Plurihormonal Pituitary Adenomas Research Articles

Case Report A Rare Case of Plurihormonal Pituitary Adenoma Associating Cushing's Disease and Silent Prolactinoma

Plurihormonal pituitary adenomas are rare conditions that secrete two or more pituitary hormones. The association of prolactin with other hormones is described but associated with ACTH is uncommon. We report a rare case of mixed adenoma associating Cushing’s disease and silent prolactin adenoma in 21 years old male patient. This case highlights an unusual plurihormonal pituitary adenoma case with a rare association between ACTH and prolactin. It pathogeny is less clearly define.

Plurihormonal pituitary macroadenoma:\xa0 a case report

BackgroundPlurihormonal pituitary adenomas are a unique type of pituitary adenomas that secrete two or more pituitary hormones normally associated with separate cell types that have different immunocytochemical and ultrastructural features. Although they represent 10–15% of all pituitary tumors, only a small fraction of plurihormonal pituitary adenomas clinically secrete multiple hormones. The most common hormone combinations secreted by plurihormonal pituitary adenomas are growth hormone, prolactin, and one or more glycoprotein hormones. The most common hormonal symptom is acromegaly (50%). The aim of this case report is to bring awareness about this rare type of pituitary adenomas and to describe the unique presentation of our patient, even though plurihormonal pituitary adenomas are known mostly as a clinically silent tumors.Case presentationHerein, we describe an unusual case of plurihormonal pituitary adenoma with triple-positive staining for adrenocorticotropic hormone, growth hormone, and prolactin. The patient is a 65-year-old Egyptian woman who presented with mass effect symptoms of the pituitary tumor, which primarily manifested as severe headache and visual field defects. She also presented with some cushingoid features, and further analysis confirmed Cushing’s disease; slightly high prolactin and normal growth hormone levels were observed. She underwent transsphenoidal surgery and has been in remission thus far. Only a few cases have been reported in the literature, but none has exhibited silent acromegaly or mass effect symptoms as the initial presentation.ConclusionThis case highlights an unusual plurihormonal pituitary adenoma case with a rare combination of secreted hormones; mass effect symptoms were dominant, as were uncommon visual field defects. Our case further proves that immunohistochemical analyses of all pituitary hormones are needed to ensure correct diagnosis and to alert clinicians to the need for more rigorous follow-up due to the higher morbidity of these patients. Our case report approval number Federal Wide Assurance NIH, USA is FWA00018774 IRB registration number with OHRP/NIH is IRB00010471.

Immunohistochemical Profile of Nonfunctioning Pituitary Adenomas

Background: Nonfunctioning pituitary adenomas (NFPAs) are neuro-endocrine tumors without clinical and laboratory signs of anterior pituitary hormonal hypersecretion. The recent World Health Organization classification is based on the adenohypophyseal cell lineages and requires immunohistochemical evaluation of adenohypophyseal hormones and pituitary transcription factors. There are few data regarding the age and sex prevalence of different cell-types nonfunctioning adenomas and clinical data correlations. Objective: To discover the immunohistochemical profile of large cohort of NFPAs. Materials and Methods: The study includes 100 consecutive cases of endoscopically transsphenoidally removed nonfunctional pituitary adenomas, immunohistochemically assessed for anterior pituitary hormones and transcription factors. Clinical presentation, imaging, laboratory hormonal data and immunohistochemical staining features have been analyzed. All patients (64 women and 36 men) have been divided into four age groups: 20-34 (A) years old, 35-44 (B) years old, 45-59 (C) years old, 60-70 (D) years old. Peculiarities of immunohistochemical profile have been statistically analyzed in those age groups. Results: Most tumors (97%) were macroadenomas with mass effect symptoms. In the groups of silent corticotroph and Pit-1 adenomas most of the patients had subclinical symptoms of hormonal hypersecretion. The proportions of silent gonadotroph adenomas have appeared to be increased with age with predominant prevalence in group D (60%) in women and group C (78, 6%) in men. The proportions of silent Pit-1 adenomas decreased with age with maximum rate in group A (77,8%) in women and in group A (50%) in men. The incidence of silent corticotroph adenomas was different: increasing with age in women with maximum (36,8%) in group C and decreasing from young age (30%-0%) in men age groups B-D respectively. Plurihormonal pituitary adenomas from different cell lineages were found only in women, with maximum incidence rate (17,6%) in group B. The incidence of “null cell” adenomas didn’t differ in men and women in group B and C but was much more higher in men in groups A and D (16,7% vs 0% and 33% vs 6,6% respectively). Conclusions: The different age and sex prevalence of NFPAs, revealed in our study, may be helpful in diagnosing and optimal treatment of NFPAs.

