Primary tumors of the posterior pituitary: A systematic review

In 2017, the World Health Organization established that pituicytoma, granular cell tumor (GCT), spindle cell oncocytoma (SCO) and sellar ependymomas (SE) are posterior pituitary tumors (PPT). They probably arise from the pituicytes and may constitute a unique histopathological entity. We carried out a systematic review using PubMed’s database. A total of 266 patients with pathological diagnosis of PPT (135 pituicytomas, 69 GCT, 47 SCO, 8 SE and 7 mixed histology tumors) were analyzed. Gender distribution was identical and median age at diagnosis was 48?±?21.8 years. Main presentation symptoms were visual disorders (n?=?142; 58.1%), headache (n?=?99; 40.5%), hypopituitarism (n?=?84; 34.4%), hypercortisolism (n?=?10; 4.1%), polyuriapolydipsia (n?=?6; 2.4%) and acromegaly features (n?=?5; 2.0%). On MRI, 122 (47.6%) patients showed sellar with suprasellar extension masses, 67 (23.1%) were suprasellar and 63 (24.6%) exclusively sellar. Median tumor size was 22.0?±?14.2 mm. Two hundred sixty four patients underwent surgery, transphenoidal access was selected in 132 (64.4%) and craniotomy in 58 (28.3%). Complications were hypopituitarism (n?=?70; 42.1%), diabetes insipidus (n?=?55; 33.1%) and hemorrhage (n?=?50; 30.1%). Tumor persisted in 93 patients (45.6%) and recurred in 13 (6.4%). Regarding comparison between main types of PPT, SCO patients were diagnosed later (60.0 vs 47.0 vs 47.0 years, p?=?0.023), the tumor was larger 25.0 mm [10.8] vs 20.0 mm [14.2] vs 2.0 mm [15.0] and they were frequently sellar with suprasellar extension tumors (71.7% vs 46.2% vs 32.8%, p?=?0.003) compared to pituicytoma and GCT. In conclusion, PPT are rare tumors and have been misdiagnosed mainly as non-functioning pituitary adenomas. Different types of PPT share similar epidemiology, clinical manifestations and surgical outcomes. Surgery is the only curative option but complications and subtotal resection are common.

     

Contribution of sellar dura integrity to symptom manifestation in pituitary adenomas with intratumoral hemorrhage

Purpose

Although hemorrhage within pituitary adenomas frequently exacerbates the symptoms, there are many grades of severity. Moreover, the contributing factors for symptom severity are still controversial.

Methods

This retrospective study included 82 patients who underwent transsphenoidal surgery for pituitary adenomas with intratumoral hemorrhage. The grades of preoperative symptoms were classified into group A, asymptomatic or minor symptoms; group B, moderate symptoms sufficient for complain; and group C, severe symptoms disturbing daily life.

Results

The hemorrhage volume within an adenoma was significantly higher in group C (92.6%) than in groups A (48.6%) and B (58.7%). Both headache and diplopia were dominant in group C, occurring in 72.2% and 27.8% of the patients, respectively. In group C, there was no significant difference in frequency between adenoma extensions into the sphenoid sinus (0%) and involvement of the cavernous sinus of Knosp grade 4 (0%), and extensions into the suprasellar region were not common (38.9%). The most distinctive feature was that “no extrasellar extension” was found only in group C (41.2%), and “multidirectional extension” was not detected in this group (0%). Multiple regression analysis revealed that the most powerful determining factors were the high frequencies of intratumoral hemorrhage and lack of extrasellar and multidirectional extensions.

Conclusion

Rapid volume expansion of a hematoma and lack of extension or unidirectional extension might lead to significant compression of the sellar and surrounding structures. Of note, the integrity of the sellar dura might contribute to the acute onset of symptom manifestations caused by hemorrhage in pituitary adenomas.

