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Pituitary Tumors

The pituitary is an endocrine (hormone-producing) gland located in the brain, behind the bridge of the nose. It is only about the size of a pea, but plays a vital role as the 'master gland' by making hormones that regulate growth and the activity of other glands around the body. There are different types of tumors that can develop in the pituitary. The most common type is pituitary adenoma, which is usually slow growing and benign - these can affect people of all ages, but more women are more affected than men, particularly between ages 30-60. There are many other types of pituitary tumors, including pituitary carcinoma (malignant) and spindle cell oncocytoma, pituicytomas, granular cell tumor. The tumors may be classed as 'secretory' (honrmone producing) or 'non-functional' (non or reduced hormone producing). They are also classed by size: most are microadenomas (small tumors), but a minority are macroadenomas (larger tumours).

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  • PubMed search for publications about Pituitary Tumors - Limit search to: [Reviews]

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    MeSH term: Pituitary Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Okuda T, Fujita M, Kato A
Significance of Elevated HMGB1 Expression in Pituitary Apoplexy.
Anticancer Res. 2019; 39(8):4491-4494 [PubMed] Related Publications
BACKGROUND/AIM: High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein that exerts a range of proinflammatory actions when it is secreted extracellularly. We hypothesized that HMGB1 released from damaged cells in pituitary apoplexy would exacerbate the neurological symptoms due to acute inflammation.
PATIENTS AND METHODS: All the patients included in this study suffered from non-functioning pituitary adenoma. Four patients with apoplexy and three patients without apoplexy were included in this study. They underwent endonasal transsphenoidal endoscopic surgery to resect the tumors. We conducted enzyme-linked immunosorbent assay (ELISA) to measure HMGB1 in the surgical specimens.
RESULTS: Patients with apoplexy expressed HMGB1 at significantly higher levels than those in the non-apoplexy group (p=0.0478).
CONCLUSION: HMGB1 may be involved in subacute inflammation of pituitary apoplexy. Further work is needed to elucidate the detailed biological significance of HMGB1 in this disease.

Lemelin A, Lapoirie M, Abeillon J, et al.
Pheochromocytoma, paragangliomas, and pituitary adenoma: An unusual association in a patient with an SDHD mutation. Case report.
Medicine (Baltimore). 2019; 98(30):e16594 [PubMed] Related Publications
RATIONALE: Pituitary adenomas and paragangliomas are both rare endocrine diseases. Paragangliomas (PGL)/pheochromocytomas (PHEO) are part of an inherited syndrome in about 30% to 40% of cases. Among familial cases, mutations of the succinate dehydrogenase (SDH) subunit genes (succinate dehydrogenase subunit [SDH]B, SDHC, SDHD, succinate dehydrogenase subunit AF2 [SDHAF2] , and SDHA) are the most common cause.
PATIENT CONCERNS: We here report a 31-year-old patient with a known SDHD mutation whose disease has been revealed by a left PHEO during childhood and who presented at age 29 years a large paraganglioma of the right jugular foramen, a concomitant PHEO of the left adrenal and 2 retroperitoneal paragangliomas. A pituitary incidentaloma was found during investigations on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) (FDG-PET).
DIAGNOSIS: A pituitary magnetic resonance imaging (MRI) confirmed the presence of a 14 mm pituitary macroadenoma. The pituitary function was normal except for hypogonadotropic hypogonadism. On examination of the fundus, a diagnosis of Pseudo Foster-Kennedy syndrome was made due to a venous compression of the right jugular vein caused by the paraganglioma (PGL). The pituitary adenoma was not compressive to the optic chiasm.
INTERVENTIONS: A treatment with acetazolamide was started in order to improve intracranial hypertension. The patient couldn't benefit of a surgical approach for the paraganglioma of the right jugular foramen; the patient has been treated with stereotactic radiosurgery (Gamma Knife).
OUTCOMES: The most recent MRI revealed that the right jugular foramen PGL is stable and the latest visual assessment demonstrated stability despite a recent reduction in acetazolamide dosage. A surveillance by MRI of the pituitary adenoma has been planned.
LESSONS: The association of a pituitary adenoma to paragangliomas within a same patient is very uncommon and raises the question of related physiopathological mechanisms.

Nawal CL, Chejara RS, Meena PD, et al.
Severe Hyponatremia as an Uncommon Presenting Feature of Pituitary Macroadenoma.
J Assoc Physicians India. 2018; 66(8):96-98 [PubMed] Related Publications
Hyponatremia is a common electrolyte disturbance, but less commonly utilized and require a thorough evaluation to unmask etiology. It has variety of causes and is rarely due to hypopituitarism. Hyponatremia is a very early complication of pituitary tumor. Here, we report a case, who presented to us with hyponatremia and eventually thorough work-up led us to a diagnosis of Non-functioning pituitary macroadenoma.