Patients with true mixed growth hormone and prolactin-secreting pituitary adenoma: a case series of 12 patients

Objective: Mixed growth hormone (GH) and prolactin (PRL) secreting adenomas are the most common type of plurihormonal pituitary adenomas. We assessed the clinical presentations and impacts of transsphenoidal surgery (TS) on patients with mixed GH and PRL adenomas including surgical outcomes, complications, and prognosis.Method and patients: Twelve patients (7 males, 5 females) were operated in the neurosurgery department of Qilu hospital affiliated to Shandong University, Shandong, China. We analyzed hormone levels of preoperation, postoperation (within 24 h) and at 12-month follow-up and correlated levels with tumor volumes.Results: The remission rate was 66.7% (8/12), the recurrence rate was 16.7% (2/12), the cause-specific mortality was 0 and the overall mortality rate was 16.7% (2/12) due to stroke and myocardial infarction respectively. A significant drop was seen in GH, PRL, and Insulin-like-growth-factor-1 (IGF-1) levels between preoperation and postoperation with mean values from 52.6 to 9.9 ng/ml (p = 0.0015), from 321.6 to 190.9 ng/ml (p = 0.0026) and from 815.7 to 230.6 ng/ml (p = 0.0004), respectively. This drop was more significant between preoperation and follow-up with mean values from 52.6 to 3.0 ng/ml (p = 0.002), from 321.6 to 61.6 ng/ml (p < 0.0001), and from 815.7 to 195.0 ng/ml (p = 0.0001), respectively. However, there was no significant correlation between tumor volume and all of the hormone levels.Conclusions: Most mixed GH and PRL adenomas are aggressive with a high risk of recurrence and mortality.

Clinicopathologic Characteristics and Surgical Treatment of Plurihormonal Pituitary Adenomas

Plurihormonal pituitary adenomas (PPAs) have recently been divided into 2 subtypes: pituitary specific transcription factor 1-positive plurihormonal pituitary adenomas (PIT-1+ PPAs) and plurihormonal adenomas with unusual immunohistochemical combinations (PAwUIC). The purpose of this study was to review patients with PPAs, elucidate their clinicopathologic characteristics, and present the surgical results. Records were analyzed for 665 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenomas between 2007 and 2018. Data were reviewed for 27 patients who met the definition of PPAs and delineated regarding clinical, radiologic, pathologic features, and surgical outcomes. Of the 27 patients, 18 had PAwUIC, and 9 patients were diagnosed with PIT-1+ PPAs. Twenty-four patients (88.8%) had macroadenomas, including 6 giant adenomas (≥4 cm) (22.2%). Cavernous sinus invasion was found in 12 patients (44.4%). Pathologic examinations showed high aggressivity in nearly half of the patients. Most patients with PAwUIC (77.8%) had features of nonfunctioning pituitary adenomas, and only 4 had features of hormone-secreting pituitary adenomas. Gross total resection rates were 57.1% for PAwUIC and 77.8% for PIT-1+ PPAs. The remission rate for hormone-secreting pituitary adenomas was 100% in this case series. Mean follow-up was 74.4 ± 33 months (range, 6-121 months) for overall groups. To our knowledge, this is the first study to describe the clinicopathologic features of newly classified PPAs, which are characterized by aggressive behavior with higher values of percentage of cavernous sinus invasion. Relevant pathologic diagnosis of PPAs is crucial for appropriate management and follow-up.

