring 2×2×2 cm. The lesion was removed using a transsphenoidal approach. The abscess was drained, and gram stain revealed polymorphonuclear cells and gram-positive cocci. The postoperative course was uneventful. Ceftriaxone and metronidazole were continued for 6 wks. The patient also received hydrocortisone and continued thyroid hormone replacement. During a 6-mo follow up, the patient's headaches disappeared, and the bitemporal hemianopsia and impaired visual acuity abated. Predisposing factors for pituitary abscesses in primary lesions include immunosuppression and pituitary irradiation, surgery, or infarction. Approximately one-third of pituitary abscesses arise within other lesions. The clinical manifestations are non-specific. Magnetic resonance imaging shows a cystic lesion with central low intensity and rim enhancement after administration of contrast. When a pituitary abscess is diagnosed, surgical procedures should be performed promptly via a transsphenoidal (preferably) or transcranial approach.

Syndromes de Cushing : physiopathologie, étiologie et principes thérapeutiques

The most frequent cause of Cushing's syndrome is iatrogenic, as Cushing's syndrome is the unavoidable consequence of long-term glucocorticoid treatment using more than 7.5 mg prednisone per day. The most frequent cause of endogenous Cushing's syndrome is Cushing's disease (CD), which is an ACTH dependent hypercortisolism linked to a pituitary corticotroph adenoma. This adenoma is often very small, its diagnosis may require bilateral inferior petrosal sinus sampling and the first line treatment of CD is transsphenoidal surgery by an expert neurosurgeon. The second line treatments include drugs that can act either on the pituitary adenoma or on adrenal steroidogenesis, pituitary radiotherapy or bilateral adrenalectomy. Ectopic ACTH dependent Cushing's syndrome is linked either to poorly differentiated endocrine tumors with a very poor prognosis, such as small cell lung cancer, or to well differentiated endocrine tumors, such as bronchial carcinoid tumors, which have a good prognosis when treated by surgery, but may be very difficult to localize. Adrenal Cushing's syndromes, which are independent of pituitary ACTH secretion, include adrenal cortex carcinoma, which requires abdominal surgery with extended adrenalectomy by an expert surgeon, adrenal adenoma which is treated by laparoscopic unilateral adrenalectomy and bilateral macronodular hyperplasia, whose surgical treatment may require unilateral or bilateral adrenalectomy. Treatment of Cushing's syndrome generally leads to spectacular clinical results, which must not hide the fact that the reversibility of some signs is actually incomplete. This underlines the need for a timely multidisciplinary management of the patients by an expert team.

Extensive experience in the management of macroprolactinomas

Macroprolactinomas are pituitary tumours that can be managed with dopamine agonists (DA), surgery and radiotherapy. We aimed to assess the outcomes of these treatment modalities. Retrospective case-note study of patients managed in a single tertiary referral centre. One hundred patients (68 male) diagnosed with macroprolactinoma between 1971 and 2009. We assessed the response to first-line treatment in terms of reduction in serum prolactin, endocrine status, symptomatic improvement and tumour shrinkage. Patients were divided into a group that received only DA therapy and a group that received surgery, radiotherapy or both, with or without a DA. We compared pituitary function at baseline and at last clinic visit between the two groups. In total, there were 1170 patient years of follow-up. Pituitary surgery was performed in 29/100 patients. Fourteen patients received pituitary radiotherapy (8/14 surgery also). At last clinic visit, the nonmedical therapy group had a higher risk of gonadotrophin deficiency (77·4% vs 44·8%, P = 0·0037), TSH deficiency (54·8% vs 25·4%, P = 0·0009) and ACTH deficiency (56·2% vs 17·2%, P = 0·0001). When last reviewed, 23/29 (79·3%) patients who underwent surgery and 10/14 (71·4%) patients who received radiotherapy were taking a DA. Treatment with a DA alone is associated with better outcomes in terms of pituitary function and as such represents the optimal first-line therapy for macroprolactinomas. Surgery and radiotherapy should be reserved for patients who are either intolerant of or resistant to DAs. Following surgery and/or radiotherapy, the majority of patients still require a DA for control of prolactin hypersecretion.

