Silent Pituitary Adenomas Research Articles

Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma.

Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH) but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS) melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

Male Gonadotroph Adenoma: Report of Three Cases and a Review of the Literature

We herein report three cases of gonadotroph adenoma in men (36-72 years of age) presenting with visual impairment and suprasellar masses measuring approximately 20 to 30 mm in diameter. Endocrinological examinations were normal, except for slightly increased follicle stimulating hormone (FSH) levels in two cases. Based on the tentative diagnosis of non-functioning pituitary adenoma, transsphenoidal surgery was performed, which revealed that the tumors consisted of FSH- and LH-positive cells. As gonadotroph adenoma is very common among patients with clinically silent pituitary adenoma, it should be diagnosed using pathological examinations.

Neurocysticercosis, Meningioma, and Silent Corticotroph Pituitary Adenoma in a 61-Year-Old Woman

We report here the case of a 61-year-old woman who presented with hydrocephalus and cystic and solid lesions in sella turcica, suprasellar areas, and third ventricle. After ventriculoperitoneal shunt she developed cognitive changes and the cystic lesions enlarged. Magnetic resonance imaging (MRI) demonstrated multiple cysts and a solid lesion in the sella and around the anterior clinoid process. With diagnosis of neurocysticercosis she underwent craniotomy. Pathologic examination documented two different lesions: viable and dead cysticerci with inflaming infiltration and a left anterior clinoidal meningioma. At the second surgery, six weeks later via transnasal transsphenoidal approach a silent corticotroph pituitary adenoma was removed which was studied by histology, immunohistochemistry, and electron microscopy. To our knowledge, the occurrence of these three different lesions in the sellar area was not described before.

Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature

Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.

Isolated sixth cranial nerve palsy as the presenting symptom of a rapidly expanding ACTH positive pituitary adenoma: a case report

BackgroundPituitary adenoma may present with neuro-ophthalmic manifestations and, typically, rapid tumor expansion is the result of apoplexy. Herein, we present the first case of an isolated sixth cranial nerve palsy as initial feature of a rapidly expanding ACTH positive silent tumor without apoplexy.Case PresentationA 44 year old female with a history of sarcoidosis presented with an isolated sixth cranial nerve palsy as the initial clinical feature of a rapidly expanding ACTH positive silent pituitary adenoma. The patient underwent emergent transsphenoidal hypophysectomy for this rapidly progressive tumor and subsequently regained complete vision and ocular motility. Despite tumor extension into the cavernous sinus, the other cranial nerves were spared during the initial presentation.ConclusionsThis case illustrates the need to consider a rapidly growing pituitary tumor as a possibility when presented with a rapidly progressive ophthalmoplegia.

Intracranial tumors in Kuwait: a 15-year survey

The dearth of literature on intracranial tumors (ICT) in Kuwait has necessitated this study whose objective is epidemiological. It is based on the records of the Department of Pathology, Al-Sabah Hospital, Kuwait, where virtually all brain biopsies in Kuwait were examined. Between 1995 and 2009, 439 males (53.41%) and 383 females (46.59%) had primary intracranial tumors (PICT). Most (69%) were younger than 50 years, with 16% children and adolescents and 4% elderly (≥70 years); meningioma (28%), pituitary adenoma (19%), glioblastoma (15%), astrocytoma (13%), and medulloblastoma (5%) were the most common. In childhood and adolescence, astrocytoma (35.34%) and medulloblastoma (22.56%) predominated. The mean age-adjusted incidence rate/100,000 was: PICT: 3.02; astrocytic tumors: 0.93; meningioma: 0.96; pituitary adenoma: 0.44; and medulloblastoma: 0.13. All showed a declining trend which was only statistically significant for medulloblastoma (P = 0.007). A modest correlation between the percentage of elderly in the general population and incidence rates was found (r = 0.411). Tumors with significant male preponderance were high-grade astrocytic tumors, silent pituitary adenoma (SA), and nerve sheath tumor. Meningioma had a female to male ratio of 2.24. The peak frequency for functional pituitary adenoma and females was in the age range of 20-29 years, while for SA and males it was 40-49 years. About 5% of ICT were metastatic, with cancers of breast (26%), lung (17%) and gastrointestinal (11%) origin as the most common. In conclusion, the epidemiology of PICT in Kuwait is characterized by low incidence rates and a distinct age distribution.

