Suprasellar adrenocorticotropic hormone-secreting ectopic pituitary adenoma: case report and literature Review

OBJECTIVE AND IMPORTANCE: Functional ectopic pituitary adenomas are rare and can be misdiagnosed as extensions of pituitary adenomas when they are located in the vicinity of the normal gland. In this report, we present a case of an ectopic adrenocorticotropic hormone-secreting suprasellar pituitary adenoma that caused Cushing's disease. A literature review of previously reported ectopic pituitary adenomas is included to illustrate the diverse clinical manifestations of this disease entity. CLINICAL PRESENTATION: An 11-year-old boy was noted to have hirsutism, a buffalo hump, and unexplained weight gain consistent with Cushing's syndrome. Laboratory investigations revealed that the boy had elevated adrenocorticotropic hormone and serum cortisol levels unsuppressed by dexamethasone. Magnetic resonance imaging scans were suggestive of a pituitary adenoma with suprasellar extension. INTERVENTION: The initial transsphenoidal approach failed to achieve complete surgical resection. A repeat operation in which the pterional approach was used revealed a suprasellar pituitary adenoma without association with intrasellar contents. The patient's cushingoid symptoms improved significantly 3 months after surgery. CONCLUSION: Ectopic pituitary adenomas should be considered in the differential diagnosis for all patients with Cushing's syndrome. Furthermore, surgical approaches should be chosen carefully once the diagnosis of ectopic pituitary adenoma is made.     

Ectopic pituitary adenoma of the third ventricle. Case report

Ectopic pituitary adenomas without associated intrasellar adenomas are rare and are usually located in the sphenoid sinus. Most have been reported without modern radiological, endocrinological, or electron microscopic (EM) documentation. The case of a 47-year-old man with a third ventricular, ectopic, clinically nonsecretory pituitary adenoma, which was shown to be a gonadotrophic adenoma by immunohistochemical and EM study, is reported. Neurological examination, extensive neurodiagnostic imaging, surgical anatomical observation, and endocrinological evaluation showed no evidence of neoplasia outside the third ventricle.     

Resection of suprasellar tumors by using a modified transsphenoidal approach. Report of four cases

Generally accepted contraindications to using a transsphenoidal approach for resection of tumors that arise in or extend into the suprasellar region include a normal-sized sella turcica, normal pituitary function, and adherence of tumor to vital intracranial structures. Thus, the transsphenoidal approach has traditionally been restricted to the removal of tumors involving the pituitary fossa and, occasionally, to suprasellar extensions of such tumors if the sella is enlarged. However, conventional transcranial approaches to the suprasellar region require significant brain retraction and offer limited visualization of contralateral tumor extension and the interface between the tumor and adjacent structures, such as the hypothalamus, third ventricle, optic apparatus, and major arteries. In this paper the authors describe successful removal of suprasellar tumors by using a modified transsphenoidal approach that circumvents some of the traditional contraindications to transsphenoidal surgery, while avoiding some of the disadvantages of transcranial surgery. Four patients harbored tumors (two craniopharyngiomas and two hemangioblastomas) that arose in the suprasellar region and were located either entirely (three patients) or primarily (one patient) within the suprasellar space. All patients had a normal-sized sella turcica. Preoperatively, three of the four patients had significant endocrinological deficits signifying involvement of the hypothalamus, pituitary stalk, or pituitary gland. Two patients exhibited preoperative visual field defects. For tumor excision, a recently described modification of the traditional transsphenoidal approach was used. Using this modification, one removes the posterior portion of the planum sphenoidale, allowing access to the suprasellar region. Total resection of tumor was achieved (including absence of residual tumor on follow-up imaging) in three of the four patients. In the remaining patient, total removal was not possible because of adherence of tumor to the hypothalamus and midbrain. One postoperative cerebrospinal fluid leak occurred. Postoperative endocrinological function was worse than preoperative function in one patient. No other new postoperative endocrinological or neurological deficits were encountered. This study demonstrates the feasibility of using a modified transsphenoidal approach for resection of certain suprasellar, nonpituitary tumors.     

