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Ceccato, Filippo (2019) Personalized medical treatment for pituitary adenoma. [Ph.D. thesis]

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Abstract (italian or english)

Introduction and Aim: Pituitary adenomas are common neoplasms, with a reported prevalence of about one case in 1000 subjects. Patients with pituitary adenomas show significant morbidity due to pituitary hormone hypersecretion or deficiencies, mass effects and infiltration of the surrounding tissues. Although trans-sphenoidal surgery and radiotherapy are largely used to treat patients with pituitary adenomas, the overall long-term remission rate is not complete, beside side effects of surgery or brain irradiation. Therefore, medical treatments with pituitary-directed drugs are increasingly used in patients with secreting pituitary adenomas, especially when surgery fails or is not indicated, or awaiting for effects of radiotherapy. Somatostatin analogues (SSA) have been the mainstay of the medical treatment of GH-secreting adenomas, and nowadays are also used to treat ACTH-secreting pituitary adenomas, since these tumours express several types of somatostatin receptors (SSTR), with the prevalence of SSTR type 2 in the GH-secreting PA and of SSTR type 5 in the ACTH-secreting. Regrettably, 50% of patients with GH- secreting and 60% with ACTH- secreting pituitary adenomas do not respond to medical treatment with pituitary-directed drugs, or present only a partial hormonal reduction. Receptor desensitization, internalization and intra-cellular trafficking of SSTR could explain at least partially the lack of response, hence more data and knowledge about these cellular processes are urgently needed. Moreover, pituitary adenomas are not always benignant: some aggressive cases (up to 15-20% in all series) are characterized by rapid regrowth after first surgery, invasion of the surrounding structure, resistance to medical therapy, therefore the term Pituitary Neuroendocrine Tumor (PitNET) should be actually used.
The aims of this PhD project are to describe the role of medical treatment in patients with PitNET, in order to study the efficacy of available compounds; applicate the combination of medical treatment in clinical practice; analyse the differential effects (if existing) of medical treatment compared to surgery (considered the best curative treatment).
Materials and methods: Among our cohort of patients (120 with GH-, 134 with ACTH-, 171 with PRL-, 6 with TSH- secreting PitNET, 150 with non-secreting PitNET), we retrospectively and prospectively analysed clinical, radiological and pathological features of patient. Considering the treatment of aggressive PitNET or patients with Cushing’s Syndrome, we focused our attention to everolimus, temozolomide (TMZ) and metyrapone (MET) treatment. In some case, primary cell culture were used to study the effect of medical treatment.
Results: Regarding medical treatment, we considered the use of everolimus, TMZ, cabergoline and MET.
1. In a patient with tuberous sclerosis complex (TSC) and silent gonadotroph PitNET we tested the efficacy of everolimus, observing a reduction of cell viability after an in vitro treatment of PitNET’s derived primary cells. TSC analysis retrieved no disease-associated variants with the exception of the heterozygous intronic variant c.4006-71C>T found in TSC2: the computational tools predicted a gain of a new splice site with consequent intron retention, not confirmed by an in-vitro analysis of patient’s lymphocyte derived RNA.
2. Regarding TMZ in aggressive PitNET, we conducted an Italian survey on 31 patients: 11 patients (35.5%) had reduction of the tumor during TMZ treatment, while 6 patients (19.4%) had progression of disease. Median follow-up after start of TMZ was 18 months. Seven patients presented disease progression. The 2-yr recurrence-free survival was 62% (95% C.I., 34 -99%). Seven patients died of progressive disease. The 2-yr and 4-yr survival rates were 90% (95% C.I., 77-100%) and 56% (95% C.I., 26-85%). Moreover, we treated a patient with a combined cabergoline+TMZ treatment, achieving excellent results.
3. Considering MET in patients with Cushing’s Syndrome, patients were treated with a median dose of 1000 mg for 9 months. UFC and LNSC decreased quickly after the first month of treatment (-67% and -57% from baseline), with sustained UFC normalization up to 12 and 24 months (in 13 and 6 patients, respectively). UFC and LNSC normalized later (after 3-6 months) in patients with severe hypercortisolism (>5-fold baseline UFC). Regarding last visit, 70% and 37% of patients normalized UFC and LNSC, respectively. Body weight reduction (-4kg) was observed after UFC normalization. Severe side-effects were not reported, half female patients complained hirsutism, and blood pressure was not increased.
4. In patients with acromegaly, a significant proportion of patients developed Central Adrenal Insufficiency (CA) over time: while primary or secondary medical treatment did not contribute to the risk of CAI, repeated surgery or radiotherapy affected pituitary-adrenal axis. CAI was diagnosed in 18% of patients (10/57) after surgery, and in 53% (9/17) after radiotherapy (p=0.01).
Considering those aspects related to predict the effects of medical treatment with SSA in acromegaly, we studied the role of AIP-AHR and GIPR pathway. Considering AIP-AHR axis, involved in the detoxification of endocrine disruptors and chemical pollutants, we observed that acromegaly is more biochemically severe and resistant to SSA treatment in patients living in highly polluted areas, especially if they also carry specific AHR and/or AIP gene variants. Moreover, we found a stimulatory effect of IGF-1 on GIP promoter support in GIPR-expressing somatotropinomas, suggesting a novel molecular pathway able to induce GH-secreting PitNET.
Conclusions: In this complex scenario, understanding the physio-pathology of PitNET is the beginning of personalized treatment. In clinical practice, a multidisciplinary team for the management of patients is fundamental, to suggest the correct treatment plan, tailored to the patient.