     

Sellar and suprasellar mixed germ cell tumor mimicking a pituitary adenoma

Germ cell tumors (GCT) are a heterogeneous group of lesions whose origin is not well established. Several cases of primary intrasellar germinomas have been reported, however non-germinomatous GCT have rarely been described. We report the case of a young adult male patient with a mixed GCT that presented with a sellar tumor with suprasellar extension. The patient seeked medical attention because of seizures and magnetic resonance imaging evidenced a tumor of the sellar region. Hyperprolactinemia was also present and dopamine agonist therapy was started. As there was a rapid tumor growth and the patient had concomitant central diabetes insipidus and elevated testosterone levels, a GCT was suspected and confirmed by elevated serum concentration of β-human chorionic gonadotrophin. Patient underwent surgical resection of the tumor and histopathological examination confirmed the diagnosis of a mixed GCT. Chemotherapy was initiated, followed by conventional radiotherapy. In conclusion, although pituitary adenomas respond for the vast majority of sellar tumors, concomitant symptoms such as central diabetes insipidus and rapid tumor growth should raise the suspicion of a diverse diagnosis. The present report intend not only to show a rare case of sellar and suprasellar mixed GCT but also to remind clinicians that if laboratory findings do not fit into patient’s diagnosis (such as high testosterone levels in our patient), then the diagnosis should be reviewed.     

Clinical features of nonpituitary sellar lesions in a large surgical series

Context Pituitary adenomas are the most common lesions in the sellar region, but other pathologies need to be considered in the differential diagnosis. Objective To assess the prevalence of unusual sellar masses in a large series of patients and identify clinicopathological factors that may aid the pre‐operative diagnosis. Design Retrospective case series. Patients We analysed the records of 1469 transsphenoidal procedures performed between 1998 and 2009. One hundred sixteen cases (7·9%) were not pituitary adenomas. Measurements Final pathological diagnosis. Results One hundred sixteen patients (45 men, 71 women; mean age (±SD): 45 ± 17 years) with nonadenomatous lesions were divided into four major aetiological groups: cystic lesions (CYS) (53%); benign neoplasms (BEN) (22%); malignancies (MAL) (16%) and inflammatory lesions (INF) (9%). Rathke’s cysts, the most common lesions, represented 42% of all cases. Twenty‐five per cent of malignant lesions were metastases, and some of the MAL (e.g., fibrosarcoma, lung metastasis) had a radiographical appearance suggestive of a pituitary adenoma. The most common presenting symptoms were visual field impairment (51%) and headache (34%). Pre‐operative pituitary dysfunction was present in 58% of cases, with hyperprolactinaemia (35%), hypogonadism (23%) and hypocortisolism (23%) found most frequently. Postoperative resolution of headache and visual symptoms occurred in 63% and 65% of patients, respectively. Hyperprolactinaemia resolved in 77% of cases. Conclusions A substantial minority of sellar masses are not pituitary adenomas. While they frequently present with the symptoms, hormone abnormalities and radiographical appearance typical of pituitary tumours, the possibility of a nonadenomatous lesion needs to be considered in the differential diagnosis.     

Primary pituitary lymphoma in immunocompetent patient: diagnostic problems and prolonged follow-up

Primary pituitary lymphoma in immunocompetent patients is a rare disease and has been described in less than 20 cases. Moreover, low-grade lymphomas constitute only 3% of all primary central nervous system lymphoma. The objective of this report is to report a low-grade primary pituitary lymphoma, diagnostic problems and to give more evidence about the evolution of this rare disease. A 49 y.o. woman was referred to our clinic with symptoms of hypopituitarism. A diagnostic work-up showed mild anemia, an erythrocyte sedimentation rate of 122 mm/h and a negative Elisa test for HIV. Panhypopituitarism was confirmed and the MRI showed a 20 mm sellar and suprasellar enhancing mass with a thickening of the pituitary stalk, chiasmal compression and bitemporal hemianopsia. She underwent transsphenoidal resection only 10 months later for non medical reasons. During this period she was clinically asymptomatic on hormonal replacement therapy. A new MRI showed regression of the suprasellar extension and invasion to the left cavernous sinus. A firm and infiltrative mass was found during transsphenoidal surgery, and only partial resection was performed. Biopsy showed a low-grade lymphoplasmacytic lymphoma. Staging was negative for other localizations. She was given chemotherapy and localized radiotherapy. Four years after surgery, the sellar MRI showed a 10 mm residual sellar mass with the persistence of a cavernous sinus invasion and she is considered to be in remission. The neurosurgeon and clinician should consider primary pituitary lymphoma as a potential cause of a sellar mass, especially in the presence of diabetes insipidus and an enhancing invasive mass. Neurosurgical biopsy is crucial for a correct diagnosis and prognosis could be better than classic CNS primary lymphomas.     

