Ovarian hyperstimulation syndrome due to follicle-stimulating hormone-secreting pituitary adenomas

Purpose

Gonadotroph adenomas are pituitary adenomas with inefficient and variable secretory characteristics, that is why they are usually considered as a subgroup of nonfunctioning pituitary adenomas (NFPA) and are recognized only at immunohistochemistry. When gonadotroph adenomas secrete active hormones, they may cause spontaneous ovarian hyperstimulation syndrome (OHSS) in premenopausal women. Aim of our study is to describe three women with OHSS diagnosed before the removal of the adenoma and to calculate the prevalence of OHSS in premenopausal women with a clinical diagnosis of NFPA.

Methods

We reviewed clinical records of premenopausal women that underwent neurosurgery for NFPA at our centre between 1993 and 2014. OHSS was diagnosed in patients with high levels of FSH, suppressed LH, hyperestrogenism, abdominal symptoms, polymenorrhea, enlarged ovaries with cysts or previous surgery for ovarian cysts.

Results

171 women were included into the study; 62 (36.6%) had a gonadotroph adenoma diagnosed at immunohistochemistry. Two patients were retrospectively diagnosed as having OHSS due to gonadotroph adenoma and three had OHSS diagnosed before neurosurgery. The prevalence of OHSS was 2.9% in the overall group of patients with NFPA and 8.1% among patients with a gonadotroph adenoma detected at immunohistochemistry.

Conclusions

Frequency of OHSS due to a gonadotroph adenoma is not negligible. Increased awareness of the characteristic clinical and hormonal picture should permit an early detection of this condition in premenopausal women with a pituitary adenoma.

     

Double pituitary adenomas are most commonly associated with GH- and ACTH-secreting tumors: systematic review of the literature

Introduction

Double adenomas in the pituitary gland are a rare occurrence. The ability to cure a hormone-producing adenoma with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined.

Methods

Following PRISMA guidelines, we performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: “double pituitary adenomas”, “multiple pituitary adenomas” and only papers where multiple or truly separate double pituitary adenomas were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included.

Results

We reviewed papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1 with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary adenomas were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting.

Conclusion

Double pituitary adenomas are rare but most commonly found with GH- or ACTH-producing tumors. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing’s Disease.

     

Pituitary tumour apoplexy within prolactinomas in children: a more aggressive condition?

Objectives

To evaluate clinical presentations, diagnosis and management of paediatric patients presenting with pituitary apoplexy.

Methods

A retrospective case series describing a cohort of paediatric patients presenting with this condition from 2010–2016 to a tertiary referral children’s hospital in the United Kingdom.

Results

Pituitary apoplexy is a rare condition that seems to have a higher relative incidence in children than adults. Our series suggests that pituitary apoplexy in paediatric patients with adenomas appears more common than previously described. All our patients required surgery, either as an acute or delayed procedure, for visual compromise. Two patients had commenced growth hormone (GH) for GH deficiency two weeks prior to the onset of pituitary apoplexy.

Conclusions

With only a limited number of published case reports surrounding this topic our case series contributes to help further understand and manage this condition.

     

Management of cystic prolactinomas: a review

Introduction

Cystic prolactinoma is a variant of prolactin-secreting pituitary adenoma. The strategies for the management of cystic prolactinoma have not been addressed thoroughly in clinical guidelines.

Methods

A literature search was performed using Pubmed to review the current approaches to the treatment of cystic prolactinoma.

Results

Transsphenoidal resection is an effective and relatively safe approach for the treatment of cystic prolactinoma, however, morbidity of surgery is dependent on the skill of the surgeon. Emerging studies allude to the efficacy and safety of dopamine agonists in the management of cystic prolactinoma. Dopamine agonists are associated with considerable rates of clinical improvement and tumor shrinkage, hence reducing the need for surgical intervention.

Conclusions

Recent studies suggest that dopamine agonist therapy may be an effective and safe treatment option in a considerable portion of patients with cystic prolactinomas. We suggest that dopamine agonists should be considered as a first-line therapy for cystic prolactinoma in the absence of indications for early surgical intervention.

