Grading system may predict recurrence, progression of pituitary neuroendocrine tumors

Posted on June 27, 2017 by MaryO

The risk for recurrence or progression of pituitary neuroendocrine tumors in adults is significantly associated with age and tumor type, according to findings published in The Journal of Clinical Endocrinology & Metabolism.

Gérald Raverot, MD, PhD, of Hospices Civils de Lyon, Federation d’Endocrinologie du Pole Est in France, and colleagues evaluated 374 adults (194 women) who underwent surgery for a pituitary neuroendocrine tumor (mean age at surgery, 51.9 years) between February 2007 and October 2012 to test the value of a new classification system on prognostic relevance.

Tumors were classified using a grading system based on invasion on MRI, immunocytochemical profile, Ki-67 mitotic index and p53 positivity. Noninvasive tumors were classified as grade 1a, noninvasive but proliferative tumors were grade 1b, invasive tumors were grade 2a, invasive and proliferative tumors were grade 2b and metastatic tumors were grade 3.

Macroadenomas were the most common type of tumor based on MRI classification (82.1%), followed by microadenoma (13.6%) and giant adenoma (4.3%).

Information on grade was available for 365 tumors; grade 1a was the most common (51.2%), followed by grades 2a (32.3%), 2b (8.8%) and 1b (7.7%).

The progression-free survival analysis included 213 participants from the original cohort during a mean follow-up of 3.5 years. A recurrent event occurred in 52 participants, and progression occurred in 37 participants. The risk for recurrence and/or progression was associated with age (P = .035), tumor type (P = .028) and grade (P < .001). The risk for recurrence and/or progression was increased with grade 2b tumors compared with grade 1a tumors (HR = 3.72; 95% CI, 1.9-7.26) regardless of tumor type. Invasion was significantly associated with recurrence in grade 2a tumors (HR = 2.98; 95% CI, 1.89-4.7), whereas proliferation was not significantly associated with prognosis for grade 1b (HR = 1.25; 95% CI, 0.73-2.13).

“This prospective study confirms the usefulness of our previously proposed classification and may now allow clinicians to adapt their therapeutic strategies according to prognosis, but may also be used to stratify patients and evaluate therapeutic efficacy in future clinical trials,” the researchers wrote. “Further progress can be expected, in particular if an improved understanding of molecular abnormalities associated with pituitary tumorigenesis generates better biomarkers.” – by Amber Cox

Disclosures: The researchers report no relevant financial disclosures.

From https://www.healio.com/endocrinology/neuroendocrinology/news/in-the-journals/%7B4dbd524c-4534-42e3-a1dc-4e3a0d82a0f1%7D/grading-system-may-predict-recurrence-progression-of-pituitary-neuroendocrine-tumors

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A retrospective analysis of postoperative hypokalemia in pituitary adenomas after transsphenoidal surgery

Posted on May 23, 2017 by MaryO

Abstract.

Background

Pituitary adenoma is one of the most common intracranial neoplasms, and its primary treatment is endoscopic endonasal transsphenoidal tumorectomy. Postoperative hypokalemia in these patients is a common complication, and is associated with morbidity and mortality. This study aimed to analyze the etiopathology of postoperative hypokalemia in pituitary adenomas after endoscopic transsphenoidal surgery.

Methods and Materials

This retrospective study included 181 pituitary adenomas confirmed by histopathology. Unconditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Repeated measures ANOVA was used to analyze change in serum potassium levels at different time points.

Results

Multiple Logistic regression analysis revealed that only ACTH-pituitary adenoma (OR = 4.92, 95% CI [1.18–20.48], P = 0.029) had a significant association with postoperative hypokalemia. Moreover, the overall mean serum potassium concentration was significantly lower in the ACTH versus the non-ACTH group (3.34 mmol/L vs. 3.79 mmol/L, P = 0.001). Postoperative hypokalemia was predominantly found in patients with ACTH-pituitary adenoma (P = 0.033).