Schwannoma in Sellar Region Mimics Invasive Pituitary Macroadenoma: Literature Review With One Case Report

In central nervous system, schwannomas, as ubiquitous tumors, mostly originate from sensory nerves like auditory and trigeminal nerves. However, intrasellar schwannomas are extremely rare. They are often misdiagnosed as pituitary adenomas.We report a rare case of schwannoma in the sellar region—a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological test.We represent a 65-year-old woman who had suffered from headaches, hypothyroidism, and visual disturbance. Her MRI revealed an abnormal sellar region mixed-signal mass lesion with suprasellar, left parasellar, and sellar floor invasiveness. We present detailed analysis of the patient''s disease course and review relevant literatures. Written informed consent was obtained from the patient for publication of this article. A copy of the written consent is available for review by the editors of MEDICINE. Because this article does not involve any human or animal trials, there is no need to conduct special ethic review and the ethical approval is not necessary.When surgically treated, her specimen revealed a typical histopathology pattern of schwannoma. The patient''s symptoms improved a lot after surgery and he continues to be under observation.Despite its rarity, intrasellar schwannoma should be considered in the differential diagnosis of sellar lesions that mimic pituitary adenomas.     

Long term outcome following repeat transsphenoidal surgery for recurrent endocrine-inactive pituitary adenomas

It is widely accepted that the standard first-line treatment for most endocrine inactive pituitary macroadenomas (EIA) is surgery, usually via a transsphenoidal approach. What is less clear is what approach to take when these tumors recur, especially when this recurrence involves areas which are difficult to surgically remove tumor from, such as the suprasellar region or cavernous sinuses. We present long term follow-up for a series of 81 patients who underwent repeat surgery for recurrent non-secreting pituitary adenomas. We analyzed data collected from all adult patients undergoing their second microsurgical transsphenoidal resection of a histologically proven endocrine-inactive pituitary adenoma at the University of California at San Francisco between January 1970 and March 2001. Data for these patients were collected by review of medical records, mail, and/or telephone interviews. Visual function, anterior pituitary function, and tumor control rates were analyzed for the series. Records were available for a total of 81 recurrent EIA patients. The median time between their initial and repeat operations was 4.1 years. The mean tumor size was 2.2 ± 0.2 cm. A total of 35/81 patients had greater than 5 years of follow-up. A total of 24/81 patients had greater than 10 years of follow-up. Over one half of these patients presented with visual disturbance, and we found that 39% of these patients experienced improved vision with a second surgery. More importantly, no one with normal vision suffered any appreciable decline in vision. Approximately, 35% of patients with pre-operative anterior pituitary dysfunction recovered function after surgery in our series; and no patient’s function worsened. A total of 4/52 (8%) patients with greater than 2 years of post-op follow-up experienced a clinically meaningful tumor recurrence requiring additional treatment. Our data suggest that when performed by experienced transsphenoidal surgeons, durable tumor control can be obtained in these frequently locally aggressive tumors with acceptable rates of post-operative morbidity.     

Immunohistochemical detection of estrogen receptor alpha in pituitary adenomas and its correlation with cellular replication

With the aim of evaluating the relationship between pituitary tumorigenesis and the presence of estrogen receptor-alpha (ERalpha) by immunohistochemistry (IH) and their relevance to patients' clinical presentation, hormonal phenotypes of adenomas, preoperative neuroimaging findings, and the index of cellular replication MIB-1, a study was conducted with material from 91 women and 67 men with pituitary adenomas. The patients had acromegaly (29.7%), Cushing's disease (14.6%), hyperprolactinemic syndrome (20.9%), and clinically nonfunctioning tumors (34.8%). Of the patients, 14.6% had microadenomas, 52.5% had macroadenomas with or without suprasellar growth, 28.5% had invasive macroadenomas and in 4.4% the adenoma was not visualized. IH showed that 43 were positive for growth hormone (GH), 16 for corticotropin (ACTH), 18 for prolactin (PRL), 18 for PRL+GH, 6 for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), 15 had a plurihormonal reaction, and 42 had nonfunctioning adenomas. The presence of ERalpha was positive in 9/158 adenomas with a median value for the percentage of labeled cells of 42.89%, and in 6/16 controls (autopsy samples) with a median value for the percentage of labeled cells of 0.024%. ERalpha was significantly more prevalent in controls than in patients with adenomas (37.5 versus 5.7%; p = 0.001); however, the mean ERalpha concentration in adenomas was significantly greater than in controls (42.89 versus 0.024%; p < 0.001). No significant difference in the concentration of ERalpha was found across the clinical presentations, hormonal phenotypes or findings of preoperative CT. Among the ERalpha-positive adenomas, ERalpha values were significantly greater in invasive macroadenomas (80%) than in microadenomas (3.33%). MIB-1 values did not differ significantly between ERalpha-positive and -negative adenomas, nor did the correlation between ERalpha values and the MIB-1 index attain significance in the total sample, even when only ERalpha-positive adenomas and positive MIB-1 indexes were considered. It was concluded that, when present in pituitary tumors, ERalpha exhibits a high concentration, and is more common in nonfunctioning and invasive adenomas, but absent in ACTH-secreting ones.     

