Benserazide and nomifensine in the diagnosis of prolactin-secreting pituitary adenomas

1982 ◽  
Vol 101 (2) ◽  
pp. 171-179 ◽  
Author(s):  
A. E. Pontiroli ◽  
G. Loda ◽  
A. Roggia ◽  
P. Scagliola ◽  
L. Falsetti

Abstract. Benserazide, an inhibitor of dopa-decarboxylase, stimulates prolactin (Prl) release in normal women and in puerperae; nomifensine, a dopaminergic drug able to release dopamine and to inhibit its re-uptake at the post-synaptic level, inhibits Prl release in the same subjects. Similar modifications of Prl release are evident in selected cases of non-tumoural hyperprolactinaemia, while neither drug modifies Prl release in patients with a Prl-secreting pituitary adenoma. The aim of our study was to compare the effect of these drugs in patients with a Prl-secreting pituitary adenoma, in patients with 'functional' hyperprolactinaemia and in patients with minor abnormalities of sellar tomography. Neither drug modified Prl release in patients with macro- or microadenomas; several patients in the remaining groups failed to respond to one or both tests, the concordance between the two tests averaging 75%. Patients responding to both tests, to one test or to neither test showed progressively higher basal Prl levels. Since benserazide and nomifensine can indicate the presence of a pituitary adenoma earlier than sellar tomography, our results indicate that patients with no Prl response to one or to both tests probably harbour a pituitary adenoma which cannot yet be revealed by sellar tomography.

2019 ◽  
Vol 26 (11) ◽  
pp. 800-818
Author(s):  
Zujian Xiong ◽  
Xuejun Li ◽  
Qi Yang

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yi Zhang ◽  
Cheng Chen ◽  
Min Lin ◽  
Kan Deng ◽  
Huijuan Zhu ◽  
...  

Abstract Background Functional gonadotroph adenomas (FGAs) are rare adenomas that most commonly secrete FSH. However, solitary LH-secreting pituitary adenomas are unusual. Case presentation A 30-year-old woman with elevated LH and normal FSH presented with inability to conceive. An MRI revealed an enlarged sella turcica and an intrasellar mass. Treatment with transsphenoidal resection led to normalization of LH and estradiol, as well as successful pregnancy. And we reviewed 6 cases of LH-secreting pituitary adenomas from 1981 to 2020. Conclusions Our case is unique because of the LH-secreting pituitary adenoma without FSH hypersecretion. This case indicates that pituitary adenoma should be considered when other diseases causing infertility have been excluded.


2016 ◽  
Vol 15 (6) ◽  
pp. NP95-NP104 ◽  
Author(s):  
Zhang kun ◽  
Yang yuling ◽  
Wang dongchun ◽  
Xie bingbing ◽  
Li xiaoli ◽  
...  

Pituitary adenomas usually develop temozolomide resistance, which could compromise the anticancer effects of temozolomide. Suppression of hypoxia-inducible factor 1α has been shown to sensitize glioblastoma cells to temozolomide treatment according to previous reports. However, whether and how the suppression of hypoxia-inducible factor 1α could sensitize pituitary adenomas to temozolomide treatment are still poorly understood. In the present study, using hypoxia-inducible factor 1α knockdown strategy, we demonstrated for the first time that hypoxia-inducible factor 1α knockdown could inhibit temozolomide-induced autophagy in rat pituitary adenoma GH3 cells and thus increase antitumor efficacy of temozolomide. Furthermore, we found hypoxia-inducible factor 1α knockdown could block autophagy process through neutralizing lysosomal pH value but not inhibiting autophagy induction. Finally, we found hypoxia-inducible factor 1α could regulate lysosomal pH value through regulating full length presenilin 1 expression, and exogenous reexpression of presenilin 1could restore lysosome acidic levels. Our data indicated hypoxia-inducible factor 1α knockdown could be a potential approach to improve the efficacy of temozolomide therapy for pituitary adenomas.


Neurosurgery ◽  
2008 ◽  
Vol 62 (3) ◽  
pp. 717-723 ◽  
Author(s):  
Alvaro Campero ◽  
Carolina Martins ◽  
Alexandre Yasuda ◽  
Albert L. Rhoton

Abstract OBJECTIVE To evaluate the anatomic aspects of the diaphragma sellae and its potential role in directing the growth of a pituitary adenoma. METHODS Twenty cadaveric heads were dissected and measurements were taken at the level of the diaphragma sellae. RESULTS The diaphragma sellae is composed of two layers of dura mater. There is a remarkable variation in the morphology of the diaphragm opening. The average anteroposterior distance of the opening was 7.26 mm (range, 3.4–10.7 mm) and the average lateral-to-lateral distance was 7.33 mm (range, 2.8–14.1 mm). CONCLUSION The variability in the diameter of the opening of the diaphragma sellae could explain the growth of pituitary tumors toward the cavernous sinus or toward the suprasellar region.