     

Pathology of GH-producing pituitary adenomas and GH cell hyperplasia of the pituitary

Introduction

Histologic, immunohistochemical and electron microscopic studies have provided conclusive evidence that a marked diversity exists between tumors which secrete growth hormone (GH) in excess. GH cell hyperplasia can also be associated with acromegaly in patients with extrapituitary GH—releasing hormone secreting tumors or in familial pituitary tumor syndromes.

Materials and methods

A literature search was performed for information regarding pathology, GH-producing tumors and acromegaly.

Results

This review summarizes the current knowledge on the morphology of GH-producing and silent GH adenomas, as well as GH hyperplasia of the pituitary.

Conclusion

The importance of morphologic classification and identification of different subgroups of patients with GH-producing adenomas and their impact on clinical management is discussed.

     

Pituitary tumors in MEN1: do not be misled by borderline elevated prolactin levels

Purpose

The objective of this case report is to demonstrate that the simple expedient of measuring periodic prolactin levels in patients with MEN1 who have modest hyperprolactinemia and normal pituitary MRI scans is insufficient to monitor for the development of pituitary adenomas.

Methods

Review of relevant literature and chart review.

Results

A 25 year old man with known MEN1 manifested by hyperparathyroidism and a gastrin-producing neuroendocrine tumor was found to have a prolactin [PRL] level of 20.0 ng/mL [1.6–16 ng/mL] but a normal pituitary MRI scan. The impression then was that he had prolactinoma too small to be visualized on the MRI. Over the next 3.5 years his PRL levels remained in this mildly elevated range but he then presented with severe headaches and visual field defects. An MRI showed a 3.1 × 1.7 × 1.9 cm pituitary adenoma with compression of the optic chiasm and invasion of the left cavernous sinus. Surgery revealed a gonadotroph adenoma and he subsequently required gamma knife radiotherapy for residual tumor. Postoperative PRL levels were normal.

Conclusions

Small, intrasellar microadenomas may be associated with elevated PRL levels due to possible direct hormone production [prolactinoma] or possibly to interference with portal vessel blood flow. In monitoring hyperprolactinemic MEN1 patients for the development of pituitary adenomas, measurement of PRL levels is insufficient and periodic MRI scans are necessary at a more frequent interval than every 3–5 years. This may also pertain to patients with “idiopathic” hyperprolactinemia.

     

Radiotherapy with concurrent temozolomide for the management of extraneural metastases in pituitary carcinoma

Background

Pituitary carcinomas (PC) are uncommon neuroendocrine tumors, accounting for 0.1 % of all pituitary tumors. The diagnosis of PC is based on the presence of metastases from a pituitary adenoma, and not by local invasion or pathological features alone. PC is typically resistant to therapy, with a median overall survival of only 31 months. There is no standard treatment for PC, but maximal safe resection and radiation are performed when possible. Encouraging preliminary data on the use of temozolomide (TMZ)-based therapy has been previously reported.

Methods

We report the response to therapy and safety of radiation with concurrent temozolomide (RT/TMZ) in 2 adult patients with heavily pretreated PC and extraneural metastases.

Results

Both patients had prior history of pituitary macroadenoma. At the time of diagnosis of PC, Ki-67 % was 24.2 and 10 %, with positive p53 staining in one case. Metastatic sites included lymph nodes, liver and bone. Case-1 received RT/TMZ to the tumor bed in the skull base and to the metastases in the cervical lymph nodes. Case-2 received RT/TMZ to recurrent tumor involving portacaval lymph nodes. Both patients achieved excellent long-term control of the sites of treated extraneural metastases, with no significant acute or delayed toxicity.

Conclusions

RT/TMZ was safely delivered and might provide sustained control of extraneural metastases in PC. Although this retrospective report has limitations, RT/TMZ can be considered as a therapeutic option for the management of extraneural metastases in PC.

     

Nationwide shift from microscopic to endoscopic transsphenoidal pituitary surgery

Purpose

Transsphenoidal pituitary surgery can be carried out with either an operating microscope or with an endoscope, but the relative frequency of both techniques is unknown.