The clinical significance of MIB-1 labeling index in pituitary adenomas

Pituitary adenomas are unique in several ways—they are rarely malignant and yet can be invasive of several compartments. Recurrences in tumors with bland histological features that have been radically excised are a reason for frustration faced by endocrinologists and neurosurgeons in treatment of pituitary adenomas. Several attempts have therefore been made to determine the growth potential of pituitary adenomas. The aim of the present study was to define the biological significance of the MIB-1 labelling index (MIB-1 LI) in pituitary adenomas. The study included 159 cases of surgically treated pituitary adenoma seen in a single institution. MIB-1 LI was not found to be related to age or gender. The mean MIB-1 LI for clinically functional adenomas was marginally higher than that for clinically non-functional adenomas. There was a significant difference in the MIB-1 LI for tumors with a maximum diameter of more than 4 cm at a MIB-1 LI of ≥2%, however this difference was not statistically significant at a higher MIB-1 LI cut off value of >3%. The mean MIB-1 LI was significantly higher in tumors causing hydrocephalus and in those with cavernous sinus invasion and not when invasion was defined as invasion by tumor in any direction. We conclude that large pituitary macroadenomas, tumors filling the third ventricle causing hydrocephalus and tumors with true cavernous sinus invasions are more likely to have a higher proliferation index. Close follow up of tumors showing these imaging features would be recommended.     

Stereotactic radiofrequency ablation of tumors at the hepatic venous confluence

BackgroundRadiofrequency ablation (RFA) is subject to “heat-sink” effects, particularly for treatment of tumors adjacent to major vessels.MethodsIn this retrospective study, 104 patients with 137 tumors (40 HCC, 10 ICC and 54 metastatic liver tumors) close to (≤1 cm from) the hepatic venous confluence underwent stereotactic RFA (SRFA) between June 2003 and June 2018. Median tumor size was 3.7 cm (1.4–8.5) for HCC, 6.4 cm (0.5–11) for ICC and 3.8 cm (0.5–13) for metastases. Endpoints comprised safety, local tumor control, overall and disease-free survival.ResultsThe overall major complication rate was 16.0% (20/125 ablations), where 8 (40%) were successfully treated by the interventional radiologist in the same anesthetic session and did not prolong hospital stay. 134/137 (97.8%) tumors were successfully ablated at initial SRFA. Local recurrence (LR) developed in 19/137 tumors (13.9%). The median and overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 51.5 months, 73.5%, 67.0%, and 49.7% for HCC, 14.6 months, 60.0%, 32.0% and 32.0% for ICC and 38.1 months, 91.4%, 56.5% and 27.9% for metastatic disease, respectively.ConclusionSRFA represents a viable alternative to hepatic resection for challenging tumors at the hepatic venous confluence.     

Necrotizing infundibulo-hypophysitis: an entity too rare to be true?

We report a young woman with sudden and severe retroorbital headache, neck pain, and a large sellar mass extending to the suprasellar cistern. A presumptive diagnosis of non-secreting pituitary macroadenoma undergoing apoplexy was made and transphenoidal surgery performed. Histopathology revealed mononuclear infiltration and marked non-hemorrhagic necrosis of the anterior pituitary consistent with a diagnosis of necrotizing infundibulo-hypophysitis. The possible pathogenesis of this rare variant of hypophysitis is discussed.     

