Value of dynamic MRI imaging in pituitary adenomas Indrajit I K, Chidambaranathan N, Sundar K, Ahmed I – Indian J Radiol Imaging

Posted on June 24, 2015 by MaryO

Objectives : MRI has proven to be the best imaging modality in the evaluation of pituitary tumors. Dynamic Imaging is technically a new tool, which has emerged with lot of promise in the evaluation of pituitary adenomas, particularly in accurate delineation of those microadenomas with no contour abnormality and in differentiating residual/recurrent adenoma from surrounding post operative tissue. Dynamic MR imaging is not only useful in the evaluation of pituitary microadenomas but has an equally important role in the assessment of macroadenoma as well. This study analyses and reviews the value of dynamic MR Imaging in pituitary adenomas and postoperative pituitary tumors.

Materials and Methods : A prospective MR Study was undertaken in twenty-five consecutive patients with suspected pituitary adenomatous lesions. These patients were subjected to dynamic MR imaging at our Department from Jan 1997 to Dec 1998. The study was performed on a 0.5T super conducting MR imaging system with Fast Spin echo technique. Gadodiamide (0.1 mmol/Kg) was administered over sixty seconds by hand injection. Dynamic coronal images were obtained simultaneously from three different portions of the gland. Fifteen images were obtained from each of the three portions at an interval of twenty to thirty seconds between the images.

Result : Dynamic MRI was performed in nineteen patients with microadenoma and six cases of macroadenoma. Dynamic MRI study was of diagnostic value in comparison with routine contrast MRI in eleven of the nineteen patients. Dynamic study did not add to the diagnosis and was merely of confirmatory value in remaining eight patients. Dynamic MRI study was used to identify the optimal time for delineation of the adenomatous tumor, by virtue view of the simultaneous differential contrast enhancement patterns between normal pituitary gland and adenoma. Further the enhancement pattern of the normal pituitary gland, the adenomatous nodule and the optimal delineation were individually assessed. This evaluation revealed the average time in seconds for onset of enhancement and the peak enhancement of normal pituitary gland were 43.1 and 111.9 seconds respectively. In comparison the pituitary adenomatous nodules exhibited an average time of 105.8 seconds for onset of enhancement and 188.1 seconds for peak enhancement. The average time in seconds for optimal tumor delineation was 93.9 seconds.

Conclusion : Dynamic MR Imaging has emerged as a technically refined tool in the evaluation of pituitary adenomas. The key questions in evaluation of pituitary adenomas include the presence or absence of a tumor, the number, the location of adenoma nodule, the invasive effects on adjacent structures and the post therapy status of adenoma. Clearly, dynamic MR Imaging is the foremost imaging modality answering these vital questions in patients with pituitary adenomas.

via Value of dynamic MRI imaging in pituitary adenomas Indrajit I K, Chidambaranathan N, Sundar K, Ahmed I – Indian J Radiol Imaging.

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PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia

Posted on March 31, 2015 by MaryO
Eur J Endocrinol. 2015 Mar 6. pii: EJE-14-1113. [Epub ahead of print]

PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia – a single-center study of 60 cases.

Thiel A1, Reis AC2, Haase M3, Goh G4, Schott M5, Willenberg HS6, Scholl UI7.

Author information

Abstract

Objective: Cortisol excess due to adrenal adenomas or hyperplasia causes Cushing’s syndrome. Recent genetic studies have identified a somatic PRKACAL206R mutation as a cause of cortisol-producing adenomas.

We aimed to compare the clinical features of lesions with PRKACA mutations to those with CTNNB1 mutations and to search for similar mutations in unilateral hyperplasia or tumors co-secreting aldosterone.

Design, patients and methods: 60 patients with cortisol excess who had adrenalectomies at our institution between 1992 and 2013 were assessed, and somatic mutations were determined by Sanger sequencing. 36 patients had overt Cushing’s syndrome, the remainder were subclinical. 59 cases were adenomas (three bilateral), one was classified as hyperplasia. Four tumors had proven co-secretion of aldosterone.

Results: Among cortisol-secreting unilateral lesions without evidence of co-secretion (n=52), we identified somatic mutations in PRKACA (L206R) in 23.1%, CTNNB1 (S45P, S45F) in 23.1%, GNAS (R201C) in 5.8% and CTNNB1 plus GNAS (S45P, R201H) in 1.9%. PRKACA and GNAS mutations were mutually exclusive. Of the co-secreting tumors, two (50%) had mutations in KCNJ5 (G151R and L168R). The hyperplastic gland showed a PRKACAL206R mutation, while patients with bilateral adenomas did not have known somatic mutations. PRKACA-mutant lesions were associated with younger age, overt Cushing’s syndrome and higher cortisol levels versus non-PRKACA-mutant or CTNNB1-mutant lesions. CTNNB1 mutations were more significantly associated with right than left lesions.