Methods

All microscopic and endoscopic transsphenoidal pituitary surgeries were extracted from the Centers for Medicare and Medicaid Services Part B data files between the years 2003 and 2013. National and state-level trends were compared over time.

Results

Endoscopic surgery significantly increased and microscopic surgery significantly decreased over the years 2003–2013. Thirty-eight of 48 states increased their use of endoscopic surgery, while 38 of 48 states decreased their use of microscopic surgery.

Conclusions

Nationwide data show a clear trend for an increasing use of endoscopic transsphenoidal surgery at the expense of microscopic surgery. The underlying causes of these trends are unknown, but clearly deserve further investigation.

     

Epidemiology,clinical presentation and diagnosis of non-functioning pituitary adenomas

Purpose

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed.

Method

A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs.

Results

They account for 14–54% of pituitary adenomas and have a prevalence of 7–41.3/100,000 population. Their standardized incidence rate is 0.65–2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm.

Conclusion

This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.

     

Advances in malignant peritoneal mesothelioma

Background

Malignant mesothelioma is a rare, insidious, and aggressive tumor arising from the mesothelial surface of pleural and peritoneal cavities, the pericardium, or the tunica vaginalis, with an increasing incidence worldwide, high misdiagnosis rate, and overall negative prognosis. A total of 20 % of all cases is peritoneum in origin.

Methods

The present study is a review of literatures focusing on the advances in epidemiology, clinical presentations, radiological features, diagnosis, misdiagnosis, management, and prognostic factors of malignant peritoneal mesothelioma (MPM) occurred in the past decades.

Results

Asbestos, SV40, and radiation exposures have been demonstrated to be correlated with the pathogenesis of MPM. The main presentations are abdominal distension and pain. Computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) play an important role in the preoperative imaging and staging. Definitive diagnosis is made on the basis of immunohistochemistry. Prognostic factors have been identified and verified. Negative indicators include advanced age, male gender, poor performance status, non-epithelial histology, and absence of surgery. The management of MPM has evolved from single chemotherapy to multimodality treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), chemotherapy, radiotherapy, and immunotherapy. Promising results have been achieved after a combined treatment of CRS and HIPEC, with an elevated median survival time of 29.5–92 months and a 5-year survival rate of 39–63 %.

Conclusions

CRS and HIPEC represent the standard treatment strategy for selected patients with MPM, and patients with unresectable tumors can benefit from the combined treatment of chemotherapy, radiotherapy, and immunotherapy.

     

Corticotrophic pituitary carcinoma with cervical metastases: case series and literature review

Purpose

Pituitary tumors are the second most common intracranial tumors, however, pituitary carcinoma is a rare clinical entity which represents only 0.1–0.2% of all pituitary tumors. Diagnosis of pituitary carcinoma requires the presence of metastasis. Early identification of pituitary carcinoma is difficult, and only recently have guidelines been published for the treatment of aggressive pituitary tumors. We present two cases from our institution, with a review of other cases available in literature in order to better characterize this rare disease.

Methods

A retrospective review of two patients with pituitary carcinoma treated at a tertiary medical center was performed. The MEDLINE database was searched for all cases of pituitary carcinoma. Information for age at diagnosis, sex, pituitary tumor type, latency period from pituitary tumor to presentation of carcinoma, sites of metastasis, number of surgical therapies, radiation and chemotherapy, and survival after diagnosis were collected.

Results

A total of 69 studies were available for review for a total of 72 unique cases. The average age at diagnosis was 46.3 years. The most common tumors were ACTH-secreting (34.7%), Prolactin-secreting (23.6%), and Null Cell (15.3%). The average latency period from pituitary tumor diagnosis to metastasis was 9 years. All patients underwent surgical therapy during their treatment, with an average of 2.76 procedures. The mortality rate was 54.8% with average time to death after diagnosis of approximately 10 months.

Conclusions

Pituitary carcinoma is a rare disease with high mortality rate and is a diagnostic and treatment challenge. Further study is required but is difficult due to its low incidence.