Ectopic pituitary gland simulating a suprasellar tumor

A case report of ectopic pituitary gland in the suprasellar region of a normal 39-year-old woman with persistent headaches is presented. The embryological development of the pituitary gland is briefly reviewed, with a discussion of the relevant literature. No previous report of normal pituitary tissue in a suprasellar location in the absence of tumor could be found.     

Adjuvant γ-Knife Radiosurgery for a Resected Suprasellar Pituitary Adenoma with Atypical Immunohistochemistry: Case Report

A resected suprasellar mass was found to be an ectopic pituitary adenoma on light microscopy, but immunohistochemistry revealed unusual staining patterns. Residual disease was demonstrated on postoperative studies and -knife radiosurgery was used for treatment. The literature on ectopic pituitary tumors was reviewed. We concluded that postoperative stereotactic radiosurgery (SRS) for ectopic, suprasellar pituitary adenomas (and variants thereof) is an appropriate management option for persistent disease.     

Ectopic pituitary adenoma located at the pituitary stalk. Case report

Suprasellar located ectopic pituitary adenomas are unusual tumors. We report a rare case of suprasellar prolactinoma arising from the pars tuberalis in a 37-year-old woman. Menstrual disregulation and bitemporal hemianopsia were the main complaints. Blood tests revealed hyperprolactinemia. In magnetic resonance the tumor was totally supradiaphragmatic. Pterional craniotomy and total tumor excision was performed. The pituitary stalk was preserved. Histopathologic diagnosis was a pituitary adenoma immunoreactive for prolactin. Pituitary hormonal functions returned to normal at 6 months postoperatively. No complications were seen in the postoperative period. An ectopic adenoma should be suspected in a patient with suprasellar tumor and hyperprolactinemia. Surgical excision of this tumor may result with normal pituitary functions and normal visual acuity.     

Technical aspects and surgical strategy for removal of corticotroph pituitary adenoma

The development of transsphenoidal microsurgery and the refinement of endocrinological and radiological diagnostic procedures have afforded therapeutic options appropriate for each individual case in patients with pituitary-dependent hypercortisolism. Compared with other secreting pituitary tumors, the corticotroph adenoma seems to be the most biologically active tumor. Clinical evidence of hypercortisolism mainly occurs at an early stage of tumor growth when the tumor is very small, below the detection threshold of modern imaging techniques. While the treatment of large tumors remains difficult due to the non-discrete boundary lines of the tumor and extension or invasion, surgical removal of very tiny tumors requires reliable preoperative or peroperative identification in order to achieve total tumor resection for clinical remission and pituitary preservation to prevent hypopituitarism. We reviewed all the current surgical techniques or clever surgical procedures used to achieve both goals with the lowest complication rate. We report here the state-of-the-art of surgical management of corticotroph pituitary adenoma focusing on preoperative radiological and biological data required for performing guided intrasellar surgical exploration and reliable tumor identification. Different technical aspects of the nasosphenoidal approaches are reported as well as the modified transdiaphragmatic or transtubercular transcisternal approaches to tumors in a suprasellar localization or lying along the pituitary stalk. The advantages of minimally invasive surgical techniques such as intrasellar endoscopic surgery are discussed. Adapted surgical techniques for second transnasal surgery indicated for recurrent tumors are described. Guidelines are given for peroperative tumor identification with macroscopic assessment or histological control with frozen section biopsies. Different techniques for tumor removal are discussed from selective microadenomectomy to enlarged pituitary resection and total hypophysectomy. Methods for preoperative guidance of total tumor removal are proposed including histological or biological assessment of normal adjacent pituitary tissue. the strategy of surgical intrasellar exploration and tumor resection is outlined using a set of algorithms. The first is devoted to positive preoperative documentation of the tumor. The second is proposed for the surgical scenario where there is no preoperative MRI evidence of the tumor. Special strategies are discussed for ectopic adenoma or multiple tumors. Revision surgical management after surgical failure or tumor recurrence is described. Special guidelines for surgical treatment of large clinically silent corticotroph macroadenomas are given with emphasis on the high risk of recurrence in comparison with other silent pituitary tumors such as gonadotroph or immunonegative adenomas.     