SAT-LB081 Growth Hormone and Prolactin Secreting Plurihormonal Pituitary Adenomas, Experience of a National Health Institute in Mexico

Introduction Pituitary adenomas represent approximately 15% of all intracranial neoplasms. Those with the ability to produce more than one hormone are called plurihormonal pituitary adenomas. They are divided into monomorphic, single cell type may produces two or more hormones, and plurimorphic, different cell types may produce multiple hormones. Materials and methods We performed a retrospective review of all patients diagnosed with hyperprolactinemia and acromegaly secondary to pituitary adenoma during the period 2004-2018. Then, we identified 10 patients with high serum levels of PRL and IGF-1. Six of these patients were excluded due to hyperprolactinemia secondary to pituitary stalk compression. We collected clinical, biochemical and medical imaging information. We compared the clinical and biochemical characteristics before and after treatment. Results We identified 4 female patients with GH/PRL-secreting plurihormonal pituitary adenoma. The average age at diagnosis was 25 years-old (20-32). We documented high serum levels of IGF-1 with average of 818 ng/mL (474-1340 ng/ml) and PRL with average of 185.62 ng/mL (120.95 to 280.13 ng/ml). On admission, a pituitary Magnetic Resonance Imaging (MRI) revealed macroadenoma, with mean diameter 23.5 mm (18-32 mm). All patients were prescribed cabergoline in average dose of 0.75 mg (0.5-1 mg) per week. Half of the patients had their IGF-1 ng/mL plasma level normalized. PRL ng/ml plasma levels were decreased in all patients. In their last pituitary MRI, the size of the macroadenoma decreased in all patients (8.1mm), with a mean diameter of 15.4 mm. Conclusion We consider that the primary management of the plurihormonal pituitary adenomas is the use of dopamine receptor agonists; in case there is not a clinical or biochemical control of the disease, we suggest to evaluate using additional therapy. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SUN-291 17 Year Old Male with Galactorrhea and Elevations in Prolactin and ACTH in the Setting of a Pituitary Microadenoma

Pituitary adenomas are uncommon in children with an incidence of 0.1 per million. Prolactinomas are the most frequent, followed by ACTH-secreting adenomas, whereas TSH-, GH- and non-functioning adenomas are less frequently encountered. Plurihormonal pituitary adenomas, though extremely rare have also been reported, with ACTH/Prolactin and ACTH/GH being the most common. (Lubov B. Mitrofanova, 2017) A 17 year old male presented with bilateral ‘milky’ areolar discharge for the past 2 weeks. He also had a history of chronic headaches and decreased energy for the past 6 months. Initial evaluation at his PCP’s office showed an elevated prolactin of 90.2 ng/mL (4.0-15.2) and normal TSH and free T4. At presentation to endocrinology, physical exam showed weight of 106.8 kg >99%ile, height of 182.8 cm, 85%ile, BMI of 32, 98%ile, and blood pressures 117/50 mmHg, 50th/10th%ile respectively. He was also noted to have circumferential acanthosis nigricans of the neck, gynecomastia, Tanner V pubic hair, and 20 mL testes bilaterally; no striae, nuchal adiposity or areolar discharge was noted. Subsequent biochemical testing at 0900 showed prolactin, 100.7 ng/mL (4.0-15.2), ACTH, 177 pg/mL (<47), cortisol, 21.6 ug/dL (5.3-22.5), FSH 0.8 mU/mL (1.5-12.4), LH 1.5 mU/mL (1.8-10.8), with T4, TSH and IGF-1 within normal limits. An MRI of the brain showed a 3 mm microadenoma in the adenohypophysis. Given elevated prolactin, ACTH and high normal morning cortisol, there were concerns for Cushing’s disease, and midnight salivary cortisols were obtained, which were normal: 0.033, 0.036 and 0.040 ug/dL (<0.259). He was then started on cabergoline, titrated up to 0.5 mg twice a week. After 3 months, he had resolution of the areolar discharge and a decrease in headache frequency as well as improved energy. His repeat labs showed prolactin, 8.4 ng/mL, AM cortisol 17.4 ng/mL, though ACTH was quantity not sufficient. Hyperprolactinemia is most commonly caused by a pituitary adenoma, and symptoms in men include gynecomastia, areolar discharge, fatigue and decreased libido. Plurihormonal adenomas, though a rarity, must be considered when an adenoma is confirmed by imaging, and should trigger screening for other pituitary hormonal abnormalities. Treatment with D2-receptor agonists has been shown to be an effective treatment for some plurihormonal adenomas, likely dependent on D2 receptor expression of the particular adenoma in question (Shalini Kunasegaran, 2017). Lubov B. Mitrofanova, P. V. (2017). Plurihormonal cells of normal anterior pituitary: Facts and conclusions. Oncotarget, 8(17): 29282-29299. Shalini Kunasegaran, M. S. (2017). An unusual case of Cushing's syndrome due to bihormonal ACTH-prolactin secreting pituitary macroadenoma with rapid response to cabergoline. BMJ Case Reports, 10.1136/bcr-2017-219921 .