Kim HY, Kim ST, Kim HJ, et al.
Differentiation of postoperative changes and residual tumors in dynamic contrast-enhanced sella MRI after transsphenoidal resection of pituitary adenoma.
Medicine (Baltimore). 2019; 98(27):e16089 [PubMed] Free Access to Full Article Related Publications
To establish magnetic resonance imaging (MRI) features that differentiate residual tumors from postoperative surgical changes following the transsphenoidal approach of a pituitary adenoma.We analyzed residual enhancements at the tumor bed in 52 patients who underwent dynamic contrast-enhanced sella MRI within 48 hours after surgery and at 6 to 28 months. Patients were divided into 2 groups defined by either peripheral or nodular enhancement patterns. For each group, we measured the maximum thickness of the residual enhancing portion and compared differences in the residual tumor and postoperative changes.Among the tumors examined in the 52 patients, 19 residual tumors showed nodular (n = 16) and peripheral (n = 3) enhancement patterns, and 33 postoperative changes showed nodular (n = 3) and peripheral (n = 30) enhancement patterns. The mean residual tumor thickness was 7.1 mm (range, 2.9-16.8 mm) and 1.9 mm (range, 1.0-7.4 mm) in the postoperative change. Receiver operating characteristic curve analysis revealed that a 3.9-mm thickness was associated with 89% sensitivity, 97% specificity, and 94% accuracy for diagnosis of residual tumor.On immediate postoperative MRI, residual enhancement with greater than 3.9-mm thickness and nodular pattern suggest residual pituitary adenoma tumor.

Sollfrank L, Lettmaier S, Erdmann M, Uslu U
Panniculitis Under Successful Targeted Inhibition of the MAPK/ERK Signaling Pathway in a Patient With BRAF V600E-mutated Spindle Cell Oncocytoma of the Pituitary Gland.
Anticancer Res. 2019; 39(7):3955-3959 [PubMed] Related Publications
BACKGROUND: Spindle cell oncocytoma (SCO) is a rare non-neuroendocrine neoplasm of the pituitary gland. In general, surgical excision and radiation therapy is performed. However, local recurrences are frequently seen, requiring repeated surgical and radio-oncological interventions. Thus, mutational analysis of the tumor and targeted therapy may represent a valuable therapy option in these patients.
CASE REPORT: A 38-year-old female patient with past medical history of 6 surgeries (two transsphenoidal and four transcranial), radiation therapy, and chemoradiation therapy due to several recurrences of a SCO, presented for follow-up imaging. MRI of the brain showed growth of a tumor in the right parasellar region consistent with a new local recurrence, which due to its size and location was considered to be not resectable. Molecular analysis of a previously surgically removed tumor showed a BRAF V600E mutation and thus, combined targeted inhibition of the MAPK/ERK signaling pathway using a BRAF inhibitor and a MEK inhibitor was started. Due to drug-induced panniculitis, MEK inhibitor had to be stopped and BRAF inhibitor only was continued, which was well tolerated by the patient. Subsequent imaging revealed tumor regression already four weeks after therapy initiation and no disease progression has been observed to date.
CONCLUSION: A SCO patient with BRAF V600E mutation was successfully treated using targeted inhibition of the MAPK/ERK signaling pathway. Under therapy, tumor regression was observed and the patient has been free of progressive disease for more than two years now. Thus, mutational analysis and targeted inhibition may offer an effective treatment option for SCO patients, while potential side-effects to this therapy, like observed in our case, can occur and needs to be adequately treated.

Hu Y, Zhang N, Zhang S, et al.
Differential circular RNA expression profiles of invasive and non-invasive non-functioning pituitary adenomas: A microarray analysis.
Medicine (Baltimore). 2019; 98(26):e16148 [PubMed] Free Access to Full Article Related Publications
Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors, and some exhibit locally invasive or even clinically aggressive behavior. Circular RNAs (circRNAs) are a reinvented class of non-coding RNAs that play important roles in tumor initiation and progression.CircRNA microarray assays were performed in 4 invasive and 4 non-invasive NFPAs, and 4 typically differential expression circRNAs were selected for validation using quantitative reverse transcription-polymerase chain reaction. The diagnostic and prognostic values of tested cirRNAs were further evaluated. Bioinformatics analysis and a literature review of potential miRNAs targets involved in pituitary tumor invasion were performed.A specific circRNA expression profile was detected between invasive and non-invasive NFPAs, including 91 upregulated and 61 downregulated circRNAs in invasive tumors. The dysregulation of the 4 circRNAs has been confirmed. The expression of hsa_circRNA_102597, a downregulated circRNA, was significantly correlated with tumor diameter (P < .05) and Knosp grade (P < .01). Hsa_circRNA_102597 alone or in combined with Ki-67 index was able to accurately differentiate invasive from non-invasive NFPAs as well as predict tumor progression/recurrence. Fourteen aberrantly expressed circRNAs might be involved in the invasiveness of pituitary adenomas via seven predicted potential miRNA targets.CircRNAs are participated in pituitary tumor invasion, and may be used as novel diagnostic and prognostic biomarkers in NFPAs.