Abstract (a different language)

Introduzione e scopo: Gli adenomi ipofisari sono neoplasie frequenti, con una prevalenza di un caso ogni 1000 soggetti. I pazienti con adenoma ipofisario possono presentare segni e sintomi in correlazione alla secrezione autonoma (o deficitaria) di ormoni ipofisari, oppure possono presentarsi come “effetto massa” dovuto alla lesione occupante spazio in loggia ipofisaria. Sebbene la chirurgia e la radioterapia siano state molto utilizzate in passato, il controllo a lungo termine non è completo, sia in termini di secrezione che di lesione adenomatosa, esponendo comunque il paziente agli effetti collaterali dell’intervento o dell’irradiazione. Pertanto, la terapia medica è sempre più utilizzata, non solo nelle recidive post-chirurgiche, ma anche quando ulteriori interventi sono inefficaci, o in attesa degli effetti della radioterapia. Gli analoghi della somatostatina (SSA) sono stati per anni la principale terapia degli adenoma GH-secernenti, e al giorno d’oggi vengono utilizzati anche in quelli ACTH-secernenti, dato il loro effetto differenziale sui recettori della somatostatina (SSTR), soprattutto il tipo 2 nei GH-secernenti e il tipo 5 negli ACTH-secernenti. Purtroppo, fino al 50% dei pazienti non risponde in maniera soddisfacente alle terapie mediche, pertanto una maggior conoscenza della biologia cellulare ipofisaria è necessaria, per capire quale sia la strategia migliore per il paziente. Inoltre, in alcuni casi gli adenomi non sono sempre benigni (circa il 15-20% delle principali serie descritte in letteratura), caratterizzandosi per la resistenza alle terapie convenzionali, l’invasione dei tessuti locali o la rapida crescita. In tali casi, il termine Tumore Neuroendocrino Ipofisario (PitNET) viene recentemente proposto in letteratura.
Lo scopo di questa tesi di dottorato è di studiare gli effetti delle terapie mediche in pazienti con PitNET; per sviluppare nuove strategie terapeutiche, per capire l’efficacia dei farmaci disponibili e per testare la loro combinazione.
Materiali e metodi: I pazienti che sono seguiti presso l’ambulatorio ipofisi dell’Unità Operativa di Endocrinologia dell’Azienda Ospedaliero-Universitaria di Padova (120 con PitNET GH-secernenti, 134 ACTH-secernenti, 171 PRL-secernenti, 6 TSH- secernenti e 150 PitNET non funzionanti) sono stati seguiti in uno studio retrospettivo e prospettico. I dati clinici, bioumorali, di terapia, radiologici e patologici sono stati raccolti e analizzati. Tra le varie terapie mediche, maggior risalto è stato dato all’everolimus e alla temozolomide (TMZ) nei PitNET aggressivi e al metirapone (MET) in pazienti con Sindrome di Cushing. In casi selezionati sono state allestite linee cellulari derivanti dall’adenoma del pazienti (primarie).

Risultati: in termini di terapia medica abbiamo analizzato
1. In un paziente con sclerosi tuberosa e PitNET silente abbiamo testato l’efficacia dell’everolimus in colture primarie, osservando una generale riduzione della vitalità cellulare. Abbiamo poi riscontrato una nuova variante del gene TSC2, gli studi in silico predicono la ritenzione di un introne con perdita di un sito di splicing, che andrà confermato in ulteriori studi funzionali.
2. Considerando la terapia con TMZ in PitNET aggressivi abbiamo raccolto i dati di 31 pazienti provenienti da uno studio multicentrico italiano. 11 casi hanno presentato una riduzione del PitNET, con una mediana di terapia di 18 mesi. Il 90% e il 60% dei pazienti erano liberi da malattia a 2 e 4 anni dalla terapia con TMZ. Abbiamo poi trattato un paziente con TMZ e cabergolina, ottenendo ottimi risultati.
3. 31 pazienti con Sindrome di Cushing sono stati trattati per 9 mesi con 1000 mg di MET. I parametri ormonali (cortisoluria e cortisolo salivare notturno) si sono ridotti rapidamente già dopo un solo mese di terapia, normalizzando la secrezione di cortisolo fino a 12 e 24 mesi. I pazienti con ipercorticismo severo (>5 volte i valori normali al baseline) hanno raggiunto il controllo biochimico di malattia più lentamente, tuttavia il 70% dei pazienti normalizzava la cortisoluria all’ultima visita, con una riduzione media di peso di 4kg. In generale il MET era ben tollerato, senza importanti effetti collaterali.
4. Nei pazienti con acromegalia, lo sviluppo di insufficienza surrenalica centrale (CAI) non è trascurabile nel follow-up. Mentre la terapia medica non aumenta il rischio di CAI, il 18% dei pazienti (10/57) svilippa iposurrenalismo dopo la chirurgia, mentre il 53% (9/17) lo sviluppa dopo la radioterapia.
Analizzando in vitro gli aspetti che potrebbero predire la efficacia della terapia con SSA nei pazienti con acromegalia, abbiamo studiato i pathway molecolari di AIP-AHR e del GIPR. L’asse AIP-AHR, coinvolto nella detossificazione di varie molecole interferenti endocrine e inquinanti chimici, si trova maggiormente mutato in pazienti acromegalici con malattia più severa e con minor risposta agli SSA, soprattutto se vivono in zone molto inquinate. Abbiamo inoltre scoperto un ruolo promuovente del recettore dell’IGF-1 nel recettore del GIP, coinvolto nella tumorogenesi ipofisaria e quindi nuovo aspetto da studiare nei PitNET GH-secernenti.
Conclusioni: Comprendere a fondo la fisiopatologia dei PitNET è l’inizio della personalizzazione della terapia medica, sempre più usata oggigiorno. Nella pratica clinica quotidiana, pertanto, un team multidisciplinare è fondamentale per proporre al paziente il corretto piano terapeutico, personalizzato secondo le proprie caratteristiche biologiche.

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EPrint type:Ph.D. thesis
Tutor:Scaroni, Carla
Ph.D. course:Ciclo 31 > Corsi 31 > SCIENZE CLINICHE E SPERIMENTALI
Data di deposito della tesi:24 May 2019
Anno di Pubblicazione:27 March 2019
Key Words:Pituitary Neuroendocrine Tumors, Medical Treatment, Personalized Medicine
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/13 Endocrinologia
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina
Codice ID:11954
Depositato il:07 Nov 2019 12:42
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1. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: A cross-sectional study in the province of Liège, Belgium. J Clin Endocrinol Metab. 2006;91(12):4769-4775. doi:10.1210/jc.2006-1668 Cerca con Google

2. Nieman LK, Biller BMK, Findling JW, et al. The Diagnosis of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540. doi:10.1210/jc.2008-0125 Cerca con Google

3. Katznelson L, Laws ER, Melmed S, et al. Acromegaly: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. doi:10.1210/jc.2014-2700 Cerca con Google

4. Chanson P, Raverot G, Castinetti F, et al. Management of clinically non-functioning pituitary adenoma. Ann Endocrinol (Paris). 2015;76(3):239-247. doi:10.1016/j.ando.2015.04.002 Cerca con Google