Plurihormonal Pit-1 lineage adenoma presenting as meningitis with recurrence after somatostatin analogue.

SummaryA 21 year-old woman was found to have a pituitary macroadenoma following an episode of haemophilus meningitis. Biochemical TSH and GH excess was noted, although with no clear clinical correlates. She was treated with a somatostatin analogue (SSA), which restored the euthyroid state and controlled GH hypersecretion, but she re-presented with a further episode of cerebrospinal fluid (CSF) leak and recurrent meningitis. Histology following transsphenoidal adenomectomy revealed a Pit-1 lineage plurihormonal adenoma expressing GH, TSH and PRL. Such plurihormonal pituitary tumours are uncommon and even more unusual to present with spontaneous bacterial meningitis. The second episode of CSF leak and meningitis appears to have been due to SSA therapy-induced tumour shrinkage, which is not a well-described phenomenon in the literature for this type of tumour.Learning points:Pit-1 lineage GH/TSH/PRL-expressing plurihormonal pituitary adenomas are uncommon. Moreover, this case is unique as the patient first presented with bacterial meningitis.Inmunohistochemical plurihormonality of pituitary adenomas does not necessarily correlate with biochemical and clinical features of hormonal hypersecretion.Given that plurihormonal Pit-1 lineage adenomas may behave more aggressively than classical pituitary adenomas, accurate pathological characterization of these tumours has an increasing prognostic relevance.Although unusual, a CSF leak and meningitis may be precipitated by SSA therapy of a pituitary macroadenoma via tumour shrinkage.

Hypersecretion of ACTH and PRL from pituitary adenoma in MEN1, adequately managed by medical therapy.

SummaryA 54-year-old man had gastrinoma, parathyroid hyperplasia and pituitary tumor. His family history indicated that he might have multiple endocrine neoplasia type 1 (MEN1). MEN1 gene analysis revealed a heterozygous germline mutation (Gly156Arg). Therefore, we diagnosed him with MEN1. Endocrinological tests revealed that his serum prolactin (PRL) and plasma adrenocorticotropic hormone (ACTH) levels were elevated to 1699 ng/mL and 125 pg/mL respectively. Immunohistochemical analysis of the resected pancreatic tumors revealed that the tumors did not express ACTH. Overnight 0.5 and 8 mg dexamethasone suppression tests indicated that his pituitary tumor was a PRL-ACTH-producing plurihormonal tumor. Before transsphenoidal surgery, cabergoline was initiated. Despite no decrease in the volume of the pituitary tumor, PRL and ACTH levels decreased to 37.8 ng/mL and 57.6 pg/mL respectively. Owing to the emergence of metastatic gastrinoma in the liver, octreotide was initiated. After that, PRL and ACTH levels further decreased to 5.1 ng/mL and 19.7 pg/mL respectively. He died from liver dysfunction, and an autopsy of the pituitary tumor was performed. In the autopsy study, histopathological and immunohistochemical (IHC) analysis showed that the tumor was single adenoma and the cells were positive for ACTH, growth hormone (GH), luteinizing hormone (LH) and PRL. RT-PCR analysis showed that the tumor expressed mRNA encoding all anterior pituitary hormones, pituitary transcription factor excluding estrogen receptor (ER) β, somatostatin receptor (SSTR) 2, SSTR5 and dopamine receptor D (D2R). PRL-ACTH-producing tumor is a very rare type of pituitary tumor, and treatment with cabergoline and octreotide may be useful for controlling hormone levels secreted from a plurihormonal pituitary adenoma, as seen in this case of MEN1.Learning points:Although plurihormonal pituitary adenomas were reported to be more frequent in patients with MEN1 than in those without, the combination of PRL and ACTH is rare.RT-PCR analysis showed that the pituitary tumor expressed various pituitary transcription factors and IHC analysis revealed that the tumor was positive for PRL, ACTH, GH and LH.Generally, the effectiveness of dopamine agonist and somatostatin analog in corticotroph adenomas is low; however, if the plurihormonal pituitary adenoma producing ACTH expresses SSTR2, SSTR5 and D2R, medical therapy for the pituitary adenoma may be effective.