Conclusions

ACTH-pituitary adenomas may be an independent factor related postoperative hypokalemia in patients despite conventional potassium supplementation in the immediate postoperative period.

Cite this as

You L, Li W, Chen T, Tang D, You J, Zhang X. (2017) A retrospective analysis of postoperative hypokalemia in pituitary adenomas after transsphenoidal surgery. PeerJ5:e3337 https://doi.org/10.7717/peerj.3337

Read the entire article at https://peerj.com/articles/3337/

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Primary Adrenal Insufficiency (PAI)

Posted on May 6, 2017 by MaryO
05.05.2017, 05:18 by SciDoc Publishers International Journal of Clinical Therapeutics and Diagnosis (IJCTD)
 Al-Jurayyan NA
Background: Primary adrenal insufficiency (PAI) in children is an uncommon, but potentially fatal. The current symptoms include weakness, fatigue, anorexia, abdominal pain, weight loss, orthostatic hypotension, salt craving and characterized by hyperpigmentation.
Material and Methods: This is a retrospective, hospital based-study, conducted at King Khalid University Hospital (KKUH), during the period January 1989 and December 2014. Review of medical record of patient diagnosed with primary adrenal insufficiency. The diagnosis was based on medical history, physical examination and low levels of glucocorticoids and raised adrenocorticotropic hormone (ACTH). Appropriate laboratory and radiological investigations were also reviewed.
Results: During the period under review, January 1989 and December 2014, a total of 125 patients with the diagnosis of primary adrenal insufficiency were seen. Inherited disorders like congenital adrenal hyperplasia and hypoplasia were common, 85.5%. However, variable autoimmune mediated etiologic diagnosis accounted for, 13%, were also seen. The appropriate various laboratory and radiological investigations should be planned.
Conclusion: Although, congenital adrenal hyperplasia was the commonest etiology, however, congenital adrenal hypoplasia should not be over looked. The diagnosis of PAI can be challenging in some patients, and therefore appropriate serological and radiological investigations should be done.

REFERENCES

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Comparison of MRI techniques for detecting microadenomas in Cushing’s disease

Posted on April 29, 2017 by MaryO
1Department of Neurological Surgery and 2Department of Radiology, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia
ABBREVIATIONS ACTH = adrenocorticotropic hormone; CMRI = conventional MRI; DMRI = dynamic contrast-enhanced MRI; FSH = follicle-stimulating hormone; IPSS = inferior petrosal sinus sampling; SE = spin echo; SGE = spoiled-gradient echo 3D T1 sequence; SPGR = spoiled gradient–recalled acquisition; VIBE = volumetric interpolated breath-hold examination.

INCLUDE WHEN CITING Published online April 28, 2017; DOI: 10.3171/2017.3.JNS163122.

Correspondence Edward H. Oldfield, Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA 22908. email: .
OBJECTIVE

Many centers use conventional and dynamic contrast-enhanced MRI (DMRI) sequences in patients with Cushing’s disease. The authors assessed the utility of the 3D volumetric interpolated breath-hold examination, a spoiled-gradient echo 3D T1 sequence (SGE) characterized by superior soft tissue contrast and improved resolution, compared with DMRI and conventional MRI (CMRI) for detecting microadenomas in patients with Cushing’s disease.

METHODS

This study was a blinded assessment of pituitary MRI in patients with proven Cushing’s disease. Fifty-seven patients who had undergone surgery for Cushing’s disease (10 male, 47 female; age range 13–69 years), whose surgical findings were considered to represent a microadenoma, and who had been examined with all 3 imaging techniques were included. Thus, selection emphasized patients with prior negative or equivocal MRI on referral. The MRI annotations were anonymized and 4 separate imaging sets were independently read by 3 blinded, experienced clinicians: a neuroradiologist and 2 pituitary surgeons.