2018 ◽  
Vol 79 (01) ◽  
pp. 091-114 ◽  
Author(s):  
Avital Perry ◽  
Christopher Graffeo ◽  
Christopher Marcellino ◽  
Bruce Pollock ◽  
Nicholas Wetjen ◽  
...  

Background Pediatric pituitary adenoma is a rare skull base neoplasm, accounting for 3% of all intracranial neoplasms in children and 5% of pituitary adenomas. Compared with pituitary tumors in adults, secreting tumors predominate and longer disease trajectories are expected due to the patient age resulting in a natural history and treatment paradigm that is complex and controversial. Objectives The aims of this study were to describe a large, single-institution series of pediatric pituitary adenomas with extensive long-term follow-up and to conduct a systematic review examining outcomes after pituitary adenoma surgery in the pediatric population. Methods The study cohort was compiled by searching institutional pathology and operative reports using diagnosis and site codes for pituitary and sellar pathology, from 1956 to 2016. Systematic review of the English language literature since 1970 was conducted using PubMed, MEDLINE, Embase, and Google Scholar. Results Thirty-nine surgically managed pediatric pituitary adenomas were identified, including 15 prolactinomas, 14 corticotrophs, 7 somatotrophs, and 4 non-secreting adenomas. All patients underwent transsphenoidal resection (TSR) as the initial surgical treatment. Surgical cure was achieved in 18 (46%); 21 experienced recurrent/persistent disease, with secondary treatments including repeat surgery in 10, radiation in 14, adjuvant pharmacotherapy in 11, and bilateral adrenalectomy in 3. At the last follow-up (median 87 months, range 3–581), nine remained with recurrent/persistent disease (23%).Thirty-seven publications reporting surgical series of pediatric pituitary adenomas were included, containing 1,284 patients. Adrenocorticotropic hormone (ACTH)-secreting tumors were most prevalent (43%), followed by prolactin (PRL)-secreting (37%), growth hormone (GH)-secreting (12%), and nonsecreting (7%). Surgical cure was reported in 65%. Complications included pituitary insufficiency (23%), permanent visual dysfunction (6%), chronic diabetes insipidus (DI) (3%), and postoperative cerebrospinal fluid (CSF) leak (4%). Mean follow-up was 63 months (range 0–240), with recurrent/persistent disease reported in 18% at the time of last follow-up. Conclusion Pediatric pituitary adenomas are diverse and challenging tumors with complexities far beyond those encountered in the management of routine adult pituitary disease, including nuanced decision-making, a technically demanding operative environment, high propensity for recurrence, and the potentially serious consequences of hypopituitarism with respect to fertility and growth potential in a pediatric population. Optimal treatment requires a high degree of individualization, and patients are most likely to benefit from consolidated, multidisciplinary care in highly experienced centers.


Author(s):  
Kent Tadokoro ◽  
Colten Wolf ◽  
Joseph Toth ◽  
Cara Joyce ◽  
Meharvan Singh ◽  
...  

Abstract Objectives Ki-67/MIB-1 is a marker of cellular proliferation used as a pathological parameter in the clinical assessment of pituitary adenomas, where its expression has shown utility in predicting the invasiveness of these tumors. However, studies have shown variable results when using Ki-67/MIB-1 association with recurrence. The purpose of this study is to determine if a high Ki-67/MIB-1 labeling index (LI) is predictive of recurrence in pituitary adenomas. Methods A retrospective chart review was performed for patients undergoing pituitary adenoma resection with at least 1 year of follow-up. Additionally, systematic data searches were performed and included studies that correlated recurrence rate to Ki-67/MIB-1 LI. Our institutional data were included in a synthesis with previously published data. Results Our institutional review included 79 patients with a recurrence rate of 26.6%. We found that 8.8% of our patients had a high Ki-67/MIB-1 LI (>3%); however, high Ki-67/MIB-1 was not associated with recurrence. The systematic review identified 244 articles and 49 full-text articles that were assessed for eligibility. Quantitative analysis was performed on 30 articles including our institutional data and 18 studies reported recurrence by level of Ki-67/MIB-1 LI. Among studies that compared Ki-67/MIB-1 ≥3 vs. <3%, 10 studies reported odds ratios (OR) greater than 1 of which 6 were statistically significant. A high Ki-67/MIB-1 had higher odds of recurrence via the pooled odds ratio (OR = 4.15, 95% confidence interval [CI]: 2.31–7.42). Conclusion This systematic review suggests that a high Ki-67/MIB-1 should prompt an increased duration of follow-up due to the higher odds of recurrence of pituitary adenoma.


Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1690-1700 ◽  
Author(s):  
Erica Gentilin ◽  
Federico Tagliati ◽  
Carlo Filieri ◽  
Daniela Molè ◽  
Mariella Minoia ◽  
...  

Abstract The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting with such pathways may help in achieving disease control also in the settings of ACTH-secreting pituitary adenomas. We investigated the expression of 10 miRNAs among those that were found as most dysregulated in human pituitary adenoma tissues in the settings of a murine ACTH-secreting pituitary adenoma cell line, AtT20/D16v-F2. The selected miRNAs to be submitted to further investigation in AtT20/D16v-F2 cells represent an expression panel including 5 up-regulated and 5 down-regulated miRNAs. Among these, we selected the most dysregulated mouse miRNA and searched for miRNA targets and their biological function. We found that AtT20/D16v-F2 cells have a specific miRNA expression profile and that miR-26a is the most dysregulated miRNA. The latter is overexpressed in human pituitary adenomas and can control viable cell number in the in vitro model without involving caspase 3/7-mediated apoptosis. We demonstrated that protein kinase Cδ (PRKCD) is a direct target of miR-26a and that miR26a inhibition delays the cell cycle in G1 phase. This effect involves down-regulation of cyclin E and cyclin A expression via PRKCD modulation. miR-26a and related pathways, such as PRKCD, play an important role in cell cycle control of ACTH pituitary cells, opening new therapeutic possibilities for the treatment of persistent/recurrent Cushing's disease.


2021 ◽  
Vol 17 (1) ◽  
pp. 11-19
Author(s):  
R. Nikolaiev ◽  
L. Rostomyan ◽  
A. Beckers ◽  
O. Khyzhnyak ◽  
M. Mykytyuk ◽  
...  

Background. This article presents a review of the current literature on the role of the genetic component in the etiology and pathogenesis of hormone-active pituitary adenomas secreting growth hormone (GH) and clinically manifesting by acromegaly and/or gigantism (multiple endocrine neoplasia 1 (MEN-1), McCune-Albright syndrome, Carney complex, X-linked acrogigantism (X-LAG), familial isolated pituitary adenoma — FIPA). Materials and methods. To identify mutations in the AIP gene and to verify FIPA, 26 patients of the Ukrainian population (19 women and 7 men) were examined in whom acromegaly was diagnosed in adolescence or young age, and genetic analysis was performed. To determine the genetic determinism in the development of GH-secreting pituitary adenoma and differential diagnosis of FIPA and MEN-1 syndromes by sequencing method (MLPA — ligation-dependent probe amplification), the genes MLPA, P244-C1 were studied involving exons 1–6 MEN1 gene, (MLPA, P017-D1) AIP gene. Results. Among those examined, only two patients had AIP gene mutations. In one patient, genetic screening for MEN1 gene mutation was negative and no clinical symptoms suggestive of McCune-Albright syndrome were detected. A variant heterozygous missense c.714C>G (p.Cys238Trp) was found in the AIP gene. This AIP gene assay is compatible with a genetic predisposition to develop pituitary adenoma. The offspring of this patient has a 50% chance of inheriting this variant, acromegaly, hypersomatotropinemia, MEN-1 syndrome, familial isolated pituitary adenoma. Another patient was diagnosed with MEN syndrome type 1 (Wermer syndrome): insulinoma, parathyroid gland adenomas (2), primary hyperparathyroidism with a heterozygous c.134A>G variant (p.Glu45Gly) found in the MEN1 gene. The presence of the c.l34A>G (p.Glu45Gly) class variant 4 is likely to be pathogenic. The prevalence of this variant in the general population is unknown, so it is very rare. Conclusions. The genetic analysis is appropriate in pediatric and young patients or those with GH-secreting macro/giant pituitary adenoma diagnosed at a young age (under 35), regardless of family history. In patients with a history of a disease, genetic analysis is recommended in any case to identify FIPA and to predict the further course of the disease and the effectiveness of treatment with somatostatin analogues.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Siroj Dejhansathit ◽  
Subhanudh Thavaraputta ◽  
Genevieve LaPointe ◽  
Ana Marcella Rivas Mejia