     

The dangers of the “Head Down” position in patients with untreated pituitary macroadenomas: case series and review of literature

Purpose

Cavernous sinus syndrome is a rare phenomenon, characterized by simultaneous neuropathies of cranial nerves III–VI. Various pathological processes have been reported as precipitating etiologies, including infection, inflammation, vascular lesions, and neoplasms.

Purpose

We report a unique case series of cavernous sinus syndrome attributable to prolonged Trendelenburg or prone positioning during non-cranial procedures and review the pertinent literature to enlighten on this rare but catastrophic phenomenon.

Methods

Retrospective case series.

Results

In the past year we encountered two patients who presented with acute cavernous sinus syndrome upon awakening from non-cranial operations. One patient underwent an extensive urologic resection of a bladder malignancy positioned in Trendelenburg for approximately 4 h. The second patient underwent a lumbar laminectomy and discectomy in prone position. Both patients were discovered to have infarcted large pituitary macroadenomas as the etiology of their acute ophthalmoplegias, and transnasal, transsphenoidal resection was performed acutely to decompress the cavernous sinus contents. Pathologic analysis of the resected specimens in each case confirmed necrotic, infarcted pituitary adenoma. Both patients made a complete recovery with no evidence of residual or recurrent tumor in short term follow-up.

Conclusion

We report a brief case series of acute cavernous sinus syndrome resulting from dependent positioning during non-cranial operations in patients with pituitary macroadenoma. Although rare, this highlights a potential danger of “head down” positioning in patients with intracranial pathology—particularly in or around the sella and cavernous sinus. Despite multiple cranial neuropathies upon presentation, both patients made complete recovery following surgical decompression of the cavernous sinuses.

     

Patients cured of acromegaly do not experience improvement of their skull deformities

Purpose

Acromegaly is a rare disease that is associated with many co-morbidities. This condition also causes progressive deformity of the skull which includes frontal bossing and cranial thickening. Surgical and/or medical management can cure this condition in many patients, but it is not understood if patients cured of acromegaly experience regression of their skull deformities.

Methods

We performed a retrospective analysis on patients treated at our dedicated pituitary center from 2009 to 2014. We looked at all MRI images taken during the treatment of these patients and recorded measurements on eight skull dimensions. We then analyzed these measurements for changes over time.

Results

29 patients underwent curative treatment for acromegaly within our timeframe. The mean age for this population was 45.0 years old (range 19–70) and 55.2 % (n = 16) were female. All of these patients were treated with a transsphenoidal resection for a somatotropic pituitary adenoma. 9 (31.1%) of these patients required further medical therapy to be cured. We found statically significant variation in the coronal width of the sella turcica after therapy, which is likely attributable to changes from transsphenoidal surgery. None of the other dimensions had significant variation over time after cure.

Conclusion

Patients cured of acromegaly should not expect natural regression of their skull deformities. Our study suggests that both frontal bossing and cranial thickening do not return to normal after cure.

     

Management of pituicytomas: a multicenter series of eight cases

Purpose

Pituicytomas and spindle cell oncocytomas (SCOs) are two rare neoplasms of the sellar and suprasellar region, known to be challenging as they are extremely vascular and almost always misdiagnosed, altering our surgical planning and the patients’ outcomes. Also we argue that recent update concerning the pathology findings of these tumors should be more widely generalized to our practice.

Methods

This is a retrospective multicenter study, reporting the clinical manifestations, radiological characteristics, histopathological features, treatment strategies and long-term outcomes of patients who have been treated for a Pituicytoma at various institutions in Paris, France over the past 10 years. In addition, we compared our results to the world literature in order to identify similarities concerning the radiographic diagnosis and the treatment strategies of these tumors.

Results

Eight patients were operated on in four different hospitals. Misdiagnosis was constant before surgery, pituitary adenoma or craniopharyngioma being suspected. During surgery (transsphenoidal approach: six cases, transcranial approach: two cases) unusual tumors were noted, with important bleeding in most cases. Complete resection could be obtained in five patients. Pathological diagnosis was confirmed in all cases. During the follow up two recurrences occurred. One was subsequently treated with radiotherapy, the other underwent a second surgery.

Conclusion

Recent updates concerning the histological diagnosis of pituicytomas should be generalized to our practice in order to provide a better understanding of this rare pathology and its natural course.