The clinical spectrum of TSH-expressing pituitary adenomas

Background: Thyroid-stimulating hormone (TSH)-expressing pituitary adenomas are a rare but important entity with a spectrum of clinical manifestations. Here, we report our experience with managing TSH-expressing pituitary adenomas over eleven years – the largest single-centre data published to date. Methods: We reviewed retrospectively all patients with histopathologically-proven TSH-expressing pituitary adenomas presenting to our centre between 2002 and 2012 inclusive. Data were obtained on clinical presentation, biochemical status, tumour size, management, histopathological results, and long-term outcomes. Results: 32 patients (16 males) were identified. Mean age at presentation was 52.9 years, and mean follow-up was 79 months. Visual disturbance was the commonest presenting complaint in 34%, and 25% of the patients were clinically hyperthyroid at presentation. 84% of the patients had plurihormonal pituitary adenomas. All patients initially underwent transsphenoidal surgery, one underwent post-operative radiotherapy. 31% (10) patients had recurrence; two of these had an empty pituitary fossa on initial post-operative imaging. One patient died, from an indirect cause. The clinically active and silent tumours (defined by the presence or absence of clinical hyperthyroidism, respectively) behaved in a similar manner, including with respect to recurrence rates. Conclusions: TSH-expressing pituitary adenomas have a wide clinical spectrum. Patients are often clinically euthyroid but may have signs or symptoms of derangements in other pituitary hormones. Visual disturbance is common. Despite radiological evidence of clearance following surgery, and extended follow-up, TSH-expressing pituitary adenomas may still recur. Our data supports the need for close long-term follow-up of such patients, and supports the notion that the clinically silent tumours are not a benign entity.

Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the literature

Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more than one hormone that cannot be explained by normal adenohypophysial cytodifferentiation. The most common combinations in these adenomas include growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub-units (β-TSH, β-FSH, β-LH and αSU). The authors report two cases of a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH. They both underwent successful transphenoidal hypophysectomy (TSH). Long-term post-operative follow-up revealed no evidence of tumour recurrence. Due to the multiple secretions and plurihormonal characteristics clinical diagnosis of composite pituitary adenomas can be difficult. The authors discuss the diagnosis and management of composite pituitary adenomas and review the literature regarding this rare phenomenon.

Concurrent somatotroph and plurihormonal pituitary adenomas in a cat

An 8-year-old, male neutered, domestic longhair cat was referred for investigation of insulin-resistant diabetes mellitus. Routine haematology, serum biochemistry, urinalysis (including culture), total T4 and urine creatinine:cortisol ratio were unremarkable, but markedly increased insulin-like growth factor-1 concentration was identified and a pituitary mass was subsequently documented. The cat was treated conservatively with the dopamine agonist L-deprenyl and was re-presented 16 months later for worsening polyuria, polydipsia, polyphagia, marked lumbar muscle atrophy, development of a pendulous abdomen and marked thinning of the abdominal skin. Hyperadrenocorticism was diagnosed based on abdominal ultrasonography, dexamethasone suppression testing and endogenous adrenocorticotropic hormone (ACTH). The cat was treated with trilostane (30 mg q24h PO) and showed some clinical improvement, but developed an opportunistic fungal infection and skin fragility syndrome 4.5 months after commencing treatment, and was euthanased. A double-pituitary adenoma comprising a discrete somatotroph adenoma and a separate plurihormonal adenoma (positive immunoreactivity for ACTH, melanocyte-stimulating hormone and follicle-stimulating hormone) was identified on post-mortem examination. These two pituitary adenomas were suspected to have arisen as independent neoplastic entities with the plurihormonal tumour either being clinically silent at the initial presentation or having developed over the subsequent 16 months.

Analysis of differential gene expression in plurihormonal pituitary adenomas using bead-based fiber-optic arrays