Neuroendoscopic transventricular surgery for suprasellar cystic mass lesions such as cystic craniopharyngioma and Rathke cleft cyst

Cystic mass lesions in the suprasellar cistern are often associated with neurological deficits, cognitive disorders, and endocrinological impairments. Many surgical approaches are available to treat these mass lesions, but are technically difficult and cannot remove the lesion completely without risking damage to neurological and endocrinological functions due to the proximity to the surrounding structures. Neuroendoscopic transventricular surgery was performed using a ventricular fiberscope for three patients with craniopharyngiomas and two patients with Rathke cleft cysts, with gamma knife radiosurgery for craniopharyngiomas. The endoscopic transventricular approach is safe and minimally invasive for congenital benign suprasellar cystic lesions, especially arachnoid cysts.     

Suprasellar ectopic pituitary adenoma: case report and review of the literature

The occurrence of a totally suprasellar ectopic pituitary adenoma in a 71-year-old man is described. The tumor was attached to the pituitary stalk, extending upward toward the third ventricle. No intrasellar lesion was observed. Histological examination revealed a pituitary adenoma with large numbers of eosinophilic cells with moderate nuclear polymorphism and rare mitosis. Immunohistochemical staining revealed that the tumor cells were strongly positive for anti-adrenocorticotropic hormone antibody. A review of five previously reported intracranial ectopic pituitary adenomas revealed that two were silent corticotropic tumors and two occurred with Cushing's syndrome.     

Suprasellar peri-infundibular ectopic prolactinoma--case report

A 21-year-old man presented with bitemporal hemianopia and hyperprolactinemia. Magnetic resonance (MR) imaging showed a suprasellar cystic tumor in contact with the pituitary stalk. The diagnosis was craniopharyngioma. Intraoperatively, there was no clear continuity between the tumor and the tissue of the anterior lobe of the pituitary gland. The pituitary stalk and the diaphragma sellae were intact, and their morphology remained almost completely normal after the tumor was removed. The histological diagnosis was prolactin-producing pituitary adenoma. Postoperatively, the bitemporal hemianopia improved, and the serum prolactin levels returned to normal. The final diagnosis was suprasellar ectopic pituitary adenoma arising in the peri-infundibular region. Follow-up MR imaging at 1 year showed a normal pituitary stalk and pituitary gland, with no evidence of residual tumor.     

Suprasellar peri-infundibular ectopic adenohypophysis in fetal and adult brains

Ectopic anterior pituitary cells, identified by histological, electron microscopic, and immunohistochemical methods, were consistently found in the leptomeninges of the suprasellar peri-infundibular region of fetal brains. The cell groups were not in continuity with the pars tuberalis of the adenohypophysis. Suprasellar peri-infundibular ectopic pituitary cells, which showed no neoplastic character, were found in 15 of 20 "normal" adult brains that were similarly examined. This finding sheds new light on the possible origin of intracranial ectopic pituitary adenomas.     

Non-Neoplastic Cystic Lesions of the Sellar Region Presentation, Diagnosis and Management of Eight Cases and Review of the Literature

Summary  The differential diagnosis of a sellar lesion includes pituitary adenoma, cranio-pharyngioma, tumour cyst, benign cyst, and other less common lesions such as aneurysm, squamous cell carcinoma and metastases. Pure cystic lesions within the sella turcica are not uncommon and may appear clinically and radiologically as pituitary adenoma. Intrasellar cysts are broadly classified as neoplastic or non-neoplastic; the latter may be primary lesions of the pituitary fossa or they may arise from the parasellar region and invade into the sella. The lesions occupy space and may cause disturbance of pituitary function; if they extend into the suprasellar region they can affect visual fields and acuity. Non-neoplastic cystic lesions usually appear well defined radiologically and have distinct pathological features. Modern imaging modalities, such as computed axial tomography and magnetic resonance imaging, are important complementary tools of investigation for reaching a differential diagnosis, and for surgical planning. Most non-neoplastic sellar cysts can be approached through the trans-sphenoidal route, but large lesions with suprasellar extension may require transcranial surgery.  We report the presentation and management of eight cases (four males, four females, all adult) of non-neoplastic cyst involving the sella turcica and the parasellar region. Investigations included computed tomography scan of the head for all and magnetic resonance imaging for six (75%) patients. Work-up included endocrinological and opthalmological evaluations. All presented with headache; six (75%) had visual acuity change, two (25%) had evidence of visual field defects, four (50%) had optic atrophy on fundoscopy, three (37.5%) had endocrine symptoms and hormone reduction was found in four (50%).     