     

Predictive role of dynamic contrast enhanced T1-weighted MR sequences in pre-surgical evaluation of macroadenomas consistency

Purpose

Our hypothesis was that pituitary macroadenomas show different areas of consistency detectable by enhanced magnetic resonance imaging (MRI) with Dynamic study during gadolinium administration.

Materials and methods

We analysed 21 patients with pituitary macroadenomas between June 2013 and June 2015. All patients underwent trans-sphenoidal surgery and neurosurgeon described macroadenomas consistency. Similarly, two neuroradiologists manually drew regions of interest (ROIs) inside the solid-appearing portions of macroadenoma and in the normal white matter both on dynamic and post-contrast acquisitions. The ratio between these ROIs, defined as Signal Intensity Ratio (SIR), allowed obtaining signal intensity curves over time on dynamic acquisition and a single value on post-contrast MRI. SIR values best differentiating solid from soft macroadenoma components were calculated and correlated with pathologic patterns. A two-sample T test and empiric receiver operating characteristic (ROC) curve of SIR was performed.

Results

According to ROC analysis, the SIR value of 1.92, obtained by dynamic acquisition, best distinguished soft and hard components. All the specimens from soft components were characterized by high cellularity, high representation of vascularization and micro-haemorrhage and low percentage of collagen content. The reverse was evident in hard components.

Conclusions

We demonstrated that dynamic MRI acquisition could distinguish with good accuracy macroadenomas consistency.

     

Single center study of 53 consecutive patients with pituitary stalk lesions

Background

The etiological spectrum of pituitary stalk lesions (PSL) is wide and yet specific compared to the other diseases of the sellar and suprasellar region. Because of the pituitary stalk’s (PS) critical location and role, biopsies of these lesions are rarely performed, and their underlying pathology is often a conundrum for clinicians. A pituitary MRI in association with a clinical context can facilitate their diagnosis.

Aim

To present the various causes of PSL—their clinical, hormonal, histopathological, and MRI characteristics in order to gain better insight into this pathology.

Method

A retrospective observational study consisting of 53 consecutive patients with PSL of the mean age 32?±?4.2 years (range 6–67), conducted at the Department for Neuroendocrinology, Clinical Center of Serbia 2010–2018.

Results

Congenital malformations were the most common cause of PSL in 25 of 53 patients (47.1%), followed by inflammatory (9/53; 16.9%) and neoplastic lesions (9/53; 16.9%). The exact cause of PSL was established in 31 (58.4%) patients, of whom 23 were with congenital PS abnormalities and 8 with histopathology of PSL (7 neoplastic and 1 Langerhans Cell Hystiocytosis). A probable diagnosis of PSL was stated in 12 patients (22.6%): 6 with lymphocytic panhypophysitis, while Rathke cleft cyst, tuberculosis, dissemination of malignancy in PS were each diagnosed in 2 patients. In 10 patients (18.8%), the etiology of PSL remained unknown.

Conclusion

Due to the inability of establishing an exact diagnosis, the management and prognosis of PSL are difficult in many patients. By presenting a wide array of causes implicated in this condition, we believe that our study can aid clinicians in the challenging cases of this pathology.

     

Risk-adapted,long-term management in childhood-onset craniopharyngioma

Purpose

This report is a review of findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients with special regard to clinical trials and long-term management.

Methods

Literature search on Pubmed for paper published after 1994.

Results

Craniopharyngiomas are rare, embryonic malformations of the sellar/parasellar region with low histological grade. Clinical manifestations are related to increased intracranial pressure, visual impairment, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized, therapy of choice is complete resection, with care taken to preserve hypothalamic and optic functions. In patients with unfavorable tumor location (i.e. involvement of hypothalamic areas), recommended therapy is limited hypothalamus-sparing surgical strategy followed by irradiation. Irradiation has proven effective in treatment of recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas can result in serious sequelae, mainly hypothalamic syndrome.

Conclusions

It is crucial that craniopharyngioma be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients’ by experienced multidisciplinary teams in the context of multicenter trials.

     

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.