Sidaraite A, Vilkeviciute A, Glebauskiene B, et al.
Association of ApoE haplotype with clinical evidence of pituitary adenoma.
Gene. 2019; 706:154-161 [PubMed] Related Publications
PURPOSE: To evaluate the association of the presence, invasiveness, hormonal activity and recurrence of pituitary adenoma (PA) with ApoE genotypes and alleles.
MATERIALS AND METHODS: Our study group included 142 patients with PA and the control group included 256 healthy individuals. The genotyping of ApoE (rs7412 and rs429358) was performed using a real-time PCR method.
RESULTS: After statistical analysis we found that ApoE genotype E2/E3 was associated with 2.6-fold increased odds of active PA (OR = 2.609; 95%CI: 1.380-4.932; p = 0.003), while the presence of ApoE E3/E3 decreased odds of active PA by 65% (OR = 0.343; 95%CI: 0.205-0.575; p < 0.001). The frequency of the allele ε3 was lesser in the PA group (74.3% vs. 83%, p = 0.003) when compared to controls but it was statistically significantly more frequent in the invasive PA than in the noninvasive PA subgroup (80.4% vs. 65.5%, p = 0.005). The ApoE E2/E4 genotype was more frequent in the noninvasive PA subgroup (10.3% vs. 0%, p = 0.003) than in the invasive PA subgroup. The ApoE E4/E4 genotype was more frequent in the recurrent than in the non-recurrent PA subgroup (6.6% vs. 0%, p = 0.006). No associations between ApoE polymorphisms and Ki-67 labelling index were found.
CONCLUSION: The ApoE E2/E3 genotype is associated with the presence of PA while the ApoE genotype E2/E4 is associated with noninvasive PA development. The allele ε3 could possibly have a protective effect against PA. The genotype E4/E4 is associated with the development of recurrent PA.

Pailhoriès H, Chenouard R, Eveillard M, et al.
A case of Ureaplasma parvum meningitis in an adult after transphenoidal ablation of craniopharyngioma.
Int J Infect Dis. 2019; 84:5-7 [PubMed] Related Publications
We report the case of a Ureaplasma parvum meningitis in an immunocompetent patient, 17 days after surgical ablation of a craniopharyngioma. Presence of U. parvum in the cerebrospinal fluid was assessed by 16S rDNA sequencing and U. parvum specific PCR. This article details a surprising complication in an adult of a transphenoidal surgery for ablation of a craniopharyngioma. This is the first case, to our knowledge, of U. parvum meningitis in an adult patient.

Ho PL, Chen YC, Teng CH, et al.
Acute parkinsonism as an unexpected consequence of pituitary adenoma resection: A case report.
Medicine (Baltimore). 2019; 98(17):e15261 [PubMed] Related Publications
INTRODUCTION: Transsphenoidal resection of pituitary tumors is a surgery performed through the nose and sphenoid sinus to remove pituitary tumors. Disorders of sodium balance are common after transsphenoidal surgery involving the pituitary gland. Here, we report the clinical features of an original case of acute onset parkinsonism later confirmed to be secondary to transsphenoidal resection of pituitary adenoma.
PATIENT CONCERNS: A 36-year-old female had received transsphenoidal pituitary resection for pituitary adenoma. Eight days after the surgery, she suffered from acute onset general weakness and nausea/vomiting. She was diagnosed with hyponatremia for which she was treated. Acute onset ataxia, bilateral hand tremor, and dysarthria were then noted on the 4th day of hyponatremia treatment.
DIAGNOSIS: Based on history, clinical manifestation, and MRI brain images, a diagnosis of acute parkinsonism caused by isolated extrapontine myelinolysis (EPM) was made.
INTERVENTIONS: Patient was treated with levodopa/carbidopa.
OUTCOMES: Patient's symptoms and signs improved gradually and 2 month follow-up MRI brain showed significant resolution of the bilateral lentiform nuclei hyperintensities on the T2-weighted images. Her neurological deficits had subsided completely.
LESSONS: This case highlights an unexpected association between transsphenoidal resection of pituitary tumors and acute parkinsonism which is a treatable manifestation of EPM. Correction of hyponatremia following transsphenoidal pituitary resections should be preceded cautiously because even gradual correction of hyponatremia can produce myelinolysis.

Hamidi O, Van Gompel J, Gruber L, et al.
Endocr Pract. 2019; 25(4):340-352 [PubMed] Related Publications

Rui QH, Ma JB, Liao YF, et al.
Effect of lncRNA HULC knockdown on rat secreting pituitary adenoma GH3 cells.
Braz J Med Biol Res. 2019; 52(4):e7728 [PubMed] Free Access to Full Article Related Publications
Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.

Shen DW, Li YL, Hou YJ, et al.
MicroRNA-543 promotes cell invasion and impedes apoptosis in pituitary adenoma via activating the Wnt/β-catenin pathway by negative regulation of Smad7.
Biosci Biotechnol Biochem. 2019; 83(6):1035-1044 [PubMed] Related Publications
Pituitary adenomas (PA) are commonly occurring benign neoplasms. Identification of molecular pathway resulting in pituitary tumorigenesis remains challenges in endocrine oncology. The present study was conducted with aim of investigating the role of microRNA-543 (miR-543) in PA development. Up-regulated miR-543 and downregulated Smad7 were observed in PA tissues. Afterwards, the specific mechanism of miR-543 and Smad7 in PA were determined with the use of ectopic expression, depletion and reporter assay experiments. Smad7 was confirmed as a target gene of miR-543. HP75 cells treated with overexpressed miR-543 exhibited increased cell proliferation, migration and invasion, while decreased cell apoptosis as well as expression of Cleaved caspase-3 and Cleaved caspase-8 were observed. Suppression of miR-543 contributed to an opposite trend to the above findings. Based on the findings, the inhibition of miR-543 was found to play a tumor suppressive role in PA through the down-regulation of Wnt/β-catenin pathway by negatively regulating Smad7.