Unexpected enlargement of clinically silent pituitary gonadotroph adenoma induced by goserelin acetate given as treatment for prostate cancer

International Journal of UrologyVolume 18, Issue 1 p. 83-84 Unexpected enlargement of clinically silent pituitary gonadotroph adenoma induced by goserelin acetate given as treatment for prostate cancer Yusuke Ito md , Yusuke Ito md Department of Urology, Yokosuka Kyosai Hospital, Kanagawa, Japan[email protected]Search for more papers by this author Yusuke Ito md , Yusuke Ito md Department of Urology, Yokosuka Kyosai Hospital, Kanagawa, Japan[email protected]Search for more papers by this author First published: 16 November 2010 https://doi.org/10.1111/j.1442-2042.2010.02676.xCitations: 8Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume18, Issue1January 2011Pages 83-84 RelatedInformation

Immunoexpression of endoglin and CD‐34 in various human pituitary adenoma types

Angiogenesis is a crucial event in tumor growth, invasion and development of metastasis. Endoglin (CD‐105), a disulfide‐linked homodimeric cell membrane glycoprotein of 180 kDa, located on chromosome 9q and binds to several components of the TGF beta family. In contrast to other endothelial cell markers, endoglin can be demonstrated only in proliferating endothelial cells. We investigated endoglin immunoexpression in various surgically removed human pituitary tumor types and compared the results with CD‐34 immunoexpression. For immunohistochemistry, the streptavidin‐biotin‐peroxidase complex method was used and the number of vessels were counted in 10 low power fields. Results show that endoglin immunostains fewer vessels than CD‐34 in every pituitary adenoma type. The number of endoglin immunopositive vessels is highest in untreated prolactinomas and subtype 3 silent pituitary adenomas and lowest in subtype 1 silent corticotroph adenomas and GH adenomas exposed to somatostatin analogs and prolactinomas exposed to dopamine agonists. Our findings are consistent with the view that endoglin is upregulated in proliferating endothelial cells and its expression can be used as an indicator of vascular neoformation in pituitary tumors. The low levels of endoglin expression in pituitary tumors exposed to somatostatin or dopamine agonists suggests that these therapeutic drugs can inhibit angiogenesis.

Collision Tumors of the Sella: Craniopharyngioma and Silent Pituitary Adenoma Subtype 3: Case Report

Collision tumors of the sella turcica are rare and consist mainly of more than one type of pituitary adenoma, usually a corticotropin- and a prolactin-producing adenoma. The association of a craniopharyngioma and a pituitary adenoma is rare. Herein, we report the first case of an association between craniopharyngioma and silent pituitary adenoma subtype 3. It involved a 12-year-old boy who underwent a frontal craniotomy with surgical removal of a calcified sellar tumor. Histology revealed an adamantinomatous craniopharyngioma; however, by electron microscopy, there was conclusive evidence of adenoma cells showing the ultrastructural features of silent pituitary adenoma subtype 3. Endocrine and neuroimaging as well as detailed immunohistochemical and ultrastructural studies were undertaken. The literature is also reviewed.

Adenoma related pituitary apoplexy disclosed by ptosis after routine cardiac surgery: occasional reappearance of a dismal complication

Sir: Pituitary apoplexy is characterized by a sudden onset of headache, visual symptoms, altered mental status, and hormonal dysfunction. This condition usually stems from an acute expansion of a pituitary adenoma, which may deprive the anterior pituitary gland and the tumor itself of vascular supply, thus causing ischemia and subsequent necrosis [1, 2]. During cardiac surgery, cardiopulmonary bypass-induced cerebral edema may contribute to the critical enlargement of silent pituitary adenomas [3]. Cardiopulmonary bypass may also cause infarction and/or hemorrhage in pituitary adenomas in view of an increase susceptibility to hypoperfusion or ischemia of the abnormal pituitary tissue and/or to an increased risk of bleeding as a result of anticoagulation [4, 5]. We present herein the case of a 70year-old man with exertional angina and diagnosis of three-vessel coronary artery disease admitted for elective coronary bypass surgery. Past medical history revealed hypercholesterolemia, peripheral vascular disease and chronic obstructive pulmonary disease. Neurological examination on admission was normal. After conventional general anesthesia and systemic heparin administration, on cardiopulmonary bypass, myocardial revascularization was achieved by anastomosis of the left internal mammary artery to the left anterior descending coronary artery, and vein grafts to the first diagonal, obtuse marginal, and right coronary arteries, respectively. Aortic cross clamp time and total cardiopulmonary bypass time were 64 and 118 min, respectively. In view of an initial uneventful post-operative course, the patient was awakened and extubated 4 h later. Soon thereafter, he started complaining of headache and visual field defects, with diplopia. Neurological examination revealed initially sole ptosis of the left eye, followed by unilateral dilated pupil with a left globe deviated inferiorly and laterally with inability to adduct or abduct. Funduscopy revealed neither papilloedema nor hemorrhage. He was conscious at all time, with no evidence of hypotension or shock, requiring volume and/or inotropic adjustment. An urgent brain CT-scan demonstrated a sellar mass with suprasellar extension. Magnetic resonance imaging confirmed the sellar tumor suggestive of pituitary macroadenoma extended to the left cavernous sinuses (Fig. 1a, b). On T2-weighted images, the lesion was isointense but showed increased signal intensity on T1-weighted images, suggestive of hemorrhage. There was no infarct or hemorrhage seen elsewhere in the brain. Tests of serum at early morning showed the following levels: thyroxine 0.8 lg/L (normal range 0.9–1.8 lg/L), luteinizing hormone 0.9 IU/L (normal range 2.4–15.9 IU/L), prolactin 0.7 lg/L (normal range 2.8–29.9 lg/ L), cortisol 5 lg/dL (normal range 5–25 lg/dL), TSH 0.5 mIU/L (normal range 0.4–4 mIU/L), ACTH 7 ng/L (normal range 9–52 ng/L), FSH 1.3 IU/L (normal range 1–14 IU/L), GH 0.9 ng/mL (normal