5. McCormack A, Dekkers OM, Petersenn S, et al. Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol. 2018;178(3). doi:10.1530/EJE-17-0933 Cerca con Google

6. Nieman LK, Biller BMK, Findling JW, et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(8):2807-2831. doi:10.1210/jc.2015-1818 Cerca con Google

7. Giustina A, Chanson P, Bronstein MD, et al. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab. 2010;95(7):3141-3148. doi:10.1210/jc.2009-2670 Cerca con Google

8. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273-288. doi:10.1210/jc.2010-1692 Cerca con Google

9. Losa M, Picozzi P, Redaelli MG, Laurenzi A, Mortini P. Pituitary Radiotherapy for Cushing’s Disease. Neuroendocrinology. 2010;92(1):107-110. doi:10.1159/000314299 Cerca con Google

10. Minniti G, Traish D, Ashley S, Gonsalves A, Brada M. Fractionated stereotactic conformal radiotherapy for secreting and nonsecreting pituitary adenomas. Clin Endocrinol (Oxf). 2006;64(5):542-548. doi:10.1111/j.1365-2265.2006.02506.x Cerca con Google

11. Sav A, Rotondo F, Syro L V., Di Ieva A, Cusimano MD, Kovacs K. Invasive, Atypical and Aggressive Pituitary Adenomas and Carcinomas. Endocrinol Metab Clin North Am. 2015;44(1):99-104. doi:10.1016/j.ecl.2014.10.008 Cerca con Google

12. Pivonello R, Martino MC De, Cappabianca P, et al. The medical treatment of Cushing’s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab. 2009;94(1):223-230. doi:10.1210/jc.2008-1533 Cerca con Google

13. Vierimaa O, Georgitsi M, Lehtonen R, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science. 2006;312(5777):1228-1230. doi:10.1126/science.1126100 Cerca con Google

14. Daly AF, Vanbellinghen J-F, Khoo SK, et al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab. 2007;92(5):1891-1896. doi:10.1210/jc.2006-2513 Cerca con Google

15. Beckers A, Aaltonen LA, Daly AF, Karhu A. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr Rev. 2013;34(2):239-277. doi:10.1210/er.2012-1013 Cerca con Google

16. Occhi G, Regazzo D, Trivellin G, et al. A novel mutation in the upstream open reading frame of the CDKN1B gene causes a MEN4 phenotype. PLoS Genet. 2013;9(3):e1003350. doi:10.1371/journal.pgen.1003350 Cerca con Google

17. Iacovazzo D, Caswell R, Bunce B, et al. Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta Neuropathol Commun. 2016;4(1):56. doi:10.1186/s40478-016-0328-1 Cerca con Google

18. Melmed S. Aryl hydrocarbon receptor interacting protein and pituitary tumorigenesis: another interesting protein. J Clin Endocrinol Metab. 2007;92(5):1617-1619. doi:10.1210/jc.2007-0595 Cerca con Google

19. Jaffrain-Rea M-L, Rotondi S, Turchi A, et al. Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations. Endocr Relat Cancer. 2013;20(5). doi:10.1530/ERC-12-0322 Cerca con Google

20. Gadelha MR, Kasuki L, Korbonits M. The genetic background of acromegaly. Pituitary. 2017;20(1):10-21. doi:10.1007/s11102-017-0789-7 Cerca con Google

21. Reincke M, Sbiera S, Hayakawa A, et al. Mutations in the deubiquitinase gene USP8 cause Cushing’s disease. Nat Genet. 2015;47(1):31-38. doi:10.1038/ng.3166 Cerca con Google

22. Perez-Rivas LG, Theodoropoulou M, Ferraù F, et al. The Gene of the Ubiquitin-Specific Protease 8 Is Frequently Mutated in Adenomas Causing Cushing’s Disease. J Clin Endocrinol Metab. 2015;100(7):E997-1004. doi:10.1210/jc.2015-1453 Cerca con Google

23. Occhi G, Jaffrain-Rea ML, Trivellin G, et al. The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas: Mutational hot-spot or founder effect? J Endocrinol Invest. 2010;33(11). doi:10.3275/6956 Cerca con Google

24. Lania A, Mantovani G, Spada A. Genetic abnormalities of somatostatin receptors in pituitary tumors. Mol Cell Endocrinol. 2008;286(1-2):180-186. doi:10.1016/j.mce.2007.08.013 Cerca con Google

25. Oriola J, Lucas T, Halperin I, et al. Germline mutations of AIP gene in somatotropinomas resistant to somatostatin analogues. Eur J Endocrinol. 2013;168(1):9-13. doi:10.1530/EJE-12-0457 Cerca con Google

26. Cannavò S, Ferraù F, Ragonese M, et al. Increased prevalence of acromegaly in a highly polluted area. Eur J Endocrinol. 2010;163(4):509-513. doi:10.1530/EJE-10-0465 Cerca con Google

27. Tapella L, Sesta A, Cassarino MF, Zunino V, Catalano MG, Pecori Giraldi F. Benzene and 2-ethyl-phthalate induce proliferation in normal rat pituitary cells. Pituitary. 2017;20(3):311-318. doi:10.1007/s11102-016-0777-3 Cerca con Google

28. Fortunati N, Guaraldi F, Zunino V, et al. Effects of environmental pollutants on signaling pathways in rat pituitary GH3 adenoma cells. Environ Res. 2017;158:660-668. doi:10.1016/j.envres.2017.07.015 Cerca con Google

29. Dietrich C, Kaina B. The aryl hydrocarbon receptor (AhR) in the regulation of cell-cell contact and tumor growth. Carcinogenesis. 2010;31(8):1319-1328. doi:10.1093/carcin/bgq028 Cerca con Google

30. Chanson P, Salenave S, Kamenicky P, Cazabat L, Young J. Pituitary tumours: acromegaly. Best Pract Res Clin Endocrinol Metab. 2009;23(5):555-574. doi:10.1016/j.beem.2009.05.010 Cerca con Google

31. Occhi G, Losa M, Albiger N, et al. The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells. J Neuroendocrinol. 2011;23(7):641-649. doi:10.1111/j.1365-2826.2011.02155.x Cerca con Google