An electrophysiological study of cultured human pituitary cells

The electrophysiological properties of tumoral pituitary cells were studied in 4 types of human adenomas including prolactinomas, growth-hormone-secreting tumors, adrenocorticotropinhormone-secreting adenoma and “non-functioning” tumors. Only 9% of the cells from prolactinomas and ACTH tumors were excitable but they never elicited spontaneous action potentials. These cells did not respond to substances known to act on the hormone-releasing process (thyreoliberin, dopamine). However, 37% of the cells cultured from growth-hormone-secreting adenomas and from “non-functioning” tumors displayed action potentials. The action potential was calcium-dependent i.e., it was blocked by cobalt, nickel and methoxyverapamil and could be recorded in a sodium-free medium. Thyreoliberin triggered action potentials, whereas dopamine and γ-aminobutyric acid inhibited electrical activity.These results show that human tumoral pituitary cells in culture are able to generate Ca²⁺-dependent action potentials. The data from growth-hormone-secreting tumors are in good agreement with the stimulus-secretion coupling concept; however, differences in the response of cells cultured from other types of human pituitary tumors suggest that each type of adenoma has specialized membrane properties.     

Significant improvement of intractable headache after transsphenoidal surgery in patients with pituitary adenomas; preoperative neuroradiological evaluation and intraoperative intrasellar pressure measurement

Object

Headache is the most common symptom of both primary and metastatic brain tumor, and is generally considered the primary symptom in patients with large pituitary adenomas. However, patients with small pituitary adenomas rarely complain of intractable headache, and neurosurgeons are unsure whether such small adenomas actually contribute to headache. If conventional medical treatments for headache prove ineffective, surgical removal of the adenoma can be considered as an alternative management strategy.

Methods

We conducted a retrospective review of 180 patients who underwent transsphenoidal surgery (TSS) for pituitary adenomas at Kanazawa University Hospital between 2006 and 2014. Patients with acute phase intratumoral hemorrhage were excluded. We identified nine patients with intractable headache as the chief complaint associated with small pituitary adenoma (diameters 15.8 ± 2.6 mm, 11–20 mm), non-functioning in eight, and prolactin-secreting in one. The preoperative neuroradiological studies and headache characteristics were assessed retrospectively, and the intrasellar pressure evaluation was performed during TSS in the last seven patients.

Results

All nine patients had complete or substantial resolution of their formerly intractable headache after TSS. Headaches consisted of ocular pain ipsilateral to the adenoma localization within the sella in four cases and bifrontal headache in five. Magnetic resonance imaging of these patients revealed small diaphragmatic foramen, which were so narrow that only the pituitary stalk could pass. Computed tomography scans showed ossification beneath the sellar floor in the sphenoid sinus, presellar type in six cases, and choncal type in three. The adenomas included cysts in seven cases. There was no cavernous sinus invasion. Intrasellar pressure measurements averaged 41.5 ± 8.5 mmHg, range 34–59, significantly higher than in control patients without headache (n = 12), namely 22.2 ± 10.6 mmHg (16–30).

Conclusion

In this study, the authors demonstrated the validity of TSS in the treatment of intractable headache associated with pituitary adenoma. The presence of ocular pain, especially ipsilateral to the adenoma, integrity of the diaphragm sella, and ossification in the sphenoid sinus, cyst or hemorrhage and the absence of cavernous sinus invasion were the indications for TSS for patients complaining of intractable headache and having pituitary adenomas.

     

Primary sellar melanocytic tumor: report of new case and literature review

Context primary sellar melanocytic tumors are extremely rare, and they can mimic hormonally inactive pituitary macroadenoma both clinically and radiologically. Objectives the aim of this study was to describe a new case of primary sellar melanocytic tumor, and place it in the context of published literature. Design this is a case report. Patient the case of a 61-year-old woman presenting with a 2-month history of fatigue and progressive bitemporal hemianopia is described. Endocrine investigation revealed anterior pituitary insufficiency and hyperprolactinemia without diabetes insipidus. Magnetic resonance imaging demonstrated a sellar tumor mass with suprasellar extension compressing the optic chiasm, and intense gadolinium enhancement. Transsphenoidal surgical excision of the pituitary tumor was undertaken. Histological examination showed a melanocytic tumor. An extensive search failed to find evidence of any other primary or secondary site. Due to the presence of significant tumor residue at 3-month follow-up, another surgical resection was done followed by post-operative stereotactic radiotherapy of the sellar region. Conclusion Primary sellar melanocytic tumors are exceptional lesions presenting most often as a tumor syndrome and/or anterior pituitary insufficiency mimicking a non-secreting pituitary macroadenoma. The management of these tumors consists of surgical removal of the tumor. However, surgery is often incomplete and stereotactic fractionated radiotherapy is frequently indicated.     