Modification of hormonal secretion in clinically silent pituitary adenomas

Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

Silent Familial Isolated Pituitary Adenomas: Histopathological and Clinical Case Report

Familial isolated pituitary adenoma (FIPA) is a rare condition independent of Carney Complex or MEN1. An international multicenter study recently described 28 nonfunctioning pituitary adenomas in 26 families with only two homogeneous nonsecreting phenotype families consistent of silent GH and silent gonadotroph adenomas, respectively. We present the clinical, genetic, and morphological analysis of two silent pituitary adenomas occurring in a man and his daughter, and discuss the differential diagnosis associated with their histological, immunohistochemical, and ultrastructural features. The patients developed invasive nonsecreting macroadenomas manifesting only with compressive symptoms. Genetic analysis in the father showed no MEN-1 germ-line mutation. Tissue samples obtained after paraseptal trans-sphenoidal surgery were studied by immunohistochemistry for adenohypophyseal hormones, low molecular weight cytokeratins (CAM 5.2), proliferation markers, and anterior pituitary transcription factors (Pit-1 and SF-1) and by electron microscopy for secretory granules. The clinical, histological, and immunohistochemical features of the lesions posed a differential diagnosis between a null cell adenoma and a silent corticotroph adenoma (Type II); on the basis of immunohistochemical stains for cytokeratin and adenohypophysis cell lineage markers, tumor behavior and ultrastructural studies we concluded for the second. The reported cases represent an as yet undescribed example of homogeneous family with silent corticotroph adenomas (Type II). Our observations support the trend for more aggressive behavior in nonsecreting FIPAs as compared with sporadic adenomas.

Clinical Tumor Growth and Comparison with Proliferation Markers in Non-functioning (Inactive) Pituitary Adenomas

As the development of clinically silent pituitary adenomas is not yet fully understood, the radiologically measured growth of inactive pituitary adenomas should be compared with adenoma classification and immunostainings for proliferation markers. In 32 patients with non-functioning adenomas (NFA) from 45 operations with retrospectively available preoperative series of magnetic resonance imaging (MRI) we measured the largest growing diameter (LGD) in mm/ year. The adenomas were immunostained for Ki-67 (MiB-1), PCNA, p53 protein, IGF- and PTH-related protein. The positive nuclei for MiB-1, PCNA, and p53 protein were counted and their labelling indices (LI) were calculated. The clinical measurements were compared with these data and were statistically analysed (Spearman test, Whitney-U-test). The growth rate per year was available in 28 cases. We chosed three grades of LGD: less than 1.5 mm in diameter in 9 patients (32%), between 1.5 and 3.0 mm in 11 patients (39%) and more than 3.0 mm in 8 patients (29%). MiB-1 positive nuclei were found in 42% of adenomas, PCNA positive nuclei in 58% and p53 positive nuclei in 16%. IGF 1 was immuno-stained in 84% of adenomas. The mean LI for MiB-1 was 0.12 in adenomas growing less than 1.5 mm and 0.34 in adenomas growing more than 1.5 mm per year. For non-invasive adenomas, the MiB-1 LI was 0.03, for invasive adenomas it was 0.126 and for strongly invasive adenomas 0.212. The MiB-1 LI was lower in null cell adenomas than in FSH/LH adenomas. All these data for MiB-1 showed no statistically significant differences (p<0.05). PCNA LI in adenomas growing less than 1.5 mm per year was 0.51 in contrast to LI of 1.12 for those growing more than 1.5 mm. In non-invasive adenomas the PCNA LI was 0.796, in invasive adenomas 0.655 and in diffuse strongly invasive ones 1.011. Null cell adenomas had a lower PCNA LI than FSH/LH cell adenomas. Statistically significant differences were measured for the growth rate und the PCNA expression. P53 was immunostained in invasive adenomas only. There were no correlations to the clinical growth rate, but p53 expression correlated significantly to numbers of MiB-1 positive nuclei and PCNA positive nuclei. IGF-I expression was found to correlate inversely with age of patients. We recommend the use of PCNA if correlations to progression of tumor growth are wanted.