32. Volz A, Göke R, Lankat-Buttgereit B, Fehmann H-C, Bode HP, Göke B. Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. FEBS Lett. 1995;373(1):23-29. doi:10.1016/0014-5793(95)01006-Z Cerca con Google

33. Gremlich S, Porret A, Hani EH, et al. Cloning, Functional Expression, and Chromosomal Localization of the Human Pancreatic Islet Glucose-Dependent Insulinotropic Polypeptide Receptor. Diabetes. 1995;44(10):1202-1208. doi:10.2337/diab.44.10.1202 Cerca con Google

34. Seino Y, Fukushima M, Yabe D. GIP and GLP-1, the two incretin hormones: Similarities and differences. J Diabetes Investig. 2010;1(1-2):8-23. doi:10.1111/j.2040-1124.2010.00022.x Cerca con Google

35. Mazzuco TL, Chabre O, Feige JJ, Thomas M. Aberrant GPCR expression is a sufficient genetic event to trigger adrenocortical tumorigenesis. Mol Cell Endocrinol. 2007;265-266:23-28. doi:10.1016/j.mce.2006.12.034 Cerca con Google

36. Albiger NM, Occhi G, Mariniello B, et al. Food-dependent Cushing’s syndrome: from molecular characterization to therapeutical results. Eur J Endocrinol. 2007;157(6):771-778. doi:10.1530/EJE-07-0253 Cerca con Google

37. Occhi G, Losa M, Albiger N, et al. The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells. J Neuroendocrinol. 2011;23(7):641-649. doi:10.1111/j.1365-2826.2011.02155.x Cerca con Google

38. Umahara M, Okada S, Ohshima K, Mori M. Glucose-dependent insulinotropic polypeptide induced growth hormone secretion in acromegaly. Endocr J. 2003;50(5):643-650. doi:10.1507/endocrj.50.643 Cerca con Google

39. Umahara M, Okada S, Ohshima K, Mori M. Glucose-dependent insulinotropic polypeptide induced growth hormone secretion in acromegaly. Endocr J. 2003;50(5):643-650. doi:10.1507/endocrj.50.643 Cerca con Google

40. Peracchi M, Porretti S, Gebbia C, et al. Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly. Eur J Endocrinol. 2001;145(1):R1-4. http://www.ncbi.nlm.nih.gov/pubmed/1415859. Vai! Cerca con Google

41. Han S, Gao W, Jing Z, Wang Y, Wu A. How to deal with giant pituitary adenomas: transsphenoidal or transcranial, simultaneous or two-staged? J Neurooncol. 2017;132(2):313-321. doi:10.1007/s11060-017-2371-6 Cerca con Google

42. Chatzellis E, Alexandraki KI, Androulakis II, Kaltsas G. Aggressive pituitary tumors. Neuroendocrinology. 2015;101(2):87-104. doi:10.1159/000371806 Cerca con Google

43. Di Ieva A, Rotondo F, Syro L V., Cusimano MD, Kovacs K. Aggressive pituitary adenomas-diagnosis and emerging treatments. Nat Rev Endocrinol. 2014;10(7):423-435. doi:10.1038/nrendo.2014.64 Cerca con Google

44. Saeger W, Lüdecke DK, Buchfelder M, Fahlbusch R, Quabbe H-J, Petersenn S. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol. 2007;156(2):203-216. doi:10.1530/eje.1.02326 Cerca con Google

45. Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER. Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg. 2011;114(2):336-344. doi:10.3171/2010.8.JNS10290 Cerca con Google

46. Ceccato F, Occhi G, Regazzo D, et al. Gonadotropin secreting pituitary adenoma associated with erythrocytosis: Case report and literature review. Hormones. 2014;13(1). Cerca con Google

47. Raverot G, Dantony E, Beauvy J, et al. Risk of Recurrence in Pituitary Neuroendocrine Tumors: A Prospective Study Using a Five-Tiered Classification. J Clin Endocrinol Metab. 2017;102(9):3368-3374. doi:10.1210/jc.2017-00773 Cerca con Google

48. Vieira JO, Cukiert A, Liberman B. Evaluation of magnetic resonance imaging criteria for cavernous sinus invasion in patients with pituitary adenomas: logistic regression analysis and correlation with surgical findings. Surg Neurol. 2006;65(2):130-5; discussion 135. doi:10.1016/j.surneu.2005.05.021 Cerca con Google

49. Manara R, Maffei P, Citton V, et al. Increased rate of intracranial saccular aneurysms in acromegaly: An MR angiography study and review of the literature. J Clin Endocrinol Metab. 2011;96(5). doi:10.1210/jc.2010-2721 Cerca con Google

50. Shimon I, Jallad RS, Fleseriu M, Yedinak CG, Greenman Y, Bronstein MD. Giant GH-secreting pituitary adenomas: Management of rare and aggressive pituitary tumors. Eur J Endocrinol. 2015;172(6):707-713. doi:10.1530/EJE-14-1117 Cerca con Google

51. Nomikos P, Buchfelder M, Fahlbusch R. The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical “cure.” Eur J Endocrinol. 2005;152(3):379-387. doi:10.1530/eje.1.01863 Cerca con Google

52. Inoshita N, Nishioka H. The 2017 WHO classification of pituitary adenoma: overview and comments. Brain Tumor Pathol. 2018;35(2):51-56. doi:10.1007/s10014-018-0314-3 Cerca con Google

53. Lopes MBS. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol. 2017;134(4):521-535. doi:10.1007/s00401-017-1769-8 Cerca con Google

54. Ceccato F, Scaroni C, Boscaro M. Clinical use of pasireotide for cushing’s disease in adults. Ther Clin Risk Manag. 2015;11. doi:10.2147/TCRM.S37314 Cerca con Google

55. Ceccato F, Barbot M, Zilio M, Albiger N, Mantero F, Scaroni C. Therapeutic strategies for Cushing’s syndrome: An update. Expert Opin Orphan Drugs. 2015;3(1). doi:10.1517/21678707.2015.991714 Cerca con Google

56. Castinetti F, Morange I, Jaquet P, Conte-Devolx B, Brue T. Ketoconazole revisited: a preoperative or postoperative treatment in Cushing’s disease. Eur J Endocrinol. 2008;158(1):91-99. doi:10.1530/EJE-07-0514 Cerca con Google