Ambulatory diagnosis and outpatient management of patients with hypophyseal adenomas

In 88 patients with adenomas of the pituitary gland, among them 24 hormone-inactive tumours, 27 somatotropic adenomas and 37 prolactinomas, anamnestic data, clinical, endocrinologic and localisation-diagnostic findings as well as therapeutic measures were evaluated. Main symptoms were headache and visual disturbances. 78 of the 88 patients with adenomas of the pituitary gland were able to work at the time, when the diagnosis was made. In about 32% of the patients partial defects of the visual field were present and in 35% in the cranial computed tomogram a suprasellar and parasellar, respectively, expansion of the tumour and thus an advanced stage of the disease was established. The number of the residual findings and recidivations, respectively was great in all the three forms of the adenomas of the pituitary gland. In the prolactinomas and the somatotropic adenomas of the pituitary gland a medicamentous secondary therapy with dopamine agonists is possible. The therapy with bromocriptine reveals good results particularly in prolactinomas.     

Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center

Pituitary tumors are challenging tumors in the sellar region. Surgical approaches to the pituitary have undergone numerous refinements over the last 100 years. The introduction of the endoscope have revolutionized pituitary surgery. The aim of this study is to report the results of a consecutive series of patients undergoing pituitary surgery using a pure endoscopic endonasal approach and to evaluate the efficacy and safety of this procedure. We reviewed the data of 228 consecutive patients who underwent endonasal transsphenoidal adenoma removal over an 10-year period. Pre- and post-operative hormonal status (at least 3 months after surgery) were analyzed and compared with clinical parameters presented by the patients. Tumor removal rate, endocrinological outcomes, and complications were retrospectively assessed in 228 patients with pituitary adenomas who underwent 251 procedures between December 1998 and December 2007. There were 93 nonfunctioning adenomas, 58 growth hormone-secreting, 41 prolactin-secreting, 28 adrenocorticotropin hormone secreting, 7 FSH-LH secreting and 1 thyroid-stimulating hormone-secreting adenomas. Gross total removal was achieved in 79.3% of the cases after a median follow-up of 61.5 months. The remission results for patients with nonfunctioning adenomas was 83% and for functioning adenomas were 76.3% (70.6% for GH hormone-secreting, 85.3% for prolactin hormone-secreting, 71.4% for ACTH hormone-secreting, 85.7% for FSH-LH hormone-secreting and 100% for TSH hormone-secreting), with no recurrence at the time of the last follow-up. Post-operative complications were present in 35 (13.9%) cases. The most frequent complications were temporary and permanent diabetes insipidus (six and two cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (two cases) and CSF leaks (eight cases). There was no death related to the procedure in this series. The endoscopic endonasal approach for resection of pituitary adenomas, provides acceptable results representing a safe alternative procedure to the microscopic approach. This less invasive method, associated with a small number of complications, provides excellent tumor removal rates and represents an important tool for the achievement of good results in the pituitary surgery, mainly for the complete removal of large adenomas.     

Rare sellar lesions.

Sellar masses are associated most commonly with pituitary adenomas. Many other neoplastic, inflammatory, infectious, and vascular lesions, however, may affect the sellar region and mimic pituitary tumors. These lesions must be considered in a differential diagnosis. This article describes the characteristics of rare sellar masses that provide clues to their differential diagnosis.     

Silent corticotroph adenomas

Silent corticotroph pituitary adenomas (SCA) are defined as pituitary adenomas showing positive staining for adrenocorticotrophic hormone in immunohistochemical studies, but not associated with perioperative clinical or laboratory features of hypercortisolaemia. They account for 1.1-6% of surgically removed pituitary adenomas. Currently, two distinct pathologic subtypes of SCA are recognised. Their pathogenesis remains unclear. They present with local mass effects (headache, visual deterioration, cranial nerve palsies, endocrine dysfunction). The lack of manifestations of cortisol excess has not been conclusively explained. In surgical series, most tumours are macroadenomas with suprasellar extension present in 87-100% of the cases; this is in contrast to Cushing's disease, which is mostly attributed to microadenomas. Surgery remains the main therapeutic approach. Attempts to identify predictors of recurrence have not been successful. Management and follow-up protocols should be planned taking into account their potential aggressive behaviour, particularly upon recurrence. The development of florid pituitary Cushing's syndrome and local recurrence followed by metastatic disease (occasionally outside the central nervous system) have been rarely reported.