Hu A, Zhang Y, Zhao X, et al.
CBX1 is a direct target of miR-205-5p and contributes to the progression of pituitary tumor.
Pharmazie. 2019; 74(3):154-156 [PubMed] Related Publications
MicroRNAs (miRs) are crucial regulators for tumorigenesis through negatively regulating their target genes expression in the manner of 3'-untranslated region (3'-UTR) binding. MiR-205-5p has been reported to function as a tumor suppressor in several cancer types. The aim of this study was to investigate the role of miR-205-5p/chromobox homolog 1 (CBX1) axis in human pituitary tumors. The expression of miR-205-5p was firstly examined by quantitative real-time PCR and the results revealed that miR-205-5p expression was declined in pituitary cell lines compared with normal cell line. Overexpression of miR-205-5p effectively decreased cell proliferation and cell migration. Based on the results of bioinformatic analysis, luciferase reporter assay, and western blot, we identified CBX1 as a direct target of miR-205-5p. Notably, overexpression of CBX1 promoted cell proliferation and migration. The effects of miR-205-5p overexpression on cell proliferation and migration can be reversed by CBX1 overexpression. Based on these findings, we deducted that miR-205-5p inhibits the cell proliferation and migration through directly targeting CBX1.

Pasyechko N, Naumova L, Krytskyy T, Kulchinska V
Georgian Med News. 2019; (287):26-29 [PubMed] Related Publications
Currently, lots of young couples are facing infertility. One of the relatively rare causes of female infertility is prolactinoma - hormonally active pituitary tumor that secretes excessive quantity of prolactin. Excessive prolactin production is leading to anovulation and women infertility. We propose for your attention a case report management of patient with prolactinoma. Long and adequate administration of inhibitors of prolactin secretion leads to regression of the tumor size up to its complete disappearance, which allows patients with prolactinoma not only to get pregnant, but also to nurse and give birth to healthy children.

Wong EH, Al-Witri A, Chong J, et al.
An alternative technique for pituitary tumour removal: Sequential endoscopic-microscopic pituitary procedure (SEMPP).
J Clin Neurosci. 2019; 64:94-97 [PubMed] Related Publications
Several authors have reported advantages of the purely endoscopic (PE) approach over traditional purely microscopic (PM) techniques for many sinus and anterior skull base procedures. However, in pituitary surgery, the PE approach carries a number of limitations. Experienced microscopically-trained neurosurgeons are required to master the endoscopic technique which has a steep learning curve due to its one-handed nature and optically-distorted 2-dimensional view. We describe our novel technique, the sequential endoscopic and microscopic pituitary procedure (SEMPP) which does not require microscopically-trained neurosurgeons to alter their technique. We compare SEMPP with the PE approach in terms of outcome and safety. Retrospective chart review of consecutive SEMPP cases performed at our institution between January 2010 and December 2013 was conducted. Operative time, gross total resection rate, resolution of endocrine and visual dysfunction, hospital length of stay, cerebrospinal fluid (CSF) leak rate and revision rates were recorded. 32 patients were identified (50% female, mean age 53.0 years), and 33 SEMPP cases. Mean operating time was 132 min (range 90-200). 69% of patients experienced gross total resection. Most patients (81.3%) with preoperative visual deficit either experienced complete resolution or improved symptoms. The remainder experienced no change in vision. 12.5% (n = 4) of patients experienced intraoperative CSF leaks. All were repaired intraoperatively or with conservative management. Two patients (6.3%) experienced epistaxis managed with conservative measures. The SEMPP technique demonstrates comparable outcomes, complication rates and operative time to PE and PM techniques described in the literature.

Li YL, Zhang S, Guo XP, et al.
Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China.
Arch Endocrinol Metab. 2019 Mar-Apr; 63(2):157-166 [PubMed] Related Publications
OBJECTIVES: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study.
SUBJECTS AND METHODS: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery.
RESULTS: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level.
CONCLUSION: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.