57. Castinetti F, Guignat L, Giraud P, et al. Ketoconazole in Cushing’s Disease: Is It Worth a Try? J Clin Endocrinol Metab. 2014;99(5):1623-1630. doi:10.1210/jc.2013-3628 Cerca con Google

58. Verhelst JA, Trainer PJ, Howlett TA, et al. Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing’s syndrome. Clin Endocrinol (Oxf). 1991;35(2):169-178. doi:10.1111/j.1365-2265.1991.tb03517.x Cerca con Google

59. Valassi E, Crespo I, Gich I, Rodríguez J, Webb SM. A reappraisal of the medical therapy with steroidogenesis inhibitors in Cushing’s syndrome. Clin Endocrinol (Oxf). 2012;77(5):735-742. doi:10.1111/j.1365-2265.2012.04424.x Cerca con Google

60. Daniel E, Aylwin S, Mustafa O, et al. Effectiveness of Metyrapone in Treating Cushing’s Syndrome: A Retrospective Multicenter Study in 195 Patients. J Clin Endocrinol Metab. 2015;100(11):4146-4154. doi:10.1210/jc.2015-2616 Cerca con Google

61. Godbout A, Manavela M, Danilowicz K, Beauregard H, Bruno OD, Lacroix A. Cabergoline monotherapy in the long-term treatment of Cushing’s disease. Eur J Endocrinol. 2010;163(5):709-716. doi:10.1530/EJE-10-0382 Cerca con Google

62. Lila AR, Gopal RA, Acharya S V, et al. Efficacy of cabergoline in uncured (persistent or recurrent) Cushing disease after pituitary surgical treatment with or without radiotherapy. Endocr Pract. 2010;16(6):968-976. doi:10.4158/EP10031.OR Cerca con Google

63. Palui R, Sahoo J, Kamalanathan S, Kar SS, Selvarajan S, Durgia H. Effect of cabergoline monotherapy in Cushing’s disease: an individual participant data meta-analysis. J Endocrinol Invest. 2018;41(12):1445-1455. doi:10.1007/s40618-018-0936-7 Cerca con Google

64. Pecori Giraldi F, Ambrogio AG, Andrioli M, et al. Potential Role for Retinoic Acid in Patients with Cushing’s Disease. J Clin Endocrinol Metab. 2012;97(10):3577-3583. doi:10.1210/jc.2012-2328 Cerca con Google

65. Occhi G, Regazzo D, Albiger NM, et al. Activation of the dopamine receptor type-2 (DRD2) promoter by 9-cis retinoic acid in a cellular model of cushing’s disease mediates the inhibition of cell proliferation and ACTH secretion without a complete corticotroph-to-melanotroph transdifferentiation. Endocrinology. 2014;155(9). doi:10.1210/en.2013-1820 Cerca con Google

66. Vilar L, Albuquerque JL, Lyra R, et al. The Role of Isotretinoin Therapy for Cushing’s Disease: Results of a Prospective Study. Int J Endocrinol. 2016;2016:8173182. doi:10.1155/2016/8173182 Cerca con Google

67. Boscaro M, Ludlam WH, Atkinson B, et al. Treatment of pituitary-dependent Cushing’s disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab. 2009;94(1):115-122. doi:10.1210/jc.2008-1008 Cerca con Google

68. Colao A, Petersenn S, Newell-Price J, et al. A 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med. 2012;366(10):914. http://www.ncbi.nlm.nih.gov/pubmed/22397653. Vai! Cerca con Google

69. Lacroix A, Gu F, Gallardo W, et al. Efficacy and safety of once-monthly pasireotide in Cushing’s disease: a 12 month clinical trial. lancet Diabetes Endocrinol. 2018;6(1):17-26. doi:10.1016/S2213-8587(17)30326-1 Cerca con Google

70. Colao A, Boscaro M, Ferone D, Casanueva FF. Managing Cushing’s disease: the state of the art. Endocrine. 2014;47(1):9. doi:10.1007/s12020-013-0129-2 Cerca con Google

71. Vilar L, Naves LA, Azevedo MF, et al. Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing’s disease. Pituitary. 2010;13(2):123-129. doi:10.1007/s11102-009-0209-8 Cerca con Google

72. Barbot M, Albiger N, Ceccato F, et al. Combination therapy for Cushing’s disease: Effectiveness of two schedules of treatment. Should we start with cabergoline or ketoconazole? Pituitary. 2014;17(2). doi:10.1007/s11102-013-0475-3 Cerca con Google

73. Feelders RA, de Bruin C, Pereira AM. Pasireotide Alone or with Cabergoline and Ketoconazole in Cushing’s Disease. N Engl J Med. 2010;362(19):1846-1848. doi:10.1056/NEJMc1000094 Cerca con Google

74. Lönn L, Kvist H, Ernest I, Sjöström L. Changes in body composition and adipose tissue distribution after treatment of women with Cushing’s syndrome. Metabolism. 1994;43(12):1517-1522. http://www.ncbi.nlm.nih.gov/pubmed/7990705. Vai! Cerca con Google

75. Pirlich M, Biering H, Gerl H, et al. Loss of body cell mass in Cushing’s syndrome: effect of treatment. J Clin Endocrinol Metab. 2002;87(3):1078-1084. doi:10.1210/jcem.87.3.8321 Cerca con Google

76. Geer EB, Shen W, Strohmayer E, Post KD, Freda PU. Body composition and cardiovascular risk markers after remission of Cushing’s disease: a prospective study using whole-body MRI. J Clin Endocrinol Metab. 2012;97(5):1702-1711. doi:10.1210/jc.2011-3123 Cerca con Google

77. Barahona M-J, Sucunza N, Resmini E, et al. Persistent body fat mass and inflammatory marker increases after long-term cure of Cushing’s syndrome. J Clin Endocrinol Metab. 2009;94(9):3365-3371. doi:10.1210/jc.2009-0766 Cerca con Google

78. Ragnarsson O, Glad CAM, Bergthorsdottir R, et al. Body composition and bone mineral density in women with Cushing’s syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity. Eur J Endocrinol. 2015;172(1):1-10. doi:10.1530/EJE-14-0747 Cerca con Google