Endoscopic endonasal infrasellar approach to the sellar and suprasellar regions: technical note

We report a technical variation of the endoscopic endonasal approach to the sellar and suprasellar regions which relies on the use of a 45-degree angled endoscope. The so-called "infrasellar approach" aims at excising lesions situated within the intermediate and posterior lobes of the pituitary gland without damaging the anterior lobe, thus potentially minimizing endocrinological morbidity. In this regard the endoscopic infrasellar approach might be advantageous in selected cases when compared with the traditional transsphenoidal approach with the microscope. We describe the technique and illustrate it with representative clinical cases.     

Intracavernous Sinus Ectopic Adrenocorticotropin-Secreting Tumours Causing Therapeutic Failure in Transsphenoidal Surgery for Cushing's Disease

Summary  Background. The major cause of surgical failure in the treatment of Cushing's disease lies in unsuccessful identification of adenomas. In the present study, we investigated the pathogenesis of negative exploration in transsphenoidal surgery for Cushing's disease by analyzing neuro-imaging studies, endocrinological examination and selective venous sampling.  Methods. Thirty patients with ACTH-dependent Cushing's syndrome that met the endocrinological criteria for Cushing's disease were treated by transsphenoidal microsurgery. Depending on positive or negative identification of adenomas during the surgery, selective adenomectomy, partial hypophysectomy or subtotal hypophysectomy was performed.  Findings. All nine patients who underwent selective adenomectomy showed endocrinological remission and did not need any hormone replacement therapy. Of the 12 patients who underwent partial hypophysectomy, 11 showed normalization of hypercortisolism but seven needed permanent replacement of hydrocortisone. Four patients underwent subtotal hypophysectomy because no adenoma could be identified in spite of detailed exploration, and three of them showed remission but with permanent requirements of hydrocortisone and other pituitary hormones. Five patients, whose hypercortisolism persisted after initial surgery, underwent total hypophysectomy as secondary transsphenoidal surgery, and only one of them showed endocrinological remission. Of the six patients with surgical failure, four were thought to be rare cases in whom the ACTH-secreting tumours may have occurred ectopically in the cavernous sinus without direct contact with the pituitary gland. Endocrinologically, these four patients showed a low or no response to corticotropin releasing hormone (CRH) stimulation, and for three of them, radiation therapy to the sellar region including the cavernous sinus was effective for persistent hypercortisolemia.  Interpretation. Recognition of an ectopic intracavernous sinus ACTH-secreting tumour as a pathological entity for Cushing's disease may not only enhance the diagnostic accuracy but also be important for determining the optimal surgical mode for persistent Cushing's disease.     

Flexible endoscope-assisted endonasal transsphenoidal surgery for pituitary tumors.

We have performed rigid endoscope-assisted endonasal transsphenoidal microsurgeries for pituitary tumors in 230 patients. Recently, we further introduced the use of a flexible endoscope to inspect the tumor bed and suprasellar structures more extensively. We report our experience with the flexible endoscope in endonasal transsphenoidal surgery for pituitary tumors. The endoscopes were used to complement the microscope in visualization. The flexible endoscopes were used in 34 recent cases with suprasellar and/or lateral tumor extension. During or after removal of the main tumor bulk, the flexible endoscope together with a rigid endoscope was used to inspect the tumor cavity, especially at the blind spot of the microscope. Despite limited resolving power, in all the 34 cases the flexible endoscope was a highly efficient tool permitting extensive visualization of almost the whole surgical area, even in narrow surgical fields and spaces not visible with an operating microscope or a rigid endoscope, and allowing continuous change of viewing angle. The residual tumor situated laterally or in the suprasellar areas that could not be reached and was impossible to remove by a rigid endoscope could be dissected and extirpated under a flexible endoscope using grasping forceps in 5 patients with pituitary adenoma and all the craniopharyngioma cases. The flexible endoscope may be more efficient in the lateral and suprasellar areas than the rigid endoscope in compensating for the narrow surgical field in endonasal pituitary surgery, despite its limited resolving power. Surgeons should make the best use of the advantages of each instrument.     