RESULTS

Forty-eight surgical specimens contained an adenoma (46 ACTH-staining adenomas, 1 prolactinoma, and 1 nonfunctioning microadenoma). DMRI detected 5 adenomas that were not evident on CMRI, SGE detected 8 adenomas not evident on CMRI, including 3 that were not evident on DMRI. One adenoma was detected on DMRI that was not detected on SGE. McNemar’s test for efficacy between the different MRI sets for tumor detection showed that the addition of SGE to CMRI increased the number of tumors detected from 18 to 26 (p = 0.02) based on agreement of at least 2 of 3 readers.

CONCLUSIONS

SGE shows higher sensitivity than DMRI for detecting and localizing pituitary microadenomas, although rarely an adenoma is detected exclusively by DMRI. SGE should be part of the standard MRI protocol for patients with Cushing’s disease.

Full text at http://thejns.org/doi/full/10.3171/2017.3.JNS163122

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The Cables1 Gene in Glucocorticoid Regulation of Pituitary Corticotrope Growth and Cushing Disease

Posted on March 14, 2017 by MaryO

Audrey Roussel-Gervais 1 Catherine Couture 1 David Langlais 1 Shinobu Takayasu 1 Aurelio Balsalobre 1 Bo R. Rueda 2 Lawrence R. Zukerberg 2 Dominique Figarella-Branger 3, 4 Thierry Brue 5 Jacques Drouin 2

Details

1 Laboratoire de Génétique Moléculaire
2 MGH – Massachusetts General Hospital [Boston]
3 LA CONCEPTION – Hôpital de la Conception [CHU – APHM]
4 ACPNP – Service d’Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone – APHM]
5 CRN2M – Centre de recherche en neurobiologie – neurophysiologie de Marseille
Abstract :
Context: Cushing disease (CD) is due to pituitary corticotrope adenomas that produce unrestrained ACTH secretion and have lost the negative feedback exerted by glucocorticoids (GCs). GCs also restrain corticotrope proliferation, and the mechanisms of this inhibition are poorly understood.
Objective: The aim of the study was to identify cell cycle regulatory genes that are regulated by GCs and the glucocorticoid receptor and to assess regulatory genes that have a rate-limiting action on corticotrope proliferation and may be disregulated in CD.
Design: The mouse corticotrope tumor cells AtT-20 were used to identify GC-regulated genes that contribute to control of cell cycle progression. Surgery sections from patients with CD were used to assess expression of CABLES1 in corticotrope adenomas.
Methods: Gene expression profiling, small interfering RNA knockdowns, cell cycle analyses, and genetic manipulations were performed in AtT-20 cells. Sequencing of chromatin immunoprecipitation for pituitary-restricted transcription factors and RNA polymerase II were used to identify regulatory elements and genes that bind GR and are direct transcriptional targets. A panel of previously well-characterized corticotrope adenomas was used to correlate expression of CABLES1 with that of other markers. Results: GCs altered expression of 3 positive and 3 negative regulators of cell cycle progression. Two Myc genes (L-Myc and N-Myc) and E2F2 are repressed by GCs, whereas genes for the negative regulators of the cell cycle, Gadd45, Gadd45, and Cables1 are activated by GCs. Cables1 small interfering RNA knockdown strongly stimulates AtT-20 cell proliferation and antagonizes the growth inhibition produced by GCs. The Gadd45 and Cables1 genes have the hallmarks of direct GC targets. CABLES1 is expressed in normal human pituitary cells, but expression is lost in 55% of corticotrope adenomas, and this is strongly correlated with the loss of p27 Kip1 expression.
Conclusions: CABLES1 is a critical regulator of corticotrope proliferation that defines a pathway often inactivated in CD and links proliferation to GC resistance. (J Clin Endocrinol Metab

Document type :

Journal articles
Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2016, 101 (2), pp.513-522. <10.1210/jc.2015-3324>

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