79. Wagenmakers M, Roerink S, Gil L, et al. Persistent centripetal fat distribution and metabolic abnormalities in patients in long-term remission of Cushing’s syndrome. Clin Endocrinol (Oxf). 2015;82(2):180-187. doi:10.1111/cen.12639 Cerca con Google

80. Melmed S, Casanueva FF, Klibanski A, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013;16(3):294-302. doi:10.1007/s11102-012-0420-x Cerca con Google

81. Andersen M. Management of endocrine disease: GH excess: diagnosis and medical therapy. Eur J Endocrinol. 2014;170(1):R31-41. doi:10.1530/EJE-13-0532 Cerca con Google

82. Andries M, Glintborg D, Kvistborg A, Hagen C, Andersen M. A 12-month randomized crossover study on the effects of Lanreotide Autogel and Octreotide long-acting repeatable on GH and IGF-l in patients with acromegaly. Clin Endocrinol (Oxf). 2007;68(3):473-480. doi:10.1111/j.1365-2265.2007.03067.x Cerca con Google

83. Caron PJ, Bevan JS, Petersenn S, et al. Tumor shrinkage with lanreotide autogel 120 mg as primary therapy in acromegaly: Results of a prospective multicenter clinical trial. J Clin Endocrinol Metab. 2014;99(4):1282-1290. doi:10.1210/jc.2013-3318 Cerca con Google

84. Carmichael JD, Bonert VS, Nuño M, Ly D, Melmed S. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: A meta-analysis. J Clin Endocrinol Metab. 2014;99(5):1825-1833. doi:10.1210/jc.2013-3757 Cerca con Google

85. Muhammad A, Coopmans EC, Delhanty P, et al. Efficacy and Safety of switching to Pasireotide in Acromegaly Patients controlled with Pegvisomant and Somatostatin Analogues: PAPE extension study. Eur J Endocrinol. 2018;179(5):269-277. doi:10.1530/EJE-18-0353 Cerca con Google

86. Shimon I, Adnan Z, Gorshtein A, et al. Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine. 2018;62(2):448-455. doi:10.1007/s12020-018-1690-5 Cerca con Google

87. Freda P, Gordon M, Kelepouris N, Jonsson P, Koltowska-Haggstrom M, van der Lely A. Long-Term Treatment with Pegvisomant as Monotherapy in Patients with Acromegaly: Experience from Acrostudy. Endocr Pract. 2015;21(3):264-274. doi:10.4158/EP14330.OR Cerca con Google

88. Van Der Lely AJ, Biller BMK, Brue T, et al. Long-term safety of pegvisomant in patients with acromegaly: Comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab. 2012;97(5):1589-1597. doi:10.1210/jc.2011-2508 Cerca con Google

89. Kasuki L, Vieira Neto L, Gadelha MR. Cabergoline treatment in acromegaly: Cons. Endocrine. 2014;46(2):220-225. doi:10.1007/s12020-014-0183-4 Cerca con Google

90. Marazuela M, Ramos-Leví A, Sampedro-Núñez M, Bernabeu I. Cabergoline treatment in acromegaly: pros. Endocrine. 2014;46(2):215-219. doi:10.1007/s12020-014-0206-1 Cerca con Google

91. Puig Domingo M. Treatment of acromegaly in the era of personalized and predictive medicine. Clin Endocrinol (Oxf). 2015;83(1):3-14. doi:10.1111/cen.12731 Cerca con Google

92. Oh MC, Aghi MK. Dopamine agonist-resistant prolactinomas. J Neurosurg. 2011;114(5):1369-1379. doi:10.3171/2010.11.JNS101369 Cerca con Google

93. Moraes AB, Marques Dos Santos Silva C, Vieira Neto L, Gadelha MR. Giant prolactinomas: The therapeutic approach. Clin Endocrinol (Oxf). 2013;79(4):447-456. doi:10.1111/cen.12242 Cerca con Google

94. Knizhnik A V., Roos WP, Nikolova T, et al. Survival and death strategies in glioma cells: autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage. PLoS One. 2013;8(1):e55665. doi:10.1371/journal.pone.0055665 Cerca con Google

95. Marchesi F, Turriziani M, Tortorelli G, Avvisati G, Torino F, De Vecchis L. Triazene compounds: mechanism of action and related DNA repair systems. Pharmacol Res. 2007;56(4):275-287. doi:10.1016/j.phrs.2007.08.003 Cerca con Google

96. Lim S, Shahinian H, Maya MM, Yong W, Heaney AP. Temozolomide: a novel treatment for pituitary carcinoma. Lancet Oncol. 2006;7(6):518-520. doi:10.1016/S1470-2045(06)70728-8 Cerca con Google

97. Fadul CE, Kominsky AL, Meyer LP, et al. Long-term response of pituitary carcinoma to temozolomide. Report of two cases. J Neurosurg. 2006;105(4):621-626. doi:10.3171/jns.2006.105.4.621 Cerca con Google

98. Raverot G, Castinetti F, Jouanneau E, et al. Pituitary carcinomas and aggressive pituitary tumours: Merits and pitfalls of temozolomide treatment. Clin Endocrinol (Oxf). 2012;76(6):769-775. doi:10.1111/j.1365-2265.2012.04381.x Cerca con Google

99. Raverot G, Burman P, McCormack A, et al. European society of endocrinology clinical practice guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. 2018;178(1):G1-G24. doi:10.1530/EJE-17-0796 Cerca con Google

100. Ceccato F, Lombardi G, Manara R, et al. Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center. J Neurooncol. 2015;122(1). doi:10.1007/s11060-014-1702-0 Cerca con Google

101. Orlova KA CP. The tuberous sclerosis complex. Ann N Y Acad Sci. 2010;(1184):87-105. doi:10.1111/j.1749-6632.2009.05117.x. Cerca con Google

102. Curatolo P, Bombardieri R JS. Tuberous sclerosis. Lancet. 2008;372:657-668. doi:doi: 10.1016/S0140-6736(08)61279-9. Cerca con Google

103. Tyburczy ME, Dies KA, Glass J, et al. Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing. PLoS Genet. 2015;11(11):1-17. doi:10.1371/journal.pgen.1005637 Cerca con Google

104. Dworakowska D, Grossman AB. Are neuroendocrine tumours a feature of tuberous sclerosis? A systematic review. Endocr Relat Cancer. 2009;16(1):45-58. doi:10.1677/ERC-08-0142 Cerca con Google