A case of ectopic pituitary adenoma occurring in the sphenoid sinus

Ectopic pituitary adenomas are relatively rare tumors. We present a case of ectopic pituitary adenoma occurring in the sphenoid sinus. A 63-year-old woman was referred to our hospital complaining of headache. She had no endocrinological abnormalities. Magnetic resonance imaging showed a tumor in the sphenoid sinus, adjacent to the sellar floor and appearing as a low-signal on T1-weighted image and a high signal on T2-weighted image. No connection between the normal pituitary gland and tumor was observed. Using an endonasal-transsphenoidal approach assisted with neuro-endoscopy, we performed total removal of the tumor. No connection between the normal pituitary gland and the tumor was found. Histopathological analysis showed a pituitary adenoma. As demonstrated by our case report, differential diagnosis of a tumor occurring in the sphenoid sinus must include consideration of the existence of an ectopic pituitary adenoma.     

Pituitary apoplexy with localized hematoma in the suprasellar region

The authors report a case of a patient with a pituitary tumor, in which pituitary apoplexy occurred only in the suprasellar part of the tumor. A 26-year-old woman suffered from abrupt worsening of vision and headache. A CT scan showed a dumb-bell-shaped tumor extending to the suprasellar region, in which an irregularly shaped low density area suggesting a liquidized hematoma was seen. The rapid worsening of her symptoms was highly indicative of pituitary apoplexy. The first operation was performed through the transsphenoidal route. There was no evidence of intratumoral hematoma in the intrasellar tumor, which could be removed successfully. However, the suprasellar mass could not be reached because of the hardness of the diaphragma sellae and the presence of a normal pituitary gland. MRI and CT cisternography after this first operation showed a narrow opening of the diaphragma sellae. The second operation using right frontotemporal craniotomy disclosed a suprasellar mass, which consisted of an old hematoma and a necrotic tumor. The tumor was sub-totally removed. The patient's visual acuity improved after the second operation. Although transsphenoidal surgery is the treatment of choice in patients with pituitary apoplexy, the selection of the surgical route should be made only after careful neuroradiological evaluation with regard to the extrasellar extension of the tumor.     

Lymphoid adenohypophysitis, with special reference to 2 cases with sellar tumors spontaneously disappearing on the CT

Lymphoid adenohypophysitis is an autoimmune disorder. Eighteen percent of the multipartums are reported to have autoantibodies to pituitary tissues. The symptoms in lymphoid adenohypophysitis, such as hypopituitarism and sellar tumors, exhibit spontaneous remission. The pituitary is a feasible target organ in other autoimmune diseases of the endocrine system. Of these patients, 19/287 showed a positive immune reaction with pituitary tissue antigens. Our three female patients with sellar and suprasellar mass were clinically diagnosed as having lymphoid adenohypophysitis, because of the spontaneous regression of tumors, or presence of immunologically and endocrinologically abnormal findings. The first case was a 31-year-old woman who had amenorrhea and galactorrhea syndrome for two years after delivery of her second child. CT scan revealed a supraseller enhanced mass lesion. She had concomitant signs of recurrent meningeal irritations. The number of cells in the CSF increased, though the protein concentration increased only slightly. During a one-year close observation, the suprasellar mass spontaneously regressed. The second patient was a 66-year-old woman. In 1945, she underwent hysterectomy and oophorectomy for appendicitis followed by adnexitis. She was admitted because of episodes of headache, vomiting and visual field defect in 1983. CT scan also showed a contrast enhanced mass in the suprasellar region. She had two episodes of high fever. After the treatment with antibiotics and anti-inflammatory agents for 4 months, the tumor disappeared. The third case was a 20-year-old female. She had neither neurological nor endocrinological abnormality, except for attacks of vertigo, nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnetic resonance imaging after transsphenoidal surgery of clinically non-functional pituitary macroadenomas and its impact on detecting residual adenoma