Abstract Background: Unlike nonfunctioning gonadotroph pituitary adenomas, functioning gonadotroph pituitary adenomas (FGA) are an uncommon type of pituitary tumors that secrete biologically active gonadotropins (LH, FSH, or both). Clinical Case: A 23-year-old man with no previous medical history presented to the emergency department with three months history of progressive decreased vision and decreased libido. He denied headache, seizure, erectile dysfunction, or weakness. On physical examination, his visual acuity was significantly reduced on the right eye and was only able to perceive light. He had a visual field narrowing on the left eye. Gynecomastia was noted bilaterally and testicles were found to be enlarged (Orchidometer &gt;25 mL). Complete blood count was significant for hemoglobin of 19.2 g/dL (N, 13.7-17.5 g/dL), and hematocrit of 57.0% (N, 40.1-51.0%). Pituitary function tests were as follow: FSH &gt;200.0 mIU/mL (N, 1.5-12.4 mIU/mL), LH 17.0 mIU/mL (N, 1.7-8.6 mIU/mL), total testosterone 41.3 nmol/L (N, 8.6-29.0 nmol/L), free testosterone 1.263 nmol/L (N, 0.148-0.718 nmol/L), and bioavailable testosterone 29.609 (N, 2.110-8.920 nmol/L). Prolactin, TSH, GH, and ACTH were all within the normal range. Magnetic resonance imaging (MRI) showed a sellar mass involving the planum sphenoidal measuring 5.8 x 5.2 x 5.6 cm with optic chiasm displaced superiorly, in addition, subfalcine herniation with mild hydrocephalus was also noted. The patient underwent orbitozygomatic approach resection of the pituitary tumor. Histological examination was consistent with a pituitary adenoma. Cells stained positive for transcription factor steroidogenic factor 1 (SF 1), FSH, LH, and alpha-subunit consistent with a gonadotroph adenoma. They were negative for transcription factor Pit 1 stain and the remaining pituitary hormones including ACTH, GH, prolactin, and TSH stain. Postsurgical hormone assessment showed a significant decline in FSH and LH to 2.3 and 0.4 mIU/mL, respectively and testosterone level decreased to &lt; 0.087 nmol/L on postoperative day 18. The patient’s vision improved postoperatively prior to discharge but he lost follow up thereafter. Conclusion: Most patients with functioning gonadotroph pituitary adenoma present with large tumors that are detected based on the occurrence of symptoms of compression that result from the enlarging sellar mass. Most patients, particularly men and postmenopausal women, do not develop symptoms of hormone excess and the lack of symptomatology results in delay in diagnosis. Our patients presented with significant polycythemia which resulted from excess testosterone and could have prompted earlier tumor detection if he had presented in an earlier stage. The incidence of polycythemia in male patients with functioning gonadotroph pituitary adenoma has previously been described in the literature in a few case reports.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi158-vi158
Author(s):  
Syed Ather Enam ◽  
Fauzan Alam Hashmi ◽  
Sanam Mir Ghazi ◽  
Ahsan Ali Khan ◽  
Muhammad Bilal Tariq ◽  
...  

Abstract BACKGROUND Giant pituitary adenomas (GPA) are uncommon and highly variable in morphology and extension. There is no scoring system that considers all the dimensions of adenoma invasion. We developed a new Giant Pituitary Adenoma score and report our surgical experience and evaluate outcomes after resection of these tumors in accordance with the preoperative score. METHODS We developed a novel scoring system for classifying giant pituitary adenomas, and 11-year data of GPA surgery at our center was collected retrospectively, based on this scoring system. GPA Score considered tumor’s parasellar extension, encasement of cavernous internal carotid artery (ICA), suprasellar extension &gt; 2 cm, suprasellar extension &gt; 4cm and retrosellar extension. Maximum possible score was 9. The scoring system was applied to 53 patients of GPA who underwent surgical resection between January 1, 2006, and December 2017. The Lundin-Pederson (ABC/2) method was used to calculate the tumor volume both pre- and post-resection and linear regression was used to assess the relationship between extent of tumor resection and GPA score. RESULTS The median age of the study population was 42.08 ± 16.49 years. The mean maximum diameter of the pituitary adenomas was 5.0 cm (range 4.0 cm-8.5cm) while the mean volume of the adenomas was 27.3 cm3 (range 10 cm3-149 cm3). There were 3 cases of score 2, 5 cases of score 3, 13 cases of score 4, 20 cases of score 5, 9 cases of score 6 and 3 cases of score 7. The range of tumor volumes of tumors for scores from 2-7 was 17.3 cm3 to 65.8 cm3 and GPA score was correlated with the percent residual tumor using linear regression that was statistically significant (p= 0.001). CONCLUSION GPA Score is a reliable scoring system to predict the extent and subsequent difficulty in tumor resection in GPA.


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