Conclusions: PRKACAL206R is present not only in adenomas, but also in unilateral hyperplasia and is associated with more severe autonomous cortisol secretion. Bilateral adenomas may be caused by yet-unknown germline mutations.

PMID:
25750087
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/25750087

Filed under: adrenal, Clinical trials, Cushing's, Treatments | Tagged: , , , , , , , , | 1 Comment »

Day 3 Coverage of ENDO 2015

Posted on March 7, 2015 by MaryO

ENDO_2015

 

OR24-Adrenal Tumors: Clinical Implications of the Recent Molecular and Genetic Findings

Long term follow-up of a pivotal phase 2 study of Ultratrace® Iobenguane I-131 (AZEDRA) in patients with malignant relapsed/refractory pheochromocytoma/paraganglioma
C Jimenez, DA Pryma, DC Sullivan, JK Schwarz, RB Noto, N Stambler, T Armor, JD Jensen, RJ Israel

OR27-Hyperandrogenic Ovarian Dysfunction — Winner: Outstanding Abstract Award

The neurokinin B receptor antagonist AZD4901 decreases LH and testosterone secretion in women with PCOS: A randomized, double-blind, placebo-controlled clinical trial
JT George, R Kakkar, J Marshall, ML Scott, R Finkelman, T Ho, S McIntosh, JD Veldhuis, RA Anderson, L Webber

OR28-Lipids – Liver, Muscle, and Patient Bench to Bedside

Diagnosing familial hypercholesterolemia (FH) in the United States: Results from the CASCADE FH patient registry
Z Ahmad, C Newman, E O’Brien, P Shrader, EM deGoma, CD Ahmed, PM Moriarty, MRF Linton, MD Shapiro, PB Due, CM Ballantyne, WA Neal, D Duffy, L Hudgins, LC Hemphill, JA Underberg, KE Watson, SS Gidding, S Baum, K Wilemon, D Pickhardt, I Kindt, DJ Rader, M Roe, JW Knowles

OR30-Neuroendocrinology

Assessment of primary cancers in growth hormone-treated pediatric patients compared to population databases: An epidemiological analysis of a large, multinational, prospective observational study
CJ Child, AG Zimmermann, N Jia, LL Robison, JH Bramswig, WF Blum

Hypophysitis in the age of cancer immunotherapy: Experience in a large cancer center
MJoelle Pitteloud, R Dadu, ME Cabanillas, K Shah, MI-N Hu, MA Habra, SG Waguespack

OR34-Testosterone Replacement Therapy: Risks and Benefits

The association between testosterone use and major adverse cardiovascular events (MACE): An exploratory retrospective cohort analysis of two large, contemporary, coronary heart disease clinical trials
S Janmohamed, G Cicconetti, CE Koro, RV Clark, E Tarka

Oral Presentations in Reproductive Science–Winner: Oral Abstract Award in Reproductive Science

Effects of androgens and estrogens on cardiometabolic parameters in young adult men
EW Yu, H Lee, S-AM Burnett-Bowie, SC Hirsch, G Abrishamian-Garcia, LF Borges, DW Goldstein, AP Taylor, KE Wulczyn, AF Moore, JS Finkelstein

PP27-Hyperandrogenic Ovarian Dysfunction

Role of insulin resistance and hyperandrogenemia in early vascular dysfunction in adolescents with PCOS
SK Bartz, MC Caldas, R Krishnamurthy, R Krishnamurthy, FF Bacha

SAT 379-412-Cushing’s Syndrome

Does a normal urine free cortisol result rule out Cushing’s syndrome?
ST Sharma, LK Nieman

SAT 418-443-Biochemical, Genetic and Pharmacological Studies of the Pituitary and Hypothalamus

Clinical and molecular differences between invasive and non-invasive pituitary adenomas
DA Cano, M Mendez-Muros, E Venegas, N Gros, E Dios, N Garcia-Hernandez, A Madrazo-Atutxa, I Martin-Scheffer, E Cardenas, A Kaen, F Roldan, A Soto-Moreno

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Long-term remission and recurrence rate in a cohort of Cushing’s disease: the need for long-term follow-up

Posted on June 9, 2014 by MaryO

Pituitary. 2014 Apr 19. [Epub ahead of print]


Aranda G1, Enseñat J, Mora M, Puig-Domingo M, Martínez de Osaba MJ, Casals G, Verger E, Ribalta MT, Hanzu FA, Halperin I.