105. Yeung RS, Katsetos CD, Klein-Szanto A. Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis. Am J Pathol. 1997;151(5):1477-1486. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1858083&tool=pmcentrez&rendertype=abstract. Vai! Cerca con Google

106. Kazlauskaite R, Evans AT, Villabona C V, et al. Corticotropin Tests for Hypothalamic-Pituitary- Adrenal Insufficiency: A Metaanalysis. J Clin Endocrinol Metab. 2008;93(11):4245-4253. doi:10.1210/jc.2008-0710 Cerca con Google

107. Ospina N, Al Nofal A, Bancos I, et al. ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2016;101(2):427-434. doi:10.1210/jc.2015-1700 Cerca con Google

108. Ceccato F, Antonelli G, Barbot M, et al. The diagnostic performance of urinary free cortisol is better than the cortisol: Cortisone ratio in detecting de novo Cushing’s Syndrome: The use of a LC-MS/MS method in routine clinical practice. Eur J Endocrinol. 2014;171(1). doi:10.1530/EJE-14-0061 Cerca con Google

109. Antonelli G, Ceccato F, Artusi C, Marinova M, Plebani M. Salivary cortisol and cortisone by LC-MS/MS: Validation, reference intervals and diagnostic accuracy in Cushing’s syndrome. Clin Chim Acta. 2015;451. doi:10.1016/j.cca.2015.10.004 Cerca con Google

110. Zatelli MC, Minoia M, Filieri C, et al. Effect of everolimus on cell viability in nonfunctioning pituitary adenomas. J Clin Endocrinol Metab. 2010;95(2):968-976. doi:10.1210/jc.2009-1641 Cerca con Google

111. Van Der Pas R, De Bruin C, Leebeek FWG, et al. The hypercoagulable state in Cushing’s disease is associated with increased levels of procoagulant factors and impaired fibrinolysis, but is not reversible after short-term biochemical remission induced by medical therapy. J Clin Endocrinol Metab. 2012;97(4):1303-1310. doi:10.1210/jc.2011-2753 Cerca con Google

112. Jalali S, Monsalves E, Tateno T, Zadeh G. Role of mTOR Inhibitors in Growth Hormone-Producing Pituitary Adenomas Harboring Different FGFR4 Genotypes. Endocrinology. 2016;157(9):3577-3587. doi:10.1210/en.2016-1028 Cerca con Google

113. Di Pasquale C, Gentilin E, Falletta S, et al. PI3K/Akt/mTOR pathway involvement in regulating growth hormone secretion in a rat pituitary adenoma cell line. Endocrine. 2018;60(2):308-316. doi:10.1007/s12020-017-1432-0 Cerca con Google

114. Jouanneau E, Wierinckx A, Ducray F, et al. New targeted therapies in pituitary carcinoma resistant to temozolomide. Pituitary. 2012;15(1):37-43. doi:10.1007/s11102-011-0341-0 Cerca con Google

115. Donovan LE, Arnal A V, Wang S-H, Odia Y. Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L) mutation treated with everolimus therapy. CNS Oncol. 2016;5(4):203-209. doi:10.2217/cns-2016-0011 Cerca con Google

116. Rushworth RL, Torpy DJ. Modern Hydrocortisone Replacement Regimens in Adrenal Insufficiency Patients and the Risk of Adrenal Crisis. Horm Metab Res. 2015;47(9):637-642. doi:10.1055/s-0035-1548869 Cerca con Google

117. Ronchi CL, Ferrante E, Rizzo E, et al. Long-term basal and dynamic evaluation of hypothalamic-pituitary-adrenal (HPA) axis in acromegalic patients. Clin Endocrinol (Oxf). 2008;69(4):608-612. doi:10.1111/j.1365-2265.2008.03270.x Cerca con Google

118. Burgers AMG, Kokshoorn NE, Pereira AM, et al. Low incidence of adrenal insufficiency after transsphenoidal surgery in patients with acromegaly: a long-term follow-up study. J Clin Endocrinol Metab. 2011;96(7):E1163-70. doi:10.1210/jc.2010-2673 Cerca con Google

119. Yedinak C, Hameed N, Gassner M, Brzana J, McCartney S, Fleseriu M. Recovery rate of adrenal function after surgery in patients with acromegaly is higher than in those with non-functioning pituitary tumors: a large single center study. Pituitary. 2015;18(5):701-709. doi:10.1007/s11102-015-0643-8 Cerca con Google

120. Sherlock M, Reulen RC, Alonso AA, et al. ACTH Deficiency, Higher Doses of Hydrocortisone Replacement, and Radiotherapy Are Independent Predictors of Mortality in Patients with Acromegaly. J Clin Endocrinol Metab. 2009;94(11):4216-4223. doi:10.1210/jc.2009-1097 Cerca con Google

121. Mercado M, Gonzalez B, Vargas G, et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J Clin Endocrinol Metab. 2014;99(12):4438-4446. doi:10.1210/jc.2014-2670 Cerca con Google

122. Luini A, Lewis D, Guild S, Schofield G, Weight F. Somatostatin, an inhibitor of ACTH secretion, decreases cytosolic free calcium and voltage-dependent calcium current in a pituitary cell line. J Neurosci. 1986;6(11):3128-3132. http://www.ncbi.nlm.nih.gov/pubmed/2430073. Vai! Cerca con Google

123. Kamenický P, Droumaguet C, Salenave S, et al. Mitotane, Metyrapone, and Ketoconazole Combination Therapy as an Alternative to Rescue Adrenalectomy for Severe ACTH-Dependent Cushing’s Syndrome. J Clin Endocrinol Metab. 2011;96(9):2796-2804. doi:10.1210/jc.2011-0536 Cerca con Google

124. Khalil RB, Baudry C, Guignat L, et al. Sequential hormonal changes in 21 patients with recurrent Cushing’s disease after successful pituitary surgery. Eur J Endocrinol. 2011;165(5):729-737. doi:10.1530/EJE-11-0424 Cerca con Google

125. Ceccato F, Barbot M, Zilio M, et al. Performance of salivary cortisol in the diagnosis of Cushing’s syndrome, adrenal incidentaloma, and adrenal insufficiency. Eur J Endocrinol. 2013;169(1). doi:10.1530/EJE-13-0159 Cerca con Google