Summary. Summary.   Background and Purpose: In clinically non-functional pituitary macroadenomas, prospective follow-up magnetic resonance imaging (MRI) was conducted after transsphenoidal surgery both to study the changes of the sellar contents at the post-operative site over time and to assess the amount of residual adenoma tissue.   Methods: A total of 50 patients with clinically non-functional pituitary macroadenomas were treated by transsphenoidal tumour resection and were examined by MRI before and directly after surgery (early MR) and 3 months (intermediate MR) and 1 year after surgery (late MR). Changes in the sellar contents over time and the degree of tumour excision were studied on T1-weighted enhanced and unenhanced scans. All patients underwent complete neuro-ophthalmological and endocrinological assessments before and 3 months after surgery. For the interpretation of the post-operative images the results of the endocrinological examinations after surgery were also taken into account.   Results: The maximum size of tumour extension on coronal T1-weighted images ranged from 1.2 cm to 5.0 cm (mean 2.3 cm). Despite tumour resection, early post-operative images still showed a persistent mass in the sella in 83% that was usually caused by post-operative haemorrhage, fluid collection and implanted fat material. However, rapid improvement in visual symptoms was noted in 89%. Changes in the sellar region at the early post-operative site markedly hindered the interpretation of MR images for detecting residual tumour tissue, which was suspected in half of the patients (1 intrasellar, 13 suprasellar, and 11 parasellar). Regression of the post-operative mass in the sella was present 3 months after surgery, resulting in a 50% change in the volume of the coronal sellar extension, which also improved the reliability in interpreting the post-operative MR images. On the intermediate MR images residual tumour tissue was detected in 30% of the patients (4 intrasellar, 2 suprasellar and 9 parasellar). Because the suprasellar mass descended over time, an increasing rate of tumour remnant within the sella was seen 3 months following surgery. Before surgery the pituitary gland was visible superiorly or posterosuperiorly to the macroadenomas in 35 patients. However, at the early post-operative site the remaining gland was only visible in 12 patients. Under the condition that endocrinological function tests confirmed adequate hormonal function, the remaining gland was detectable by MRI in 36 patients 3 months after surgery.   Conclusion: Delayed regression of the sellar contents after transsphenoidal surgery of pituitary macroadenomas was demonstrated by this prospective MR study. Owing to the changes at the post-operative site, it was difficult to interpret early post-operative images and detect residual adenoma tissue. With respect to the delayed regression of the sellar contents, the interpretation of post-operative images for detection of residual adenoma was improved 3 months after surgery. At this time, residual adenoma tissue was found in 30% of clinically non-functional macroadenomas, mostly at the parasellar and, after descent from the suprasellar space, at the intrasellar site.     

A case of pleomorphic TSH-producing pituitary adenoma with calcification

We reported a rare case of pleomorphic TSH-producing pituitary adenoma with calcification and reviewed the literature. A 25-year-old female was admitted to our hospital with a complaint of anterior neck swelling. An endocrinological examination demonstrated elevated serum levels of free triiodothyronine (FT3: 5.6 pg/ml), free thyroxin (FT4: 2.2 ng/dl), TSH (5.85 microIU/ml), and TSH a-subunit (5.9 ng/ml), whereas a physical examination revealed no goiter. CT scan showed a suprasellar isodensity mass with dense calcification. Contrast-enhanced T1-weighted images revealed a less enhancing tumor extending from the left upper portion of pituitary fossa into suprasellar cistern. The patient underwent gross total removal of the tumor via the right pterional approach. Microscopically, medium-sized to enlarged tumor cells with marked pleomorphism and prominent calcification were observed.The tumor cells displayed positive reaction for TSH (beta-subunit). The MIB-1 index averaged 2.9%. The histological diagnosis was a pleomorphic TSH-producing pituitary adenoma. Postoperatively, the serum levels of FT3, FT4, TSH, and TSH alpha-subunit decreased to normal range. Follow-up MR images showed no evidence of recurrent tumor 3 years after the resection. All of six patients with densely calcified TSH-producing pituitary adenoma, previously reported in the literature, remained well without tumor recurrence. We suggest that this type of TSH-producing pituitary adenoma may be associated with favorable prognosis despite histologically pleomorphic appearance.