Silent Corticotroph Cell Pituitary Adenoma in a Struma Ovarii

This is the first report of a silent corticotroph cell pituitary adenoma arising in a struma ovarii. The patient, a 79-year-old woman, was found to have an asymptomatic left-sided adnexal mass confirmed by vaginal sonography to be a complex cystic and solid tumor. Pathological analysis demonstrated an 8-cm partially cystic struma ovarii in which there was a focus of predominantly basophilic adenohypophyseal cells arranged in a diffuse pattern, adjacent to mature neural tissue containing numerous Herring bodies. The epithelial lining cells of the colloid-filled small and cystic follicles were immunoreactive for thyroglobulin. The pituitary cells were predominantly immunoreactive for adrenocorticotropic hormone, in addition to synaptophysin.

Abundant hypermethylation of SOCS-1 in clinically silent pituitary adenomas

Janus kinase (JAK)/signal transducers and activators of transcription (STAT) cascade are required for cytokines, growth factors, G-proteins and hormones (growth hormone and prolactin). Gatekeepers in this pathway are the suppressor of cytokine signalling (SOCS) family of proteins. Their expression level is epigenetically regulated by DNA methylation. We have investigated the CpG island methylation status of SOCS-1 in a cohort of pituitary adenomas (PA; n=57), craniopharyngiomas (CP; n=30) and normal pituitary tissue (NP; n=11) using methylation sensitive single-strand conformation polymorphism analysis (MS-SSCP) and direct sequencing. SOCS-1 hypermethylation was identified in 51% (29/57) of surgical specimens obtained from PA patients. 83% of these tumours were clinically silent. In contrast, no methylation of SOCS-1 was observed in CPs or NPs. Quantitative real-time PCR and western blot analysis confirmed reduced SOCS-1 expression in the majority of pituitary adenomas. The data is compatible with epigenetic silencing of the SOCS-1 gene and constitutive activation of the JAK-STAT pathway in PA. This appears to contribute particularly to those tumours characterized by a hormone-inactive status.

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

Histopathological Review of Silent Pituitary Somatotroph Adenoma

Silent pituitary somatotroph adenoma is an adenoma that expresses growth hormone (GH) and GH mRNA and has ultrastructural features common to somatotroph adenoma, without evidence of acromegaly. Forty-one silent somatotroph adenomas were reported in the literature, and their relatively common clinical symptoms include amenorrhea and/or galactorrhea. Random GH and insulin-like growth factor-1 levels are within normal in nearly half of the patients, whereas random PRL level is elevated in about 80% of patients. Generally, the GH immunostaining of silent somatotroph adenoma is weaker than that of classical somatotroph adenoma. Tissue culture studies indicate silent somatotroph adenoma has a very low basal secretory capacity of GH. Most of the silent somatotroph adenomas reported in the literature are sparsely granulated adenomas. The mechanism of silence may be attributed to unknown translational abnormalities of GH gene product, impaired secretion of GH, lack of biological activity of secreted GH, or it may represent an early stage of classical somatotroph adenoma. Meticulous endocrinological and histopathological examination may be helpful for the identification of silent somatotroph adenoma among patients with clinically non-functioning adenomas, especially female patients with amenorrhea and/or galactorrhea.

Nearly Silent Pituitary Adenoma Presenting as Blood‐Tinged Sputum

Nearly Silent Pituitary Adenoma Presenting as Blood‐Tinged Sputum

Nearly silent pituitary adenoma presenting as blood-tinged sputum

Nearly silent pituitary adenoma presenting as blood-tinged sputum

Identification of a silent pituitary somatotropic adenoma based on a paradoxic response of growth hormone on a thyrotropin-releasing hormone or gonadotropin-releasing hormone provocation test

Preoperative endocrinologic identification and surgical removal of a silent somatotropic adenoma among patients with either amenorrhea or galactorrhea, or both, are beneficial for the restoration of menstruation and ovulation. Paradoxic rises of serum growth hormone in either a thyrotropin-releasing hormone or a gonadotropin-releasing hormone provocation test and high serum growth hormone levels were noted in the 3 patients with a silent somatotropic adenoma. (Am J Obstet Gynecol 2001;184:286-8.)