Effects of stereotactic surgery after acromegaly – Long-term results from the German Acromegaly Registry

Background: The effects of conventional pituitary radiotherapy (RT) have been well described. Currently, conventional radiotherapy has been widely replaced by stereotactic radiosurgery (SRS). In small studies with observation times ranging from 0.5 to 10 years, biochemical remission rates of 20%-85% and hypopituitarism rates of 0%-69% were found with SRS. However, it is known that the full effects of radiotherapy may occur even later after 15 – 20 years. These long-term data are still lacking for SRS. Methods: We included all patients with a follow-up visit at least two years after SRS from the German Acromegaly Registry. We analyzed the rates of remission (by IGF-1 normalization) in Patients not receiving medical therapy at the last visit, the rates of patients still requiring medication, and the rates of hypopituitarism after SRS. We observed the results in the last visit with available information and divided the observation times after SRS into 5-year slots. Results: There were 200 patients with SRS in the Registry (63 Gammaknife, 29 Linac, 8 Cyberknife, 100 not further specified). Among those patients without medication, IGF-1 was normalized in 64% and 95% after 2 – 5 and 10 – 15 years, respectively. The rates of patients requiring medication showed no trend and ranged between 65% and 85% during the whole observation period of 2 – 25 years. The rate of gonadotropic, corticotropic, thyrotropic deficiency was 42%, 30%, and 22%, respectively, after 2 – 5 years and showed a constant increase to 67%, 67%, and 67%, respectively, after 15 – 25 years. Conclusion: Our results on the long-term effects of SRS are disappointing. There is a high rate of patients still requiring medication and the long-term rates of hypopituitarism are higher than described in previous studies of shorter duration.

Thyrotropin-Secreting Pituitary Adenomas: Outcome of Pituitary Surgery and Irradiation

Our objective was to describe the effects of surgery and radiotherapy on hormonal control and tumor mass in short- and long-term follow-up of TSH-secreting pituitary adenomas (TSHomas). This was a retrospective multicenter study. We collected data of 70 TSHomas (70% macroadenomas). The mean follow-up was 64.4 (range 3-324) months. Overall, 97% of patients were treated with surgery; in 27% of them radiotherapy was associated. After surgery, 75% of patients normalized thyroid function, 58% normalized both pituitary imaging and hormonal profile, 9% developed pituitary deficiencies, and 3% had tumor or hormonal recurrence, all within the first 2 years after surgery. Presurgical medical treatment did not significantly improve surgical outcome (63% vs 57%). Radiotherapy controlled hypersecretion in 37% of patients within 2 years, whereas 32% of patients developed new pituitary deficiencies from 18 to 96 months from treatment. At last follow-up, 80% of patients normalized thyroid function, whereas 20% were currently on medical treatment: 85% with somatostatin analog (SSA) alone and 15% with SSA combined with methimazole. Subjects who achieved disease control had surgery as the only treatment in 80% of cases and surgery combined with irradiation in 20%. Surgery remains the first-choice treatment for TSHoma. If surgery is successful, recurrence is rare. When surgery is unsuccessful or contraindicated, SSA and radiotherapy are effective in controlling hyperthyroidism and tumor growth in the majority of patients. The effects of radiotherapy on TSH secretion and tumor mass are greater within the first years after treatment, whereas pituitary deficiencies may occur several years later.

Editorial: Gamma Knife radiosurgery and nonfunctioning pituitary adenomas

The publication of Lee et al. is a useful and well-written addition to the literature.1 They analyze, based on a review of previous studies and their own experience, the advantages and disadvantages of Gamma Knife radiosurgery (GKRS) in the treatment of patients with clinically nonfunctioning pituitary adenomas. The results of GKRS are also compared with those produced by conventional resection. Clinically nonfunctioning pituitary adenomas represent the most frequent pituitary adenoma type among pituitary tumors. Medical treatment is not available, and pituitary tumor irradiation has several significant disadvantages. Thus, the question is, Gamma Knife surgery or conventional resection? The authors conclude that in older patients (older than 70 years) and in patients with other comorbidities in whom surgical intervention is contraindicated, initial GKRS is an acceptable alternative. Obviously, as the authors emphasize, an experienced team is needed to decide which treatment to use and to undertake the GKRS. One great disadvantage of GKRS is that the tumor is not investigated by pathologists. Morphological investigation is of crucial importance. Several diseases can mimic pituitary adenomas: for example, other primary intrasellar neoplasms, metastatic tumors, inflammatory diseases, and others. We have seen several metastatic carcinomas arising from the lung, colon, and other organs, which were mis diagnosed as pituitary adenomas! Another reason morphological investigation is important is that it allows one to draw conclusions regarding the growth potential of tumor cells. We can assess the Ki 67 nuclear labeling index, a valuable method of revealing the cell proliferation rate. Maybe in the future new drugs will be developed, which will permit medical therapy. Advances in molecular/genetic methods may provide an alternative treatment option as well. Obviously, more studies are needed to decide whether one should use GKRS and in which patients. (http://thejns.org/doi/abs/10.3171/2013.10.JNS132248) Disclosure