Author information

 Abstract

OBJECTIVE:

Transsphenoidal surgery is the procedure of choice in Cushing disease (CD), with immediate post-operative remission rates ranging between 59 and 94 % and recurrence rates between 3 and 46 %, both depending upon the definition criteria and the duration of the follow-up. Our aim was to assess the rate of remission, recurrence and persistence of the disease after the first treatment and to identify predictors of remission in the CD population of our center.

METHODS:

Retrospective cohort study of the patients diagnosed of CD and with follow-up in our center between 1974 and 2011. We analyzed 41 patients (35 women and 6 men) with a mean age at diagnosis of 34 ± 13 years. The mean follow-up was 14 ± 10 years (range 1-37 years) and the median of follow-up period was 6.68 years.

RESULTS:

Thirty-five (85.4 %) patients underwent transsphenoidal surgery as first treatment option. Histopathological evidence of a pituitary adenoma was registered in 17 (48.5 %) patients. Thirty-two (78 %) patients achieved disease remission after the first treatment, 21 (65.6 %) of them presented disease recurrence. Persistent disease was observed in 9 (22 %) patients. Twelve (29.3 %) subjects developed post-surgical adrenal insufficiency, 7 of which (70 %) achieved stable remission. Two parameters were found to be significant predictors of remission after the first treatment: age at disease diagnosis and the development of adrenal insufficiency (cortisol ❤ μg/dl) in the immediate post-operative state.

CONCLUSIONS:

We report a high recurrence rate, at least partially attributable to the long follow-up time. Early post-surgery adrenal insufficiency predicts remission. Hypopituitarism was also very prevalent, and strongly associated with radiotherapy. These results lead us to the conclusion that CD needs a life-long strict follow-up.

PMID:

 

24748528

 

[PubMed – as supplied by publisher]

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Genetic variations associated with hyperplasias, adenomas of adrenal cortex

Posted on February 27, 2014 by MaryO

Beuschlein F. N Engl J Med. 2014;doi:10.1056/NEJMoa1310359.

Genetic variations of the catalytic subunit of cyclic protein kinase A, or PKA, were linked to the development of bilateral adrenal hyperplasias and unilateral cortisol-producing adrenal adenomas. These effects may activate corticotropin-independent Cushing’s syndrome, according to data published in The New England Journal of Medicine.

“The current study suggests that more than one-third of cortisol-producing adenomas associated with overt Cushing’s syndrome have unique somatic mutations in PRKACA (which encodes the main catalytic subunit of PKA), resulting in constitutive PKA activation,” Felix Beuschlein, MD, of the University of Munich, and colleagues wrote.

The researchers performed an exome sequencing of tumor-tissue specimens from 10 patients with cortisol-producing adrenal adenomas and evaluated their recurrent mutations in candidate genes in 171 additional patients with adrenocortical tumors, according to data.

Somatic mutations in PRKACA were discovered in eight of 10 adenomas. These somatic mutations also were identified in 22 of 59 unilateral adenomas (37%) from patients with overt Cushing’s syndrome; mutations were not detectable in 40 patients with subclinical hypercortisolism or in 82 patients with other adrenal tumors, according to data.

Five of the 35 patients with cortisol-producing hyperplasias appeared to be carriers of the germline duplication of the genomic region on chromosome 19 that includes PRKACA, researchers wrote.

In vitro study data indicated that PKA catalytic subunit genetic mutations impaired inhibition by the PKA regulatory subunit, and cells from patients with germline chromosomal gains appeared to increase the protein levels of the subunit.

“Because PRKACA mediates most of the effects of inactivating PRKAR1A mutations and because mutations of PRKAR1 are associated with a variety of tumors in humans and mice, we would speculate that somatic PRKACA defects might also play a role in other forms of endocrine and nonendocrine tumors,” researchers wrote.

Disclosure: Beuschlein reports financial ties with the European Community, HRA Pharma, Novartis, Viropharma, and Wilhelm-Sander Stiftung.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B22954d9a-0fc9-4e80-b80a-d74bbdfea1a9%7D/genetic-variations-associated-with-hyperplasias-adenomas-of-adrenal-cortex

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