Plurihormonal pituitary adenomas (PHPAs) are defined as those pituitary adenomas secreting two or more hormones that differ in chemical composition, immunoreactivity, and biologic effects. Since the pathogenesis of these adenomas is not well understood, our study aimed to explore mechanisms underlying the pathogenesis of PHPAs. We used bead-based fiber-optic arrays (Illumina Human GeneChip WG-6 v3.0) to examine the gene expression profiles in seven PHPAs compared with three normal pituitary glands. Four differentially expressed genes were chosen randomly for validation by quantitative real-time reverse-transcription polymerase chain reaction. We then performed pathway analysis of all differentially expressed genes using the Kyoto Encyclopedia of Genes and Genomes. Our array analysis showed significant increases in the expression of 6 genes and decreases in 334 genes and 15 expressed sequence tags in the PHPAs. Bioinformatic analysis showed that genes HIGD1B, EPS8, ECT2, and BTG2 might play an important role in the tumorigenesis and progression of PHPAs. Pathway analysis showed that the p53 and Notch signaling pathways may play an important role in tumorigenesis and progression of PHPAs, and extracellular matrix (ECM)-receptor interactions likely play a role in the inhibition of invasion and metastasis in these tumors. Our data suggested that there are numerous aberrantly expressed genes and pathways involved in the pathogenesis of PHPAs. Bead-based fiber-optic arrays combined with pathway analysis of gene expression data appears to be a valid method for investigating the pathogenesis of tumors.

Plurihormonal gonadotroph cell pituitary adenoma: report of a unique case

Pituitary adenomas producing primarily FSH and to a lesser extent GH, LH, alpha-subunit, TSH and PRL without clinical or laboratory evidence of increased hormone release have not previously been reported. Our aim was to obtain some insight into the possible cytogenesis of this unusual tumor. A 65-year-old woman presented with headaches. Magnetic resonance imaging (MRI) demonstrated a sellar mass. Pituitary hormone assays showed normal blood levels. The tumor was removed by the transsphenoidal approach. By light microscopy, the adenoma was chromophobic, weakly PAS-positive, and immunoreactive mainly for FSH (85%) and to a lesser extent for GH (30%), LH (15%), alpha-subunit (3%), TSH (2%), and PRL (1%). Although double immunostaining showed hormone reactivities to be localized largely in separate distinct cells, the tumor was ultrastructurally monomorphous, i.e., consisted of a single-cell type, resembling gonadotrophs. The cytogenesis of plurihormonal pituitary adenomas is not fully understood. Further investigations are required to clarify the basis for their plurihormonality despite an ultrastructural gonadotroph phenotype.

Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is mandatory for correct classification.

We studied the clinicopathological characteristics of plurihormonal pituitary adenomas. The study material included 167 plurihormonal adenomas, which consisted of 31% of the surgically removed pituitary adenomas that we collected during a 12-year period. The mean age of patients with plurihormonal adenoma was 45.7 years (range 13-75 years). There were 86 men and 81 women. All tumours were fully classified by immunohistochemical staining for seven pituitary hormones or subunits. Thirty immunohistochemical subtypes of plurihormonal adenomas were recognized. Hormonal symptoms were present in 70% of patients, while serum hormonal levels were increased in 89% of patients. Most patients had symptoms related to only one of the hormones and only 7% of patients had symptoms related to two hormones. The most common hormonal symptom was acromegaly (50%); symptoms related to hyperprolactinaemia ranked second (20%). Double immunostaining of all the possible combinations of the hormones was performed in 30 selected tumours, and they all showed mixtures of hormones in individual adenoma cells in any hormonal combinations studied. The latter finding supported the view that plurihormonal adenomas are monomorphous adenomas. Plurihormonal adenomas are common pituitary adenomas. Immunohistochemical staining of all pituitary hormones is mandatory for correct classification.

Immunohistochemical demonstration of tenascin in human pituitary glands and adenomas

The expression of tenascin in 8 cases of normal fetal and adult human pituitary glands and in 51 cases of human pituitary adenomas was investigated immunohistochemically with the use of polyclonal antibodies against human tenascin. The immunohistochemical study demonstrated that tenascin is expressed in both fetal and adult normal epithelial cells of the anterior lobe of pituitary glands and in tumor cells of pituitary adenomas, which suggests that tenascin is synthesized by normal pituitary cells as well as by pituitary adenoma cells. Plurihormonal pituitary adenomas, especially those producing 4 or 5 different hormones, tended to show the highest incidence of positive immunoreactivity for tenascin, suggesting that tenascin may be involved in the aggressive behaviour of plurihormonal adenomas.

Basic Fibroblast Growth Factor Expression by Two Prolactin and Thyrotropin-Producing Pituitary Adenomas.