Ruggeri AG, Cappelletti M, Giovannetti F, et al.
Proposal of Standardization of Closure Techniques After Endoscopic Pituitary and Skull Base Surgery Based on Postoperative Cerebrospinal Fluid Leak Risk Classification.
J Craniofac Surg. 2019; 30(4):1027-1032 [PubMed] Related Publications
Postoperative cerebrospinal fluid (CSF) leak still represents the main limitation of endonasal endoscopic surgery. The aim of the study is to classify the risk of postoperative leak and to propose a decision-making protocol to be applied in the preoperative phase based on radiological data and on intraoperative findings to obtain the best closure.One hundred fifty-two patients were treated in our institution; these patients were divided into 2 groups because from January 2013 the closure technique was standardized adopting a preoperative decision-making protocol. The Postoperative CSF leak Risk Classification (PCRC) was estimated taking into account the size of the lesion, the extent of the osteodural defect, and the presence of intraoperative CSF leak (iCSF-L). The closure techniques were classified into 3 types according to PCRC estimation (A, B, and C).The incidence of the use of a nasoseptal flap is significantly increased in the second group 80.3% versus 19.8% of the first group and the difference was statistically significant P < 0.0001. The incidence of postoperative CSF leak (pCSF-L) in the first group was 9.3%. The incidence of postoperative pCSF-L in the second group was 1.5%. An analysis of the pCSF-L rate in the 2 groups showed a statistically significant difference P = 0.04.The type of closure programmed was effective in almost all patients, allowing to avoid the possibility of a CSF leak. Our protocol showed a significant total reduction in the incidence of CSF leak, but especially in that subgroup of patients where a leak is usually unexpected.

Kim LH, Kim JH, Namgoong S, et al.
A PHLDB1 variant associated with the nonfunctional pituitary adenoma.
J Neurooncol. 2019; 142(2):223-229 [PubMed] Related Publications
PURPOSE: Previous studies have revealed that PHLDB1 single-nucleotide polymorphisms (SNPs) are associated with glioma risk. Nonetheless, the association between PHLDB1 SNPs and the risk of pituitary adenoma has not been studied. The present study evaluated the association of PHLDB1 SNPs with the risk of pituitary adenomas.
METHODS: We genotyped 27 PHLDB1 tagging and exon SNPs in a case-control study that included 148 patients who got a diagnosis of nonfunctional pituitary adenoma (NFPA) and 375 normal controls within the Korean population. Statistical analyses of the association between PHLDB1 SNPs and the NFPA risk were conducted using logistic regression.
RESULTS: We detected an association between a PHLDB1 SNP and the risk of NFPA in the Korean population. Rs67307131 in intron 2 was significantly associated with NFPA (odds ratio [OR] = 2.15, 95% confidence interval [CI] 1.44-3.20; P = 0.0002 in the dominant model). In the referent analysis, a higher OR and stronger association (lower P value) were observed among patients with the "C/T" genotype (OR = 2.39, 95% CI 1.60-3.58; P = 0.00002). In a functional analysis with a SNP annotation tool, this SNP was predicted to be a CpG site and copy number variant; these properties are associated with susceptibility to diseases.
CONCLUSIONS: Our findings suggest that genetic variation of PHLDB1 may be associated with the risk of NFPA. This is the first report of an association between PHLDB1 variants and NFPA. Further research is needed to confirm the impact of this SNP on NFPA susceptibility.

Choudhary C, Hamrahian AH, Bena JF, et al.
Endocr Pract. 2019; 25(7):684-688 [PubMed] Related Publications

Kawaguchi T, Ogawa Y, Tominaga T
Early surgical intervention for patients with possible clinically silent somatotroph adenoma: a case series.
J Med Case Rep. 2019; 13(1):85 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Clinically silent somatotroph adenoma is characterized by elevated serum growth hormone but without the clinical symptoms of acromegaly, and it is considered rare. The natural history is not well understood, progress to symptomatic is uncertain, and treatment strategy has not been established.
CASE PRESENTATION: The first patient was a 48-year-old-Asian woman who presented with serum growth hormone 6.99 ng/ml and insulin-like growth factor 1 of 476 ng/ml, but no characteristic features of acromegaly. Five years after initial diagnosis, she presented with acromegalic facial appearance. Transsphenoidal surgery achieved gross total removal and endocrinological remission. The second patient was a 40-year-old-Asian woman who presented with serum growth hormone 31.14 ng/ml and insulin-like growth factor 1 of 709.6 ng/ml, but no characteristic features of acromegaly. Three years after initial diagnosis, she presented with acromegalic facial appearance. Transsphenoidal surgery achieved gross total removal and endocrinological remission. The third patient was a 64-year-old-Asian woman who presented with serum growth hormone 6.0 ng/ml and insulin-like growth factor 1 of 341 ng/ml, but no characteristic features of acromegaly. Eight months after initial diagnosis, hand enlargement was detected. Transsphenoidal surgery achieved gross total removal and endocrinological remission.
CONCLUSION: Due to its potential for evolving to symptomatic disease, the risks of surgery and observation for patients with somatotroph adenoma should be carefully compared from the viewpoint of better health outcome.