126. Carroll TB, Javorsky BR, Findling JW. POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL. Endocr Pract. 2016;22(10):1216-1223. doi:10.4158/EP161380.OR Cerca con Google

127. Cannavo S, Messina E, Albani A, et al. Clinical management of critically ill patients with Cushing’s disease due to ACTH-secreting pituitary macroadenomas: effectiveness of presurgical treatment with pasireotide. Endocrine. 2016;52(3):481. http://www.ncbi.nlm.nih.gov/pubmed/25877016. Vai! Cerca con Google

128. Dekkers OM, Horváth-Puhó E, Jørgensen JOL, et al. Multisystem Morbidity and Mortality in Cushing’s Syndrome: A Cohort Study. J Clin Endocrinol Metab. 2013;98(6):2277-2284. doi:10.1210/jc.2012-3582 Cerca con Google

129. Pas R van der, Bruin C de, Pereira AM, et al. Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease. Pituitary. 2013;16(4):536-544. doi:10.1007/s11102-012-0452-2 Cerca con Google

130. Findling J, Fleseriu M, Newell-Price J, et al. Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing’s disease: 12-month, Phase III pasireotide study. Endocrine. 2016;54(2):516-523. doi:10.1007/s12020-016-0978-6 Cerca con Google

131. Plat L, Leproult R, L’Hermite-Baleriaux M, et al. Metabolic Effects of Short-Term Elevations of Plasma Cortisol Are More Pronounced in the Evening Than in the Morning. J Clin Endocrinol Metab. 1999;84(9):3082-3092. doi:10.1210/jc.84.9.3082 Cerca con Google

132. Raff H. Cushing’s syndrome: diagnosis and surveillance using salivary cortisol. Pituitary. 2012;15(1):64-70. doi:10.1007/s11102-011-0333-0 Cerca con Google

133. Ceccato F, Boscaro M. Cushing’s Syndrome: Screening and Diagnosis. High Blood Press Cardiovasc Prev. 2016;23(3). doi:10.1007/s40292-016-0153-4 Cerca con Google

134. Ferraù F, Korbonits M. Metabolic comorbidities in Cushing’s syndrome. Eur J Endocrinol. 2015;173(4):M133-M157. doi:10.1530/EJE-15-0354 Cerca con Google

135. Snijder MB, Visser M, Dekker JM, et al. The prediction of visceral fat by dual-energy X-ray absorptiometry in the elderly: a comparison with computed tomography and anthropometry. Int J Obes Relat Metab Disord. 2002;26(7):984-993. doi:10.1038/sj.ijo.0801968 Cerca con Google

136. Rothney MP, Catapano AL, Xia J, et al. Abdominal visceral fat measurement using dual-energy X-ray: association with cardiometabolic risk factors. Obesity (Silver Spring). 2013;21(9):1798-1802. doi:10.1002/oby.20223 Cerca con Google

137. Terzolo M, Allasino B, Pia A, et al. Surgical remission of Cushing’s syndrome reduces cardiovascular risk. Eur J Endocrinol. 2014;171(1):127-136. doi:10.1530/EJE-13-0555 Cerca con Google

138. van der Pas R, Leebeek FWG, Hofland LJ, de Herder WW, Feelders RA. Hypercoagulability in Cushing’s syndrome: prevalence, pathogenesis and treatment. Clin Endocrinol (Oxf). 2013;78(4):481-488. doi:10.1111/cen.12094 Cerca con Google

139. Koutroumpi S, Spiezia L, Albiger N, et al. Thrombin generation in Cushing’s Syndrome: do the conventional clotting indices tell the whole truth? Pituitary. 2014;17(1):68-75. doi:10.1007/s11102-013-0467-3 Cerca con Google

140. Erem C, Nuhoglu I, Yilmaz M, et al. Blood coagulation and fibrinolysis in patients with Cushing’s syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels. J Endocrinol Invest. 2009;32(2):169-174. http://www.ncbi.nlm.nih.gov/pubmed/19411818. Vai! Cerca con Google

141. Barbot M, Daidone V, Zilio M, et al. Perioperative thromboprophylaxis in Cushing’s disease: What we did and what we are doing? Pituitary. 2015;18(4). doi:10.1007/s11102-014-0600-y Cerca con Google

142. Kastelan D, Dusek T, Kraljevic I, et al. Hypercoagulability in Cushing’s syndrome: the role of specific haemostatic and fibrinolytic markers. Endocrine. 2009;36(1):70-74. doi:10.1007/s12020-009-9186-y Cerca con Google

143. Sosa-Eroza E, Espinosa E, Ramírez-Rentería C, Mendoza V, Arreola R, Mercado M. Treatment of multiresistant prolactinomas with a combination of cabergoline and octreotide LAR. Endocrine. 2018;61(2):343-348. doi:10.1007/s12020-018-1638-9 Cerca con Google

144. Casanueva FF, Barkan AL, Buchfelder M, et al. Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement. Pituitary. 2017;20(5):489-498. doi:10.1007/s11102-017-0838-2 Cerca con Google

145. Losa M, Bogazzi F, Cannavo S, et al. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. J Neurooncol. 2016;126(3). doi:10.1007/s11060-015-1991-y Cerca con Google

146. Lin AL, Sum MW, Deangelis LM. Is there a role for early chemotherapy in the management of pituitary adenomas? Neuro Oncol. 2016;18(10):1350-1356. doi:10.1093/neuonc/now059 Cerca con Google

147. Bengtsson D, Schrøder HD, Andersen M, et al. Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab. 2015;100(4):1689-1698. doi:10.1210/jc.2014-4350 Cerca con Google

148. Moisi M, Cruz AS, Benkers T, et al. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review. Cureus. 2016;8(6). doi:10.7759/cureus.658 Cerca con Google

149. Almalki MH, Aljoaib NN, Alotaibi MJ, et al. Temozolomide therapy for resistant prolactin-secreting pituitary adenomas and carcinomas: A systematic review. Hormones. 2017;16(2):139-149. doi:10.14310/horm.2002.1729 Cerca con Google

150. Chen C, Yin S, Zhang S, et al. Treatment of aggressive prolactinoma with temozolomide: A case report and review of literature up to date. Medicine (Baltimore). 2017;96(47):e8733. doi:10.1097/MD.0000000000008733 Cerca con Google

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