We investigated the expression of basic fibroblast growth factor (bFGF) in an aggressive type of PRL and TSH-producing pituitary adenoma. Immunocytochemistry and electron microscopy were used to characterize the tumors removed from two patients. lmmunoassays were used to measure hormone and bFGF levels in vitro and in vivo. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect bFGF mRNA expression by these tumors. Morphologically, these tumors were characterized by an unusual plurihormonal pattern with expression of PRL and TSH and the ultrastructural characteristics of the silent subtype 3 adenoma; in addition, both adenomas displayed marked interstitial fibrosis. bFGF was measurable in the circulation of these patients ranging from 7.5-20.5 pg/mL (normal < 1 pg/mL). bFGF concentrations were reduced following surgical adenomectomy. bFCF in culture media was present in concentrations of 197-387 pg/24h/10(5) cells. bFGF mRNA expression was identified in both adenomas examined. bFGF levels were unaltered in the culture media and in the serum of patients following GnRH and TRH treatment. In conclusion, the expression of bFGF by these plurihormonal pituitary adenomas suggests the possibility that it may play a role in the development of fibrosis and tumor cell proliferation of this unusual type of pituitary neoplasm.

Hormone production andc-myc protein labeling in plurihormonal pituitary adenomas

The biological activity of plurihormonal pituitary adenomas was compared with that of tumors producing only one hormone by evaluating the percentage ofc- myc protein-labeled cells and ultrastructural characteristics. Twenty-five pituitary adenomas producing 3 or more hormones and 14 adenomas producing only I hormone were studied. Tissue sections were stained immunohistochemically using antibodies for pituitary hormones andc- myc protein, and they were examined by electronmicroscopy. DNA extracted from ethanol-fixed, paraffinembedded tissue was analyzed for p53 mutations by polymerase chain reaction and singlestrand conformation polymorphism analysis. The percentage ofc- myc protein-labeled cells in adenomas producing 4 or 5 pituitary hormones was significantly higher (p < 0.01 ) than in those producing 3 or 1 hormones. There were no p53 mutations in plurihormonal adenomas. Pituitary adenomas producing 4 or 5 pituitary hormones demonstrate biological aggressiveness; therefore, multihormone production reflects aggressive capacity rather than degree of differentiation.

Hormone secretion in vitro by plurihormonal pituitary adenomas of the acidophil cell line.

Pituitary tumors producing GH and PRL are morphologically classified as monomorphous bihormonal acidophil stem cell adenomas (ASCAs) which cause hyperprolactinemia and two tumor types which are usually associated with acromegaly, the monomorphous plurihormonal mammosomatotroph adenomas (MSAs) and bimorphous mixed somatotroph-lactotroph adenomas. We studied 12 MSAs, 2 ASCAs, and 10 mixed adenomas in vitro to assess the secretory behavior of these tumors diagnosed by immunohistochemistry and electron microscopy. GH release by MSAs and all but one mixed tumor was greater than that of PRL; the opposite was true of the ASCAs. One mixed tumor which caused impotence and hyperprolactinemia contained predominantly lactotrophs and released greater amounts of PRL than of GH in vitro. All 12 MSAs and 6 of 10 mixed tumors released alpha-subunit of glycoprotein hormones. Incubation with GHRH increased release of GH and PRL by all tumors and of alpha-subunit when present; the responses of all hormones were parallel among MSAs whereas among mixed adenomas, GH and alpha-subunit had greater responses than PRL. TRH stimulated GH, PRL, and alpha-subunit release by MSAs in parallel; among mixed adenomas, PRL response was generally greater than that of GH or alpha-subunit. SRIH markedly reduced GH release by all MSAs; it inhibited GH and alpha-subunit release by mixed tumors more than it affected PRL. Bromocriptine inhibited GH, PRL, and alpha-subunit release by most MSAs and mixed tumors but did not inhibit GH or PRL release by ASCAs. This study demonstrates release of GH, PRL, and alpha-subunit by these morphologically classified plurihormonal tumors in vitro. Variable quantities of GH and PRL released by the different tumor types correlate with immunohistochemical and clinical data. The dynamic studies indicate that regulation of GH, PRL, and alpha-subunit release can be affected by GHRH, TRH, SRIH, and bromocriptine in these adenomas and suggest differences in receptor status. Our data strengthen the view that these three plurihormonal adenomas of the acidophil cell line are not only morphologically but also functionally different and warrant separation.

Hormone secretion in vitro by plurihormonal pituitary adenomas of the acidophil cell line

Hormone secretion in vitro by plurihormonal pituitary adenomas of the acidophil cell line