Crouzeix G, Morello R, Thariat J, et al.
Quality of Life but not Cognition is Impacted by Radiotherapy in Patients with Non-Functioning Pituitary Adenoma.
Horm Metab Res. 2019; 51(3):178-185 [PubMed] Related Publications
Non-functioning pituitary adenomas (NFPA) are benign neoplasms that are first treated by surgery and secondary radiation therapy in case of residual tumor or regrowth. The consequences of surgery and radiotherapy are still debated. The objective of the work was to assess the impact of surgery, radiotherapy (RT) and pituitary deficiencies on long term health-related quality of life (QoL) and cognitive function among NFPA patients. Forty-six NFPA patients were studied after 9.6±7.5 years follow-up using: i) the MoCA questionnaire to detect mild cognitive disabilities, ii) the McNair and Kahn scale to assess perceived cognitive impairment, iii) the HADS questionnaire to score anxiety and depression, and iv) the SF-36 and QLS-H questionnaires to assess QoL. All NFPA patients had surgery and 54% patients had radiation therapy (RT+). The MoCA score was abnormal in 41% NFPA patients. Neither the type of surgery nor radiotherapy influenced the prevalence of cognitive disabilities. The depression score was higher in RT+than RT- patients. Overall, no alteration in SF-36 and QLS-H QoL scales were observed in NFPA patients when compared with the French reference population. Among NFPA patients, mental composite score, general health and vitality scores were altered in RT+compared to RT- patients. The presence of multiple pituitary axis deficiencies worsened general health and vitality scale scoring. Consistent follow-up had a beneficial impact on psycho-emotional dimensions of health. Surgery and radiotherapy had no adverse effects on cognitive functions, however, QoL was altered in RT+patients. These latter alterations may be partly related to pituitary hormone deficiencies.

Corlan AS, Cîmpean AM, Melnic E, et al.
VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas.
Eur J Histochem. 2019; 63(1) [PubMed] Free Access to Full Article Related Publications
Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

Raman R, Raman A
A pituitary tumor turned-to-be a glioma: A surgical case from the Madras General Hospital 1928.
Indian J Cancer. 2018 Oct-Dec; 55(4):424-427 [PubMed] Related Publications
A three-page paper entitled "A case of glioma (embryonal neurocytoma) of the brain simulating pituitary tumour," written by K. G. Pandalai, Surgeon at the Madras General Hospital, and T. B. Menon, Pathologist at the Madras Medical College, was published in the Indian Medical Gazette. This paper refers to an occasional finding of a brain tumor (a glioma), presurgically diagnosed as a pituitary tumor, in 1928. This was close to the period when surgeons across the developed world believed in that cancers were by no means common among the native people of India as it was in Europe. Leopold Rogers of the Bengal Medical Service, Calcutta, in 1925 refuted this belief indicating that malignant tumors were equally common in Bengal (India) and England. Nevertheless, this report by Pandalai and Menon strikes a unique chord since the tumor was subsequently determined as a glioma - an embryonal neurocytoma -- with adequate evidences drawn from the state-of-the-art volume "A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis" by Percival Bailey and Harvey Cushing published in Philadelphia in 1926. This Pandalai--Menon report impresses as pioneering and trailblazing, on a brain tumor detected in 1928, given that earliest exclusive departments of neurosurgery were established in Christian Medical College, Vellore, and Madras Medical College, Madras, by Jacob Chandy and Balasubramanian Ramamurthi, respectively, nearly two decades later.

Losa M, Donofrio CA, Gemma M, et al.
Pretreatment with somatostatin analogs does not affect the anesthesiologic management of patients with acromegaly.
Pituitary. 2019; 22(2):187-194 [PubMed] Related Publications
PURPOSE: Acromegaly may be associated with an increased risk of complex intraoperative management and anesthetic complications. No study addressed whether pretreatment with somatostatin receptor ligands (SRLs) affects anesthesiologic management.
METHODS: We studied 211 consecutive acromegalic patients who had a recorded intraoperative computerized anesthetic record (ICAR) available for analysis. Ninety-six (45.5%) patients were SRL-pretreated while 115 patients were treatment naïve.
RESULTS: Treatment with SRLs reduced mean basal growth hormone level from 23.8 ± 4.2 to 5.9 ± 1.3 µg/L. Normalization of insulin-like growth factor-1 was achieved in 26 patients (27.1%). The frequency of comorbidities at surgery was similar in the two groups. Five patients with difficult intubation were naïve (4.3%) as compared with 5 SRL-pretreated patients (5.2%; P = 1.0). ICAR registration did not show any significant change of intraoperative vital parameters in the two groups of patients as well as in the intraoperative utilization of drugs. Total duration of anesthesia and surgery were similar in the two groups. Four patients with an intraoperative adverse event were naïve (3.5%) as compared with 4 SRL-pretreated patients (4.2%; P = 1.00). Remission of disease occurred in 83 of 114 naïve patients (72.8%) and in 57 of 93 SRL-pretreated patients (61.3%; P = 0.11).
CONCLUSIONS: SRL-pretreatment of patients with acromegaly had no significant impact on intraoperative anesthesiologic management. Despite a better Cormack-Lehane score in SRL-pretreated than in naïve patients, the rate of difficult intubation was similar in both groups. SRL-pretreatment did not affect the rate of surgical remission or complications as well.

Graillon T, Castinetti F, Chabert-Orsini V, et al.
Functioning gonadotroph adenoma with severe ovarian hyperstimulation syndrome: A new emergency in pituitary adenoma surgery? Surgical considerations and literature review.
Ann Endocrinol (Paris). 2019; 80(2):122-127 [PubMed] Related Publications
The authors reported 2 cases of functioning gonadotroph pituitary adenoma (FGPA) revealed by an ovarian hyperstimulation syndrome (OHSS) in young women. In the first case, OHSS was observed after GnRH analog injection. Pelvic echography revealed multiple voluminous ovarian cysts. Dopamine agonist posology failed in estradiol hypersecretion control, which necessitated endoscopic endonasal transsphenoidal surgery. The patient experienced improvement in pelvic pain as estradiol hypersecretion decreased during the first few postoperative days. Outcome was favorable, and her menstrual cycle was normal after two months. The second case was a young girl with spontaneous pelvic pain and elevated plasma FSH and estradiol levels. FGPA was confirmed on cerebral MRI. Dopamine agonists were introduced, and surgical removal of the pituitary tumor was scheduled for 7 days later. In the meantime, the patient was admitted and underwent surgery for bilateral adnexal torsion related to OHSS. The pituitary tumor was removed one week later. Outcome was favorable, and estradiol and FSH plasma levels were normal after 3 months. The ovarian cysts were no longer visible on echography after 3 months. Given the lack of efficacy of the current standard medical therapy, surgical removal of pituitary adenomas is the reference treatment for FGPA. The authors suggest that severe OHSS related to FGPA should be considered as a relative surgical emergency and that surgery should not be unduly delayed, given the unpredictable risk of adnexal torsion, particularly in case of voluminous ovarian cysts. The authors performed a literature review on this topic.

Mittal A, Mishra S, Yadav K, Rajput R
Uncontrolled diabetes as a rare presenting cause of pituitary apoplexy.
BMJ Case Rep. 2019; 12(2) [PubMed] Related Publications
Pituitary apoplexy is a rare endocrine emergency. The extent to which hyperglycaemia is a contributory risk factor in the precipitation of pituitary apoplexy is not known. A 38-year-old man with poorly controlled diabetes presented to the emergency department with sudden onset of nausea and headache with drooping of his right eyelid for about 4 days. On physical examination, he had orthostatic hypotension, ptosis of the right eye, lateral and downward positioning of the eye and absent pupillary reflex. Visual field testing of the left eye revealed superolateral quadrantanopia. MRI of the brain showed pituitary macroadenoma with necrosis. Investigations showed hyperglycaemia, decreased T3, T4 with normal Thyroid stimulating hormone (TSH), low serum Leutinizing hormone (LH), Follicle stimulating hormone (FSH), testosterone and low normal serum prolactin levels. About 21% of non-functioning pituitary adenomas present with apoplexy as was seen in our patient. It is likely that his uncontrolled diabetes precipitated this episode of apoplexy as hyperosmolarity and dehydration, caused by hyperglycaemia can lead to changed pituitary microvascular environment increasing the risk of pituitary infarction.

Ságová I, Pávai D, Kantárová D, et al.
The combination of acromegaly and Klinefelter syndrome in one patient.
Vnitr Lek. Winter 2019; 65(1):51-54 [PubMed] Related Publications
Acromegaly is a rare disorder usually caused by a benign tumour of the pituitary gland. Long-term presence of elevated growth hormone (GH) and insulin like growth factor 1 (IGF1) levels accompanying this disease is associated with complications such as cardiomyopathy, diabetes mellitus, sleep apnoea and arthropathy. Incidence of acromegaly is 3-4 patients per million per year. Klinefelter syndrome (KS) is the most common sex chromosome disorder occuring in about 1/500 live male births. Common physical features include particularly small testes, among other symptoms are tall stature, reduced muscle tone, delayed pubertal development, lack of secondary male sex characteristics and gynecomastia. We present a 32-year-old man suffering from both acromegaly and 47, XXY Klinefelter syndrome. The patient with typical acromegalic features. Laboratory tests revealed high level of GH which was not suppressed after glucose administration, high level of IGF1, low testosterone concentration with high concentation of luteinizing hormone and follicle stimulating hormone. A magnetic resonance imaging scan revealed a 25 × 18 × 18 mm macroadenoma involving the pituitary gland. A diagnosis of acromegaly was established. After this examination trans-sphenoidal resection was performed. Histopathologic and immunohistochemical findings revealed growth hormoneproducing pituitary adenoma. The presence of infertility with clinical features such as small testes, lack of secondary male sex characteristics and laboratory findings revealed hypergonadotropic hypogonadism that could not be explained by the diagnosis of acromegaly. A chromosomal karyotyping revealed a 47, XXY, confirming the diagnosis of KS. Testosterone replacement therapy wasn´t begun because of patient disagreement Postoperatively elevated plasma concentration of GH and IGF1 levels persist. Treatment by somatostatin analogues (lanreotid) was initiated at dose 120 mg every 28 days. Control magnetic resonance imaging of the sella demonstrated a residue of pituary adenoma size 14 × 14 × 7 mm. The patient is currently undergoing endoscopic revision of the residue. acromegaly - growth hormone - IGF1 - Klinefelter syndrome - testosterone.

Cole TS, Jahnke H, Godzik J, et al.
Use of a wrist-mounted device for continuous outpatient physiologic monitoring after transsphenoidal surgery: a pilot study.
Pituitary. 2019; 22(2):156-162 [PubMed] Related Publications
PURPOSE: Patients who undergo transsphenoidal surgery can experience hormonal, electrolyte, and fluid disturbances in the postoperative period leading to outpatient readmissions for medical management. Our goal was to determine whether use of a wrist-mounted physiologic tracking device is feasible in this setting and whether changes or trends in these parameters after discharge can help predict aberrant physiology in these patients.
METHODS: Wrist-mounted physiologic tracking devices that transmit data via Bluetooth to a mobile device were used to monitor patients. Preoperative baseline data and postoperative data were aggregated daily to compare within-patient and between-patient trends.
RESULTS: Of 11 patients enrolled in the study, 1 was readmitted for symptomatic hyponatremia. Device data completeness ranged from 78 to 93% with the exception of oxygen saturation (25% completeness). The patient with hyponatremia had a significantly lower baseline level of activity compared with other patients. Nonreadmitted patient activity variables (steps, calories, and distance) decreased by 48-52% after the operation (P < 0.001). The activity variables for the patient with hyponatremia were statistically unchanged after the operation; however, the patient did experience a significant decrease in heart rate compared with baseline.
CONCLUSION: Deployment of a wrist-based physiologic tracking device is feasible for surgical patients in elective clinical practice. Overall, the device was associated with good patient adherence and high patient satisfaction. Patient activity significantly decreased after surgery. A significant decrease in heart rate was detected in a patient with hyponatremia who required readmission, which reflects the known intravascular volume expansion in this state.

Sickler T, Trarbach EB, Frassetto FP, et al.
Filamin A and DRD2 expression in corticotrophinomas.
Pituitary. 2019; 22(2):163-169 [PubMed] Related Publications
PURPOSE: Filamin A (FLNA) expression is related to dopamine receptor type 2 (DRD2) expression in prolactinomas. Nevertheless, in corticotrophinomas, there are few studies about DRD2 expression and no data on FLNA. Therefore, we evaluated FLNA and DRD2 expression in corticotrophinomas and their association with tumor characteristics.
METHODS: DRD2 and FLNA expression by immunohistochemistry, using H-score, based on the percentage of positive cells in a continuous scale of 0-300, were evaluated in 23 corticotrophinomas samples from patients submitted to neurosurgery. In six patients, treatment with cabergoline was indicated after non curative surgery.
RESULTS: Twenty-two patients were female and one male. Regarding tumor size, 10 were micro and 12 were macroadenomas. DRD2 expression was found in 89% of cases and did not correlate with FLNA expression. Moreover, the response to cabergoline, observed in 33% of the cases, did not correlate with DRD2 nor FLNA expression. FLNA expression was not associated with clinical and tumor characteristics, except for sphenoid sinus invasion.
CONCLUSIONS: In our cohort of corticotrophinomas, DRD2 expression was not associated with FLNA expression nor to the response to CAB. Nonetheless, FLNA expression could be related to tumor invasiveness.

Moria Y, Kortbawi R, El-Asmar N, Arafah BM
Increased androgen secretion in patients with prolactinomas: the impact of altered HPA function.
Pituitary. 2019; 22(2):170-178 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Earlier studies suggested that hyperprolactinemia was associated with elevated serum DHEA-S levels. The importance of DHEA-S measurements in the diagnosis of adrenal insufficiency prompted us to assess adrenal androgen levels in hyperprolactinemic subjects with normal or impaired function.
METHODS: Prospective study including 122 medically treated and 26 surgically patients with prolactinomas. Serum PRL, DHEA and DHEA-S levels were measured before and repeatedly after cabergoline therapy and also in the perioperative period of surgically treated patients.
RESULTS: Serum PRL levels decreased (P < 0.001) in all 101 medically treated patients with normal HPA function from 728.3 ± 1507 reaching 29.1 ± 39 and 14.9 ± 24.4 µg/L at 3 and 12 months, respectively. Concurrently serum DHEA-S levels decreased (P < 0.001) from 245.9 ± 196 to 216.2 ± 203.3 and to 169.7 ± 121.1 µg/dl at 3 and 12 months, respectively. These effects were reversed in 19 patients who discontinued treatment and were re-demonstrated after therapy resumption. Among the 22 surgically treated patients with normal HPA, peri-operative PRL levels decreased rapidly (P < 0.001) with a parallel decline in serum DHEA-S levels (P = 0.03). Strong correlations were noted between PRL and DHEA-S decrements observed with medical or surgical therapy. Medically (n = 21) and surgically (n = 4) patients with impaired HPA function had very low DHEA-S values that were unchanged despite marked reductions in PRL secretion.
CONCLUSION: Hyperprolactinemia is associated with a reproducible and reversible increase in serum DHEA-S that was observed in medically- and surgically-treated patients with normal HPA function. Thus, a normal age- and gender-adjusted serum DHEA-S level continues to imply normal HPA function even among hyperprolactinemic subjects.

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